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Probing vestibular contributions during dynamic locomotor tasks using the techniqe of galvanic vestibular… Bent, Leah Rachel 2002

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PROBING VESTIBULAR CONTRIBUTIONS  DURING  L O C O M O T O R TASKS USING THE TECHNIQUE OF VESTIBULAR  DYNAMIC GALVANIC  STIMULATION by  L E A H RACHEL BENT B.Sc. (Hons), University of Guelph, 1996 M.Sc. University of Guelph, 1998  A THESIS S U B M I T T E D IN P A R T I A L F U L F I L L M E N T OF T H E REQUIREMENTS FOR T H E D E G R E E OF DOCTOR OF PHILOSOPHY in  T H E F A C U L T Y OF G R A D U A T E STUDIES (School of Human Kinetics) We accept this thesis as conforming to the required standard  T H E UNIVERSITY OF BRITISH C O L U M B I A September, 2002 © Leah Rachel Bent, 2002  In  presenting  degree freely  at  this  the  thesis  in  partial  fulfilment  University  of  British  Columbia, I agree that the  available for  copying  of  department publication  this or of  reference and study.  thesis for by  this  his  scholarly  or  thesis for  her  of  //MA/  (2/88)  may  representatives.  It  financial gain shall not  tfl?Jg7lCS  The University of British Columbia Vancouver, Canada  DE-6  the  requirements  for  be is  granted  an  advanced  Library shall make  I further agree that permission  purposes  permission.  Department  of  by  understood  for  the that  be allowed without  it  extensive  head  of  my  copying  or  my  written  ABSTRACT  Assessment of the vestibular system, its function and contribution to movement control during locomotor tasks in humans, has been examined in the past using various techniques, and only very recently using Galvanic Vestibular Stimulation (GVS). Studies utilizing G V S have indicated that vestibular information may have a larger role during dynamic tasks, such as locomotion, than during quiet standing. However, the nature of vestibular contributions and their timing during dynamic tasks have not been addressed. The current thesis examines vestibular contributions during specific dynamic tasks. The purpose was to determine i f vestibular information was more heavily weighted at specific times during these dynamic tasks, and based on those findings address the possible roles that vestibular information has in successful task completion. Four studies were conducted that examined vestibular contributions in forward walking, step initiation, gait initiation and steady-state locomotion. Binaural bipolar G V S was delivered at specific times to probe the presence of vestibular contributions. The results of the four studies collectively contributed to four main conclusions. First, vestibular information has greater sensory weighting during the more dynamic phases of a task, even in the presence of vision. Second, the magnitude of the response is dependent on both the magnitude of the vestibular perturbation and the phase in the gait cycle at which the stimulation is delivered during the task. Third, the vestibular contribution during locomotor tasks has different roles, and is therefore differentially modulated, in the control of upper body versus lower limb movement. Finally, the up-regulation of vestibular information for the control of lower limb movement demonstrates gait phase dependency, which is greatest during double support in the gait cycle. To date, such a conclusion of phase related vestibular modulation has not been reached in any locomotor task examining vestibular contributions in humans. The observation of greatest vestibular up-regulation during double support leads to the postulation that vestibular information is important for the purpose of assessing the success of postural strategies during locomotion, as well as providing information on body position to facilitate programming of limb trajectory during locomotor tasks.  iii  Table of Contents  ABSTRACT  ii  Table of Contents  iii  Table of Figures  vii  CONTRIBUTION OF T H E A U T H O R ACKNOWLEDGEMENTS C H A P T E R 1 Introduction and Literature Review 1.1  General Introduction 1.1.1 Thesis Overview  1.2  x xi 1 1 4  Summary and goals of thesis  4  1.2.1 Testable Hypotheses  5  1.2.1.1  Experiment 1  5  1.2.1.2  Experiment II, parts I and II  5  1.2.1.3  Experiment III  6  1.2.1.4  Experiment IV  6  1.3  Statement of Ethics  6  1.4  Senses involved in postural control  7  1.4.1 Vision and Somatosensory information  7  1.4.1.1  Vision.  7  1.4.1.2  Somatosensory  8  1.4.2 The vestibular system: anatomy andfunction 1.4.3 What are the roles of the vestibular system? 1.5  The vestibular system: How to study it 1.5.1 How do we test the vestibular system? 1.5.2 Advantages of using GVS as a technique  9 11 13 13 14  1.5.3 What does GVS do? What system is affected, otoliths or semicircular canals? 15  1.6  1.5.4 What is the response to GVS?  16  1.5.5 Sensory integration - why study integration?  18  The vestibular system: Which tasks are best to study and why? 1.6.1 Why examine vestibular contributions during dynamic tasks?  21 21  1.6.1.1  Animal and patient based evidence  21  1.6.1.2  Dynamic responses to G V S  22  iv  1.6.1.3  Platform Perturbations  24  1.6.2 Rationale for the Selection of tasks in the present research  25  1.6.2.1  Step initiation  25  1.6.2.2  Gait initiation  25  1.6.2.3  Steady state gait  27  C H A P T E R 2 General Methods  •  28  2.1  Subject Preparation and Equipment  28  2.2  Galvanic Vestibular Stimulation  29  2.3  Statistics  30  C H A P T E R 3 Experiment 1  31  3.1  Introduction  31  3.2  Methods  32  3.2.1 Subject preparation  and Equipment  32  3.2.2 Test Procedures  32  3.2.3 Data Reduction  33  3.3  Results  33  3.4  Discussion  37  3.5  Bridging Summary  38  C H A P T E R 4 Experiment II part 1  39  4.1  Introduction  39  4.2  Methods  41  4.2.1 Subject Preparation  and Equipment  41  4.2.2 Test Procedures  41  4.2.3 Data Reduction  42  4.3  Results  43  4.4  Discussion  46  4.5  Bridging Summary  50  C H A P T E R 5 Experiment II part II  51  5.1  Introduction  51  5.2  Methods  53  5.2.1 Subject preparation  and Equipment  53  5.2.2 Test Procedures  54  5.2.3 Data Reduction  55  V  5.3  Results  57  5.4  Discussion  63  5.5  Bridging Summary  67  C H A P T E R 6 Experiment III  68  6.1  Introduction  68  6.2  Methods  71  6.2.1 Subject Preparation  6.3  6.4  6.5  and Equipment  71  6.2.2 Test Procedures  72  6.2.3 Data Reduction  72  Results  74  6.3.1 Upper Body Response  74  6.3.2 Lower Body Response  79  Discussion  82  6.4.1 Upper Body Response - vision occluded  82  6.4.2 Upper Body Response - vision present  83  6.4.3 Lower Body Response- vision occluded  84  6.4.4 Lower Body Response- vision present  86  Bridging Summary  87  C H A P T E R 7 Experiment IV  88  7.1  Introduction  88  7.2  Methods  90  7.2.7 Subject Preparation  and Equipment  90  7.2.2 Test Procedures  91  7.2.3 Data Reduction  92  7.3  Results  93  7.4  Discussion  98  C H A P T E R 8 Conclusions and General Discussion 8.1  General Findings 8.1.1 Up-regulation  103 103  in dynamic phase  103  8.1.2 Phase dependency - Upper Body  104  8.1.3 Lower limb phase dependency  105  8.1.4 Vestibular up-regulation  106  during Double Support  8.1.5 Vestibular roles in dynamic movement control  107  C H A P T E R 9 References  vii  Table of Figures Figure 3.1 Results are shown for four individual subject's raw displacement data, (a) G V S polarity has a significant effect on locomotor trajectory as demonstrated by the conditions R3, N and L3. Data from three representative subjects (1,4, and 6) illustrate the increasing magnitude of the response in conjunction with an increase in G V S for (b) a symmetrical subject (c) an asymmetrical subject with the asymmetry towards the left anode and (d) a subject demonstrating a less intense response to the stimulus 35 Figure 3.2 A n average of the cumulative sum of the slopes (CSS) for all subjects (n=9) is represented. Data are included that demonstrate displacement of the first 280 cm from the start position. Slopes were calculated between each of the eight points, 40 cm apart, including the starting position. CSS allows for observation of the individual changes from one location to another, in addition to additive changes that contribute to the trajectory deviations. Asymmetry can be observed between the magnitudes of R and L anode stimulation. L I , L2, L3 and R l , R2, R3 are the three intensity levels of stimulation used on the Left and right side respectively. N represents the no stimulation control trial 36 Figure 4.1 A ) Transverse plane view of the average CoP (thick lines) and C o M (thin lines) trajectories, as well as the initial and terminating positions of the left and right external malleoli and fifth metatarsal heads, across subjects for conditions without (centre CoP/CoM trajectories; filled circles for foot markers) and with stimulation (extreme left and right CoP/CoM trajectories; squares for stance side anode and triangles for swing side anode for foot markers). B) Relative C o M positions at 8 different points during stepping with the anode electrode over the stance (thick line with squares) and swing (thin line with triangles) limbs. C) Relative CoP positions at 8 different points during stepping with the anode electrode over the stance (thick line with squares) and swing (thin line with triangles) limbs. The asterisks indicate significant differences (p<0.05) between conditions of stimulation versus no stimulation 44 Figure 4.2 Mean CoP trajectory (A, B , E, F) and time integral (C, D, G, H) data in the anteriorposterior (A to D) and lateral (E to H) directions during the initial (left column) and latter (right column) phases of step execution. CoP trajectories are shown for conditions of no G V S (dashed lines), G V S with the anode electrode over the swing limb (thin lines) and G V S with the anode electrode over the stance limb (thick lines). Positive integrals (light grey bars) indicate movement to the swing limb and negative integrals (dark bars) indicate movement to the stance limb. CoP trajectory data (A, B , E, and F) are normalized to foot width (lateral data) or length (anterior-posterior data). The asterisks indicate significant differences (p<0.05) between conditions. (T02 toe-off of the stance limb, HC2 heel contact of the stance limb) 45 Figure 4.3 Mean absolute roll (frontal plane) angles of the trunk for conditions with G V S relative to non-GVS data. The initial deviation at G V S onset has been removed. The asterisks indicate significant differences (p<0.05) between conditions 47 Figure 5.1 Group averages are presented for a) Kinematic roll data from the head, trunk and pelvis (degrees) and b) kinetic M - L CoP (cm) over the time period 100 ms before the onset of the G V S perturbation until the time the auditory tone sounded 1500 ms later. Gray solid lines represent trials where the G V S anode was on the side of the swing leg, black solid lines are trials where the G V S anode was on the side of the stance leg and the dashed line represents no stimulation. Positive shifts in body roll and CoP indicate movement to the  viii  right (swing side) and negative shifts represent movement to the left (stance side). Data is separated into eyes closed in the left hand column, and eyes open in the right hand column. Vertical dotted lines represent onset of G V S (left) and tone (right) 58 Figure 5.2 M - L CoP (thick lines) and M - L C o M (thin lines) over a normalized time base averaged across all subjects. Trials with anode on the swing side are represented by grey lines, anode on the stance side are black lines and trials with no stimulation are dashed lines. Trials with no stimulation are labeled ECSP for eyes closed, and EOSP for eyes open. Important events during the step are labeled along the x-axis and are highlighted on the graphs with thin dotted lines. M - L CoP and C o M are expressed in cm 59 Figure 5.3 Group means are presented for a) Kinematic roll data from the head, trunk and pelvis (degrees) and b) kinetic M - L CoP time series (cm) and integrals (normalized to foot width). Data are presented from M - L CoP onset until toe off of the first foot (swing limb). Vertical dotted lines represent the events: maximum posterior CoP excursion (AP max) and Toe-off of the swing limb (Toe-off 1). hi time series graphs, lines represent G V S with anode on the side of the swing limb (gray), G V S with anode on the side of the stance limb (black) and no stimulation (dashed lines). Bar graphs represent the positive (gray) and negative (black) integrals of the M - L CoP time series data. Positive shifts on all graphs refer to movement to the right (towards the swing limb) and negative shifts represent movement to the left (towards the stance limb). Data are separated into eyes closed (left column) and eyes open (right column). EOSP and ECSP represent trials with no stimulation with eyes open and closed respectively 61 Figure 5.4 Group means are presented for a) Kinematic roll data from the head, trunk and pelvis (degrees) and b) kinetic M - L CoP time series (cm) and integrals (normalized to foot width). Data are presented from heel contact of the swing limb (HC1) until the end of stimulation. Vertical dotted lines represent Heel contact of the swing limb (HC1) (indicated with arrows), toe off of the stance limb (T02), heel contact of the stance limb (HC2) and the end of stimulation. In time series graphs, lines represent GVS with anode on the side of the swing limb (gray), G V S with anode on the side of the stance limb (black) and no stimulation (dashed lines). Bar graphs represent the positive (gray) and negative (black) integrals of the M - L CoP time series data. Positive shifts on all graphs refer to movement to the right (towards the swing limb) and negative shifts represent movement to the left (towards the stance limb). Data are separated into eyes closed (left column) and eyes open (right column). EOSP and ECSP represent trials with no stimulation with eyes open and closed respectively 62 Figure 6.1 Absolute roll responses in head, trunk and pelvis in the frontal plane (degrees) averaged across subjects (with control subtracted out) with the eyes occluded (left column) or open (right column). Positive roll values indicate roll toward the right, in response to anode right stimulation and negative values indicate roll toward the left, in response to anode left stimulation. Each condition, A P A (light grey), TO (dark grey) and H C (black), are aligned to the onset of stimulation for the trial, indicated by a vertical dotted line. The horizontal axis indicates divisions of 100 ms time epochs. Arrows indicate the onset of counter roll of the head. Figures at the bottom illustrate the specific events at which stimulation occurs 75 Figure 6.2 Absolute head roll responses (frontal plane) averaged across subjects with the eyes open (open circles) and eyes occluded (filled circles) are presented for the three conditions A P A (light grey), TO (dark grey) and H C (black). Control trials are subtracted out. Positive  ix  roll values are roll to the right in response to anode right stimulation, negative values indicate roll to the left in response to anode left stimulation. A) vertical line indicating time of significant visual attenuation (600ms after stimulation). B) vertical line indicating time of average peak head roll 76 Figure 6.3 Peak magnitude of absolute roll responses in the frontal plane for head, trunk and pelvis (degrees) are presented. Trials with eyes occluded are in the left column and eyes open in the right column. Significant differences between events are shown with asterisks. Peak magnitude of segment roll is attenuated with vision. Significance tested at p<0.01.... 78 Figure 6.4 Foot placement changes during forward locomotion with G V S delivered at one of three times (APA; light grey, TO; dark grey, H C ; black) or without G V S (no stimulation; shaded) with the eyes occluded (A) or open (B). Foot prints indicate the position of the foot at each step (cm). Stimulation with anode left is displayed in the left column, anode right in the right column. Note that due to the time of stimulation, 'Step One' after stimulation for H C trials are the second step in the diagram. For both A P A and TO 'Step One' after stimulation is the first step documented. Asterisks indicate significant differences between the stimulation trial indicated (APA, TO or HC) and no stimulation. Significance tested at p< 0.01 81 Figure 7.1 Segment roll (frontal plane) data is presented from the head, trunk, and pelvis averaged across subjects. Data have been normalized to specific events in the gait cycle (heel contact: H C , mid-stance: M S , toe-off: TO, second right heel contact: RHC2, second toe-off with right limb: RT02) as indicated by the vertical dashed lines (percentage). H C (Black line), M S (dark grey line) and TO (light grey line) trials are presented (control trials subtracted out). In stimulation trials, galvanic vestibular stimulation (GVS) was delivered at one of the three events indicated by the arrows. Positive roll represents movement to the right, negative roll is movement to the left. No significant differences were found for the magnitude of roll between the three event conditions for head, trunk or pelvis roll. Note, phase 4 (300%-400%) is proportionally longer in duration than the other phases 95 Figure 7.2 Foot placement data averaged across subjects are presented. Data are aligned to the right foot, which is the foot that corresponds to the onset of stimulation for heel contact: H C (black), mid-stance: M S (dark grey) and toe-off: TO (light grey). The first step, taken with the left foot represents 'Step One' after stimulation for the trials where stimulation is delivered at H C and M S . The next step, taken with the right foot, is 'Step Two' after stimulation for the H C and M S trials, but is 'Step One' after stimulation for TO trials. The following step with the left foot represents 'Step Two' for the TO trials. Data are presented in both directions in metres. Significant differences are found by 'Step Two' after stimulation, between H C and no stimulation for both polarities (left and right) and also in 'Step Two' for TO (anode right) from no stimulation, indicated by asterisks 96 Figure 7.3 a) Foot displacement (metres) and b) C o M displacement data (metres) averaged across subjects for the stimulation trials (control trials subtracted out) where stimulation was delivered at heel contact (HC), mid-stance (MS), or toe-off (TO), with the anode left (HCL, M S L , TOL) or right (HCR, MSR, TOR). 'Step One' represents the magnitude of deviation from non-stimulation trials in the first step after stimulation. Similarly, 'Step Two' represents the second step after stimulation. A significant difference in displacement was found between H C and M S for both foot placement and C o M displacement in response to the stimulation, indicated by asterisks. H C and M S were averaged across right and left conditions for testing. Standard deviation bars are shown 97  xi  ACKNOWLEDGEMENTS  First and foremost I would like to thank my supervisory committee, Dr. Tim Inglis, Dr. Brad McFadyen and Dr. Dave Sanderson for their patience, mentorship and invaluable advice throughout my Ph.D. I would like to express my deep gratitude to my co-supervisors, Brad McFadyen and Tim Inglis for their guidance and support, which made this thesis possible. Thank you for challenging me, and for providing the opportunity to accomplish all that I have during my Ph.D. Many thanks to Guy St-Vincent for his incredible patience and expertise. Sincere appreciation also to Francois Comeau, Martin Gerin-Lajoie, Marie-Claude Simard, and the rest of the Quebec crew for their time and commitment to this work, and making me feel at home. Thank you to all of the subjects who participated in this research and to my lab mates Cari Wells, Paul Kennedy, Michael Hunt, Kelly Moore and Gunter Siegmund who made those long days in the lab fly by. Special thanks to Paul and Cari for the fabulous figures. Finally, I would like to thank my husband Jesse. Without your love and support through the years this selfish endeavour would not have been possible.  1  C H A P T E R 1 Introduction and Literature Review 1.1  G e n e r a l Introduction  Of the sensory systems involved in postural control, the vestibular system is the least understood as far as its capacity to provide useful information for maintaining equilibrium. When assessing the importance of sensory information in balance we understand the impact of a healthy visual system and the necessity of our sense of touch and kinesthetic body awareness, but rarely do we consider how vestibular input helps us function while performing everyday activities. In particular, the control of balance in a stationary task requires maintenance of the centre of mass (CoM) within the confines of the base of support (BoS) (Das and McCollum 1988, Dietz and Duysens 2000). As bipeds, humans must control a C o M that is fairly high above a relatively small BoS. Successful maintenance of equilibrium in this task is not difficult provided we have use of visual, somatosensory and vestibular information. Control of equilibrium during more complex dynamic tasks such as locomotion, however, is only beginning to be understood, specifically the understanding of vestibular contributions to equilibrium control. Recent evidence indicates that vestibular information is not critical for triggering automatic postural responses evoked by support surface translation (Horak et al. 1994, Inglis and MacPherson 1995, Inglis et al. 1995). In addition, reports have shown that vestibular input appears to have a minor role in the control of quiet standing (Fitzpatrick and McCloskey 1994, Hlavacka et al. 1996). Specifically, it has been indicated that there is little to no role for vestibular information in the perception of sway, suggesting a greater importance for proprioception, and visual input during standing balance (Fitzpatrick and McCloskey 1994). In contrast, a reduction of vestibular afferent input has been shown to cause major deficits in the control of complex tasks, such as locomotion, that are dynamic in nature (Igarashi et al. 1970, Marchand and Amblard 1984, Inglis and MacPherson 1995, Peruch et al. 1999). The importance of vestibular contributions during dynamic tasks may not be surprising given the nature of the vestibular system and its measurement of acceleration. Both Igarashi et al. (1970) and Marchand and Amblard (1984) produced evidence showing that labyrinthectomized cats and squirrel monkeys exhibited extreme difficulty in completing complex dynamic tasks consisting of navigating a rotating rail apparatus. Subsequent work with vestibular deficient human participants demonstrated that although these individuals were capable of standing, and even walking forward with their eyes closed, they exhibited compensatory alterations during walking in their step width (Krebs et al. 2002), gait speed (Glasauer et al. 1994, Tucker et al. 1998) and duration of double support (Tucker, 1998). Furthermore these subjects exhibited great difficulty performing complex navigational locomotor tasks such as walking successfully without vision  2  through a previously traversed non-linear path (Peruch et al. 1999). To investigate the implications of these previous reports, which suggest a larger role for vestibular information during dynamic tasks (voluntary and involuntary), vestibular contributions were examined during forward walking and during the task of taking a voluntary step forward. Experiment I examined whether compensatory postural responses were exhibited during walking that could be considered large, relative to those previously observed in quiet standing, while using similar levels of vestibular perturbation. If so, this would suggest that vestibular information is indeed used to a greater extent during such dynamic tasks as forward locomotion. In addition, the secondary goal of Experiment I was to determine i f increasing the magnitude of the perturbation would result in a concurrent increase in the compensatory response. Observations from Experiment I revealed large responses to the vestibular perturbation, which were graded to the magnitude of stimulation. The evidence provided by the data in Experiment I support the hypothesis of a greater role for vestibular information during dynamic tasks. However, it is not clear precisely how and when this information is used in the control of movement. The next goal was to attempt to specify when the importance or "gain" of vestibular information is increased during a task. To examine this issue a forward step was observed in Experiment II, because it combined both static and dynamic postural goals during the transition from one standing posture to another. B y delivering a vestibular perturbation beginning 1500 ms prior to the initiation of a forward step it was possible to identify vestibular contributions while the subjects were standing, and then initiating and completing the step task. The results of this study support the findings from Experiment I, indicating a larger role for vestibular information during the more dynamic phase of the step task. Interestingly, despite application of the stimulus 1500 ms prior to the step onset, there was an absence of any vestibular response during the initiation of the step. The occurrence of a response later in the step suggests a difference in vestibular processing across the individual phases of the step task. These phases relate to the transition in dynamic state from a stationary position, into the step task. Although it has been demonstrated that visual information largely compensates for a vestibular deficit, visual input cannot substitute for the loss of vestibular information (Marchand and Amblard 1984, Lacour et al. 1997a). Visual flow cues can often be destabilizing, as the absence of useful vestibular and somatosensory information in the presence of optic flow can create the illusion of self-movement. A small number of studies have examined visual-vestibular interactions in patients with vestibular deficiencies (Peruch et al. 1999, Borel et al. 2001) or while using the technique of Galvanic Vestibular Stimulation (GVS) (Britton et al. 1993, Fitzpatrick et al. 1994b, Day and Bonato 1995, Bent et al. 2002). However, most research has ignored the  3  possible interaction between vision and vestibular information for controlling dynamic movement by focusing on trials without vision (Smetanin et al. 1988, Severac Cauquil and Day 1998, Day et al. 1997, Inglis et al. 1995). If the contribution of vestibular information in the successful completion of dynamic tasks is to be understood, vestibular information must eventually be put in perspective with the availability of other sensory modalities. To this aim Experiment II (part II) included both stepping with the eyes closed and with the eyes open, with the notion of providing a better understanding of how visual and vestibular information interact to help maintain equilibrium. Vestibular contribution alone and the integration of vision with vestibular information were demonstrated to differ across the dynamic phases (the transition from a stationary phase to a dynamic phase) of the voluntary step task. These observations led to the proposition that changes were due to 'dynamic' phase-dependent modulation and resulted in the development of Experiment III. Further investigation of phase-dependent vestibular modulation was performed using G V S as a means to probe vestibular contributions at specific times during the initiation of gait. Phase dependent modulation in Experiment III was examined with respect to the phases of the gait cycle, such as single and double support. The concept of phase-dependent modulation based on events in the gait cycle is not new, and is certainly not without precedent in other sensory systems. Research during the dynamic task of locomotion has demonstrated phase related changes in the contribution of cutaneous information (Zehr and Stein 1999, Wand et al. 1980, Forssberg et al. 1979, Eng et al. 1994), muscle afferent input (Yang and Stein 1991, Sinkjaer et al. 1996, Capaday and Stein 1986) and visual information (Hollands and MarpleHorvat 1996). The initiation of gait was chosen for this study to enable examination of a task that was transitional, but did not involve the additional task of re-establishing a stationary equilibrium position such as during gait termination. The results provided evidence of vestibular regulation in the magnitude of both the upper body roll response and foot placement changes. The magnitude of changes to foot placement were found to be dependent on the event during initiation that the stimulation was delivered. In contrast, differences in the magnitude of upper body roll demonstrated an increase that appeared to follow the transition from a stationary position to the more dynamic phase of the task. The final study aimed to clarify the separation between the roles of vestibular contribution to upper body and lower limb control. It was hypothesized that phase dependent modulation of the upper body in Experiment III was due to dynamic changes during the transition from standing to gait initiation, and therefore would not be apparent i f upper body roll was examined during a steady-state. Changes to foot placement provided evidence of vestibular modulation linked to gait events, in support of the findings of Experiment III. The results also  4  confirmed the hypotheses of upper body control based on the transition in dynamic state from standing into gait initiation. 1.1.1 Thesis Overview The following section summarizes the goals and hypotheses of the thesis. The document continues with a literature review of relevant topics. Three sections are devoted to background research under the following areas, 1) sensory contributions in postural control, 2) Vestibular research techniques and the benefits of using the chosen technique of galvanic vestibular stimulation, 3) Rationale for the selection of the tasks chosen for the thesis research. Chapter 2 outlines the general methods common to the separate thesis experiments. Chapters 3 through 7 report the four experiments as follows, Chapter 3; Experiment I, Chapter 4 and 5; Experiment II sections I and II, Chapter 6; Experiment III, and Chapter 7; Experiment IV. Chapter 8 integrates the findings from the separate chapters and provides a general discussion of the conclusions of the thesis. 1.2  S u m m a r y and goals of thesis  The overall goal of this thesis is to determine the contributions of vestibular information during such dynamic tasks as forward walking, step initiation, gait initiation and steady-state gait. The response to G V S , at least in the upper body, has been well documented and is, therefore, a useful indicator of the degree of vestibular involvement at a particular time during a task based on the magnitude of the response. One additional goal is to investigate the integration of vestibular information with visual input by introducing visual manipulations. This line of examination serves to clarify the interaction of these two sensory systems, as the nature of their integration has been a topic of controversy. Based on these two goals, the thesis aims to gain insight into the potential roles for vestibular information in healthy young individuals performing dynamic tasks.  5  1.2.1 Testable Hypotheses Four studies were completed over the course of the thesis. Based on the rationale presented in section 1.1, ten hypotheses were developed. The hypotheses that were tested in each experiment are outline below: 1.2.1.1 Experiment I Experiment I involves Galvanic Vestibular Stimulation delivered at three different magnitudes, and two different polarities of stimulation during walking with the eyes closed. Based on evidence of increased vestibular contributions during dynamic tasks, and reports of incremental changes in the magnitude of the response in relation to the stimulation intensity during quiet standing (Coats 1973), the following hypotheses are proposed: 1 A)  Deviation in path trajectory is observed that is dependent on the polarity of the stimulation, with compensation occurring in the direction of the anode electrode.  IB)  A n increase in the intensity of the G V S perturbation results in an increase in the trajectory of the compensatory deviation. 1.2.1.2 Experiment II, parts I and II Experiment II part I includes the delivery of G V S 1500 ms prior to, and maintained  during the task of taking a step with the eyes closed. In part II the effects of vision are addressed. Based on evidence of increases in vestibular contributions during dynamic tasks and reports of visual attenuation during quiet stance, the following hypotheses are proposed:  2A)  Upper body segment roll (of the head, trunk and pelvis) and whole body sway (demonstrated through CoP changes) are observed with the deviation towards the anode electrode.  2B)  Greater deviations in upper body roll and CoP are observed during the more dynamic phase of the task.  2C)  Visual information is given highest sensory weighting and greatly attenuates both the roll of the upper body and changes in CoP in both quiet standing and during the more dynamic phase of the task.  6  1.2.1.3 Experiment III In Experiment III G V S is delivered during the process of initiating gait. The stimulus onset coincides with three events, the anticipatory postural adjustment (APA), toe-off (TO) of the swing limb, and heel contact (HC) of the swing limb. Evidence indicating feed-forward control during the initiation of gait, and reports of phase dependent changes across the step task of Experiment II as well as in other sensory systems, led to the following hypotheses:  3 A)  The G V S perturbation during the A P A does not result in changes to upper body roll or changes in foot placement.  3B)  Delivery of G V S at TO and H C results in polarity dependent responses that are observed in both upper body roll and changes in foot placement.  3C)  The magnitude of the response to G V S is different between T O and H C for both upper body roll and changes in foot placement, demonstrating modulation of vestibular information based on the event. 1.2.1.4 Experiment IV In the final study, Experiment IV, G V S is delivered during steady-state gait. The onset  of the stimulation is given at three different times that coincide with the events of the right limb; heel contact (HC), mid-stance (MS), and toe-off (TO). Based on the conclusions of phase dependent modulation in Experiments II and III, and evidence of separate control of upper and lower body responses, the following hypotheses are proposed: 4A)  Modulation of vestibular information is demonstrated in the foot placement responses to G V S , based on the event in the gait cycle at which GVS is delivered.  4B)  Upper body roll does not demonstrate vestibular modulation based on the event in the gait cycle that stimulation is delivered. 1.3 Statement of Ethics  A l l of the experiments documented in this thesis were conducted in accordance with the ethical guidelines of the University of British Columbia and Experiments II to IV were approved by the ethics committee of the Quebec Rehabilitation Institute and carried out at the Centre for Interdisciplinary Research in Rehabilitation and Social Integration.  