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Electromyographic muscle responses to single acoustic stimuli and repeated acoustic stimuli in supine.. Nichol, David Daniel 2008

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ELECTROMYOGRAPHIC MUSCLE RESPONSES TO SINGLE ACOUSTIC STIMULI ANDREPEATED ACOUSTIC STIMULI 1N SIJP1NE SUBJECTSbyDAVID DANIEL NICHOLB .H. Sc., McMaster University, 2005A THESIS SUBMITTED IN PARTIAL FULFILLMENT OFTHE REQUIREMENTS FOR THE DEGREE OFMASTER OF SCIENCEinTHE FACULTY OF GRADUATE STUDIES(Human Kinetics)THE UNIVERSITY OF BRITISH COLUMBIA(Vancouver)July2008© David Daniel Nichol, 2008AbstractElectromyographical (EMG) motor responses may be elicited by loud acoustic stimuli inhumans and vary based on presentation methods and body position. The purpose of this studywas to investigate the EMG responses caused by different presentation methods of acousticstimuli in a supine body position. Participants lay supine and maintained a voluntary plantarflexion contraction during trials. Auditory stimuli were presented from a speaker in frontofparticipants’ face. EMG was recorded from right orbicularis oculi (OOc) and bilaterally fromstemocleidomastoid (SCM), medial gastrocnemius, deltoid and soleus muscles. Single acousticstimuli (SAS) (40 ms, 124 dB tones), were presented to participants with ten minutes betweenstimuli. Repeated acoustic stimuli (RAS) (40 ms, 124 dB tones), werepresented repeatedly atintervals of 3-5 sec. Ten participants in a control condition wereexposed to six or more SAS and210 RAS during testing. Pre-pulse stimuli (40 ms, 85 dB tones) werepresented 100 ms beforeboth the RAS and SAS for 8 participants in the experimentalcondition. These participants wereexposed to 3 SAS plus pre-pulse and 3 SAS, then to a totalof 200 RAS and 200 RAS plus prepulse presented pseudorandomly. Five participants were exposed to210 RAS stimuli at 85 dB asa follow-up control condition. EMG signals were rootmean squared and trigger-averaged to theonset of the acoustic stimulus for the different conditions.Similar responses were rendered fromSAS and RAS in voluntarily contracting lower limbmuscles. SAS response amplitudes werevariable within single muscles across trials. RAS exposuresrendered an averaged response in allparticipants tested which lasted for 500 ms at a 7-8 Hzoscillation in the voluntarily contractingsoleus muscles. This response appears to be similar to SASresponses but of smaller amplitudeand only visible after the averaging of multipletrials. Responses to the 85 dB RAS stimuli alsooccurred in voluntarily contracting muscles. Pre-pulses showedinhibition in the OOc muscle inthe SAS condition. The observations suggest thatin humans, an EMG response may be elicitedin contracting lower limb muscles by SAS and RASand these responses may be related.11Table of ContentsAbstract.iiTable of Contents iiiList of Tables ivList of Figures vAcknowledgements viIntroduction 1Materials and Methods 6Participants 6Apparatus 6Stimuli 7Experimental Procedure 7Data Analysis 9Statistical Analysis 10Results 11Single Acoustic Stimulus (SAS) 11Repeated Acoustic Stimulus (RAS) 18Pre-pulse 22Discussion 28SAS Responses 28RAS Responses 29Pre-Pulses in SAS Trials 32Pre-pulses in the RAS Trials 33Pathway Associated with SAS and RAS (both to 124 dB and 85dB) 34Limitations 34Conclusions 35References 36Appendix 1: Literature Review 41The Anatomy and Neurophysiology of the Auditory System 42Single Acoustic Stimulus Reflex 44Reticulospinal Tract 45Single Acoustic Stimulus Pathway 47Evidence Supporting the SAS Pathway 48SAS Response 50SAS Responses during Static and Dynamic Tasks 52Pre-pulse Inhibition 54Pre-Pulse Inhibition Processing and Pathway 55Repeated Acoustic Stimuli (RAS) Reponse 57Appendix 2: Single Acoustic Stimulus Responses 63Appendix 3: Single Acoustic Stimuli Across Six Trials 66Appendix 4: Repeated Acoustic Stimuli Responses 69Appendix 5: SAS Responses and SAS with Pre-Pulses Responses 72Appendix 6: RAS Responses and RAS with Pre-Pulses Responses 76Appendix 7: UBC Research Ethics Board Certificate of Approval80111List of TablesTable 1. Number of SAS exposures for each participant in the control condition 13Table 2. Average onset latencies, peak onsets and peak amplitudes for the SAS,RASand85dBRAS 17Table 3. Right OOc muscles SAS and SAS with Pre-Pulse peak latencies andpeak amplitudes 23ivList of FhrnresFigure 1. Raw EMG of one participants SAS response in all muscles12Figure 2. Rectified EMG of the SCM, Deltoid and Soleus muscles ofsix SASresponses in one individual14Figure 3. Participants averaged EMG SAS responses in the right and leftsoleusmuscles16Figure 4. Averaged RAS responses of all muscles measured in one participant19Figure 5. One participant’s averaged RAS responses with and without the inclusionof exposures with SAS responses present20Figure 6. All participants averaged EMG RAS responses in the left soleus muscle 21Figure 7. One participant’s averaged RAS responses in the soleus muscles in trialswith and without pre-pulse stimuli 25Figure 8. 85 dB RAS responses compared to 124 dB RAS and RAS with pre-pulsetrials in one participant27Figure 9. Average RAS reflexes recorded in the left soleus muscles of allparticipants in pilot data58Figure 10. Average RAS reflexes recorded in the left and right soleus in onepilot participant 60Figure 11. Average RAS reflexes recorded in the left and right soleus muscles of onepilot participant with and without the presence of SCM activity 61Figure 12. Average RAS reflexes recorded in the left and right soleus muscles of onepilot participant with and without the presence of OOc activity 61VAcknowledgementsFirstly I would like to thank my supervisor, Dr. Timothy Inglis, for providing me withguidance and support throughout my degree. Thank you for introducing me to the world ofresearch and allowing me with the opportunity to move to the west coast. I would like to thankmy committee members, Drs. Mark Carpenter and Jean-Sébastien Blouin, for their advice andinsight throughout the project. Thank you to my lab mates: Brynne Elliott, Greg Lee Son andMelanie Roskell and the rest of the basement folk for all your help, support and friendshipthroughout my degree. Special thanks to Melanie Lam for her editing skills. I would like to thankall of the people who participated in my experiment and all the pilot experiments I conductedand I would like to thank everyone in War Gym for tolerating the constant noise I producedwhile testing. I would like to thank all my friends, both old and new, who have supported methrough this process. Finally, I would like to thank my Mom, Dad, Ian and Kate for always beingthere for me and allowing me to pursue the opportunities that I am given.viIntroductionA startle reflex is a motor response to an unexpected auditory, visual and/or tactilestimulus detected by the different sensory systems either independently orcollectively1(Delwaide & Schapens, 1995; Landis & Hunt, 1939; Quednow et al.,2006; Yeomans et al.,2002). Responses to loud acoustic startle stimuli vary between participants butmost peopledemonstrate eye closure and contraction of the neck muscles (Brownet al., 1991a). Generalizedresponses to sudden acoustic stimuli include trunk flexion, abduction of the arms,flexion of theelbows, pronation of the forearms (Brown et al., 1991a),extensor contractions (Rossignol,1975), and electromyographic (EMG) responses indistal musculature2(Brown et al., 1991b;Nieuwenhuijzen et al., 2000). A response to a single acoustic stimulus has inthe past beenclassified as a startle response when there is a burstingpattern ofmuscle EMG activity that is ofgreater amplitude than normal background activityin the orbicularis oculi (OOc) andstemocleidomastoid (SCM) muscles (Brown et a!., 1991b;Carlsen et a!., 2003). Startle responsesto acoustic stimuli may be foundthroughout the body’s musculature as the bursting pattern ofmuscle EMG activity following the evoking stimulus(Brown et al., 199 ib; Deiwaide &Schapens, 1995; Nieuwenhuijzen etal., 2000; Rossignol, 1975). Acoustic startle experimentstypically use intensities above 110 dBs but no louderthan 130 dB (Brown et a!., 1991a; Brownet al., 1991b; Csornor et al., 2006;Deiwaide & Schepens, 1995; Grosse & Brown, 2003;Nieuwenhuijzen et al., 2000; Valls-Solé et al., 1999a;Valls-Solé et a!., 2005). For the purposeof the present experiment, responsesthat would be classified as a startle by the presence of aSCM EMG bursting activity followingthe stimulus were termed a single acoustic stimulus(SAS) response. In some literature,startle responses throughout the body are no longer definedFor more information on the auditorysystem, see Appendix 1: The Anatomy and Neurophysiology of theAuditorySystem2For more information on the startlereflex/SAS reflex, see Appendix 1: Single Acoustic Stimulus Reflex1as such once SCM responses no longer occur (Brown et al., 1991b; Carisen et a!., 2003). Toavoid confusion of terms, the term SAS response was defined as responses to acoustic tones withlong interstimulus intervals with SCM EMG responses, and as the responses to acoustic toneswith short interstimulus intervals that render SCM EMG responses. Small amplitude musclereflex responses to loud acoustic stimuli with short interstimulus intervals, with no SCM EMGresponse present were termed repeated acoustic stimuli (RAS) responses in the present study.Both animal and human research has investigated the pathway through which the SASresponse travels to evoke muscular responses3.The reflex is proposed to propagate through thenucleus reticularis pontis caudalis (PnC or RPC) in the reticularformation and via thereticulospinal tract. Descending nerve fibers in the reticulospinal tract then synapse at spinallevels with lower motor neurons, either directly and possibly indirectlythrough interneuronsbefore reaching the neuromuscular junctions to elicit subsequentmuscle responses4(Davis et a!.,1982; Yeomans & Frankland, 1996).The SAS response throughout the body’s musculature seems to decline inamplitude, orin some cases disappears all together, after repeated exposure to the acousticstimulus. Thisdecline in SAS response amplitude is referred to as habituation (Brown et al., 1991b;Cadenheadet al., 1999; Geyer & Braff, 1982; Quednow et a!., 2006)and is thought to be caused by adecrease in the synaptic transmission in the neural circuitinvolved (Carisen et al., 2003; Kandel,1991) or a change in receptor sensitivity (Weber et al.,2002). There is research that hasdemonstrated that after as few as 2 trials, the SAS response may no longer be elicited (Brownetal., 1991b). The eye blinks and neck muscle responses typicallyrequire the longest amount ofexposure to habituate and do not always disappear (Davis, 1982). To elicitmultiple SASFor more information on the SAS pathway, see Appendix 1:Single Acoustic Stimulus PathwayFor more information on the reticulospinal tract, see Appendix1: Reticulospinal Tract2responses in a participant, the stimuli are presented randomly with long periods of time betweenstimuli to ensure that one does not anticipate the SAS (Brown et al., 1991a).Single acoustic stimulus responses are sensitive to body position in the lower limbs andEMG muscle responses in the legs are more evident in standing versus sitting conditions(Brown et al., 1991a; Delwaide & Schepens, 1995; Nieuwenhuijzen et al., 2000; Rossignol,1975). Standing also displays shorter reflex latency times with tibialis anterior (TA) latencies of80 ms and 70 ms in the soleus (Brown et al., 1991a). In contrast, seated TA latencies arerecorded at 120 ms and 130 ms in the soleus (Brown et al., 1991a). SAS while in a lying supinebody position displays longer onsets than standing in the non-contracting lower limb muscleswith TA responses in the range of 88-126 ms and soleus responses in the range of 98-154 ms(Bisdorffet al., 1994; Kofler et al., 2001; Stell et al., 1995). It is not known what kind ofinfluence a supine position with lower limb muscle contraction will have on responses.Alternative means of presenting single acoustic stimuli have been assessed in ourlaboratory to investigate if responses can be elicited that do not habituate. A response to soundstimuli that does not habituate could be an important clinical tool in spinal cord patients for theassessment of spinal cord intactness. In pilot studies, 124 dB acoustic stimuli were presentedusing short random intervals of three to five seconds between each sound for 14 minutes whileparticipants were lying down in a supine position. This method promoted habituation of thetypical SAS responses after the first 2-10 stimuli. After SAS habituation, the repeated 124 dBsounds rendered a response visible after trigger-averaging muscle EMG to the onset of theacoustic stimulus. The response was evident in participants soleus muscles which werecontracting at a specific submaxirnal level. We have designated this presentationmethod as“repeated acoustic stimuli” (RAS) to differentiate it from SAS and wehave named the EMGFor more information on the SAS responses, see Appendix1: SAS Responses during Static and Dynamic Tasks3response found in muscles after averaging the RAS response6.SASand RAS responses areseperated by identifying and extracting SAS EMG responses from withinRAS trials. The SASresponse appears as a bursting pattern of SCM muscle EMG following theacoustic stimulus andare therefore not included in RAS response averaging.Pre-pulse inhibition is a well studied effect of SAS responses (Filion et al.,1998) andmay be a means of determining experimentally if arelationship exists between RAS and SASresponses. The SAS reflex may be altered by thepresentation of a stimulus 30-500 ms prior tothe SAS eliciting stimulus (Filion et al., 1998).The pre-stimulus decreases the amplitude orcompletely inhibits the SAS response and is referredto as pre-pulse inhibition7(Filion et al.,1998). When a pre-pulse occurs, it is thought that signalsfrom the pedunculopontine tegmentalnucleus (PPTg) are sent through cholinergicprojections and inhibit the SAS centre neurons inthe nucleus reticularis pontis caudalis (nRPC) in thePnC8 (Blumenthal, 1996; Valls-Solé et al.,1 999a). It is through the nRPC that the SAS stimuliare relayed to the reticulospinal tract (Davis,1982; Yeomans & Frankland, 1996). Pre-pulseinhibition is typically measured by