"Arts, Faculty of"@en . "Psychology, Department of"@en . "DSpace"@en . "UBCV"@en . "Lacoste, Diane"@en . "2010-05-29T17:05:02Z"@en . "1984"@en . "Master of Arts - MA"@en . "University of British Columbia"@en . "This study examined two possible genetic markers of Huntington's chorea: eye movements and electrodermal responsivity. Seven subjects in the early stages of Huntington's disease were compared to twenty-nine subjects in each of two other groups, a group of subjects at-risk for Huntington's chorea and a group of controls. Subjects completed a series of smooth pursuit and saccadic eye tracking tasks as well as listened to soft tones, loud tones, and sounds while electrodermal activity was recorded.\r\nVisual inspection of the eye movement data revealed that the Huntington's chorea group performed the poorest, across all the eye tracking tasks. Data analyses showed that the at-risk subjects, when compared with control subjects, tracked with a greater lag when the target moved at the greatest speed. There were no differences between the two groups on similar eye tracking tasks at the target's slower speeds. The at-risk and the control groups performed the vertical smooth pursuit, horizontal saccadic, and vertical saccadic tracking tasks equally well, at all target speeds. No differences between the at-risk and the control group emerged when direction of eye movement (right, left, up or down) was analyzed. Subjects in both groups tracked more poorly when they moved their eyes to the right in the horizontal tasks.\r\nThe electrodermal data yielded uniformly negative results indicating that there were no differences between the three groups in their responsiveness to soft tones, to loud tones or to the sounds of a barking dog and a newsroom teletype. The positioning of the three groups on the dependent measures were as described in previous research in that the Huntington group was the least responsive and the control group the most responsive. However, mean responsivity, as measured by amplitude, latency to response, the number of spontaneous skin conductance responses emitted, and the number of subjects who failed to respond did not significantly differentiate the groups. An examination of habituation did not support the hypothesis that the Huntington subjects would be fast habituators or that they would not habituate at all. \r\nThis study supports previous research which found differences in the smooth pursuit eye tracking of at-risk and Huntington subjects when compared with normal controls. The overlap among the three groups suggests, however, that individual differences are too large to use smooth pursuit eye tracking as a genetic marker of Huntington's chorea. In contrast with previous research, there is no support for the contention that electrodermal indices of responsiveness can be used as markers."@en . "https://circle.library.ubc.ca/rest/handle/2429/25166?expand=metadata"@en . "EYE MOVEMENTS AND ELECTRODERMAL RESPONSIVITY AS POSSIBLE GENETIC MARKERS OF HUNTINGTON'S CHOREA B.A., M c G i l l U n i v e r s i t y , 1979 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF THE FACULTY OF GRADUATE STUDENTS (Department of P s y c h o l o g y ) We a c c e p t t h i s t h e s i s a s c o n f o r m i n g t o t h e r e q u i r e d s t a n d a r d THE UNIVERSITY OF BRITISH COLUMBIA J u l y 1984 \u00C2\u00A9 D i a n e L a c o s t e , 1984 by D i a n e L a c o s t e MASTER OF ARTS i n In presenting t h i s thesis i n p a r t i a l f u l f i l m e n t of the requirements for an advanced degree at the University of B r i t i s h Columbia, I agree that the Library s h a l l make i t f r e e l y a v a i l a b l e for reference and study. I further agree that permission f o r extensive copying of t h i s t h e s i s f o r scholarly purposes may be granted by the head of my department or by h i s or her representatives. I t i s understood that copying or p u b l i c a t i o n of t h i s thesis f o r f i n a n c i a l gain s h a l l not be allowed without my written permission. Department of The University of B r i t i s h Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 DE-6 (3/81) A b s t r a c t T h i s s t u d y examined two p o s s i b l e g e n e t i c m a r k e r s of H u n t i n g t o n ' s c h o r e a : eye movements and e l e c t r o d e r m a l r e s p o n s i v i t y . Seven s u b j e c t s i n t h e e a r l y s t a g e s of H u n t i n g t o n ' s d i s e a s e were compared t o t w e n t y - n i n e s u b j e c t s i n e a c h o f two o t h e r g r o u p s , a g r o u p of s u b j e c t s a t - r i s k f o r H u n t i n g t o n ' s c h o r e a and a g r o u p of c o n t r o l s . S u b j e c t s c o m p l e t e d a s e r i e s of smooth p u r s u i t and s a c c a d i c eye t r a c k i n g t a s k s as w e l l as l i s t e n e d t o s o f t t o n e s , l o u d t o n e s , and sounds w h i l e e l e c t r o d e r m a l a c t i v i t y was r e c o r d e d . V i s u a l i n s p e c t i o n o f t h e eye movement d a t a r e v e a l e d t h a t t h e H u n t i n g t o n ' s c h o r e a g r o u p p e r f o r m e d t h e p o o r e s t , a c r o s s a l l t h e eye t r a c k i n g t a s k s . D a t a a n a l y s e s showed t h a t t h e a t -r i s k s u b j e c t s , when compared w i t h c o n t r o l s u b j e c t s , t r a c k e d w i t h a g r e a t e r l a g when t h e t a r g e t moved a t t h e g r e a t e s t s p e e d . T h e r e were no d i f f e r e n c e s between t h e two g r o u p s on s i m i l a r eye t r a c k i n g t a s k s a t t h e t a r g e t ' s s l o w e r s p e e d s . The a t - r i s k and t h e c o n t r o l g r o u p s p e r f o r m e d t h e v e r t i c a l smooth p u r s u i t , h o r i z o n t a l s a c c a d i c , and v e r t i c a l s a c c a d i c t r a c k i n g t a s k s e q u a l l y w e l l , a t a l l t a r g e t s p e e d s . No d i f f e r e n c e s between t h e a t - r i s k and t h e c o n t r o l g r o u p emerged when d i r e c t i o n o f eye movement ( r i g h t , l e f t , up o r down) was a n a l y z e d . S u b j e c t s i n b o t h g r o u p s t r a c k e d more p o o r l y when t h e y moved t h e i r e y e s t o t h e r i g h t i n t h e h o r i z o n t a l t a s k s . The e l e c t r o d e r m a l d a t a y i e l d e d u n i f o r m l y n e g a t i v e r e s u l t s i n d i c a t i n g t h a t t h e r e were no d i f f e r e n c e s between t h e t h r e e g r o u p s i n t h e i r r e s p o n s i v e n e s s t o s o f t t o n e s , t o l o u d t o n e s o r t o t h e sounds of a b a r k i n g dog and a newsroom t e l e t y p e . The p o s i t i o n i n g o f t h e t h r e e g r o u p s on t h e d e p e n d e n t measures were as d e s c r i b e d i n p r e v i o u s r e s e a r c h i n t h a t t h e H u n t i n g t o n g r o u p was t h e l e a s t r e s p o n s i v e and t h e c o n t r o l g r o u p t h e most r e s p o n s i v e . However, mean r e s p o n s i v i t y , as measured by a m p l i t u d e , l a t e n c y t o r e s p o n s e , t h e number of s p o n t a n e o u s s k i n c o n d u c t a n c e r e s p o n s e s e m i t t e d , and t h e number o f s u b j e c t s who f a i l e d t o r e s p o n d d i d n o t s i g n i f i c a n t l y d i f f e r e n t i a t e t h e g r o u p s . An e x a m i n a t i o n of h a b i t u a t i o n d i d n o t s u p p o r t t h e h y p o t h e s i s t h a t t h e H u n t i n g t o n s u b j e c t s w o u l d be f a s t h a b i t u a t o r s o r t h a t t h e y would not h a b i t u a t e a t a l l . T h i s s t u d y s u p p o r t s p r e v i o u s r e s e a r c h w h i c h f o u n d d i f f e r e n c e s i n t h e smooth p u r s u i t eye t r a c k i n g of a t - r i s k and H u n t i n g t o n s u b j e c t s when compared w i t h normal c o n t r o l s . The o v e r l a p among t h e t h r e e g r o u p s s u g g e s t s , however, t h a t i n d i v i d u a l d i f f e r e n c e s a r e t o o l a r g e t o use smooth p u r s u i t eye t r a c k i n g as a g e n e t i c marker o f H u n t i n g t o n ' s c h o r e a . In c o n t r a s t w i t h p r e v i o u s r e s e a r c h , t h e r e i s no s u p p o r t f o r t h e c o n t e n t i o n t h a t e l e c t r o d e r m a l i n d i c e s o f r e s p o n s i v e n e s s can be u s e d as m a r k e r s . - i v T a b l e of C o n t e n t s I n t r o d u c t i o n 1 Method 22 R e s u l t s 38 D i s c u s s i o n 72 R e f e r e n c e s 85 A p p e n d i c e s 95 A p p e n d i x A 95 A p p e n d i x B 97 A p p e n d i x C 98 A p p e n d i x D 99 A p p e n d i x E 100 A p p e n d i x F 101 A p p e n d i x G 104 A p p e n d i x H 106 A p p e n d i x I 107 A p p e n d i x J 110 V L i s t of T a b l e s 1. Demographic And Q u e s t i o n n a i r e S c o r e Means 23 2. Means F o r H o r i z o n t a l Smooth P u r s u i t Eye Movements ...45 3. Means F o r V e r t i c a l Smooth P u r s u i t Eye Movements 52 4. Means F o r H o r i z o n t a l S a c c a d i c Eye T r a c k i n g ; R i g h t And L e f t Eye Movements 54 5. Means F o r V e r t i c a l S a c c a d i c Eye T r a c k i n g ; Up And Down Eye Movements 56 6. Means F o r S k i n C o n d u c t a n c e L e v e l s To S o f t T o n e s ; R i g h t And L e f t Hands 58 7. Means F o r S k i n C o n d u c t a n c e L e v e l To Loud T o n e s ; R i g h t And L e f t Hands 59 8. Means F o r S k i n C o n d u c t a n c e Response To S o f t T o n e s ; R i g h t And L e f t Hands 61 9. Means F o r S k i n C o n d u c t a n c e Response To L o u d T o n e s ; R i g h t And L e f t Hands 63 10. Number Of N o n r e s p o n d e r s To S o f t And Loud T o n e s 65 11. Mean Number Of T r i a l s To H a b i t u a t i o n To S o f t And Loud T o n e s ; R i g h t And L e f t Hands 67 12. Mean Number Of S p o n t a n e o u s S k i n C o n d u c t a n c e R e s p o n s e s To S o f t And Loud T o n e s ; R i g h t And L e f t Hands 69 13. Means F o r R e s t i n g S k i n C o n d u c t a n c e And F i r s t S k i n C o n d u c t a n c e Response To The Dog And T e l e t y p e S t i m u l i ; R i g h t And L e f t Hands 70 v i L i s t of F i g u r e s 1. Eye T r a c k i n g R e c o r d s Of Two S u b j e c t s From E a c h Group On H o r i z o n t a l Smooth P u r s u i t A t .4 Hz 40 2. H o r i z o n t a l Smooth P u r s u i t Eye T r a c k i n g C o l l a p s e d Over D i r e c t i o n Of Eye Movement; Phase Lag 46 3. H o r i z o n t a l Smooth P u r s u i t Eye T r a c k i n g C o l l a p s e d Over D i r e c t i o n Of Eye Movement; Phase L a g ; 1.2 Hz. Non-m o n i t o r Task 47 4. H o r i z o n t a l Smooth P u r s u i t Eye T r a c k i n g C o l l a p s e d Over D i r e c t i o n Of Eye Movement; Phase L a g ; 1.2 Hz. M o n i t o r Task 48 5. H o r i z o n t a l Smooth P u r s u i t Eye T r a c k i n g C o l l a p s e d Over D i r e c t i o n Of Eye Movement; Median RMS .- 51 6. M a g n i t u d e Of S k i n C o n d u c t a n c e R e s p o n s e s E l i c i t e d By S o f t T o n e s , C o l l a p s e d Over Hands 62 7. M a g n i t u d e Of S k i n C o n d u c t a n c e R e s p o n s e s E l i c i t e d By Loud T o n e s , C o l l a p s e d Over Hands 64 v i i Acknowledgement T h i s t h e s i s would not have been p o s s i b l e w i t h o u t t h e e x p e r t i s e and h e l p of my s u p e r v i s o r , B i l l I a c o n o , as w e l l as t h a t o f M a r g a r e t and M i k e . My s i n c e r e t h a n k s t o a l l o f t h o s e who p a r t i c i p a t e d as s u b j e c t s and e s p e c i a l l y t o t h e members of t h e H u n t i n g t o n S o c i e t y f o r i n s p i r i n g me i n my work. I am e v e r l a s t i n g l y g r a t e f u l t o my f r i e n d s a t s c h o o l , as w e l l as t o D a v i d C r o c k e t t , D i a n e , R i c h a r d , and Norman f o r t h e i r i m p o r t a n t m o r a l s u p p o r t . C e t t e t h e s e e s t d e d i e a mon c o u s i n L u c i e n , q u i e t a i t s i b i e n aime p a r sa f a m i l l e . 