7  1.4 Senses involved in postural control  1.4.1 Vision and Somatosensory information 1.4.1.1 Vision Vision provides information about the surrounding environment, about the motion of oneself relative to that environment as well as postural information about movement of body segments within the environment (Rossignol, 1996). Many studies have demonstrated that removal of visual information drastically decreases stability, as evidenced by measurements of sway in both young (Edwards 1946, Fitzpatrick et al. 1994a, Day et al. 1993) and elderly individuals (Judge et al. 1995, Woollacott et al. 1986, Colledge et al. 1994). Edwards (1946) reported an increase in sway of up to 100% when vision was eliminated, via eye closure or in a non-lit environment. Judge and colleagues (1995) found a substantial decrease in stability with removal of vision, specifically noting an increase in loss of balance by five to seven times when the proprioceptive information was also unstable. This was corroborated by Colledge et al. (1994) and Fitzpatrick et al. (1994b), both of whom reported an increased dependency on visual information when visual occlusion was accompanied by a decrease in the reliability of somatosensory information. Fitzpatrick et al. (1994b) further claimed that an increased dependency on visual information only exists when somatosensory information is unreliable. The importance of visual information is also apparent during locomotion, as has been demonstrated by alterations to optic flow during forward progression (Rossignol 1996). Visual perturbations induced by rooms that move in the direction of forward progression (Lee and Thomson 1982), as well as illusions of backward or forward velocity changes while walking (Konczak 1994, Lackner and Dizio 1993, Prokop et al. 1997) have demonstrated compensatory strategies during locomotion that accommodate for the contradictory, but dominant visual information. Other studies have demonstrated the importance of visual information during locomotion in the planning of an upcoming task (Hollands et al. 1995, Hollands and MarpleHorvat 1996, Patla and Rietdyk 1993, Patla et al. 1996). Hollands et al. (1995) reported visual fixation on the next of a progression of stepping stones at the point of successful foot contact on the previous stone. Fixation continues until the foot is placed safely on the stone in view. Hollands and Marple-Horvat (1996) went on to demonstrate that planning for accurate targeted stepping occurs during the last 100 ms of the stance phase, and likely involves peripheral images of the target prior to saccades for foveal fixation. Patla and colleagues (1991) have demonstrated that changes in locomotor directions cannot take place within the same step when the visual cue is given after heel contact. Although, these researchers report that small alterations in step length or width can be made within the same step cycle. As well, Patla et al. (1996), Patla and Rietdyk  8  (1993)and McFadyen and Winter (1991) have reported differences in obstacle avoidance strategies depending on the perceived height and depth of the object, demonstrating a reliance on visual input for on-line negotiations during locomotion. These findings are supported by research by Drew and colleagues (1996) that has demonstrated the importance of visual cueing in programming of the appropriate muscle sequence for obstacle avoidance. Pyramidal Tract Neuron (PTN) recordings in the cat were shown to increase in firing upon the approach of an obstacle. The researchers attributed the altered firing to visual modification of PTNs to facilitate accurate muscle activation for obstacle avoidance. Recent literature has highlighted the differences that exist in successful obstacle avoidance tasks dependent on the type of visual information that is available. The presentation of static visual cues using stroboscopic lights (with varying intervals) compared to continuous visual information, including dynamic movement cues, significantly affects the successful outcome of the task. Sherk and Fowler (2001) were able to show that cats were more successful at negotiating a pathway littered with a high density of small objects when continuous dynamic visual information was available to help with foot guidance. These data collectively demonstrate that vision plays a primary role in postural control, specifically indicating an importance in quiet stance, and more complex tasks such as walking and obstacle avoidance. 1.4.1.2 Somatosensory Somatosensory information refers to several groups of receptors relaying information about limb position, movement direction and speed, tactile cues, and pain. Cutaneous information and muscle afferent inputs are able to contribute information related to position and movement, and are therefore proposed to play a role in maintaining balance. Skin mechanoreceptors in the feet are thought to transduce pressure information regarding location of the C o M relative to the stability boundaries of the BoS (Maki et al. 1999, Magnusson et al. 1990b, W u and Chiang 1997). This has been demonstrated by a decrease in stability with a cooling of the skin on the soles of the feet, and therefore decreased information from the skin receptors (Perry et al. 2000, Santos et al. 2000, Magnusson et al. 1990a). Reduced stability has also been shown through the use of vibration (Kavounoudias et al. 1998, 1999a), or by anesthetizing the soles of the feet (Horak et al. 1990). In addition, decreases in cutaneous information have been examined naturally through degenerative neuropathic disorders (Inglis et al. 1994, van Deursen and Simoneau 1999). Proprioceptive information has been shown to have a role in determining limb position (Goodwin et al. 1972, Inglis et al. 1991) as well as contributing to behaviours used to modulate dynamic postural control (Zehr and Stein 1999, Allum et al. 1998). This has been verified by removal of spindle receptor information using ischemic blocks, which results in a reduced ability  9  to monitor sway (Thoumie and Do 1996, Diener et al. 1984, Horak et al. 1990) and a decreased ability to generate compensatory changes in propulsive force during treadmill walking (Figura et al. 1986). The use of vibration to generate compensatory movements in standing (Smetanin et al. 1988, Popov et al. 1986, Kavounoudias et al. 1999b, Hlavacka et al. 1995, Hlavacka et al. 1996) and walking (Bove et al. 2001), as well as balance testing through sway referencing (Nashner 1983, Nashner and Wolfson 1974, Horak et al. 1994), also demonstrates the contributions of this sensory information in controlling postural stability. Dietz and Duysens (2000) have reported the importance of load receptors, mainly thought to have contributions from golgi tendon organs, in the control of balance. The role of these receptors involve monitoring of stationary posture, as well as regulating transitions between stance and swing phases of gait, using phase dependent modulation of the receptor information (Pearson 1995, Pang and Yang 2000). Thus, the combination of information from these separate systems provides crucial information to the CNS on body position. Integration of this information with other sensory systems provides an abundant source of information to utilize for the planning and execution of tasks, enabling accurate monitoring of body segment position, and the maintenance of static or dynamic equilibrium. 1.4.2 The vestibular system: anatomy andfunction The vestibular system in humans is housed in a bony labyrinth in the inner ear, inside of which there is a membranous labyrinth that encases the vestibular organs. The vestibular end organs, located on each side of the head, include the three semi-circular canals: anterior (superior), posterior and horizontal and the otolith organs: the saccule and utricle. The semicircular canals are oriented with the anterior and posterior ducts projecting 45° from the sagittal midline. The horizontal ducts are oriented roughly 30° above the earth horizontal plane. The semicircular canals detect angular acceleration and are oriented orthogonal to each other in order to encode for acceleration in the three dimensions. Each canal functions in concert with a canal located in the contralateral vestibular apparatus. Information from the horizontal canals are integrated together to code for movement, whereas the alignment of the vertical canals enable the anterior canal from one side to correspond with information from the posterior canal of the other side. Coding of rotational acceleration in this manner allows for heightened fidelity of the signal. The otolith organs are designed to encode linear acceleration and are sensitive to the influence of gravity such that they are also able to code for static tilt. For this reason they are able to provide information of orientation with respect to vertical in a gravity-based environment. The orientation of the saccule, with its hair receptors in the gravitational plane make this sensory  10  organ susceptible to the influence of gravity on a regular basis. The utricle on the other hand is oriented to code for medio-lateral and anterior-posterior movement in the standing individual. Although the vestibular end organs are linear and angular accelerometers, it has been demonstrated that the vestibular system codes in velocity (ie. velocity information is relayed to the CNS) (Purves et al. 1997). The opposite, but complimentary information provided by the right and left labyrinth allows for precise, detailed information of movement. In addition, there is an inherent robustness in the otolith coding where depolarization of specific cells coincides with hyperpolarization of the mirroring cells, again increasing the fidelity of the code. The vestibular nerve projects from the end organs to ipsilateral vestibular nuclei, which are separated into medial, lateral (Deiter's), superior and inferior (descending) nuclei. Each of the end organs has specific projections to individual nuclei in the vestibular nucleus complex. The semicircular canals have their strongest projections to the medial and superior nuclei where they indirectly innervate oculomotor muscles via projections through the medial longitudinal fasciculus to control eye movements (vestibular-ocular reflex; VOR). Each horizontal canal is able to activate appropriate eye musculature for movement of both eyes in the compensatory direction (head movement left, eye movement right). Vertical canals on the other hand must act in conjunction with each other to activate synchronous movement of both eyes. The otolith organs have also been demonstrated to contribute to the V O R . The lateral vestibular nuclei (LVN) receive the greatest contributions from the otolith organs and in turn project to the cerebellum, the reticular formation, the thalamus, and the spinal cord (both cervical and lumbar). These descending projections to the spinal cord have been well documented as having facilitatory effects on ipsilateral extensor muscle activity (Grillner et al. 1971, Wilson and Peterson 1981, Wilson and Yoshida 1969). In addition, they are thought to have an influence on rhythmic behaviours (Orlovsky 1972b, Matsuyama and Drew 2000), as well as in postural control (Welgampola and Colebatch 2001a), and have been implicated in compensatory responses to galvanic vestibular stimulation (Fitzpatrick et al. 1994b, Britton et al. 1993) (GVS: see section 1.5.2). The peripheral vestibular afferents, which lead from the end organs to the vestibular nuclei have been shown to have an average firing baseline (100Hz mean frequency), which provides the opportunity for both an increase or decrease in firing code to detect movement of the head in a particular direction. Although the vestibular system has been documented as having its strongest roles in eye stabilization in a moving environment (VOR), and in head stabilization in space (vestibulo-collic reflex; V C R ) , it has also been shown to play a significant role in more complex movement, including balance and postural control, when combined with other sensory information (Hlavacka et al. 1996). The firing code contains information, which helps relate the  11  orientation of the head with respect to the body (with integration from neck proprioception), and the orientation of the head relative to the support surface (with integration of proprioceptive input and plantar pressure information) (Pozzo et al. 1995). However, these are just a sample of some of the roles of the vestibular system. 1.4.3 What are the roles of the vestibular system? The most prominent functions of the vestibular system involve its role in head stabilization (VCR) and eye control (VOR). Complex interactions occur between the vestibular nuclei and their projections (ie. to neck muscles, and to eye muscles) during voluntary movements to allow gaze and image fixation to occur. V O R is an important reflex that enables stabilization of the foveal image for object visual capture. This reflex allows humans and animals to fixate on an object during movement, which may be critical in determining postural strategies around or over an object or physical capture of an object i f it is prey. Head movement for path visualization (Vallis et al. 2001, Hollands et al. 2001) and gaze in a viewer centred environment (Ivanenko et al. 2000) have been shown to have a role in locomotion and postural control. Therefore stabilization of the eyes and head play an integral role in postural strategies. Head stabilization during locomotion (Pozzo et al. 1990) and during complex balance activities (Pozzo et al. 1995) results from a strong attenuation of head movement in space. Pozzo and colleagues (1990) demonstrated that to enable visual fixation of a target, vertical translations of the head during locomotion were coupled to rotation in the pitch plane, which was suggested to be mediated by otolith projections to neck muscles (VCR). These researchers also speculated that head stabilization about the horizontal plane makes it simpler for the integration of gravity and linear motion for the interpretation of body movement in space. It was later reported, with similar implications, that stabilization of the head vertically makes it easier to make the transition from the head centred reference frame to the exocentric reference frame for postural control (Pozzo etal. 1995). Although vestibular information appears to have the strongest influence in controlling V O R , and V C R , more roles have become apparent, as indicated by the research of Pozzo and colleagues (1990, 1995). Evidence suggests the vestibular system does not have strong connections to motorneuronal pools in the lower limbs via vestibulospinal pathways, although connections are apparent when specific balance testing is performed (Fitzpatrick et al. 1994b, Britton et al. 1993, Watson and Colebatch 1997) or when vestibular neurons are directly activated (Orlovsky et al. 1972a). Research has provided evidence of vestibular contributions to whole body postural control through short and medium latency activation of triceps surae in response to galvanic vestibular stimulation (GVS). These short and medium latency responses are thought to  12  have a direct role in maintaining balance (Welgampola and Colebatch 2001a). Recent evidence using the application of GVS suggests that the medium latency response observed in the soleus muscle is due to polysynaptic connections from vestibular nuclei, via the vestibulo-spinal pathway, to the soleus motoneuron pool (Kennedy and Inglis 2001). This was established using an H-reflex test pulse to measure the influence of the descending vestibulospinal drive to the excitation, or inhibition of the motoneuron pool. Alterations in the size of the H-reflex response were observed to occur in these subjects despite their prone position. This observation suggests that the medium latency response, although largely affected by postural influences during standing, is likely to result from specific vestibulospinal connections not directly involved with balance while prone. Modulation of both the medium latency and short latency response to G V S was also demonstrated by Welgampola and Colebatch (2001a). These researchers reported that increases in available postural sensory information (vision, tactile cues) were able to alter the size of the G V S evoked E M G response suggesting that these vestibulospinal connections are involved in postural control. Observations of dynamic tasks have indicated that vestibular information is important for modulating the magnitude (Allum et al. 1985, MacPherson and Inglis 1993, Inglis et al. 1995, Hlavacka et al. 1999) and end position (Inglis et al. 1995) of responses to perturbation. In addition, vestibular input has been shown to have a role in monitoring the position of the head in a voluntary dynamic head tilting task (Severac Cauquil and Day 1998). These studies have suggested that vestibular feedback is used to assess the postural response, or the voluntary movement to determine whether the task was completed successfully. The use of vestibular input in this manner has been termed sensory reafference. Day and colleagues (1997) have also demonstrated evidence of a large role for vestibular information in helping maintain the body segments in an upright position relative to a gravity based vertical reference frame during quiet stance. Although the importance of vestibular information is often overlooked in the context of other sensory information, existing research implicates vestibular information as a strong contributor in the maintenance of postural stability, especially in dynamic tasks. Therefore, vestibular information appears to have a much larger role than simply head stabilization and eye control.  13  1.5 T h e vestibular system: H o w to study it  1.5.1 How do we test the vestibular system? Several techniques, including examination of patient populations, vestibular deficient animals and the use of caloric vestibular stimulation, have been used to assess the vestibular system, its function and contribution to movement control. To a large extent researchers have looked at the ability of humans (Horak et al. 1994, Glasauer et al. 1994, Shupert and Horak 1996, Runge et al. 1998, Magnusson et al. 1990b) and animals (Igarashi et al. 1970, Marchand and Amblard 1984, Inglis and MacPherson 1995, Lacour et al. 1997b) to function without an intact vestibular system. Marchand and Amblard (1984) found, as did other researchers (Lacour et al. 1997b, Xerri and Lacour 1980), that removal of the vestibular system in cats resulted in a remarkable recovery of the ability to perform simple daily tasks, indicating that the cats were able to adapt to their new equilibrium state. However, what they also discovered was that these animals had a large deficit in their ability to function during complex dynamic tasks, such as walking along a rotating rail. Similarly, Peruch et al. (1999) reported that patients within one month of undergoing a unilateral vestibular neurotomy were able to make accurate navigational rotations around a room by using other sensory cues while moving to target locations. However, it was postulated that patients never fully recovered a proper internal representation of their body in space, leading to deficits in their ability to perform complex navigational tasks. Another technique used to assess vestibular activity is caloric vestibular stimulation (CVS) (Kubo et al. 1997, Stockwell 1997). Besides being quite unpleasant for the patients involved, the stimulation is also somewhat unreliable (see section 1.5.2, next section). This technique involves introducing different temperatures of water into the inner ear so as to indirectly affect the firing rates of the vestibular afferents. Caloric irrigation specifically affects 1  the receptors in the semi-circular canals resulting in the changes to the firing frequency of the peripheral vestibular afferents, depending on the position of the head. Changes in the firing rates of the peripheral vestibular afferents mimic changes encountered with actual movement of the head in space. Finally, a technique called galvanic vestibular stimulation (GVS) has regained interest as an assessment tool. G V S involves the application of electrodes over the mastoids processes, where the current is delivered to the peripheral vestibular afferents. Application of the electrodes is generally binaural (behind both ears) and bipolar (one side cathode, the other side anode). Other configurations are also used, such as monopolar (one polarity) or monaural (behind one ear). The application of bipolar stimulation results in an alteration in firing rate where there is a decrease in afferent firing (anode) on one side, while there is an increase (cathode) on the other  14  side. One advantage to using the technique of G V S is the ability to apply the current for a specific amount of time. In fact there are many benefits to this technique as will be described in the following section. 1.5.2 Advantages of using GVS as a technique There are several inherent problems with using C V S or patient and animal vestibular deficient populations, which limit the possibility of establishing the precise vestibular contribution to postural control. One strength of the caloric vestibular test, developed primarily for clinical application to assess patients, is that it is one of the only devised tests that can distinguish between lesions in one ear versus the other. However, this technique primarily assesses function of the semi-circular canals (Stockwell 1997, Goldberg et al. 1984) in addition to having a very slow reaction time (Proctor 1988). One of the largest problems with C V S however, is the inability to calibrate the stimulation (Stockwell 1997). The temperature and amount of fluid differs for different individuals making it difficult to control the degree of stimulation. In addition the caloric effect wears off over an unpredictable period of time making the effect transient and difficult to control. Proctor and Glackin (1985) attempted to assess the potential causes of the variability in caloric testing by examining the test, re-test reliability. These researchers examined nystagmus and oculomotor tests in addition to postural tasks. They determined that the largest factor in the variance was the psychophysical condition (alertness) of the subjects. For these reasons the results obtained with this technique are somewhat unreliable in their conclusions. Vestibular testing using subjects and animals with vestibular lesions (or removal) proves to be an effective method of determining individual postural abilities with a compromised vestibular system. However, researchers have noted considerable compensatory strategies in individuals over a period of months and years post-trauma (Lacour et al 1997a). Individuals have developed the ability to use other sensory modalities to partially replace their vestibular loss. This adaptation to the vestibular deficit draws attention to the possibility that these results may not accurately reflect the roles of the uncompensated vestibular system. The technique of galvanic vestibular stimulation (GVS) although devised initially as a clinical tool for the assessment of vestibular lesions has proved to be a valuable tool for investigations into vestibular contributions in postural control (Coats and Stoltz 1969). The establishment of a clinical use for the technique was largely based on observed galvanic nystagmus responses. Coats and Stoltz (1969) decided, based on previous undocumented occurrences of galvanic induced sway, to develop a system that would be able to produce a measurable body sway movement. They found they could induce predictable body sway at  15  threshold levels as low as 0.5 mA, which was considerably lower than the 2.0 m A necessary to evoke the nystagmus response (which was reported as painful). From their study, they were able to report distinct body sway towards the anodal electrode and were the first to document the appearance of opposite body sway when the stimulus was removed (off effect). Since that time, postural research has benefited from the ability to now apply a discreet reversible stimulation at a specific intensity (adjustable to each participant's threshold) to assess vestibular roles in different tasks. The G V S perturbation is temporary so there is less concern with long term adaptation. In addition, there is a predictable lag time from stimulus onset until the beginning of the compensatory response allowing for delivery of the perturbation at specific times during postural tasks. For these reasons, using the technique of G V S as a tool has enabled many important observations regarding vestibular contributions to balance and postural control in healthy individuals. 1.5.3 What does GVS do? What system is affected, otoliths or semicircular canals? Although it is not known specifically how G V S is interpreted by the CNS, there is some evidence as to how G V S may be evoking a response from the system. Several studies have indicated that the application of G V S directly affects the first order vestibular afferents and not the end organs themselves (Spiegal and Scala 1943, Coats and Stoltz 1969, Moore et al. 1991). Coats and Stoltz (1969) examined the effects of G V S in a number of subjects previously diagnosed with either end organ lesions or lesions of the VIII cranial nerve. Based on their findings of galvanic distinction between the location of lesion, they concluded that galvanic stimulation effects manifest themselves through alteration in firing at the level of the peripheral vestibular afferent. Goldberg et al. (1982) have demonstrated that in the squirrel monkey, the delivery of G V S resulted in an asymmetric response in firing rate in the left and right peripheral afferents based on the location of the anode and cathode. The cathodal current resulted in an increase in the firing rate and the anodal current decreased the firing rate of the peripheral vestibular afferents. The change in firing rate is similar to that observed with natural head tilt in the direction of the cathode. Further work by Goldberg (2000) focused on the specific afferents that are susceptible to the galvanic stimulation. He reported that irregular firing afferents were easier to recruit at lower levels of stimulation intensity. He also documented that irregular afferents more frequently innervated the otolith organs of the vestibular apparatus than the semicircular canals, suggesting that G V S primarily recruited otolith afferents. Support for selective recruitment of otolith afferents was provided by Watson and Colebatch (1998b). These researchers demonstrated that E M G responses in sternocleidomastoid to a click stimulation (evoked using a lOOdB, 0.1 ms  16  audio click) were similar to E M G evoked with the delivery of GVS. As a result of the known otolith role in click responses (McCue and Guinan 1994), it was concluded that GVS also has a selectivity for activation of otoliths afferents. Low levels of GVS have also been shown to cause ocular torsion, which is an indicator of otolith afferent contribution (Zink et al. 1997). With increasing levels of GVS, prominent nystagmus is evident, which suggests increasing involvement of semi-circular canal information at higher intensities (Pfaltz 1970). It has, therefore, been suggested that the majority of GVS studies, which use stimulation ranges of 0.5 mA-2 mA, are recruiting afferents that receive contributions primarily from the otolith organs. Recent and somewhat contradictory work by Zhou et al. (2000) suggested that different afferents in the vestibular system code for translation versus tilt. These researchers concluded that regular firing afferents code for head orientation in space, following head tilt, and not linear translation. They also suggested that the regular firing afferents innervate the semicircular canals, indicating that these end organs are responsible for coding head tilt. The result of all of this information is the realization that it is still not known definitively how GVS physiologically affects the system. The benefit is that despite this realization, it does not prevent the valuable use of this technique in assessing the presence of vestibular contributions to postural control. 1.5.4  What is the response  to GVS?  The direction of the vestibulomotor response to GVS can be altered based on the position of the head in space (Lund and Broberg 1983, Nashner and Wolfson 1974, Hlavacka and Njiokiktjien 1985, Tokita et al. 1988), the perception of the position of the head in space (Popov et al. 1986) as well as the direction of gaze (Ivanenko et al. 1999). Application of both binaural bipolar (Britton et al. 1993, Fitzpatrick et al. 1994b, Nashner and Wolfson, 1974) and monaural monopolar (Smetanin and Popov 1990, Watson and Colebatch 1997) GVS have been shown to evoke different latency responses measured as E M G or CoP changes in relation to the onset of stimulation. Vestibulospinal projections have connections to extensor muscles in animals (Orlovsky 1972a, Matsuyama and Drew 2000) and have been implicated for their involvement in postural control responses for stability. In addition, indirect evidence of vestibulospinal connections has been demonstrated in humans (Kennedy and Inglis 2001, Britton et al. 1993). Nashner and Wolfson (1974) measured the response in the gastrocnemius and soleus muscles bilaterally in standing subjects while GVS was delivered binaurally at low intensities. Subjects were instructed to turn their head 90° towards the right or left shoulder. The resultant GVS response was altered from sway in the coronal plane with the head facing forward, to sway in the sagittal plane when the head was turned. The GVS response with the head facing to the side was  17  measured in the soleus and tibialis anterior muscles due to their postural control effect in the sagittal plane. In fact, research results highlight two distinct responses, which occur in the soleus EMG at short and medium latencies when GVS is delivered with the head facing to the side. When the anode is placed on the anterior ear, the short latency response creates an excitation of soleus. This early response in soleus has been reported to occur at a latency of 56 ms (Fitzpatrick et al. 1994b), 60 ms (Britton et al. 1993), and 50 ms (Watson and Colebatch, 1997). This response is a burst in soleus, which is opposite to the medium latency (soleus inhibition) response and has been suggested to result from a polysynaptic vestibulospinal connection (Watson and Colebatch 1998a). Recent work has shown that the short latency response disappears with age, in correlation with the loss of hair cells in the vestibular apparatus (Welgampola and Colebatch 2001c). The soleus medium latency response is inhibitory and has been reported for GVS perturbations in the sagittal plane with a latency of 100 ms (Nashner and Wolfson 1974), 115 ms (Britton et al. 1993), 105 ms (Fitzpatrick et al. 1994b), and 80-100 ms (Watson and Colebatch 1997). This medium latency inhibitory response in soleus is opposite to the early (short latency) response and has been suggested to result in the prolonged, late, forward sway towards the anode electrode (Fitzpatrick et al. 1994b, Smetanin and Popov 1990). Day and colleagues (1997) have also reported EMG changes occurring at 120 ms in response to a vestibular perturbation in the coronal plane. The latency and direction of these responses (towards the anode) were found to correlate with EMG responses previously reported in the sagittal plane. Use of the H-reflex technique has demonstrated that the GVS evoked medium latency response can affect the size of the H-reflex, independent of postural influences. Therefore these medium latency responses may be representative of specific vestibulospinal connections for purposes other than postural control (Kennedy and Inglis 2001). Kennedy and Inglis (2001) however, propose that these vestibulo-spinal connections are influenced by sensory input during postural tasks. Indeed, the prolonged forward sway in response to GVS has been proposed by several researchers to be postural in nature. Fitzpatrick and colleagues (1994b) attribute the sway response to a compensatory movement in the opposite direction to that of an illusory movement. Smetanin and Popov (1990), although they describe their concepts differently, agree with Fitzpatrick's group (1994b) by indicating that they believe the prolonged sway is due to changes to the spatial perceptual system as a result of the GVS perturbation. Evidence by Welgampola and Colebatch (2001a) also suggests that both the short and medium latency changes are in fact modulated by postural information. These researchers demonstrated a reduction in the size of the short and medium latency EMG response as additional sensory cues were introduced into a standing task.  18  The short and medium latency responses have also been shown to exist in the arm, but only when the arm is participating in balance control. These latencies were reported as 41 ms and 138 ms for the short and long latency responses respectively (Britton et al. 1993). The short latency response occurred in the soleus at approximately 60 ms compared to the latency in the arm of 35-40 ms which, based on conduction velocity, indicated that the onset of the responses were initiated by a motor centre that projected to both cervical and lumbar regions (Britton et al. 1993). In contrast, the late response was demonstrated to occur at a latency of 120 ms in the leg and 138 ms in the arm indicating different functional control from the early latency response. Britton et al. (1993) noted parallels between the distal to proximal muscle activation occurring with GVS and those that have been previously reported in support surface translations. In addition to the GVS vestibulospinal influences onto the motoneuron pool and the resultant E M G response, there are longer latency changes that occur in relation to the stimulation. GVS causes movement of the body towards the anode, depending on head position, perception of head position and gaze. Day and colleagues (1997) have described in detail, the body segment changes that occur when bipolar binaural GVS is applied to the mastoid processes of healthy subjects. In addition to the lean towards the anode (Coats and Stoltz 1969, Coats et al. 1973, Nashner and Wolfson 1974, Lund and Broberg 1983), Day et al. (1997) observed roll of the individual segments of the body in the coronal plane. Specifically, in response to GVS the magnitude of segment roll was greatest in the head, then in the trunk and least in the pelvis, essentially giving rise to a lateral bend as well as a sway in the body GVS response. In light of the results, Day et al. (1997) suggested the observed changes in segment orientation resulted from a response to the perception of a tilt in the support surface. They disagreed with the proposal that GVS evokes movement of the body to maintain an internal perception of vertical (Hlavacka et al. 1995), since an attempt to maintain a vertical position in the presence of GVS would give rise to strictly a lean and not differential movement of body segments. What they may not have considered is a dual role of vestibular information, which generates a sway to accommodate a change in verticality, and independent control of segments to alter their alignment relative to each other. 1.5.5  Sensory  integration  - why study  integration?  Although balance is optimal with contributions from visual, vestibular and somatosensory inputs, evidence that balance can be sustained in the absence of one sensory system demonstrates that there is redundancy between them. However, it is only through the integration of sensory information that we are fully capable of optimally operating in an environment where we are consistently experiencing challenges to equilibrium.  