the change ofthe SAS blink reflex response of the OOc (Valls-Solé etal., 1999a). To lessen the likelihood ofthe pre-pulse itself eliciting a response,intensities of 95 dB or lower should be used in humansas pre-pulses of 95dB and above mayevoke SAS responses (Hoffman, 1984). Pre-pulseinhibition has been investigated in OOc and SCMmuscles (Valls-Solé et al., 1999a; Valls-Soléet al., 2005) but not in many of the muscles thatrender EMG muscle responses to SAS.The purpose of the present experiment was to investigatethe similarities and differencesbetween single acoustic stimuli responses and therepeated acoustic stimuli responses whenparticipants are in a supine position. Renderingreflexes in supine body positions can bedifficult, as postural engagement is knownto influence the occurance of other descending6For more information on the RAS response, seeAppendix 1: Repeated Acoustic Stimuli (RAS) ResponseFor more information on the pre-pulse inhibition, seeAppendix 1: Pre-Pulse Inhibition8For more information on the pre-pulseinhibition pathway, see Appendix 1: Pre-Pulse Inhibition Processing andPathway4reflexive responses. Without postural engagement, the vestibulspinal reflex ceases. The supinebody position was chosen in this experiment to show that postural engagement is not necessaryfor these reflexes to occur and that they may differ from reflexes that are influenced by posturalengagement. We hypothesized that SAS EMG muscle responses would be evoked by a loudacoustic stimulus (124 db) and that after repeated exposures, SAS EMG muscle responses wouldhabituate. Once SAS responses habituate, averaged RAS EMG muscle responses withinparticipants may be evoked in soleus muscles contracting at a specific submaximal level. Wealso hypothesized that SAS responses would be inhibited by the presence of pre-pulse stimuli.SAS EMG muscle response amplitude would decrease in all muscles when a 85 dB pulsepreceded a 124 dB SAS pulse. Pre-pulse stimuli were not anticipated to decrease EMG responseamplitude of the averaged RAS response within participants as they were believed to be separateresponses from SAS responses. We anticipate that all participants will display reflexes to soundsthat will not completely habituate.5Materials and MethodsParticipantsA total of eighteen volunteers were recruited (9 males and 9 females, aged 18-30) forthree testing procedures. Ten participants (5 males and 5 females, aged 18-26) were assigned tothe control condition and the remaining eight participants (4 males and 4 females, aged 18-30)were assigned to the pre-pulse condition. 5 participants (2 males and 3 females, aged 18-30)were randomly selected from the entire pool of participants to complete an additional 85 dBprotocol. Participants were healthy, with no known hearing deficits or disorders, past or currentneurological disorders, head trauma, or sensory or motor dysfunctions of the lower extremities.Volunteers gave their informed written consent and the study was conducted in accordance withthe ethical guidelines established by the University of British Columbia.ApparatusSurface EMG signals were recorded from the muscle bellies of the right OOc (on theedge of the lateral orbital rim and the edge of the inferior orbital rim), the right and left SCM, theright and left medial gastrocnemius, the right and left deltoid muscles (mid-muscle belly) and theright and left soleus muscles. EMG was collected using bipolar preamplified Ag/AgC1 surfaceelectrodes using a Grass P511 AC Amplifier. Electrical impedance was decreased by theremoval of excess debris at collection sites by shaving and swabbing the area with alcohol. Theelectrodes were placed parallel to the muscle fibers to accurately detect conduction velocity.Grounding electrodes were placed on the participant’s medial and lateral malleoli, clavicles andacromion process. EMG was collected at a sampling rate of 4545.45 Hz for two participants and3846.15 Hz for the rest of the participants with signals amplified (2x104),with a high-pass-filterat 30 Hz and a low-pass filter at 1 KHz. The signal was sent from the amplifier to the6analog/digital (AD) converter (CED Micro 1401) for sampling and was controlled by a programwritten with Spike2 version 5.13 sofiware. The difference in sampling rates for the participantswas due to Spike2 software assigning sampling rates and was not done intentionally.StimuliThe SAS and the RAS were 40 ms duration, 1000 Hz, 124 dB pulses. The tones weredelivered through a Pioneer SX-650 amplifier. The acoustic pre-pulse stimulus and the 85 dBRAS were 40 ms duration, 1000 Hz, 85 dB pulses. Both acoustic stimuli werepresented via aloud speaker (Sentry/RH-30-L) placed in front of the participant’s face at a distance of 30 cmfrom both ears. The stimulus intensities were calibrated using a Cirrus (modelCR:25 1B) sound-level meter at a distance of 30 cm from the speaker. In pre-pulse exposures there was aninterstimulus interval of 100 ms between the end of the pre-pulse stimuli and the onset of theSAS/RAS. Based on previous literature, stronginhibition typically occurs with the lead intervaltime (the time between the pre-pulse and SAS) within therange of 100-l4Oms (Blumenthal,1996; Csomor et al., 2005; Csomor et al., 2006; Quednow etal., 2006; Schwarzkopfet al.,1993).Experimental ProcedureQuiet stance EMG biofeedback from each of the soleus muscleswas measured withparticipants standing quietly upright with their feetclose together but not touching and their armsat their sides for 1 minute. Background EMG of thesoleus was measured for each muscle andseparate horizontal cursors were set at the approximateroot mean square (RMS) average EMGresponse seen for each muscle. The level measured ineach soleus was used as a target activationlevel to achieve and maintain while participantswere lying. This level was chosen in an attemptto achieve a constant level ofactivation for each participant throughout the experiment and to7replicate the level of soleus activation used during the postural task of quiet stance. Participantswere asked to lie down on a clinical examination bed with their feet against a stationary platformperpendicular to the bed. To prevent movement participants’ ankles were restrained to keep theirfeet flat against the platform and to maintain an ankle angle of 90 degrees. During the trials,participants maintained a plantar flexion contraction of both feet at the level of the horizontalcursors set from their standing position. A computer screen was placed in the participants uppervisual field giving them online visual feedback of their soleus muscles level of activation as wellas their target RMS activation level.In the control condition the ten participants were exposed to two protocols. First theywere exposed to the SAS protocol followed by the RAS protocol. In the experimental conditionthe eight participants were exposed to two protocols. First they were exposed to the SAS/prepulse SAS protocol, followed by the RAS/pre-pulse RAS protocol. Fiveparticipants received the85 dB protocol following their RAS protocol (3 participants from the experimentalcondition and2 from the control condition).In the control condition, participants were exposed to the SAS protocol, which had aminimum often minutes in between stimuli to avoid habituation (1hour duration minimum).The interstimulus interval of ten minutes was established through pilot work and is greater thanthe time used in some literature (Rossignol, 1975). A minimum of 6 SAS exposures weremeasured in all participants before they proceeded to the RAS protocol. The RAS protocolconsisted of 210 RAS, presented with a randomly determined interstimulus interval of 3-5seconds between the end of the last stimulus and the begimiing of the following stimulus for theduration of the trial.For the experimental condition participants were exposed to the SAS/pre-pulse SASprotocol, 3 SAS and 3 SAS preceded by pre-pulses in random order, with aminimum oftenminutes between stimuli. In pre-pulse exposures there was aninterstimulus interval of 100 ms8between the end of the pre-pulse stimuli (85 dB) and the onset of the SAS/RAS (124 dB). TheRAS/pre-pulse RAS protocol followed with four blocks of trials with 115 stimuli in each block.Stimuli were presented with an interstimulus interval of 3-5 seconds between the end of the laststimulus and the beginning of the following stimulus for the duration of the trials. The blockconsisted of 115 pseudorandomly selected RAS alone, or RAS with pre-pulse stimuli. After thefour blocks of trials, over 200 RAS with pre-pulse stimuli and200 RAS alone stimuli had beenpresented in total.The 85 dB protocol was the same as the control condition RAS protocol but the RAS wasan 85 dB stimulus rather than 124dB stimulus.All trials were examined for SCM activation. SCM responses that followed acousticstimuli onset by 20 ms or longer were deemed SAS responses andit was this criteria that wasused to separate SAS responses from RAS responses. These responses were visually confirmed.The 20 ms criteria was chosen based on 20 ms being the fasted known response to a SAS.Thisresponse time of 20 ms has been found in the OOc muscles (Brown et al., 1991a).Data AnalysisSurface EMG signals were root mean squared (RMS) at a time contant of 0.02 secondsand trigger-averaged to the onset of the acoustic stimulus using both Spike2 v5.13software(Cambridge Electronic Design, Cambridge UK) and MATLAB 7 (MathWorksInc., Natick,MA). Surface EMG signals were also examined with no RN/IS in their raw statesand as rectifiedEMG using Spike2 v5.13 software. Averageswere performed seperately for each participant inthe control condition for their SAS and RAS responses, in the experimental conditionfor theirSAS/pre-pulse SAS responses, RAS/pre-pulse RASresponses and for the 85 dB RAS protocolresponses. The EMG averages were analyzed from 400 msbefore the acoustic stimulus to 1.5sec after the stimulus. The onset latencies,the peak latencies (time to peak) and peak response9amplitudes of the EMG responses were determined using Matlab 7.0. Onset latencies weredetermined based on responses at least 20 ms following stimuli that Were two standarddeviations above the trigger-averaged mean background EMG level prior to the acousticstimulus. All onsets were visually confirmed. Peak latencies were determined from the time ofthe acoustic stimulus onset until the maximum muscle responses. Peak response amplitude wasthe difference in voltage between the peak response and the averaged background activationlevel prior to the stimulus.Statistical AnalysisThe reliability of the size of the SAS amplitude in the control condition was examinedusing a intraclass correlation (ICC), a one-way random effect model based on six trials. In thecontrol condition, a paired-samples t-test was used to examine the difference of peak responseamplitude and peak response latency between SAS and RAS responses. In the pre-pulsecondition, the peak amplitudes of the SAS and RAS responses, with and without pre-pulses weresubjected to a two-way Tone (SAS, RAS) X Pre-pulse (present, absent) repeatedmeasuresANOVA. A p-value of .05 was used to indicate statistical significance using SPSS 10.0 software.10ResultsSingle Acoustic Stimulus (SAS)A representative participant’s raw EMG data with no rectification may be seen in Figure1 depicting a strong SAS response with activation of multiple muscles following the stimulus.Bursting activity is evident in the EMG of all muscles except the soleus, with the largestresponses in the OOc and SCM muscles. The duration of the response rangesfrom 50-400 ms. Atotal of 94 SAS responses were elicited across participants. Table 1 summarizes the number ofSAS responses from each participant from the control condition. Three SASresponses werecollected from each of the 8 participants in the experimental RAS condition with and withoutpre-pulses.The amplitude of the SAS responses in all muscles varied across participants over thecourse of the testing. Variability in amplitude was not necessarily due to habituation becausesome later SAS responses had a greater amplitude than earlier ones (see Figure 2). It is alsoevident that responses may be variable within muscle groups on different sides of the body, asresponses may be larger on one side, or only present on one side (Figure 2). The amplitudes ofSAS responses for the first six trials in all participants can be found in Appendix 3 for the rightOOc, right and left soleus, SCM, medial gastrocnemius and deltoid muscles.Intraclass correlation of peak response amplitude across SAS trials was 0.69 (CI 0.46 to0.89) for right OOc responses, 0.75 (CI .54 to .91) for left SCM, 0.82 (CI .65 to .94) for rightSCM, 0.61 (CI. .36 to .85) for the left medial gastrocnemius, 0.23 (CI .01 to .59) for the rightmedial gastrocnemius, 0.16 (CI. -.02 to .52) for the left deltoid, 0.19 (CI .01 to .55) for the rightdeltoid, 0.35 (CI. .12 to .70) for left soleus and 0.33 (CI .10 to .68) for right soleus. The ICCsmeasured the proportion of variance in response amplitudes (McGraw et al., 1996). The SASresponse amplitudes were only relatively stable for the OOc and SCM muscles.11SASSTIMULUSROOCRSCMLSCMRDELIDELI- —100 msFigure 1: Raw EMG trace of right OOc, right and left SCM, right andleft deltoid, right and left soleus and right and left medial gastroc ofone participant upon exposure to one SAS stimulus. The shaded arearepresents the timing and duration of the SAS stimulus.49_4>hWp*4RSOLLSOLRMGASLMGAS—., ..----—I-.t -% J .-.-—0.25 my12ControlsParticipant Number ofSAS2 63 94 95 76 67 68 69 710 8total 70Table 1. Number of SAS exposures for each participant in thecontrol condition13SAS I SAS3 SAS4 SASS 5A58Left SCMRighi SCMtxLeft Dekakiuk —__________________m:Right Deftoid_____J..