1 I n t r o d u c t i o n H u n t i n g t o n ' s c h o r e a (HC) i s an i n h e r i t e d c h r o n i c d e g e n e r a t i v e d i s o r d e r c h a r a c t e r i z e d by g r a d u a l m e n t a l d e t e r i o r a t i o n and c h o r e i f o r m movements. O v e r t m a n i f e s t a t i o n s of t h e d i s e a s e a p p e a r r e l a t i v e l y l a t e i n t h e a f f e c t e d i n d i v i d u a l ' s l i f e , o f t e n a f t e r t h e y have c o m p l e t e d t h e i r f a m i l i e s ( B r u y n , 1968), t h u s e n s u r i n g t h a t t h e d i s e a s e w i l l be p a s s e d from g e n e r a t i o n t o g e n e r a t i o n . A r e l i a b l e means f o r e a r l y d e t e c t i o n of t h e gene c a r r i e r s among t h e o f f s p r i n g of a p a r e n t w i t h HC i s a c t i v e l y b e i n g s o u g h t ( P a u l s o n , 1976). U n t i l r e c e n t l y ( G u s e l l a e t a l . , 1983), no p r e d i c t i v e t e s t o f any t y p e f o r t h e s e a s y m p t o m a t i c c a r r i e r s was a v a i l a b l e ( K l a w a n s , G o e t z , & P e r l i k , 1980). The p r e s e n t r e s e a r c h e v a l u a t e s p s y c h o p h y s i o l o g i c a l m e asures t h a t c o u l d d i s t i n g u i s h c a r r i e r s from n o n - c a r r i e r s among t h o s e a t - r i s k f o r HC. The c l i n i c a l d i a g n o s i s o f H u n t i n g t o n ' s c h o r e a c u r r e n t l y r e s t s on t h e p r e s e n c e of a c o n f i r m e d f a m i l y h i s t o r y a n d / o r t h e r e s u l t s of a b r a i n a u t o p s y of an a f f e c t e d p a r e n t . T h e s e d a t a c a n o n l y be b r o u g h t t o be a r once t h e a t - r i s k i n d i v i d u a l b e g i n s h i m s e l f t o m a n i f e s t symptoms of t h e d i s o r d e r . W i t h t h e a d v e n t of t h e G8 DNA marker d i s c o v e r e d t h i s y e a r ( G u s e l l a e t a l . , 1983), p r e s y m p t o m a t i c d i a g n o s i s of H u n t i n g t o n ' s may e v e n t u a l l y ,be p o s s i b l e i n a p p r o x i m a t e l y h a l f o f t h e f a m i l i e s w i t h H u n t i n g t o n ' s p r o v i d e d a b l o o d sample from an a f f e c t e d p a r e n t i s a v a i l a b l e . The new t e s t f a c e s t h e same k i n d s o f p r o b l e m s t h a t c o n f r o n t t h e t r a d i t i o n a l c l i n i c a l d i a g n o s t i c i a n . A 2 d e g r e e of u n r e l i a b i l i t y e x i s t s i n c a s e s where t h e p a r e n t w i t h HC d i e d b e f o r e m a n i f e s t i n g symptoms. A d i a g n o s i s of HC i s a l s o d i f f i c u l t t o r e a c h i n i n d i v i d u a l s whose f a m i l y h i s t o r y i s n o t o b v i o u s l y one o f H u n t i n g t o n ' s d i s e a s e p e r s e . One o f t h e p r o b l e m s a s s o c i a t e d h i s t o r i c a l l y w i t h H u n t i n g t o n ' s c h o r e a i s t h e f r e q u e n c y w i t h w h i c h i t i s m i s t a k e n f o r o t h e r d i s o r d e r s , n o t a b l y s c h i z o p h r e n i a , A l z h e i m e r ' s d i s e a s e , m u l t i p l e s c l e r o s i s , P a r k i n s o n ' s d i s e a s e , and a gamut o f o t h e r c e r e b r o s p i n a l d e g e n e r a t i v e d i s o r d e r s i n v o l v i n g a t a x i a s . Such d i a g n o s e s may be s c a t t e r e d i n a p e d i g r e e making a c l i n i c a l d i a g n o s i s o f HC t h a t much l e s s c e r t a i n . A p r e d i c t i v e t e s t f o r H u n t i n g t o n ' s d i s e a s e t h a t c o u l d overcome t h e s e d i f f i c u l t i e s i e . be a p p l i c a b l e i n s u s p e c t e d c a s e s o f HC where l i t t l e d e f i n i t i v e f a m i l y i n f o r m a t i o n was a v a i l a b l e w o u l d be welcome. Two t y p e s o f d e t e c t i o n s t u d i e s have been p e r f o r m e d . The f i r s t a p p r o a c h f o c u s e s on d e v e l o p i n g s e n s i t i v e d e t e c t i o n d e v i c e s t o d i a g n o s e t h e d i s e a s e a t i t s t r u e i n c e p t i o n . F o r example, P e t a j a n , J a r c h o , and Thurman (1979) r e c o r d e d t h e f i r i n g r a t e s of s i n g l e motor n e u r o n s i n an a t t e m p t t o measure m i c r o c h o r e a d u r i n g t h e v o l u n t a r y movements o f 17 s u b j e c t s w i t h ' H C . A l l but two of t h e 'HC s u b j e c t s showed e x c e s s i v e r e c r u i t e m e n t o f motor u n i t s , i . e . p o o r motor c o n t r o l . The p u r p o s e and a d v a n t a g e of t h i s a p p r o a c h l i e s i n t h e r a p i d i t y w i t h w h i c h a s u s p e c t e d c a s e o f H u n t i n g t o n ' s c o u l d be d i a g n o s e d were t h i s t e s t t o p r o v e p r e d i c t i v e o f c h o r e a . As i t i s , a d i a g n o s i s o f H u n t i n g t o n ' s i s o f t e n r e a c h e d some two t o s e v e n 3 y e a r s a f t e r t h e f i r s t s u b t l e s i g n s o f t h e d i s e a s e ' s a c t u a l b e g i n n i n g s (Hayden, 1981). The P e t a j a n e t a l . (1979) s t u d y f u r t h e r s u b d i v i d e d t h e i r 17 ' c h o r e i c ' s u b j e c t s i n t o t h r e e g r o u p s : 3 s u b j e c t s w i t h a l i k e l y d i a g n o s i s o f HC, 4 w i t h a p o s s i b l e d i a g n o s i s of HC and 10 w i t h a d e f i n i t i v e d i a g n o s i s of HC as shown by pneumoencephalogram, by b r a i n a u t o p s y , by c o m p u t e r i z e d a x i a l tomography s c a n s o r by c l i n i c a l s i g n s . I f t h i s t y p e o f e l e c t r o m y o g r a p h i c a l measure was p r e d i c t i v e , t h e t h r e e l i k e l y and f o u r p o s s i b l e c h o r e i c s c o u l d be d i a g n o s e d d e f i n i t i v e l y . The s e c o n d a p p r o a c h t o t h e e a r l y d e t e c t i o n o f gene c a r r i e r s f o c u s e s on t h e i s s u e of p r e s y m p t o m a t i c d i a g n o s i s and may a t t e m p t t o i d e n t i f y b i o c h e m i c a l , p h y s i o l o g i c a l o r n e u r o p s y c h o l o g i c a l a b n o r m a l i t i e s w h i c h p r e c e d e any s i g n s o f t h e d i s e a s e i n t h e p o p u l a t i o n a t - r i s k . T h e s e s t u d i e s have c o v e r e d n e u r o l o g i c a l m e asures ( e . g . , B a r o , 1973; a b n o r m a l m u s c l e t o n e ) , n e u r o p h y s i o l o g i c a l measures ( e . g . , P a t t e r s o n , B a g c h i , & T e s t , 1948; slow, low v o l t a g e E E G ) , n e u r o e n d o c r i n o l o g i c a l measures ( e . g . , Hayden, V i n i k , P a u l , & B e i g h t o n , 1977; d i s t u r b e d p r o l a c t i n r e l e a s e ) , p s y c h o l o g i c a l measures ( e . g . , Goodman, H a l l , T e r a n g o , P e r r i n e , & R o b e r t s , 1966; p e r s o n a l i t y c h a n ge, d e m e n t i a ) , and n e u r o c h e m i c a l measures ( e . g . , Manyan, H a r e , K a t z , & G l a e s e r , 1977; d e c r e a s e d c e r e b r o s p i n a l f l u i d GABA). So f a r , none of t h e s e a r e a s o f i n v e s t i g a t i o n has been s u c c e s s f u l i n d i f f e r e n t i a t i n g c a r r i e r s f r o m n o n - c a r r i e r s . Common r e s e a r c h s t r a t e g i e s i n v o l v e 4 c o m p a r i n g c o n f i r m e d HC p a t i e n t s o r t h e i r p r o g e n y on t h e v a r i a b l e ( s ) under i n v e s t i g a t i o n f o r q u a n t i t a t i v e or q u a l i t a t i v e d i f f e r e n c e s w i t h a g r o u p of n o r m a l c o n t r o l s o r b r a i n - d a m a g e d p a t i e n t samples ( K l a w a n s , G o e t z , & P e r l i k , 1980). The m a j o r a s s u m p t i o n u n d e r l y i n g t h i s l a t t e r a p p r o a c h i s t h a t t h e gene f o r HC i s a c t i v a t e d and i t s e f f e c t s d e t e c t a b l e l o n g b e f o r e t h e a p p e a r a n c e of o v e r t symptoms. The p u r p o s e o f t h e p r e s e n t s t u d y was t o i n v e s t i g a t e t h e u t i l i t y of two g e n e t i c a l l y i n f l u e n c e d p s y c h o p h y s i o l o g i c a l m e a s u r e s - - e y e movements and e l e c t r o d e r m a l a c t i v i t y - - a s p o s s i b l e m a r k e r s of H u n t i n g t o n ' s c h o r e a . A g e n e t i c marker f o r HC c a n be d e f i n e d as a b i o l o g i c a l or p s y c h o l o g i c a l c h a r a c t e r i s t i c w h i c h when o b s e r v a b l e , i d e n t i f i e s t h e p r e s e n c e of t h e HC g e n o t y p e . T h i s marker i s assumed t o be p r e s e n t b o t h b e f o r e and d u r i n g t h e d i s e a s e . The marker r e f l e c t s a m e a s u r a b l e a l t e r a t i o n i n t h e s t r u c t u r e o r f u n c t i o n i n g of t h e c a r r i e r w h i c h i s t e m p o r a l l y s t a b l e . I d e a l l y , t h e g e n e t i c marker s h o u l d a p p e a r i n a l l i n d i v i d u a l s who w i l l d e v e l o p H u n t i n g t o n ' s c h o r e a and i n none o f t h o s e who do n o t p o s s e s s t h e gene. W h i l e t h i s i d e a l may be p o s s i b l e w i t h some t y p e s o f b i o c h e m i c a l c h a r a c t e r i s t i c s , i t i s n o t l i k e l y t o be a c h i e v e d u s i n g p s y c h o p h y s i o l o g i c a l t e c h n i q u e s . T h a t some p e r s o n s not a t - r i s k w i l l show t h e p s y c h o p h y s i o l o g i c a l c h a r a c t e r i s t i c i s l i k e l y b e c a u s e t h e r a n g e of i n d i v i d u a l d i f f e r e n c e s i n p s y c h o p h y s i o l o g i c a l r e s p o n d i n g i n n o r m a l s i s g r e a t enough t h a t o v e r l a p w i t h c l i n i c a l l y d e v i a n t g r o u p s w i l l o c c u r . In 5 a d d i t i o n , t h a t some p e r s o n s w i t h t h e gene w i l l n o t have t h e marker must a l s o be e x p e c t e d b e c a u s e a wide v a r i e t y o f f a c t o r s i n a d d i t i o n t o t h e p r e s e n c e of t h e gene may a f f e c t t h e e x p r e s s i o n of t h e p s y c h o p h y s i o l o g i c a l c h a r a c t e r i s t i c . M o r e o v e r , a l t h o u g h HC i s d e t e r m i n e d by a s i n g l e d o m i n a n t gene, i t s p h y s i c a l and c l i n i c a l c o r r e l a t e s a r e known t o v a r y c o n s i d e r a b l y a c r o s s i n d i v i d u a l s . T h a t p s y c h o p h y s i o l o g i c a l c h a r a c t e r i s t i c s may show s i m i l a r v a r i a b i l i t y i s p e r h a p s t o be e x p e c t e d . T h i s v a r i a t i o n has l e d some r e s e a r c h e r s t o s p e c u l a t e t h a t t h e r e may be more t h a n one HC g e n o t y p e t o a c c o u n t f o r t h e d a t a (Myers, Madden, Teague, & F a l e k , 1982). I t would however, seem more l i k e l y t h a t t h e r e were e n v i r o n m e n t a l e v e n t s o r o t h e r genes a l t e r i n g o r m a s k i n g t h e e x p r e s s i o n o f t h e HC gene. J u s t as s u c h f a c t o r s a l t e r or mask t h e e x p r e s s i o n of t h e gene i t s e l f , t h e y may a l s o be e x p e c t e d t o c o l o u r t h e g e n e t i c marker s u c h t h a t p e r f e c t i d e n t i f i c a t i o n i n t h o s e t r u l y a t - r i s k w i l l n o t be p o s s i b l e ( I a c o n o , 1982b). A v a r i e t y of b e n e f i t s f o l l o w f r o m u t i l i z i n g eye movements and e l e c t r o d e r m a l r e s p o n s i v i t y a s p o s s i b l e g e n e t i c m a r k e r s of HC: (1) Such measures a r e a t l e a s t p a r t i a l l y under g e n e t i c c o n t r o l . T h e r e i s a l i t e r a t u r e e x a m i n i n g t h e e f f e c t o f h e r e d i t y on p s y c h o p h y s i o l o g i c a l r e s p o n s e s . T h i s r e s e a r c h i n d i c a t e s t h a t o c u l o m o t o r c o n t r o l i s d e t e r m i n e d i n p a r t by g e n e t i c f a c t o r s ( I a c o n o & L y k k e n , 1979a, 1979b; Holzman, K r i n g l e n , L e v y , & Haberman, 1980; I a c o n o & L y k k e n , 1981; 6 I a c o n o , 1982a) and r e f l e c t s a t e m p o r a l l y s t a b l e t r a i t . I a c o n o & L y k k e n (1979b, 1981) s t u d i e d a sample o f 32 p a i r s of n o r m a l m o n o z y g o t i c t w i n s on smooth p u r s u i t , s a c c a d i c and e y e -hand c o o r d i n a t i o n t r a c k i n g t a s k s and f o u n d i n t r a c l a s s c o r r e l a t i o n c o e f f i c i e n t v a l u e s r a n g i n g from .54 t o .83. Holzman e t a l . , (1980) d e t e r m i n e d t h a t two g r o u p s o f 21 m o n o z y g o t i c (MZ) and 30 d i z y g o t i c (DZ) t w i n p a i r s who were d i s c o r d a n t f o r s c h i z o p h r e n i a were n o n e t h e l e s s c o n c o r d a n t f o r bad eye t r a c k i n g . 81% o f t h e MZ t w i n s were bad t r a c k e r s as compared t o 67% t o t h e DZ t w i n s on smooth p u r s u i t t a s k s . I a c o n o ( 1 9 8 2 a ) , i n an e x t e n s i o n of e a r l i e r r e s e a r c h , r e p o r t e d t w o - y e a r r e t e s t r e l i a b i l i t y c o e f f i c i e n t s of .60 o r g r e a t e r f o r v a r i o u s m e a sures of eye t r a c k i n g . T h e r e were s i g n i f i c a n t l y d i f f e r e n t i n t r a c l a s s c o r r e l a t i o n s - - . 6 8 as compared t o .35--on a measure o f smooth p u r s u i t eye t r a c k i n g p e r f o r m a n c e i n 34 n o r m a l MZ and 24 n o r m a l DZ t w i n p a i r s . T h e r e was l e s s e v i d e n c e t h a t a measure of p h a s e l a g \u00E2\u0080\u0094 w h i c h r e f l e c t e d t h e d e g r e e t o w h i c h t h e s u b j e c t ' s e y e s l a g g e d t h e t a r g e t t o be f o l l o w e d - - w a s g e n e t i c a l l y i n f l u e n c e d . C o n c o r d a n c e r a t e s f o r s a c c a d i c eye movement l a t e n c i e s were not s i g n i f i c a n t l y d i f f e r e n t i n t h e two s e t s o f t w i n p a i r s . The h e r e d i t a r y i n f l u e n c e s on e l e c t r o d e r m a l a c t i v i t y have n o t been a s w e l l i n v e s t i g a t e d b u t t h e major t w i n s t u d i e s t h a t e x i s t s u g g e s t t h a t v a r i o u s a s p e c t s of e l e c t r o d e r m a l a r o u s a l a r e p a r t i a l l y d e t e r m i n e d by g e n e t i c f a c t o r s . E a r l i e r s t u d i e s o f t h e g e n e t i c s o f e l e c t r o d e r m a l r e s p o n s i v i t y were not 7 i n c l u d e d i n t h i s r e v i e w b e c a u s e t h e y a r e n o t s t r i c t l y c o m p a r a b l e w i t h t h e newer r e s e a r c h s i n c e t h e y were f r a u g h t w i t h numerous m e t h o d o l o g i c a l d i f f i c u l t i e s . L a d e r and Wing (1966) i n a s t u d y o f 11 m o n o z y g o t i c and 11 d i z y g o t i c . , t w i n p a i r s r e p o r t e d s i g n i f i c a n t l y h i g h e r c o r r e l a t i o n s f o r t h e MZ t w i n s f o r r a t e of h a b i t u a t i o n as w e l l as f o r t h e number of s p o n t a n e o u s s k i n c o n d u c t a n c e r e s p o n s e s t h e y e m i t t e d . Hume (1973) examined 44 p a i r s o f m o n o z y g o t i c t w i n s and 51 p a i r s of d i z y g o t i c t w i n s on measures of s k i n p o t e n t i a l r e s p o n s e t o t o n e s as w e l l a s t o a c o l d p r e s s o r ; measures of s p o n t a n e o u s s k i n p o t e n t i a l r e s p o n s e s d u r i n g r e s t ; a measure o f h a b i t u a t i o n r a t e ; and a measure o f t h e number of s p o n t a n e o u s r e s p o n s e s d u r i n g t h e h a b i t u a t i o n t a s k . He r e p o r t e d t h a t m o n o z y g o t i c t w i n s were more a l i k e (homogeneous) t h a n t h e d i z y g o t i c t w i n s i n t h e i r r e s p o n s i v i t y , and c o n c l u d e d t h a t g e n e t i c f a c t o r s e x e r t e d a s i g n i f i c a n t e f f e c t . The i n t r a c l a s s c o r r e l a t i o n c o e f f i c i e n t s on t h e o t h e r m e a sures r a n g e d between .11 and .37 p r o v i d i n g o n l y weak s u p p o r t f o r t h e h y p o t h e s i s t h a t t h e r e i s some g e n e t i c d e t e r m i n a t i o n o f t h e s e o t h e r r e s p o n s e s . I a c o n o & L y k k e n ( 1 9 7 9 c ) , m e a s u r i n g h a b i t u a t i o n r a t e i n 35 p a i r s o f MZ t w i n s r e