19  The presence of postural compensations to G V S suggests that the vestibular system plays a role in the maintenance of stability, even during quiet stance. However, the magnitude of the vestibular response is modifiable based on the availability of other sensory information and on the specifics of the task. Therefore these influences will dictate the weighting of vestibular information and consequently the size of the response. The concept of weighting infers that a sensory system will increase or decrease in its contributions to movement or postural control relative to the contributions from other sensory systems. For example, when the eyes are closed, both vestibular and somatosensory information are weighted more heavily to compensate for the lack of visual information. This is demonstrated by larger responses to vestibular (Welgampola et al. 2001a) and somatosensory (Wu and Chiang 1997) perturbations when the eyes are closed. In addition, weighting may also refer to the importance that the CNS puts on a particular sensory system given the situation. For the duration of the thesis, the weighting of vestibular information based on its individual sensory importance to a task will be referred to as up or down-regulation. We rely on information from other sensory systems to infer spatial orientation, as input from the vestibular organs can be ambiguous for movement. The input from the otoliths does not differentiate between static tilt and linear acceleration. Therefore critical information, such as that derived from cutaneous receptors and proprioceptive afferents as well as vision is used to help determine motion and orientation of the body. Britton and colleagues (1993) stated that vestibular compensatory responses, recorded as E M G activity, were only prominent i f the vestibular information served as the dominant source of information. They illustrated this by demonstrating a reduced E M G magnitude for the medium latency response when subjects opened their eyes or used haptic cues for orientation. Fitzpatrick et al. (1994b) showed a similar phenomenon by asking subjects to close their eyes on an unstable spring-loaded support surface. The unstable support surface resulted in unreliable proprioceptive information. The E M G response related to the G V S perturbation was shown to increase when the proprioceptive information was unreliable indicating a possible re-weighting of vestibular information when proprioceptive signals were compromised. When subjects opened their eyes, while on the unstable platform, there was a significant reduction in the G V S induced response, demonstrating a large visual influence. However, when the subject stood on a stable platform, the G V S E M G response was not attenuated in the presence of vision relative to the baseline E M G . Fitzpatrick and colleagues (1994b) concluded that vision does not factor into the re-weighting of the vestibular information unless the proprioceptive information is unreliable, and therefore visual inputs have a relatively minor effect on the gain of vestibular responses if appropriate proprioceptive cues are available. Nashner and Wolfson (1974), in addition to reporting head position and sagittal sway  20  went on to establish the effect of other sensory modalities on the G V S evoked sway response. Using a servo (sway referenced) platform participants were subjected to a situation, similar to that in Fitzpatrick and colleague's study (1994b), in which proprioceptive information became unreliable. In doing so, Nahsner and colleagues (1974) hypothesized that the vestibulomotor response to G V S would increase as the importance of vestibular information increased relative to proprioception. In effect, the medium latency E M G response reported by the researchers at 100 ms did not change in magnitude or latency. This was in direct contrast to reports by Fitzpatrick et al. (1994b) who documented significant increases in E M G when proprioceptive information was unreliable. The conflict may have arisen due to differences in the perturbation devices. Fitzpatrick et al. (1994b) were able to reduce the reliability of proprioceptive information from the beginning of the task by submitting subjects to a spring loaded unstable platform. Nashner and Wolfson (1974) removed appropriate proprioceptive feedback at the time of the response by not allowing the compensatory movement to change ankle angle. Instead of changes to the 100 ms evoked response, Nashner and Wolfson (1974) reported a later compensatory response that evolved as subjects C o M deviation moved beyond the stability boundaries. This C o M deviation was due to the sway referenced platform and the reduced ability to correctly execute the initial sway response. Therefore they believed that the change in proprioceptive information did not have an effect on the E M G response, when in fact i f the proprioceptive information was disturbed in advance, alteration of the G V S response would have occurred. Modulation of the G V S response was also demonstrated by a reduction of whole body segment roll with an increasing BoS width (Day et al. 1997). Each of the head, trunk and pelvis segments were significantly reduced in roll magnitude as the BoS widened from feet together to 16 cm (intermalleolar distance). However, the relative roll of the segments did not change with the increased width. The associated E M G was also reduced as the width increased. At 16 cm there was no measurable E M G in either the hip abductors or the ankle plantar flexors, suggesting that the increased stability through a large BoS decreased vestibular contributions to postural control. Disappearance, or attenuation of both the short and medium latency response in soleus, and tibialis anterior E M G was also demonstrated in studies where subjects were allowed to sit down, as noted previously (Fitzpatrick 1994b, Britton et al. 1993, Day et al. 1997), were provided with haptic cues (Welgampola and Colebatch 2001a, Britton et al. 1993), or if the trunk was supported (Fitzpatrick et al. 1994b). These findings support the conclusion that vestibular contributions are decreased when appropriate somatosensory information is available. Several reports have demonstrated attenuation of the G V S response when vision is present in quiet standing individuals (Day and Bonato 1995, Britton et al. 1993, Smetanin and  21 Popov 1990). In the study performed by Day and Bonato (1995), compensatory movement in response to GVS was measured as lateral movement of a marker on the seventh cervical vertebra (C7).  Results from this study indicated the degree of lateral translation of the individual. When  comparing the presence and absence of visual input, these researchers reported a substantial attenuation of the sway response when vision was available. In agreement with Day and Bonato (1995), Smetanin and Popov (1990) reported significant attenuation of the CoP sway responses (both short and medium latency) when vision provided orientation in space (via a visual target). However, the sway response was not attenuated when the visual information was referenced to the head (a target affixed to a rod attached to the subject's head) which does not provide an external reference cue for assessing translation. This suggests a dual vestibular role in quiet standing; control of whole body sway (body translation), and control of intersegmental alignment (segment roll). Visual information appears to not affect the GVS response for alignment. This is likely due to vestibular contribution in combination with proprioception being sufficient for monitoring head and body inter-segmental tilt. In contrast, whole body lateral shift is important to monitor for maintenance of equilibrium. The addition of vision as a sensory source helps to ensure the protection of stability. In light of the evidence suggesting the importance of sensory integration during postural tasks it is necessary to implement testing procedures, which take into consideration the availability of all sensory contributions to postural control. B y including or removing specific aspects of sensory information, one is better able to control and account for the information that is used to produce the observed response.  1.6 The vestibular system: Which tasks are best to study and why? 1.6.1  Why examine  1.6.1.1  vestibular  contributions  during  dynamic  tasks?  Animal and patient based evidence  Vestibular organs respond to linear and angular acceleration, which infers an active role of the vestibular system in dynamic-balance control. Evidence exists in both animal research (Igarashi et al. 1970, Marchand and Amblard 1984, Lacour et al. 1997b) and in studying patient populations (Borel et al. 2002, Peruch et al. 1999, Sasaki et al. 2001, Glasauer et al. 1994, Pozzo et al. 1991), in support of a larger role for vestibular information during dynamic tasks in comparison to quiet standing. In particular, animal studies have enabled the assessment of both acute and chronic models to assess how the removal of vestibular contributions can affect the successful completion of specific tasks. Igarashi et al. (1970) reported that, following unilateral  22  or bilateral labyrinthectomy, squirrel monkeys regained the ability to move about the environment, but complex dynamic postural control, such as negotiating a revolving rail apparatus, was compromised for many weeks in the unilateral and indefinitely in the bilateral animals. Similarly Marchand and Amblard (1984) showed that bilateral labyrinthectomized cats were unable to accomplish complex tasks. While the animals were capable of completing a simple wide plank locomotion task, suggesting visual compensation for their vestibular deficit, the cats were not able to walk across a narrow plank, indicating an essential contribution of vestibular information in performing tasks with high equilibrium demands. Deficits in complex dynamic postural control have also been demonstrated in humans with vestibular lesions, such as compromised spatial orientation during walking (Peruch et al. 1999), decreased ability to stabilize the head during dynamic tasks (Pozzo et al. 1991, Pozzo et al. 1995, Borel et al. 2001, Borel et al. 2002), and increased incidence of veering during path navigation (Cohen et al. 2000, Glasauer et al. 1994). Cohen and colleagues (2000) examined locomotor path trajectories of individuals with unilateral chronic vestibulopathy. These individuals had greater difficulty walking forward than age-matched controls, and veered from the path sooner when vision was removed. In addition, it was shown by Peruch and colleagues (1999) that one week following a unilateral vestibular neurotomy, patients were not able to accurately navigate a previously traversed path with their eyes closed. Visually guided navigation (using a virtual visual environment) was also affected in these patients, indicating that such complex spatial orientation requires integration of visual and vestibular information at a high level. Similar studies with patients after the completion of a vestibular neurotomy found that the orientation of subjective vertical was altered within the one week following the operation. Subjects tended to orient their head towards their lesioned side due to an altered perception of where vertical was (Borel et al. 2001). Similarly during the dynamic task of deep knee bends, unilateral vestibular neurotomy patients demonstrated deficits in both orientation of the head and trunk in space, and a decreased ability to stabilize the head in space. These findings collectively support the conclusion that vestibular information is critical in generating an accurate perception of the body in space to enable accurate and successful performance of complex tasks, specifically those which are dynamic in nature. 1.6.1.2 Dynamic responses to G VS The implementation of G V S during movement has provided evidence, to suggest that the vestibular system may have a larger role in dynamic tasks than during quiet stance, supporting previous patient and animal data. A n increased importance for vestibular information during dynamic tasks is highlighted in both involuntary movement due to vibration (Smetanin et al.  23  1988, Hlavacka et al. 1995, Hlavacka et al. 1996) and platform perturbation (Inglis et al. 1995, Inglis and MacPherson 1995, Hlavacka et al. 1999) as well as in voluntary tasks such as sagittal or frontal lean (Smetanin et al. 1988, Severac Cauquil and Day 1998), walking (Fitzpatrick et al. 1999, Bent et al. 2000a) and taking a step (Bent et al. 2002). The greater role for vestibular information during walking and other dynamic tasks is indicated by larger postural responses to galvanic vestibular stimulation (GVS) during such activities. Smetanin and colleagues (1988) noted a larger vestibular influence on the spatial perception system during either actual movement, or the illusion of movement. During either voluntary forward lean to bring the trunk to a flexed position, vibration induced forward lean, or the illusion of forward lean caused during vibration while restrained, the resultant M - L response to monaural G V S was largely enhanced compared to the G V S response in quiet stance. These researchers believe that not only does actual movement affect postural control centres causing a greater weighting of vestibular information, but the illusion of movement also results in larger compensatory responses to G V S . Severac Cauquil and Day (1998) confirmed these reports in voluntary leaning in the frontal plane with superimposed G V S . They demonstrated that the increased postural lean induced by G V S was only larger if the G V S induced vestibular error coincided with the performance of the dynamic task. Coincident onset of G V S and lean resulted in larger compensatory deviation than the delivery of G V S at the end of the lean, from a stationary position. As well G V S onset prior to movement, followed by performance of the lean (while G V S was still applied), resulted (when summed) in a total sway that was equivalent to G V S onset coincident to lean. These results indicated a relationship between the vestibular signal and dynamic movement. When movement occurred during the G V S perturbation, compensatory corrections were exaggerated, suggesting greater weighting of vestibular information during these tasks. Severac Cauquil and Day (1998) proposed that the vestibular system may have two roles during dynamic activities, which result in the increased compensatory response to G V S . Vestibular information is used largely for the control of orientation to maintain equilibrium, such as during quiet stance. In fact, they suggest there is a portion of the dynamic response, which is purely the static equilibrium response that is evoked in quiet standing. In addition, they suggested the vestibular system may be involved in the monitoring of the task in order to control movement of the head in space. The increased sway is proposed to result from vestibular upregulation during the task to provide information for monitoring the successfulness of the movement. Up-regulation of vestibular information for this purpose is termed sensory reafference and is in agreement with the theory developed by Inglis et al. (1995) in reference to the magnitude increase of postural corrections to platform perturbations (PP). As Severac  24  Cauquil and Day (1998) indicate, this purely dynamic response is added on to the static response to produce the increased GVS evoked sway during movement. 1.6.1.3  Platform  Perturbations  Further evidence supporting a larger GVS response during dynamic tasks is presented in studies observing compensatory responses to platform perturbations (Hlavacka et al. 1999, Inglis et al. 1995). Onset of GVS 500 ms prior to a platform perturbation has demonstrated that the net response (baseline platform response removed) to GVS in this dynamic situation is larger than the response of GVS on its own (Hlavacka et al. 1999, Inglis et al. 1995). Inglis et al. (1995) also examined the effect of GVS given during platform perturbations moving at different velocities. The results indicated that the response was larger when GVS was combined with the platform perturbation, with the greatest peak movement of CoP (forward or back depending on polarity) resulting from the fastest velocity, demonstrating that the vestibular system may have a larger role in higher velocity movements. Inglis et al. (1995) suggested that the increase in response to the vestibular perturbation was due to the important role that vestibular information plays in determining i f the correct postural response was executed. The latency of the reported GVS effects at 1.5-2.5s after movement onset indicated the possibility of a vestibular role in sensory reafference to help determine if the initial automatic postural adjustment was magnitude appropriate to establish and to maintain postural equilibrium. A vestibular role in determining vertical orientation was also highlighted by the change in final equilibrium position, which was biased towards the anode, suggesting a realignment of body orientation with a new internal vertical. Differences in final equilibrium position were also reported by Hlavacka et al. (1999) in a study examining response magnitudes associated with differing delay times between GVS onset and platform perturbation. These researchers found the largest shift in the final equilibrium position when GVS was presented 500 ms prior to the onset of the platform shift. This was due to the coincident timing of the GVS response peak and the onset of the platform shift. The second largest response was observed when GVS and platform shift occurred at the same time. Delays of 1.5 and 2.5 s resulted in the smallest perturbations. The increase in the time between GVS and the onset of platform perturbation decreased the resultant GVS response. This result suggests subjects had adequate time to establish a new stable position (relative to a new vertical) prior to the onset of platform perturbation. In a sense the two perturbations (GVS and PP) were treated as two separate events, and therefore had a response that was equivalent to the summation of the two. It was suggested by Hlavacka et al. (1999), as by Inglis et al. (1995) that the increased magnitude of the response to the GVS at 500 ms prior to shift is a result of sensory  25  reafference (feedback) of the postural movement indicating that the postural response needed to be adjusted in magnitude to establish the new perceived equilibrium position. 1.6.2 Rationale for the Selection of tasks in the present research The series of tasks that were chosen for the following research were chosen primarily because they represent tasks in which we participate daily. In addition, the goal was to investigate vestibular contributions during dynamic tasks, where empirical evidence has indicated larger responses to vestibular perturbations, suggesting a larger role for vestibular information in the successful completion of these tasks. The four studies outlined in this thesis will examine natural walking (beginning after one step), step initiation, gait initiation and the non-transitional task of steady-state gait (beginning after two steps). The preliminary study incorporated natural walking as a logical progression from other dynamic tasks, such as whole body leaning (Smetanin et al. 1988), voluntary lateral head tilts (Severac Cauquil and Day 1998), and dynamic platform perturbations (Inglis et al. 1995, Hlavacka et al. 1999) where an increased response to a vestibular perturbation has been demonstrated. The basic goal of the first project was to investigate the response to a vestibular perturbation during a voluntary locomotor task where the base of support was in transition, and not simply during a dynamic task with an unchanging BoS, such as leaning. The results from this preliminary study suggested a large increase in the use of vestibular information during walking as compared to what has been described previously for quiet standing, leading to the development of the next three studies. 1.6.2.1  Step  initiation  Step initiation is different from gait initiation in that it involves both the initiation and the termination of gait in two steps. The initial phase of the task is similar, in that equilibrium must be disturbed in order for the execution of the step to take place. Much like gait initiation, step initiation is characterized by a posterior and lateral shift of the CoP towards the swing limb (Lyon and Day 1997). This is promptly followed by the termination process whereby the CoP moves in front of the C o M and lateral in order to maintain the C o M within the confines of the base of support while equilibrium is restored (Jian et al. 1993). What is unique about this task is that in addition to involving both an initiation and a termination phase, it includes both a standing phase and a dynamic phase, which are soon followed by another standing phase. Essentially, this task provides the opportunity to look at processes that take place in the monitoring of balance across a series of transient periods. 1.6.2.2  Gait  initiation  Gait initiation is the transient period between upright standing and steady state gait  26  (Breniere and Do 1986, Couillandre et al. 2000, Mann et al. 1979). Gait initiation is interesting to study since it has well defined anterior-posterior (Crenna and Frigo 1991, Burleigh and Horak 1996) and medio-lateral (Mann et al, 1979, Mcllroy and Maki 1993, Lyon and Day 1997) events. The task of initiating gait features a destabilization of the body in order to begin walking, therefore making it a posturally challenging task likely to involve much sensory processing (Mann et al. 1979, Couillandre et al. 2000). Gait initiation is characterized by bilateral activation of tibialis anterior (TA) and inhibition of Soleus (Sol) causing a backward displacement of centre of pressure (CoP) and forward progression of the centre of mass (CoM) concomitant to activation of peroneal and/or hip abductor muscles of the swing limb to generate a lateral CoP shift in the direction of the swing limb (Mann et al. 1979, Breniere and Do 1986, Crenna and Frigo, 1991). In quiet stance the CoP position is located slightly in front of the ankles and is centered between the two feet within the base of support (BoS) (Mann et al. 1979, Crenna and Frigo 1991, Lyon and Day 1997). The BoS is the area defined by the maximum traverse distance between the left and right margins of the feet in contact with the ground (Mcllroy and Maki 1993). In quiet stance in healthy adults the C o M is held quite accurately within a small region that is directly above the CoP. The location of the CoP results from forces acting on the floor surface to control the position of the C o M within the BoS, while the location of the C o M is determined by the position of the body segments (Patla etal. 1990). During gait initiation, the BoS is reduced, becoming associated with the area beneath the stance foot. Before the foot is removed from the ground there is a shift in the CoP towards the swing limb. This lateral shift in the centre of pressure results from an asymmetrical vertical force produced for the purpose of moving the body C o M over the stance foot prior to swing leg lift ( Massion 1992, Mcllroy and Maki 1993, Rogers and Pai 1990, Mouchnino et al. 1992). This postural shift is called an anticipatory postural adjustment (APA). It is a predictive method of controlling posture, which acts to minimize resultant forces of forth coming movements (gait initiation) to enable the body to remain in a state of equilibrium. If an individual were to voluntarily lift a foot without first performing an A P A in the task of gait initiation they would need to control the imposed lateral instability after the foot was lifted. As a result, such voluntary movements are invariably preceded by the presence of medio-lateral A P A s which help defend against the lateral instability created when lifting one foot from the ground (Massion, 1992, Mcllroy and Maki 1993, Lyon and Day 1997). The onset and termination of gait initiation is not clearly defined. Most agree that the onset is depicted by a shift in CoP backwards and towards the swing limb (Jian et al. 1993, Mann et al. 1979, Lyon and Day 1997). Mcllroy and Maki (1999) more specifically defined the onset  27  of the A P A in gait initiation as the point when the M - L CoP was displaced a distance of greater than 4 mm above baseline sway towards the swing limb. The end of the gait initiation phase is less clearly agreed upon. Mann and colleagues (1979) indicated that steady state gait does not actually occur until at least three steps into gait. Jian and colleagues (1993) demonstrated that 90% of steady-state velocity is reached by first heel contact, but warn that full steady-state velocity is not achieved until the end of the second step. Others (Breniere and Do 1986, Lyon and Day 1997, Couillandre et al. 2000) indicate that the gait initiation phase is finished by first heel contact, via assessment of C o M velocity, which by this time has reached the value to be obtained during steady state gait. Criteria is discussed in the following section for the definition of steady-state gait used in the thesis.  1.6.2.3  Steady state gait  The time of onset for steady-state gait is disputed in the literature. Wearing and colleagues (1999) insist that "gait protocols should ideally involve a minimum preamble of at least three steps if representative [steady-state] gait patterns are to be obtained, (pp. 256)" Similar thoughts are echoed by other researchers who indicate at least two or three steps are needed for subjects to reach steady-state gait, which is determined by velocity of the C o M (Gormley et al. 1993, Jian et al. 1993, Nissan and Whittle 1990). For the purpose of the thesis, steady-state gait is considered to be achieved by the end of the second step, although data are not sampled until after step three. Steady-state gait has been well studied with respect to both sagittal (Winter et al. 1987, Winter et al. 1992), and frontal plane (MacKinnon and Winter 1993) control. Aspects of the gait process are well defined, such as the relative timing of single support and double support, the pattern of displacement of the CoP, and the muscles involved in generating a normal gait pattern (Winter 1990). This knowledge enables assessment of compensatory gait strategies used during periods of imposed instability. As a result, sensory contributions to the process can be studied. Jian et al. (1993) in their study concluded that" the maintenance of the whole body balance and posture during transient gait [such as during gait initiation] is even more challenging [than steady-state gait] because the destabilizing forces are far greater, pp 16). This implies that processes, which occur during steady-state gait, are more stable than those that take place at gait initiation or termination. For this reason, steady-state gait is interesting to study, since it implies that it may necessitate a reduced involvement of sensory feedback information, and may rely more heavily on planned feed forward control.  28  CHAPTER 2 General Methods 2.1 Subject Preparation and E q u i p m e n t  Similarities exist in the methods of data collection for Experiments II through IV. The following will be a detailed description of the methods common to these three studies. Brief outlines of these methods are then repeated in the individual method sections in each of the respective chapters (4 to7). The specific methodology involved in the collection of Experiment I will be reported within the chapter addressing that study (chapter 3). Healthy subjects between the ages of 18 and 45 were recruited for the thesis experiments. Individuals were excluded if they had a previous history of motion sickness, epilepsy, neurological or musculo-skeletal problems, or were pregnant. Subjects were informed of the protocol and were asked to provide written consent. A l l procedures were approved by the local ethics committees (University of British Columbia and the ethics committee of the Quebec Rehabilitation Institute) prior to data collection. For Experiments II through TV (chapters 4-7) three dimensional (3D) kinematic data were collected using an Optotrak (NDI inc, model 3020; two position sensors) motion measurement system. The resolution of this system is reported as 0.01 mm up to a distance of 2.25 m. This would allow for a resolution of much less than 0.01°. However, due to the possibility of calibration error and marker movement on the skin, the resolution has been adjusted and is reported throughout the document with a resolution of 0.01°. In each of the three studies subjects were prepared by affixing three non-collinear infrared light-emitting diodes (IREDs) on each segment to determine the segment position and orientation. Data from IREDs were relayed to the data collection system through a 'strober' device. Individual strobers were affixed to a Velcro belt around the subject's waist. In Experiments II and III, 27 IREDS were tracked. Three non-collinear IREDS were placed on each of the following segments: the foot (fifth metatarsal, lateral heel and dorsum of foot), shank (head of fibula, mid shank, lateral malleolus), and thigh (lateral femoral condyle, greater trochanter, mid thigh) bilaterally, as well as the pelvis (three IREDS affixed to a triangular structure placed over the sacrum at the level of the posterior superior iliac spines), the trunk (two markers were placed at the level of T8 under each inferior angle of the scapula, with the third positioned on the spinal column at the level of T12), and the head. IREDS for the head in Experiment II were placed bilaterally on the skin over the posterior aspect of the zygomatic arch (anterior to each ear), and a third on the forehead. Head markers for Experiments III and IV were affixed to a rigid triangular structure that was placed on the right anterior aspect of the head.  29  For project TV a total of 15 IREDs were affixed to the feet, pelvis, trunk and head only. The placement locations for these IREDs were as reported for Experiment III, except a triangle with three markers was placed on the side of each foot. Various anatomical landmarks were also assessed in all three experiments using the Optotrak system to enable calculation of segment length and C o M location. Calibration of the subject was performed at the onset of each experimental session to locate the IREDs with respect to the global reference system. If any marker was dislodged or moved during any trial an additional calibration was performed to ensure accurate IRED recordings. Data were collected at a frequency of 100 Hz in Experiment II and IV. In experiment III data were sampled at 75 Hz due to the number of channels being sampled and the limitations of the system. For C o M calculations, principle axes and C o M were first defined for each segment (MISCHAC Inc). Total body C o M position was then calculated for each data sample. In Experiments II and III total body C o M position was calculated using a 9 segment model (feet, shanks, thighs, and pelvis, trunk, head). In Experiment TV total body C o M was estimated using a calculation based on the head, trunk and pelvis segments alone. Kinematic data interpolation, filtering and calculation of segment linear and angular displacement, velocity and acceleration in three dimensions were performed (Kingait, M I S H A C , Waterloo Ontario). Additional calculations were performed using custom made software. Kinematic data were filtered using a zero lag, fourth order butterworth filter with a cut-off frequency of 6 Hz. Three force platforms (AMTI, model OR6-5) were used in Experiments II, III and IV. Data from all 18 channels (6 degrees of freedom per force platform) were digitized at 1000 Hz and filtered using a zero lag, fourth order butterworth filter with a cut off frequency of 50Hz. CoP displacement was calculated for each plate as the moment divided by the vertical force. The net CoP for all plates is calculated as the sum of the individual, local CoP of each plate in global coordinates. Data from the force platforms were also used to identify specific events and trigger the onset of stimulation in Experiments II-IV. Details are explained in the individual chapters. Video data were recorded during each testing session to allow qualitative assessment of the results and for presentation purposes. 2.2 Galvanic Vestibular Stimulation Bipolar, binaural Galvanic Vestibular Stimulation (GVS) was used in all experiments. Stimulation was delivered through two 9 cm carbon rubber electrodes that were placed on the 2  skin over the mastoid processes behind the ears of each subject. Before the electrodes were placed, the skin was cleaned with rubbing alcohol and conductance electrode gel was applied to the back of each electrode to improve conductance. Care was taken to ensure the electrodes fit  30  behind each ear, and 'pro wrap' was wrapped around the head, over the ears to secure electrode placement. Stimulation was delivered by a Grass Stimulator (Model Grass S48) through a constant current stimulus isolation unit ( A M Systems 2200). The intensity of the stimulation varied for each subject and was based on subject thresholds determined prior to data collection. The duration of the stimulation varied between experiments. During all experiments duration was adapted to ensure that the task was complete by the time the stimulation was turned off. This precaution was used to ensure that the responses recorded were due to the application of the stimulation, and not a possible effect resulting from the removal of the perturbation (Coats and Stoltz 1969). Threshold testing was performed in all four Experiments. Subjects stood with their feet at their natural stance width for testing in Experiments I and II. To facilitate determination of thresholds, testing in Experiments III and IV were performed during stance with the feet together (but not touching). Subjects were instructed to close their eyes and relax during the testing session. Periodically, subjects were allowed to open their eyes and re-orient themselves to the room and to shift their feet so as to prevent them from becoming unstable or fatigued while standing. G V S was delivered beginning with a current level of 0.05 m A and was incremented by 0.05 m A until threshold was reached. Determination of threshold was indicated at the current level when movement of the subject towards the side of the anode was observed by the experimenters, or i f subjects reported sensations of dizziness, or perceived movement. Anodal threshold was determined for both sides of each individual. The intensity of stimulation during Experiment I was set at one, two, or three times threshold. For Experiments II-rV the level used was set at three times the individual anodal threshold for all trials. Experiments III and IV used a minimum current of 1mA. 2.3 Statistics  Statistics were calculated using repeated measures A N O V A s . Tukey's Honestly Significant Difference (HSD) post-hoc tests were also used. Testing was done with p<0.05 in all studies, except Experiment III where p<0.01 was used due to multiple A N O V A s . Further statistical details are given in each individual chapter.  31  CHAPTER 3 Experiment I Magnitude effects of galvanic vestibular stimulation on the trajectory of human gait. (Published: Neuroscience Letters 279: 157-160, 2000)  3.1  Introduction  In recent years, galvanic vestibular stimulation (GVS) has proved to be a valuable technique for studying the role of the vestibular system in the control of standing balance in the human (Day et al. 1997). Previous work demonstrated that firing rates of the peripheral vestibular afferents were increased by galvanic currents at the cathode electrode, and decreased at the anode electrode (Minor and Goldberg 1991). During quiet stance, G V S evokes a body sway response in the direction of the anodal ear (Lund and Broberg 1983). While it has been suggested that the G V S evoked sway is a compensatory reaction to an illusory movement in the opposite direction (Fitzpatrick et al. 1994b), it may also function as a protective mechanism organized to prevent falls by guiding and improving the accuracy of voluntary motion of the head in space (Day et al. 1997, Severac Cauquil and Day 1998). In most G V S studies to date, fixed stimulation levels are commonly applied to all subjects. The minimum level of G V S required to evoke a postural response has not been investigated. Certain studies have attempted to adjust the level of stimulation for each individual (Inglis et al. 1995, Lobel et al. 1998, Hlavacka et al. 1999). Here we will demonstrate the importance of incorporating threshold concepts when investigating the magnitude effects of G V S during human locomotion. Despite progress, many questions remain unanswered with respect to balance control and equilibrium during locomotion. Following a bilateral loss of vestibular inputs, a large deficit in dynamic locomotor balance has been observed in both cats (Marchand and Amblard 1984) and monkeys (Igarashi et al. 1970) walking on a rotating surface. These experiments suggest the importance of vestibular information in complex tasks that require high-level balance information. Previously, the role of the vestibular system during walking in humans has been assessed using caloric vestibular stimulation (CVS) (Kubo et al. 1997), and by studying patients with vestibular pathology (Glasauer et al. 1994, Pozzo et al. 1991). Unlike these other methods, G V S can be applied at different phases during locomotion, with little discomfort to the subject and with reduced concerns of adaptation. G V S can be altered in both amplitude and duration, and finally, G V S is a highly controllable vestibular stimulus with respect to the known onset latency of its effects (Fitzpatrick et al. 1999, Lobel et al. 1998, Lobel et al. 1999). To date, a limited number of studies have utilized GVS to investigate the contribution of  32  the vestibular system during movement (Fitzpatrick et al. 1999, Inglis et al. 1995, Severac Cauquil and Day 1998, Smetanin et al. 1988). Only very recently has there been an investigation of the effects of G V S on walking in humans (Fitzpatrick et al. 1999). Fitzpatrick and colleagues (1999) have demonstrated that G V S during walking causes subjects to deviate in the anodal direction, similar to responses observed in quiet stance. In addition to observing a G V S polarity dependent deviation in progression, we report for the first time that the level of G V S can be used to manipulate the magnitude of this deviation during locomotion. 3.2 Methods  3.2.1 Subject preparation and Equipment Nine healthy young subjects participated in the study (4 men, 5 women, 22-28 years). Each provided written consent and indicated no history of motion sickness, epilepsy, or any neurological or musculo-skeletal problems. Video data were collected using a Panasonic digital video camera (model VW-D5100) that was mounted on the ceiling (6m high) perpendicular to the plane of locomotor progression. The view of the camera covered an area of 3.64 m wide by 4.86 m long. Reflective markers were placed on each acromion process of the subject. Binaural, bipolar G V S was delivered using two 9 cm carbon-rubber electrodes placed over the subject's 2  mastoid processes. A Grass stimulator (Type S48) delivered a square-wave pulse lasting 6-8s through a constant current stimulus isolation unit ( A M Systems 2200). G V S onset occurred upon first heel contact, triggered by foot switches underneath a thin wooden board. Industrial headphones were provided to remove any audio cues. G V S thresholds were determined separately for anode electrodes on the right and left mastoid processes for each subject prior to the onset of the experiment. Subjects stood at a natural stance width (Average 13 cm intermalleolar distance) with their eyes closed as they received square wave pulses of stimulation lasting 3 s, with pauses of random length (3-7 s) between stimuli. Threshold testing started at 0.05 mA and increased in 0.05 m A increments until threshold was reached. Threshold determination was based on definitive visible observations of sway, in conjunction with verbal reports of disorientation, related to the temporal onset of stimulation. If unsure of a response at a particular stimulus level, the experimenters increased the level and then reduced it again to help distinguish a real perturbation. 