‘iLLulFigure 2: Rectified right and left SCM, right and leftDeltoid and rightand left Soleus responses to SAS in order of exposureof oneparticipant. SAS 1 being the first SAS exposure, SAS2 thesecond,through to SAS6 the sixth SAS exposure.Left SoleusjIiiidI1Ililtj‘h1ftrqI[frr03SOC rns14Responses in the tonically activated soleus muscles are not clearly visible in some of thesingle trials as is the case in Figure 1. However, across trials responses are present in the soleusas shown in Figure 2. The amplitude of response with respect to the level of background EMGvaries between participants. Some participants display an inhibition of response followed byfacilitation, while others exhibit facilitation followed by inhibition. The number of responsepeaks vary from one large peak to multiple and in some cases peaks are not discemable. Toexamine soleus responses to SAS more indepthly, responses within participants and acrossparticipants were averaged (see Figure 3). The overall average between participants seen inFigure 3 depicts a clear SAS response peak in both the right and left soleus muscles and thispeak is clearly represented in many of the participants’ average responses. SAS response onsetlatency and peak times did vary between participants as did the amplitude of the peaks (seeAppendix 2). Average response onsets, peak onsets and amplitudes of the lower limb musclesmay be found in Table 2.15SI1MULUSOVERALLAVERAGEP1P2p3P4P7A41plo500msLEFT SOLEUS RIGHT SOLEUSFigure 3: Overall group averaged EMG SAS responses of the left andright soleus muscles and individual’s averaged SAS responses. AllEMG responses shown are the maximum peak to peakrepresentation.P1 through PlO represent participants one through ten.P616SAS RAS 85 dB RASOnset Latency(ms)RSOLLSOLRMGASLMGASPeak Latency(ms)RSOLLSOLRMGASLMGASAmplitude ofPeak (mV)RSOLLSOLRMGASLMGASTable 2. Average onset latencies, peak onsets and amplitudes ofSAS, RAS and 85dB RAS responses in the soleus and medialgastrocnemius musclesAverage n Average n74.3 ± 13.169.9±11.667.6 ± 21.580.8 ± 9.8Average91098n40.9 ± 3.847.3 ± 5.443.8 ± 5.742.5 ± 5.891010994 ± 6.779.2 ± 23.166.6 ± 13.197.9 ± 23.15554111.2±16.9106.4 ± 10.992.3 ± 14101.1 ±8.591010999.3 ± 5.796.5 ± 6.5101.1 ±4.799.2 ± 6.210101010103.0 ± 9.36118.9±15.398.4 ± 7.7137.16 ± 2055550.01 07 ± 0.00290.0099 ± 0.00200.0052 ± 0.00150.0085 ± 0.0053101010100.0032 ± 0.00050.0027 ± 0.00050.0035 ± 0.00090.0025 ± 0.0005101010100.0013 ± 0.000240.0015 ± 0.00030.0011 ± 0.00020.00057 ± 0.00009555517Repeated Acoustic Stimulus (RAS)A RAS response was evoked in all 10 participants when they were presented with arepeated auditory stimulus of 124 dB. An average of 198 trials (range of 188-207 acrosssubjects), were root mean squared, and trigger-averaged to the onset of the acoustic stimulus. Anaverage EMG response from the right OOc, and bilaterally from the SCM, deltoid, soleus andmedial gastrocnemius within one subject is shown in Figure 4. This average did not incorporateresponses that induced a SAS response as indicated by SCM activation following the stimulus.These SAS responses were present in an average of 5.8% of trials and were removed from RASresults. However, whether or not the trial included SAS responses does not appear to change theshape of the reflex as may be seen in Figure 5 (the darker line includes all 210 trials in theaverage and the lighter line includes 189 of the 210 trials in the average). The RAS averageincluding the SAS responses was not different from the RAS average excluding SAS responses.The ROOc muscle response consisted of a single peak following the stimulus. Those musclesthat held tonic activation during the trials (i.e., soleus and medial gastroc) showed excitationfollowing the stimuli. Oscillatory responses in the EMG can be seen following the initial peakand in the soleus an average of 4 oscillations occurred in participants. The oscillations finishedafter an average of 500 ms from stimulus onset and the frequency of these oscillations was onaverage 7-8 Hz. Average RAS response times and amplitudes of the lower limb muscles may befound in Table 2. There was considerable variation in the EMG onset latency of the responses inthe soleus and medial gastrocnemius muscles during RAS responses (Appendix 4). The time ofthe first peak in the soleus and medial gastrocnemius muscles also varied between participants,but the ranges were similar for each of the four muscles. The responses in the left soleus of allcontrol participants can be seen in Figure 6. The first facilitationlpeak was not always the largestresponse rendered in participants and responses between participants varied. Response peakonset and amplitudes of all muscles are found in Appendix 4.18Auditory1Stimu’usROOC —RSCMLSCMRDELLDELRSOLLSOLhRMGASLMGASlOOmsFigure 4: Average RAS response of the right OOc, right and leftSCM, right and left deltoid, right and left soleus and right and leftmedial gastrocnemius of one participant.0.005 mV19R SOLLSOLRMGASLMGASFigure 5: A single participants averaged RAS responses in the soleusand medial gastroc muscles. The lighter line is the trace ofthe averageof trials where SAS responses (SCM activation) were not includedinthe average (21 trials were removed from the 210total trials) and thedarker line represents the averaged RAS response with allexposuresincluded.AUDITORYSTIMULUS____RAS WITH TRIALSWITH SCM ACTIVATIONRAS WITHOUT TRIALSWITH SCM ACTIVATION500 ms20AudftoryStimu’usIAVERAGEP1 LSOLP2 LSOLP3 LSOLP4LSOLP5 LSOLP6 LSOLP7 LSOLPB LSOLP9 LSOLP1OLSOLFigure 6: Overall group averaged EMG RAS responses of the leftsoleus muscles and individuals averaged RAS responses. The shadedarea represents the time the auditory stimulus was presented.100 ms0.005 mV21No statistically significant difference in peak response time between SAS and RASresponses was found for any of the muscles tested. On the other hand, SAS evoked responseswere larger than RAS responses for the right soleus [t(l,7)=2.5, p 0.042], the left soleus[t(l,9)=3.9, p 0.003], the right deltoid [t(l,6)=2.7, p 0.034], the left deltoid [t(l,9)=2.5, p=0.031], the right OOc [t(1,9)=4.9, p= 0.002], the right SCM [t(l,8)=3.3, p 0.012] and the leftSCM [t(l,7)=3.2, p= 0.016].Pre-pulseTwo averaged responses were determined for each pre-pulse protocol participant, a SASresponse and a pre-pulse/SAS response. Decreases in the amplitude of the peak responses due topre-pulses were only consistent in the OOc muscles in the SAS plus pre-pulse trials for allparticipants (see Table 3). Different participants displayed increases while othersdecreases inpeak amplitude for remaining eight muscles in pre-pulse trials (seeAppendix 5).22Pre-pulse withROOC SAS SASPercentPeak time Peak Amplitude Peak time Peak Amplitude Amplitude of PPParticipant (ms) (my) (ms) (mV)(PSAS/SAS*100)1 53.18 0.03913 49.28 0.02025 51.82 116.1 0.17446 149.12 0.04931 28.33 79.18 0.22775 139.76 0.012655 5.64 62.8 0.08345 54.74 0.02293 27.55 54.22 0.10491 180.84 0.07994 76.26 59.68 0.01522 46.42 0.01449 95.27 75.28 0.05576 74.5 0.02465 44.28 125.2 0.24745 173.82 0.15913 64.3Table 3. Right OOc peak time and amplitudes of each participantsaverage SAS and average pre-pulse plus SAS exposures and thepercent decrease in amplitude when pre-pulse was present23An average of 219 (range of 185 to 251 pulses) RAS stimuli were root mean squared andtrigger-averaged to the onset of the acoustic stimulus and an average of 224 (range of 208 to242) pre-pulse plus RAS stimuli were root mean squared and trigger-averaged to the onset of the124 dB RAS stimulus for each of the 8 participants. Soleus and medial gastroc musclesconsistently yielded responses as were found in the RAS experiment but the influence of prepulses had no consistent effect among participants. No common decreases or increases werefound amongst all participants for the other muscles in pre-pulse trials (refer to Appendix 6).The peak amplitudes of the SAS and RAS responses, with and without pre-pulses weresubmitted to a 2 Tone type (SAS, RAS) x 2 Pre-pulse (present, absent) repeated measuresANOVA. The analysis revealed a significant Pre-pulse x Tone interaction [F(1,7)=7.5, p=O.O29jin the right OOc. Tukey’s post hoc analysis shows that SAS response amplitudes were largerthan SAS with pre-pulse responses and RAS responses in the right OOC (ij<0.005). However, inall other muscles there was no effect of pre-pulse in RAS or SAS responses.Pre-pulse acoustic stimuli (85 dB) may have caused an early response in the soleus andmedial gastrocnemius muscles that preceded the onset of the 124 dB tone (Figure 7). Thisresponse was clearly observed in 5 of the 8 participants. The effect of the 85 dB stimulus as acontaminating factor was further investigated by replacing the 124 dB tone with an 85 dB tone inthe RAS protocol.24AudftoryStimuliLSOLRSOL1Figure 7: Average RAS response of the right and left soleus with andwithout the presence of a pre-pulse stimulus of a second participant.The shaded areas represent the duration of the auditory stimuli. Thelighter line is the averaged pre-pulse with RAS trials. NOTE Aresponse can be seen in this subject after the 85dB pre-pulse precedingthe 124 dB pulse.OOO5 mVRASPre-pulse preceding RAS500 ms25An average of 197 (range of 183-203) trials were root mean squared and trigger-averagedto the onset of the acoustic stimulus for each participant and the onset and peak timings weredetermined (Table 2). The onset, peak time, peak amplitude and overall shape of the 85 dBcontrol response appear to have the same characteristics as the first peak of the RAS/Pre-pulseresponse (bottom of Figure 8). This first peak occuring before the 124 dB stimulus waspresented. In the top of Figure 8, the 85 dB control protocol response appears tohave the sameonset and peak time as the RAS response but at a smaller amplitude.26LSOLFigure 8: Average 85 dB responses in the soleus muscles of oneparticipant compared to the average RAS response (Top) and averageRAS plus pre-pulse response (Bottom) in the same participant000385 dB pulseRASat124dBRSOLLSOL— 85dB pu’se— Pre-pulse preceding RASRSOL100 ms27DiscussionResponses to the single acoustic stimuli and repeated acoustic stimuli were measured inall participants. Responses to loud acoustic stimuli do not completely habituate over time asRAS responses were found in all participants after exposure to over 200 stimuli. Responseswere also measured in the voluntarily contracting lower limbs in response to RAS at 85 dB.Evidence in these experiments suggests that RAS and SAS responses may be related responsesand therefore may travel through the same pathway. Pre-pulse inhibition occurred in the OOcmuscles in the SAS protocol but not in any other muscles tested and not in the RAS protocol.SAS ResponsesThe amplitude of the SAS EMG responses in the SCM and all muscles varied withinparticipants over the course of the testing and did not readily habituate (Cadenhead et al., 1999;Geyer & Braff, 1982; Quednow et al., 2006). Indeed, responses sometimes were of largeramplitude later in testing than in the first trial. This variability in amplitude has been found inblink responses in a habituation study by Omitz and Guthrie (1989), but they referred to thesefindings as “transient short-term sensitization,” and suggested the results occurred by chance.Based on the testing procedure used in this experiment, it is impossible to predict which trialswould render larger SAS responses, and even if a response would be produced at all.The variability of the responses also had an impact on the pre-pulse trials and in turnaffected what information and results could be drawn from these trials. It is impossible to knowif a trial would render a small SAS response regardless of whether or not a pre-pulse was presentand also whether the pre-pulse can inhibit the response.Average onsets calculated for SAS responses were comparable to previous studies for theOOc and SCM muscles while in a supine body position (Bisdorff et al., 1994; Kofler et al., 2001;Stell et al., 1995). Onsets were faster then previously reported onsets for OOc, SCM and deltoid28muscles in the standing and seated conditions (Brown et al., 1991a; Brown et al., 1991b; Grosse& Brown, 2003). Average soleus onsets were shorter than those reported from supineparticipants with relaxed soleus muscles (Kofler et al., 2001). Soleus onsets were, however,similar to those recorded in standing participants at 69.9 ± 11.6 ms in the left soleus and 74.3 ±13.1 ms in the right soleus (Brown et al., 1991a). It should be noted that in this experiment, thecriteria for onset was 2 SD above the background levels of EMG RMS. In other experiments,onsets were determined by visual inspection of unrectified EMG (Brown et al., 1991 a; Brown etal., 199 ib) and this difference in how onsets were determined could cause this discrepancy. Thefact that contracting the soleus versus not contracting the soleus while in the supine positionaffects onsets, poses some question. If reflexive responses are present while seated andcontracting the soleus or TA, the latencies are similar to those exhibited while seated and relaxed(Deiwaide & Schepens, 1995). It is not clear why there is a difference with respect to onsetlatencies associated with muscle contraction between the seated and supine body positions.It is important to note that this study showed variability in response onset times bothbetween and within participants and this is not uncommon when testing participants maintainingthe same position (Brown et al., 1991b; Kofler et al., 2001). To gain a better idea of a typicalresponse time a larger number of SAS responses should be recorded from more individuals.RAS ResponsesRAS responses were consistently present in both the 10 RAS control participants andthose 8 participants in the experimental pre-pulse condition that were exposed to RAS. RASresponses can be identified after the data has been averaged, but cannot be seen otherwise due totheir small size. The oscillation in the response is not present in the average of SAS trials. SAStrials did have much fewer responses to average and it is not known what an average of 200 SASresponses would look like. The onset and duration of the RAS response oscillation coincides29with a spinal excitability reported following loud acoustic stimuli, measured through H-reflexes(Liegeois-Chauvel et al., 1989; Rossignal & Jones, 1976). This excitabilitybegins 50 ms afteracoustic stimulus onset, with a peak amplitude at 100-130 ms after stimulus andexcitabilitylasting a mean duration of 200 ms with a range of 120-460 ms (Liegeois-Chauvel et al., 1989;Rossignal & Jones, 1976).The RAS response maintains the same shape and amplitude with and withouttheinclusion of trials that contained a stereotypical SAS response (SCM activation following thestimulus) (see Figure 5). If SAS responses differed from RAS responses, onecould expect achange in the outcome of the RAS results with and