p o r t e d a s i g n i f i c a n t i n t r a - c l a s s c o r r e l a t i o n c o e f f i c e n t of .60 when d a t a g a t h e r e d o v e r t h r e e s e s s i o n s h e l d a t two month i n t e r v a l s were c o l l a p s e d o v e r s e s s i o n s . T e s t - r e t e s t c o r r e l a t i o n s r a n g e d from .50 t o .68 i n d i c a t i n g t h a t t h e r e was some s t a b i l i t y of t h e s k i n c o n d u c t a n c e r e s p o n s e o v e r t i m e . The h a b i t u a t i o n 8 c r i t e r i o n a d o p t e d i n t h i s r e s e a r c h was d e f i n e d as t h e number of t r i a l s t o two c o n s e c u t i v e z e r o ( a m p l i t u d e ) s k i n c o n d u c t a n c e r e s p o n s e s . (2) P s y c h o p h y s i o l o g i c a l r e s p o n s e s t a p g l o b a l c a p a c i t i e s i . e . t h e y depend on t h e p r o p e r f u n c t i o n i n g of a l l a r e a s of t h e b r a i n as a w h o l e . I f any one f u n c t i o n i s d i s t u r b e d , t h i s may show up as a r e s p o n s e d e f i c i t . T h e s e g l o b a l ( m o l a r ) t y p e s of m easures can be h e l d i n c o n t r a s t t o t h e s p e c i f i c ( m o l e c u l a r ) measurement a p p r o a c h e s p o p u l a r i n most r e s e a r c h on H u n t i n g t o n ' s c h o r e a . I n v e s t i g a t i o n s b a s e d on a s i n g l e enzyme or a s p e c i f i c t y p e of c e l l membrane, w h i l e v a l i d , n e c e s s a r i l y i g n o r e o t h e r v a r i a b l e s w h i c h may p l a y a r o l e i n t h e d e v e l o p m e n t o f HC. However, t h e complex and g l o b a l n a t u r e o f t h e s e p s y c h o p h y s i o l o g i c a l m e asures w i l l i n i t s e l f make i t d i f f i c u l t t o i s o l a t e a p a r t i c u l a r a r e a of t h e b r a i n as r e s p o n s i b l e f o r t h e o b t a i n e d r e s u l t s . A s e r i e s of s t u d i e s would be r e q u i r e d t o d e l i n e a t e t h e o r i g i n s o f any o b s e r v e d d e f i c i t s . T h i s s t u d y s i m p l y p r o p o s e d t o d e t e r m i n e i f o c u l o m o t o r f u n c t i o n and e l e c t r o d e r m a l a c t i v i t y a r e d i s t u r b e d i n i n d i v i d u a l s w i t h H u n t i n g t o n ' s d i s e a s e o r i n t h e p r o g e n y a t -r i s k t o d e v e l o p c h o r e a . To t h i s end, a g r o u p of c h o r e i c s i n t h e e a r l y s t a g e s of HC were added t o t h e s t u d y . ( 3 ) P s y c h o p h y s i o l o g i c a l t e c h n i q u e s a r e a d v a n t a g e o u s i n t h a t t h e y a r e a n o n i n v a s i v e means o f e x a m i n i n g b r a i n f u n c t i o n . (4) These t e c h n i q u e s make p o s s i b l e t h e use o f e x t r e m e l y s e n s i t i v e e l e c t r o n i c e q u ipment and p o w e r f u l computer a n a l y s e s . 9 The p r o p o s e d s e a r c h f o r g e n e t i c m a r k e r s o f c h o r e a i s a l s o p a r t o f an e f f o r t t o w a r d s u n d e r s t a n d i n g t h e e t i o l o g y of a b n o r m a l e l e c t r o d e r m a l a c t i v i t y ( G r u z e l i e r & V e n a b l e s , 1972; I a c o n o , I979d) and of smooth p u r s u i t eye t r a c k i n g d e f i c i t s (Holzman, P r o c t o r , Y a s i l l o , M e l t z e r , & H u r t , 1974; S h a g a s s , Amadeo, & O v e r t o n , 1974; I a c o n o , T u a s o n , & J o h n s o n , 1981) w h i c h a r e r e p e a t e d l y f o u n d i n s c h i z o p h r e n i a (See I a c o n o , 1982b, f o r an i n d e p t h r e v i e w of g e n e t i c m a r k e r s f o r s c h i z o p h r e n i a ) . The p o s s i b i l i t y e x i s t s t h a t t h e r e a r e s i m i l a r i t i e s between t h e p s y c h o p h y s i o l o g i c a l r e s p o n s e s p r o d u c e d by some s c h i z o p h r e n i c s and t h o s e of c h o r e i c s . The a d v a n t a g e i n s u c h a c o m p a r i s o n l i e s i n t h e f a c t t h a t , u n l i k e t h e s i t u a t i o n f o r s c h i z o p h r e n i a , HC i s a d i s o r d e r o f d e f i n i t e g e n e t i c o r i g i n and of known n e u r o l o g i c and b i o c h e m i c a l f e a t u r e s ( e g . t h e b a s a l g a n g l i a a r e s h r u n k e n , GABA l e v e l s a r e r e d u c e d e t c . ) . I f as a r e s u l t of t h i s i n v e s t i g a t i o n , s i m i l a r i t i e s on t h e s e v a r i a b l e s between s c h i z o p h r e n i c s and c h o r e i c s a r e r e v e a l e d , more s p e c i f i c h y p o t h e s e s c o n c e r n i n g t h e s t r u c t u r a l o r b i o c h e m i c a l d e f e c t s o f s c h i z o p h r e n i a c o u l d be a d v a n c e d . The use of n e u r o l o g i c a l p o p u l a t i o n s w i t h known a r e a s of s t r u c t u r a l damage c a n a l s o c o n t r i b u t e t o t h e 'mapping' o f w h i c h b e h a v i o u r a l d e f i c i t s a r e r e s u l t i n g from w h i c h p a r t i c u l a r CNS p r o c e s s i n g a b n o r m a l i t y . The r e s t r i c t e d n e u r o p a t h o l o g y o f H u n t i n g t o n ' s c h o r e a makes i t p o s s i b l e t o a s c e r t a i n a c o r r e l a t i o n between a n e u r o n a l d e f i c i t and m e n t a l o r p s y c h o l o g i c a l symptoms ( C o y l e , Schwarz, B e n n e t t , & 10 C o m p o c h i a r o , 1977; O scar-Berman, 1978). By w o r k i n g 'backward' i n t h i s manner, i t would be p o s s i b l e t o a p p l y t h e r e s u l t s o b t a i n e d w i t h HC p a t i e n t s t o s c h i z o p h r e n i c p a t i e n t s who showed s i m i l a r b e h a v i o u r d e f i c i t s . T y p e s o f Eye Movements T h e r e a r e two forms o f c o n j u g a t e eye movements of i n t e r e s t t o t h e p r e s e n t r e s e a r c h : s a c c a d i c and smooth p u r s u i t eye movements. A s a c c a d e s e r v e s t o s h i f t t h e e y e s from one s t a t i o n a r y p o i n t i n t h e v i s u a l f i e l d t o t h e n e x t , a t v e l o c i t i e s up t o 550 d e g r e e s / s e c o n d ( F u c h s , 1976). The s a c c a d i c s y s t e m b r i n g s v i s u a l t a r g e t s o n t o t h e f o v e a and i s t h e most f r e q u e n t l y u s e d eye movement. Smooth p u r s u i t movements a r e slow (1 t o 40 d e g r e e s / s e c o n d ) , s w e e p i n g r o t a t i o n s of t h e e y es g e n e r a t e d i n r e s p o n s e t o a moving t a r g e t . E y e b a l l v e l o c i t y i s matched t o t h e t a r g e t ' s v e l o c i t y . A s t a b l e image i s t h u s m a i n t a i n e d on t h e f o v e a . The two s y s t e m s n o r m a l l y i n t e r a c t when t a r g e t v e l o c i t y e x c e e d s 40 d e g r e e s / s e c o n d . The s a c c a d i c s y s t e m p r o d u c e s s t e p - l i k e jumps i n eye p o s i t i o n so t h a t r e t i n a l s l i p p a g e ( e y e s l a g g i n g e x c e s s i v e l y b e h i n d t h e t a r g e t ) c a u s e d by t h e l i m i t e d s p e e d of t h e smooth p u r s u i t s y s t e m i s c o r r e c t e d . Smooth p u r s u i t eye movements a r e g e n e r a l l y c o n s i d e r e d t o be i n v o l u n t a r y s i n c e t h e p r e s e n c e o f an e x t e r n a l moving o b j e c t i s u s u a l l y r e q u i r e d f o r t h e s y s t e m t o f u n c t i o n . S a c c a d e s , w h i l e h i g h l y a u t o m a t i c once i n i t i a t e d , c a n be p r o d u c e d a t w i l l and a r e deemed ' v o l u n t a r y ' . O c u l o m o t o r D i s t u r b a n c e s A s s o c i a t e d w i t h H u n t i n g t o n ' s c h o r e a D i s t u r b a n c e s i n b l i n k i n g and s t a r i n g have l o n g been d e s c r i b e d i n c h o r e i c s ( H u n t i n g t o n , 1872) a l t h o u g h t h e i d e n t i f i c a t i o n o f i m p a i r e d o c u l a r m o t i l i t y p e r se as a f e a t u r e o f HC i s more r e c e n t (Andre-Thomas, A b e l y , A j u r i a g u e r r a , & E u l i e r , 1945; Dereux, 1945). I m p a i r e d eye movements a r e p r e s e n t \" i n more t h a n 50% o f t h e c a s e s w i t h w e l l - e s t a b l i s h e d c h o r e a \" ( P e t i t & M i l b l e d , 1973, p . 2 8 7 ) . T h i s f i g u r e may r e a c h 80% when more p r e c i s e t e c h n i q u e s f o r r e c o r d i n g eye m o t i o n a r e a p p l i e d (Hayden, 1981). The i n c i d e n c e o f t h e most s e r i o u s d e f e c t , a r e d u c t i o n i n v e r t i c a l s a c c a d i c v e l o c i t y may a f f e c t t w o - t h i r d s ( P e t i t , T i l l o y , D h e d i n , & M i l b l e d , 1971) t o v i r t u a l l y a l l HC s u b j e c t s examined ( A v a n z i n i , G i r o t t i , C a r a c e n i , & S p r e a f i c o , 1979). S i n c e t h e more a d v a n c e d c a s e s o f c h o r e a a r e u s u a l l y e x c l u d e d from r e s e a r c h on t h e b a s i s of f r a n k d e m e n t i a or i n a b i l i t y t o c o n t r o l head movements w e l l enough t o t r a c k a t a r g e t , t h e s e s t u d i e s may be b i a s e d t o w a r d f i n d i n g a l o w e r i n c i d e n c e of o c u l o m o t o r a b n o r m a l i t i e s t h a n a c t u a l l y e x i s t s . The motor m a n i f e s t a t i o n s ( i n c l u d i n g eye movement d y s f u n c t i o n ) of some c h o r e i c s a r e known t o change f o r t h e worse o v e r t h e c o u r s e o f t h e d i s e a s e ( S t a r r , 1967) so t h a t s t u d i e s i n w h i c h t h e b u l k of t h e s u b j e c t s a r e i n t h e e a r l i e r s t a g e s o f c h o r e a a r e l i k e l y t o u n d e r e s t i m a t e t h e p r e v a l e n c e o f o c u l o m o t o r a b n o r m a l i t i e s . The most c o n s p i c u o u s d i s t u r b a n c e of o c u l a r m o t i l i t y i n c h o r e i c s o c c u r s w i t h v e r t i c a l s a c c a d e s d i r e c t e d i n an upward 1 2 g a z e . T h e s e s a c c a d e s may be e n t i r e l y a b s e n t ( \" p a r a l y z e d \" ) o r s e r i o u s l y i m p a i r e d . The e a r l i e s t r e p o r t s of p a t i e n t s l i t e r a l l y u n a b l e t o l i f t t h e i r e y e s t o a p o i n t above them (Dereux, 1945; S c h i l d e r , c i t e d i n i n B r u y n , 1968) have been r e c e n t l y c o n f i r m e d ( P e t i t e t a l . , 1971; S t a r r , 1967; P e t i t & M i l b l e d , 1973). When p r e s e n t , s a c c a d e s a r e c h a r a c t e r i z e d by s i g n i f i c a n t r e d u c t i o n s i n v e l o c i t y , a s w e l l a s i n c r e a s e d l a t e n c y and s m a l l e r a m p l i t u d e s ( A v a n z i n i e t a l . , 1979; Oepen, C l a r e n b a c h , & Thoden, 1981). P e t i t and M i l b l e d (1973, p. 287) have s t a t e d t h a t \" t h e v e l o c i t y was so d e c r e a s e d t h a t t h e e y e s a p p e a r e d t o move i n an o i l b a t h \" . T h e s e d e f i c i t s a r e p r e s e n t t o a l e s s e r d e g r e e i n h o r i z o n t a l s a c c a d e s and v e r t i c a l s a c c a d e s i n a downward d i r e c t i o n . I m p a i r e d s a c c a d e s a r e o f t e n a c c o m p a n i e d by c o m p e n s a t o r y b l i n k i n g and head movements. The l a r g e r s a c c a d e s t e n d t o be p e r f o r m e d even more s l o w l y o r t h e y d i s i n t e g r a t e i n t o s m a l l e r c o r r e c t i v e s a c c a d e s . S t a r r (1967, p. 562) s p e c u l a t e s t h a t \"a d i s t u r b a n c e o f r a p i d movements i s a g e n e r a l f e a t u r e of H u n t i n g t o n ' s c h o r e a and n o t m e r e l y a p e c u l i a r i t y o f t h e e x t r a o c u l a r m u s c l e s . \" The s l o w e r , smooth p u r s u i t eye movements a r e a l s o a l t e r e d i n HC. F o l l o w i n g movements a r e p e r f o r m e d more r a p i d l y and e a s i l y b u t a r e i r r e g u l a r i n a m p l i t u d e and o f t e n j e r k y i n a p p e a r a n c e ( A v a n z i n i e t a l . , 1979; Oepen, C l a r e n b a c h , & Thoden, 1981). T h i s j e r k i n e s s i s a t t r i b u t e d t o t h e p r e s e n c e o f c o r r e c t i v e s a c c a d e s and i t o c c u r s p r e d o m i n a n t l y a t h i g h e r t a r g e t v e l o c i t i e s ( i e . 30\u00C2\u00B0/second o r m o r e ) . Oepen and h i s 1 3 a s s o c i a t e s r e p o r t e d t h a t j e r k i n e s s was e s p e c i a l l y n o t i c e a b l e i n p a t i e n t s w i t h ' m a n i f e s t ' c h o r e a , p r e s u m a b l y i m p l y i n g t h e more a d v a n c e d c a s e s . The i n c l u s i o n of H u n t i n g t o n s u b j e c t s i n t h e p r e s e n t r e s e a r c h i s a l s o a r e f l e c t i o n o f t h e s t a t e of t h e a r t as c o n c e r n s HC r e s e a r c h w i t h eye movement m e a s u r e s . I t i s no e x a g g e r a t i o n t o say t h a t t h e a p p a r e n t c o n s i s t e n c y i n t h e t y p e s of a b n o r m a l i t i e s r e p o r t e d i n t h e eye movement l i t e r a t u r e on H u n t i n g t o n ' s d i s e a s e a r e o n l y matched by t h e c o n s i s t e n t l y f l a w e d d e s i g n s , a n a l y s e s and so f o r t h e n c o u n t e r e d i n t h e s e r e p o r t s . C o m p a r i s o n s between s t u d i e s c a n o n l y be made t e n t a t i v e l y s i n c e t h e r e c o r d i n g t e c h n i q u e s a r e a l l d i f f e r e n t ( e . g . eye movements c a n be r e c o r d e d w i t h e l e c t r o n y s t a g m o g r a p h y , i n f r a r e d r e c o r d i n g s , c i n e m a t o g r a p h y , p h o t o e l e c t r i c c o r n e a l l e n s e s e t c . ) o r t h e measures t a k e n a r e vague and i m p r e c i s e ( e . g . no s t a n d a r d eye t r a c k i n g t a s k i s u s e d ) . A few of t h e s t u d i e s have no c o n t r o l g r o u p s ; o t h e r s mix c h o r e i c p a t i e n t s w i t h r i g i d , a k i n e t i c p a t i e n t s . Some o f t h e s u b j e c t s i n c l u d e d a r e so a d v a n c e d i n t h e d i s e a s e t h a t a n t e r o g r a d e l e s i o n s s e c o n d a r y t o t h e ones b a s i c t o HC may have been i n v o l v e d . Sample s i z e s a r e o f t e n s m a l l ; a few s t u d i e s a r e b a s e d on s i n g l e c a s e s . 