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Eye movements and electrodermal responsivity as possible genetic markers of Huntington’s chorea 1984

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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 © 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 — 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°/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 — 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 — 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 — 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 — 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 — 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 — 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 — 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 < « 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 !« 1 tl 1 UliflllHlUPIf I B ™ 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 , £ < . 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, £ < . 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 •z. 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— -r r r- <w ^ \n T r — r Jo i t r y LOO: 0»£ ' O 6>* too- I 1 < _</) «o O XT ;K «r» • -J' <C Qr — i Ufc ^ J? _ i a. <C UI 48 & <c ce V- IU >- UI Ol: Qi. 3 a . W /"V b 0>l O sk O a: h •X-Ui x: ui U- o> X o ui Q CO* <x <: _J _i O Co J * o 5 O •A ,00 C< In i n r n r t - Ad . c * 1 rori- 1 CM C* I 1* <3Z 5; £ ui _ i a . 3T. <C UJ* "i I I 1 1 1 r 1 1 1 r- ^ Si. cr- co t+. ^ ? •fl" -̂ «n ei- - 49 n o n m o n i t o r c o n d i t i o n s . C o n t r a s t i n g g r o u p means may not be a s e n s i t i v e t e s t o f g r o u p d i f f e r e n c e s i f a s m a l l number o f a t - r i s k s u b j e c t s c o n s i s t e n t l y s c o r e o u t s i d e t h e ran g e of n o r m a l s c o r e s . F i g u r e s 3 and 4 show t h e d i s t r i b u t i o n of s c o r e s f o r t h e a t - r i s k and c o n t r o l s u b j e c t s . 1.2 Hz was c h o s e n f o r t h e s e f i g u r e s , s i n c e t h e ANOVA had f o u n d t h e g r e a t e s t d i f f e r e n c e i n th e d i s t r i b u t i o n of t h e s c o r e s f o r t h i s t a r g e t s p e e d . A p o s t - hoc e x a m i n a t i o n o f t h e p r o p o r t i o n o f t h e h i g h e r phase l a g s c o r e s a c r o s s s u b j e c t s i n t h e a t - r i s k and c o n t r o l g r o u p s f o u n d t h a t t h e r e were n i n e s u b j e c t s a t - r i s k who t r a c k e d w i t h more t h a n t h i r t y s a m p l i n g p o i n t s o f l a g a s compared t o one n o r m a l c o n t r o l . Y a t e s ' c o r r e c t e d c h i - s q u a r e w i t h one d e g r e e o f free d o m was s i g n i f i c a n t , X 2 = 6 . 1 9 , p_<.0l. F o r t h e a n a l y s e s o f t h e median RMS p e r f o r m a n c e s c o r e s , a four-way ANOVA w i t h r e p e a t e d measures on t h r e e f a c t o r s ( f r e q u e n c y , t a s k , d i r e c t i o n o f eye movement) was computed. No s i g n i f i c a n t g r o u p e f f e c t , F (1 , 40) = 0. 03 , p_<.85, was r e v e a l e d . D i r e c t i o n e f f e c t s were p r e s e n t , whereby eye movements t o t h e r i g h t were l i n k e d t o h i g h e r RMS s c o r e s , F(1 , 40) = 36. 72 , p_<.0l, i n d i c a t i n g t h a t 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 r a c k i n g i n t h e r i g h t w a r d d i r e c t i o n . T a s k , F(1,40)=23.39, p < . 0 l , and f r e q u e n c y , F(1.62,61.6)=79.29, P_<.01, e = . 8 l , e f f e c t s were s i g n i f i c a n t . As e x p e c t e d , t h e n o n m o n i t o r t a s k s were more p o o r l y t r a c k e d t h a n were t h e m o n i t o r t a s k s . The h i g h e r f r e q u e n c i e s were a s s o c i a t e d w i t h a 50 g r e a t e r median RMS v a l u e , i n d i c a t i n g t h a t t r a c k i n g d e t e r i o r a t e d as t h e t a r g e t f r e q u e n c y i n c r e a s e d . A s i g n i f i c a n t i n t e r a c t i o n of f r e q u e n c y and g r o u p , F(1.62,61.6)=3.41 , p_<.05, e=.8l, was u n c o v e r e d . The median RMS measure s i m i l a r l y u n v e i l e d t h a t some of t h e a t - r i s k s u b j e c t s were p o o r a t r e p r o d u c i n g t h e t a r g e t p a t t e r n a t t h e 1.2 Hz f r e q u e n c y . T h a t i s , w h i l e t h e p e r f o r m a n c e o f b o t h g r o u p s d e t e r i o r a t e d a s t h e t a r g e t moved a t g r e a t e r s p e e d s , more of t h e a t - r i s k s u b j e c t s p r o d u c e d i m p a i r e d eye t r a c k i n g a t t h e h i g h e s t f r e q u e n c y . A p o s t - h o c e x a m i n a t i o n of t h e s e d a t a r e v e a l e d t h a t t h e r e were s e v e n a t - r i s k and t h r e e c o n t r o l s u b j e c t s who gave median RMS s c o r e s i n d i c a t i v e o f p o o r t r a c k i n g . An a n a l y s i s r e s u l t e d i n a Y a t e s ' c o r r e c t e d c h i - s q u a r e w i t h one d e g r e e of fre e d o m , X 2 = 1.21, p_<.27, w h i c h was n o t s i g n i f i c a n t . T h e r e were no o t h e r 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 . R e f e r t o F i g u r e 5. V e r t i c a l SPEM a n a l y s i s The phase l a g d a t a were a n a l y z e d v i a two-way ANOVAs w i t h r e p e a t e d measures on d i r e c t i o n o f eye t r a c k i n g . Group ( a t - r i s k , c o n t r o l ) was t h e between f a c t o r . T a b l e 3 p r e s e n t s t h e means f o r t h e v e r t i c a l smooth p u r s u i t t r a c k i n g t a s k . The a t - r i s k and c o n t r o l g r o u p 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 e x t e n t t o w h i c h t h e i r e y e s l a g g e d t h e t a r g e t , F ( 1 , 3 8 ) = .01, p_<.92. 