without the SAS response presence. If theSAS responses were unrelated to the RAS responses then they could have caused achange inamplitude, or a shift in onset, or peak time, impacting the typical RAS responses. Thefact thatthe removal of SAS trials from within RAS trials does not greatly affect the shapeof RASresponses during averaging suggests that the two responses may be related.SAS responses may be seen on individual trials but are more clearly distinguished in thesoleus muscles when averaging multiple trials as aconsequence of the high variability. RASresponses are only visible after averaging. SAS and RAS responsesin the soleus muscles couldin fact be the same response but of differing magnitudes. Whenlooking at Figures 3 and 6 theresponses look similar and peak response times are not statisticallydifferent.Overall peak response amplitudes were larger in muscles in the SAS condition comparedto the RAS condition. RAS were loud and of similarnature to SAS but were repeated for alonger period of time. The larger response in the SAS conditionmay be due to the moresurprising nature of the stimulus as it was unexpectedlypresented and may have caused aninherent protective response. Smaller responsesoccurred in the RAS procedure as one becamemore familiar with the tones and how frequentlythey were presented. Some sort of inhibitoryeffect, or filtering of the acoustic stimuli could beoccuring within the system that does not30completely attenuate the responses. Theories exist to explain the decline in SAS responses.There may be a reduction in synaptic transmission of excitatory signals as there is decrease ofthe neurotransmitter available (Rimpel et al., 1982), and this may be due to a change in receptorsensitivity which leads to a decrease in excitatory signaling in the PnC (Weber et al., 2002). It ispossible that when the tones are more unexpected a SAS response occurs and as tones becomemore expected and large responses habituate, and smaller RAS responses occur. The habituationof the SAS response is well documented (Brown et al., 1991b; Cadenhead et al., 1999; Geyer &Braff, 1982; Quednow et al., 2006) but the idea that responses to acoustic stimulihavecompletely habituated once SCM activation ceases, is incorrect. The RAS responses clearlydemonstrate that a response to the stimulus is still propagating through thespinal cord to musclesafter repeated exposures. The response is of smaller magnitude, but the body isstill eliciting areaction.It is difficult to compare responses between all the differentmuscles measured as it is notknown what factors impact RAS responses. Voluntarymuscle contraction may have had animpact as lower body muscles in the legs were contractingduring trials and it is in these musclesthat responses are most consistent. In previous experimentsin our lab some voluntary musclecontraction work has been conducted during RAS. It ispossible to elicit RAS responses in thenon-contracting TA muscles while soleus muscles arecontracting in some individuals, but whenmuscles in the legs are not contracting, no RASresponses are measured in either the soleus, orthe TA. Voluntary muscle contraction also affects onsetlatencies, as SAS responses havedifferent onset latencies in the soleus in the supine positionwhen relaxed (Kofler et al., 2001)compared to when contracting, as found by this study.The SCM and deltoid muscles were notvoluntarily contracting in this experiment and elicitedRAS responses in only some individuals.It is not known what factors effects whichmuscles are responsive to RAS. It is important to notethat postural engagement is not necessary forRAS responses to be evoked as participants in a31supine position during the entire experiment elicited such responses. It is unknown if responsesvary at different spinal levels (e.g. upper versus lower body). The voluntary contraction of thelower limbs during the trials is driven by activation descending through thecorticospinal tract.The reflex to the loud sound is thought to propagate through the reticulospinal pathway to renderresponses in the contracting muscles. RAS needs to be further investigated to better understandthe various muscle responses of the body and what factors may alter responses.Pre-Pulses in SAS TrialsThe right OOc muscles in all participants showed inhibition with pre-pulse exposures inthe SAS condition. No other muscles had consistent inhibition across allparticipants. Pre-pulseinhibition is typically measured and found in the eye muscles (Blumenthal, 1996; Cadenhead etal., 1999; Csomor et al., 2005; Csomor et al., 2006; Quednow et al., 2006; Schwarzkopfet al.,1993) but is not often tested in other muscles of the body. This can beattributed to the rapidonset of habituation of SAS responses in muscles otherthan eye muscles, making it difficult fortesting inhibition (Meincke et a!., 2005). Pre-pulse inhibition hashowever been found in theSCM (Valls-Solé et al., 1999a; Valls-Solé et al., 2005) but under differing testingproceduresfrom our experiment. In both of these experiments, participants were testedin a seated position,which requires more SCM activation than while in a supineposition. The stimuli also varied,with a 130 dB SAS and with 70 dB pre-pulses (Valls-Solé et al., 1999a)and an electrical, tactilepre-pulse stimuli (Valls-Solé et al., 2005). A reaction time task was also a component of oneexperimental procedure, paired with the pre-pulses and loud stimuli(Valls-Solé et al., 2005).Loud acoustic stimuli are known to affect reaction timetasks, but the causal mechanisms relatingthe two are not known (Carisen et al., 2003; Valls-Solé et al.,1999). In our experiment, someparticipants had larger responses in muscles with pre-pulse exposureswhile others had smallerresponses. The lack of consistency in inhibition within participantsbetween muscles most likely32has to do with the variability of response size to SAS. It is not known which trials wouldhaverendered a large or a small SAS response without the presence of a pre-pulse, letalone with thepresence of a pre-pulse. Therefore, a conclusion cannot be made with respect to whetheranyinhibition is due to a pre-pulse exposure or whether the smaller response size would haveoccurred regardless. It is interesting to note that the right OOc had consistent inhibitionwhile theother muscles did not.Pre-pulses in the RAS TrialsIn our experiment pre-pulses inhibition was not found in RAS trials.This finding mayhave been confounded by the response to the 85 dB pre-pulse. The 85 dB tone hastimings thatare very similar to the louder 124 dB sounds as maybe seen in Table 2. The amplitudes ofthe 85dB responses were smaller than those found with 124 dB tones but do havesimilar onsets andpeaks to both the SAS and RAS responses. As participants responded to the 85 dB tone and thetone itself causes RAS responses, it makes it difficult to assesfully whether pre-pulse inhibitionof the main peak occurred in response to the 124 dB pulse.Based on this finding of a response tothe 85 dB tone, it is possible that this confounded the SASresponses in the same way. Toinvestigate if pre-pulses can have an inhibitory effect on RAS responseamplitudes, differentdecibel levels would have to be investigated. Research could be done toreveal what intensitytone does not render a muscular response after repeated exposures. The pre-pulse tonewouldhave to be at this intensity, or lower to avoid possible confounding of the SAS and RASresponses. It may not be possible however to find an intensity that does not cause a RASresponse. Sounds at low intensities, like the 85 dB tone, couldstill excite the PnC to a certainextent and result in a small descending response.33Pathway Associated with SAS and RAS (both to 124 dB and 85dB)A muscular response pathway to sound seems sensitive to loud (124dB) and muchquieter noises (85dB). Responses vary in amplitude depending on whether there is one exposureto the sounds or repeated exposures. Even after habituation becomes apparent in the muscles,after the data is averaged, responses may still be present in the contracting muscles of the lowerlimbs.It has been proposed that the SAS response travels through the reticulospinal tract toelicit a response in the body (Brown et al., 1991a; Davis, 1982; Grosse & Brown, 2003;Yeomans & Frankland, 1996). Evidence in our experiments supports the theory that SAS andRAS responses are related, or are the same response and therefore probably propagate throughthe brainstem and down the spinal cord through the reticulospinal tract. If it is truethat SAS andRAS responses both travel through the reticulospinal tract, then both may beused as methods totest reticulospinal tract intactness. If a spinal cord injury patient only has apartial spinal cordlesion and they maintain the ability to engage muscles below the lesion, this may be a way to testif the reticulospinal tract is intact by testing for RAS or SAS responses in those voluntarilycontracting muscles.LimitationsIn this experiment responses were measured on both sides of the body and SAS responsesvaried within a single trial on each side. A single trial may have activated one side of the body toa greater extent than the other side. A future study wouldhave to be designed to investigatewhether responses vary between sides of the body and look at what may causethis variability inresponses.This experiment was not designed to compare onset latencies of contractingversus non-contracting muscles while in the supine position. To testif contraction versus non-contraction of34the lower limb muscles while in the supine position affects onsets statistically, both conditionswould have to be conducted in one experiment for comparison.ConclusionsThe results of the present study have shown that similar responses may be rendered fromsingle acoustic stimuli and repeated acoustic stimuli in voluntarily contracting lower limbmuscles. SAS response amplitudes are variable within single muscles across trials. Apparenthabituation to sounds in some muscles after repeated exposure does not mean that all muscleshave habituated and stopped responding. RAS exposures render an averaged response in allparticipants tested. This response appears to be similar to SAS responses but of smallermagnitude and only visible after the averaging of multiple trials. SAS and RAS responses sharemultiple commonalities suggesting that they are related responses. 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Hoboken, NJ:John Wiley & Sons, Inc.Valls-solé, J., Valldeoriola, F., Molinuevo, J.L., Cossu, G., & Nobbe, F. (1999a). Pre-pulsemodulation of the startle reaction and the blink reflex in normal human subjects.Experimental Brain Research, 129, 49-56.Valls-solé, J., Rothwell, J.C., Goulart, F., Cossu, G., & Mufloz, E. (1999b). Patterned ballisticmovements triggered by a startle in healthy humans. Journal ofPhysiology, 5 16,3, 931-938.Valls-solé, J., Kofler, M., & Kumru, H. (2005). Startle-induced reaction time shortening is notmodified by pre-pulse inhibition. Experimental Brain Research, 165, 541-548.Vidailhet, M., Rothwell, J.C., Thompson, P.D.,Lees, A.J., & Marsden, C.D. (1992). Theauditory startle response in the Steele-Richardson-Olszekski Syndromeand Parkinson’sDisease. Brain, 115,4, 1181-1192.39Weber, M., Schnitzler, H.U., & Schmid, S. (2002). Synaptic plasticity in the acoustic startlepathway: the neuronal basis for short-term habituation? European Journal ofNeuroscience, 16, 1325-1332.Yeomans, J.S., Li, L., Scott, B.W., & Frankland, P.W. (2002). Review: Tactile, acoustic andvestibular systems sum to elicit the startle reflex. Neuroscience and BiobehavioralReviews, 26, 1-11.Yeomans, J.S., & Frankland, P.W. (1996). Review: The acoustic startle reflex: neurons andconnections. Brain Research Reviews, 21, 301-3 14.40Appendix 1: Literature Review41Literature Review:The Anatomy and Neurophysiology of the Auditory SystemThe auditory system is one of the primary sensory systems in the human body.Incircumstances where an individual is exposed to unexpected auditory stimulus, one may bestartled and elicit varying responses. Understanding the auditory system is importantin theunderstanding of the startle reflex. For the purposes of this review a startle stimuluswill bereferred to as single acoustic stimulus (SAS).The external ear, or the auricle, is designed to direct sound waves into theexternalauditory canal. The tympanic membrane seperates theexternal auditory canal and the middle ear.Alternation between high and low-pressure sound waves causesthe tympanic membrane tovibrate and the distance it moves is dependent on the frequencyand intensity of the waves. Thetympanic membrane arid the round window of the inner ear areconnected by small bones calledthe auditory ossicles. These bones are attached to the middleear by ligaments and connected toeach other by synovial joints. The malleus isthe bone connected to the tympanic membrane andit transmits the vibration from the membrane to the incus,which then transmits the vibration tothe stapes which is attached to the round window.The movement of the stapes causes the ovalwindow to move in and out which give rise to fluid pressure waveswithin the perilymph fluid ofthe cochlea within the inner ear. The cochleais a component of the bony labyrinth which is aseries of cavities in the temporal bone. The cochleais composed of three channels: the cochlearduct, the scala vestibuli and the scala tympani. Thecochlear duct is seperated from the scalavestibuli by the vestibular membrane and the scalatympani by the basilar membrane. Perilymphis within the scala tympani and the scalavestibuli and endolymph is within the cochlear duct.The pressure waves move the walls of the scalavestibuli, the scala tympani and move thevestibular membrane. The movement of the vestibularmembrane creates pressure waves in the42endolymph and these waves cause the basilar membrane to vibrate. The organ of Corti rests onthe basilar membrane and contains hair cells, which are the receptors associated with hearing.There are inner hair cells in a single row and outer haircells composed of three rows. Each haircell has a hair bundle of 30-100 stereocilia at the end which extend into the endolymph (Tortora& Derrickson, 2006).The hair bundles are embedded in the tectorial membrane, a flexible gelatinousmembrane that shifts with the movement of