1 4 O c u l o m o t o r D i s t u r b a n c e s i n O t h e r D i s o r d e r s D e v i a n t p u r s u i t eye t r a c k i n g p a t t e r n s have been o b s e r v e d i n a v a r i e t y of c l i n i c a l d i s o r d e r s , i n c l u d i n g P a r k i n s o n ' s d i s e a s e ( S h i b a s a k i , T s u j i , & K u r o i w a , 1979), m u l t i p l e s c l e r o s i s , m y o t o n i c d y s t r o p h y , s p i n o c e r e b e l l a r d y s f u n c t i o n (von Noorden & P r e z i o s i , 1965), and s c h i z o p h r e n i a (Holzman e t a l . , 1974). As s u c h , d e v i a n t t r a c k i n g may be u s e d as an i n d e x o f c e n t r a l n e r v o u s s y s t e m p a t h o l o g y . Thus i f a s t r u c t u r a l o r b i o c h e m i c a l d e f e c t i s p r e s e n t i n t h e HC gene c a r r i e r , i t may be r e v e a l e d a s a s u b t l e i m p a i r m e n t of s a c c a d i c o r smooth p u r s u i t eye t r a c k i n g . What makes t h e o c u l o m o t o r s y s t e m p a r t i c u l a r l y u s e f u l i n t h i s r e s p e c t i s i t s p h y s i c a l c o m p l e x i t y and i t s s e n s i t i v i t y . P r a c t i c a l l y e v e r y l e v e l and p a r t o f t h e b r a i n i s i n v o l v e d i n some shape o r form i n t h e o p e r a t i o n and c o n t r o l of t h e e y e s ( B a c h - y - R i t a , 1973; Henn & Cohen, 1973). B e c a u s e t h e v i s u a l s y s t e m i s so e x t e n s i v e i t i s l i a b l e t o be s u b j e c t e d t o any n e u r o n a l damage t h a t t h e a b n o r m a l gene may b r i n g a b o u t . Damage i n one a r e a may w e l l a f f e c t t h e o u t p u t of t h e r e s t of t h e s y s t e m . P i r o z z o l o and Hansch (1981) s u g g e s t t h a t t h e r e i s a s t r o n g r e l a t i o n s h i p between d e g r e e of c o r t i c a l s t r u c t u r a l i n t e g r i t y and s i m p l e o c u l o m o t o r r e a c t i o n t i m e i n demented p a t i e n t s . A l s o t h e s m a l l s i z e o f t h e motor u n i t s r e g u l a t i n g t h e e x t r a o c u l a r m u s c l e s may make t h e s e u n i t s p a r t i c u l a r l y s u s c e p t i b l e t o t h e e f f e c t s o f breakdowns a t h i g h e r l e v e l s o f c o n t r o l (Holzman e t a l . , 1974). 1 5 T y p e s o f E l e c t r o d e r m a l Phenomena A s k i n c o n d u c t a n c e r e s p o n s e (SCR; a l s o c a l l e d a s k i n c o n d u c t a n c e o r i e n t i n g r e s p o n s e ) i s r e c o r d e d as a p h a s i c , waveform p a t t e r n p r o d u c e d when t h e r e i s an i n c r e a s e i n e c c r i n e sweat g l a n d s e c r e t i o n . T h i s i n c r e a s e d s e c r e t i o n t a k e s p l a c e when t h e o r g a n i s m i s p r e s e n t e d w i t h n o v e l s t i m u l a t i o n o r w i t h s t i m u l i t h a t have a c q u i r e d s i g n a l v a l u e ( R a s k i n , 1973). I t i s t h e o r i z e d t h a t SCRs p r e c e d e c o g n i t i v e p r o c e s s i n g o f s u c h s t i m u l i and s u b s e r v e a s e l e c t i v e a t t e n t i o n mechanism (Kahneman, 1973). The o r g a n i s m ' s a t t e n t i o n i s t h u s f o c u s e d and m a i n t a i n e d on t h o s e s t i m u l i r e l e v a n t t o i t s s u r v i v a l . The sweat g l a n d s a r e i n n e r v a t e d by t h e s y m p a t h e t i c b r a n c h o f t h e a u t o n o m i c n e r v o u s s y s t e m . E l e c t r o d e r m a l h a b i t u a t i o n can be d e f i n e d as a d e c r e a s e i n \u00E2\u0080\u0094 f o l l o w e d by a d i s a p p e a r a n c e o f \u00E2\u0080\u0094 t h e s k i n c o n d u c t a n c e r e s p o n s e as a r e s u l t of r e p e a t e d e x p o s u r e t o a s t i m u l u s ( L y n n , 1966). T y p i c a l l y , e l e c t r o d e r m a l h a b i t u a t i o n i s seen as a r a p i d d i m i n u t i o n of SCR a m p l i t u d e i n t h e f i r s t and s e c o n d r e p e t i t i o n s o f t h e s t i m u l u s . R e s p o n s e a m p l i t u d e c o n t i n u e s t o d e c r e a s e and t h e SCR d i s a p p e a r s e n t i r e l y somewhere between t h e t h i r d and t w e n t i e t h s t i m u l u s p r e s e n t a t i o n . The a c t u a l number ( e g . 3, 10 o r 20) of t h e s t i m u l u s p r e s e n t a t i o n s o c c u r r i n g b e f o r e t h e SCR f i n a l l y d i s a p p e a r s v a r i e s a c r o s s i n d i v i d u a l s . S t i m u l u s p r o p e r t i e s have been shown t o a f f e c t h a b i t u a t i o n . F o r example, low i n t e n s i t y s t i m u l i n e a r t h e t h r e s h o l d f o r p e r c e p t i o n and h i g h i n t e n s i t y s t i m u l i p r o d u c e a b n o r m a l l y l a r g e 16 s k i n c o n d u c t a n c e ( o r i e n t i n g ) r e s p o n s e s and s t a r t l e r e a c t i o n s , r e s p e c t i v e l y . The i n d i v i d u a l c o n s e q u e n t l y h a b i t u a t e s s l o w l y t o r e p e a t e d p r e s e n t a t i o n s o r does not h a b i t u a t e a t a l l . In g e n e r a l , h a b i t u a t i o n i s i n v e r s e l y p r o p o r t i o n a l t o s t i m u l u s i n t e n s i t y (Thompson, B e r r y , R i n a l d i , & B e r g e r , 1978). A r o u s a l a l s o a f f e c t s h a b i t u a t i o n , w i t h h i g h l e v e l s o f a r o u s a l a s s o c i a t e d w i t h d e l a y e d SCR h a b i t u a t i o n ( B o h l i n , 1976). H a b i t u a t i o n i s seen as a c e n t r a l l y d e t e r m i n e d f orm of i n f o r m a t i o n p r o c e s s i n g w h i c h has s u r v i v a l v a l u e f o r t h e o r g a n i s m s i n c e i t l e a v e s t h e o r g a n i s m f r e e t o a t t e n d t o more s i g n i f i c a n t s t i m u l i i n i t s e n v i r o n m e n t . E l e c t r o d e r m a l h a b i t u a t i o n r e f l e c t s a u t o n o m i c n e r v o u s s y s t e m a r o u s a l but c a n n o t be e x p l a i n e d as a ' f a t i g u i n g ' o f t h e n e u r o n s ( S o k o l o v , 1960) as any change i n t h e s t i m u l u s w i l l e l i c i t a new r e s p o n s e . H a b i t u a t i o n depends on c h a n g e s i n a c t i v i t y o c c u r i n g a t two l e v e l s : ( i ) i n t h e p e r i p h e r a l s y s t e m \u00E2\u0080\u0094 i n t h i s s t u d y , an i n c r e a s e or d e c r e a s e i n sweat g l a n d a c t i v i t y ( i i ) c e n t r a l l y \u00E2\u0080\u0094 as an i n c r e a s e o r d e c r e a s e i n t h e f i r i n g r a t e s of e x c i t a t o r y and i n h i b i t o r y n e u r o n s . E l e c t r o d e r m a l A c t i v i t y i n H u n t i n g t o n ' s c h o r e a S t u d i e s of e l e c t r o d e r m a l a c t i v i t y i n p a t i e n t s w i t h H u n t i n g t o n ' s c h o r e a a r e p r a c t i c a l l y n o n - e x i s t e n t , p e r h a p s b e c a u s e h a b i t u a t i o n i s n o t d i r e c t l y o b s e r v a b l e , as a r e eye movements. Lawson ( 1 9 8 1 ) , i n a p i l o t s t u d y , examined s k i n c o n d u c t a n c e r e s p o n s e s i n a sample of 25 HC p a t i e n t s . Twenty of t h e t w e n t y - f i v e c h o r e i c s were f o u n d t o be n o n r e s p o n d e r s t o 1 7 a s e r i e s o f a u d i t o r y s t i m u l i . T h a t i s , t h e y e m i t t e d no SCR t o a v a r i e t y o f t o n e s , t o phonemes and t o w h i t e n o i s e t h a t t h e y h e a r d . Of t h e r e m a i n i n g f i v e s u b j e c t s , t h r e e showed an o c c a s i o n a l s m a l l a m p l i t u d e r e s p o n s e and two were normal r e s p o n d e r s . Of p o t e n t i a l s i g n i f i c a n c e i s Lawson's o b s e r v a t i o n t h a t \" t h e few r e s p o n d i n g s u b j e c t s ( i n v a r i a b l y t o t h e phonemes) who gave o n l y 1 o r 2 SCRs may p o i n t t o f a s t h a b i t u a t i o n as a d i s t i n c t c a t e g o r y among t h e r e s p o n d e r s \" . (Lawson, 1981, p. 3 4 ) . O s c a r - B e r m a n and Gade (1978) measured a v a r i e t y of e l e c t r o d e r m a l i n d i c e s o f a r o u s a l i n 7 c h o r e i c s . The g r o u p of c h o r e i c s was one of 4 b r a i n - d a m a g e d g r o u p s i n c l u d e d i n a s t u d y o f K o r s a k o f f ' s syndrome p a t i e n t s . The i n v e s t i g a t i o n r e v e a l e d t h a t t h e c h o r e i c s u b j e c t s gave s i g n i f i c a n t l y r e d u c e d o r i e n t i n g r e s p o n s e s t o t h e f i r s t two a u d i t o r y s t i m u l u s p r e s e n t a t i o n s as compared t o t h e a p h a s i c , t h e P a r k i n s o n and t h e n ormal s u b j e c t s . They were s t i l l s i g n i f i c a n t l y l e s s r e s p o n s i v e t h a n t h e f o r m e r two g r o u p s even a f t e r 12 s t i m u l u s p r e s e n t a t i o n s . From t h e i n f o r m a t i o n g i v e n i n t h e a r t i c l e , i t was i m p o s s i b l e t o d e t e r m i n e t h e number of s t i m u l u s p r e s e n t a t i o n s i t t o o k b e f o r e t h e n o r m a l s and t h e HC g r o u p showed t h e same l e v e l of r e s p o n s i v e n e s s . The c h o r e i c p a t i e n t s a l s o e x h i b i t e d a s i g n i f i c a n t l y l o w e r r a t e of h a b i t u a t i o n . W h i l e no d e f i n i t i o n o f h a b i t u a t i o n was g i v e n i n t h e Lawson s t u d y , t h e s e two s t u d i e s seem t o s u p p o r t e a c h o t h e r i n t h e i r c o n c l u s i o n s . The r e d u c e d SCR and r e l a t i v e l y r a p i d h a b i t u a t i o n t h a t has been r e p o r t e d i n c o n n e c t i o n w i t h HC p a t i e n t s may s u g g e s t t h a t 18 H u n t i n g t o n ' s c h o r e a i n v o l v e s a r e d u c t i o n o f a r o u s a l t o i n c o m i n g s t i m u l a t i o n (Oscar-Berman & Z o l a - M o r g a n , 1978). The c e n t r a l n e u r a l mechanisms by w h i c h t h i s may come ab o u t a r e unknown a l t h o u g h t h e hippocampus and t h e r e t i c u l a r a c t i v a t i n g s y s t e m have been i m p l i e d ( S o k o l o v , 1960). A r o u s a l i s b e l i e v e d t o f a c i l i t a t e memory and l e a r n i n g p r o c e s s e s by s e n s i t i z i n g t h e o r g a n i s m t o s i g n i f i c a n t s t i m u l i ( R o u t t e n b e r g , 1968). O s c a r -Berman and Gade (1978) s p e c u l a t e t h a t t h e h y p o r e a c t i v e a r o u s a l e x h i b i t e d by t h e i r g r o u p of HC s u b j e c t s may u n d e r l i e t h e i r d i f f u s e i n t e l l e c t u a l i m p a i r m e n t . In a d d i t i o n , n o r m a l o r i e n t i n g r e s p o n s i v i t y (and t h e r e f o r e h a b i t u a t i o n ) has been l i n k e d t o t h e i n t e g r i t y of t h e t h a l a m i c r e t i c u l a r s y s t e m and i t s p r o j e c t i o n s t o and from t h e f r o n t a l c o r t e x ( R o z i n , 1976) as w e l l as t o f r o n t a l c o r t e x i n t e g r i t y ( P r i b r a m & M c G u i n e s s , 1975). The f r o n t a l c o r t e x i s known t o be one o f t h e e a r l i e s t and most a f f e c t e d s t r u c t u r e s i n t h e c h o r e i c b r a i n ( B a r b e a u , C h a s e , & P a u l s o n , 1973). One o f t h e d i f f i c u l t i e s i n e v a l u a t i n g t h e l i t e r a t u r e on e l e c t r o d e r m a l r e s p o n d i n g i n H u n t i n g t o n ' s d i s e a s e i s t h a t t h e r e a r e s u c h l a r g e d i s c r e p a n c i e s i n t h e methods, i n t h e s u b j e c t s a m p l e s , i n t h e t y p e s o f s t i m u l i s u b j e c t s were r e q u i r e d t o r e s p o n d t o , and i n t h e ways of s c o r i n g t h e s k i n c o n d u c t a n c e r e s p o n s e a m p l i t u d e s , t h e h a b i t u a t i o n r a t e s , t h e l a t e n c i e s t o o n s e t , t h e number of s p o n t a n e o u s s k i n c o n d u c t a n c e r e s p o n s e s e t c . t h a t a r e t y p i c a l l y m e asured. Many s t u d i e s g i v e vague d e t a i l s o r no i n f o r m a t i o n a t a l l on c r u c i a l a s p e c t s o f t h e i r 19 r e s e a r c h . F o r example, h a b i t u a t i o n r a t e i s l e f t u n d e f i n e d o r s i m p l y p l o t t e d i n c h a r t s w i t h no e x p l a n a t i o n s . Eye Movements and E l e c t r o d e r m a l A c t i v i t y as M a r k e r s o f H u n t i n g t o n ' s c h o r e a Over t h e p a s t t e n y e a r s , a s m a l l number of s t u d i e s have d e a l t w i t h e i t h e r d e v i a n t eye t r a c k i n g o r e l e c t r o d e r m a l r e s p o n s i v e n e s s as p o s s i b l e m a r k e r s of H u n t i n g t o n ' s c h o r e a . T h e s e s t u d i e s g e n e r a l l y a t t e m p t e d t o d e m o n s t r a t e t h a t i m p a i r e d eye movements o r d e c r e a s e d r e s p o n s i v e n e s s o c c u r a t a h i g h e r f r e q u e n c y i n p r o g e n y a t - r i s k f o r H u n t i n g t o n ' s c h o r e a t h a n i n n o r m a l s . S i n c e e a c h o f f s p r i n g o f a c h o r e i c p a r e n t has a 50% c h a n c e of i n h e r i t i n g t h e gene, i t i s e x p e c t e d , t h e o r e t i c a l l y , t h a t about 50% of t h e i n d i v i d u a l s i n a p r o g e n y sample ( i . e . t h e c a r r i e r s ) would e x h i b i t a b n o r m a l SCRs or d e v i a n t eye t r a c k i n g . The o t h e r h a l f o f t h e sample would be e x p e c t e d t o g i v e n o r m a l r e s p o n s e s . In a s t u d y of eye movement, t w e n t y - e i g h t p r o g e n y were examined by P e t i t e t a l . ( 1 9 7 1 ) , 18 o f whom showed no eye t r a c k i n g d e f i c i t . The r e m a i n i n g 10 p r e s e n t e d a v a r i e t y o f a b n o r m a l i t i e s i n c l u d i n g : i n c r e a s e d o c u l a r l a t e n c y , s m a l l a m p l i t u d e r e s p o n s e s , o v e r l y l a r g e s a c c a d e s , e s p e c i a l l y i n a v e r t i c a l d i r e c t i o n . Oepen, C l a r e n b a c h , and Thoden (1981) f o u n d t h a t e i g h t o f t h e i r t e n p r o g e n y d i s p l a y e d some form o f o c u l o m o t o r a b n o r m a l i t y . T h e s e s u b j e c t s had d i f f i c u l t i e s w i t h p e n d u l a r p u r s u i t movements and s l o w e d v e r t i c a l v o l u n t a r y s a c c a d e s . T h e r e i s u n f o r t u n a t e l y no i n d i c a t i o n o f t h e e x a c t n a t u r e of t h e d e f i c i e n c i e s i n v o l v e d . 