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 t h e i r RMS s c o r e s , F (1 , 40) =0. 00, £ < . 9 8 . T h e r e was an e f f e c t due t o d i r e c t i o n , F ( 1,40)=5.30, p<.03 whereby s u b j e c t s i n b o t h g r o u p s had g r e a t e r RMS s c o r e s when t h e y t r a c k e d t h e d o t as i t HORIZONTAL SMOOTH PURSUIT EYE TRACKING COLLAPSED OVER DIRECTION OF EYE MOVEMENT. NONMONITOR MONITOR o o o CO s z < Q U i s 600 500 400 300 200 100- § Q 0 - soo- 400 300 200 100- HUNTINGTQNS f f AT-RISK l-«---;?Ti CONTROLS T l O U l .8 1.2 .4 .8 1.2 FREQUENCY IN HZ. 52 T a b l e 3 Means f o r V e r t i c a l Smooth P u r s u i t Eye Movements a b Group Phase Laq M e d i a n RMS Up Down Hunt i n g t o n 15.43 899 892 .. (61.5) (245) (214) A t - R i s k -6.88 470 41 1 (25.1) (186) (172) C o n t r o l -11.15 451 433 (29.6) (270) (252) 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 of 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 o f v i s u a l a r c . b 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 . 53 moved up t h e s c r e e n . 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 were u n c o v e r e d . S a c c a d i c Eye T r a c k i n g A n a l y s e s A v a l u e o f p_<.05 was u t i l i z e d as t h e c r i t e r i o n f o r t h e a t t a i n m e n t of s i g n i f i c a n c e i n a l l a n a l y s e s . The d a t a from one a t - r i s k s u b j e c t were not a v a i l a b l e due t o a m e c h a n i c a l f a i l u r e d u r i n g t h e l a b o r a t o r y t e s t s e s s i o n . 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 A n a l y s e s The median l a t e n c i e s t o i n i t i a l movement a r e p r e s e n t e d i n T a b l e 4. S e v e r a l two-way a n a l y s e s o f v a r i a n c e w i t h r e p e a t e d m easures on d i r e c t i o n were p e r f o r m e d . Group ( a t - r i s k , c o n t r o l ) was t h e o n l y o t h e r f a c t o r . The g r o u p s e x h i b i t e d s i m i l a r l a t e n c i e s , F ( 1 , 40 ) = . 53 , p_<.47. The r a n g e o f o c u l o m o t o r s a c c a d i c r e a c t i o n t i m e s f o r t h e g r o u p s was 209-223 m i l l i s e c o n d s i e . h i g h l y u n i f o r m r e a c t i o n t i m e s were a p p a r e n t . R i g h t w a r d s a c c a d i c eye movements, F ( 1 , 40 ) = 5 . 03 , p_<.03 were l i n k e d t o i n c r e a s e d l a t e n c i e s . The median a m p l i t u d e s a s s o c i a t e d w i t h 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 a r e c o n t a i n e d i n T a b l e 4. Two-way ANOVAs w i t h r e p e a t e d m e asures on d i r e c t i o n were p e r f o r m e d . T h e r e were no d i f f e r e n c e s i n t h e s i z e o f t h e movements p r o d u c e d by t h e two g r o u p s , F (1 , 40) =0 . 00 , p_<.97. R i g h t w a r d eye movements were of g r e a t e r a m p l i t u d e , F (1,40)=8.74, p_<c.0l. S i m i l a r ANOVAs f o r t h e median r e s p o n s e d u r a t i o n measure y i e l d e d no main e f f e c t f o r g r o u p , F(1,40)=.68, p_<.44. T h e r e were no d i f f e r e n c e s f o u n d between t h e a t - r i s k and t h e n o r m a l T a b l e 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 ( R ) o r L e f t ( L ) Eye Movements a b a L a t e n c y A m p l i t u d e D u r a t i o n G roup R L R L R L H u n t i n g t o n 227 236 20.45 -20.72 1 13 1 1 1 (32) (53) (2.4) (4.1 ) (7) (11) A t - R i s k 223 209 1 9.70 -19.18 96 97 (35) (31 ) (1.7) (1.6) (6) (5) C o n t r o l 221 212 19.61 -19.21 92 92 (27) (24) (1.5) ( 1.3) (14) (13) 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 m i l l i s e c o n d s . b V a l u e s a r e i n d e g r e e s of v i s u a l a r c . 55 c o n t r o l g r o u p s , i n t h e d u r a t i o n of t h e i r s a c c a d i c eye movements. M e d i a n d u r a t i o n s c o r e s were not a f f e c t e d by t h e d i r e c t i o n t h e e y e s were t r a c k i n g t h e t a r g e t , F ( 1 , 4 0 ) = . 1 5 , p_<.70. 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 i n any of t h e median l a t e n c y , median a m p l i t u d e , o r median r e s p o n s e d u r a t i o n a n a l y s e s . 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 A n a l y s e s Two-way a n a l y s e s o f v a r i a n c e w i t h g r o u p ( a t - r i s k , c o n t r o l ) and d i r e c t i o n of eye movement (upward, downward) as t h e two f a c t o r s were computed. T a b l e 5 c o n t a i n s t h e mean l a t e n c y and d u r a t i o n o f 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 . . E x a m i n i n g t h e median l a t e n c y t o o n s e t , no main e f f e c t by g r o u p was u n c o v e r e d , F ( 1 , 4 0 ) = . 