3.2.2 Test Procedures Seven conditions were tested: 3 levels of stimulation for both right (R) and left (L) sides, and no stimulation. The three levels of stimulation consisted of one (LI, R l ) , two (L2, R2), and three (L3, R3) times the subject's individual anodal G V S threshold for each side. Forty-  33  five trials, 5 of each stimulation condition and 15 no stimulation were performed randomly. A l l trials were performed with eyes closed. Subjects were required to begin walking from a natural stance width with their preferred limb, based on the limb chosen for initiation during practice trials prior to data collection. The use of this limb was maintained throughout the remainder of the trials. Initial foot position was marked to provide a constant starting location and foot width. Subjects were given practice trials to become accustomed to walking without vision, and to find a comfortable cadence. A t the onset of each trial, subjects faced forward, although no specific target was used, and initiated walking at their preferred speed upon a verbal command of "Ready, Set, Go". Subjects were required to maintain their cadence throughout the trials, and not to anticipate stopping. Subject's eyes remained closed while they were guided back to the start position in order to prevent visual feedback of locomotor deviation. 3.2.3 Data Reduction Using Peak Motus motion measurement software (Peak Performance Technologies), the midpoint trajectory of the R and L shoulder markers was obtained. Trials were cut off at a distance 280 cm from the starting location to allow comparison between subjects. Subject deviations out of camera view prior to the 280 cm cut off were rejected. This occurred in only 6 of 405 trials. Slopes of the trajectories, from the line of progression, were calculated at every 40 cm, beginning from the start position, which approximates an average step length (Glasauer et al. 1994). Each individual slope was calculated as the change in medial-lateral position from the point before, divided by 40 cm to produce a unitless number. The cumulative sum of slopes (CSS) was then computed for each section over the locomotor trajectory. A 3-way repeated measures A N O V A (stimulation, by stimulation magnitude, by progression position) was performed to determine the point during locomotion when conditions differed from one another. Post-hoc analyses were run using Tukey's Honestly Significant Difference (HSD) tests. Significance was determined at p<0.05. 3.3 Results G V S thresholds during quiet stance for the R and L anode of each subject ranged from 0.2 to 0.5 m A in agreement with other studies (Hlavacka et al. 1999, Inglis et al. 1995). Although all subjects demonstrated thresholds within this range, R and L thresholds were asymmetrical in six of the nine subjects. Asymmetries between the right and left thresholds ranged from 0.05 mA to 0.15 mA.  34  A l l subjects responded to the G V S with a deviation in walking trajectory toward the anode. Figure 3.1a is the raw displacement data from one representative subject showing five trials for each of the L3, no stimulation (N), and R3 conditions. During both L3 and R3 conditions, the subject began to deviate very early in the locomotion and continued to do so until instructed to stop walking. Figures 3.1b-d are examples of mean trajectory data for three individual subjects for all seven conditions. In response to progressively increasing G V S intensity, greater lateral deviations were observed in all nine subjects. Asymmetrical responses to both magnitude and polarity of G V S were also observed (2/9 L , 3/9 R, asymmetry). Figure 3.1c is an example of such asymmetry for one subject where the responses to anode L trials deviated further from normal than the anode R trials. Significant differences in CSS were shown for all conditions except between R3 and R2 (p < 0.05). However, significant deviations between conditions were reached at different points during forward progression. B y 40 cm into progression (point 2) L I , L2, and L3 were significantly different from N , and L I was different from L3. L I and L2 became different at point 5 and L2 from L3 by point 8. Both R2 and R3 were significantly different from R l and N by point 2. R l wasn't different from N until point 5. Figure 3.2 shows the average across subjects for the progressive increase in the magnitude of CSS at each 40 cm of forward progression as well as prior to locomotion where CSS is zero (point 1). The CSS continually increases, representing a maintenance or an increase in the magnitude of lateral deviation during locomotion, with each position significantly greater in cumulative slope than the last (Figure 3.2). This indicates that there was no evidence of subjects turning back in from the deviation, likely due to the nature of the instructions that did not indicate a specific locomotor target. As has been demonstrated recently by Fitzpatrick et al. (1999), G V S during walking caused subjects to deviate towards the anodal ear. However, in contrast to Fitzpatrick et al. (1999), the present study observed deviations in trajectory that were directly related to the level of G V S . A vestibular stimulus of one, two and three times the G V S threshold (range of stimuli 0.2-1.5 mA) resulted in an increasing amplitude of deviation in the walking trajectory.  \  35  I  0.5m  0.5m  T h r x3 T h r x2 T h r xl N o stini  Thrx 1  0.5m  .5m  0.5m 0.5m  Figure 3.1 Results are shown for four individual subject's raw displacement data, (a) G V S polarity has a significant effect on locomotor trajectory as demonstrated by the conditions R3, N and L3. Data from three representative subjects (1, 4, and 6) illustrate the increasing magnitude of the response in conjunction with an increase in G V S for (b) a symmetrical subject (c) an asymmetrical subject with the asymmetry towards the left anode and (d) a subject demonstrating a less intense response to the stimulus.  36  2.5  CSS  L3  L2  LI  N  Rl  R2  R3  Figure 3.2 A n average of the cumulative sum of the slopes (CSS) for all subjects (n=9) is represented. Data are included that demonstrate displacement of the first 280 cm from the start position. Slopes were calculated between each of the eight points, 40 cm apart, including the starting position. CSS allows for observation of the individual changes from one location to another, in addition to additive changes that contribute to the trajectory deviations. Asymmetry can be observed between the magnitudes of R and L anode stimulation. L I , L2, L3 and R l , R2, R3 are the three intensity levels of stimulation used on the Left and right side respectively. N represents the no stimulation control trial.  37  3.4 Discussion The use of G V S , although not novel as a tool, is new as a technique for perturbing humans during locomotion. Other studies have questioned the contribution of vestibular information in dynamic balance by utilizing C V S (Kubo et al. 1997) or by recruiting vestibular patients (Glasauer et al. 1994, Pozzo et al. 1991). The observations from these studies support data from animal models that indicate a strong role of the vestibular system in dynamic balance control (Igarashi et al. 1970, Marchand and Amblard 1984). However, both vestibular lesion studies and C V S have limitations in their ability to assess vestibular contribution. G V S has the advantage of creating a temporary and distinct vestibular perturbation resulting in the benefit of recording novel responses to vestibular errors. In the present study, deviation of individuals towards the anode may be explained partially by reports that G V S causes an increase in the firing rate of afferents on the side of the cathode and a decrease on the side of the anode in monkeys (Minor and Goldberg 1991). Increased firing on the cathodal side has been proposed to give one the illusion that, in a static position, the body is leaning in that direction and so compensation to maintain the whole body C o M within the limits of the base of support results in movement in the anodal direction (Day et al. 1997). Alternate studies suggest that the body utilizes vestibular information to maintain a reference body vertical, resulting in a compensatory movement towards 'perceived vertical' after vestibular information indicates movement in the cathodal direction (Hlavacka et al. 1996). In the present study, compensatory placement of the limbs in the first step was observed in most subjects in response to the high stimulus trials. The observed direction of the compensation suggests that subjects were responding to vestibular information that reported movement of body position (CoM location), or the reference vertical, in the cathodal direction. This resulted in placement of the limbs that would best prevent a further deviation of the C o M and would re-align 'vertical'. While the present experiment does not examine the specific nature of G V S the results suggest that the altered vestibular information during locomotion may have a profound effect on a subject's individual body reference frame. Finally, in contrast to Fitzpatrick et al. (1999), all subjects in our study demonstrated a graded increase in deviation as the intensity of the GVS increased. This observation demonstrates the ability of the vestibular system to differentiate between graded levels of information and contribute to an altered response magnitude. Most subjects did not show equal responses to GVS on both R and L sides. Importantly, these asymmetries were not correlated to the asymmetries found in G V S threshold determination, hi a series of pilot tests with three of the same subjects, we noted that L3 and R3 G V S caused noticeable deviations in walking trajectory even with eyes  38  open. We also observed that with running, trajectory was not greatly affected by G V S until the transition occurred when preparing to stop (unreported observations). This may indicate a hierarchical importance of vestibular information with slower paced dynamic tasks having precedence over static balance and running. A n explanation may lie in that slower paced ambulation may demand a greater need to attend to vestibular information during the frequent periods of unstable C o M location and limb support position during the step cycle. It may also indicate an importance for vestibular information during the transition between tasks, such as the initiation and termination of gait.  3.5 Bridging Summary  The results from the above study are in support of recent evidence indicating larger vestibular contributions in dynamic tasks than during the maintenance of stability in quiet stance (Inglis et al. 1995, Severac Cauquil and Day 1998, Hlavacka et al. 1999, Smetanin et al. 1988). It was shown that varying degrees of vestibular perturbation led to incremental changes in postural compensation, demonstrating the sensitivity of the system to changes in the magnitude of input. However, despite evidence of an increased importance for vestibular input during dynamic equilibrium control, studies to date have not been detailed enough in the description of both kinetic and kinematic measures to describe the nature of the influence of vestibular information on the movement of the body and its segments. In addition, it remains to be determined whether such information is prioritized differently over different phases of a dynamic task. The following work is based on the proposition that vestibular information is used differently throughout the initiation and execution of a dynamic task and compensated for differently within frontal and sagittal planes. Research by Brandt et al. (2000, 2001) indicated that vestibular subjects were more stable running than walking because use of vestibular information was decreased during the more automated task of running than during slow ambulation. Trials conducted during pilot testing also examined running briefly and found that instability occurred during the transition to establish the stable stationary end position, and not during the running task itself. Therefore, the initiation of a single step has been chosen for the following study because it combines both the initiation and termination of locomotion and has well defined medio-lateral and anterior-posterior mechanical behaviours. As well, the execution of a single step allows the investigation of the transition from quiet standing to the dynamic task of stepping. This will enable isolation of the time when vestibular information becomes more heavily relied upon for controlling dynamic equilibrium.  39  CHAPTER 4 Experiment II part I Vestibular contributions across the execution of a voluntary forward step. (Published: Experimental Brain Research 143: 100-105, 2002) 4.1 Introduction The vestibular system provides direct information about the orientation of the head in space. In conjunction with other sensory input, this information has a role in establishing and maintaining total body equilibrium (Day et al. 1997, Hlavacka et al. 1995, Lund and Broberg 1983). Vestibular contributions to postural control during quiet standing have been disputed (Fitzpatrick and McCloskey 1994), although evidence does support a minor role in the maintenance of an upright posture (Hlavacka et al. 1996, Coats and Stoltz 1969, Coats 1973, Britton et al. 1993, Watson and Colebatch 1997). In contrast, much less is known about the vestibular system's contributions to the control of equilibrium when the body is in motion, specifically concerning voluntary bipedal locomotion. The study of vestibular function during human locomotion has primarily involved three approaches including patients with vestibular deficits (Peruch et al. 1999, Glasauer et al. 1994), caloric vestibular stimulation (CVS; Kubo et al. 1997, Proctor and Glackin 1985) and, only recently, galvanic vestibular stimulation (GVS; Bent et al., 2000a; Fitzpatrick et al. 1999; Jahn et al., 2000). Peruch et al. (1999) have studied the ability of unilateral vestibular-deficient patients to navigate between different locations and suggest that cues from the vestibular system are necessary to update internal representations of the environment. In contrast, Glasauer et al. (1994) have argued that the vestibular system is not used for the control of linear path displacement. These authors observed that, during forward walking to a target, blindfolded, bilaterally labyrinthine-defective subjects walked the correct linear distance, but took a laterally displaced path. For their part, Kubo et al. (1997) have found that subjects who receive unilateral ice water C V S prior to walking on a treadmill have greater lateral sway of the hip, but no changes in head and neck displacement. These authors concluded that vestibular information plays a small role in maintaining upper body balance during locomotion. Unlike the use of patient populations or C V S , G V S provides controlled and reversible perturbations to information arising from the vestibular system over a single testing period. B y directly affecting the irregular firing afferents of the 8 cranial nerve (Minor and Goldberg, th  1991), G V S provides a controlled perturbation of vestibular information, allowing one to probe the influence that such information has during motor tasks (Day et al. 1997, Coats and Stoltz, 1969). Bent et al. (2000a) and Fitzpatrick et al. (1999) have both demonstrated that G V S causes subjects to deviate towards the side of the anode electrode during walking. Bent et al. (2000a)  40  also found that trajectory deviations during walking increase with G V S magnitudes, showing the graded sensitivity of the locomotor control system to vestibular-related information. In addition, Jahn et al. (2000) have shown that vestibular influences during locomotion are speed dependent, with much less lateral deviation during running than during walking. Overall, studies of G V S perturbed locomotion have provided support for a vestibular role during locomotor tasks, but this technique has yet to be properly exploited. To date, most studies using G V S have looked at vestibular contributions to whole body posture during upright standing. These studies have supported the notion that vestibular information contributes to the vertical orientation of the body (Hlavacka et al. 1996, Inglis et al. 1995, Hlavacka et al. 1999, Day et al. 1997). The few studies that have looked at additional voluntary movement or support surface perturbations, simultaneous to the application of G V S , have shown that G V S effects vary according to perturbation velocity (Inglis et al. 1995), the voluntary movement speed (Smetanin et al. 1988), and the timing of the G V S relative to the movement phase (Inglis, et al. 1995, Smetanin et al. 1988, Severac Cauquil and Day 1998, Hlavacka et al. 1999). In particular, these results suggest that vestibular information may play a greater role for tasks when the relationship between body centre of mass (CoM) and base of support (BoS) is dynamic versus when it is relatively static. Such thinking has led to the hypothesis of vestibular involvement in sensory reafference to ensure successful execution of a movement goal (Inglis et al. 1995, Severac Cauquil and Day. 1998). If vestibular sensory reafference is important during these BoS perturbations, then it must be presumed to also have implications for locomotion when equilibrium states are truly dynamic. However, although we know that locomotor behaviour is affected when vestibular information is perturbed, the influence that vestibular information has on the dynamic control of locomotion remains unclear. In order to begin addressing these issues, the present work studied the effects of G V S during forward stepping at natural speeds. This locomotor task was chosen because it combines both static and dynamic postural goals during the transition from one standing posture to another. In addition, the patterns of body destabilization and centre of mass displacement underlying the initiation of gait (Breniere and Do 1986, Mann et al. 1979) and stepping (Lyon and Day 1997, Couillandre et al. 2000) are stereotypic and well known, and the termination of gait has been shown to be biomechanically the reverse of initiation (Jian et al. 1993, Jaeger and Vanitchatchavan 1992). As well, earlier work in cats by Jell et al. (1985) has raised questions about the involvement of vestibular information (Dieter's nucleus) during gait initiation. For their part, Lyon and Day (1997) have claimed that step initiation is a ballistic preset motor program that does not attend to sensory information once initiation has begun. Therefore, it was hypothesized here that a constant galvanic vestibular stimulation applied 1500 ms prior to step  41  execution would differentially affect equilibrium control across the pre-planned initiation phase, the more dynamic stepping phase and the termination phase. Primarily, differences were expected in the Medio-lateral (M-L) displacement of the total body centre of mass (CoM) and centre of pressure (CoP), representing equilibrium control in the presence of a vestibular evoked postural perturbation. With these M - L compensations, some effects on the forward progression of the body were also expected. Some of the results have been presented in abstract form (Bent et al., 1999). 4.2 M e t h o d s 4.2.1 Subject  Preparation  and  Equipment  Six healthy subjects (three men and three women), with no previous history of motion sickness, epilepsy, or neurological or musculoskeletal problems, provided informed written consent before participating. The mean age of the subjects was 24.8 (±3.0) years. The mean body mass and height were 77.62 (±16.89) kg and 175.5 (±9.37) cm respectively. Subjects were prepared by placing three non-collinear infrared markers on the head, the trunk and the pelvis, as well as bilaterally on the feet, the legs and the thighs. For GVS, a 9 cm  2  carbon rubber electrode coated with electrode gel was placed over each mastoid process. Stimulation consisted of a square wave pulse delivered from a stimulator (Model Grass S48) through a constant current stimulus isolation unit ( A M Systems 2200). GVS magnitude was set to three times each subject's response threshold (average intensity of 1.2 mA) determined prior to data collection as described by Bent et al. (2000). During the experiment, the designation of the left or right electrodes as anode or cathode could be achieved by simply changing the polarity of the connection at the isolation unit. 4.2.2  Test  Procedures  During testing, subjects stood barefoot on separate force platforms with their eyes closed and arms crossed. They were instructed to step forward onto a single platform upon hearing an auditory tone. Natural standing width was determined prior to data collection and marked for each subject. Three conditions of galvanic vestibular stimulation were used. These included no stimulation, GVS with the anode electrode on the side of the swing limb and GVS with the anode electrode on the side of the stance limb. Stepping without GVS served as control trials. GVS, when used, was delivered 1500 ms before the auditory tone, and continued for 6 seconds. Catch trials with no cue to step were given for 50 % of the time. Trials where the force data indicated anticipation of the auditory cue were rejected. Optotrak (model 3020) data from the infra-red  42  markers were sampled at 100 Hz and the force platform (AMTI) data were digitized at 1000 Hz. Five trials were collected for each condition. 4.2.3 Data Reduction Analyses focused on the three dimensional total body C o M and CoP displacements. For C o M calculations, principle axes and centres of mass were first defined for each segment (MISCHAC Inc). Total body C o M was then calculated for each data sample. Total CoP data were calculated from the simultaneous recordings of the three force plates used. Eight specific events were chosen during the stepping task for comparisons across conditions for both C o M and CoP. These events included the auditory signal to step (Tone), the initial lateral CoP displacement referred to as the anticipatory postural adjustment (APA), the maximum posterior excursion of the CoP displacement (APmx), toe-off of the stepping limb (TOl), heel contact of the stepping limb (HC1), toe-off of the stance limb (T02), heel contact of the stance limb (HC2), and the termination of stepping indicated by stable CoP trajectories (End). Time integrals of the CoP data were also calculated over the initial part of stepping from onset of A P A to T O l , as well as for the latter part of stepping from HC1 to the end of the locomotor task. These time integrals provided a quantification of the amount of total CoP displacement over the initial and latter parts of stepping. The end of the stepping phase for all conditions was determined as the point in time when the M - L CoP trajectory leveled out to a baseline with minimal deviations (closest to zero). This indicated that the subject had completed the task and had re-established a stable position. The stepping phase M - L CoP data were corrected for each trial by aligning CoP and C o M . This correction avoided over inflation of calculated integrals due to final stance position by minimizing biases introduced by CoP shifts related to unequal weighting of the limbs post stepping. B y doing this, the focus was put on differences between the conditions in the stepping phase, and not on the final static position. The time integral data were normalized to the full-scale data range for each condition. For all CoP and C o M data, positive values indicated movement toward the stepping limb while negative values indicated movement toward the stance limb. Finally, roll angles of the trunk were determined over the same eight locomotor events mentioned above for all conditions. First a local reference frame for the trunk was aligned with this segment's principle axes and located at its estimated centre of mass. Absolute movements about the anterior-posterior axis of this local reference frame were calculated relative to the laboratory reference frame using a Cardanic rotation sequence. A repeated measures A N O V A was used to test for main effects across G V S conditions at specific locomotor events once initial lateral movement due to G V S onset was removed. A  43  Tukey's post hoc analysis was applied in the case of significant main effects. Significance was set atp<0.05. 4.3  Results  Despite the fact that subjects stood, on average, with their feet 265.1 (± 35.6) mm apart (between lateral malleoli), the onset of G V S caused small lateral shifts in both CoP and C o M position towards the side of the anode electrode. When the anode was situated over the stepping limb the mean magnitudes of the shifts were 1.4 (± 4.0) mm for C o M and 1.7 (± 3.8) mm for CoP. When the anode electrode was situated over the stance limb, mean shifts in C o M and CoP were -1.3 (± 2.3) mm and -2.1 (± 2.1) mm respectively. These polarity-specific shifts were accompanied by small, significant (F , =4.285, p=.0453) head rolls that were also to the side of 2  10  the anode electrode whether it be over the stepping (0.4 ± 0.5 degrees) or stance (-0.6 ± 0.7 degrees) limbs. Following these slight shifts at G V S onset, subjects maintained the shifted position until initiation of stepping occurred. For the data reported below, further changes in CoP and C o M displacements will be presented relative to the initially shifted positions. Figure 4.1 A presents the mean trajectories of the total body C o M and CoP, as well as the mean positions and relative orientations of the external malleolus and fifth metatarsal head markers for each limb, for the three stepping conditions. G V S related deviations of the C o M and CoP trajectories from non-stimulated conditions (central lines for each variable) were always to the side of the anode electrode. When the C o M and CoP positions were analysed relative to nonG V S stepping at the 8 specific events across the task, no effects of G V S were found in the anterior-posterior direction. In the lateral direction, at the same points in time, significant differences were found only for the C o M position (Figures 4.1 B and C). Although significant C o M deviations (F , i =13.293, p=0.0015) only began at the point of second toe-off (i.e. 2  0  beginning swing phase of the stance leg) and were significant for all other events to follow, qualitative differences could be seen to occur as early as H C I , within the more dynamic stepping phase. Had time derivative data, such as velocities or accelerations been analysed, differences observed at H C I might have reached significance. Regardless, it is clear that, after an initial lateral shift upon G V S onset, no other effects were seen until the more dynamic phase of the locomotor task.  44  A - F E E T POSITIONS and C o M / C o P T R A J E C T O R I E S  g g a: ID UJ H I- 0)  150 mm  O Q- L A T E R A L  Direction of stepping  Metatarsal head  External Malleolus  C - C o P POSITIONS  B - C o M POSITIONS  100 mm  100 mm END HC2 T02 HC1 T01 APmx APA TONE  Figure 4.1 A) Transverse plane view of the average CoP (thick lines) and C o M (thin lines) trajectories, as well as the initial and terminating positions of the left and right external malleoli and fifth metatarsal heads, across subjects for conditions without (centre CoP/CoM trajectories; filled circles for foot markers) and with stimulation (extreme left and right CoP/CoM trajectories; squares for stance side anode and triangles for swing side anode for foot markers). B) Relative C o M positions at 8 different points during stepping with the anode electrode over the stance (thick line with squares) and swing (thin line with triangles) limbs. C) Relative CoP positions at 8 different points during stepping with the anode electrode over the stance (thick line with squares) and swing (thin line with triangles) limbs. The asterisks indicate significant differences (p<0.05) between conditions of stimulation versus no stimulation.  45  g  T 0 2 HC2  1.0 cm  0.5 c m  500 ms  50 ms  c  0.8 0.6 0.4 0.2 0 -0.1  ANODE STANCE  NO G V S  ANODE SWING  ANODE STANCE  j-  NO G V S  ANODE SWING  T 0 2 HC2 i  i  1.0 cm  1.0 cm  50 ms  500 ms  H  —  p<0.05  0.6 0.4 0.2 -0.2  ANODE NO G V S STANCE  ANODE SWING  ANODE STANCE  NO G V S  ANODE SWING  Figure 4.2 Mean CoP trajectory (A, B, E , F) and time integral (C, D , G , H) data in the anterior-posterior (A to D) and lateral (E to H) directions during the initial (left column) and latter (right column) phases of step execution. CoP trajectories are shown for conditions of no G V S (dashed lines), G V S with the anode electrode over the swing limb (thin lines) and G V S with the anode electrode over the stance limb (thick lines). Positive integrals (light grey bars) indicate movement to the swing limb and negative integrals (dark bars) indicate movement to the stance limb. CoP trajectory data (A, B , E , and F) are normalized to foot width (lateral data) or length (anterior-posterior data). The asterisks indicate significant differences (p<0.05) between conditions. (T02 toe-off of the stance limb, HC2 heel contact of the stance limb).  46  Lateral positions of the ankle markers between the initial and terminating positions showed no differences in foot orientation across conditions. Although there were no significant differences in CoP at each event, and no polarity specific changes in lateral foot positioning, Figure 4.1 A still shows that some CoP deviations were evident. Figure 4.2 presents the anterior-posterior and lateral time-series and time integral data for the CoP displacements over the initial and latter phases of stepping. No significant differences were found for either the initial (F i =0.814, p=0.4703) or latter (F , =l-899, p=.20) 2>  0  2  10  phases in the anterior-posterior direction (Figures 4.2A to D). Lateral CoP displacement was also not significantly different (F i =0.256, p=0.7790) over the initial phase (Figures 4.2 E and G). 2;  0  However, significant lateral CoP deviations (F io=24.382, p=0.0001) to the side of the anode 2>  electrode were found in the latter phase (Figures 4.2 F and H). In particular, these significant changes occurred after second heel contact. Therefore, CoP trajectory deviations did occur, but only well after the C o M deviations, suggesting that initial control of body movement is from the top down, while late control during termination is from the bottom up. When absolute trunk roll angles were evaluated relative to the non-GVS conditions, it was found that subjects always rolled to the side of the anode electrode (Figure 4.3). As seen for C o M deviations, there was also a small trunk roll toward the side of the anode electrode immediately following G V S onset (0.2 degrees; p=0.0886). Following the signal to step, trunk roll deviations were observed as early as HC1, once the subject entered the more dynamic phase, but were not significantly different until second toe-off (F ,io=5.067, p=.0302), concurrent with 2  C o M deviations.  4.4 D i s c u s s i o n  Galvanic vestibular stimulation caused an initially small lateral displacement of the body C o M and CoP, accompanied by a significant roll of the head towards the anode electrode during quiet standing. With maintained vestibular stimulation there were no further effects on step initiation behaviour during the initial phase. Once the body was in motion, G V S related deviations in C o M trajectory were evident during actual displacement of the limbs for stepping, and preceded CoP deviations that occurred after heel contact of the stance limb during step termination. In general, these findings show that vestibular information is used differently across the initial and latter parts of step execution. The lack of G V S effects during the early initial phase, suggests that step initiation for humans may be unaffected by vestibular influences. This has already been shown to be the case  47  Figure 4.3 Mean absolute roll (frontal plane) angles of the trunk for conditions with G V S relative to nonG V S data. The initial deviation at G V S onset has been removed. The asterisks indicate significant differences (p<0.05) between conditions.  48  in gait initiation in cats (Jell et al., 1985). This hypothesis is further supported by the knowledge that the biomechanical parameters of gait initiation are tightly structured (Breniere and Do, 1986; Lepers et al., 1999; Das and McCullum 1988), and that step initiation is believed to be a ballistic activity pre-planned by the central nervous system (Lyon and Day, 1997). However, while the present results support this pre-programming hypothesis, a certain level of plasticity must also be presumed to exist. In particular, initial shifts in body posture created by G V S were obviously integrated and accounted for in order to allow the same initiation behaviour to be carried out about the new position, as that observed during non-stimulated trials. Such an integration of the new posture would most certainly exploit input from somatosensory information. Once body motion began, the present data showed that continuing to perturb vestibular information influenced postural control in the medial-lateral direction only. Although the G V S was only directed laterally, significant perturbations in M L momentum and CoP control, such as seen in the present study, could conceivably still affect forward progression. The fact that no A P effects were found is not trivial, but may even suggest separate control for the two directions with differential processing of vestibular information. Further work would be needed to confirm such a hypothesis. One immediate explanation as to why significant M L G V S effects occurred only later in stepping could be simply related to the decreased base of support associated with locomotion. However, there are a number of factors that do not support this theory. First, there were no significant responses in C o M or CoP displacements at the point when the swing limb first lost contact with the floor (TOl). Qualitative changes in the time-series data did not appear until first heel contact, after which they became significant for trunk roll and C o M displacements at second toe-off, when the stance limb lost floor contact, and continued to be different for all subsequent events. Second, CoP displacements remained unaffected until step termination, following second heel contact. Finally, even foot placements were unchanged from initial to final positions. If support base were an issue, changes in C o M and CoP would have been expected much earlier, and foot placements, would have changed depending on the side of the anode electrode. Therefore, the results do not advocate an explanation based simply on support base changes. A more likely explanation for the results is that control is initiated from the top down. Upper body movements, rather than CoP positioning, are exploited to influence the C o M position. The simultaneous changes in upper body roll angles with C o M deviations directly support this theory. In addition, the present results also suggest that there is a phase dependency of the vestibular influences over the lateral C o M displacements. Despite the continuing tonic level of perturbation to vestibular information throughout step execution, it was shown (see  49  Figure 4.3) that roll angles varied considerably between stationary and dynamic-based events, with differences beginning at H C I , and the greatest deviations to the side of the anode electrode occurring at second heel contact. It is likely that the process of terminating the step has a large influence on the weighting of vestibular information and therefore the increased roll response. During this phase it becomes critical for the body to have control of the C o M in order to come to a successful stop. Only after this re-establishment of standing position did roll angles decrease again and CoP changes became predominant Further work is needed to probe this idea of phase dependent control by the vestibular system for locomotor tasks, but such a hypothesis is not without precedent in other sensory systems for locomotor control (Zehr and Stein 1999). Recently, Severac Cauquil and Day (1998) discussed the possibility of two components of vestibular contributions to dynamic tasks. One component is for balance, and the other is for providing sensory reafference to monitor head movement. Greater G V S effects during stepping may indicate phases of the locomotor task where vestibular information is increasingly up-regulated for optimizing either balance or sensory reafference. The exact parameter to be controlled is difficult to say with the present data, but it is obvious that erroneous vestibular information from G V S does not homogeneously affect body roll responses across step execution. Finally, with respect to step termination, the predominant CoP control would provide guidance of the C o M to its final position. Previous work has shown that CoP trajectories during gait termination are reversed from those of gait initiation (Jian et al., 1993, Jaeger and Vanitchatchavan 1992). The fact that in the present study, G V S caused asymmetrical changes to CoP trajectories that depended on the side of the anode electrode suggests that, unlike the initiation phase of the locomotor task, vestibular information plays a significant role during termination. Thus, although initiation can then be seen as a feedforward, ballistic phase, termination appears to be controlled more on-line, integrating sensory, including vestibular, information to control C o M position. Just how vestibular information affects the CoP trajectories, that are themselves related to lower limb control (Winter et al., 1996), is still to be discovered. Presumably, involvement of other somatosensory information is critical. In fact, future work is necessary in order to detail the actual level of control offered by sensory information during the dynamic phases of locomotor tasks. Are they purely reactive in nature, or do they offer information that can be used proactively to guide the body through the changing locomotor goals. In conclusion, the present results have shown that vestibular information is used differently across the execution of a voluntary locomotor task, such as stepping forward without vision. The initiation of the step appears to incorporate the new posture, resulting, in part, from  50  vestibular signals. Following initiation, only the latter stepping and termination phases are influenced by varying vestibular information, and only in the lateral direction. In short, such vestibular influences appear to be phase dependent. Future considerations for this research will need to further address the phase dependent nature of the G V S response, as well as dissociating the vestibular contributions to the focal and balance components of locomotion. In addition, the inclusion of vision will no doubt have a great influence over these effects (Britton et al. 1993, Day and Bonato 1995, Smetanin and Popov 1990). Therefore, the interaction of visual and vestibular information during such dynamic tasks will also need to be addressed. 