20 To d a t e , o n l y one e a r l y d e t e c t i o n s t u d y o f t h e e l e c t r o d e r m a l c h a r a c t e r i s t i c s of p r o g e n y a t - r i s k e x i s t s . Lawson (1981) r e p o r t e d t h a t of 52 a t - r i s k s u b j e c t s , 17 (35%) e m i t t e d no s k i n c o n d u c t a n c e r e s p o n s e t o a s e r i e s o f t w e n t y -f o u r a u d i t o r y s t i m u l i . T h i s r a t e of n o n r e s p o n d i n g i s w e l l above t h e 7% base r a t e i n t h e n o r m a l p o p u l a t i o n r e p o r t e d by V e n a b l e s ( 1 9 7 7 ) . F o r example, 7.7% o f Lawson's n o r m a l c o n t r o l g r o u p were n o n r e s p o n d e r s . T h e r e i s no m e n t i o n i n t h e a r t i c l e o f whether o r n o t t h e r a t e of h a b i t u a t i o n of t h e p r o g e n y was measured. P r e s e n t S t u d y The g o a l o f t h e p r e s e n t r e s e a r c h was t o c o n t r i b u t e t o t h e l i t e r a t u r e by c o m p a r i n g \" e l e c t r o d e r m a l r e s p o n s i v i t y i n a sample of HC p r o g e n y t o t h e r e s p o n s i v i t y o f a g r o u p o f n o r m a l c o n t r o l s . I t a l s o s e r v e d as an a t t e m p t t o r e p l i c a t e t h e f i n d i n g s o f o c u l o m o t o r a b n o r m a l i t i e s i n t h e eye t r a c k i n g p e r f o r m a n c e o f i n d i v i d u a l s a t - r i s k f o r H u n t i n g t o n ' s d i s e a s e a s r e p o r t e d by e a r l i e r r e s e a r c h e r s . The s p e c i f i c h y p o t h e s e s a r e o u t l i n e d b elow. H y p o t h e s e s The p u r p o s e o f t h e p r o p o s e d s t u d y was t o i n v e s t i g a t e t h e p o t e n t i a l v a l u e of e l e c t r o d e r m a l c h a r a c t e r i s t i c s and a b n o r m a l eye movement a s g e n e t i c m a r k e r s f o r H u n t i n g t o n ' s c h o r e a . More s p e c i f i c a l l y , t h e major h y p o t h e s e s c o n c e r n i n g t h e s e m e a s u r e s were: 1) t h a t more o f t h e p r o g e n y a t - r i s k t h a n t h e n o r m a l c o n t r o l 21 subjects would either (i) show fast habituation or ( i i ) give no or smaller amplitude skin conductance responses when presented with the auditory s t i m u l i . 2) that the choreic subjects would (i) be electrodermal 'nonresponders' ( i i ) or be fast habituators (of those choreics who did give an electrodermal response). 3) that more of the progeny a t - r i s k than the normal controls would have some deficiency in visu a l tracking and that these d e f i c i e n c i e s would show up most frequently when they tracked upwardly moving targets. 4) that the choreic group would be poor eye trackers i . e . show more de f i c i e n c i e s than any other group being investigated. 22 Method S u b j e c t s H u n t i n g t o n and A t - R i s k S u b j e c t s S u b j e c t s were r e c r u i t e d from a t l e a s t t h r e e d i f f e r e n t s o u r c e s v i a p r e s e n t a t i o n s a n d / o r a d e t a i l e d i n f o r m a t i o n s h e e t ( A p p e n d i x A) d e s c r i b i n g t h e p r o p o s e d r e s e a r c h p r o j e c t . The e x p e r i m e n t e r a t t e n d e d m o n t h l y m e e t i n g s o f t h e B r i t i s h C o l u m b i a c h a p t e r of t h e H u n t i n g t o n S o c i e t y and c o n t i n u e d t o r e c r u i t s u b j e c t s t h r o u g h b r i e f p r e s e n t a t i o n s and t h e i n f o r m a t i o n s h e e t . T h r o u g h t h i s n etwork, i t was a l s o p o s s i b l e t o t a p i n t o a p o o l of s u b j e c t s who d i d n o t a t t e n d t h e m e e t i n g s o r who a t t e n d e d i r r e g u l a r l y . Two s e p a r a t e g r o u p s of i n d i v i d u a l s were s o u g h t . The f i r s t c o n s i s t e d of c h o r e i c s i n t h e e a r l y s t a g e s of t h e d i s e a s e . A f u n c t i o n a l d e f i n i t i o n of e a r l y was a p p l i e d . S u b j e c t s had t o be c u r r e n t l y w o r k i n g , o r a b l e t o cook and do h o u s e h o l d work or s t i l l be a b l e t o d r i v e t h e i r c a r s . Seven male s u b j e c t s i n t h e e a r l y s t a g e s o f H u n t i n g t o n ' s c h o r e a t o o k p a r t . The age span f o r t h i s g r o u p was 31 t o 67. The mean number o f y e a r s s i n c e t h e c h o r e i c s u b j e c t s had been d i a g n o s e d as h a v i n g H u n t i n g t o n ' s d i s e a s e was 3.38 y e a r s , w i t h a range o f 8 months t o 7 y e a r s . Two of t h e se v e n c h o r e i c s u b j e c t s were t a k i n g i s o n i a z i d \u00E2\u0080\u0094 a n e x p e r i m e n t a l d r u g t r e a t m e n t f o r H u n t i n g t o n ' s c h o r e a \u00E2\u0080\u0094 o n e was t a k i n g a h y p n o t i c , and t h e o t h e r f o u r were n o t t a k i n g any d r u g s . The s e c o n d and l a r g e s t g r o u p c o n s i s t e d o f a t - r i s k i n d i v i d u a l s who were symptom-free. E i g h t male and t w e n t y - o n e f e m a l e a t - r i s k s u b j e c t s whose a g e s r a n g e d 23 T a b l e 1 Demographic and Q u e s t i o n n a i r e S c o r e s D e m o g r a p h i c s Q u e s t i o n n a i r e S c o r e s a G r o u p Aqe Sex E d u c a t i o n BDI STAIT STAIG M F H u n t i n g t o n 41.0 7 0 12.6 11.6 38.9 43.4 N=7 (12.1) (2.2) (8.9) (11.2) (11.3) A t - R i s k 31.6 8 21 12.7 3.5 33.4 35.3 N=29 (10.2) (2.2) (4.1 ) (9.5) (9.6) C o n t r o l 28.8 1 1 18 13.9 1 .9 31 .5 32.8 N=29 (11.9) (1.9) (2.2) (8.5) (6.3) N o t e . S t a n d a r d d e v i a t i o n s a r e g i v e n i n p a r e n t h e s e s . N o t e . The v a l u e s g i v e n a r e f o r t h e Beck D e p r e s s i o n I n v e n t o r y ( B D I ) , t h e S t a t e - T r a i t A n x i e t y I n v e n t o r y , Form X-1, ( S T A I T ) , and t h e S t a t e - T r a i t A n x i e t y I n v e n t o r y , Form X-2, ( S T A I G ) . a Number o f y e a r s s u b j e c t s engaged i n a f u l l - t i m e c o u r s e of e d u c a t i o n . 24 from 15 t o 50 y e a r s p a r t i c i p a t e d . One a t - r i s k s u b j e c t was t a k i n g an a n a l g e s i c , a n o t h e r , a n t i h i s t a m i n e s , and a t h i r d s u b j e c t , a h y p n o t i c . A t - r i s k s u b j e c t s were o t h e r w i s e d r u g -f r e e . A f a m i l y and p e r s o n a l h i s t o r y g i v e n t o t h e e x p e r i m e n t e r s e r v e d a s t h e b a s i s f o r e s t a b l i s h i n g a t - r i s k o r e a r l y H u n t i n g t o n s t a t u s . T a b l e 1 p r o v i d e s i n f o r m a t i o n r e g a r d i n g t h e mean age and e d u c a t i o n of t h e a t - r i s k and t h e H u n t i n g t o n g r o u p . C o n t r o l S u b j e c t s C o n t r o l s u b j e c t s were r e c r u i t e d and s c r e e n e d i n i n t e r v i e w s c o m p l e t e d by t h e p e r s o n n e l of t h e M.A.P. ( M a r k e r s and P r e d i c t o r s ) R e s e a r c h P r o j e c t , and t h e n t e s t e d i n t h e l a b o r a t o r y by t h e e x p e r i m e n t e r or a l a b o r a t o r y t e c h n i c i a n on t h e eye movement and e l e c t r o d e r m a l m e a s u r e s . The M.A.P. P r o j e c t i s an e x t e n s i o n o f t h e W o r l d H e a l t h O r g a n i z a t i o n I n t e r n a t i o n a l P i l o t S t u d y on S c h i z o p h r e n i a and i s c u r r e n t l y i n v e s t i g a t i n g s c h i z o p h r e n i a i n t h e Lower M a i n l a n d . S u b j e c t s were r e c r u i t e d by p a r t i c i p a t i n g p r o f e s s i o n a l s a t t a c h e d t o t h e F a i r m o u n t F a m i l y P r a c t i c e C l i n i c of t h e V a n c o u v e r G e n e r a l H o s p i t a l , t o t h e REACH Community H e a l t h C l i n i c , and t o t h e Broadway Employment C e n t e r ( P l e a s e c o n s u l t A p p e n d i x B ) . In a d d i t i o n , c o n t r o l s u b j e c t s were a l s o r e c r u i t e d t h r o u g h two p o s t e r s e s s i o n s on H u n t i n g t o n ' s d i s e a s e g i v e n d u r i n g t h e a n n u a l UBC Open House i n March 1981 and i n M a r c h 1982. S u b j e c t s were p a i d twenty d o l l a r s f o r t h e i r p a r t i c i p a t i o n . S e l e c t i o n c r i t e r i a i n c l u d e d : a b s e n c e of n e u r o l o g i c a l d i s e a s e , 25 no h i s t o r y of p s y c h i a t r i c t r e a t m e n t , and a b s e n c e of o t h e r d e b i l i t a t i n g p h y s i c a l c o n d i t i o n s . S u b j e c t s were a l s o s c r e e n e d f o r d r u g or a l c o h o l a b u s e . In a d d i t i o n , t h e r e was no f a m i l y h i s t o r y of p s y c h i a t r i c i l l n e s s . S u b j e c t s were e x c l u d e d i f t h e y had any p r o b l e m s w i t h t h e i r e y e s o r v i s i o n t h a t c o u l d n o t be c o r r e c t e d by g l a s s e s o r i f t h e i r age f e l l o u t s i d e t h e r a n g e o f 15 t o 54 y e a r s . ( A p p e n d i x C c o n t a i n s t h e i n t a k e q u e s t i o n n a i r e ) . P a r t i c i p a n t s under s i x t e e n y e a r s o f age were r e q u i r e d t o f i l l i n a c o n s e n t f o r m s i g n e d by t h e i r l e g a l g u a r d i a n or p a r e n t . E l e v e n male and e i g h t e e n f e m a l e s whose ages r a n g e d f r o m 16 t o 60 to o k p a r t i n t h e r e s e a r c h as n o r m a l s u b j e c t s . T a b l e 1 c o n t a i n s f u r t h e r i n f o r m a t i o n r e g a r d i n g t h e mean age and e d u c a t i o n o f t h e c o n t r o l g r o u p . S e t t i n g and A p p a r a t u s A l l s e s s i o n s took p l a c e i n a l a b o r a t o r y i n t h e H e a l t h S c i e n c e s C e n t r e H o s p i t a l on UBC campus. A s i x c h a n n e l Beckman R612 Dynograph was u s e d t o r e c o r d e l e c t r o d e r m a l a c t i v i t y , and t h e v e r t i c a l and h o r i z o n t a l e l e c t r o o c u l o g r a m ( a b b r e v i a t e d VEOG and HEOG, r e s p e c t i v e l y ) . C a l i b r a t i o n was v e r i f i e d p r i o r t o e a c h r e c o r d i n g . A l l eye t r a c k i n g s i g n a l s and a r e c o r d of t a r g e t movement were s i m u l t a n e o u s l y r e c o r d e d o n t o m a g n e t i c t a p e w i t h a V e t t e r Model A FM r e c o r d e r f o r l a t e r a n a l y s i s . A D i g i t a l PDP 11/23 computer ( D i g i t a l E quipment C o r p o r a t i o n ) was u s e d t o d i g i t i z e and q u a n t i f y t h e p s y c h o p h y s i o l o g i c a l m e a s u r e s . A l l e l e c t r o d e s u s e d t o g a t h e r eye t r a c k i n g d a t a were 26 f i l l e d w i t h Redux e l e c t r o d e p a s t e ( H e w l e t t - P a c k a r d ) . E l e c t r o d e s i t e s f o r t h e eye t r a c k i n g t a s k s were massaged w i t h t h e Redux p a s t e t o d e c r e a s e s k i n r e s i s t a n c e . The a r e a of s k i n i n c o n t a c t w i t h t h e e l e c t r o l y t e was .95 cm 2. Whenever p o s s i b l e , e l e c t r o d e s were s o a k e d - - p r i o r t o r e c o r d i n g - - i n an e l e c t r o l y t e s o l u t i o n of a s i m i l a r c o n c e n t r a t i o n as t h e e l e c t r o d e p a s t e . T h i s h e l p e d t o e n s u r e s t a b i l i t y o f r e c o r d i n g . D u r i n g t h e eye movement r e c o r d i n g s , s u b j e c t s ' h e a ds were h e l d i n p l a c e by an a d j u s t a b l e head r e s t ( w i t h a c h i n and f o r e h e a d r e s t b a r ) mounted o n t o a T e k t r o n i x RM15 o s c i l l o s c o p e . T h i s e n s u r e d t h a t a l l s u b j e c t s t r a c k e d t h e t a r g e t from an e q u a l d i s t a n c e (29 cm). The head r e s t a l s o r e d u c e d t h e l i k e l i h o o d o f a r t e f a c t s i n t h e eye t r a c k i n g d a t a due t o s m a l l head movements. The o s c i l l o s c o p e c o n t r o l p a n e l was c o v e r e d w i t h b l a c k f e l t t o m i n i m i z e d i s t r a c t i o n . A b l a c k , P l e x i g l a s s t u n n e l e x t e n d i n g from t h e o s c i l l o s c o p e s c r e e n t o t h e head r e s t was a l s o u s e d f o r t h i s p u r p o s e . H o r i z o n t a l eye movements were r e c o r d e d t h r o u g h a m o d i f i e d Type 9806A A-C c o u p l e r u s i n g t i m e c o n s t a n t s o f 3 s e c o n d s ( f o r smooth p u r s u i t t r a c k i n g ) and 10 s e c o n d s ( f o r s a c c a d i c eye t r a c k i n g ) . Eye b l i n k s d u r i n g t h e h o r i z o n t a l t r a c k i n g t a s k s were r e c o r d e d t h r o u g h a s i m i l a r c o u p l e r u s i n g a t i m e c o n s t a n t o f 0.1 s e c o n d s . V e r t i c a l eye movements d u r i n g b o t h smooth p u r s u i t and s a c c a d i c eye t r a c k i n g were a l s o r e c o r d e d w i t h a Type 9806A A-C c o u p l e r , u s i n g a t i m e c o n s t a n t o f 3 s e c o n d s . 