6 2 , p_<.44. T h e r e was no s i g n i f i c a n t e f f e c t f o r d i r e c t i o n o f eye movements, F(1,40)=2.90, p_<.l0. The a n a l y s i s o f t h e median d u r a t i o n o f t h e s a c c a d i c eye movements showed t h a t t h e a t - r i s k and c o n t r o l g r o u p s p r o d u c e d movements of e q u a l d u r a t i o n , F (1 , 40 ) = 1 .89, p_<.l8. Eye movements i n t h e upward d i r e c t i o n were of l o n g e r d u r a t i o n , F( 1 , 40 ) =4 1 .24, p_<.0l . E l e c t r o d e r m a l D a t a A n a l y s e s D a t a from t w e n t y - n i n e a t - r i s k , t w e n t y - n i n e c o n t r o l s and s e v e n H u n t i n g t o n c h o r e a s u b j e c t s were examined. T h e r e were no v a r i a n c e p r o b l e m s a s s o c i a t e d w i t h t h e e l e c t r o d e r m a l d a t a t h a t would p r e c l u d e i n c l u d i n g t h e e a r l y H u n t i n g t o n g r o u p i n t h e e l e c t r o d e r m a l a n a l y s e s . T a b l e 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(U) and Down(D) Movements a a L a t e n c y D u r a t i o n Group U p_ U H u n t i n g t o n 269 239 90 91 (22) (38) (36) (15) A t - R i s k 226 220 95 73 (38) (48) (18) (13) C o n t r o l 235 198 89 69 (31) (48) (18) (14) 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 m i l l i s e c o n d s . 57 T o n i c S k i n C o n d u c t a n c e L e v e l A n a l y s e s E l e c t r o d e r m a l d a t a c o l l e c t e d from a t - r i s k , c o n t r o l and e a r l y H u n t i n g t o n c h o r e a s u b j e c t s were a n a l y z e d . A t h r e e way ANOVA w i t h r e p e a t e d measures on hand and t o n e t r i a l s a s f a c t o r s was u n d e r t a k e n t o examine s k i n c o n d u c t a n c e l e v e l t o th e s o f t t o n e s . T a b l e 6 c o n t a i n s t h e means f o r t h e s k i n c o n d u c t a n c e l e v e l s t o t h e s o f t t o n e s . T h e r e was no s i g n i f i c a n t e f f e c t of g r o u p , F(2,47)=1.23, £ < . 3 0 . As e x p e c t e d , t h e r e was an o r d e r e f f e c t on t h e t o n e s , F (1.53,88.8) = 12 . 28, p<.01, e=.27, w i t h s k i n c o n d u c t a n c e l e v e l d r o p p i n g p r o g r e s s i v e l y as s u b j e c t s l i s t e n e d t o a l l e i g h t s o f t t o n e s . T h e r e were no l a t e r a l i t y d i f f e r e n c e s , F(1,47)=2.78, p_<. 1 1 ; s k i n c o n d u c t a n c e l e v e l s were s i m i l a r a c r o s s t h e l e f t and r i g h t h a n d s . The r e s t i n g o r t o n i c s k i n c o n d u c t a n c e l e v e l t o l o u d t o n e s was examined u s i n g a s i m i l a r t h r e e - w a y r e p e a t e d measures a n a l y s i s o f v a r i a n c e , i n c l u d i n g g r o u p , hand and t o n e t r i a l s a s f a c t o r s . The t h r e e g r o u p s were f o u n d t o be s t r i c t l y c o m p a r a b l e , F ( 2 , 4 5 ) = . 7 4 , p_<.48. L a t e r a l i t y d i f f e r e n c e s a g a i n d i d n o t r e a c h s i g n i f i c a n c e , F ( 1 , 4 7 ) = 2 . 3 1 , p<.14. An o r d e r e f f e c t f o r t o n e s was f o u n d , F ( 3 . 3,155.1)=4.69, 2<.01, e=.30, i n d i c a t i n g t h a t s u b j e c t s r e s p o n d e d most t o t h e e a r l i e r t o n e s i n t h e s e q u e n c e . 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 i n any of 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 d a t a . T a b l e 7 c o n t a i n s t h e 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 t o t h e l o u d t o n e s . T a b l e 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 t o S o f t T o n e s ; R i g h t ( R ) and L e f t ( L ) Hands H u n t i n g t o n A t - R i s k C o n t r o l Tones R. L R L R L 1 4.73 3.85 3.10 2 .95 4.14 4.06 (3.72) (2.62) (2.54) (2 .53) (3.02) (2.66) 2 4.64 3.72 3.06 2 .85 4.16 4.12 (3.61) (2.56) (2.51) (2 .50) (3.07) (2.71 ) 3 4.63 3.65 2.92 2 .67 4.10 4.12 (3.48) (2.43) (2.46) (2 .49) (3.00) (2.79) 4 4.86 3.56 2.87 2 .60 3.89 3.93 (3.25) (2.31) (2.48) (2 .45) (2.79) (2.61) 5 4.42 3.62 • 2.79 2 .51 3.74 3.81 (3.13) (2.41) (2.47) (2 .37) (2.70) (2.57) 6 4.36 3.56 2.76 2 .56 3.63 3.69 (3.02) (2.29) (2.49) (2 .34) (2.64) (2.52) 7 4.30 3.52 2.70 2 .49 3.51 3.57 (2.93) (2.22) (2.46) (2 .31 ) (2.57) (2.48) 8 4.24 3.43 2.68 2 .45 3.43 3.49 (2.96) (2.17) (2.49) (2 .27) (2.52) (2.43) Mean 4.52 3.61 2.86 2 .64 3.83 3.85 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 r e p o r t e d a r e i n micromhos. 59 T a b l e 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 t o Loud T o n e s ; R i g h t ( R ) and L e f t ( L ) Hands H u n t i n g t o n A t - R i s k C o n t r o l T o n es R L R L R L 1 4.50 (3.46) 3.65 (2.44) 3.07 (2.56) 2.78 (2.33) 3.80 (3.08) 3.82 (2.83) 2 4.55 (3.51 ) 3.70 (2.45) 3.47 (2.65) 3.15 (2.38) 4.21 (3.44) 4.21 (3.22) 3 4.54 (3.48) 3.66 (2.46) 3.47 (2.74) 3.19 (2.49) 4.45 (3.58) 4.28 (3.25) 4 4.38 (3.33) 3.62 (2.40) 3.52 (2.80) 3.19 (2.52) 4.42 (3.57) 4.28 (3.29) 5 4.20 (3.04) 3.47 (2.20) 3.33 (2.62) 3.06 (2.40) 4.26 (3.50) 4.20 (3.29) 6 4.17 (2.93) 3.45 (2.16) 3.31 (2.58) 3.03 (2.34) 4.24 (3.47) 4. 18 (3.31) 7 4.10 (2.85) 3.42 (2.15) 3.21 (2.53) 2.93 (2.28) 4.15 (3.56) 4.20 (3.36) 8 4.06 (2.78) 3.36 (2.09) 3.11 (2.53) 2.82 (2.24) 4.04 (3.42) 4.11 (3.30) 9 4.04 (2.72) 3.36 (2.10) 3.10 (2.55) 2.81 (2.24) 3.97 (3.38) 4.05 (3.29) 10 4.04 (2.79) 3.40 (2.15) 2.96 (2.39) 2.73 (2.21) 3.87 (3.30) 3.97 (3.25) 1 1 4.17 (2.72) 3.50 (2.22) 2.94 (2.30) 2.71 (2.21 ) 3.87 (3.32) 3.99 (3.27) 12 4.12 (2.71 ) 3.46 (2.20) 3.02 (2.56) 2.77 (2.30) 3.80 (3.22) 3.93 (3.22) Mean 4.52 3.61 2.. 