the endolymph. Stereocilia are positioned by heightwithin a bundle, from tallest to shortest. The movement of the tectorial membrane causes thebending of the hair cell bundles. As a pressure wave travels in the endolymph the membranesoscillate causing hair cells to bend at different times yielding differing responses. When thestereocilia bend in the direction of the taller stereocilia depolarization occurs. Withdepolarization action potentials are sent down the hair cell to synapse withfirst-order sensoryneurons and motor neurons from the cochlear branch of the vestibulocholear (VIII) nerve. In thecase where the hairs bend away from the taller stereocilia, repolarization takes place. Theinnerhair cells are less abundant than the outer hair cells, but synapse with 90-95% of the first-ordersensory neurons in the cochlear nerve for the relaying of auditory information to the brain. Theouter hair cells mostly synapse with the motor neurons of the cochlear nerve (Tortora &Derrickson, 2006).The first-order sensory neurons from the vestibulocochlear nerveterminate at themedulla oblongata, the inferior part of the brainstem, at the cochlear nuclei of the same side thesound was detected. Second order neurons then sendauditory signals to the superior olivarynuclei on both sides of the brain. Axons from both the olivarynuclei and the cochlear nucleirelay information to the inferior colliculus of the midbrain,and from there to the medialgeniculate nucleus of the thalamus. The thalamusthen projects the auditory signal to the primary43auditory area located in the superior temporal gyrus of thecerebral cortex for the perception ofsound (Tortora & Derrickson, 2006).The sounds we hear are our perception of sound waves and theloudness of sounddepends on the intensity of the sound wave. Sound intensity varies by theamplitude of thevibration of the wave and is measured in decibels (dB).A decibel is a logarithmic unit ofmeasurement where an increase of one decibel represents an increase of soundintensity bytenfold. It is used to quantify sound levels and uses thereference of 0 dB as the threshold ofnormal hearing; where one may perceive a soundfrom silence. Normal conversation has beenmeasured to be around 60 decibels (dB) while a jackhammeris approximately 90-110 dB. Thelevel at which sounds become uncomfortable to the normalear is roughly 120 dB. Beyond 140dB, sound becomes painful and damaging to the ear. Itis important to note that because dB arenot a linear scale but a logarithmic scale, a one decibelincrease represents a tenfold increase insound. The change from 110 to 120 dB istherefore a much greater increase then the change from80 to 90 dB (Tortora & Derrickson, 2006).Single Acoustic Stimulus ReflexThe Single Acoustic Stimulus reflex may be instigated byloud unexpected noises, visualstimuli and/or tactile stimuli. The SAS reflex is thought tobe a mechanism common amongstmost mammals that has evolved as a protectivebehaviour (e.g. in response to an unexpectedenemy attack) (Quednow et al., 2006; Yeomans,Li, Scott & Frankland, 2002). Muscle flexionfollowing a startling stimulus is typically seenbilaterally and is aimed to protect sensitive areasof the body for a short period of time while thestartling stimuli can be assessed in order to selecteither a flight or fight response. Despite theloss of the motor coordination, cognitive attention,and visual input during SAS responses, thehuman body is still able to protect itself fromphysical harm (Yeomans et al., 2002).44In circumstances where the head, neck or upper body is unexpectedly hit, there arethreesystems that may respond independently or collectively to yield the SAS response: thesomatosensory, the vestibular andfor the auditory system (Yeomans et al., 2002). The actualphysical force acting upon the head will directly affect the somatosensory system(through thetrigeminal system in the head). Skin and muscle can be physically displaced causing cutaneousreceptors in the skin and receptors within muscles, ligaments and joints to activate in turnsignaling changes to the body. Linear and angular accelerations of the head are then detected bythe semicircular ducts and otolith organs of thevestibular system within the inner ear. Thesemicircular ducts detect angular acceleration of the head in space through hair cell receptors.Movement of the head causes fluid within circular ducts, known as endolymph,to flow in onedirection and bend the hair cells, which then fire as they aredirectionally sensitive toacceleration. The otolith organs, the utricle and the saccule detect linearacceleration of the headthrough the firing of hair cell receptors within an otolithicmembrane embedded with otoconia(small crystals). The movement of the head shifts the otolithic membrane andbends the haircells, which then fire in response to the direction of acceleration associated withthe path ofmovement (Fitzpatrick & Day, 2004). Sound waves are detected by the auditory systemandrelayed to the brain (Tortora & Derrickson,2006). All three systems use rapidly conductingmechanoreceptors that elicit fast responses and relayinformation to the pertinent brain centersfor assessment, interpretation and responses (Yeomans etal., 2002).Reticulospinal TractAn unexpected blow to the head results in acombination of muscle contractions in thebody that are controlled via descending input fromthe reticulospinal, or vestibulospinal tracts inthe spinal cord (Blumenfeld, 2002; Davis, 1982).Larger amplitude responses to a SAS areelicited when a combination of signals are relayed from theacoustic, trigeminal and vestibular45systems rather than from a single system (Li, Steidi & Yeomans, 2001). A convergence ofinformation has been proposed where the reticulospinal tract receives information from theauditory, trigeminal and vestibular systems and the vestibulospinal tract receives informationfrom the vestibular system (Yeomans et al., 2002).The reticulospinal tract is thought to be the main pathway through which the SASreflextravels to the bodies musculature (Delwaide & Schepens, 1995; Li et al., 2001).Thereticulospinal tract originates in the reticular formation of the brainstem. The reticular formationis an area in the central core of the brainstem with a great deal ofconnectivity and it is a site forthe convergence and divergence of information. A single cell within this area may respond tomany different stimuli and modalities and relay the informationit receives to other areas withinthe brainstem. Specifically the reticulospinal tract is known to controlmovement as it connectsto both the spinal cord and the cerebellum. Thereticular formation itself contains neural circuitryto initiate simple and complex reflexes andcomplex patterns of movement (Nolte, 2002).The reticulospinal tract descends from the medial area of the pontinereticular formationand the rostral medullary reticular formation. The reticulospinalneurons carry projections fromthe reticular formation that influence and control spinal motorneurons and the sensitivity ofspinal reflexes. The tracts relay information from the basal ganglia,vestibular nuclei, areas of thecerebral cortex such as somatosensory and motor cortex, as well as motor commandsgeneratedfrom within the reticular formation itself (Nolte, 2002). It isknown to send motor inputs for gait-related movements, for the maintenance of posture, andfor control of fine musculature in thedistal arm and hands (Blumenfeld, 2002; Davis, 1982; Riddle,Edgley & Baker, 2007).The vestibulospinal tract sends motor inputs for head and neckpositioning as well as forthe maintenance of whole body posture andbalance based on input it receives from thevestibular system (Blumenfeld, 2002; Fitzpatrick &Day, 2004). Second order vestibular neuronsfrom the vestibular nucleus are thought toproject to the reticular formation, specifically to the46nucleus reticularis pontis caudalis which is within the caudal pontine reticular formation (PnC)(Li et al., 2001). As the vestibular system projects to both the vestibulospinal and thereticulospinal tract, the vestibulospinal tract may in theory also influence SAS responses. Thetrigeminal and auditory systems have multiple synapses and also project to the PnC that thenproject information to the reticulospinal tract. The SAS reflex is thought to travel from thesomatosensory, the vestibular and the auditory systems, through the reticular formation and thendescend through the reticulospinal and/or vestibulospinal tract.Single Acoustic Stimulus PathwayTo elicit a response, a SAS is an unanticipated, loud and sharp stimulus (Deiwaide &Schapens, 1995; Quednow et al., 2006). Much research has been done to investigate in detail thepathway through which the SAS response travels to produce the reflexive response. Animalstudies have identified a SAS response pathway and it is thought that this pathway may besimilar in humans. Davis (1982) has established a pathway in rats using bilateral lesioning atspecific neural structures. The sound is detected in the inner ear by the hair cells of the spiralganglion in the cochlea and synapse on to the cochlear root neurons in the cochlear nerve. Thecochlear root neurons then project directly on to the posteroventral cochlear nucleus (VCN),which in turn synapses at the dorsal and ventral nuclei of the lateral lemniscus as well as theventrolateral tegmental nucleus (VLTg). The VLTg is thought to be an area where auditory,tactile, and vestibular information are integrated. From these areas there is another synapse inthe ventromedial region of the nucleus reticularis pontis caudalis (PnC or RPC). Once signalsreach the PnC, axons run from their cell bodies down to the spinal cord through thereticulospinal tract. The reticulospinal tract travels down the anteromedial colunm of the spinalcord, specifically the medial longitudinal fasciculus on the midline, where it bifurcates and formsthe ventral funiculi. Nerve fibers that travel down the reticulospinal tract then synapse in the47spinal cord with lower motor neurons directly and possibly indirectly through interneuronsbefore reaching the neuromuscular junction to send impulses to the responding muscles (Davis,1982; Yeomans & Frankland, 1996).Evidence Supporting the SAS PathwayThe SAS response is reduced or eliminated in animals with injuries to the midbrainreticular formation (Davis, 1982). This is also seen in humans with damage totheir reticularformation. Steele-Richardson-Olszewski syndrome causes widespread pathological changesinthe human brain stem and includes degeneration of the pontinereticular formation. People withthis syndrome show a reduced SAS reflex response (Vidailhet et al.,1992). These findings helpsupport the idea that the reticular formation acts as a SAS response relay centre, indicating thepossible importance of this structure in the SAS reflex.As described above, the PnC is located within the reticular formation and is proposedtobe a main component of the SAS reflex circuit throughrat models. Evidence of the SAS reflexpropagating through the PnC in people has been supported by a positron emissiontomography(PET) study. In a study presented by Piassiota, Frans, Fredrikson, LângstrOm & Flaten(2002),participants were subjected to startling acoustic stimuli and had higher cerebral blood flow in anarea of the pons which anatomically corresponds to thelocation of the PnC. The increase inactivity in this area after SAS responses is thoughtto be evidence of the PnC having an activerole in SAS response in humans.Evidence suggests that the SAS response propagates from the caudal brainstem tothemusculature in humans as it does in animals (Brown, Day, Rothwell, Thompson &Marsden,1991 a). The order of muscle recruitment may indicatecircuitry through the caudal brainstem.SAS elicit SCM muscle responses more rapidly thanmasseter or mentalis muscle responses. TheSCM is a neck muscle innervated by the eleventh cranialnerve, the masseter is innervated by the48fifth, and the mentalis by the seventh and both latter muscles are located in the face. Thisactivation pattern would indicate that the reflex is first sent from around the eleventhcranialnerve area in the caudal brainstem, rostrally (upwards) to the superior cranial nerves involvedwith motor activation, as well as down the brainstem, caudally to lower levels in the brainstemand spinal cord (Brown et al., 1991 a). The SAS reflex appears to follow a different route thanresponses elicited in muscles by transcranial magnetic stimulation of the motor cortex.Magneticstimulation of motor neurons in the cortex elicits responses of muscles sent through thecorticospinal pathway. The conduction velocities of the SAS responses in thelimbs and torsoappears to be moderately slow in comparison to the conduction velocities of the corticospinalresponses. The reflex latencies to the SAS are greater than those elicited by magneticstimulation of the motor cortex (Brown, Rothwell, Thompson, Britton, Day & Marsden, 1991b).This may be indicitive of the reflex following a pathway different from the corticospinalpathway, and provides further evidence that it may follow thereticulospinal pathway.The SAS reflex results in a bilateral muscle response. These responses are seen in thefiring behaviour of motor units of homologous muscles on both sides of the body with atendency to synchronously discharge in the 10-20 Hz bandwidth (Grosse & Brown,2003). Whena participant attempts to mimick a general muscularSAS response in the absence of a SAS,bilateral coherence in the 10-20 Hz bandwidth is no longer demonstratedin homologousmuscles. Intentional muscular contractions are sent fromthe brain via the corticospinal system,which sends separate outputs to each side of the body anddrives synchronization of motor unitsover a 15-30 Hz bandwidth (Grosse & Brown, 2003; Kilner,Baker, Salenius, Jousmaki, Han &Lemon, 1999). The reticulospinal tract is thought to be thepathway through which thesehomologous muscular responses travel at the 10-20Hz band.Responses demonstrated in the 10-20 Hz band should indicate reticulospinal drive and responsesoutside of this bandwith mayindicate an alternate route or reflex.49SAS ResponseA SAS response may be elicited by any unexpected sound. SASexperiments typicallyuse intensities above 110 dBs but no louder than 124 dB. The duration ofthese SAS tones rangefrom 30-50 