27 One cm A g / A g C l Beckman b i o p o t e n t i a l e l e c t r o d e s were p l a c e d n e a r t h e o u t e r c a n t h i of t h e r i g h t and l e f t e y e s f o r h o r i z o n t a l r e c o r d i n g s . E l e c t r o d e s were a l s o p l a c e d above t h e eyebrow and below t h e lower l i d of t h e dominant eye f o r t h e v e r t i c a l EOG. T h e s e e l e c t r o d e s a l s o r e c o r d e d e y e b l i n k s i n t h e EOG. F o r t h e smooth p u r s u i t t a s k s , s u b j e c t s w a t c hed a s p o t o f l i g h t d r i v e n by a s i n e wave g e n e r a t o r (Wavetek D i g i t a l VCG model 113) o r a r e c t a n g u l a r wave g e n e r a t o r ( u s e d i n I a c o n o & L y k k e n , 1979a, 1979b). The d o t t r a v e r s e d t h e s c r e e n of t h e c a t h o d e r a y o s c i l l o s c o p e b o t h v e r t i c a l l y and h o r i z o n t a l l y . To t e s t , s a c c a d i c eye t r a c k i n g , t h e t a r g e t s p o t moved a b r u p t l y from s i d e t o s i d e as w e l l as up and down a t i r r e g u l a r i n t e r v a l s v a r y i n g from 1.5 t o 4 s e c o n d s . F o r t h e s a c c a d i c t r a c k i n g t a s k s , t h e t a r g e t was d r i v e n as a r e c t a n g u l a r wave by t h e r e c t a n g u l a r wave g e n e r a t o r . The t a r g e t was a 5 mm c i r c l e w i t h a 1 mm d o t i n t h e m i d d l e . The d o t t r a v e r s e d 20 d e g r e e s o f v i s u a l a r c d u r i n g t h e h o r i z o n t a l eye t r a c k i n g t a s k s , and i t t r a v e r s e d 10 d e g r e e s of v i s u a l a r c d u r i n g t h e v e r t i c a l t r a c k i n g t a s k s . Poor eye t r a c k i n g p e r f o r m a n c e has been n o t e d i n s u b j e c t s who a r e l e s s a t t e n t i v e t o t h e t a s k demands. T h e s e i n d i v i d u a l s p r o d u c e smooth p u r s u i t movements i n t e r r u p t e d by s a c c a d e s w i t h o u t b e i n g aware of d o i n g so ( I a c o n o & L y k k e n , 1979a). To r e d u c e t h e c o n f o u n d i n g e f f e c t s o f i n t e r - s u b j e c t v a r i a b i l i t y i n a t t e n t i v e n e s s , a m o n i t o r t a s k was i n c l u d e d t h a t r e q u i r e d 28 s u b j e c t s t o m o n i t o r a p e r i o d i c c h a n g e s i n t h e s t i m u l u s b e i n g t r a c k e d . D u r i n g t h i s t a s k , t h e d o t i n t h e c e n t e r of t h e c i r c l e a p p e a r e d and d i s a p p e a r e d u n p r e d i c t a b l y . S u b j e c t s s i g n a l e d t h e p r e s e n c e or a b s e n c e of t h e d o t by p r e s s i n g o r r e l e a s i n g a h a n d - h e l d p u s h b u t t o n s w i t c h . The use of t h i s m o n i t o r t a s k has been shown t o improve smooth p u r s u i t t r a c k i n g ( I a c o n o & L y k k e n , 1979a, 1979b). S k i n c o n d u c t a n c e was r e c o r d e d on two c h a n n e l s u s i n g two Type 9844 s k i n c o n d u c t a n c e c o u p l e r s . One cm Beckman b i o p o t e n t i a l A g / A g C l e l e c t r o d e s were a t t a c h e d t o t h e m e d i a l p h a l a n g e s of t h e f i r s t and s e c o n d f i n g e r s of e a c h hand, u s i n g a s t a n d a r d d o u b l e a d h e s i v e c o l l a r s y s t e m . T h i s s y s t e m i n v o l v e d f i r s t a p p l y i n g an a d h e s i v e c o l l a r w i t h a c e n t e r h o l e .95 cm 2 i n d i a m e t e r on t h e a p p r o p r i a t e p h a l a n g e s . A s e c o n d a d h e s i v e c o l l a r was t h e n a p p l i e d t o t h e e l e c t r o d e c a p . The e l e c t r o d e was n e x t f i l l e d w i t h e l e c t r o l y t e p a s t e , and t h e two c o l l a r c e n t e r s were a l i g n e d , and p r e s s e d f i r m l y t o g e t h e r . T h i s e n s u r e d t h a t t h e s k i n s u r f a c e a r e a i n c o n t a c t w i t h t h e e l e c t r o l y t e was .95 cm 2. A s t a n d a r d e l e c t r o l y t e medium ( p h y s i o l o g i c a l s a l i n e m i x e d w i t h c o m m e r c i a l l y a v a i l a b l e U n i b a s e n e u t r a l o i n t m e n t ) was empl o y e d . A one cm A g / A g C l Beckman b i o p o t e n t i a l e l e c t r o d e was a f f i x e d t o t h e s h i n of t h e r i g h t l e g ' and s e r v e d as t h e g r o u n d e l e c t r o d e . D u r i n g t h e e l e c t r o d e r m a l a c t i v i t y t a s k s , s u b j e c t s were p r e s e n t e d w i t h t o n e s b i n a u r a l l y t h r o u g h AKG K240 headphones. The t o n e s were g e n e r a t e d by an a u d i o o s c i l l a t e r t h a t was t r i g g e r e d t o p r o d u c e 29 t h e t o n e s e q u e n c e by s i g n a l s r e c o r d e d on a tape.. T h i s t a p e was p l a y e d on a Sanyo s t e r e o c a s s e t t e d e c k . P r o c e d u r e E a c h s u b j e c t had some knowledge of t h e r e s e a r c h r a t i o n a l e and o f t h e measures t h a t would be t a k e n p r i o r t o t h e a c t u a l t e s t i n g s e s s i o n . P a r t i c i p a n t s were a s s i g n e d a code number t o e n s u r e a n o n y m i t y and c o n f i d e n t i a l i t y . Once s u b j e c t s had a r r i v e d , t h e y were a s k e d t o c o m p l e t e c o n s e n t forms ( A p p e n d i x D p r e s e n t s t h e MAP c o n s e n t f o r m s ) . P a r e n t a l c o n s e n t was r e q u i r e d f o r m i n o r s ( A p p e n d i x E c o n t a i n s t h e p a r e n t a l c o n s e n t f o r m ) . S u b j e c t s were i n f o r m e d t h a t t h e y c o u l d w i t h d r a w a t any t i m e w i t h o u t p r e j u d i c e . No s u b j e c t s w i t h d r e w . V o l u n t e e r s who wore c o n t a c t l e n s e s were r e q u i r e d t o use t h e i r e y e g l a s s e s s i n c e t h e c o n t a c t l e n s e s i n t r o d u c e b l i n k a r t e f a c t s i n t h e eye movement r e c o r d i n g s . S u b j e c t s were t o l d t h a t f o r e t h i c a l r e a s o n s , no i n d i v i d u a l r e s u l t s w o u l d be g i v e n o u t . S u b j e c t s were r e q u i r e d t o c o m p l e t e t h e Beck D e p r e s s i o n I n v e n t o r y a s w e l l a s t h e S t a t e - T r a i t A n x i e t y I n v e n t o r y (Forms X-1 and X - 2 ) . The BDI, t h e STAI t o d a y and t h e STAI g e n e r a l q u e s t i o n n a i r e s were i n c l u d e d t o c o n t r o l f o r t h e e f f e c t s o f d e p r e s s i o n and a n x i e t y on t h e e l e c t r o d e r m a l m e a s u r e s . A n x i e t y i s a s s o c i a t e d w i t h h i g h e r s k i n c o n d u c t a n c e l e v e l s , s m a l l e r s k i n c o n d u c t a n c e r e s p o n s e s , ( N e a r y & Zuckerman, 1976; K a t k i n , 1975), and s l o w e r r a t e s o f h a b i t u a t i o n ( M altzman, S m i t h , K a n t o r & M a n d e l , 1971). D e p r e s s i o n has been l i n k e d t o d e c r e a s e d e l e c t r o d e r m a l r e s p o n s i v i t y ( I a c o n o , L y k k e n , P e l o q u i n , Lumry, V a l e n t i n e , & 30 T u a s o n , 1983). I t was, i n a d d i t i o n , i m p o r t a n t t o t a k e i n t o a c c o u n t t h e f a c t t h a t t h e r e were i t e m s on e a c h of t h e s e q u e s t i o n n a i r e s t h a t r e l a t e d t o t h e s ymptomatology of H u n t i n g t o n ' s c h o r e a . On t h e BDI f o r example, t h e HC s u b j e c t i s l i a b l e t o c h o o s e 3, on i t e m 'S', s i n c e H u n t i n g t o n ' s c h o r e a i s a s s o c i a t e d w i t h a major w e i g h t l o s s ( A p p e n d i x F ) . Items 'B', ' I ' , 'L', 'M', 'N', and 'U' may a l s o be m e a s u r i n g symptoms of HC. In t h e STAI g e n e r a l q u e s t i o n n a i r e , i t e m s 22 and 28 may be t a p p i n g i n t o t h e symptoms of H u n t i n g t o n ' s c h o r e a as w e l l ( A p p e n d i x G c o n t a i n s t h e S t a t e - T r a i t A n x i e t y I n v e n t o r y ) . I t c o u l d be a r g u e d t h a t t h e s e i t e m s m a g n i f y r a t h e r t h a n change t h e d i r e c t i o n o f t h e HC s c o r e s . I t may be t h e c a s e t h a t an i n d i v i d u a l w i t h HC i s more l i k e l y t o be d e p r e s s e d or t o be more a n x i o u s t h a n an i n d i v i d u a l who does not have t o d e a l w i t h a d i s e a s e . S u b j e c t s were a l s o r e q u i r e d t o g i v e i n f o r m a t i o n r e l a t i v e t o t h e i r age, e d u c a t i o n , and d r u g use ( A p p e n d i x H c o n t a i n s t h e m e d i c a t i o n i n f o r m a t i o n s h e e t ) . Age i s known t o a f f e c t eye t r a c k i n g p e r f o r m a n c e i n a p o s i t i v e , l i n e a r f a s h i o n i e . t h e g r e a t e r t h e age, t h e p o o r e r t h e eye t r a c k i n g ( K u e c h e n m e i s t e r , L i n t o n , M u e l l e r , & W h i t e , 1977; S h a r p e & S y l v e s t e r , 1978). V a r i o u s d r u g s have been shown t o a f f e c t eye t r a c k i n g ( W i l k i n s o n , Kime & P u r n e l l , 1974; Holzman, L e v y , U h l e n h u t h , P r o c t o r & Freedman, 1975). Most o f t h e commonly u s e d a n t i p s y c h o t i c s s u c h as t h e p h e n o t h i a z i n e s do not a f f e c t eye t r a c k i n g p e r f o r m a n c e , s i n c e s t u d i e s i n v e s t i g a t i n g t h e t r a c k i n g 31 of s c h i z o p h r e n i c o r m a n i c - d e p r e s s i v e p o p u l a t i o n s have shown t h a t s u c h s u b j e c t s , when t h e y a r e t a k e n o f f m e d i c a t i o n , t r a c k as w e l l as t h e y do when t h e y a r e t a k i n g m e d i c a t i o n ( I a c o n o & K o e n i g , 1983). Sex was not a n a l y z e d as t h e r e i s no r e l a t i o n between gen d e r and eye t r a c k i n g p e r f o r m a n c e ( P i v i k , 1979; S h a g a s s , Amadeo & O v e r t o n , 1974; Holzman e t a l . , 1974). S i m i l a r l y , g e n d e r i s not a s i g n i f i c a n t f a c t o r i n e l e c t r o d e r m a l r e s p o n s i v i t y ( C a s t l e m a n , Brennan & Kimmel, 1978). The g e n e r a l p r o c e d u r e of e l e c t r o d e p l a c e m e n t and t h e p r e s e n t a t i o n of t h e v i s u a l and a u d i t o r y t a s k s was e x p l a i n e d t o e a c h s u b j e c t as t h e s u b j e c t was s e a t e d i n f r o n t of t h e o s c i l l o s c o p e . E l e c t r o d e s were f i l l e d , a t t a c h e d t o t h e s u b j e c t s , and s e c u r e d w i t h s u r g i c a l t a p e . E a r r i n g s , b r a c e l e t s and s w e a t e r s t h a t would i n t e r f e r e w i t h e l e c t r o d e p l a c e m e n t were removed. A t a p e d , s t a n d a r d i z e d , v e r b a l d e s c r i p t i o n of t h e p u r p o s e of t h e s t u d y was t h e n p l a y e d and s u b j e c t s were a s k e d t o t a k e deep b r e a t h s , t o cough, t o move t h e i r head and t o b l i n k so t h a t t h e s e a r t e f a c t s c o u l d be r e c o g n i z e d s h o u l d t h e y o c c u r l a t e r on i n t h e s e s s i o n . Task i n s t r u c t i o n s were p r o v i d e d f r o m t h e same p r e - t a p e d c a s s e t t e f o r e a c h s u b j e c t . T h r o u g h o u t t h e eye t r a c k i n g t a s k s , s u b j e c t s were r e m i n d e d t o r e l a x t h e i r f a c i a l m u s c l e s , t o r e f r a i n from b l i n k i n g , t o h o l d t h e i r heads s t i l l , and t o f o l l o w t h e t a r g e t c l o s e l y . In a d d i t i o n , d u r i n g t h e s a c c a d i c t r a c k i n g t a s k s , s u b j e c t s were i n s t r u c t e d t o a v o i d moving t h e i r e y e s b e f o r e t h e t a r g e t a c t u a l l y moved. S u b j e c t s 32 t h e n v i s u a l l y t r a c k e d a .4 Hz s i n u s o i d a l t a r g e t w h i l e t h e EOG c h a n n e l s were c a l i b r a t e d . T h i s e n s u r e d t h a t s u b j e c t s were f a m i l i a r i z e d w i t h t h e t a s k and c o u l d f o l l o w i n s t r u c t i o n s c o r r e c t l y . B o t h v e r t i c a l and h o r i z o n t a l smooth p u r s u i t eye movements (SPEMs) were r e c o r d e d . The s u b j e c t s t r a c k e d s i n u s o i d a l t a r g e t s h o r i z o n t a l l y f o r 20 c y c l e s a t t h r e e d i f f e r e n t f r e q u e n c i e s : .4 Hz, .8 Hz and 1.2 Hz. The t r a c k i n g t a s k s were r e p e a t e d a s e c o n d t i m e w h i l e s u b j e c t s engaged i n t h e m o n i t o r t a s k . A s i n u s o i d a l v e r t i c a l SPEM t e s t a t .4 Hz c o n c l u d e d t h e smooth p u r s u i t t r a c k i n g t a s k s . V e r t i c a l and h o r i z o n t a l s a c c a d i c EOG t a s k s were p r e s e n t e d n e x t . The s u b j e c t h o r i z o n t a l l y t r a c k e d a r e c t a n g u l a r wave t a r g e t w h i c h had an a v e r a g e f r e q u e n c y o f .2 Hz f o r 20 c y c l e s e a c h . A s i m i l a r v e r t i c a l s a c c a d i c t a s k ended t h e s a c c a d i c eye t r a c k i n g t a s k s . In t h e s e c o n d h a l f of t h e s e s s i o n , s k i n c o n d u c t a n c e e l e c t r o d e s were a t t a c h e d t o t h e s u b j e c t who was r e q u e s t e d t o h o l d t h e arms and f i n g e r s s t i l l so as t o r e d u c e c o n t a m i n a t i o n of t h e d a t a by movement a r t e f a c t s . A 5 m i n u t e r e s t i n g p e r i o d commenced and e n s u r e d t h a t t h e SCR r e a d i n g s were s t a b i l i z e d . The s u b j e c t was a s k e d t o w i l f u l l y cough t o d e t e r m i n e what a t y p i c a l r e s p o n s e m i g h t l o o k l i k e . T h i s gave t h e e x p e r i m e n t e r t h e t i m e t o c a l i b r a t e t h e s k i n c o n d u c t a n c e c h a n n e l . The s u b j e c t was t h e n g i v e n headphones t o wear, t h r o u g h w h i c h a s e r i e s of s o f t and l o u d t o n e s were h e a r d . E i g h t 85 db t o n e s 33 were p r e s e n t e d , f o l l o w e d by t e n 105 db t o n e s a t 1,000 Hz. Tones l a s t e d 1 s e c o n d e a c h . The i n t e r t o n e i n t e r v a l s were 20-40 s e c o n d s l o n g , of 30 s e c o n d s d u r a t i o n on a v e r a g e . A r e l a x a t i o n i n d u c i n g s e t o f i n s t r u c t i o n s was d e l i v e r e d p r i o r t o t h e commencement of t h e t o n e p r e s e n t a t i o n and s u b j e c t s were i n f o r m e d t h a t t h e t a s k was a measure o f t h e i r a b i l i t y t o i g n o r e t h e d i s t r a c t i n g t o n e s w h i l e t h e y c o n c e n t r a t e d on becoming c o m p l e t e l y r e l a x e d (See A p p e n d i x I ) . T h e s e i n s t r u c t i o n s were i n c l u d e d t o r e d u c e i n t e r s u b j e c t v a r i a b i l i t y w i t h r e s p e c t t o t h e s i g n i f i c a n c e t h e s u b j e c t s a t t a c h e d t o t h e t o n e s by f o c u s i n g t h e i r a t t e n t i o n on t h e t a s k of becoming r e l a x e d ( I a c o n o & L y k k e n , 1 9 7 9 c ) . A f t e r t h e t o n e p r e s e n t a t i o n , s u b j e c t s were t h e n i n s t r u c t e d t o f o c u s t h e i r a t t e n t i o n on two f a m i l