86 2.64 3.83 3.85 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 r e p o r t e d a r e i n micromhos. 60 S k i n C o n d u c t a n c e Response (SCR) A n a l y s e s A t h r e e - w a y ANOVA w i t h r e p e a t e d measures on hand ( r i g h t and l e f t ) and s o f t t o n e t r i a l s (1 t o 8) was p e r f o r m e d w i t h SCR as t h e d e p e n d e n t v a r i a b l e . The means a r e p r e s e n t e d i n T a b l e 8. R e s u l t s i n d i c a t e d t h a t a l l t h r e e g r o u p s r e s p o n d e d s i m i l a r l y t o t h e s e r i e s of s o f t t o n e s t h e y h e a r d , F ( 2 , 4 7 ) = . 4 9 , p_<.53. T h e r e was an o r d e r e f f e c t on t h e t o n e s , F ( 2 . 5 2 , 1 18.4) = 6.03, p_<. 01 , e=.36, i n t h a t s u b j e c t s i n a l l g r o u p s t e n d e d t o r e s p o n d l e s s t o t h e l a t e r t o n e s t h a n t o t h e e a r l i e r t o n e s . T h e r e were no d i f f e r e n c e s between t h e hands i n terms o f d e g r e e of r e s p o n s i v i t y , F ( 1 , 4 7 ) = . 5 9 , p_<.45. See F i g u r e 6. A s e c o n d t h r e e - w a y r e p e a t e d measures a n a l y s i s of v a r i a n c e , w i t h t h e same f a c t o r s as i n t h e p r e v i o u s a n a l y s i s , r e v e a l e d no 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 n t h e i r r e s p o n s i v i t y t o l o u d t o n e s , F (2,47)=.56, p_<.58. Th e s e means a r e p r e s e n t e d i n T a b l e 9. T h e r e was no d i f f e r e n c e i n r e s p o n s i v i t y a c r o s s t h e hands, F ( 1 , 4 7 ) = . 0 1 , p_<.9l. T o nes a g a i n e v i d e n c e d an o r d e r e f f e c t , F (2 . 3 1 ,1 08 . 6) = 7 . 41 , p_<.0l, e=.21, w i t h s u b j e c t s r e s p o n d i n g most t o t h e e a r l i e r t o n 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 p r e s e n t i n t h e SCR d a t a . P l e a s e r e f e r t o F i g u r e 7. T a b l e 8 a Means f o r 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 S o f t T o n e s ; R i g h t ( R ) and L e f t ( L ) Hands Hunt i n g t o n At - R i s k C o n t r o l Tones R L R L R L 1 0.19 (0.38) 0. 13 (0.23) 0.26 (0.45) 0.21 (0.36) 0. (0. 35 44) 0.37 (0.38) 2 0.03 (0.05) 0.02 (0.04) 0.14 (0.27) 0.09 (0.16) 0. (0. 19 31 ) 0.22 (0.32) 3 0.02 (0.04) 0.02 (0.04) 0.06 (0.15) 0.07 (0.19) 0. (0. 10 17) 0.14 (0.27) 4 0. 10 (0.23) 0.05 (0.12) 0.05 (0.13) 0.04 (0.09) 0. (0 . 09 22) 0.10 (0.23) 5 0.05 (0.11) 0.05 (0.11) 0.03 (0.09) 0.02 (0.06) 0. (0. 04 11) 0.05 (0.13) 6 0.04 (0.12) 0.03 (0.08) 0.04 (0.15) 0.03 (0.09) 0. (0. 03 09) 0.03 (0.09) 7 0.07 (0.18) 0.04 (0.10) 0.04 (0.09) 0.04 (0.11) 0. (0. 03 1 1 ) 0.05 (0.13) 8 0.24 (0.58) 0.14 (0.34) 0.02 (0.09) 0.02 (0.12) 0. (0. 00 02) 0.01 (0.04) Mean 0.09 0.06 0.08 0.07 0. 10 0.12 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 r e p o r t e d a r e i n micromhos. MAGNITUDE OF SKIN CONDUCTANCE RESPONSES ELICITED BY SOFT TONES, COLLAPSED OVER HANDS #^.-,W» HUNTINGTONS f'< — - - • AT-RISK Pfwwwf CONTROLS SOFT TONES T a b l e 9 a Means f o r S k i n C o n d u c t a n c e Response t o Loud T o n e s ; R i g h t ( R ) and L e f t ( L ) Hands Hunt i n g t o n At - R i s k C o n t r o l Tones R L R L R L 1 0.65 (1.02) 0.49 (0.64) 0.75 (1.15) 0.70 (0.98) 0.87 (0.42) 0.79 (1.14) 2 0.37 (0.62) 0.27 (0.33) 0.50 (0.70) 0.50 (0.57) 0.50 (0.69) 0.57 (0.63) 3 0.32 (0.38) 0.28 (0.30) 0.39 (0.65) 0.45 (0.64) 0.43 (0.57) 0.48 (0.59) 4 0.15 (0.14) 0.14 (0.14) 0.29 (0.55) 0.41 (0.62) 0.25 (0.43) 0.27 (0.38) 5 0.30 (0.44) 0.24 (0.33) 0.30 (0.53) 0.39 (0.66) 0.26 (0.36) 0.26 (0.32) 6 0.18 (0.18) 0.15 (0.15) 0.17 (0.52) 0.23 (0.56) 0.18 (0.21) 0.21 (0.21) 7 0.07 (0.04) 0.07 (0.04) 0.17 (0.43) 0.27 (0.53) 0.15 (0.16) 0.16 (0.18) 8 0.12 (0.10) 0.12 (0.12) 0.17 (0.45) 0.20 (0.46) 0.18 (0.24) 0.21 (0.30) 9 0.10 (0.06) 0.08 (0.03) 0.09 (0.35) 0. 10 (0.30) 0.19 (0.29) 0.18 (0.27) 10 0.31 (0.53) 0.30 (0.52) 0.14 (0.48) 0.18 (0.52) 0.15 (0.18) 0.15 (0.18) 1 1 0.22 (0.41 ) 0.23 (0.41) 0.01 (0.20) 0.07 (0.35) 0.11 (0.13) 0.10 (0.12) 1 2 0.11 (0.15) 0.10 (0.11) 0.05 (0.25) 0.07 (0.25) 0.12 (0.14) 0.14 (0.15) Mean 0.24 0.21 0.25 0.30 0.28 0.29 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 r e p o r t e d a r e i n micromhos. MAGNITUDE OF SKIN CONDUCTANCE RESPONSES ELICITED BY LOUD TONES, COLLAPSED OVER HANDS. LOUD TONES 65 T a b l e 10 Number o f N o n r e s p o n d e r s t o S o f t ( S ) and L o u d ( L ) Tones G r o u p Non- R e s p o n d e r s R e s p o n d e r s Hunt i n g t o n A t - r i sk C o n t r o l 0 (0) 7 (100) 2 (28.6) 5 (71.4) 1 3 (3.4) (10.3) 28 26 0 (0) 29 (96.6) (89.7) (100) 8 (27.6) 21 (72.4) N o t e . The v a l u e s i n p a r e n t h e s e s d e s c r i b e t h e p e r c e n t a g e of r e s p o n d e r s o r n o n r e s p o n d e r s w i t h i n e a c h g r o u p . 