4 . 5 Bridging Summary  The current study showed clear evidence of phase dependent differences in vestibular weighting across the execution of a forward stepping task in the absence of vision. The postural literature has demonstrated that visual, vestibular and somatosensory information contribute to the successful achievement of a stable posture in stationary tasks, and are also involved in the completion of dynamic locomotor goals. The nature of the integration between these sensory systems, although somewhat understood for stationary equilibrium, remains to be examined in detail during dynamic locomotor tasks. Research to date using the technique of Galvanic Vestibular Stimulation has presented conflicting evidence of the influence of vision on the resultant postural response to G V S perturbations during stationary tasks. Several studies indicate that the presence of visual input attenuates the response to G V S that is observed in both whole body movement (Smetanin and Popov 1990, Britton et al. 1993, Day and Bonato 1995) and muscle activation (Fitzpatrick et al. 1994b, Welgampola and Colebatch 2001a). However, the literature highlights that in the absence of an external visual reference cue (Smetanin and Popov 1990), or when reliable somatosensory information is available in the presence of vision (Fitzpatrick et al. 1994b), there is no attenuation of the G V S response, even when vision is available as a sensory input. These conflicting data have led to the need to further examine the integration of vestibular and visual information. Particularly of interest is the sensory integration that occurs during a dynamic task where vestibular contributions have been shown to be phase modulated.  51  CHAPTER 5 Experiment II part II Visual-vestibular interactions in postural control across the initiation of a voluntary forward step. (In Press Experimental Brain Research June, 2002) 5.1  Introduction  Recent evidence indicates that vestibular information is not critical for triggering automatic postural responses evoked by support surface translation (Horak et al. 1994; Inglis and MacPherson 1995; Inglis et al. 1995). Likewise, numerous reports have shown that vestibular input appears to have a minor role in the control of quiet standing (Fitzpatrick and McCloskey 1994; Hlavacka et al. 1996; Day et al. 1997). In contrast, reduction of vestibular afferent input leads to major deficits in the control of complex tasks, such as locomotion, that are dynamic in nature (Igarashi et al. 1970; Marchand and Amblard 1984; Inglis and MacPherson 1995; Peruch et al. 1999). Igarashi et al. (1970) reported that, following unilateral or bilateral labyrinthectomy, squirrel monkeys regained the ability to move about the environment, but complex dynamic postural control, such as negotiating a revolving rail apparatus, was compromised for many weeks in the unilateral and indefinitely in the bilateral animals. Similarly Marchand and Amblard (1984) showed that bilateral labyrinthectomized cats were unable to accomplish complex tasks. While the animals were capable of completing a simple wide plank locomotion task, suggesting visual compensation for their vestibular deficit, the cats were not able to walk across a narrow plank, indicating an essential contribution of vestibular information in performing tasks with high equilibrium demands. Deficits in complex dynamic postural control, such as compromised spatial orientation during walking, have also been demonstrated in humans with vestibular lesions. Cohen (2000) examined locomotor path trajectories of individuals with chronic vestibulopathy. These individuals had greater difficulty walking forward than age-matched controls, and veered from the path sooner when vision was removed. In addition, it was shown by Peruch and colleagues (1999) that one week following a unilateral vestibular neurotomy, patients were not able to accurately navigate a previously traversed path with their eyes closed. Visually guided navigation (using a virtual visual environment) was also affected in these patients, indicating that such complex spatial orientation requires integration of visual and vestibular information at a high level. These observations raise the question: How does vestibular information contribute to postural control and what interaction does vestibular input have with vision during complex dynamic tasks? A recent addition to the techniques available for testing vestibular contributions in  52  humans is Galvanic Vestibular Stimulation (GVS). The use of G V S has enabled researchers to assess vestibular contributions to postural control during various dynamic tasks in humans such as leaning (Smetanin et al. 1988), platform perturbations (Inglis et al. 1995), and walking (Fitzpatrick et al. 1999, Bent et al. 2000a). GVS involves the application of electrodes over the mastoid processes, which results in an increase (cathode) or decrease (anode) in the firing of vestibular afferents (Minor and Goldberg 1991). The alteration in firing is believed to change the perception of vertical, thereby resulting in a postural compensation towards the anode electrode (Popov et al. 1986; Hlavacka et al. 1996). The use of this technique has also shed light on the integration of visual and vestibular information during quiet standing (Smetanin and Popov 1990; Britton et al. 1993; Fitzpatrick et al. 1994b; Day and Bonato 1995). Day and Bonato (1995) found that the presence of a visual cue during a standing task altered the magnitude of the G V S evoked sway that subjects produced. They concluded that the visual information acted in a feedback manner to reduce the vestibular evoked response. Smetanin and Popov (1990) reported similar observations in that an external visual source was able to reduce a G V S evoked sway response. However, these researchers also reported that when the visual source was referenced to the head (a rod attached to the head), the magnitude of sway remained unaffected, demonstrating that vision dominates over vestibular information only when provided as an external reference cue. Fitzpatrick et al. (1994b) and Britton and colleagues (1993) both found that the presence of visual information could attenuate or even abolish the G V S evoked electromyography (EMG) response in soleus during standing. Fitzpatrick and colleagues (1994b), however, demonstrated that the E M G response was actually only modulated by vision when somatosensory information was unreliable. Furthermore, Welgampola and Colebatch (2001a) found a significant decrease, but not an abolishment, of the short and medium latency G V S evoked E M G responses when vision was available. They went on to show that with the addition of other sensory information such as tactile cues, or a widened support base, the vestibular response decreased further. These observations indicate complex sensory integration in postural control. Organization of multisensory input was also demonstrated by Lacour et al. (1997a) when they measured the average sway response of individuals with Menieres disease pre- and post-unilateral vestibular neurotomy. These researchers found that rapid re-weighting of sensory input occurs when one sensory mode becomes unreliable. They concluded that following surgery, visually dominant subjects relied more heavily on somatosensory information. The switch in sensory strategy was induced by an increase in postural instability post surgery, which was interpreted by the. subject as an ineffectiveness of the previously chosen visual strategy. In tasks that are more complex than quiet stance, such as gait and step initiation,  53  researchers have postulated a feedforward control program for task execution (Breniere and Do 1986; Das and McCullum 1988; Lyon and Day 1997; Couillandre et al. 2000). Lyon and Day (1997) proposed that step initiation is controlled by a ballistic motor program that is based on pretask position and the direction of the step. The feedforward nature of this task implies exclusion of sensory contributions once the step has been initiated. In support of visual feedforward mechanisms during locomotion, Hollands and Marple-Horvat (1996) reported that visual information is used prior to, but not during, swing of the stepping limb in gait. Denial of visual information during a locomotor target task did not affect subjects' ability to successfully land on targets that had been lit and then extinguished prior to foot lift. These authors suggested that motor programs to swing the leg accurately were in place by the time the limb left the ground. A vestibular correlate to these visual findings regarding contribution during locomotor initiation has been studied in animals (Jell et al. 1985), and only recently examined in humans (Bent et al. 2002). Jell and colleagues (1985) demonstrated that a bilateral lesion of Deiter's nucleus in cats did not affect the initiation of locomotion via stimulation of the mesencephalic locomotor region, suggesting that there is a minimal vestibular contribution to gait initiation. In relation to these findings, our recent work (Bent et al. 2002) has demonstrated that in humans, differences exist in the weighting of vestibular information across the initiation and completion of a stepping task. Although our finding of a minimal vestibular role during initiation supports the results of Jell and colleagues (1985), we were also able to demonstrate that vestibular information was used during the execution of the task, indicating the importance of vestibular information in successful task completion. Motivated by the controversy over the integration of visual and vestibular information, and our recent evidence of differing degrees of vestibular contribution across a step initiation task, we wanted to further investigate the potential of multiple sensory influences on balance control during a forward step. As a result, the purpose of the current study was to examine visual-vestibular interactions during the completion of a forward stepping task. This project aimed to address two questions. First, what effect does vision have on changing the importance of vestibular information during a step? And secondly, are visual and vestibular information integrated differently during different phases of the stepping task? Portions of the data have been published elsewhere in abstract format (Bent et al. 2000b). 5.2 Methods 5.2.1 Subject  preparation  and  Equipment  The experiment aimed to examine visual interaction with vestibular information during a  54  forward voluntary step. Six healthy young subjects (3 men, 3 women, 25+3 years) participated in the study. They were informed of the protocol and provided written consent. A l l participants reported no previous history of motion sickness, epilepsy, or any neurological or musculoskeletal problems. Four subjects chose to step with their right foot, while two subjects chose to step with their left foot. The data from the left steppers were inverted to enable calculation of averages, and are presented simply with respect to swing (first stepping limb) and stance (first support limb) limbs associated with the initiation process. An Optotrak three dimensional (3D) system (3020) was used to collect kinematic data for segment linear position information and the calculation of the centre of mass (CoM) location. A configuration of three non-collinear infra-red diodes (IREDs) was arranged bilaterally on the foot, leg and thigh, as well as on the pelvis, trunk and head segments. Three force platforms (AMTI model # OR6-5) were used; two under each foot, and one in front of the subject. Subjects were not instructed to target the third plate specifically. In the event that subjects did not step completely onto the third plate or did not step when required, data collection continued and the trial was recollected at the end of the pre-organized random sequence. Only 4.5 % of the total number of trials across subjects had to be recollected in this way. 5.2.2  Test  Procedures  Six stepping conditions were collected combining two vision conditions, eyes open or closed (EO, EC), and three GVS conditions (no GVS, GVS with the anode electrode on the side of the swing limb; swing, and GVS with the anode electrode on the side of the stance limb; stance). The subjects were initially instructed to not anticipate a step, and step trials were interspersed randomly with the same number of catch trials involving no stepping. Subject anticipation of stepping was monitored online from the ground reaction forces. Trials where the force data indicated anticipation of the auditory cue were rejected. Five trials were collected for each condition. Subjects were instructed initially to stand barefoot on two force platforms. Natural stance width (12.6 ± 1.51 cm between medial metatarsals) was determined prior to the onset of data collection by a series of forward and backward steps. Subjects folded their arms in front of their chest during data collection to avoid blocking IREDs. Prior to each trial, subjects were verbally instructed to open or close their eyes and to prepare themselves. The cue to step was an audio tone. The onset of GVS was delivered at random lengths of time (500-2500 ms) after the onset of data collection, and always occurred 1500 ms before the audio tone when it was present. Each stepping trial consisted of one step forward, first with the swing limb and then with the stance limb to meet the forward location of the swing limb. This enabled the trials to begin and  55  end in normal quiet stance. The speed of the step was chosen by the participant but remained constant (0.11 m/s ± 0.015 m/s). Galvanic vestibular stimulation (GVS) was delivered to the subjects using two 9 cm  2  carbon rubber electrodes placed behind the subject's ears over the mastoid processes. The skin behind the ears was rubbed with alcohol to decrease impedance. Electrode gel was used to increase the conductance of the current across the electrode-skin junction. A Grass Stimulator (Model Grass S48) was used to deliver a square wave pulse lasting 6s through a constant current stimulus isolation unit ( A M Systems 2200) that provided a current of 1mA out for each volt in. A six second stimulation enabled an ongoing stimulus for the duration of the task. GVS was delivered at a magnitude of three times a set threshold for each subject (average stimulus intensity of 1.2mA). GVS anode thresholds were determined for each subject prior to the onset of data collection as has been described previously (Bent et al. 2000a). Briefly, for threshold testing stimulation began at 0.05 mA and was increased by 0.05mA in a discrete step-like fashion until threshold was reached. Threshold determination was based on definitive visible observations of sway in the anodal direction, in conjunction with verbal reports of disorientation or light-headedness, related to the temporal onset of stimulation. When unsure of the response at a particular stimulus level, the stimulus level was increased and then brought back down to reestablish an intensity signifying an observable perturbation. 5.2.3  Data  Reduction  The analysis of the results focused on centre of pressure (CoP) displacements and body segment roll of the head, trunk and pelvis. Net CoP was calculated from the individual CoPs of the three force platforms. Principle local axes were created for each body segment from the three non-collinear markers and centred at each segment's estimated centre of mass. Segmental roll angle data were calculated from a Cardanic rotation sequence related to rotation of the local segment reference system about the forward axis of the global reference system (akin to frontal plane movement). The non-stimulation step condition served as control trials for comparison. Analyses of the data concentrated on specific temporal events similar to the methods used in our recent paper (Bent et al. 2002). Briefly, nine events were chosen to represent the task: 1) 2000 ms before the audio tone, 2) audio tone, 3) onset of M - L CoP shift (M-L onset; determined by CoP excursion past baseline of greater than 4 mm; based on CoP sway during quiet stance, Mcllroy and Maki 1999), 4) maximum posterior CoP excursion (AP max), 5) toe-off of the swing limb (TOl), 6) foot contact of the swing limb (FC1), 7) toe-off of the stance limb (T02), 8) foot contact of the stance limb (FC2), and 9) end stimulation. The events were then distributed among three phases of the movement. The first phase, labeled the stationary phase  56  encompassed the time from 2000ms before the auditory tone (therefore including the time from 500 ms before G V S onset) until the auditory tone sounded. The second phase, called the initiation phase, was defined as onset of M - L CoP displacement to toe-off of the swing limb. The final execution phase was from foot contact of the swing limb to a stable CoP cutoff (see below). M - L CoP data were normalized to foot width and time integrals were calculated in the M - L direction for the different phases in order to assess global CoP movements and provide changes that may have been missed by the event analyses. Roll data were also divided into stationary, initiation and execution phases based on specified events. To assess each phase of the task properly, it was necessary to normalize the data based on specific criteria. To enable statistical analyses of the stimulation effects during the stationary phase, the data were aligned to 2 seconds before the auditory tone (500 ms prior to G V S onset). To analyse effects during the initiation phase, M - L CoP was aligned to the CoP position at the auditory tone to remove the bias of each subject's new static position resulting from the stimulation. The integrated values during this phase were then calculated with the re-aligned data. The end of the execution phase for all conditions was determined as the point in time when the M - L CoP trajectory leveled out to a baseline with minimal deviations (closest to zero). This indicated that the subject had completed the task and had re-established a stable position. The execution phase M - L CoP data were corrected for each trial by aligning CoP and C o M . This correction avoided over estimation of calculated integrals by reducing biases introduced by unequal distribution of weight on the limbs in the final stance position post stepping. By doing this, the focus was put on the differences that existed between the conditions during the execution phase, and not on differences in the final static position. A l l integrated data were normalized to the range of positive and negative values for each condition. For all CoP, C o M and body roll data, positive values indicated movement toward the stepping limb while negative values indicated movement toward the stance limb. A two way repeated measures A N O V A (2x3) was run to test the main effects of the independent variables related to vision (eyes open or closed) and stimulation direction (anode left, anode right or no stimulation). This was done for each of the time points from the auditory tone to the end of stimulation. Testing was also performed when the data were aligned 2000 ms before the auditory tone to test the quiet stance stimulation effects. For the CoP time integrals, means from the positive/negative differences were used. A Tukey's post hoc analysis was then used in the case of a significant difference, to establish where the difference occurred between the means of the treatment conditions. Significance was tested at p<0.05.  57  5 . 3 Results In quiet stance, all subjects demonstrated a response to the stimulation by the time the audio tone was given (Figure 5.1a and b). Stimulation effects (averaged across vision conditions) included significant absolute roll of the head and trunk towards the anode electrode (F =7.589, p=0.0099, F , =6.805, p=0.0136 respectively) and movement of the CoP, first in the 2jl0  2 10  direction of the cathode (F i 9.638, p=0.0046) and then towards the anode (F ,TO 4.193, =  2i  =  2  0  p=0.0476) by the time the audio tone sounded. The timing of the CoP shifts corresponded with medium and long latency shifts reported previously in response to G V S (Nashner and Wolfson 1974; Fitzpatrick et al. 1994b). Segment movement was small, 0.53° for head roll, and 0.24° for trunk roll on average, likely due to the large natural stance width of the subjects (12.6 ±1.51 cm inter metatarsal distance). The effects, however, are within the accuracy of the measurement system and are comparable to the magnitude of effects demonstrated in the literature, with a similar stance width (Day et al. 1997). Analysis of the G V S perturbation effects comparing trials with the eyes open, and trials with the eyes closed, quite unexpectedly were not significantly different for the head (F , =0.132, p=.8777) or trunk roll (F , =1.573, p=0.2548). This novel 2 10  2 10  observation indicates that during quiet standing, the upper body roll response to the G V S perturbation was not attenuated when vision was present (Figure 5.1a). In contrast, the magnitude of the initial shift in the CoP was reduced when vision was present, compared to the deviation observed when the eyes were closed (Figure 5.1b), supporting evidence presented in the literature of visual attenuation (Smetanin and Popov 1990). Our recent data indicate that there are no substantial changes for any variables across any condition in the anterior-posterior (A-P) direction during a forward step with the eyes closed (Bent et al. 2002). Therefore, analysis during the step focused on compensation in the M - L direction (Figure 5.2). During the initiation of the step, beginning at the sound of the auditory tone, no significant changes were found in M - L CoP, or body roll of any segment (Figure 5.3a). At T 0 2 , M - L C o M (averaged across visual conditions) became significantly different between stimulation conditions (F i =19.652, p=0.0003) and remained significant for the remainder of the 2 0  events tested (Figure 5.2). Interactions were present for C o M at T 0 2 and FC2 indicating differences in the magnitude of the stimulation response between trials with and without vision. There was a significant difference in the magnitude of the C o M response when stimulation was given towards the stance limb (black line), relative to no stimulation, when the eyes were closed but not when they were open at both T 0 2 (F =6.752, p=0.0139) and FC2 (F =7.759, 2jl0  2>10  58  a)  Roll  EYES OPEN  EYES CLOSED  Auditory cue  Auditory cue  Head  Trunk  100  500  1000  1500  0.6 0.2  Pelvis  -0.2 -0.6 -1.0 1D0  500  1000  1500  000  1500  M - L CoP  _ Onset  100  500  1000  1500  J Onset No Stimulation Anode Stimulation to swing side Anode Stimulation to stance side  Figure 5.1 Group averages are presented for a) Kinematic roll data from the head, trunk and pelvis (degrees) and b) kinetic M - L CoP (cm) over the time period 100 ms before the onset of the G V S perturbation until the time the auditory tone sounded 1500 ms later. Gray solid lines represent trials where the G V S anode was on the side of the swing leg, black solid lines are trials where the G V S anode was on the side of the stance leg and the dashed line represents no stimulation. Positive shifts in body roll and CoP indicate movement to the right (swing side) and negative shifts represent movement to the left (stance side). Data is separated into eyes closed in the left hand column, and eyes open in the right hand column. Vertical dotted lines represent onset of G V S (left) and tone (right).  59  ECSPCoP  ECSPCoM  EC Swing CoP  EC Swing CoM  EC Stance CoP  EC Stance CoM  Figure 5.2 M - L CoP (thick lines) and M - L C o M (thin lines) over a normalized time base averaged across all subjects. Trials with anode on the swing side are represented by grey lines, anode on the stance side are black lines and trials with no stimulation are dashed lines. Trials with no stimulation are labeled ECSP for eyes closed, and EOSP for eyes open. Important events during the step are labeled along the x-axis and are highlighted on the graphs with thin dotted lines. M - L CoP and C o M are expressed in cm.  60  p=0.0092). Thus, the presence of vision attenuated the C o M response during these events. Further analysis of the step indicated that significant differences were observed in body roll by FC1 (due to pelvis roll). No differences were observed before this event (Figure 5.3a). Subjects demonstrated significant roll in the pelvis, trunk and head beginning at FC1, T 0 2 and FC2 for each segment respectively (F , =16.008, p=0.0008, F io=7.631, p=0.0097, F i =5.176, 2>  2 10  2j  0  p=0.0286) (Figure 5.4a). Significance between stimulation conditions persisted until the end of the stimulation for the pelvis roll, and up to FC2 for the trunk and head roll. It should be noted that FC2 was the last event analysed before the end of stimulation. Significant interactions between stimulation and vision were observed for trunk roll and pelvis roll, indicating a visual attenuation of the response. This evidence of visual attenuation occurred at FC2 for trunk roll (F , =7.014, p=0.0125) and at both T 0 2 (F , =5.433, p=0.0253) and FC2 (F =5.915, 2 10  2 10  2;10  p=0.0202) for pelvis roll. For both trunk roll and pelvis roll, for the significant interactions, the magnitude of roll towards the swing leg, relative to no stimulation was significant when the eyes were closed but not when vision was present. Finally, medio-lateral (M-L) CoP deviations were determined at the eight latter events during the step. No significant differences were found at any of these events. In addition, analysis of ankle markers revealed no difference in foot placement across conditions. Time integral calculations of the initial (M-L Onset to T O l ) and execution (FC1 to end stimulation) phases of the step were performed in an attempt to identify any differences missed by the event analyses, similar to the calculations presented for E C data in our previous study (Bent et al. 2002). No differences were found for the integrals calculated during the initiation of the step, for either stimulation or vision (Figure 5.3b). However, time integral calculations of the M - L CoP from FC1 until the end of stimulation revealed significant differences between stimulation conditions in this latter part of the trial (F ,i =53.595, p<0.0001) (Figure 5.4b). Differences began 2  0  after FC2, during the termination of the step. These observations concur with our recent reports, taken from trials with eyes closed only, indicating differences in M - L CoP during this phase (Bent et al. 2002). Post-hoc analysis indicated that significant differences occurred between all three stimulation conditions. In addition, there was evidence by visual inspection that the G V S integrated CoP response was attenuated when vision was present, similar to the body roll data during the execution phase. Although attenuation was not significant when vision was present (F ,io l-673, p=0.2361), the CoP data demonstrated a definite trend, with much larger responses =  2  present when the eyes were closed (Figure 5.4b).  61  a)  Roll  EYES CLOSED  EYES OPEN  1.6 1.1 0.6  Head  0.1 -0.4 100  200  3Q0  400 500  600 700  1.6 1.1 0.6 0.1  S T - ' - " r  Trunk  -0.4 100  200  300  400 500  600 700  1.6  1.6  1.1  1.1  0.6  0.6  0.1  100  200  300  400  500  600 700  100  200  3Q0  400 500  600 700  0.1  Pelvis  -0.4  -0.4 100  t>)  200  300  400 500  600 700  M - L CoP  1.0  1.0  0.5  0.5  0  0  -0.5  -0.5  .1.0  0 50 100 150 200 250 300 350 400 A-P M a x  .1.0  0 50 100 150 200 250 300 350 400; A-P Max  Toe-off 1  0.8  08  06  0.6 -I  0.4 -I  0.4 -  0.2  02 -  —•  Toe-off 1  JL  0  0  -0.2 -  -0.2  -0.4 -  -0.4  EC stance  ECSP  EO stance  EOSP  EO swing  Figure 5.3 Group means are presented for a) Kinematic roll data from the head, trunk and pelvis (degrees) and b) kinetic M - L CoP time series (cm) and integrals (normalized to foot width). Data are presented from M - L CoP onset until toe off of the first foot (swing limb). Vertical dotted lines represent the events: maximum posterior CoP excursion (AP max) and Toe-off of the swing limb (Toe-off 1). In time series graphs, lines represent G V S with anode on the side of the swing limb (gray), G V S with anode on the side of the stance limb (black) and no stimulation (dashed lines). Bar graphs represent the positive (gray) and negative (black) integrals of the M - L CoP time series data. Positive shifts on all graphs refer to movement to the right (towards the swing limb) and negative shifts represent movement to the left (towards the stance limb). Data are separated into eyes closed (left column) and eyes open (right column). E O S P and ECSP represent trials with no stimulation with eyes open and closed respectively.  62  Roll  a)  EYES OPEN  EYES CLOSED  Head  Trunk  Pelvis  - 200 600 1000 1400 1800 2200  200 600 1000 1400 1800 2200 HCI  T02 HC2  End Stim  HCI  T()2 HC2  End Stim  0.7 05  0.3  I  0 1  -0.1 -0.3 -0.5  EC stance  ECSP  EC swing  EO stance  EOSP  EO swing  Figure 5.4 Group means are presented for a) Kinematic roll data from the head, trunk and pelvis (degrees) and b) kinetic M - L CoP time series (cm) and integrals (normalized to foot width). Data are presented from heel contact of the swing limb (HCI) until the end of stimulation. Vertical dotted lines represent Heel contact of the swing limb (HCI) (indicated with arrows), toe off of the stance limb (T02), heel contact of the stance limb (HC2) and the end of stimulation. In time series graphs, lines represent G V S with anode on the side of the swing limb (gray), G V S with anode on the side of the stance limb (black) and no stimulation (dashed lines). Bar graphs represent the positive (gray) and negative (black) integrals of the M - L CoP time series data. Positive shifts on all graphs refer to movement to the right (towards the swing limb) and negative shifts represent movement to the left (towards the stance limb). Data are separated into eyes closed (left column) and eyes open (right column). EOSP and ECSP represent trials with no stimulation with eyes open and closed respectively.  