i a r sounds and r e q u e s t e d t o t r y t o i d e n t i f y them. They were t h e n p r e s e n t e d w i t h a dog b a r k i n g and a t e l e t y p e ( t a p e d from a sound e f f e c t s r e c o r d ) . T h e s e sounds were i n c l u d e d i n an a t t e m p t t o c o n t r a s t s u b j e c t s ' e l e c t r o d e r m a l r e s p o n s i v i t y t o ( m e a n i n g l e s s ) t o n e s w i t h t h e i r r e s p o n s e t o ( m e a n i n g f u l ) s o u n d s . At t h e end o f t h e two hour s e s s i o n , t h e e l e c t r o d e s were removed and t h e s u b j e c t s ' q u e s t i o n s a n s w e r e d . S u b j e c t s were t h e n a s k e d i f t h e y wanted a b r i e f summary o f t h e o v e r a l l r e s u l t s of t h e s t u d y s e n t t o them once t h e d a t a were a n a l y z e d . Q u a n t i f i c a t i o n o f M e a s u r e s Eye T r a c k i n g T a s k s D a t a from e a c h SPEM t a s k as w e l l a s from t h e t a r g e t 34 c h a n n e l a s s o c i a t e d w i t h t h e t a s k were r e c o r d e d on m a g n e t i c t a p e s . T h e s e t a p e s were t h e n d i g i t i z e d by t h e computer and th e d a t a s t o r e d on f l o p p y d i s k s . The computer s t o r e d t h e f i r s t t w e nty c y c l e s of b o t h t h e eye t r a c k i n g and t h e t a r g e t c h a n n e l , a l i g n i n g t h e two c h a n n e l s so t h a t c y c l e s 1, 2, e t c . of t h e t a r g e t and t h e t r a c k i n g d a t a c o u l d be compared f o r phase l a g d i f f e r e n c e s . The phase l a g s c o r e e s s e n t i a l l y m e asures t h e d e g r e e t o w h i c h t h e e y e s move a h e a d o r f a l l b e h i n d t h e t a r g e t a s t h e e y e s a t t e m p t t o t r a c k i t . A l a r g e l a g i n d i c a t e s p o o r t r a c k i n g ; a l a g v a l u e c l o s e t o z e r o i n d i c a t e s ' n e a r p e r f e c t s y n c h r o n y o f t h e e y e s ' and t h e t a r g e t ' s movements. A p o s i t i v e l a g i n d i c a t e s t h a t t h e e y e s a r e l a g g i n g b e h i n d t h e t a r g e t . The b e s t s i x t e e n c y c l e s f r o m e a c h eye t r a c k i n g t a s k were t h e n s e l e c t e d f o r a n a l y s i s . T h i s u s u a l l y r e s u l t e d i n t h e f i r s t s i x t e e n c y c l e s of a t t e m p t e d t r a c k i n g b e i n g s e l e c t e d as t h e s i x t e e n b e s t c y c l e s . C r i t e r i a f o r r e j e c t i n g c y c l e s were e s t a b l i s h e d a s f o l l o w s : (1) The f i r s t c y c l e o f \" t r a c k i n g \" was r e j e c t e d i f t h e s u b j e c t d i d n ot t r a c k t h e e n t i r e f i r s t c y c l e . (2) C y c l e s a s s o c i a t e d w i t h an extreme EOG s i g n a l t h a t was o u t -o f - b o u n d s on t h e FM t a p e were r e j e c t e d . (3) C y c l e s were d e l e t e d i f t h e s u b j e c t was o b v i o u s l y n ot a t t e n d i n g t o t h e t a s k e .g. t h e s u b j e c t t a l k e d d u r i n g t h e t a s k . Once t h e b e s t s i x t e e n c y c l e s were c h o s e n , t h e program d i v i d e d e a c h c y c l e of t r a c k i n g ( a s w e l l a s d i v i d i n g t h e 35 c o r r e s p o n d i n g c y c l e from t h e t a r g e t c h a n n e l ) i n t o 500 a m p l i t u d e d a t a p o i n t s . E a c h c y c l e of t r a c k i n g was s t a n d a r d i z e d t o have a mean of z e r o and a s t a n d a r d d e v i a t i o n of one and c e n t e r e d a b o u t a h o r i z o n t a l a x i s s e t e q u a l t o t h e mean. T h i s e n s u r e d t h a t t h e two s e t s of c y c l e s were e x p r e s s e d i n t h e same u n i t s of measurement and h ence were c o m p a r a b l e . The s e c o n d measure o f smooth p u r s u i t eye t r a c k i n g p e r f o r m a n c e - - t h e RMS(root mean s q u a r e ) e r r o r d e v i a t i o n s c o r e \u00E2\u0080\u0094 was t h e n c a l c u l a t e d from t h e two c h a n n e l s and m u l t i p l i e d by 1,000. An RMS e r r o r s c o r e was computed i n d i v i d u a l l y f o r e a c h of t h e s i x t e e n c y c l e s . The median RMS s c o r e was u t i l i z e d i n s u b s e q u e n t d a t a a n a l y s e s b e c a u s e t h e median i s l e s s s e n s i t i v e t o i n f l a t i o n by momentary i n a t t e n t i o n t h a t c o u l d g r o s s l y d i s t o r t one o r two c y c l e s . The median RMS s c o r e i s a l s o u n a f f e c t e d by b l i n k s i n t h e eye t r a c k i n g r e c o r d ( I a c o n o e t a l . , 1982). A low RMS s c o r e i n d i c a t e d t h a t t h e s u b j e c t t r a c k e d w e l l ( i e . t h e eye t r a c k i n g c h a n n e l d a t a showed l i t t l e d e v i a t i o n f r o m t h e t a r g e t c h a n n e l d a t a ) and t h a t t h e shape o f t h e eye t r a c k i n g d a t a c l o s e l y a p p r o x i m a t e d t h e shape of t h e c y c l e s i n t h e t a r g e t c h a n n e l . A h i g h RMS s c o r e r e p r e s e n t e d a p o o r t r a c k i n g p e r f o r m a n c e . The s a c c a d i c eye t r a c k i n g t a s k s were s i m i l a r l y d i g i t i z e d on FM t a p e s and s t o r e d on f l o p p y d i s k s . The computer t h e n i d e n t i f i e d s a c c a d i c eye movements i n t h e b e s t s i x t e e n c y c l e s o f t r a c k i n g . The b e s t c y c l e s were c h o s e n i n t h e same way as t h e c y c l e s f o r t h e smooth p u r s u i t eye t r a c k i n g t a s k s . A 36 minimum v e l o c i t y (40 d e g r e e s / s e c o n d ) and a minimum d u r a t i o n (40 msecs) c r i t e r i o n were u s e d t o i d e n t i f y a s a c c a d e . I t s v e l o c i t y , d u r a t i o n and a m p l i t u d e were me a s u r e d . The a m p l i t u d e was c a l c u l a t e d as t h e d i f f e r e n c e between t h e peak o f t h e s a c c a d i c eye t r a c k i n g movement and t h e t r o u g h a t t h e eye movement o n s e t . S k i n C o n d u c t a n c e M e a s u r e s The s c o r i n g p r o t o c o l f o r t h e e l e c t r o d e r m a l m e asures i s p r e s e n t e d i n A p p e n d i x J . T o n i c or r e s t i n g s k i n c o n d u c t a n c e l e v e l was c a l c u l a t e d i n t h e l e f t and r i g h t hands a t t h e s t a r t of e a c h t o n e o r sound. T h i s e s t a b l i s h e d a b a s e l i n e o f r e s p o n s i v i t y t o t h e s o f t t o n e s , t o t h e l o u d t o n e s , and t o t h e two s o u n d s - - t h e dog b a r k and t h e t e l e t y p e . A s k i n c o n d u c t a n c e r e s p o n s e was d e f i n e d as any r e s p o n s e o c c u r r i n g one t o f o u r s e c o n d s a f t e r t o n e o n s e t . A s p o n t a n e o u s s k i n c o n d u c t a n c e r e s p o n s e was c o u n t e d i f i t o c c u r r e d t e n s e c o n d s a f t e r s t i m u l u s o n s e t and b e f o r e t h e o n s e t of t h e n e x t t o n e . The m o d i f i e r ' s p o n t a n e o u s ' r e s t r i c t s t h i s r e s p o n s e t o t h o s e SCRs t h a t o c c u r e d w i t h o u t t h e t h e p r e s e n t a t i o n of any s t i m u l i . To e s t a b l i s h whether a s u b j e c t was a r e s p o n d e r o r a n o n r e s p o n d e r , r e s p o n s e s were c o u n t e d i f t h e y were g r e a t e r t h a n .05 micromhos i n a m p l i t u d e . T h i s minimum s i z e was a d o p t e d t o h e l p c o n t r o l f o r movement a r t e f a c t s i n t h e d a t a . E l e c t r o d e r m a l h a b i t u a t i o n was deemed t o have t a k e n p l a c e when s u b j e c t s gave t h r e e c o n s e c u t i v e r e s p o n s e s of l e s s t h a n .05 micromhos i n a m p l i t u d e . The t h r e e z e r o r e s p o n s e s c r i t e r i o n was a d o p t e d t o e n s u r e 37 c o m p a r a b i l i t y w i t h o t h e r r e s e a r c h d e a l i n g w i t h e l e c t r o d e r m a l h a b i t u a t i o n i n H u n t i n g t o n ' s c h o r e a . The t i m e t h a t e l a p s e d between t h e t o n e i n i t i a t i o n and t h e b e g i n n i n g o f t h e s k i n c o n d u c t a n c e r e s p o n s e was a d o p t e d a s t h e measure of r e s p o n s e l a t e n c y . The a m p l i t u d e of t h e f i r s t r e s p o n s e , as w e l l as t h e a m p l i t u d e o f t h e b i g g e s t r e s p o n s e ( c a l c u l a t e d as t h e l a r g e s t s k i n c o n d u c t a n c e v a l u e r e a c h e d d u r i n g t h e s t i m u l u s minus t h e p r e s t i m u l u s t o n i c l e v e l ) t o t h e dog and t e l e t y p e s t i m u l i were c a l c u l a t e d i n a d d i t i o n t o t h e r e s t i n g s k i n c o n d u c t a n c e f o r t h e d a t a a n a l y s e s of t h e s o u n d s . 38 R e s u l t s In a l l a n a l y s e s , t h e d e g r e e s o f freedom u t i l i z e d were a d j u s t e d t o t a k e a c c o u n t of p o s s i b l e d e p e n d e n c i e s c r e a t e d i n th e s c o r e s by t h e i n c l u s i o n of members from t h e same f a m i l y . One d e g r e e of fr e e d o m was a s s i g n e d p e r n u c l e a r f a m i l y . E i g h t e e n a t - r i s k f a m i l i e s and twenty-two c o n t r o l f a m i l i e s p a r t i c i p a t e d . The a d j u s t m e n t i n v o l v e d c o m p u t i n g F t e s t s u t i l i z i n g t h e a p p r o p r i a t e l y r e d u c e d number o f d e g r e e s of fre e d o m i n t h e f o r m u l a (See W i n e r , 1971). Demographic V a r i a b l e s and Q u e s t i o n n a i r e A n a l y s e s The means f o r t h e d e m o g r a p h i c v a r i a b l e s c o r e s , a s w e l l as t h e means f o r t h e q u e s t i o n n a i r e s c o r e s a r e c o n t a i n e d i n T a b l e 1. A one-way ANOVA w i t h g r o u p as t h e o n l y f a c t o r e xamined t h e i n t e r r e l a t i o n s h i p s between t h e g r o u p s ( i e . H u n t i n g t o n , a t - r i s k , and c o n t r o l ) on t h e s e v a r i a b l e s and on t h e q u e s t i o n n a i r e s c o r e s . T h e r e was no s i g n i f i c a n t d i f f e r e n c e between t h e g r o u p s i n terms of age, F(2,44)=2.64, 2 < \u00C2\u00AB 0 8 . The g r o u p s d i f f e r e d on t h e BDI s c o r e s , F(2,42)=13.71, p_<.05. The H u n t i n g t o n s u b j e c t s had h i g h e r s c o r e s on t h e BDI t h a n e i t h e r of t h e o t h e r two g r o u p s of s u b j e c t s . T h e r e was a d i f f e r e n c e between t h e g r o u p s i n e d u c a t i o n , F (2, 44) =4. 03 , p_<.02. A Newman-Keuls m u l t i p l e range t e s t i n d i c a t e d t h a t t h e c o n t r o l s u b j e c t s had more y e a r s o f e d u c a t i o n t h a n t h e a t - r i s k b u t not th e c h o r e i c s u b j e c t s . The g r o u p s d i d n o t d i f f e r on t h e i r STAI g e n e r a l s c o r e s , F(2,41)=3.00, 2 < ' 0 6 * S c o r e s f o r t h e STAI t o d a y were c o m p a r a b l e a c r o s s a l l g r o u p s , F(2,39)=1 .24, p_<.30. 39 Eye T r a c k i n g D a t a A n a l y s e s P r e l i m i n a r y A n a l y s e s As a r e s u l t o f s e v e r a l ANOVAs d e s i g n e d t o t e s t f o r s i g n i f i c a n t d i f f e r e n c e s between t h e g r o u p s , i t was r e v e a l e d t h a t t h e v a r i a n c e s of t h e g r o u p s on t h e smooth p u r s u i t eye t r a c k i n g t a s k s were c o n s i d e r a b l y h e t e r o g e n e o u s , and B a r t l e t t c h i - s q u a r e t e s t s of h o m o g e n e i t y of v a r i a n c e w i t h p_<.00C)1 were t y p i c a l . I n s p e c t i o n of t h e g r o u p v a r i a n c e s i n d i c a t e d t h a t t h e v a r i a n c e s f o r t h e H u n t i n g t o n g r o u p were o f t e n t h r e e t o t e n t i m e s t h a t of t h e o t h e r two g r o u p s ; and i n t h e eye t r a c k i n g t a s k s i n v o l v i n g t r a c k i n g a t a r g e t a t a h i g h f r e q u e n c y , t h e v a r i a n c e f r o m t h e H u n t i n g t o n ' s g r o u p c o u l d be as much as f i f t y t i m e s l a r g e r t h a n t h e v a r i a n c e s o f t h e a t - r i s k and t h e c o n t r o l g r o u p s . V a r i a n c e s on some s a c c a d i c eye t r a c k i n g t a s k s were s i m i l a r l y much l a r g e r i n t h e H u n t i n g t o n g r o u p , o r f o r some t a s k s much s m a l l e r t h a n t h e v a r i a n c e s i n t h e a t - r i s k o r t h e c o n t r o l g r o u p s c o r e s . V i s u a l i n s p e c t i o n of t h e d a t a c l e a r l y showed t h a t t h e H u n t i n g t o n g r o u p was t r a c k i n g i n a h i g h l y d e v i a n t f a s h i o n f r o m what would be e x p e c t e d on s u c h t a s k s . Examples of n o r m a l , a t - r i s k , and H u n t i n g t o n eye t r a c k i n g r e c o r d s a r e c o n t a i n e d i n F i g u r e 1. The c o m p u t e r i z e d eye t r a c k i n g a n a l y s e s were t h e r e f o r e r e s t r i c t e d t o a c o m p a r i s o n of t h e eye t r a c k i n g p e r f o r m a n c e o f t h e no r m a l c o n t r o l s and t h e a t - r i s k s u b j e c t s . H i g h l y u n e q u a l v a r i a n c e s a r e known t o l i m i t t h e v a l i d i t y o f t h e p r o b a b i l i t y s t a t e m e n t s g e n e r a t e d by t h e ANOVA F t e s t s . 40 FIG.1 EYE TRACKING RECORDS OF TWO SUBJECTS FROM EACH GROUP ON HORIZONTAL SMOOTH PURSUIT AT .4 HZ. llllliSfflif li#Mliii! M i l TA i f I IB R 1 i G .li 1 E\" ill 1 ii r i'f f M l \" / 71 !