ms. The combination of sound intensity and duration willelicit an SAS response. Itis also important to note that these stimuli are typically presentedwith a fast rise to stimulusintensity time and stimuli are typically presented binaurally (Brown etal., 1991 a; Brown et al.,1991b; Csomor et a!., 2006; Delwaide & Schepens, 1995; Grosse &Brown, 2003;Nieuwenhuijzen, Schillings, Van Galen & Duysens, 2000).Responses to the SAS vary betweenparticipants. Most participants generally respond with eye closure andflexion of the neckmuscles. Greater responses also include trunk flexion, someabduction of the arms, flexion of theelbows, pronation of the forearms (Brown etal., 1991 a), extensor contractions (Rossignol,1975), and responses in distal musculature, likethe soleus or tibialis anterior (Brown et al.,1991b, Nieuwenhuijzen et al., 2000).The systemic SAS response seems to decline in amplitudeand in some cases disappearsall together after repeated exposure (Quednow et al., 2006).The decline in SAS responseamplitude with repeated exposure is referred to ashabituation. There is research that hasdemonstrated that after as few as 2 trials, the SAS responsemay no longer be elicited (Brown etal., 1991b). The eye blinks and neck muscle responses typicallyrequire the longest amount ofexposure to habituate and do not always disappearbut rather decrease in amplitude (Davis,1982). One way to deal with the issue of habituation is topresent SAS randomly over longperiods of time so the stimuli may remain unexpected(Brown et al., 1991 a; Nieuwerthuijzen etal., 2000; Rossignol, 1975; Russolo, 2002). For example,Brown and colleagues (1991a)randomly presented an auditory stimulus onceevery 20 minutes. In contrast Nieuwenheijzen etal. (2000) presented stimuli at aninter-stimulus interval of 1.5 to 2.5 minutes to avoidhabituation.50The eye blink is used as a main indicator of a SAS response by some researchers,whileothers rely on contraction of the sternocleidomastoid (SCM) as the marker of SAS responses.Electromyography (EMG) is used to measure orbicularis oculi (0Cc) during the presentationofacoustic stimulus to identify muscle activity. These blink responses vary between individualswith a range of onsets from 25 and 69 ms (Brown et al., 1991a). Blink responses are muchfasterthan the onset of the SCM responses which range between 40 to 136 ms. Another detail tonoteis that eye blink and SCM responses persist in spite of the habituation in the muscle responses inthe rest of the body outlined previously (Brown et al., 1991a). It appears that there is a blinkreflex in response to sound that is separate from the SAS blink reflex. This blink reflex to soundis termed the auditory blink reflex and appears to have a shorter latency and shorter duration thenan actual SAS blink reflex. It is suggested that the blink reflex may actually follow a differentpathway than the SAS blink reflex response in the OOc and the SAS reflex responses in themuscles of the rest of the body (Davis, 1982). It has proven difficult to separate the tworesponses and it is thought that both pathways may travel through the nucleusreticularis pontiscaudalis (nRPC) in the PnC. A weak auditory stimulus may activate a sufficient number ofneurons within the nRPC to evoke an auditory blink reflex. That same auditory stimulusmay beinsuffient in activating a particular threshold of neurons within the nRPC for a SAS response. Asubthreshold activation of neurons will not evoke an action potential to be sent down thereticulospinal tract for a SAS response. When an auditory stimulus reaches the threshold of SASresponse, both auditory blink response and SAS response will be sent making itdifficult todissasociate the two (Valls-Solé, Valldeoriola, Molinuevo, Cossu, & Nobbe, 1999a). As the tworeflexes are difficult to distinguish from one another, it may be incorrect to use theblink as anindicator of a SAS response and therefore a blink coupled with SCM activity may bemorereliable marker of a SAS response.51SAS Responses during Static and Dynamic TasksSAS responses are seen throughout the body including the lower limbs. SAS responsesare seen in the soleus and TA with or without the muscles being engaged in controlingposture.Standing and seated positions have been examined to identify the differences in SAS responseswhen body position is varied. The reflex appears as a bursting pattern ofmuscle EMG activitythat is of greater amplitude than normal background activity present in themuscle in a stationaryposition (Brown et al., 1991b; Deiwaide & Schepens, 1995; Nieuwenhuijzen et al., 2000;Rossignol, 1975). Standing is the most conducive position to observe SAS EMG muscleresponses in the legs as they are seen about twice as frequently as seated leg responses.Standingalso displays shorter reflex latency times with TA latencies of 80 ms and soleus 70 ms,whileseated TA latencies of 120 ms and soleus 130 ms (Brown et al., 1991a). SASresponses may alsobe seen in some participants while holding avoluntary contraction of their soleus or TA whenseated. Voluntarily contracting these muscles increasethe excitability of the motorneuron pool tolower excitation thresholds within the muscle. If the reflexiveresponses were present in a subjectwhile seated and contracting, its latency is similar to thoseexhibited while seated and relaxed(Delwaid & Schepens, 1995). The latency of the SAS reflex is shorterin the standing position,but still occurs in the seated position, with andwithout background muscle activation.To further examine the body’s response to startling stimuli indifferent conditions humangait has been examined. The phases of gait were examinedas SAS responses may be found inboth flexors and extensors with or without backgroundactivity in stationary conditions. Thelevels of activation due to SAS of the extensors or flexorswere not solely based on thebackground activity of the muscle but weredependent on the phase of gait. These findingssuggest that responses in distal musculatureoccur to maintain stability during the SAS, such asco-activation ofboth flexors and extensors during the stancephase (Nieuwenhuijzen et al.,2000).52SAS responses are found in both engaged and unengaged muscles, but responses do seemmore consistently present in cirucumstances where the maintenance of postural stability isimportant. Direct postural responses were examined with the presentation of SAS. Russolo(2002) found that SAS presented for longer periods of time (5 seconds) elicit sway towards thestimulus when presented unilaterally. When participants face their head’s forward and thestimulus is presented to the left ear, participants swayed left. When their heads were turned overtheir left shoulder and the stimulus was presented in their left ear, the participant swayedforward. No sway responses were found with bilateral SAS presentation (Russolo, 2002). Thesefindings suggest that SAS responses may be rooted around the maintenance of posture, but notcompletely dependent on posture as seated conditions may still yield responses similar tostanding.SAS do not only elicit reflexive responses but they also shorten the onset latency ofprepared movements. The paradigm used to examine the advanced preperation of motorresponse is the reaction time (RT) task. In an RT task, participants are typically instructed toconduct a movement (e.g. elbow extension to flexion) in response to a visual stimuli when a ‘go’signal is presented. Participants are encouraged to respond as quickly and accurately as possible.If a SAS is presented prior to the ‘go’ signal, motor responses are made at a shorter onsetlatency. The duration, timing and task accuracy in the EMG muscle responses are similar in boththe non-SAS and SAS RT tasks. The speeding up of a response has been shown in ballisticreaction time tasks as well as during different components of compound movements (Carlsen,Hunt, Inglis, Sanderson & Chua, 2003; Carlsen, Chua, Inglis, Sanderson & Franks, 2004; VallsSole, Rothwell, Goulart, Cossu & Mufloz, 1999b). A startling sound may therefore elicit a SASreflex response within the body, or impact upon a prepared or planned movement being made bythe body.53Pre-pulse InhibitionThe SAS reflex maybe altered by the presentation of a stimulus prior to the SAS. Theprestimulus decreases the amplitude or completely inhibits the SAS response when it precedesthe SAS by 30-500 ms and is referred to as pre-pulse inhibition. Pre-pulse inhibitioncan beproduced by vibrotactile, olfactory, visual or acoustic lead stimuli (Filion, Dawson & Schell,1998). The degree of amplitude reduction is altered by the lead interval time,its intensity and thetype of stimulation used (Hoffman, 1984). The level of pre-pulse inhibition varies depending onthe intensity of the pre-pulse with a more intense stimuli having a greaterimpact, and therefore agreater inhibition effect (Bitsios & Giakoumaki, 2005; Blumenthal, 1996). Pre-pulse inhibitionis typically measured by the change of the SAS blink reflex response of the OOc(Valls-Solé etal., 1999a). This response may be inhibited anywhere from 50-80% by pre-pulseinhibition in90-100% of normal adults tested with reliable SAS blink responses (Filion et al., 1998).Both theSAS blink reflex and the auditory blink reflex are affected in the same way by pre-pulsemodulation suggesting that at some point along their pathways they are influencedin the samemanner (Valls-Solé et al., 1999a).In circumstances where the pre-pulse is not an acoustic stimulus, the amount ofreflexinhibition appears to be dependent on the intensity and timing of the reflex-inhibiting stimulusand independent of the intensity of the SAS reflex stimulus (Hoffman & Ison, 1992). When bothpre-pulse and SAS are acoustic, the amount of SAS inhibition appears to be dependenton bothsound intensities (Blumenthal, 1996). Pre-pulse inhibition studiestypically present stimulibinuarally using pre-pulses with durations of 20-40 ms at dB levels lower than the SAS.Stronginhibition typically occurs with the lead interval time (the time between the pre-pulse and SAS)within the range of 100-l4Oms (Blumenthal, 1996; Csomor et al.,2005; Csomor et al., 2006;Quednow et al., 2006; Schwarzkopf, McCoy, Smith & Boutros,1993).54Pre-pulses may themselves be sufficient in causing a SAS response. In rats, pre-pulsestimuli of 50-60 dB may elicit SAS responses (Blumental & Goode, 1991). In humans, prepulses of 95dB and above may evoke SAS responses (Hoffman, 1984). To lessen the likelihoodof the pre-pulse itself eliciting a response, intentities of 95 dB or lower should be used inhumans. Background noise may be used to reduce the probability of SAS responses to the prepulse stimuli. Csomor and colleges (2005) employed a background noise of 70 dB with prepulses in the range of 76-88 dB (6-18 dB above the background noise). As a result, they werestill able to elicit pre-pulse inhibition of the SAS blink response using a SAS of 95, 105 and 115dB levels. Despite the benefits of using background noise, there are nonetheless detriments.Detection of the pre-pulse stimuli may not be possible if it does not overcome the loudness of thebackground noise. Background noise may also reduce the level of pre-pulse inhibition of theSAS response in response to pre-pulses and may interfere with the processing of the pre-pulsestimulus (Blumenthal, Noto, Fox & Franklin, 2006). In humans using a pre-pulse of an intesityof 95 dB or lower is safe experimentally to avoid SAS response to the pre-pulse stimulus and insituations with little to no background noise. The causation of these factors is likely linked to theprocessing and pathway of the pre-pulse inhibition.Pre-Pulse Inhibition Processing and PathwayPre-pulse inbition is thought to occur by the processing of select information within thebrain. Graham (1975) deduced that the brain attempts to protect and analyze the information ofthe first lower intensity stimulus it receives when another larger stimulus is presented followingthe first. It is a wired-in negative feedback mechanism that causes the attenuation of the loudersecond SAS while perceptually processing and analyzing the stimulus presented initially. Thistheory follows a sensory-gating mechanism wherein the brain selectively processes informationand ignores other information. In general, it is thought that when a stimulus is first perceived it is55identified and analyzed while a protective process attenuates other information until theinitialanalysis is complete. The information that is attenuated may be external information (auditory,visual, tactile), or it may be internal stimuli such as thoughts, feelings orimpulses (Geyer,Swerdlow, Mansbach & Braff 1990). This theory is supported by clinicalpopulations such asschizophrenic patients. These patients are characterized by their inability to regulateinternalstimulation and have general inhibitory deficits. Schizophrenic patients display alack, or lowerincidence of pre-pulse inhibition (Filion et al., 1998; Ludewig, Geyer,Etzensberger&Vollenweider, 2002).Work has been done to identify the pre-pulse pathwaythrough which the SAS response isinhibited. Evidence suggests that the pre-pulse affects theacoustic pathway relatively early as itinhibits both the auditory blink reflex and the SAS reflex(Valls-Solé et al., 1999a). Pre-pulsesignals are sent via subpallidal projections to thepedunculopontine tegmental nucleus (PPTg),which sends inhibitory signals through cholinergicprojections to the nucleus reticularis pontiscaudalis(nRPC) in the PnC (Valls-Solé et al., 1999a;Blumenthal, 1996). SAS are relayedthrough the PnC to the reticulospinal tract. When apre-pulse occurs, signals from the PPTg aresent through cholinergic projections and inhibit the SAScentre neurons in the nRPC. Aninhibitory signal is sent to the nRPC reguardless of whether aSAS follows a pre-pulse or not.The inhibitory signal may completely prevent a SASresponse, or reduce the response dependingon the magnitude of the SAS signal. As the intensity ofthe SAS is increased, a greater numberof excitatory SAS centre neurons are activated in the nRPC.The pre-pulse inhibitory signal fromthe PPTg neurally inhibits some of SAS centre neuronswithin the nRPC (Blumenthal, 1996). Ifthe number of neurons excited by input froma SAS is less than the number inhibited by the prepulse, then no SAS reflex should be seen.If a