63  5.4 Discussion The application of G V S to standing subjects resulted in an expected postural sway and a roll of individual body segments towards the anode electrode in a top down pattern with head roll exhibiting the largest and earliest response, and pelvis roll the smallest and latest (Day et al. 1997). However, we were surprised to find no attenuation of the G V S body roll response when vision was present during quiet stance. Day and Bonato (1995) demonstrated that the G V S response of subjects, determined by movement of a marker at the seventh cervical vertebra, was significantly reduced by vision during standing. Their findings may result from the use of only one marker, isolating lateral movement and not the roll response we are highlighting. Their finding is, however, supported by other empirical evidence indicating an attenuation of responses to G V S , such as an abolishment (Britton et al. 1993; Fitzpatrick et al. 1994b) or reduction (Welgampola and Colebatch 2001a) of the medium latency E M G responses in Soleus, in addition to a reduction in whole body movement in the anode direction (Smetanin and Popov 1990) when vision is present. Why do our data suggest a contradiction to the literature, which clearly demonstrates the effect that vision has in attenuating compensatory movements evoked by GVS? To begin, only the kinematic body roll response to the G V S perturbation showed an absence of significant visual attenuation during quiet standing in the current study. Conversely, observation of the initial kinetic M - L CoP deviation demonstrated visual attenuation. The timing of the M - L CoP shift corresponds with the medium latency component of the G V S E M G response (Nashner and Wolfson 1974) and the visual attenuation agrees with evidence of visual attenuation of this medium latency response reported in the literature (Smetanin and Popov 1990; Fitzpatrick et al. 1994b; Welgampola and Colebatch 2001a). We suggest that the distinction of visual influence on the CoP response versus the body roll response may indicate multiple sensory roles for vestibular information during quiet stance. In fact, we would propose that vestibular information during quiet stance may serve at least two separate functions. First, the movement of the CoP, which corresponds in direction and temporal onset, to the G V S evoked medium latency response (Nashner and Wolfson 1974; Smetanin and Popov 1990; Watson and Colebatch 1997) suggests a vestibular contribution to postural stability. This initial shift is thought to be associated with the resultant large postural sway towards the anode electrode (Fitzpatrick et al. 1994b). A suggested second role is the use of vestibular information to properly align, or stack, the segments of the body in order to provide a stable upright position from which to move. The observation of upper body segment roll toward the anode electrode corroborates the data presented by Day and colleagues (1997). It has been suggested by these authors that this segment roll is part of a balance protection mechanism. The visual attenuation of the CoP sway response indicates that visual information is  64  important in controlling whole body sway during quiet standing. By contrast, the absence of visual attenuation of the upper body roll response during quiet standing, suggests that alignment of the individual upper body segments does not utilize visual information to achieve the goal of an upright aligned position. Thus, visual and vestibular information appears to be integrated differently for alignment of the upper body segments versus orientation of the whole body in a gravity based environment. Smetanin and Popov (1990) reported similar observations, citing visual attenuation of G V S evoked responses. These researchers demonstrated that an external visual light source effectively reduced the magnitude of the G V S evoked push and the subsequent whole body movement towards the anode electrode, as indicated by the CoP profile. These researchers also showed that when the light source was attached to the subject's head, there was no reduction in the CoP displacement. In short, when the body rolled towards the anode electrode, the light source, attached to the head, traveled with the visual field. As a result, there was no external visual cue to indicate body position relative to vertical. Therefore, visual information is utilized in controlling whole body sway only when it is provided as an external cue to enable assessment of the body position in space. It is not surprising then, that for the task of quiet stance visual information does not play a role in body segment alignment (absence of body roll attenuation with vision), as vision does not provide information of head position relative to the trunk. Following the initial roll in response to G V S , most subjects established a new stable stationary posture. Interestingly, although preceded by 1500 ms of G V S , the initiation of the step did not demonstrate any further significant changes in body roll, or CoP movement towards the anode electrode. The lack of substantial vestibular response during this initiation phase supports recent speculation indicating the initiation of a step as a ballistic feed-forward program (Lyon and Day 1997). The implication of a pre-planned motor sequence suggests that once the movement has begun, there is no involvement of sensory information in the outcome of the task. In support of the feedforward theory, Hollands and Marple-Horvat (1996) have demonstrated that visual information is used during the stance phase of locomotion in order to help program the progression of the next swing phase. The removal of vision during various periods in the stance phase affected accurate placement of the swing limb, especially when visual removal was in the late phase of stance. Conversely, visual occlusion after toe off of the swing limb did not affect successfulness of task completion, indicating that movement after toe off during targeted locomotion was under feed-forward control. In the present study, the continuous application of stimulation for 1500 ms prior to movement may provide sufficient time for an internal reassessment of vertical. Popov et al. (1986) and Smetanin et al. (1988) introduced evidence of a spatial perception system, which has been shown to guide the direction of the G V S response, for  65  the purpose of maintaining equilibrium. The absence of a G V S response during the initiation phase in the current study suggests that a new vertical was established internally, based on the altered vestibular input, and was considered compensated for by movement towards the anode. Therefore, the initiation of the step began from a perceived neutral upright position, according to the spatial perception system, or internal representation of the body. Once subjects entered the execution phase of the step, the results emphasize both the importance of vestibular information (as reported previously Bent et al. 2002), in addition to a prominent visual influence. Body roll, CoP and C o M demonstrated evidence of compensatory actions during the execution of the step and its termination. In contrast to quiet standing, significant attenuation of the vestibular roll response was observed from T 0 2 onward, when vision was present. This suggests an important role for vision in helping to supplement the available vestibular information during this phase. What is also important to note is the probable difference in weighting of somatosensory inputs between E O and EC conditions. With the eyes closed there are only vestibular and somatosensory contributions to balance control. Integration of vestibular information with proprioceptive input is necessary to determine an accurate perception of the body in space (Lund and Broberg 1983, Hlavacka et al. 1996). Therefore it is likely that somatosensory information plays a larger role in EC trials than when the eyes are open. At H C 1 somatosensory information from both feet is available to facilitate the determination of body position in the environment. However, given that the response is larger when the eyes are closed than when open, somatosensory information isn't able to contribute as effectively as visual input, demonstrating the important role of visual information in the execution phase of the task. It is also important to address the possible changes in the step that may result from G V S evoked eye movement. Current research has indicated ocular roll of the eyes in the direction of the anode electrode upon application of G V S (Zink et al 1997, 1998). Documentation of the subjective tilt of the visual field was found to correlate with the intensity of stimulation, although the degree of ocular torsion was considerably smaller than the perceived visual tilt. It is conceivable that tilt of the visual field in this manner would be some what destabilizing and therefore may contribute to changes observed in the response to G V S . However, it is our belief that ocular torsion plays a minor role, i f any, in the responses observed in the current study for two reasons. First, during the stationary phase of the step, there were no significant differences in the degree of upper body roll with the eyes open or closed. As indicated earlier, it is proposed that subjects align their upper body segments to an internal representation of vertical, and therefore do not use visual information for relative segment orientation. Secondly, Mars and colleagues (2001) provide data suggesting that the change in subjective vertical is larger when the  66  eyes are open than when closed during G V S , indicating contributions from both a change in the internal perception of vertical and tilt of the visual field. In contrast, our data demonstrate that the presence of vision attenuates the response, suggesting that the changes observed with the eyes open are likely not a result of compensatory responses to a tilted visual field. A surprising finding is that visual attenuation of the roll response during the execution phase was only statistically significant in trunk and pelvis roll, but not for head roll. Although it has been shown that vision plays a large role in steering (Hollands et al. 2001) and foot placement during locomotion (Hollands and Marple-Horvat 1996), it appears from our data that vestibular information, likely in conjunction with somatosensory information, predominantly influences the position of the head on the trunk even when vision is present during the dynamic task of stepping. This is likely to provide a stable platform from which to view the environment. In short this work has provided, for the first time, evidence that vision has a unique role in integration with vestibular information during a dynamic task such as stepping. What is novel is that, although vestibular information is considerably more important during a dynamic task, relative to quiet standing, visual input appears to have a dominant role for successful task completion. We have shown that the integration of these two sources of sensory input differs depending on the nature of the task at hand. During a dynamic situation, visual information is critical in helping to maintain both whole body equilibrium as well as regulating relative segment orientation. In contrast, vision appears to play a minor role in controlling body segment alignment during quiet standing. It is possible that the appearance of substantial visual dominance, in the latter phase of stepping, is due to the nature of the termination of the step, where it is critical for subjects to know where their body is for successful task completion. Vision would facilitate such a process where a stable end position is critical. hi summary, compensatory responses to GVS were demonstrated in quiet standing, and again much later during the execution of the step. These compensatory responses were demonstrated in M - L C o M displacement, M - L CoP excursion and roll of individual body segments. Surprisingly, the magnitude of body roll in response to the vestibular perturbation was not altered during quiet standing whether the eyes were open or closed. In contrast, the body sway response, indicated by the CoP movement was largely reduced during this time frame. In the execution of the step, vestibular information became more important for the successful completion of the task. It was found, however, that visual information modulated this vestibular evoked response. Overall, it can be concluded that vestibular information has several roles during the execution of a voluntary step forward. Vestibular information appears to play an important role in both alignment of upper body segments, as well as in helping to maintain whole body stability in a gravity based environment. These vestibular roles are differentially integrated  67  with visual input during quiet stance and during the dynamic execution phase of a forward step. 5.5 B r i d g i n g S u m m a r y  The results from the previous two studies demonstrate the importance of vestibular information during the process of executing a forward step. It was found that vestibular information is up-regulated when the subject progresses into the 'more dynamic' phase of the stepping task. However, we cannot say definitively when this up-regulation begins during the transition from a stationary position into the dynamic task. In addition, the differential modulation of vestibular information, and the integration of vision with vestibular information across the phases of the stepping task provided evidence suggesting the presence of 'dynamic' phase dependent modulation of vestibular input. Phase dependent modulation based on the gait cycle has been demonstrated in other sensory systems during dynamic tasks, but to date has not been investigated with respect to vestibular inputs. The purpose of the following study therefore was to further examine whether the weighting of vestibular information is modulated differently at specific points in a gait initiation task. The question of when vestibular weighting is increased will be investigated by probing vestibular contributions using G V S at specific times during the gait initiation process. Gait initiation was chosen over a single step to allow a pure examination of the initiation process without the confounding challenge of terminating the task.  68  CHAPTER 6 Experiment III Is the use of vestibular information regulated differently across the initiation of walking? (In preparation for Brain Research, July 2002) 6.1 Introduction The task of locomotion is a complex activity that requires integration of available sensory information, both in a predictive (Hollands and Marple-Horvat, 1996, Drew et al. 1996) and a feedback (Zehr and Stein 1999, Pang and Yang 2000) manner. In addition, successful locomotion is equally dependent on appropriate and timely modulation of sensory and motor pathways. The regulation of sensory information during locomotion has been shown to differ across the different gait phases (double support/single support, stance phase/swing phase). Gait phase dependency is different from the 'dynamic' phase dependency previously described by Bent et al. (2002) (Chapter 4). Dynamic phase dependency refers to changes resulting from the transition from a stationary phase to a dynamic phase, whereas gait phase dependency deals with changes related to the gait cycle. Gait-phase dependent regulation of afferent information during locomotion has been demonstrated with respect to visual (Assaiante et al. 1989, Hollands and Marple-Horvat 1996), muscle stretch (muscle spindle) (Capaday and Stein 1986, Crenna and Frigo 1987, Dietz et al. 1990, Yang et al. 1991, Sinkjaer et al. 1996, Zehr and Stein 1999, Schillings et al. 1999), muscle load receptor (Golgi tendon organ) (Pearson and Collins 1993, Yang et al. 1998, Sinkjaer et al. 2000, Pang and Yang 2000), and cutaneous (Forssberg 1979, Wand et al. 1980, Eng et al. 1994, Zehr et al. 1998, Zehr and Stein 1999) afferent information. In fact, phase dependent modulation of afferent information from many sensory systems has been shown to have a substantial role in the dynamic stability and progression of gait. To date, however, phase dependent contributions from vestibular inputs, based on events during gait initiation, have yet to be examined. Phase dependent alterations have also been shown in motoneuron pool excitability through Hoffman reflex (H-reflex) testing during gait in humans. Dietz and colleagues (1990) found that during locomotion the Quadriceps H-reflex reached its peak magnitude during early stance. In contrast, the Soleus H-reflex amplitude was found to be the largest during the late stance phase of gait (Capaday and Stein 1986, Crenna and Frigo 1987). These findings both indicate facilitation of the H-reflex response for completion of the locomotor task, with increased push off propulsion in the soleus during late stance and enhanced quadriceps activity to prevent collapse at the knee in early stance. Similar results have been found using the stretch reflex technique, demonstrating positive feedback in soleus during the propulsion phase to provide  69  additional force, (Yang et al. 1991, Andersen and Sinkjaer 1996), as well as providing a functional role in ankle stabilization in early stance (Lortie et al. 1997). Further studies have supported the contributions of phase specific reflexes and their importance in generating locomotor behaviour. Pearson (1995) and Whelan et al. (1995) both support a role for muscle load receptors (lb afferents) in the transition from stance to swing during locomotion. The reflex reversal of the lb afferent from its accepted negative feedback role, to contributing positive feedback input during locomotion, facilitates the support process and propulsion phase as well as significantly contributing to the stance-to-swing transition (Pearson 1995). Specifically, the gradual reduction of force near the end of stance, signaled by group I afferents, has been shown to be crucial in initiating this transition in the cat (Hiebert et al. 1996, Pearson et al. 1998). Recently Pang and Yang (2000) were able to demonstrate a similar phenomenon in the human infant, where an increase in load on the support limb was able to induce a prolonged stance phase, whereas a reduced load caused the onset of swing. In addition to the necessity of afferent information in the propagation of a successful gait pattern, phase dependent regulation of sensory information has been shown to play a substantial role in maintaining balance to enable the task of locomotion to progress. In particular, cutaneous reflex responses highlight specific compensatory balance strategies involved in postural control during locomotion. Forssberg (1979) demonstrated that both electrical stimulation as well as tactile perturbation of the cat hindlimb during the swing phase of locomotion resulted in appropriate stumbling corrective responses. The response enabled the cat to lift the paw and clear any imposing obstacles. Similar responses were later demonstrated in humans using both real obstacle perturbations (Eng et al. 1994) and stimulation of nerves that innervate different cutaneous areas of the foot, signaling contact with an obstacle (Zehr et al. 1997, Zehr et al. 1998, Zehr and Stein 1999). These studies have provided evidence of phase dependency of cutaneous information, whereby, activation of skin receptors (on the foot dorsum, or sole) at the point of transition from stance to swing results in a different response than that obtained during the transition into stance. Load receptors have been implicated in the modulation of these cutaneous reflexes in order to help adapt the locomotor pattern to the environmental conditions (Basitaanse et al. 2000). Given the extensive study of other systems, it is surprising that little research has examined the role of vestibular information, either in facilitating the progression of gait, or in helping to maintain stability during the gait task. Studies examining vestibular contributions during locomotion have focused on gait in vestibular patients (Glasauer et al. 1994, Tucker et al. 1998, Peruch et al. 1999, Sasaki et al. 2001), gait analyses using caloric vestibular stimulation (CVS; Kubo et al. 1997), or using galvanic vestibular stimulation (GVS; Fitzpatrick et al. 1999,  70  Bent et al. 2000a, Jahn et al. 2000). The technique of G V S , where current is passed through electrodes placed over the mastoid processes, is relatively novel in the examination of vestibular contributions during locomotor tasks. Both Fitzpatrick and colleagues (1999) as well as Bent et al. (2000a) were able to demonstrate, using G V S , that vestibular information has a critical role during gait, as demonstrated by the significant deviations in trajectory toward the anode electrode. The G V S technique is useful for investigating vestibular contributions during gait as the stimulation can be applied for controlled periods of time, with altering polarities (anode/cathode). The electrical current has been shown to increase (cathode) or decrease (anode) the firing rate of the peripheral vestibular afferents (Goldberg et al. 1984), leading to changes in vestibular information, which are associated with specific postural changes during a task. These postural responses enable one to test for periods of time when vestibular information is more heavily weighted, by assessing the relative magnitude of the response. The weighting of vestibular information during dynamic tasks in both animals (Igarashi et al. 1970, Marchand and Amblard 1984, Lacour et al. 1997b) and humans (Smetanin et al. 1988, Inglis 1995, Severac Cauquil and Day 1998, Hlavacka et al. 1999, Sasaki et al. 2001, Bent et al. 2002) has been shown to exceed vestibular contributions during stationary tasks. However, specific vestibular contributions during the transition into a continuous dynamic task such as walking have not been examined. The initiation of gait is the transient period between upright standing and steady state gait, requiring movement of the centre of pressure (CoP) backwards and toward the stepping limb, causing displacement of the centre of mass (CoM) forward and toward the stance limb (Mann et al. 1979, Jian et al. 1993, Lyon and Day 1997). The process of initiating gait is regarded as an anticipatory motor program composed of invariant characteristics (Breniere and Do 1986, Das and McCollum 1989, Lepers et al. 1999), that generates the necessary forces for the progression of the first step (Breniere and Do 1986, Couillandre et al. 2000, Lyon and Day 1997) while compensating for the movement-imposed imbalances on the system (Mcllroy et al. 1993, Massion, 1992). Lyon and Day (1997) proposed that the initiation of a forward step is a ballistic feedforward motor program, which is based on the direction of the intended step and the initial stance position. They suggested that once the initiation of the movement begins, the extent to which the step can be altered is limited. This suggests that changes in sensory input during the initiation process will have little to no affect on the planned outcome of the task. A Recent investigation has identified contributions of vestibular information during a voluntary forward step using the technique of G V S (Bent et al. 2002). Results demonstrated that vestibular contributions differed across the initiation and execution of the step task. Specifically, no differences were found during the anticipatory postural adjustment (APA), whereas  71  differences became significant in the more dynamic execution phase of the step. These preliminary findings could suggest phase specific contributions of vestibular information. However, the delay of 1500ms between the onset of the vestibular perturbation and the beginning of the step may have allowed subjects to internally recalibrate their posture to a new perceived vertical before stepping, resulting in the absence of a response to the stimulation during the A P A (Bent et al. 2002). To date, the specific temporal modulation of vestibular contributions has not been investigated during any transitional locomotor task. The purpose, therefore, of the current study was to determine whether the weighting of vestibular information is different at specific points during the transitional task of gait initiation. It was predicted that differences in the magnitude of segment roll, as well as differing amplitudes of M - L foot placement would be observed, dependent on when stimulation was delivered. Such differences in magnitude and timing would indicate a change in the sensory weighting of vestibular information suggesting upregulation (increased sensitivity to the sensory input) or down-regulation (decreased sensitivity to the sensory input) of vestibular information at specific events in the process of initiating gait. Portions of the data have been presented in abstract form (Bent et al. 2001).  6.2 Methods Six subjects were recruited for the study (2 men, 4 women, 24-43 years, 169.7cm± 8.7, 62.8kg ±8.1). They were informed of the protocol and provided written consent. A l l participants reported no previous history of motion sickness, epilepsy, or any neurological or musculo-skeletal problems. 6.2.1 Subject Preparation and Equipment Subjects were prepared by placing three non-collinear infrared markers (IREDs) on the head, the trunk and the pelvis, as well as bilaterally on the feet, the legs and the thighs. Galvanic vestibular stimulation (GVS) was applied through two carbon rubber electrodes (9cm ) placed 2  behind the ears on the skin over the mastoid processes. Prior to application, the skin was cleaned with alcohol and conduction gel was applied to increase the electrode-skin conductance. Stimulation consisted of a square wave pulse delivered from a stimulator (Model Grass S48) through a constant current stimulus isolation unit ( A M Systems 2200). Prior to the onset of the study, a threshold level of stimulation current was determined for each subject (Bent et al. 2000a). Briefly, subjects were instructed to stand with their feet together. They were given increasing intensities of G V S at 0.05 m A increments until sway was observed in the direction of the anode, or subjects reported disorientation. During the data collection, G V S was delivered in a random order at an intensity of three times each subject's individual threshold with the anode on  72  the left (L) or right (R) side. The range of stimulation current was between 0.8 m A to 1.2 mA. 6.2.2 Test Procedures To begin testing, subjects stood on two force platforms with their feet side by side at their natural stance width. They were directed to maintain equal weighting on each limb to enable calculation of CoP for triggering stimulation. Foot position and orientation were marked to ensure a constant starting position (width and location on plates). Subjects were instructed to begin walking forward across a third force platform with their right limb (at a constant preferred cadence), at the sound of an auditory tone. In half of the trials vision was occluded with goggles. The goggles that were used were opaque, eliminating the detection of objects and forms, but allowing light through the lenses. Subjects were instructed to keep their eyes open inside of the goggles. Subjects continued to walk forward until they were verbally instructed to stop. During the trials, participants kept their elbows slightly flexed to allow natural arm movement during gait, and reactive postural corrections if needed, while also preventing the blocking of IREDs. In the event that subjects missed a force platform or stopped walking prematurely, another trial of the same condition was recollected after the completion of the pre-organized random sequence of trials. The need to recollect data occurred in only 4.3% of trials. Delivery of G V S was triggered at one of three events during the initiation of gait: onset of the anticipatory postural adjustment (APA), toe-off of the swing limb (TO), or subsequent heel contact of the swing limb (HC). The stimulation continued for the duration of the walk forward. At A P A , delivery of G V S was triggered by a 10% increase in the vertical force under the swing limb (right limb). Through inspection, this increase in vertical force was closely representative of the point when the M - L CoP excursion exceeded 4 mm beyond quiet stance baseline, which has been defined as the onset of an A P A (Mcllroy and Maki 1999). Stimulation at TO was triggered by a drop in vertical force below 5N under the swing limb and at H C by an increase in vertical force above 5N upon stepping onto the third force platform. Five trials for each stimulation condition (APA/TO/HC, L/R) and five control trials were collected, with vision present and with vision occluded, for a total of 70 randomly presented trials. 6.2.3 Data Reduction Optotrak (model 3020), three dimensional (3D) data from the IREDs were sampled at 100 Hz and the force platform (AMTI, model OR6-5) data were digitized at 1000 Hz. Optotrak data are reported to have a resolution of 0.01 mm at a distance of 2.25 m. Due to calibration error and increased distance of measurement, this accuracy may be slightly compromised. As a result, an estimation was made of the resolution of the data in degrees. Based on this estimation, results  73  are reported throughout the study with an accuracy of 0.01°. For C o M calculations, the principle axes and centres of mass were first defined for each segment ( M I S C H A C Inc). Total body C o M position was then calculated for each data sample. Independent body segment roll (in the frontal plane) and position data for foot placement were also calculated from the kinematic data. Movement of the upper body was defined as roll of the head, trunk, and pelvis segments. Upper body segment roll data were analysed by examination at 100 ms epochs, beginning from the stimulus until 1500 ms post-stimulation. Foot position was calculated during each step as the average location of the toe marker over a period of 100 ms with the foot in contact with the floor. The average value for foot placement was calculated during: the 100 ms after onset for A P A , the 100 ms before Toe-off for TO, and 100 ms after heel contact for the H C conditions. To determine changes in foot placement, movement of both feet was calculated with respect to a coordinate system aligned with the position of the left foot at the onset of the trial (in the mediolateral plane). For the analysis of stimulation effects between conditions, non-stimulation trials were subtracted out to highlight differences due to G V S . To first observe whether there was an effect of vision on the roll response (in the coronal plane), head roll data (representing body roll) were analysed using a 3 stimulation (L,R,N) X 3 event (APA, H C , TO) X 2 eyes (EO, EC) repeated measures A N O V A at each time point. Further analyses of the upper body roll responses (head, trunk and pelvis) were analysed separately for the vision present and vision occluded data and are discussed in detail below. Three 3 Stimulation (L,R,N) X 15 Epoch (100 ms-1500 ms) repeated measures A N O V A s were run to assess roll data for the head, trunk and pelvis for each of the event conditions (APA, TO, HC). This was followed by a 3 Stimulation (L, R, N) X 15 Epoch (100 ms-1500 ms) repeated measures A N O V A with the data from head, trunk and pelvis averaged to assess onset times for each of the event conditions. These tests were performed for both the vision present and vision occluded data. Peak roll was also assessed to determine differences in the magnitude of the response when stimulation was delivered at the three events, A P A , TO, H C . Due to the natural variability in body movement during locomotion, not linked to the stimulation, the assessment of peak roll was determined with data from the control trials subtracted out. Peak data were also assessed as absolute values in order to prevent the cancellation of left stimulation (negative) and right stimulation (positive) effects when collapsing across stimulation to calculate main effects based on event. Three 2 Stimulation (L/R) x 3 Event (APA/TO/HC) repeated measures A N O V A s were performed on the peak roll data for the head, trunk and pelvis. To assess differences in foot placement, each step was labelled as 'Step One', 'Step Two' or 'Step Three'. For A P A and TO, 'Step One' was the first step with the right limb. For  74  stimulation at H C , the next step with the left limb was considered Step One', as it was the first step after stimulation, where effects could be observed. Two 3 Stimulation (L, R, N) X 3 Event (APA, H C , TO) repeated measures A N O V A s were run separately for vision present and vision occluded trials to determine changes in foot placement with G V S . Significance was determined at p<0.01 for all A N O V A calculations in order to protect for Type I errors due to multiple A N O V A s . Post-hoc tests were run using Tukey's Honestly Significant difference (HSD) analyses with significance set at p<0.05.  6.3 Results 6.3.1 Upper Body Response When vision was occluded, significant roll towards the anode electrode (averaged across events) was observed by 450 ms following stimulation for the head (F ,i5o=17.772, p<0.0001) 30  and by 600 ms following stimulation for the trunk (F ,i5o=37.987, p<0.0001), and pelvis 30  (F3o,i5o-22.117, p<0.0001), exhibiting a top down body roll response (Figure 6.1). With the presence of full vision, the degree of body roll in response to the stimulation (represented by absolute head roll) was significantly attenuated (reduced magnitude compared to roll observed with eyes occluded) by 600 ms following stimulation (Figure 6.2) (F ,io=17.525 p=0.0005), 2  which follows previous reports for standing (Day and Bonato 1995). However, despite attenuation with vision, significant upper body roll was still observed and exhibited a similar top down response with the head reaching a significant degree of roll by 600 ms (F ,i5o=4.674, 30  pO.0001) followed by the trunk at 700 ms after stimulation (F i5o=8.546, pO.OOOl). The 30)  pelvis roll did not reach significant values when vision was present. Significant stimulation effects were observed up to 1500ms for the head and trunk, and up to 1400 ms for the pelvis roll with the eyes occluded. With vision present significant stimulation effects remained up to 1000 ms for the head roll and 1100 ms for trunk roll.  75  Eyes Occluded  Eyes Open  Head Roll (Degrees)  -4 : i J  50b  1(J00  1500  2000  2500  Trunk Roll (Degrees)  1  500  1000  1500  2000  5Q0  0 ?  KJOO  1500  2000  2500  1000 1500  2000  2500  1(J00  2000  2500  w  -2  -4  2500  i  500  2  Pelvis Roll (Degrees)  0  i  r-r i  -2  1  500  1(J00  1500  2000  -4  2500  1  5d0  1500  Stimulation  TO HC  Figure 6.1 Absolute roll responses in head, trunk and pelvis in thefrontalplane (degrees) averaged across subjects (with control subtracted out) with the eyes occluded (left column) or open (right column). Positive roll values indicate roll toward the right, in response to anode right stimulation and negative values indicate roll toward the left, in response to anode left stimulation. Each condition, APA (light grey), TO (dark grey) and HC (black), are aligned to the onset of stimulation for the trial, indicated by a vertical dotted line. The horizontal axis indicates divisions of 100 ms time epochs. Arrows indicate the onset of counter roll of the head. Figures at the bottom illustrate the specific events at which stimulation occurs.  76  Stimulus  A  B  Figure 6.2 Absolute head roll responses (frontal plane) averaged across subjects with the eyes open (open circles) and eyes occluded (filled circles) are presented for the three conditions A P A (light grey), T O (dark grey) and H C (black). Control trials are subtracted out. Positive roll values are roll to the right in response to anode right stimulation, negative values indicate roll to the left in response to anode left stimulation. A) vertical line indicating time of significant visual attenuation (600ms after stimulation). B) vertical line indicating time of average peak head roll.  77  Further analyses of the trunk and pelvis roll displacements demonstrated that each event condition (APA, TO, HC) exhibited different onset latencies for significant stimulation effects. Post-hoc analyses across the 15 epochs indicated that for the trunk and pelvis, the earliest response to G V S occurred when stimulation was delivered at H C . Specifically, when vision was occluded, trunk roll became significantly different from no stimulation trials at 500 ms for H C with the anode right and at 600 ms for H C with the anode left (F ,i o=41.120, pO.0001), 30  5  whereas significance was reached later when stimulation was delivered at A P A for both polarities (800 ms: F3o i5o 11.298, p<0.0001). Similarly, pelvis roll became significantly different from no —  i  stimulation trials at 600 ms after H C with the anode left and at 700 ms after H C with the anode right (F  30>150  =12.273, p<0.0001. Again, stimulation at A P A resulted in a delayed roll of the pelvis  reaching significance at 800 ms after stimulation for both polarities (F ,i5o=7.784, p<0.0001). A 30  similar trend was observed when vision was present, where the trunk roll reached significance earlier in the H C trials (600 ms; F3,150=5.152, p<0.0001) compared to the trials where stimulation was delivered at A P A (700 ms; F30,150=6.308, pO.0001). In short, these results highlight the presence of an earlier response in segment roll when G V S was delivered at H C , while A P A trials exhibited the latest response. Calculation of the magnitude of peak roll when vision was occluded indicated that the degree of roll reached by the head, trunk and pelvis was largest when G V S was delivered at H C compared to the other two stimulation events: A P A and TO (Figure 6.1). Main effects for event demonstrated a significant difference between the three event stimulations for the magnitude of peak head roll (F =7.561, p=0.01), trunk roll (F =7.784, p=0.0092) and pelvis roll 2jl0  2;10  (F ,io=l0.134, p=0.0039). Increases in head roll after stimulation at H C reached a magnitude of 2  2.75°, which was significantly larger than the peak roll differences reached after stimulation at A P A (2.01°; p<0.05; Figure 6.3). Trunk and pelvis roll magnitude changes both demonstrated significant differences that were similar in trend to head roll, with increases in trunk roll reaching only 2.38° after A P A , compared to 3.38° after H C , and pelvis roll increases peaking at 1.91° after A P A compared to 3.23° after HC. When vision was available, no significant differences were found between the peak magnitude of upper body roll dependent on the event, for head roll (F =1.798, p=0.2153), trunk roll (F , =0.255, p=0.7797) or pelvis roll (F =2.035, 2>10  p=0.1813)(Figure6.3).  2 10  2jl0  78  Figure 6.3 Peak magnitude of absolute roll responses in the frontal plane for head, trunk and pelvis (degrees) are presented. Trials with eyes occluded are in the left column and eyes open in the right column. Significant differences between events are shown with asterisks. Peak magnitude of segment roll is attenuated with vision. Significance tested at p<0.01.  79  6.3.2  Lower  Body  Response  In addition to upper body roll responses, application of GVS resulted in compensatory changes in foot placement. When vision was occluded subjects exhibited significant changes in foot placement within the first step compared to no stimulation trials (F io=13.727, p=0.0014). 2j  The data also demonstrated a significant interaction (F o 17.085, p<0.0001), after which a post=  4i2  hoc analysis determined that these changes occurred only in the trials when stimulation was delivered at H C (p<0.05; Figure 6.4). Neither the A P A condition nor the TO condition exhibited significant changes in foot placement during the first step. B y 'Step Two', significant stimulation main effects were maintained (F  2i20  =l 15.396, p<0.0001), and a significant interaction  (F o=7.171, p=0.0009), followed by post-hoc analyses, demonstrated that both H C and A P A 4)2  trials were significantly different from no stimulation trials (p<0.05). It wasn't until the third step after stimulation that no interactions were observed, although significant foot placement changes remained (F =259.65, p<0.0001). To test whether the absence of a significant interaction was 2>10  because all event conditions (APA, TO, HC) exhibited a significant difference from no stimulation trials (and therefore, no interaction with each other), a post-hoc Tukey's was run. A significant difference was found for H C (left and right), A P A (left and right) and TO (right) from non stimulation trials (p<0.05). When vision was present, the foot placement responses to GVS were significantly attenuated within the first step compared to vision occluded trials (F =21.808, p=0.005). In 15  addition, when vision was available, none of the stimulation conditions were different from the no stimulation trials in the first step (F =0.881, p=0.4444). B y the second step there was a 2ilo  significant stimulation effect (F =17.295, p=0.0006) as well as an interaction (F =12.923, 2il0  4)20  p<0.0001). Both A P A and H C conditions demonstrated significant changes in foot placement, but only for the stimulation with the anode on the left (p<0.05). B y 'Step Three', main effects again indicated a significant difference between stimulation and no stimulation trials (F =l9.089, 210  p=0.0004). However, there were no significant interactions during 'Step Three'. Following the examination of significant stimulation effects (stimulation versus no stimulation), differences in the magnitude of the foot placement change between the three event conditions were also found. In 'Step One' with vision occluded, the change in foot placement at HC (4.53 cm) was significantly larger than during A P A (2.46 cm) and TO (1.86 cm) trials ( F , i o l 1.555, p=0.0025). Analysis of 'Step Two' also indicated significant event main effects =  2  (F ,io 9.088, p=0.0056). Post-hoc analyses revealed that the differences were between A P A =  2  versus TO and TO versus HC. These event effects reflect significant differences in both A P A (15.13 cm) and H C (11.83 cm) from non-stimulation, but an absence of significant change in the  80  TO trials (5.49 cm). B y 'Step Three', there were no main effects for event. When vision was present, significant event main effects were demonstrated in 'Step Two' (F2,io 15.0009, =  p=0.0010). Post-hoc analyses demonstrated that the differences lay between A P A (5.84 cm) versus T O (1.50 cm) and TO versus H C (3.96 cm).  