\u00C2\u00AB 1 tl 1 UliflllHlUPIf I B \u00E2\u0084\u00A2 M i i l l ^ IMS H i t CONTROL A CONTROL B AT - RISK A AT-RISK B HUNTINGTON A HUNTINGTON B 41 The p r o b l e m o f d u b i o u s v a l i d i t y i s compounded i n t h e p r e s e n t r e s e a r c h by t h e l a r g e d i s c r e p a n c y i n sample s i z e i e . t h e e a r l y H u n t i n g t o n s u b j e c t s numbered o n l y s e v e n , t h a t i s , t h e H u n t i n g t o n g r o u p was one q u a r t e r t h e s i z e of t h e o t h e r two g r o u p s . H i g h l y u n e q u a l sample s i z e s c o m b i n e d w i t h h e t e r o g e n e i t y o f v a r i a n c e g r e a t l y l i m i t s t h e v a l i d i t y of t h e c o n c l u s i o n s t h a t can be drawn from t h e a n a l y s i s o f v a r i a n c e ( G l a s s , Peckham, & S a n d e r s , 1972; Box, 1954; Kramer, 1956). The r o b u s t n e s s o f F t e s t s t o v i o l a t i o n s does n o t h o l d up w i t h h i g h l y u n e q u a l Ns. The f r e q u e n c y o f Type I e r r o r s under s u c h c o n d i t i o n s as a r e p r e s e n t i n t h e eye t r a c k i n g d a t a c o u l d e a s i l y be t r i p l e d , l e a d i n g one t o c o n c l u d e t h a t many more s i g n i f i c a n t d i f f e r e n c e s e x i s t between t h e g r o u p s when t h e n u l l h y p o t h e s i s i s a c t u a l l y t r u e . In g e n e r a l , i f t h e sample w i t h t h e s m a l l e s t N i s a l s o t h e sample w i t h t h e l a r g e s t v a r i a n c e , t h e a c t u a l s i g n i f i c a n c e l e v e l , p g r e a t l y e x c e e d s t h e n o m i n a l s i g n i f i c a n c e l e v e l ( u s u a l l y p<.05). The eye t r a c k i n g t a s k s w ould have been s u b j e c t e d t o h i g h l y i n a p p r o p r i a t e a n a l y s e s , had t h e H u n t i n g t o n g r o u p been i n c l u d e d . T h e r e i s no c o n s e n s u s i n t h e s t a t i s t i c a l l i t e r a t u r e a s t o t e s t s t h a t c o u l d be v a l i d g i v e n s u c h c i r c u m s t a n c e s ( M i l l e r , 1981). The d i s c r e p a n c y i n sample s i z e and v a r i a n c e e x i s t e d as w e l l i n t h e s a c c a d i c eye t r a c k i n g d a t a . The p r o b l e m o f e x c e p t i o n a l l y l a r g e v a r i a n c e s e x i s t e d i n some measures ( e . g . i n t h e l a t e n c y measures of h o r i z o n t a l s a c c a d i c t r a c k i n g , but o n l y f o r l e f t w a r d eye movements) but i n o t h e r m e a s u r e s , 42 th e H u n t i n g t o n g r o u p c o n t r i b u t e d e x c e p t i o n a l l y s m a l l v a r i a n c e s when compared t o t h e o t h e r two g r o u p s . ( e . g . i n t h e a m p l i t u d e measure of b o t h up and down v e r t i c a l eye t r a c k i n g ) . The l a t t e r s i t u a t i o n g r e a t l y i n c r e a s e s t h e f r e q u e n c y of Type II e r r o r s . O t h e r s t u d i e s w i t h b r a i n - d a m a g e d p o p u l a t i o n s have e n c o u n t e r e d s i m i l a r p r o b l e m s ( H o l l o w a y & P a r s o n s , 1971; D a v i d o f f & McDonald, 1964) on measures of e l e c t r o d e r m a l r e s p o n s i v i t y . I t was c l e a r from v i s u a l i n s p e c t i o n a l o n e t h a t t h e t r a c k i n g of t h e H u n t i n g t o n g r o u p was h i g h l y d e v i a n t i n many r e s p e c t s . The t r a c k i n g of t h e H u n t i n g t o n s u b j e c t s was a l s o much worse t h a n t h a t o f s c h i z o p h r e n i c p a t i e n t s who had c o m p l e t e d t h e same t r a c k i n g t a s k s ( I a c o n o , p e r s o n a l c o m m u n i c a t i o n , December 1983). A b l i n d r a t i n g o f t r a c k i n g p e r f o r m a n c e u t i l i z i n g p h o t o c o p i e d eye t r a c k i n g r e c o r d s f o u n d t h e H u n t i n g t o n g r o u p t o be t h e w o r s t g r o u p o v e r a l l when t h e i r t r a c k i n g was compared t o p s y c h o t i c s u b j e c t s w i t h e i t h e r a f f e c t i v e o r s c h i z o p h r e n i c d i s o r d e r s on t h e .4 Hz h o r i z o n t a l smooth p u r s u i t t r a c k i n g t a s k . U s i n g t h e mean p e r f o r m a n c e s c o r e o f t h e t h r e e d i a g n o s t i c g r o u p s ( H u n t i n g t o n , s c h i z o p h r e n i c and a f f e c t i v e d i s o r d e r ) a s a c u t o f f p o i n t , s u b j e c t s were c l a s s i f i e d a s good o r p o o r t r a c k e r s . A c h i s q u a r e w i t h one d e g r e e o f f r e e d o m ( s u b j e c t s were c l a s s i f i e d a s H u n t i n g t o n o r n o n - H u n t i n g t o n ) was s i g n i f i c a n t , x 2 = 4 . 3 1 , \u00C2\u00A3 < . 0 5 , c o n f i r m i n g t h a t membership i n t h e H u n t i n g t o n g r o u p was s i g n i f i c a n t l y r e l a t e d t o p o o r t r a c k i n g p e r f o r m a n c e . 43 The i m p o r t a n t p o i n t i n t h e s e a n a l y s e s was i n any case- t o f o c u s on t h e c o m p a r i s o n of t h e a t - r i s k w i t h t h e n o r m a l c o n t r o l g r o u p t o d e t e r m i n e i f (a) t h e r e were s i g n i f i c a n t d i f f e r e n c e s between t h e g r o u p s and ( b ) , i f t h e a t - r i s k were f o u n d t o be po o r t r a c k e r s , were t h e r e s i m i l a r i t i e s i n t h e d e f i c i e n c i e s p r o d u c e d by t h e a t - r i s k g r o u p and t h e d e f i c i e n c i e s p r o d u c e d by t h e c h o r e i c g r o u p . A .05 l e v e l o f c o n f i d e n c e was a d o p t e d f o r a l l t e s t s of s i g n i f i c a n c e . The G r e e n h o u s e - G e i s s e r e p s i l o n (e) c o r r e c t i o n p r o c e d u r e ( G r e e n h o u s e & G e i s s e r , 1959) was u t i l i z e d i n t h e r e p e a t e d measures a n a l y s e s t o a d j u s t t h e d e g r e e s of fre e d o m i n t h e F - t e s t s . The p r o c e d u r e e f f e c t i v e l y r e d u c e s t h e number o f f a l s e p o s i t i v e s w h i c h w o u l d o t h e r w i s e be g e n e r a t e d (See W i n e r , 1971, p. 523, f o r a d i s c u s s i o n o f t h i s p r o c e d u r e ) . The G r e e n h o u s e - G e i s s e r p r o b a b i l i t i e s and e p s i l o n f a c t o r s f o r d e g r e e s of f r e e d o m a d j u s t m e n t a r e r e p o r t e d where a p p l i c a b l e . The e p s i l o n f a c t o r was a p p l i e d t o d e g r e e s of f r e e d o m t h a t had a l r e a d y been a d j u s t e d t o a c c o u n t f o r f a m i l i a l i n t e r d e p e n d e n c i e s i n t h e eye t r a c k i n g s c o r e s . One a t - r i s k s u b j e c t d i d n o t do t h e eye t r a c k i n g t a s k s b e c a u s e o f a v i s i o n p r o b l e m ( s t r a b i s m u s ) . The d a t a from two n o r m a l c o n t r o l s were wit h d r a w n from t h e eye t r a c k i n g a n a l y s e s , a g a i n b e c a u s e of p r o b l e m s w i t h s t r a b i s m u s . T h e s e n o r m a l s were o r i g i n a l l y s c r e e n e d f o r eye p r o b l e m s but were f o u n d , d u r i n g t h e a c t u a l t e s t i n g s e s s i o n , t o be t r a c k i n g a s s t r a b i s m i c i n d i v i d u a l s w ould. On c l o s e q u e s t i o n i n g , b o t h o f t h e s e n o r m a l c o n t r o l s u b j e c t s d e s c r i b e d a c h i l d h o o d h i s t o r y of eye p r o b l e m s . 44 Smooth P u r s u i t T r a c k i n g A n a l y s e s H o r i z o n t a l Smooth P u r s u i t Eye Movement (SPEM) A n a l y s e s F o r two s u b j e c t s , m i s s i n g d a t a f o r one t a s k was e s t i m a t e d by i n t e r p o l a t i n g d a t a p o i n t s f r o m t h e s i m i l a r t a s k s t h e y had a l r e a d y c o m p l e t e d a t d i f f e r e n t f r e q u e n c i e s . The g r o u p means f o r t h e p h a s e l a g and t h e median RMS e r r o r m e a s u r e s of SPEM t r a c k i n g a r e shown i n T a b l e 2. The d a t a from t h e a t - r i s k and n o r m a l c o n t r o l s u b j e c t s were s u b j e c t e d t o a t h r e e - w a y a n a l y s i s o f v a r i a n c e ( u s i n g D i x o n , 1981, BMDP:2V) w i t h r e p e a t e d m e a s u r e s on two f a c t o r s . The two r e p e a t e d m e asures f a c t o r s were t a r g e t f r e q u e n c y (.4 Hz, .8 Hz, 1.2 H z ) ; and t a s k ( m o n i t o r , n o n m o n i t o r ) . The between f a c t o r was g r o u p ( a t - r i s k , c o n t r o l ) . The p h a s e l a g a n a l y s i s r e v e a l e d s i g n i f i c a n t d i f f e r e n c e s between t h e g r o u p s F (1,40)=6.75, p_<.02. A t - r i s k s u b j e c t s t r a c k e d w i t h g r e a t e r p h a s e l a g ( i e . w i t h t h e i r e y e s l a g g i n g b e h i n d t h e t a r g e t ) t h a n d i d t h e n o r m a l c o n t r o l s u b j e c t s . T h e r e was a s i g n i f i c a n t t a s k e f f e c t , F(1 , 38) = 18.44, p_<.01, i n d i c a t i n g t h a t phase l a g was g r e a t e r i n t h e m o n i t o r t h a n i n t h e n o n m o n i t o r t a s k c o n d i t i o n . T h a t i s , t h e e y e s l a g g e d f u r t h e r b e h i n d t h e t a r g e t i n t h e n o n m o n i t o r c o n d i t i o n . The f r e q u e n c y a t w h i c h t h e t a r g e t moved a c r o s s t h e s c r e e n was s i g n i f i c a n t l y r e l a t e d t o phase l a g p e r f o r m a n c e , F(1.22,46.4)=101.02, \u00C2\u00A3 < . 0 1 , e=.61, i n t h a t s u b j e c t s ' e y e s l a g g e d f u r t h e r b e h i n d t h e t a r g e t a t t h e h i g h e r f r e q u e n c i e s . T h e r e were no s i g n i f i c a n t i n t e r a c t i o n e f f e c t s . F i g u r e 2 shows ph a s e l a g s c o r e s f o r t h e t h r e e g r o u p s i n t h e m o n i t o r and 45 T a b l e 2 Means f o r H o r i z o n t a l Smooth P u r s u i t Eye Movements Group H u n t i n g t o n A t - R i s k C o n t r o l Non-Phase L a g Me d i a n RMS Non-F r e q u e n c y M o n i t o r M o n i t o r M o n i t o r M o n i t o r .4 Hz -10.00 -2.14 41 1 260 (6.4) (5.9) (254) (285) .8 Hz 1 .29 1 0.29 424 238 (31.3) (6.7) (351 ) (230) .2 Hz 23.71 44. 1 4 619 355 (26.1) (55.2) (371 ) (331 ) .4 Hz -4.37 0.04 1 22 91 (10.3) (2.3) (94) (42) .8 Hz -0.64 9.32 202 1 1 3 (13.2) (6.0) (123) (42) .2 Hz 1 5.54 27.93 273 168 (21.4) (8.8) (116) (56) .4 Hz -7.37 -1 .63 139 1 07 (12.8) (2.2) (112) (41 ) .8 Hz -5.78 4.37 186 1 22 (10.1) (5.0) (121) (32) .2 Hz 1 0.67 1 9.85 230 165 (14.9) (11.4) (103) (38) N o t e . S t a n d a r d d e v i a t i o n s a r e g i v e n i n p a r e n t h e s e s . a V a l u e s a r e i n number o f s a m p l i n g p o i n t s . One s a m p l i n g p o i n t e q u a l s .04 d e g r e e s of v i s u a l a r c . b The means and s t a n d a r d d e v i a t i o n s f o r t h e RMS e r r o r s c o r e were a v e r a g e d o v e r r i g h t and l e f t eye movements. V a l u e s a r e i n a r b i t r a r y u n i t s . Z 'Old 9* 47 i ui X. a. Ui >-Ui. u. o \u00E2\u0080\u00A2z. UI 0' r- iu Z cos O 3: o FlCr-3 CO' O rtf< 4 Or O o k \ \ \ N f f S O K \ \ \ \ v v \ \ \ \ \ \ o -r\u00E2\u0080\u0094 -r r r-* too-I 1 < _-UI Ol: Qi. 3 a . W /\"V b 0>l O sk O a: h \u00E2\u0080\u00A2X-Ui x: ui U-o> X o ui Q CO* 2 micromhos) . 111 APPENDIX J At point X, the recording i s .4 cm or 4 mm below the center of the chart. Therefore, the SCL at this point i s 7-0.8 = 6.2 micromhos. In the example below, SCL = 5 micromhos. W J 4 - : ! , ! - M I. T ! \" r- |.. i - \u00E2\u0080\u0094 e \u00E2\u0080\u0094 -\u00E2\u0080\u00A2 i \u00E2\u0080\u00A2; I: I .1 i . UIK IS :!:' -I 2) s e n s i t i v i t y . This equals the setting on the preamplifier (which ranges from .05 mv/mm to .5 mv/mm) mul t i p l i e d by the setting on the preamp m u l t i p l i e r (always 3 x . l ) . The equipment i s constructed such that when the preamp m u l t i p l i e r i s set at x . l , the premp se t t i n g (which i s in m i l l i v o l t s per mm) can be read as micromhos per mm. The preamp settings that are normally used are .05, .1, .2, and .5. A setting of .05 means that one ( v e r t i c a l ) mm represents .05 micromhos. Thus, a d e f l e c t i o n of 1 cm = .5 micromhos. A de f l e c t i o n of 2 cm = . 1 micromho. The chart on the next page indicates the distances, or pen deflections, that represent 1 micromho i f the preamp i s set at the 4 commonly used settings. - ! 1 - ' . J - l - i . j ! ! I. m CSU3 vwJrda 'Msec .05 . j....; \u00E2\u0080\u00A2( ' -J,' : -5 , . } 112 APPENDIX J Scoring Skin Conductance on Charts 1. SCL 1) Draw v e r t i c a l l i n e through l e f t side of each tone. 2) Calculate tonic l e v e l for each hand at intersection of l i n e (micromhos). 3) Write tonic l e v e l on chart. 2. SCOR -/WV #\u00C2\u00A3SPo/4S\u00C2\u00A3 AFTER 7 Second MoT AFTelZ ^S\u00C2\u00A3.COMDS 1) Measure the amplitude (in mm) of each response on each hand ( i . e . d i s -tance from highest point within f sees following treatment to lowest point within }. sec following tone onset). 2) Convert mm to micromhos. 3. For the f i r s t tone of each series, calculate: 1) latency: distance (in mm) from tone i n i t i a t i o n to beginning of response 2) r i s e time: distance (in mm) from the beginning of the response to the time i t takes to reach peak amplitude 3) recovery half-time: measure the number of mm from the peak of a response to half the response amplitude (If this can't be calculated, use distance from peak to next tone.) 4. Spontaneous Responses 1) Count 10 sec from onset of each tone and draw another l i n e . 2) Count spontaneous responses from this l i n e to the onset of the next tone. C i r c l e a l l SR's on chart. 3) 2 categories of SR: (1) >^ .05 micromhos (2) < .05 micromhos U J L I ^ a kn.oLo\u00C2\u00BBv rVt.'ravct occurs e.g. coujk , 7VV>Y eweKTj) Snee-z.es, disregard SSCOR 113 APPENDIX J 5. Sounds Draw a l i n e at the beginning and end of each sound. Calculate: 1) SCL at beginning. 2) amplitude of f i r s t response to the sound. 3 ) amplitude of the maximum response to the sound; i.e., maximum SC value reached during the sound minus SCL at beginning. 4) number of discrete responses during the sound. (Remember: response latency i s 1 sec = 2.5 mm. Responses that occur within this time after the sound ends count as responses to the sound.) 6. Calculate highest and lowest SCL's during the session (independent of a response). "@en . "Thesis/Dissertation"@en . "10.14288/1.0096303"@en . "eng"@en . "Psychology"@en . "Vancouver : University of British Columbia Library"@en . "University of British Columbia"@en . "For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use."@en . "Graduate"@en . "Eye movements and electrodermal responsivity as possible genetic markers of Huntington\u00E2\u0080\u0099s chorea"@en . "Text"@en . "http://hdl.handle.net/2429/25166"@en .