66 N o n r e s p o n d e r s The number of n o n - r e s p o n d e r s t o s o f t and l o u d t o n e s i s p r e s e n t e d i n T a b l e 10. C o m b i n i n g t h e d a t a f o r t h e l e f t and r i g h t hands, i t can be seen t h a t o n l y one i n d i v i d u a l (an a t - r i s k s u b j e c t ) was a n o n r e s p o n d e r t o t h e e i g h t s o f t t o n e s . T h e r e were more n o n r e s p o n d e r s t o t h e t w e l v e l o u d t o n e s : t h r e e a t - r i s k , e i g h t n o r m a l c o n t r o l and two H u n t i n g t o n s u b j e c t s . N e a r l y o n e - t h i r d o f b o t h t h e H u n t i n g t o n and t h e n o r m a l c o n t r o l s u b j e c t s d i d n o t r e s p o n d t o t h e l o u d t o n e s . The SCR d a t a f o r t h e l o u d t o n e s were s u b j e c t e d t o a P e a r s o n c h i s q u a r e a n a l y s i s w i t h two d e g r e e s o f f r e e d o m , x 2 = 3.05, p_<.22, i n d i c a t i n g t h a t g r o u p membership c o u l d n o t be p r e d i c t e d from whether an i n d i v i d u a l 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 . H a b i t u a t i o n A n a l y s e s The a n a l y s e s of t h e h a b i t u a t i o n r a t e r e v e a l e d 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 number of t r i a l s s u b j e c t s r e q u i r e d t o r e a c h h a b i t u a t i o n i e . t o s t o p r e s p o n d i n g . The d a t a 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 of v a r i a n c e ( g r o u p x hands x t o n e l o u d n e s s ) . The g r o u p e f f e c t was n o n s i g n i f i c a n t , F ( 2 , 4 4 ) = . 1 0 , p_<.90. None of t h e main o r i n t e r a c t i o n e f f e c t s was s i g n i f i c a n t e x c e p t t h e t o n e l o u d n e s s e f f e c t w h i c h was s i g n i f i c a n t F ( 1 ,44)=18.98, £ < . 0 1 . The mean number of t r i a l s b e f o r e h a b i t u a t i o n was r e a c h e d a r e g i v e n i n T a b l e 11 f o r e a c h g r o u p . 67 T a b l e 11 Mean Number of T r i a l s t o H a b i t u a t i o n t o S o f t and Loud T o n e s ; R i g h t ( R ) and L e f t ( L ) Hand's Gr o u p Hunt i n g t o n A t - R i s k C o n t r o l Tones R L R L R L S o f t 3.14 2.86 2.28 2.03 . 2.37 2.50 Loud 3.43 5.00 6.66 6.31 5.73 5.87 68 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 (SSCR) A n a l y s e s The mean number of SSCRs p e r t o n e d u r i n g t h e p r e s e n t a t i o n of t h e s o f t and l o u d t o n e s was c a l c u l a t e d and i s g i v e n i n T a b l e 12. A t h r e e - w a y ( g r o u p x hand x t o n e l o u d n e s s ) a n a l y s i s of v a r i a n c e was computed. T h e r e were no s i g n i f i c a n t e f f e c t s o f g r o u p , F ( 2 , 4 4 ) =2.20, p_<.l2, o f hand, F(1,44)=1.41, p<.24, or of t o n e l o u d n e s s , F ( 1 , 4 4 ) = . 6 0 , p_<.44. None of t h e i n t e r a c t i o n e f f e c t s was s i g n i f i c a n t . L a t e n c y of R e s p o n s e A n a l y s e s L a t e n c y of r e s p o n s e was a n a l y s e d by a t h r e e way a n a l y s i s o f v a r i a n c e w i t h g r o u p , hand, and t o n e l o u d n e s s a s f a c t o r s . None of t h e main o r i n t e r a c t i o n e f f e c t s was s i g n i f i c a n t . The g r o u p e f f e c t was F(2,44)=.40, p<.67. The hand e f f e c t was F( 1,44) = .48, p_<.50. The t o n e l o u d n e s s e f f e c t was F( 1 ,44)=3.91 , p_<.06. D a t a A n a l y s e s R e l a t i n g t o t h e Sound S t i m u l i : Dog & T e l e t y p e T a b l e 13 c o n t a i n s t h e means f o r s k i n c o n d u c t a n c e l e v e l and t h e means f o 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 t o t h e sound s t i m u l i . T o n i c s k i n c o n d u c t a n c e l e v e l (SCL) was a s s e s s e d t h r o u g h a t h r e e way a n a l y s i s o f v a r i a n c e w i t h g r o u p , hand, and s t i m u l u s as f a c t o r s . The s t i m u l u s f a c t o r had two l e v e l s c o r r e s p o n d i n g t o t h e dog and t e l e t y p e s t i m u l i . SCL was e q u i v a l e n t a c r o s s t h e g r o u p s ; F ( 2 , 4 4 ) = . 4 5 , £ < . 6 4 . The hand e f f e c t was a l s o n o n s i g n i f i c a n t ; F (1,44)=2.02, £ < . 1 6 . The s t i m u l u s f a c t o r , however, d i d r e s u l t i n a s i g n i f i c a n t e f f e c t ; F( 1 , 44)=9.87 , p_<.0l, i n d i c a t i n g t h a t s u b j e c t s i n a l l g r o u p s 69 T a b l e 12 Mean Number o f 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 o S o f t and Loud Tones i n t h e R i g h t ( R ) and L e f t ( L ) Hands Gr o u p Hunt i n g t o n A t - R i sk C o n t r o l Tones R L R L R L S o f t .554 .518 .233 .224 .175 .171 Loud .667 .631 .284 .256 .186 .206 N o t e . A l l v a l u e s a r e measured i n micromhos. 70 T a b l e 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 ( S C L ) and F i r s t S k i n C o n d u c t a n c e Response(SCR) t o t h e Dog and T e l e t y p e S t i m u l i ; R i q h t ( R ) and L e f t ( L ) Hands a a SCL SCR Dog T e l e t y p e • Doq T e l e t y p e Group R L R L R L R L H u n t i n g t o n 5. 24 4. 35 5. 02 4. 02 0 .21 0 . 1 3 0 . 1 1 0. 08 ( 3 . 67) (2. 74) (3. 73) (2. 50) ( .28) ( . 15) ( .17) (. 11) A t - R i s k 4. 1 0 3. 70 3. 89 3. 46 0 .29 0 .31 0 .35 0. 37 ( 3 . 08) (2. 77) ( 3 . 00) (2. 62) ( .41 ) ( .46) ( .41 ) (. 55) C o n t r o l s 5. 31 5. 32 4. 85 5. 04 0 .35 0 .47 0 .40 0. 45 (4. 01 ) (3. 54) (3. 71 ) ( 3 . 47) ( .36) ( .47) ( .48) (. 55) 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 micromhos. 