greater number of excitatory SAS neurons areactivated than the number of those inhibited by the pre-pulse,a SAS reflex response will be seen.The magnitude of this response will be smallerthan the typical SAS response in the absence of a56pre-pulse stimulus. Therefore the greater the intensity of the SAS, the larger the response thatshould be seen while being inhibited by the same pre-pulse intensity (Blumenthal, 1996).Repeated Acoustic Stimuli (RAS) ReponseAlternative means of presenting SAS have been recently assessed. In a recent study(Nichol et al., 2007), SAS were presented with short random intervals between stimuli and thispresentation method was referred to as Repeated Acoustic Stimuli (RAS). The SAS werepresented at intervals of three to five seconds between each sound with 125 stimuli in a giventrial. This method promoted habituation of the typical SAS response after the first few stimuliand yet still rendered an apparent reflexive response in the soleus muscles. Responses may beseen in all subjects in the experiment in Figure 9.57P1Figure 9: Average RAS reflexes recorded in the left soleusmuscles of eachparticipant. The shaded area highlighting the RAS reflex response peak. P1through P14 represent the 14 different participants (Nicholet al., 2007).Participants were positioned in the supine position with their headfacing forward whilemaintaining a background muscle response of the soleus.The rationale for the backgroundmuscle response was to equal that of quiet stanceand was determined from a standing relaxedRASlOOms58position. This level of background activity while laying was maintained by plantarflexion withthe ankle maintained at a 90 degree angle, and the feet flat against a stationary board at 90degrees to horizontal. RAS were presented binaurally using a horn placed directly over aparticipants face at a distance of 30 cm from each ear. The RAS was a 1000 Hz, 124 dB, 40 mspulse presented randomly at 3 to 5 second time intervals between stimuli(interstimulus interval)with a fast rise to intensity. Participants surface soleus EMG responses wereroot mean squaredand averaged without the first 10 stimuli to avoid the inclusion of typical SAS EMG responses.A reflexive response was present across all participants which may be seenin the highlightedarea shown in Figure 9. All participants showed similar responsesbilaterally in their soleusmuscles (see Figure 10). The reflex begins as a positivedeflection in the EMG followed by areturn to neutral and in some participants a negative (downward)deflection that may be followedby further multi-phasic activity of lesser amplitude. The commencement ofthe reflex responsewas measured as two S.D. above background activity prior to the stimuli and was found to havean average onset latency of 65.2 ms in the right soleus (S.D.= 18.6 ms) and 69.9ms in the leftsoleus (S.D.= 13.2 ms). A peak positive response is seen at112.6 ms (S.D.= 16.2 ms) in the rightsoleus and 113.1 ms (S.D.=15.5 ms) in the left soleus. After the positivepeak response there wasa return to neutral, or a negative trough at 150-160 ms andresponses varied with someparticipants showing multi-phasic responses of decreasing amplitude for 500 ms following theinitial peak and others had no discernable peaks or troughs followingthe initial peak. The peakresponses were still present after averaging trials with no SASevoked SCM responses as seen infigure 11, and no SAS evoked OOc responses as seen in Figure12.The identifiable muscle responses to stimuli with no OOc and no SCMactivity (Figures11 & 12), typical indicators of SAS, suggests that this responsemay differ from a SAS response.Figures 10-12 show a discemable response at asimilar onset latency to that of a standing SASresponse which is 70 ms in the soleus and much shorter thanthe onset of the sitting SAS soleus59responses at 13 Oms (Brown et al., 1991 a). Standing involves engagement in posture by lowerlimb muscles like the soleus, while seated and laying conditions do not. One might assume thatthe seated and laying conditions should therefore have similar onset latencies in response to SASrather than standing and laying, although this is unknown as no laying SAS study has beenconducted. As it is in fact the standing SAS and the laying condition of this experiment that havesimilar onset latencies, responses could be dependent on body positioning rather thanengagement in posture and the responses in this experiment and SAS responses could in fact berelated. To better understand what occurs with this varying form of stimulation more researchmust be conducted to investigate similarities and differences between SAS and these newresponses.Figure 10: Average RAS reflexes recorded in the left and right soleusmuscles of one participant (Nichol et al., 2007).—Right— Leftii100 msec60Levi SoeucM civprtNO SCM ctvty prsrtFigure 11: Average RAS reflexes recorded in the left and right soleusmuscles of one participant with and without the presence of SCM activity(Nichol et aL, 2007).Figure 12: Average RAS reflexes recorded in the left and right soleus musclesof one participant with and without the presence of OOc activity (Nichol et al.,2007).Right SoeuBASOC) rnsecOO4 pktNo 0Cc ctvlty weet61The results found in this experiment show similar timing to sound-induced variations inH-reflex amplitude. A spinal excitability has been reported following loud acoustic stimuli.Thisexcitability begins 50 ms after acoustic stimulus onset, with a peak amplitude at 100-130 msafter stimulus and excitability lasting a mean duration of 200 ms with arange of 120-460 ms(Liegeois-Chauvel, Morin, Musolino, Bancaud & Chauvel, 1989; Rossignal & Jones, 1976).This audiospinal facilitation is considered a possible physiological substrate of SAS (LiegeoisChauvel et al., 1989). The potentiation of the H-reflex by the acousticstimuli also appears moreresistant to habituation than a SAS response and remains present after repeatedstimuli(Rossignal & Jones, 1976). The auditory facilitation is noted with loud stimuli of 110dB(Rossignal & Jones, 1976), as well as more ordinary environmental sounds of 80 dB(Rudell &Eberle, 1985). The facilitation is bilateral and symmetrically distributed with thesame timing ofthe soleus H-reflex in both limbs with monoaural stimulation.There is suggestion that thefacilitation may be due to an increase in motoneuron excitability in the soleusand/or due to adecrease in the presynaptic inhibition of soleus Ta fibers (Liegeois-Chauvel etal., 1989). Due tothe similarities between RAS responses and the timingof the sound-induced H reflex response, itis possible that the two are related. The RAS reflexis a new area of investigation. It is notknown if it shares conimonalities with the SAS reflex,or if it is a completely separate responseby the body.62Appendix 2: Single Acoustic Stimulus Responses63ONSET PEAK AMPLITUDERSOL (ms) (ms) (mV)1 138.12 140.98 0.0037452 50.56 0.0025253 79.7 102.32 0.0290654 95.82 127.28 0.0059955 40.44 124.68 0.02325514 44.6 195.66 0.0139715 14.18 0.00625516 110.9 124.42 0.013917 60.46 0.0059718 93.48 111.16 0.0026Mean 74.34444 111.2378 0.010728stdev 39.25023 50.86951 0.009195sterror 13.08341 16.9565 0.002908ONSET PEAK AMPLITUDERDEL (ms) (ms) (mV)1 22.84 108.2 0.091222 82.9 95.88 0.000343 63.06 115.06 0.018184 32.12 119.22 0.088525 60 101.8 0.0124414 69.08 151.98 0.013115 100.5 114.54 0.0008616 70.4 90.62 0.0042417 36.8 83.08 0.025918 197.48 0.06637Mean 59.74444 117.786 0.032117stdev 25.15065 33.84639 0.035891sterror 8.383551 10.70317 0.01135ONSET PEAK AMPLITUDERGAS (ms) (ms) (mV)1 67.72 79.82 0.0063052 37.8 47.26 0.0010453 47.46 108.3 0.0173354 51.36 105.18 0.000595 25.62 105.18 0.00333514 47.46 101.8 0.00264515 33.94 199.04 0.0052716 57.6 0.0087217 232.84 53.96 0.0043118 61.24 64.88 0.003155Mean 67.271 1 1 92.302 0.005271stdev 63.44494 44.32421 0.00488sterror 21.14831 14.01655 0.001543ONSET PEAK AMPLITUDELSOL (ms) (ms) (mV)1 121.18 139 0.0165252 51.44 55.18 0.003413 51.36 101.02 0.0111454 76.32 96.08 0.006715 32.38 84.38 0.02355514 111.68 119.48 0.01249515 32.38 51.62 0.0060516 127.02 141.58 0.006817 43.82 139.76 0.00903518 51.62 135.6 0.00336Mean 69.92 106.37 0.009909stdev 36.80797 34.45071 0.006315sterror 11.6397 10.89427 0.001997ONSET PEAK AMPLITUDELDEL (ms) (ms) (mV)1 30.76 106 0.03932 0.000063 20.16 117.92 0.096324 57.34 130.4 0.010675 48.5 80.48 0.0226514 67.22 163.16 0.1151815 27.18 170.96 0.0017516 93.22 97.9 0.0017817 42.52 124.94 0.0387818 60.98 200.08 0.01037Mean 49.76444 132.4267 0.033686stdev 22.85276 38.51273 0.040805sterror 7.61 7587 12.83758 0.012904ONSET PEAK AMPLITUDELGAS (ms) (ms) (mV)1 0.0037752 113.04 116.34 0.0006353 46.68 117.92 0.0561454 78.92 95.56 0.003895 48.5 60.98 0.00527514 108.82 115.32 0.00252515 108.82 110.64 0.0034716 68 0.0029717 57.6 139.24 0.00239518 84.12 86.2 0.003585Mean 80.8125 101.1333 0.008467stdev 27.69713 25.54644 0.016796sterror 9.792415 8.515481 0.00531164ONSET PEAK AMPLITUDERSCM (ms) (ms) (mV)1 58.26 0.0743052 64.2 0.00293 42.26 113.76 0.0174154 69.82 0.1479755 . 69.04 0.0119514 58.38 135.6 0.0358215 54.74 71.38 0.0038216 41.22 69.56 0.0285217 25.62 74.76 0.12779518 21.98 200.08 0.119225Mean 40.7 92.646 0.056973stdev 14.76654 44.97884 0.055848sterror 6.028413 14.22356 0.017661ONSET PEAK AMPLITUDEROOC (ms) (ms) (mV)1 50.78 0.100452 28.12 57.38 0.030413 156.66 0.11114 60.72 0.078815 77.62 0.0735714 56.3 0.0273215 30.04 53.7 0.0185816 20.2 54.48 0.0274217 52.14 0.0251618 21.98 78.66 0.06311Mean 24.88 69.844 0.055593stdev 5.026039 32.09499 0.034214sterror 2.513019 10.14933 0.010819LSCM23451415161718ONSET PEAK(ms) (ms)63.123.28 200.1637.58 93.4866.4465.9256.04 127.5469.373.9825.1 70.3438.62 199.3AMPLITUDE(mV)0.0923250.000850.073240.0344450.015880.044970.010420.0213850.166180.07818Mean 36.124 102.956 0.053788stdev 13.14814 54.52285 0.050236sterror 5.880025 17.24164 0.01588665Appendix 3: Single Acoustic Stimuli Across Six Trials66SAS 1 SAS 2 SAS 3 SAS 4 SAS 5 SAS 6AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDEROOc (mV) (my) (my) (mV) (mV) (mV)1 0.17813 0.12181 0.17218 0.0726 0.09858 0.195022 0.02864 0.00882 0.01056 0.04775 0.03527 0.061823 0.1486 0.30862 0.16732 0.22527 0.1223 0.158824 0.09337 0.11507 0.08988 0.11633 0.24352 0.089755 0.06962 0.08147 0.10761 0.16134 0.09084 0.0491914 0.02153 0.04237 0.04787 0.01934 0.03185 0.0132315 0.01 765 0.00724 0.00553 0.01 838 0.03195 0.0458216 0.00495 0.04104 0.04113 0.03767 0.02778 0.0237517 0.02558 0.02538 0.03944 0.02616 0.03911 0.0420518 0.09769 0.14652 0.14611 0.1368 0.0463 0.12594SAS 1 SAS 2 SAS 3 SAS 4 SAS 5 SAS 6AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDELSCM (mV) (mV) (mV) (mV) (mV) (mV)1 0.05951 0.018895 0.149355 0.12301 0.087775 0.1662452 0.00404 0.00174 0.001355 0.00195 0.001335 0.002533 0.18494 0.07139 0.18096 0.13166 0.06131 0.0832354 0.034815 0.042825 0.05449 0.037245 0.02006 0.0345555 0.00061 0.015465 0.026635 0.02548 0.02519 0.00053514 0.03516 0.06947 0.17716 0.058755 0.1735 0.0096115 0.00501 0.002855 0.01 0365 0.004815 0.036775 0.01 741516 0.001735 0.04553 0.019245 0.03127 0.02936 0.0044817 0.22122 0.21339 0.197935 0.210215 0.175445 0.2055818 0.15624 0.14269 0.127685 0.12571 0.092065 0.07223SAS I SAS 2 SAS 3 SAS 4 SAS 5 SAS 6AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDERSCM (mV) (mV) (mV) (mV) (mV) (mV)1 0.04407 0.02072 0.099545 0.10998 0.109625 0.118562 0.001 0.00065 0.000825 0.002235 0.006615 0.0087053 0.041085 0.02967 0.034215 0.05234 0.01397 0.0143454 0.17374 0.14868 0.150795 0.152305 0.1573 0.106095 0.000955 0.00801 0.011905 0.018445 0.043815 0.0037714 0.01947 0.053345 0.06972 0.02215 0.13839 0.00569515 0.00656 0.002715 0.00668 0.0036 0.014295 0.0063116 0.001875 0.050435 0.035825 0.05153 0.03377 0.0034917 0.19126 0.1539 0.139955 0.138515 0.151355 0.18087518 0.166825 0.204855 0.225965 0.20944 0.134795 0.08162567SAS I SAS 2 SAS 3 SAS 4 SAS 5 SAS 6AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDELSOL (mV) (my) (my) (mV) (mV)(mV)1 0.003295 0.00463 0.04245 0.02399 0.018115 0.025972 0.014235 0.00404 0.009355 0.009245 0.00491 0.0101853 0.002245 0.008205 0.06339 0.003645 0.036975 0.0042454 0.00871 0.00778 0.018505 0.0235 0.008245 0.011435 0.020125 0.046895 0.02147 0.064095 0.04702 0.0213414 0.013675 0.01463 0.017355 0.014865 0.0210850.01421515 0.01559 0.010335 0.006645 0.015025 0.031695 0.01279516 0.00912 0.014155 0.00381 0.00677 0.01278 0.02151517 0.011635 0.012775 0.010025 0.00929 0.03525 0.01097518 0.00379 0.009165 0.006235 0.008055 0.00765 0.03047SAS 1 SAS 2 SAS 3 SAS 4 SAS 5 SAS6AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDERSOL (mV) (mV) (mV) (mV) (mV) (mV)1 0.002955 0.005605 0.005085 0.01903 0.010575 0.0132752 0.00474 0.00628 0.00746 0.0019950.00594 0.005593 0.007045 0.021565 0.05613 0.01070.02078 0.0132454 0.012725 0.010455 0.009925 0.00968 0.0150750.0116355 0.015445 0.04344 0.028255 0.0409550.04409 0.01209514 0.005345 0.03016 0.03161 0.01549 0.049385 0.00596515 0.015845 0.01433 0.022385 0.00786 0.020080.02508516 0.019835 0.01934 0.0338 0.013530.023705 0.01770517 0.02517 0.013055 0.01365 0.02546 0.016275 0.0095218 0.001825 0.00262 0.003165 0.007135 0.00391 0.016375SAS 1 SAS 2 SAS 3 SAS 4 SAS 5 SAS 6AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDE AMPLITUDEAMPLITUDERMGAS (mV) (mV) (mV) (mV)(mV) (mV)1 0.004843 0.015225 0.012149 0.007044 0.0173210.0143762 0.004094 0.001673 0.0025080.00191 0.001281 0.0011073 0.028397 0.016703 0.114835 0.0143280.005207 0.0079024 0.000609 0.001697 0.001217 0.0015180.002288 0.0007855 0.004521 0.005368 0.006084 0.003547 0.01146 0.00573614 0.002943 0.004644 0.001586 0.0055570.009287 0.00482815 0.003118 0.003229 0.004637 0.0129210.008914 0.00909616 0.034008 0.007458 0.004457 0.027346 0.0363390.04573617 0.012432 0.00569 0.026601 0.0107110.006327 0.00969518 0.001638 0.005709 0.0140690.009527 0.004528 0.0069468Appendix 4: Repeated Acoustic Stimuli Responses69ONSET PEAK AMPLITUDERSOL (ms) (ms) (my)1 30.32 111.94 0.002512 34.72 55.18 0.002183 42 114.28 0.0024754 61.24 115.32 0.0058055 28.74 102.58 0.0021614 49.54 104.92 0.003915 28.22 101.8 0.00230516 42.78 108.3 0.00545517 50.84 91.4 0.0041218 87.5 0.001555Mean 40.93333 99.322 0.003247stdev 11.46015 18.008093 0.001484sterror 3.820049 5.6946591 0.000469ONSET PEAK AMPLITUDERDEL (ms) (ms) (mV)1 110.18 0.000822 0.000323 0.000154 0.000035 0.000214 20.68 0.0006115 44.08 141.84 0.0004516 21.2 0.0004717 55 165.5 0.0000518 58.12 127.28 