81  -8D  -30  -10  10  30  3D  -80  -30  -10  10  30  3D  Figure 6.4 Foot placement changes during forward locomotion with G V S delivered at one of three times (APA; light grey, T O ; dark grey, H C ; black) or without G V S (no stimulation; shaded) with the eyes occluded (A) or open (B). Foot prints indicate the position of the foot at each step (cm). Stimulation with anode left is displayed in the left column, anode right in the right column. Note that due to the time of stimulation, 'Step One' after stimulation for H C trials are the second step in the diagram. For both A P A and T O 'Step One' after stimulation is the first step documented. Asterisks indicate significant differences between the stimulation trial indicated (APA, T O or HC) and no stimulation. Significance tested at p< 0.01.  82  6.4 Discussion The application of G V S at specific events during the gait initiation process resulted in differences in the magnitude and timing of both the upper body roll response and changes in foot placement. The monotonic increase in the body roll response from A P A to TO to H C suggests that these changes may be due to continued up-regulation of vestibular weighting in relation to the gradual increase in the dynamic nature of the gait initiation task, and not specifically related to gait initiation events per se. Similar to upper body roll, the largest and earliest responses in foot placement were demonstrated after stimulation at H C suggesting a greater weighting of vestibular information at this time relative to the other events tested. Foot placement after stimulation at both A P A and TO failed to demonstrate immediate changes, although significant modulation was observed later in steps two and three respectively. These findings present, for the first time, evidence of vestibular modulation based on the specific time during gait initiation at which the stimulus is delivered. The differences between the upper body roll response and the lower limb change in base of support suggests a separation between the roles of the vestibular system in controlling upper body alignment versus aiding in whole body stability and locomotion. 6.4.1  Upper  Body  Response  - vision  occluded  As the subjects progressed forward from the A P A (beginning stationary: 0.07m/s) to H C (almost attaining gait speed, Breniere and Do 1986, Jian et al. 1993: 1.17m/s) there was an increase in the dynamic nature of the task. Such movement of the C o M in the forward direction has recently been shown to result in up-regulation of vestibular information during the transition from standing to a discrete locomotor movement (Bent et al. 2002). These researchers concluded that a change in the dynamic state of the movement required an increased contribution from vestibular information to maintain equilibrium and to successfully complete the step task. The results from Bent et al. (2002) are supported by observations from the current study where an increase in the magnitude of the upper body roll response was demonstrated from A P A to TO followed by another increase from TO to H C . Upper body roll responses observed in the current study are proposed to demonstrate an attempt to re-align the body with the perceived change in vertical elicited by the G V S . For successful body orientation in a gravitational reference frame, it has been shown that information from the vestibular system is integrated with various sources of somatosensory input to develop an accurate representation of the body in the environment (Lund and Broberg 1983). In addition, the weighting of vestibular information has been shown to vary dependent on the availability of other sources of sensory input (Welgampola and Colebatch 2001a). Both the A P A and H C  83  conditions maximize the opportunity to utilize somatosensory information from the foot sole and calf muscles (Sorensen et al. 2002) to relay body location in the environment because both feet are in contact with the ground. In contrast, at and following TO, assessment of the body relative to the support surface is based on information from only one foot. Following this rationale, one would then expect comparable weighting of vestibular information during A P A and HC, and therefore similar degrees of body alignment change, if modulation of vestibular information was dependent on the particular locomotor event, and consequently the presence and weighting of other sensory input. Instead the results indicated the largest upper body response to occur at H C and the smallest response after stimulation at A P A suggesting that other influencing factors are contributing to the resulting modulation. These observations support the conclusion that the magnitude of the roll response demonstrates modulation based on the dynamic state of the subject, similar to that described in the previous study (Bent et al. 2002), and not modulation based on the specific locomotor event. Therefore regulation of vestibular information for the control of upper body alignment does not exhibit the phase dependent modulation of sensory information that has been demonstrated by many other sources of sensory input (Zehr and Stein, 1999, Pang and Yang 2000). 6.4.2  Upper  Body  Response  - vision  present  When vision was present, there was no evidence of event dependent modulation of the upper body roll response, although statistically a stimulation effect remained. The initial response to GVS demonstrated a similar profile, both with and without vision, until the presence of vision attenuated the roll response compared to vision occluded trials. These findings support the observations previously reported by Day and Bonato (1995) where it was suggested that vision acted in a feedback manner to alter the vestibular response. The modulation of the GVS response by the presence of vision resulted in an attenuation by 600 ms, which was well in advance of the observed peak roll response (900 ms on average). Therefore, the attenuation with vision present occurred before differences in the event modulation could be observed. It might be speculated that similar to the eyes occluded condition, there was up-regulation of vestibular information due to the transition to a dynamic state, even when vision was present. However, this cannot be determined with the present data. What can be determined is that the attenuation of the vestibular response with visual input provides evidence that vision appears to have a greater role than vestibular information for upper body alignment during the completion of a gait initiation task.  84  6.4.3 Lower  Body  Response-  vision  occluded  Accurate placement of each foot is important in order to help progression of the C o M in the desired direction as well as to maintain stability in the frontal plane (MacKinnon and Winter 1993). The significant change in foot placement in the first step after the H C condition suggests that vestibular information was heavily weighted during the double support phase. It has been shown that both vision (Hollands and Marple-Horvat 1996), as well as muscle receptor information (Hiebert et al. 1996, Zehr and Stein 1999, Misiaszek et al. 2000, Sorensen et al. 2002), is important during the stance phase for the progression of gait. It is likely that HC is a critical time for the integration of vestibular information with these other sensory sources during the double support phase in order to plan the progression of the next step (Hollands and MarpleHorvat 1996, Patla et al. 1991). In contrast, both the A P A and TO conditions did not exhibit changes in foot placement within the first step. This observation may suggest one of two things. First, the lack of response may indicate that the perturbation was initially delivered at a time when vestibular information was largely down-regulated. Secondly, the observation of no change in foot placement may indicate an inadequate amount of time to generate the response. Foot placement changes after stimulation at TO were not seen until 'Step Three'. This late response is proposed to have occurred because the stimulus was delivered at a time when vestibular input was largely down-regulated. It is possible that although the vestibular input relayed information that kinematic changes were necessary to maintain locomotor progression, the reduced weighting of vestibular input indicated that there was no imminent danger to equilibrium and, therefore, an immediate response was not necessary. However, for the A P A condition, significant changes in foot placement were seen in the second step, which were even larger than those seen in step two after HC, which suggests that not only was vestibular information being used, but the weighting of vestibular input was probably large during A P A . One might argue that the response observed in 'Step Two' after stimulation at A P A was due to vestibular up-regulation at heel contact, and not in fact during the A P A due to the late appearance of the response. However, stimulation at TO did not result in a response immediately following heel contact or at "Step Two", demonstrating that the observed responses were indicative of vestibular contributions at the time of the event being tested, not at the subsequent heel contact. To determine whether the absence of a significant response during the first step in A P A and TO was due to a down regulation in vestibular weighting, it must also be considered whether there was sufficient time for a response to occur. It is possible that the lack of significant change in foot placement in the first step after stimulation at TO may have been due to an insufficient amount of time for the vestibular perturbation to manifest itself. There were, however, no  85  significant compensations in the next two steps after TO, indicating an alternative explanation other than insufficient time. The absence of a response in foot placement after A P A is also unlikely to be related to a time constraint. The duration of the initiation process was longer than the double support phase after HC, which saw significant changes in the foot placement within one step. Why then were there such drastic changes in the first step after delivery of the stimulation at H C and not after A P A ? The answer to this question may lie in the ability to alter the planned movement. The initiation of gait is considered to be a feed-forward process (Breniere and Do 1986, Crenna and Frigo 1987). As Lyon and Day (1997) have suggested, the feed-forward nature of a step initiation task infers that once the movement has begun, sensory perturbations do not affect the completion of the task. As a result, it is proposed that changes in sensory information that are integrated during the execution of the A P A in gait initiation are presented too late in the progression of the first step to affect its outcome, therefore resulting in no change to foot placement. In contrast, stimulation at H C occurs during a time when sensory information has been shown to affect the planning of the following step (Patla et al. 1991, Hollands and MarpleHorvat 1996) thereby providing support for the early changes observed in foot placement after H C . Despite the absence of an immediate response in 'Step One' in A P A trials, it is possible that vestibular information during the A P A is integrated with other sensory sources to generate an internal representation of the body in the environment, as large foot placement changes are observed by 'Step Two'. Although no changes in foot placement were present in the first step, a vestibular response was not completely absent during the A P A . Significant changes were observed in body roll by 450 ms (averaged across events), indicating that vestibular information is important for alignment during this phase of the initiation task. The unique vestibular regulation of upper body control and foot placement supports the idea presented recently, where it was suggested there are at least two distinct roles for vestibular information related to postural stability in quiet stance (Bent et al. in press). It is proposed in the current study that vestibular contributions to foot placement facilitate whole body postural stability, while upper body segment alignment contributes to the generation of appropriate gravitationally oriented movement. The rapid changes in foot placement that were observed in the first step after stimulation at HC, created a change in base of support size, and consequently CoP location, that may have facilitated movement of the C o M . In rightward perturbation trials (anode right), subjects widened their base of support by swinging the left leg wide. In contrast, and counterintuitive to stability, the left foot crossed over the right limb when the perturbation was to the left. It is possible that these observed foot placement patterns were related to the changes in pelvis roll that  86  were tilted down to the right in anode right trials, and tilted down to the left in anode left trials. However, these foot placement alterations are also similar to changes in foot placement reported by both Patla and colleagues (1999) and Hollands et al.  (2001)  in relation to steering during  locomotion. These researchers noted alterations in the location of foot placement as a strategy that subjects used to move their C o M during trials where they were instructed to walk to the right or left. Although our subjects maintained a forward direction, it was possible that they employed a similar strategy to maintain a stable C o M as that demonstrated for rapid movement of the C o M in a steering situation. Support for these observations are also noted by MacKinnon and Winter (1993) who indicated that the distance between CoP and C o M dictates acceleration of the C o M in the M - L direction. M - L placement of the foot further from the up-coming swing leg will result in greater C o M acceleration towards that limb, and M - L placement of the foot closer will slow the progression of the C o M in the swing direction, compared to natural walking. In the current study it is difficult to determine whether these observed changes in foot placement were implemented in an anticipatory fashion to help facilitate movement of the C o M in a new direction of progression, or whether they represented a reactionary response, for the purpose of moving the C o M back into a position of equilibrium. 6.4.4 Lower  Body  Response-  vision  present  When vision was present, smaller changes in foot placement were observed relative to the responses seen when vision was occluded. However, changes in foot placement with vision present still exhibited modulation based on the gait event at which the stimulation was delivered. These results suggest an important role for vestibular information in foot placement while walking. It is postulated that event related vestibular regulation, even in the presence of vision, indicates the importance of vestibular information in whole body stability and task progression (Jian et al. 1993, MacKinnon and Winter, 1993). Previous data has indicated that an important role also exists for visual information in lower limb control during locomotion (Hollands and Marple-Horvat, 1996). Hollands and Marple-Horvat (1996) were able to demonstrate that visual information for targeted stepping was critical in the last 100 ms prior to toe-off for successful foot placement. While it can be concluded from the current data that vision plays a substantial role in assisting with whole body stability, the persistence of vestibular modulation based on the gait event indicates that placement of the feet requires specific weighting of vestibular information to facilitate successful locomotion. Therefore, both visual and vestibular sensory sources are necessary for lower limb control during the locomotor task. In summary, the results report for the first time evidence of vestibular modulation based on the event during the gait initiation task when stimulation was delivered. Modulation based on  87  gait event, however, was only demonstrated in changes for foot placement, and was not evident in the upper body roll response. This highlights a changing role for vestibular input at specific times during the gait initiation task for lower limb control, supporting the idea that in the presence or absence of vision, vestibular regulation is essential for maintaining whole body stability and the successful progression of the locomotor task. Changes in upper body roll are believed to contribute to alignment of the body segments in a gravitational reference frame, to facilitate proper assessment of the body in the environment. Differences in the magnitude of the roll response are postulated to result from an increase in vestibular weighting during the transition into the dynamic task of initiating gait, and not specifically in relation to the locomotor events per se. Clearly the observations suggest a distinction in the contribution of the upper body versus the lower body to successful completion of the gait initiation task. These distinct roles appear to shape the vestibular contribution to upper and lower body control. Further research isolating a period of steady-state gait is the next step in determining event related regulation of both upper body roll and foot placement through vestibular control. 6.5  Bridging Summary  The results of the above study demonstrate evidence of vestibular regulation in both upper body roll (of the head, trunk and pelvis), and in foot placement. The progressive increase in body segment roll across the three events led to the conclusion that vestibular inputs contributing to upper body control are modulated based on the dynamic state of the task. In contrast, the differences seen in foot placement coincided with the events in the gait initiation process, indicating event dependent vestibular modulation. Although the results demonstrate the novel finding of event dependent modulations in the use of vestibular information for lower limb control, to truly test the occurrence of temporal modulation of vestibular input during locomotion, one must isolate a period of the task that is not confounded with issues such as the transition from a static to a dynamic state. Such influences may alter the outcome and make it difficult to ascertain responses dependent on the gait cycle alone. For this reason it is necessary to observe a steady-state task, such as during the third or fourth step after the initiation of locomotion. To further examine the presence of phase dependent vestibular modulation the next study examined vestibular contributions during steady-state locomotion.  88  CHAPTER 7 Experiment IV When is vestibular information important during walking? (In preparation for Nature Neuroscience, July 2002) 7.1  Introduction  The task of walking is deceivingly simple-looking. In truth, this complex activity is achieved with the appropriate and timely modulation of sensory information. Locomotor studies have provided insight into the involvement of somatosensory and visual information for successful gait. However, the majority of research to date has not investigated the specific contributions of vestibular information. Research examining patients with vestibular deficits during locomotor tasks has demonstrated the importance of vestibular contributions for vertical orientation (Borel et al. 2002), path integration (Cohen 2000) and segment stabilization (Pozzo et al. 1991). Subjects with bilateral vestibular deficits are able to walk forward successfully over a short distance with their eyes closed (Cohen 2000, Glasauer et al. 1994, Tucker et al. 1998), and are able to stabilize their head in the sagittal plane during walking (Pozzo et al. 1991). However, these patients tend to walk at a slower self selected pace and produce increased amounts of head movement during such locomotor tasks as hopping. Recent investigations of patients following a unilateral neurotomy revealed deficits in their ability to orient their head and trunk to vertical, as well as presenting evidence of decreased head and trunk stability during dynamic deep knee bends (Borel et al. 2002). Patients with unilateral vestibular deficits also demonstrate a marked lean towards their lesioned side and exhibit significant deviations from the path trajectory when walking slowly (Brandt et al. 2000, Brandt et al. 2001, Jahn et al. 2000). Research on healthy populations supports the conclusions reached with vestibular deficient populations. Specifically, vestibular contributions to head stabilization during dynamic tasks have been shown to enable successful gaze (Pozzo et al. 1990), as well as to provide a stable reference frame from which to generate postural responses (Pozzo et al. 1995). In addition, vestibular contributions during dynamic tasks have been proposed to play a role in determining the appropriateness of triggered postural responses (Inglis et al. 1995). Such vestibular feedback has been termed sensory reafference and is suggested to be used to assess the magnitude of the evoked postural response and to help achieve a stable end position. This end position is based in part on the internal representation of the body relative to the support surface, which is generated through the integration of vestibular and somatosensory inputs (Popov et al. 1986). Given the importance of these vestibular roles in postural control, and evidence that vestibular information  89  has a larger role during dynamic tasks (Inglis et al. 1995, Bent et al. 2002), it is surprising that vestibular information has not been further examined to determine whether there are specific periods during dynamic tasks where vestibular input is more heavily weighted. The postural nature of a task, simple (such as standing) or more complex (such as walking on a balance beam) (Hulliger et al. 1989), and the specific mechanical state during a task, stationary or dynamic (Bent et al. 2002, Severac Cauquil and Day 1998, Smetanin et al. 1988) both influence the sensitivity, or weighting, of sensory information (referred to as up or down regulation). The weighting of one sensory system at a particular time during a task is also altered by the contributions from other sensory inputs (Marchand and Amblard 1984, Horak and Hlavacka 2001). During locomotion, both vision and somatosensory information have been demonstrated to exhibit phase dependent modulation. The period of 100 ms before toe-off has been indicated as the critical time for visual sampling in order to program the limb trajectory in targeted stepping (Hollands and Marple-Horvat, 1996). Likewise, soleus H-reflex responses during voluntary movement have been shown to be the largest during the late phase of stance where the muscle facilitates propulsion (Sinkjaer et al. 1996, Yang et al. 1991). It is therefore proposed that vestibular inputs would exhibit similar characteristics of phase dependent weighting to optimize sensory contributions to the locomotor task. Some insight into the phase dependent use of vestibular information has been demonstrated in walking cats (Matsuyama and Drew 2000). Increased firing of vestibulospinal neurons (VSNs), with connections to the lumbar spinal region, was observed at heel contact of the forelimb during gait on a treadmill. These data were proposed to indicate increased vestibular contributions to facilitate antigravity activity and propulsion during the stance phase of gait of the hindlimb. Furthermore, excitatory inputs from cutaneous and muscle afferents and inhibitory influences from cerebellar projections have been shown to modulate these VSNs at the time of foot contact (Allen et al. 1972, Wilson et al. 1967), and are proposed to "sculpt" the output of the VSNs (Matsuyama and Drew 2000, pg 2253). In combination, these influences may act to alter the resultant excitatory descending inputs to the lower limbs, and thus produce a phase dependent response (Orlovsky et al. 1972b). In addition to animal research, the study of vestibular contributions during locomotor tasks has used various other methods (Kubo et al. 1997, Cohen 2000) including the technique of Galvanic Vestibular Stimulation (GVS). G V S has been employed only very recently to investigate vestibular control during walking in humans (Fitzpatrick et al. 1999, Bent et al. 2000a, Jahn et al. 2000). These studies support patient research and the importance of vestibular information during locomotion by demonstrating subject deviation from the path trajectory with the G V S perturbation. This technique involves the application of galvanic current through the  90  mastoid processes to influence the firing rate of the peripheral vestibular afferents (Goldberg et al. 1984, Minor and Goldberg 1991). Stimulation has been shown to increase (cathode) or decrease (anode) the firing of the peripheral afferents and leads to a body sway response towards the anode in quiet standing. The benefit of this technique is the ability to apply discrete perturbations to the vestibular system at selected times, enabling testing of vestibular contributions beginning at various points in the locomotor task. The magnitude of the response to the stimulation is indicative of the degree of vestibular weighting at the time of application. To examine the specific weighting of vestibular information during a locomotor task in the present study, subjects were tested during steady-state locomotion. To date, no research has attempted to determine whether vestibular information is in fact weighted more heavily at individual points in any locomotor task in humans. Therefore, the purpose was to examine whether vestibular information is regulated differently during walking. It was hypothesized that the application of GVS at specific events during the gait cycle would lead to differences in the magnitude of the response, thus indicating differential weighting of vestibular information during walking. 7.2 Methods  Eight healthy subjects (5 male and 3 female) aged 25.5 ± 6.98, (height 177.9 ± 6.2 cm, mass 70.6 ± 11.9 kg) were recruited. They were informed of the protocol and provided written consent. A l l participants reported no previous history of motion sickness, epilepsy, or any neurological or musculo-skeletal problems. Approval from the local ethics committee was obtained prior to data collection. 7.2.1 Subject  Preparation  and  Equipment  A n Optotrak 3D system (NDI inc, model 3020; two position sensors) was used to collect kinematic data (digitally sampled at 100 Hz) in order to determine linear segmental positions and to estimate body centre of mass (CoM) displacement. Three non-collinear infrared markers (IREDs) were placed on the subject's head, trunk and pelvis, and on each foot. For C o M calculations, the principle axes and centres of mass were first defined for each segment (MISCHAC Inc). Body C o M position was then estimated for each data sample as the combined C o M of the head, trunk and pelvis. Segmental roll (in the frontal plane) of the head, trunk and pelvis, as well as foot placement were also calculated from the kinematic data. Two A M T I force platforms (Advanced mechanical technology inc., model OR6-5) were staggered along the floor so that subjects walked across them during their steady-state progression (with their right and then left foot, respectively). Force data were sampled at 1000 Hz. Binaural, bipolar galvanic vestibular stimulation (GVS) was delivered via two carbon  91  rubber electrodes that were 9cm in area, and shaped to fit behind the ears. Before application of 2  the electrodes, the skin over the mastoid processes was rubbed clean and covered with conduction gel. Stimulation was delivered by a Grass Stimulator (Model Grass S48) through a constant current stimulus isolation unit ( A M Systems 2200). The intensity of the stimulation varied for each subject. As in previous experiments (Bent et al. 2000a, Bent et al. 2002) testing was performed in order to determine each subject's individual threshold for G V S intensity during standing. Briefly, subjects stood with their feet together (but not touching) and were asked to report any sensations of dizziness or disorientation while the stimulus intensity was gradually increased from 0.05 mA. The intensity of stimulation during the experiment was set at three times the individual anodal threshold (range 1.0 - 1.5 mA). 7.2.2 Test Procedures Participants stood a distance of three steps from the first force platform. Practice (3-5 trials) was given before data collection to establish a comfortable natural, walking speed, while walking with vision occluded. Instructions were given to initiate with the right lower limb and to walk forward until instructed to stop (7-8 steps, roughly 4.3 m). Participants walked with their arms against their sides and flexed at the elbow to allow arm swing during walking, while preventing the blocking of IREDs. Free arm movement also allowed use of the arms in postural strategies i f desired. Vision was occluded with a pair of custom made opaque goggles that enabled light to enter, but prevented determination of edges or objects. Subjects were instructed to keep their eyes open inside the goggles. At the end of each trial, individuals were led back to the initial starting position with the goggles on and no indication of path deviation was offered. Galvanic vestibular stimulation (GVS) was delivered at three different events for the right limb during steady-state gait: heel contact (HC) triggered by an increase in vertical force of 5 N on the first force platform (FP1); mid stance (MS; which is also coincident with mid-swing of the contralateral limb) triggered by a change in the anterior posterior (A-P) forces on FP1 from a negative value to a positive value; and toe-off (TO) triggered by a drop in vertical force below 5N on FP1. Delivery of the G V S perturbation included three different configurations including the anode electrode placed over the left mastoid process (L), the right mastoid process (R) or no stimulation (control condition). The duration of the G V S perturbation continued for the entire length of the trial (approximately 3-4 seconds). A total of 39 trials were collected during a testing session. Five trials were collected for each of the 6 stimulation conditions (Anode RJAnode L , Toe-off/Mid Stance/Heel Contact), hi addition to these 30 stimulation trials, there were 9 trials collected with no stimulation, 3 at the onset of testing, 3 at the end of testing and 3 during the block of stimulation trials.  92  7.2.3  Data  Reduction  Due to room size and camera configuration limitations, the head data were not always present at the point of first heel contact with the right limb (RHC1). As a result, data were analyzed beginning at left toe-off (LTOl), which occurred approximately 100 ms later. L T O l was selected because it was the next gait event to occur after RHC1 that could be used to normalize data. To ensure there were no differences during L T O l due to stimulation at HC1, an A N O V A was calculated for peak head roll and indicated no significant difference between stimulation and non stimulation conditions (F i4=2.506, p=0.1174). Throughout the results and 2j  discussion data are reported as occurring after stimulation at HC. A l l data were normalized based on specific events in the gait cycle. In order to enable removal of normal movement variability at the point of stimulation, the three stimulation events (HC, M S , TO) were used as anchors for time normalization. Data were normalized over 400%. The phases were comprised as follows: phase one (0-100%) from first left toe-off ( L T O l ) to right foot mid-stance (MS), phase two (100-200%)from MS to first right toe-off (TO), phase 3 (200%300%) from TO to second right heel contact (RHC2), and phase four (300-400%) from RHC2 to second right toe-off (RT02). Based on previous inspection of the data, the timing of L T O l and R T 0 2 were chosen as the point of the peak vertical velocity of the foot centre of mass (CoM) for the left and right foot respectively. The times of M S and TO were indicated based on the same criteria used for stimulation at these events. Finally, the time of RHC2 was indicated as the point when the velocity of the right foot C o M in the A-P direction first decreased below one centimetre per second (cm/s). Based on force platform data from the left foot at L H C 1 , this variable was an accurate indicator of heel contact. Once time normalized, the averaged data from the control trials (zeroed to stimulation) were then subtracted out of the stimulation trials. Following this procedure, only the residual roll responses due to stimulation remained, which could then be assessed for peak roll angle in degrees. The onset of the roll response by the head, trunk and pelvis was also assessed based on the point in time when segment roll after stimulation surpassed the average roll in a control trial plus or minus one standard deviation. Due to normalization to establish peaks, roll response data were presented in percentage of the total trial. To convert percentage into time the averaged time data from each phase was calculated from each subject. Right and left foot placements were calculated at each step as the location of the toe during foot contact with the floor. Medio-lateral (M-L) foot positions were calculated relative to left toe position at L T O l . 'Step One' following G V S at H C or M S was taken with the left foot. In TO trials 'Step One' was performed with the right foot. Therefore, to enable data averaging,  93  foot placement changes were presented in terms of 'Step One' and 'Step Two' after stimulation, not with respect to right and left foot changes. Two 3 Stimulation (L, R, N) X 3 Event (HC, M S , TO) repeated measures A N O V A s were used to assess foot placement in 'Step One' and 'Step Two'. Significant interactions were tested using Tukey's Post-hoc analyses to determine which event exhibited significant foot placement changes due to stimulation. To assess differences in the magnitude of the foot placement changes across the three event conditions (HC, M S , TO) a 2 Stimulation (R, L) X 3 Event (HC, M S , TO) repeated measures A N O V A was run for 'Step One' and 'Step Two', where the control trials were subtracted out, and the absolute values were tested. A 2 Stimulation (L, R) X 3 Event (HC, M S , TO) X 2 Polarity (No stimulation, stimulation) repeated measures A N O V A was performed to determine the presence of a significant stimulation effect between trials for peak segment roll. A 2 Stimulation (L, R) X 3 Event (HC, M S , TO) repeated measures A N O V A was then performed to assess differences in the magnitude of roll between the three event conditions with control trials subtracted out. For all statistical tests, significance was determined at p<0.05. 7.3 Results Delivery of G V S resulted in roll of the head, trunk and pelvis towards the anode electrode (Figure 7.1). The roll response of the head began earliest, followed by the trunk and pelvis exhibiting a top down response, supporting previous literature (Day et al. 1997). Segment roll onsets for a representative subject occurred at 280 ms, 680 ms, 770 ms on average for head, trunk and pelvis respectively. Significant differences in the magnitude of peak roll after stimulation were found in all three segments; head roll (2.34°; Fi =262.872, p<0.0001), trunk roll >7  (2.79°; FI,T=137.588, p<0.0001), and pelvis roll (2.70°; F,, =178.324, pO.0001) relative to 7  movement without stimulation. However, no significant differences were found for the magnitude of the peak roll response between the three events of H C , M S , and T O for the head (F , =1.592, p=0.2383), the trunk (F ,i =2.203, p=0.1473) or the pelvis (F ,, =1.993, p=0.1732) 2 14  2  4  2  4  (Figure 7.1). For foot placement, no significant changes were found at 'Step One' following the delivery of G V S (Figure 7.2). However, significant alterations in foot placement were observed by 'Step Two' (F =41.389, pO.0001) compared to trials with no stimulation (Figure 7.2). 