71 had h i g h e r r e s t i n g s k i n c o n d u c t a n c e s when t h e y were p r e s e n t e d w i t h t h e dog s t i m u l u s , t h a t i s , t h e f i r s t of t h e two sound s t i m u l i . None of t h e i n t e r a c t i o n e f f e c t s was s i g n i f i c a n t . A s i m i l a r t hree-way a n a l y s i s of v a r i a n c e was p e r f o r m e d w i t h r e s p e c t t o t h e 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 t o t h e s t i m u l i . No g r o u p d i f f e r e n c e s were f o u n d , F(2,44)=1.34, p_<.27. No o t h e r main o r i n t e r a c t i o n e f f e c t s were f o u n d t o be s i g n i f i c a n t . A n o t h e r t h r e e - w a y a n a l y s i s of v a r i a n c e r e v e a l e d t h a t t h e a t - r i s k , c o n t r o l and e a r l y H u n t i n g t o n c h o r e a g r o u p s were a l s o c o m p a r a b l e i n t h e s i z e o f t h e i r b i g g e s t r e s p o n s e t o t h e s t i m u l i , F ( 2 , 44) =. 67 , p_<.52. T h e r e were no s i g n i f i c a n t main o r i n t e r a c t i o n e f f e c t s a s s o c i a t e d w i t h t h e d a t a p e r t a i n i n g t o t h e b i g g e s t SCRs t o t h e s o u n d s . 72 D i s c u s s i o n The p u r p o s e of t h e p r e s e n t s t u d y was t o c o n d u c t an i n v e s t i g a t i o n o f t h e eye t r a c k i n g c a p a b i l i t i e s and t h e 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 of a t - r i s k and c o n t r o l p o p u l a t i o n s t o d e t e r m i n e whether 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 a sures c o u l d f u n c t i o n as 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 . In t h e a n a l y s e s r e l a t i n g t o t h e 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 p e r f o r m a n c e of t h e a t - r i s k and c o n t r o l s u b j e c t s , a 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 was f o u n d i n t h e phase l a g measure whereby a t - r i s k s u b j e c t s p u r s u e d t h e d o t w i t h t h e i r e y e s l a g g i n g f u r t h e r 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 c o n t r o l s u b j e c t s . The e y e s t y p i c a l l y l a g b e h i n d t h e t a r g e t i n n o r m a l t r a c k i n g . Good t r a c k e r s c a n f o l l o w a t a r g e t w i t h t h e i r e y e s l a g g i n g o n l y a l i t t l e b e h i n d t h e t a r g e t and w i t h o u t t h e need t o use c a t c h - u p s a c c a d e s t o c o r r e c t t h e p o s i t i o n o f t h e image on t h e r e t i n a . A l a r g e phase l a g was p r o d u c e d by some of t h e a t - r i s k s u b j e c t s when t h e t a r g e t moved a t i t s ' g r e a t e s t f r e q u e n c y , i n d i c a t i n g t h a t t h e i r eye t r a c k i n g p e r f o r m a n c e was d i f f e r e n t . The m o n i t o r t a s k was a s s o c i a t e d w i t h g r e a t e r phase l a g , as i n p r e v i o u s r e p o r t s ( s e e I a c o n o & K o e n i g , 1983). T h e r e were no d i f f e r e n c e s i n eye t r a c k i n g p e r f o r m a n c e on any of t h e h o r i z o n t a l o r v e r t i c a l s a c c a d i c t a s k s between t h e g r o u p s . A r e v i e w o f t h e l i t e r a t u r e i n d i c a t e d t h a t c h o r e i c s u b j e c t s have shown t h e g r e a t e s t i m p a i r m e n t i n t r a c k i n g v e r t i c a l l y moving t a r g e t s . T h i s f i n d i n g c o m b i n e d w i t h t h e f a c t t h a t s a c c a d i c t r a c k i n g i s g e n e r a l l y c o n s i d e r e d t h e most 73 s t r i n g e n t t e s t of eye t r a c k i n g a b i l i t y s h o u l d have p r o d u c e d t h e g r e a t e s t d i f f e r e n c e s between t h e g r o u p s . T h i s was not t h e c a s e . One p o s s i b i l i t y i s t h a t a d i f f e r e n c e between t h e g r o u p s on t h e l a t e n c y t o o n s e t measure may have been o b s c u r e d by t h e l a r g e v a r i a b i l i t y i n s a c c a d i c r e a c t i o n t i m e t h a t has been r e p o r t e d i n o t h e r r e s e a r c h w i t h c o n t r o l s u b j e c t s ( B a l o h & H o n r u b i a , 1976). W h i l e t h e c o n s i s t e n c y o f s a c c a d i c r e a c t i o n t i m e w i t h i n any p a r t i c u l a r s u b j e c t h as been e s t a b l i s h e d , a l a r g e v a r i a b i l i t y between s u b j e c t s c o u l d c o n f o u n d t h e d a t a . T h e r e was no d i r e c t i o n e f f e c t r e l a t e d t o t h e s a c c a d i c eye t r a c k i n g p e r f o r m a n c e s . The l i t e r a t u r e on eye t r a c k i n g i n H u n t i n g t o n ' s d i s e a s e s u g g e s t s t h a t c h o r e i c s u b j e c t s e x p e r i e n c e d i f f i c u l t i e s w i t h t a r g e t s moving upward. The d e f i c i e n c i e s i n t r a c k i n g upward v e r t i c a l s a c c a d e s r e p o r t e d i n t h e l i t e r a t u r e may r e f l e c t a q u a l i t a t i v e d i f f e r e n c e between c o n t r o l o r a t - r i s k s u b j e c t s and H u n t i n g t o n s u b j e c t s ' eye t r a c k i n g p e r f o r m a n c e . T h e r e were c o n s i s t e n t e f f e c t s o f d i r e c t i o n o f t r a c k i n g i n t h e h o r i z o n t a l eye movement t a s k 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 b o t h t r a c k e d more p o o r l y i n t h e r i g h t w a r d d i r e c t i o n on t h e SPEM t a s k s . The