0.00072Mean 52.4 97.78 0.000382stdev 7.372272 62.225716 0.000278sterror 4.256383 25.403542 8.79E-05ONSET PEAK AMPLITUDERGAS (ms) (ms) (mV)1 29 76.52 0.0085852 39.78 117.28 0.000763 41.22 99.98 0.0011954 52.14 105.96 0.0011755 33.16 102.06 0.0008514 91.4 109.34 0.0027415 33.68 102.32 0.00651516 33.16 123.38 0.0060717 44.86 94.78 0.00205518 39.92 79.7 0.00492Mean 43.832 101.132 0.003487stdev 18.01904 14.740123 0.002818sterror 5.698122 4.6612361 0.000891ONSET PEAK AMPLITUDELSOL (ms) (ms) (mV)1 40.44 89.28 0.005172 43.08 55.4 0.001713 48.5 109.08 0.0012154 50.32 109.08 0.0025355 31.86 105.44 0.002414 88.8 106.22 0.00584515 33.68 71.9 0.00159516 53.7 106.48 0.00279517 39.66 124.68 0.00214518 43.04 87.24 0.001305Mean 47.308 96.48 0.002672stdev 16.12125 20.59361 0.001591sterror 5.373751 6.51227 0.000503ONSET PEAK AMPLITUDELDEL (ms) (ms) (mV)1 57.6 100.94 0.000322 131.74 0.000023 24.06 0.000454 121.3 129.88 0.000035 73.98 89.06 0.0002914 77.88 88.28 0.0005615 44.86 53.96 0.0002316 36.28 155.62 0.0002217 200.08 0.0000518 48.5 126.76 0.00344Mean 65.77143 110.038 0.000561stdev 28.77941 50.40151 0.001027sterror 10.8776 15.93836 0.000325ONSET PEAK AMPLITUDELGAS (ms) (ms) (mV)1 34.72 113.7 0.004652 36.92 54.08 0.0003853 85.42 105.44 0.0022954 104.92 0.001045 38.88 102.06 0.00269514 37.58 110.12 0.00238515 24.06 102.58 0.00574516 51.1 109.86 0.00126517 40.44 115.58 0.0010218 33.68 73.72 0.00312Mean 42.53333 99.206 0.00246stdev 17.56104 19.6857 0.001698sterror 5.853681 6.225165 0.00053770ONSET PEAK AMPLITUDERSCM (ms) (ms) (mV)1 14.04 65.08 0.0014952 25.26 39.12 0.0001753 37.58 0.0002654 0.0000755 0.00025514 96.6 0.00007515 20 75.28 0.00094516 105.7 0.0000817 33.68 49.02 0.000518 98.94 0.00071Mean 23.22 70.915 0.000458stdev 8.34402 27.117495 0.000488sterror 4.17201 9.5874822 0.000154ONSET AMPLITUDEROOC (ms) PEAK (ms) (mV)1 48.14 0.062752 20.64 51 0.001263 12.88 51.1 0.01154 11.06 53.7 0.012545 12.88 65.4 0.0245214 17.82 43.04 0.0044915 23.28 46.68 0.0076216 14.7 126.5 0.0037117 10.02 41.48 0.009518 12.62 60.2 0.04431Mean 15.1 58.724 0.01 822stdev 4.259598 23.63003 0.01912sterror 1 .419866 7.472471 0.006046ONSET PEAK AMPLITUDELSCM (ms) (ms) (my)1 66.4 0.00162 24.82 32.52 0.0001253 86.72 0.002034 0.000335 0.00023514 18.6 21.2 0.0000915 74.5 0.00085516 95.56 153.02 0.0001517 16.52 111.42 0.0001718 17.56 47.2 0.000485Mean 34.612 74.1225 0.000607stdev 37.95416 45.20768 0.000723sterror 16.97361 15.98333 0.00022971Appendix 5: SAS Responses and SAS with Pre-Pulses Responses72% Pre-PulsePre-pulse inhibitionRSOL SAS andSAS(PSAS/SAS*100)Onset Peak Amplitude Peak AmplitudeParticipant (ms) (ms) (mV) Onset (ms) (ms) (mV)6 135.34 149.38 0.004 111.42 119.48 0.002 41.57 19.64 199.82 0.015 181.1 186.04 0.008 53.78 16.26 140.02 0.069 87.24 115.06 0.022 31.39 183.44 186.82 0.004 214.38 74.76 0.004 104.310 87.24 186.82 0.04 82.04 118.96 0.075 185.811 93.22 101.8 0.004 90.1 102.06 0.019 428.112 40.7 88.28 0.013 121.82 130.66 0.007 51.713 194.88 200.08 0.009 91.92 110.38 0.037 412.3Mean 96.34 156.63 0.02 122.5 119.68 0.022 109.3PercentPre-pulse Amplitude of PPLSOL SAS and SAS(PSASISAS*100)Onset Peak Amplitude Peak AmplitudeParticipant (ms) (ms) (mV) Onset (ms) (ms) (mV)6 133.26 149.6 0.006 644.42 47.2 0.004 60.97 162.64 164.5 0.007 477.24 112.98 0.003 44.48 128.58 138.5 0.037 4.56 133.78 0.011 30.89 268.72 190 0.004 105.96 107.26 0.003 70.510 26.14 98.68 0.033 74.5 102.06 0.066 201.511 135.86 141.1 0.007 47.72 110.9 0.039 539.612 41.22 198 0.012 56.56 56.82 0.006 48.913 19.64 123.1 0.07 88.54 112.2 0.051 72.5Mean 114.508 150.4 0.022 187.44 97.9 0.023 104.0PercentPre-pulse Amplitude of PPRDEL SAS andSAS(PSASISAS*100)Onset Peak Amplitude Peak AmplitudeParticipant (ms) (ms) (mV) Onset (ms) (ms) (mV)6 62.5 143.1 0.03 0.4 16.52 3E-04 1.17 26.14 147.8 5E-04 279.38 146.26 1E-04 31.18 25.36 121 0.12 51.62 53.7 2E-04 0.29 208.92 1.44 0.001 166.02 174.6 0.001 83.810 41.24 149.6 0.074 65.74 175.12 0.123 167.311 175 0.66 4E-04 82.5 130.66 0.001 297.712 57.98 153.3 0.03 0.4 22.24 9E-04 3.113 56.46 147 0.273 0.4 177.2 0.089 32.7Mean 81.7 108 0.066 80.808 112.04 0.027 40.973PercentPre-pulse Amplitude of PPLDEL SAS andSAS(PSAS/SAS*100)Onset Peak Amplitude Onset Peak AmplitudeParticipant (ms) (ms) (mV) (ms) (ms) (mV)6 43.56 148.1 0.057 26.92 59.94 0.002 2.87 21.2 133.8 2E-04 0.92 23.28 2E-04 123.58 44.34 163.4 0.014 19.64 145.74 0.003 19.19 62.02 101.3 0.018 51.1 172.78 0.00314.210 44.86 140.5 0.083 77.88 159.52 0.184 220.711 83.86 200.1 9E-04 234.66 163.16 1E-0413.812 16.52 125.7 0.005 692.26 34.46 1E-0318.513 44.86 144.2 0.225 54.48 165.76 0.178 79.0Mean 45.1525 144.6 0.05 144.73 115.58 0.046 91.5PercentPre-pulse Amplitude of PPRGAS SAS and SAS(PSASISAS*100)Onset Peak Amplitude Onset Peak AmplitudeParticipant (ms) (ms) (my) (ms) (ms) (mV)6 142.1 143.4 0.001 233.1 12.19E-04 70.97 97.12 163.9 0.002 37.06 38.36 0.00143.78 66.44 87.76 0.02 30.8232.64 0.011 54.69 66.7 75.54 0.007 1.96 2.48 0.00452.010 41.48 106 0.058 68.78 113.76 0.092 158.911 484.26 29 0.005 85.42 106.22 0.019 371.212 38.1 136.1 0.01 47.98 127.28 0.001 10.013 98.47 156.1 0.008 89.32 111.160.01 127.5Mean 129.334 112.2 0.014 74.305 68 0.017 123.9PercentPre-pulse Amplitude of PPLGAS SAS and SAS(PSASISAS*100)Onset Peak Amplitude Onset Peak AmplitudeParticipant (ms) (ms) (mV) (ms) (ms) (mV)6 41.22 166.8 0.002 120 133 0.002 90.67 218.54 83.08 0.002 224.78 41.74 0.004 177.88 50.32 122.3 0.018 92.44 111.68 0.02 113.49 70.34 111.4 0.013 101.02102.84 0.004 27.810 61.76 135.9 0.074 68.52 106.220.083 111.511 131.96 199.3 0.002 38.1 107.26 0.008454.012 77.36 97.12 0.003 14.44123.64 6E-04 22.213 92.44 136.1 0.095 32.9 112.70.044 46.8Mean 92.9925 131.5 0.026 86.525 104.89 0.02179.274PercentPre-pulse Amplitude of PPROOC SAS and SAS(PSASISAS*100)Onset Peak Amplitude Onset Peak AmplitudeParticipant (ms) (ms) (mV) (ms) (ms) (mV)6 13.4 53.18 0.039 47.46 49.28 0.02 51.87 15.48 116.1 0.174 42 149.12 0.049 28.38 15.22 79.18 0.228 33.94 139.76 0.013 5.69 12.88 62.8 0.083 22.24 54.74 0.023 27.510 12.1 54.22 0.105 33.16 180.84 0.08 76.211 40.48 59.68 0.015 17.82 46.42 0.014 95.212 20.06 75.28 0.056 74.5 0.025 44.213 18.86 125.2 0.247 19.9 173.82 0.159 64.3Mean 18.56 78.21 0.119 30.931 108.56 0.048 40.4PercentPro-pulse Amplitude of PPRSCM SAS and SAS(PSASISAS*100)Onset Peak Amplitude Onset Peak AmplitudeParticipant (ms) (ms) (mV) (ms) (ms) (mV)6 25.62 72.16 0.004 28.74 131.44 0.002 56.87 51.88 70.86 0.021 121.04 139.5 0.007 33.08 7.68 67.22 0.109 20.94 70.6 0.068 62.09 15.74 108.8 0.036 30.04 78.92 0.004 10.110 23.28 122.1 0.009 69.04 163.94 0.013 144.711 77.1 197.5 0.012 55.52 139.24 0.012 104.012 49.54 76.06 0.12 39.66 185.24 0.014 11.813 18.6 178 0.121 24.32 183.18 0.136 113.0Mean 33.68 111.6 0.054 48.663 136.51 0.032 59.4PercentPro-pulse Amplitude of PPLSCM SAS andSAS(PSASISAS*100)Onset Peak Amplitude Onset Peak AmplitudeParticipant (ms) (ms) (my) (ms) (ms) (mV)6 34.72 67.22 0.008 0.4 136.12 0.009 115.87 41.74 75.54 0.004 121.04 130.14 0.001 32.78 24.06 65.4 0.027 20.94 73.2 0.01 36.49 22.5 100.2 0.112 30.04 136.12 0.028 24.610 10.8 71.38 0.045 69.04 157.44 0.043 95.511 90.88 200.1 0.004 55.52 165.24 0.009 204.912 48.24 76.32 0.157 39.66 80.22 0.019 12.313 15.48 105.2 0.203 24.32 139.5 0.156 76.8Mean 36.0525 95.17 0.07 45.12 127.25 0.034 49.075Appendix 6: RAS Responses and RAS with Pre-Pulses Responses76PercentPre-pulse Amplitude of PPRSOL RAS and RAS(PRAS/RAS*100)Onset Peak Amplitude Peak Amplitude(ms) (ms) (mV) Onset (ms) (ms) (mV)6 66.7 90.1 0.00066 80.74 88.02 0.000375 56.87 40.96 104.14 0.00342 34.72 82.3 0.003905 114.28 75.8 102.32 0.009175 63.06 84.12 0.00698 76.19 31.86 115.32 0.00188 52.66 111.42 0.00074 39.410 72.42 109.86 0.006605 62.02 111.94 0.0051578.011 115.84 127.02 0.001005 97.9 109.6 0.00054 53.712 43.3 79.44 0.003395 48.5 81 0.00301588.813 70.6 104.14 0.004865 76.84 92.7 0.00329 67.6Avg 64.685 104.0425 0.003876 64.555 95.1375 0.002999PercentPre-pulse Amplitude of PPLSOL RAS and RAS(PRASIRAS*100)Onset Peak Amplitude Peak Amplitude(ms) (ms) (mV) Onset (ms) (ms) (mV)6 72.94 90.1 0.00102 76.32 90.1 0.00096 94.17 50.32 88.54 0.002065 38.88 79.70.002415 116.98 43.56 105.44 0.00682 58.12 83.08 0.005695 83.59 37.58 117.92 0.00156 48.24 112.720.00125 80.110 39.92 112.98 0.00679 83.08 103.880.005475 80.611 56.3 129.1 0.00116 56.3 125.980.001905 164.212 37.58 55 0.002875 47.98 100.76 0.00174 60.513 60.46 101.02 0.005375 63.84 101.54 0.003695 68.7Avg 49.8325 100.0125 0.003458 59.095 99.72 0.002892PercentPre-pulse Amplitude of PPRDEL RAS and RAS(PRAS/RAS*100)Onset Peak Amplitude Peak Amplitude(ms) (ms) (mV) Onset (ms) (ms) (mV)6 0.4 3.26 0.00037 0.4 20.68 0.0002875.77 153.02 162.12 0.00008 165.24 175.12 0.00009112.58 74.5 182.4 0.00005 3.26146.26 0.00005 100.09 0.4 2.74 0.00014 0.4 0.40.0001 71.410 0.4 4.82 0.00136 0.4 2.480.00135 99.311 9.76 19.64 0.00028 0 69.30.00035 125.012 0.4 17.82 0.00094 0.4 17.560.00092 97.913 0.4 12.62 0.00081 0.4 20.940.00077 95.1Avg 29.91 50.6775 0.000504 21.3125 56.5925 0.00048977PercentPre-pulse Amplitude of PPLDEL RAS and RAS(PRAS/RAS*100)Onset Peak Amplitude Peak Amplitude(ms) (ms) (mV) Onset (ms) (ms) (mV)6 0 5.34 0.00017 0 13.4 0.00008 47.17 0.4 24.84 0.00006 0.4 23.8 0.00007 116.78 0.4 134.04 0.00014 0.4 23.54 0.00009 64.39 79.18 93.22 0.00058 47.72 118.44 0.00025 43.110 22.24 159.26 0.00034 91.66 108.82 0.00017 50.011 99.46 125.72 0.00017 55.78 59.94 0.0001 58.812 0 138.72 0.00011 297.32 0.14 0.00006 54.513 0.92 148.86 0.00024 444.22 65.14 0.00002 8.3Avg 25.325 103.75 0.000226 117.1875 51.6525 0.000105PercentPre-pulse Amplitude of PPRGAS RAS and RAS(PRASIRAS*100)Onset Peak Amplitude Onset Peak Amplitude(ms) (ms) (mV) (ms) (ms) (mV)6 79.44 92.96 0.000385 72.94 89.58 0.00042 109.17 39.14 84.64 0.00063 32.64 80.22 0.00057 90.58 70.08 96.08 0.002685 59.68 82.3 0.002075 77.39 42.52 112.46 0.001815 39.4 47.72 0.001035 57.010 53.96 113.24 0.00424 50.58 111.42 0.00321 75.711 114.02 122.6 0.002115 49.54 124.16 0.000925 43.712 31.94 60.2 0.000535 37.58 178.76 0.000355 66.413 67.22 94.26 0.001045 73.72 83.34 0.000675 64.6Avg 62.29 97.055 0.001681 52.01 99.6875 0.001158PercentPre-pulse Amplitude of PPLGAS RAS and RAS(PRASIRAS*100)Onset Peak Amplitude Onset Peak Amplitude(ms) (ms) (mV) (ms) (ms) (mV)6 33.16 83.6 0.000675 73.46 87.5 0.000355 52.67 50.84 83.6 0.001845 44.34 77.1 0.002065 111.98 38.88 105.7 0.00132 53.58 80.22 0.001335 101.19 9.5 110.38 0.004975 33.94 108.82 0.003465 69.610 83.08 113.5 0.003925 67.48 99.98 0.003215 81.911 56.3 132.22 0.001105 40.44 83.86 0.00089 80.512 43.3 113.5 0.000525 41.22 87.76 0.000575 109.513 55.52 103.62 0.00203 70.86 85.16 0.00112 55.2Avg 46.3225 105.765 0.00205 53.165 88.8 0.00162878PercentPre-pulse Amplitude of PPRSCM RAS and RAS(PRAS/RAS*100)Onset Peak Amplitude Onset Peak Amplitude(ms) (ms) (mV) (ms) (ms) (my)6 14.7 29 0.000115 21.72 30.56 0.00008 69.67 13.14 26.66 0.00073 81.52 95.3 0.000555 76.08 37.84 76.06 0.00104 9.5 67.74 0.000575 55.39 14.18 25.88 0.000445 12.88 31.08 0.000475 106.710 249.48 88.02 0.00001 0 46.42 0.00001 100.011 13.14 51.36 0.000125 38.62 86.72 0.000205 164.012 57.6 63.32 0.00049 18.62 26.14 0.000485 99.013 30.82 75.8 0.000595 0 7.68 0.000045 7.6Avg 53.8625 54.5125 0.000444 22.8575 48.955 0.000304PercentPre-pulse Amplitude of PPLSCM RAS and RAS(PRASIRAS*100)Onset Peak Amplitude Onset Peak Amplitude(ms) (ms) (mV) (ms) (ms) (mV)6 0.4 29 0.000425 0.4 24.58 0.000405 95.37 9.76 128.84 0.000115 74.76 83.6 0.000095 82.68 49.54 69.04 0.00013 13.92 59.94 0.000055 42.39 26.14 48.76 0.000505 476.2 28.74 0.000205 40.610 0.4 4.56 0.000145 0.4 0.92 0.00017 117.211 10.02 33.68 0.000255 21.2 37.58 0.000235 92.212 133.52 166.8 0.0002 1.96 1.96 0.00007 35.013 0.4 72.42 0.000585 60.72 62.8 0.000085 14.5Avg 28.7725 69.1375 0.000295 81.195 37.515 0.000165PercentPre-pulse Amplitude of PPROOc RAS and RAS(PRAS/RAS*100)Onset Peak Amplitude Peak Amplitude(ms) (ms) (mV) Onset (ms) (ms) (mV)6 20.42 60.46046 0.012058 14.18 62.80046 0.006909 57.37 . 58.12046 0.042332 . 37.32044 0.027316 64.58 13.92 56.04046 0.052984 9.5 51.10045 0.033371 63.09 25.62 48.76045 0.002721 24.32 57.60046 0.001583 58.210 12.1 57.60046 0.065219 . 48.76045 0.05454 83.611 19.6 59.94046 0.001136 . 38.88044 0.001318 116.012 . 73.46047 0.007805 . 63.84046 0.010458 134.013 3 50.58045 0.026367 3 43.04044 0.011954 45.3Avg 15.77667 58.12046 0.026328 12.75 50.41795 0.018431 77.779Appendix 7: UBC Research Ethics Board Certificate of Approval80LJCThe University ofBritish ColumbiaOffice ofResearch ServicesClinical Research Ethics Board — Room 210,828 West 10th Avenue, Vancouver, BC V5Z1L8ETHICS CERTIFICATE OF EXPEDITED APPROVAL:RENEWAL WITH AMENDMENTS TO THE STUDYPRINCIPAL INVESTIGATOR: jDEPARTMENT:IUBCCREB NUMBER:J.Timothy InglisIIO5-706O9[NSTITUTION(S) WHERE RESEARCH WILL BE CARRIED OUT:InstitutionISiteUBC Vancouver (excludes IJBC Hospital)Other locations where the research will be conducted:Not applicableCO-INVESTIGATOR(S):3rynne ElliottvIelanie G. RoskellJean-Sébastien BlouinJave NicholSPONSORING AGENCIES:- Natural Sciences and Engineering Research Council of Canada (NSERC) - “Sensory contributions to humannovement and balance”PROJECT TITLE:Sensory contributions to human movement and balanceThe current UBC CREB approval for this study expires: April 24, 2009MENDMENT(S): &MENDMENT APPROVALDATE:IDocument Name I Version I Date I .pril 24, 2008Consent Forms:versionSensory Posture consent form April 9, 2008CERTIFICATION:En respect of clinical trials:1. The membership ofthis Research Ethics Board complies with the membership requirementsfor Research Ethicsoards defined in Division 5 ofthe Food and Drug Regulations.?. The Research Ethics Board carries out itsfunctions in a manner consistent with Good Clinical Practices.3. This Research Ethics Board has reviewed and approved the clinical trialprotocol and informed consentform forthe trial which is to be conducted by the qualfied investigator named above at the specfied clinical trial site. Thisapproval and the views ofthis Research Ethics Board have been documented in writing.The Chair of the UBC Clinical Research Ethics Board has reviewed the documentation for the above named)roject. The research study, as presented in the documentation, was found to be acceptable on ethical grounds foresearch involving human subjects and was approved for renewal by the UBC Clinical Research Ethics Board.81

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