214  Significant interactions (F =l0.822, pO.0001) followed by a post-hoc Tukey's test determined 428  that significant changes to foot placement occurred when G V S was delivered at H C for both anode right (14.9cm) and left (-9.8 cm) in comparison to no stimulation. In addition, significance was found for stimulation at T O with the anode to the right (9.8 cm) compared to no stimulation  94  trials. Further assessment of foot placement magnitude determined that there was a significant difference between event conditions (F ,i4=5.306, p=0.0193). Foot placement changes after 2  stimulation at H C (12.4 cm) were shown to be significantly larger than following stimulation at M S (6.3 cm; p<0.05) (Figure 7.3a). The foot placement changes at H C were also larger than changes after stimulation at TO (9 cm), although changes between these two events were not statistically different. C o M displacement changes were assessed at each step along with foot placement changes. Significant differences in displacement were found by 'Step Two', at the point when changes in foot placement were observed (F 8=12.036, p<0.0001) (Figure 7.3b). Post-hoc 4>2  analyses determined that C o M displacement in H C anode right, H C anode left and T O anode right trials were all significantly different from C o M displacement in trials without stimulation (p<0.05). In addition C o M displacement in H C trials (8.5 cm) was found to be significantly larger than in M S trials (4.2 cm), and larger than C o M displacement at T O (5.12), although not significantly.  95  Head Roll (Degrees)  Trunk Roll (Degrees)  Pelvis Roll (Degrees)  H C  t  MS  TO  t  t  RHC2  RT02 i HC 1  MS TO  Figure 7.1 Segment roll (frontal plane) data is presented from the head, trunk, and pelvis averaged across subjects. Data have been normalized to specific events in the gait cycle (heel contact: HC, mid-stance: M S , toe-off: T O , second right heel contact: RHC2, second toe-off with right limb: RTO2) as indicated by the vertical dashed lines (percentage). HC (Black line), M S (dark grey line) and T O (light grey line) trials are presented (control trials subtracted out). In stimulation trials, galvanic vestibular stimulation (GVS) was delivered at one of the three events indicated by the arrows. Positive roll represents movement to the right, negative roll is movement to the left. No significant differences were found for the magnitude of roll between the three event conditions for head, trunk or pelvis roll. Note, phase 4 (300%-400%) is proportionally longer in duration than the other phases.  96  Figure 7.2 Foot placement data averaged across subjects are presented. Data are aligned to the right foot, which is the foot that corresponds to the onset of stimulation for heel contact: H C (black), mid-stance: M S (dark grey) and toe-off: T O (light grey). The first step, taken with the left foot represents 'Step One' after stimulation for the trials where stimulation is delivered at H C and MS. The next step, taken with the right foot, is 'Step Two' after stimulation for the H C and M S trials, but is 'Step One' after stimulation for T O trials. The following step with the left foot represents 'Step Two' for the T O trials. Data are presented in both directions in metres. Significant differences are found by 'Step Two' after stimulation, between H C and no stimulation for both polarities (left and right) and also in 'Step Two' for T O (anode right) from no stimulation, indicated by asterisks.  97  a) Foot placement changes (m) Step One  Step Two 0.20  0.20  0.15  0.10  0.05  0.00 HCL  HCR  MSL  MSR  TOL  Ha  TOR  HCR  MSL  MSR  TOL  TOR  HCR  MSL  MSR  TOL  TOR  b) C o M Displacement (m) Step One  Step Two 0.20  0.15  0.10  0.05  0.05  0.00 HCL  HCR  MSL  MSR  TOL  TOR  HCL  Figure 7.3 a) Foot displacement (metres) and b) C o M displacement data (metres) averaged across subjects for the stimulation trials (control trials subtracted out) where stimulation was delivered at heel contact (HC), mid-stance (MS), or toe-off (TO), with the anode left (HCL, M S L , T O L ) or right (HCR, MSR, TOR). 'Step One' represents the magnitude of deviation from non-stimulation trials in the first step after stimulation. Similarly, 'Step Two' represents the second step after stimulation. A significant difference in displacement was found between H C and M S for both foot placement and C o M displacement in response to the stimulation, indicated by asterisks. H C and M S were averaged across right and left conditions for testing. Standard deviation bars are shown.  98  7 . 4 Discussion The aim of the current study was to determine i f the weighting of vestibular information was modulated during steady-state gait in humans. Vestibular regulation of the upper body was not found to differ during walking, as indicated by similar amplitudes of upper body roll in response to the G V S perturbation at each event. In contrast, significant changes in foot placement were observed, which were found to be dependent on the event at which the G V S perturbation was initiated. These findings present evidence in support of phase dependent alterations in vestibular contributions to successful locomotion, in addition to supporting previous reports of separate vestibular control for the upper and lower body that have been reported in quiet stance (Bent et al. in press). To date, no research has demonstrated such phase regulation of vestibular contributions in any locomotor task in humans. However, despite being observed for the first time, the modulation of vestibular information based on specific gait events was not unexpected. Phase dependent modulation of sensory information has been demonstrated during locomotion for vision (Hollands and Marple-Horvat 1996), cutaneous feedback (Eng et al. 1994, Zehr and Stein 1999, Wand et al. 1980), and muscle afferents (Zehr and Stein 1999, Sinkjaer et al. 1996, Yang and Stein 1990, Dietz et al. 1990). What is remarkable is that to date phase dependent modulation of vestibular information has not been studied during locomotion despite evidence of significant vestibular contributions to vertical body orientation in dynamic tasks (Borel et al. 2002, Smetanin et al. 1988), head stabilization (Pozzo et al. 1995) and path integration during locomotion (Cohen 2000, Fitzpatrick et al. 1999, Bent et al., 2000a). To successfully maintain steady-state locomotion, both appropriate propulsion and maintenance of dynamic equilibrium must be achieved. Medio-lateral placement of the feet during forward walking has been shown to be the primary means of effectively altering C o M deviations in the frontal plane (MacKinnon and Winter 1993). Movement of the C o M is determined by the magnitude of separation between the centre of pressure, defined by the placement and force distribution of each foot, and the C o M (Winter et al. 1990). B y altering the foot placement, and subsequent propulsive forces one can change the direction of the C o M acceleration. Such manipulation is purposeful for both the progression of gait and for generating reactionary responses for the maintenance of dynamic equilibrium. In light of these facts, and the current results indicating event related vestibular modulation for the control of foot placement, vestibular information appears to play a critical role in the maintenance of whole body dynamic stability that differs at specific points during locomotion. The largest change in foot placement was observed when the perturbation was initiated at H C and smallest when stimulation occurred during M S . Although foot placement measures do  99  not occur at a fixed latency following stimulation onset it is apparent that the observed effects are not due to the duration of the perturbation. Despite an estimated stimulation latency of 100 ms between stimulation at H C and stimulation at TO there were no significant differences in the magnitude of foot placement changes between these two conditions, or between TO and M S by Step Two. In addition, no trend was observed in the magnitude of foot placement changes between the three conditions in Step One. If duration of stimulation were the cause of the changes observed in Step Two, one would also expect to observe changes by Step One after stimulation. Therefore, these results suggest changes due to phase dependent vestibular modulation, with the largest vestibular contributions occurring during double support, and the smallest during single support. Why might there be up-regulation of vestibular control of limb placement after HC, during the double support phase? It has been suggested that a critical time for the programming of limb placement occurs during the double support phase. Hollands and Marple-Horvat (1996) demonstrated that, during locomotion, the planning of accurate foot placement to a previously seen target is accomplished during the last 100 ms of the stance phase. This critical period for visual sampling indicates that changes to limb trajectory in length and width are modifiable within a step cycle. Also, these researchers concluded that programming for limb placement is complete by the time the foot leaves the ground at toe-off. Therefore, the double support period could also present an opportunity for vestibular information to contribute to the programming of the foot trajectory. Patla and colleagues (1991) support the claims of Hollands and Marple-Horvat (1996) regarding the ability to alter foot placement within one step. However, Patla et al. (1991) indicated that, although changes can be made to step length and width within one step cycle, changes in direction of greater than 30° must be programmed during the previous step. Further, successful changes in direction were found to be dependent upon when the cue was given. Patla and colleagues (1991) reported that when the signal to change direction was given 300 ms after heel contact (roughly at mid swing of the contralateral limb), subjects were unable to alter direction in the subsequent step, despite changes in direction being correctly implemented with cues at either heel contact (ipsilateral) or toe-off (contralateral). These researchers concluded that at least 200 ms preceding toe-off is needed to successfully plan for a change in direction during locomotion. It would appear, therefore, that use of vestibular information during double support would provide feedback of body position in space during a time which may be critical in the programming of both the on-going as well as the subsequent step. Vestibular up-regulation at H C may also serve to provide information for monitoring the successfulness of a voluntary movement or triggered postural response. Use of vestibular  100  information in this manner has been termed sensory reafference (Inglis et al. 1995, Severac Cauquil and Day, 1998) and has been proposed to occur during both voluntary and perturbation evoked movements. In the event of a slip or trip during locomotion, specific postural strategies to maintain dynamic stability are initiated, as has been demonstrated using perturbations from moving platforms (Nashner et al. 1983), treadmills (Figura et al. 1986) and other devices (Eng et al. 1994, Wand et al. 1980, Forssberg 1979). Work in both humans (Inglis et al. 1995, Horak et al. 1994) and cats (Inglis and MacPherson 1995) has shown that responses to platform perturbations are not triggered by the vestibular system, but are instead initiated at very rapid onset latencies by somatosensory information. These rapid responses are then proposed to be modulated based on sensory reafference from vestibular information. For example, Inglis et al. (1995) demonstrated that application of GVS prior to a platform perturbation resulted in changes to the response magnitude and final equilibrium position. These researchers proposed that postural changes occurred because GVS altered the perception of the body position with respect to vertical, indicating to the CNS that the initial somatosensory evoked response would not be appropriate to bring the body back to equilibrium. Sensory reafference has also been proposed to occur during voluntary tasks. Vestibular information has been suggested to contribute to the successful attainment of a planned head position during voluntary lateral head tilts (Severac Cauquil and Day 1998), as well as possibly contributing to path trajectory during locomotion (Fitzpatrick et al. 1999). A n accurate perception of the body in the environment is necessary to produce a planned trajectory during locomotion (Cohen 2000, Fitzpatrick et al. 1999) and to successfully utilize sensory reafference to complete a task. To generate an appropriate internal representation of the body, information from the vestibular system must be integrated with proprioceptive and cutaneous sources (Lund and Broberg 1983, Hlavacka et al. 1995). During double support, two feet are on the ground, and therefore the somatosensory information relaying the location of the CoP is potentially more reliable than during M S when one limb is still in the air. During steadystate locomotion, as presented by the current results, and in perturbed walking, contact of the foot with the ground at the onset of double support may, therefore, be a critical time to assess body position. Integration of vestibular information and somatosensory input during double support would indicate whether the initial somatosensory evoked strategy was appropriate in response to a perturbation and whether the acceleration of the body relative to the base of support would result in the desired end position during both perturbed and unperturbed walking. Finally, evidence of phase dependent modulation has been recently demonstrated through recordings of vestibulospinal neurons (VSNs) with connections to lumbar spinal regions in the walking cat (Matsuyama and Drew 2000). These researchers found that the largest percentage of  101  recorded VSNs demonstrated an increased firing rate at the point of forelimb foot contact during walking on a treadmill. It was concluded that these projections have the greatest influence on extensor muscles and, therefore, act primarily during times when there is the greatest need for antigravity actions. These findings support the current data suggesting an up-regulation of vestibular information during double support. The current data also demonstrated that vestibular information has a role in upper body control in a gravitational reference frame. This is indicated by the significant roll of the body segments towards the anode electrode in response to G V S . The absence of event related modulation in the vestibular control of upper body roll suggests that vestibular involvement in the alignment of the body segments is of equal importance across the gait task. These results are based on the view that the vestibular role in upper body control is in fact to ensure alignment of the body segments in an appropriate geocentric orientation. Pozzo and colleagues (1990) have suggested that the head acts as a frame of reference during complex dynamic tasks because both the vestibular and visual systems are able to relay information regarding the head in space. In order to ensure that the information from these sensory systems is appropriate and that sensitivity to changes is optimized, the head is stabilized in space in the pitch (Pozzo et al. 1990, Pozzo et al. 1991, Shupert and Horak 1996), yaw (Cromwell et al. 2001) and roll (Pozzo et al. 1995) planes. Pozzo and colleagues (1995) indicated that the perception of self in the environment is believed to result from the integration of vestibular input and visual information (when present) with somatosensory inputs. Such integration is proposed to enable a transformation of the head based reference frame, to the exocentric reference frame and, therefore, facilitate appropriate postural responses to maintain equilibrium. Stabilization of the head on the trunk through proprioceptive input has also been proposed to aid in the translation between reference frames (Pozzo et al. 1995) and is supported by additional research examining the role of integration in generating appropriate postural responses (Lund and Broberg 1983, Horak et al. 1994, Hlavacka et al. 1995, Hlavacka et al. 1996). As a result of these previous investigations and the current data, it is proposed that vestibular information plays a critical role in the maintenance of head stabilization in a gravitational reference frame across all phases of locomotion. When integrated with somatosensory input vestibular control of the head in space enables the successful completion of complex dynamic tasks. To conclude, data has been presented that supports the novel finding of phase dependent modulation of vestibular information during locomotion. This result is important because vestibular information is often overlooked as playing a substantive role during postural tasks since the majority of phase dependent postural responses to unpredictable perturbations are based on rapid reflex loops. The observation that weighting of vestibular information is greatest during  102  double support is supported by several lines of evidence in the literature on visual and somatosensory control of locomotion. In addition to being a time of increased importance for an antigravity posture, and for propulsion, double support is a time of heightened somatosensory input, which when integrated with vestibular information is likely an important contributor in establishing representation of the body in the environment. Such integration is proposed to enable successful programming of the current and subsequent steps during locomotion. Maintenance of a stabilized reference frame is also important for successful locomotion. Vertical alignment of the body was demonstrated to have importance across all phases of the gait task, as indicated by the absence of phase dependent modulation of upper body tilt. Thus, there are dual roles for vestibular input for upper body versus foot placement control. These results indicate the complexity of vestibular contributions to successful steady-state locomotion, and specifically highlight the importance of phase dependent vestibular contributions to lower limb control.  103  CHAPTER 8 Conclusions and General Discussion 8.1 G e n e r a l Findings The goal of the thesis was to examine the use of vestibular input, and as a result determine the nature of vestibular contributions for the execution of specific dynamic tasks. The results of the four studies collectively contributed to four main conclusions. First, vestibular information has greater sensory weighting during the more dynamic phases of a task, even in the presence of vision. Second, the magnitude of the response is dependent on both the magnitude of the vestibular perturbation and the phase in the gait cycle at which the stimulation is delivered during the task. Third, the vestibular contribution during locomotor tasks has different roles, and therefore is differentially modulated, in the control of upper body versus lower limb movement. Finally, the up-regulation of vestibular information for the control of lower limb movement demonstrates gait phase dependency, which is greatest during double support in the gait cycle. 8.1.1  Up-regulation  in dynamic  phase  The observation in Experiment II that weighting of vestibular information was increased as the task progressed from a stationary position into the dynamic step task, although novel, was not altogether surprising. Recent literature has highlighted an increased importance for vestibular information in dynamic tasks such as lateral tilt of the head (Severac Cauquil and Day 1998), sagittal tilt of the body (Smetanin et al. 1988), walking (Fitzpatrick et al. 1999, Bent et al. 2002), or in response to dynamic platform shifts (Inglis et al. 1995, Hlavacka et al. 1999). instead, the observation of interest was the phase dependent nature of the vestibular response, where no postural changes were observed during the initiation phase of the task despite the continuous application of GVS beginning 1500 ms prior to the onset of movement. It was concluded that during the stationary period prior to movement subjects were able to develop a new internal reference to vertical, thus allowing them to begin the step, as i f from a non-perturbed stationary position. Progression into the 'more dynamic' phase, and concurrently up-regulation of vestibular information, resulted in large compensatory responses late in the step. The addition of vision during the step task strengthened the argument for phase modulation of sensory contributions. During the stationary response to GVS, shifts of the whole body, relayed through CoP change were attenuated when vision was available. In contrast, upper body segment roll was not attenuated during this phase comparatively between the eyes open and eyes closed trials. In the dynamic phase of the movement, as vestibular inputs were up-regulated, visual information was shown to attenuate both the CoP changes and the upper body roll  104  response. These data reporting visual-vestibular interactions support phase dependent differences across the stepping task. The results also indicate a separation between upper body and lower body control and as an extension a separation in vestibular roles during quiet stance. It was proposed that the vestibular system contributes separately to the alignment of upper body segments to facilitate the translation of a head referenced system to the environment, and to whole body stability through lower limb control. 8.1.2 Phase  dependency  - Upper  Body  The phase dependent nature of vestibular contributions, and visual-vestibular interactions found in Experiment II is echoed in the findings of Experiments III and IV. These projects specifically addressed the question of phase dependent modulation by probing vestibular contributions at distinct times during locomotion. In addition, the results from Experiments III and TV support the evidence of a segregation between upper body and lower body control, and therefore separate roles for vestibular information in successful task completion. To investigate the presence of phase dependent modulation, based on gait events, the tasks of gait initiation and steady-state gait were examined in these two final studies. The initiation of gait is the transition from quiet stance into the dynamic task of walking and is studied in Experiment III. B y delivering G V S at specific times during the initiation process it was possible to examine differences in the weighting of vestibular information across the gait events. The responses for both upper body roll of the head, trunk and pelvis, as well as lower limb foot placement demonstrated phase dependent differences in the magnitude and timing of the response between the three events tested. However, although the largest response to GVS was observed after stimulation at H C for both upper body and lower limb control, discrepancies were observed for the other two conditions. Roll of the segments was smallest when the perturbation began at the A P A , and became progressively larger in response to stimulation at TO, with the largest response after stimulation at H C . In contrast, although foot placement changes were the largest and earliest after G V S at H C , it was during 'Step Two' that differences were observed for the A P A condition and not until step three after stimulation at TO, that foot placement changes occurred. It was concluded that the vestibular information influencing the upper and lower body responses was differentially modulated. The monotonic increase in upper body roll from A P A to TO and from TO to H C was proposed to result from increasing vestibular contributions across the transition from quiet standing into the dynamic gait initiation task. These findings parallel the conclusions from Experiment II where larger roll responses late in the dynamic phase of the step task suggested increased weighting of vestibular information. Further support for this conclusion  105  is provided from the data presented in Experiment IV. Roll of the head, trunk and pelvis during steady-state locomotion demonstrated no evidence of phase dependent modulation. These results are proposed to occur because steady-state gait does not encounter a transitional phase in C o M progression as do step initiation, and gait initiation, and thus steady-state gait does not provide an opportunity to observe the vestibular up-regulation during a change in dynamic state. These data on upper body control during locomotor tasks, provide two general conclusions. First, roll of the upper body and thus vestibular control of upper body orientation and stabilization, is modulated by the transition between dynamic states across a task. Secondly, the ability to align the head in an exocentric gravitational reference frame is equally important during all phases of a steady-state locomotor task. These observations are supported by Pozzo and colleagues (1995) who report that head stabilization in a vertical reference frame is essential to be able to accurately produce an internal image of the body in space relative to a ground coordinate system. 8.1.3 Lower  limb phase  dependency  Perhaps the most important finding of these experiments, however, was the observation of phase dependent modulation of vestibular information in the control of lower limb movements. To date, such a conclusion has not been reached in any tasks examining vestibular contributions in humans. Both Experiments III and IV indicated phase modulation of vestibular control of lower limb movement based on the event during the gait cycle that stimulation was delivered. Not only was phase dependency expressed by when changes took place, but it was also exhibited in the magnitude of foot placement responses. It is important to note that these differences between conditions were due to intrinsic modulation of vestibular weighting. That is, the magnitude of the G V S response was significantly different between events of the locomotor task despite the same level of G V S input. Significant differences in trajectory were also demonstrated in the results of Experiment I, however, these changes in the magnitude of trajectory deviation were found to correlate with the increase in the vestibular perturbation, and are therefore not indicative of vestibular weighting, but rather, vestibular sensitivity to extrinsic alterations in the magnitude of the stimulation. Also of interest to note is the observation that despite similar levels of stimulation in Experiments III and IV, lower limb responses after stimulation at H C occurred in 'Step One' during Experiment III, and 'Step Two' in Experiment IV. It is possible that changes in foot placement occur later in Experiment IV because the importance of vestibular information is weighted less during steady-state gait than during gait initiation. Brandt et al. (2000, 2001) and Jahn et al. (2000) demonstrated that vestibular deficient patients were more stable while running  106  than when walking and tended to deviate less when participating in tasks of greater velocity. These researchers suggested that vestibular influences are suppressed once a "highly automatic motor partem of fast walking or running has been initiated." They further indicated that contributions from sensory input would prove destabilizing and inefficient while these automated tasks are being performed. In following with these conclusions, vestibular contributions during steady-state gait would be down-regulated comparatively to gait initiation where the transitional nature of the task necessitates greater vestibular contribution. The task of initiating gait is viewed as a posturally challenging task due to the fact that balance must be destabilized in order for gait to begin. Jian et al. (1993) reported that the initiation of gait is far more challenging than steadystate gait, due to the fact that the destabilizing forces are far greater. These thoughts are echoed by Gresty (commentary in Takei et al. 1996) who indicated that "steady-state" conditions are "predictive-automatic" and therefore vestibular deficiencies (or in this case vestibular perturbation responses) would not necessarily be demonstrated during a task such as steady-state gait. 8.1.4  Vestibular  up-regulation  during  Double  Support  In both Experiments III and TV the largest and earliest response in foot placement was observed after stimulation at HC. These observations led to the conclusion that vestibular information is weighted more heavily during double support than at any other time tested during the gait cycle. Although it was indicated that vestibular projections contribute to the basic role of antigravity activity (Orlovsky 1972a, Matsuyama and Drew 2000), three other lines of evidence were proposed in support of why this time during the gait cycle is opportune for vestibular upregulation. H C has been indicated as a critical time for planning of both the current and subsequent steps during locomotion. As well, the increased availability of somatosensory information during double support is a factor that may influence the timing of vestibular upregulation due to the integrative role of somatosensory information with vestibular input in determining body position. Finally, up-regulation of vestibular information at H C is important to assess body position in space through sensory reafference, to interpret the effectiveness of postural responses. Tucker et al. (1998) demonstrated that patients with bilateral vestibular hypofunction (B VH) when asked to walk at a self selected pace chose to walk significantly slower than the control subjects in the study. However, when asked to walk at an experimentally selected pace they were able to do so, and there were no longer significant differences in the duration of double support (which was longer in the self selected pace trials), or in the horizontal velocity of the C o M . Tucker and colleagues (1998) proposed that vestibulopathic subjects choose to walk  107  slower to enable them to take advantage of spinal reflex loops that may help to facilitate or instigate postural responses to external perturbations. The observation of activation of motorneuron pools by descending vestibular inputs by Kennedy and Inglis (2001) may support such a hypothesis. It is possible that the vestibular projections may help to set a level of excitability in control subjects during standing and at specific critical times during the gait cycle (Matsuyama and Drew 2000). If a vestibulopathic subject were to encounter a perturbation, it is feasible that they would take more time to make the appropriate response because there is a reduced gain of the selected postural synergy. As a result, a slower pace is an effective compensatory strategy because it enables more time to generate a response before the C o M becomes destabilized. Although other sensory systems are likely to trigger the response, the absence of vestibular influence may also prevent the subject from accurately scaling the response to enable control of the C o M within the perceived equilibrium position. It may be for these reasons that a reduced velocity is often observed in vestibulopathic subjects (Cohen et al. 2000). These findings lend support to the observation of vestibular up-regulation during double support. It appears double support may be a critical time to integrate vestibular input to plan the next step in healthy individuals, and is therefore compensated with slower gait in vestibular absent patients. 8.1.5  Vestibular  roles in dynamic  movement  control  Given the increased weighting of vestibular information for the control of limb movement in both gait initiation and steady-state gait, what can we say about the role of vestibular information during these two different tasks? Medial-lateral deviations in lower limb placement have been demonstrated to be a primary means of regulating balance in the frontal plane (MacKinnon and Winter 1993). This is due to the fact that control of the C o M movement is largely influenced by the position of the CoP (Winter 1990). Changes in the placement of the feet in the gait initiation study versus the steady-state gait study suggests that there may be a difference in how vestibular information is used between the two tasks. This difference may stem from the fact that there are separate goals during gait initiation and steady-state gait. During gait initiation the goal is to attain dynamic equilibrium, where as in steady-state gait, the goal is to maintain it. During initiation, by the third step after stimulation, all three of the event conditions (APA, TO, HC) exhibited a similar magnitude of foot displacement from the non-stimulation trials. In support of this, there was no difference in foot placement between the event conditions. This may suggest that differences seen in foot placement during the first two steps were primarily for the purpose of re-establishing equilibrium based on the perception that the body was not progressing in the appropriate direction, or with the appropriate speed to enable a safe and accurate initial step. Depending on when the stimulation was delivered (and therefore the degree  108  of vestibular up-regulation) there was a larger discrepancy in current body position and the perceived body position necessary to maintain stability. Therefore foot placement can be interpreted as being reactionary to a perceived destabilizing change in body position relative to a 'new vertical'. As the subjects progressed into steady-state gait a new path trajectory based on the altered vertical was obtained that was determined by the level of stimulation. The degree of path deviation was likely similar between the three event conditions because after the initial response to G V S , the perturbation was interpreted as being constant. In contrast, during steady-state locomotion, both the C o M displacement and the foot placement position demonstrated significant differences between event conditions by the third step. This may suggest that the time the stimulation was delivered, H C , M S or TO, and consequently the degree of vestibular up-regulation, alters the perception of the vestibular cues of self position used for path integration. The use of vestibular information in achieving successful path navigation has been determined through studies involving both healthy populations (Fitzpatrick et al. 1999, Jahn et al. 2000) as well as vestibular patients (Cohen 2000, Peruch et al. 1999, Takei et al. 1996) hi Experiment IV, it may be possible that the large up-regulation of vestibular information at H C was perceived to indicate that the direction the body was progressing in, or the position of the body relative to vertical, was not appropriate to complete the planned forward trajectory. In the other two conditions, with less vestibular up-regulation, the perception may be one of less of an error in trajectory, and therefore, the compensations to direction are less. The idea of using sensory reafference to guide and evaluate the successful completion of a task is not a new concept. Severac Cauquil and Day (1998) demonstrated that lateral head tilts were influenced by the application of G V S . The degree of head tilt reached was altered based on whether the G V S indicated a larger or smaller head tilt than had actually occurred. Movement towards the target was changed to reach the perceived end point. These data demonstrated that vestibular information is used to help guide the magnitude of movement based on the expected feedback that would result from accurately completing the task. Vestibular information indicating that the goal had not been reached was therefore compensated for. These findings are echoed by Fitzpatrick and colleagues (1999) where they suggested that performance of a planned forward walking trajectory towards a target uses vestibular information during the task for comparison to the expected input, to ensure completion of the task. Therefore, the objective for compensatory limb movements found in the thesis during the steady-state task are believed to be for re-establishing locomotion in the planned trajectory by making changes based on the direction error reported by the vestibular system. This may be related to changes in the perception of self trajectory (Fitzpatrick et al. 1999), or to changes in the spatial perception of vertical, and  109  consequently alteration of the internal representation of self relative to the forward trajectory (Jahn et al. 2000, Peruch et al. 1999). Either way, we can conclude that although a role for vestibular information during locomotion, for lower limb control, may be to assess the appropriateness of a postural response to a perturbation (as proposed in the thesis), vestibular information can also be used to monitor the task and is a necessary contributor to the successfulness of task completion. The main results of the thesis, while supporting previous reports of increased vestibular contributions during dynamic tasks, present the novel finding of phase dependent modulation of vestibular information. In addition, differences in vestibular modulation for controlling upper body roll versus lower limb control indicate multiple roles for vestibular input. Upper body roll to provide a stable head reference frame for accurate postural responses is equally important across all phases of a steady-state locomotor task, whereas up-regulation of vestibular information is demonstrated at specific points in the gait cycle for lower limb control. Double support was found to be the time of greatest vestibular up-regulation, both during the task of initiating gait and during steady-state progression. 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