r i g h t w a r d s a c c a d i c t a s k s were a s s o c i a t e d w i t h i n c r e a s e d l a t e n c y and g r e a t e r a m p l i t u d e s . T h e s e g r e a t e r l a t e n c i e s and a m p l i t u d e s may r e f l e c t a h a b i t u a l p a t t e r n o f v i e w i n g ( f o r example, r e a d i n g t e x t s f r o m l e f t t o r i g h t ) i n t h e s u b j e c t s i n c l u d e d i n t h i s s t u d y . H o r i z o n t a l d i r e c t i o n o f eye movement d i d n o t d i f f e r e n t i a t e t h e g r o u p s i n 74 any way. The eye movement d a t a q u a n t i f i c a t i o n t e c h n i q u e s u s e d i n t h e p r e s e n t s t u d y may have worked a g a i n s t f i n d i n g g r e a t e 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 r e c o r d s of t h e a t - r i s k g r o u p as o n l y t h e b e s t 16 c y c l e s of t r a c k i n g were u s e d i n t h e d a t a a n a l y s i s . I t i s p o s s i b l e t h a t t h e a t - r i s k g r o u p w o u l d have p r o d u c e d a h i g h e r f r e q u e n c y o f eye t r a c k i n g e r r o r s had t h e f i r s t 16 c y c l e s been a n a l y z e d . However, t h i s i s m i t i g a t e d by t h e f a c t t h a t t h e c y c l e s were o n l y r e j e c t e d when some o b v i o u s e x t r a n e o u s f a c t o r was o p e r a t i n g on t h e s u b j e c t ' s p e r f o r m a n c e , and d u r i n g t h e s e c y c l e s t h e s u b j e c t c o u l d n o t be s a i d t o be a c t u a l l y t r a c k i n g . W h i l e t h e p r e s e n t r e s e a r c h does n o t p u r p o r t t o e x p l a i n s u c h d i f f e r e n c e s , i t i s c o n s i s t e n t w i t h p r e v i o u s l i t e r a t u r e p o i n t i n g t o i m p o v e r i s h e d eye t r a c k i n g p e r f o r m a n c e i n b r a i n damaged s u b j e c t s when compared t o o t h e r p s y c h i a t r i c s a m p l e s (Oscar-Berman, 1978; Oscar-Berman & Z o l a - M o r g a n , 1978). T h a t t h e HC s u b j e c t s t r a c k e d p o o r l y a c r o s s t h e b o a r d makes any c o n c l u s i o n s r e a c h e d c o n c e r n i n g t h e l i n k between t h e d e g e n e r a t i o n o f t h e b a s a l g a n g l i a and t h e p r o d u c t i o n o f i m p a i r e d eye movements l e s s p r e c i s e t h a n i f a s i n g l e t y p e o f eye t r a c k i n g d e f i c i t had been u n c o v e r e d . V i s u a l i n s p e c t i o n o f t h e d a t a i n d i c a t e d t h a t t h e p e r f o r m a n c e of t h e H u n t i n g t o n s u b j e c t s was v e r y d i f f e r e n t f r o m what would n o r m a l l y be p r o d u c e d on s u c h t a s k s . I t was c l e a r f r o m v i s u a l i n s p e c t i o n and from b l i n d 75 r a t i n g s t h a t t h e t r a c k i n g o f 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 and 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 were worse a t eye t r a c k i n g t a s k s t h a n p s y c h o t i c p a t i e n t s w i t h a f f e c t i v e and s c h i z o p h r e n i c d i s o r d e r s . The f a c t t h a t H u n t i n g t o n s u b j e c t s were p o o r e r t r a c k e r s on 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 t a s k s c e r t a i n l y a c c o r d s w i t h p r e v i o u s r e s e a r c h . The d i s c o v e r y of s e v e r e eye t r a c k i n g d e f i c i e n c i e s i n t h i s g r o u p i s p e r h a p s a l l t h e more i m p o r t a n t g i v e n t h a t t h e g r o u p was composed of h i g h f u n c t i o n i n g c h o r e i c s u b j e c t s . R e s e a r c h t o d a t e has f o c u s e d on h o s p i t a l i z e d , o r h e a v i l y s e d a t e d s u b j e c t p o p u l a t i o n s who a r e i n t h e m i d d l e o r l a t e s t a g e s of t h e d i s e a s e . W h i l e two of t h e s u b j e c t s i n t h i s sample were u s i n g i s o n i a z i d , none were i n g e s t i n g d r u g s w h i c h a r e known t o a d v e r s e l y a f f e c t eye t r a c k i n g . T h e r e has been t o d a t e no i n v e s t i g a t i o n of t h e p o s s i b l e l o n g o r s h o r t t e r m e f f e c t s of i s o n i a z i d on eye t r a c k i n g p e r f o r m a n c e . What i s most n o t i c e a b l e a b o u t t h e eye t r a c k i n g p e r f o r m a n c e of t h e H u n t i n g t o n s u b j e c t s i s t h a t no a s p e c t o f eye t r a c k i n g was u n a f f e c t e d i e . t h e g r o u p as a whole t r a c k e d c o n s i s t e n t l y p o o r l y on a l l t h e t a s k s , even t h e e a s i e s t o n e s . W h i l e i t i s t r u e t h a t t h e mean age f o r t h e H u n t i n g t o n g r o u p was h i g h e r t h a n t h e mean age f o r t h e c o n t r o l g r o u p , age p e r se c o u l d n o t a c c o u n t f o r t h e f r e q u e n c y and s e v e r i t y o f eye t r a c k i n g d e f i c i t s e n c o u n t e r e d i n t h e 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 s i n c e a v i s u a l c o m p a r i s o n w i t h t h e o l d e r c o n t r o l s u b j e c t s c l e a r l y showed t h a t t h e c h o r e i c s u b j e c t s were much 76 p o o r e r t r a c k e r s . The H u n t i n g t o n ' s g r o u p was, however, s i g n i f i c a n t l y more d e p r e s s e d t h a n b o t h 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 ; and t e n d e d t o be more a n x i o u s (as m easured by t h e STAI g e n e r a l form) t h a n t h e c o n t r o l g r o u p . I t c o u l d be a r g u e d t h a t t h e e x t r a n e o u s e f f e c t s of a n x i e t y o r d e p r e s s i o n may have a c c o u n t e d f o r t h e H u n t i n g t o n s u b j e c t s ' eye t r a c k i n g p e r f o r m a n c e . T h i s i s u n l i k e l y s i n c e none of t h e q u e s t i o n n a i r e s c o r e s r e a c h e d c l i n i c a l c u t o f f p o i n t s i e . w h i l e t h e H u n t i n g t o n g r o u p may e x p e r i e n c e more s t a t e a n x i e t y o r be s l i g h t l y more d e p r e s s e d , t h e e f f e c t s o f t h e s e f a c t o r s p e r se a r e not s t r o n g enough t o p r o d u c e s u c h h i g h l y d e v i a n t eye t r a c k i n g p a t t e r n s . I t i s l i k e l y t o o t h a t t h e s c o r e s f o r t h e H u n t i n g t o n g r o u p were i n f l a t e d on t h e s e p a r t i c u l a r q u e s t i o n n a i r e s s i n c e as m e n t i o n e d p r e v i o u s l y , t h e r e a r e i t e m s on t h e q u e s t i o n n a i r e s t h a t t a p i n t o t h e s y m p t o m a t o l o g y o f H u n t i n g t o n ' s c h o r e a . A p o s s i b l e a l t e r n a t e e x p l a n a t i o n i s t h a t t h e eye t r a c k i n g d e f i c i t s e n c o u n t e r e d i n t h i s p o p u l a t i o n a r e not r e l a t e d t o t h e p r e s e n c e o f t h e HC gene so much as t h e y a r e s e c o n d a r y t o H u n t i n g t o n ' s d i s e a s e . T h a t i s , t h e poor eye t r a c k i n g c o u l d be a r e s u l t of t e m p o r a r y l a p s e s i n a t t e n t i o n , or d i f f i c u l t y remembering i n s t r u c t i o n s p e r t i n e n t t o t h e t a s k , s i n c e s h o r t t e r m memory p r o b l e m s and a t t e n t i o n a l d e f i c i t s a r e common t o many 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 ( W e x l e r , 1979; W i l s o n & G a r r o n , 1973; O s c a r - B e r m a n , 1978). The p r e s e n t r e s e a r c h a t t e m p t e d t o c o n t r o l f o r a t t e n t i o n a l d e f i c i t s by p r o v i d i n g 77 s u b j e c t s w i t h p r e c i s e i n s t r u c t i o n s and g i v i n g them m o n i t o r eye t r a c k i n g t a s k s t h a t r e q u i r e d p a y i n g c l o s e a t t e n t i o n t o t h e t a r g e t . In a d d i t i o n , o n l y 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 d i s e a s e were t e s t e d , m i n i m i z i n g t h e e f f e c t of c o g n i t i v e i m p a i r m e n t s . S i m p l e momentary i n a t t e n t i o n does n o t , m o r e o v e r , l e a d t o h i g h l y i m p a i r e d o r d e f i c i e n t smooth p u r s u i t t r a c k i n g movements ( P a s s , S a l z m a n , K l o r m a n , K a s k e y & K l u n , 1978). The p o o r t r a c k i n g c a n n o t be t r a c e d t o p o o r m o t i v a t i o n o r d i s i n t e r e s t i n t h e t a s k s as t h e s e i n d i v i d u a l s as a g r o u p gave e f f o r t f u l r e s p o n s e s t o t a s k s t h e y were p r e s e n t e d w i t h . I t i s l i k e l y t h a t t h e eye t r a c k i n g d e f i c i e n c i e s r e l a t e s p e c i f i c a l l y t o t h e p r e m a t u r e n e u r o n a l d e g e n e r a t i o n o c c u r r i n g i n t h e b a s a l g a n g l i a o f t h e c h o r e i c s u b j e c t s . T h i s s t u d y compared 29 a t - r i s k and 29 c o n t r o l s u b j e c t s on eye t r a c k i n g p e r f o r m a n c e measured a c r o s s v a r i o u s t a s k s , a t d i f f e r e n t f r e q u e n c i e s . The p e r f o r m a n c e s of t h e a t - r i s k g r o u p i n t h e s t u d y was g e n e r a l l y s i m i l a r t o t h a t o f t h e c o n t r o l g r o u p i n b o t h t h e v e r t i c a l smooth p u r s u i t and t h e h o r i z o n t a l and 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 t a s k s t h a t were c o m p l e t e d . T h e r e were two s t a t i s t i c a l l y 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 w h i c h i n d i c a t e d t h a t some a t - r i s k s u b j e c t s t r a c k e d d i f f e r e n t l y f r o m t h e c o n t r o l s . T hese were r e l a t e d t o h o r i z o n t a l SPEM a t h i g h t a r g e t f r e q u e n c i e s . The f i n d i n g s o f t h i s s t u d y t h u s d e p a r t r a d i c a l l y from what may have been t h e o r e t i c a l l y e x p e c t e d i f eye t r a c k i n g d e f i c i e n c i e s were f u n c t i o n i n g a s a marker f o r H u n t i n g t o n ' s c h o r e a e x c e p t i n t h e 78 h o r i z o n t a l SPEM t r a c k i n g a t h i g h t a r g e t f r e q u e n c i e s . The f i n d i n g s o f t h i s s t u d y a r e a l s o c o n t r a r y t o what may have been e x p e c t e d from p r e v i o u s r e p o r t s i n t h e l i t e r a t u r e r e g a r d i n g s a c c a d i c eye t r a c k i n g t a s k s and s u b j e c t s a t - r i s k f o r HC. The d i f f e r e n t r e s u l t s of t h e c u r r e n t s t u d y c o u l d stem from many s o u r c e s i n c l u d i n g s a m p l i n g v a r i a t i o n s , d i a g n o s t i c u n r e l i a b i l i t y , and d i f f e r e n c e s i n t h e t e c h n i q u e s u t i l i z e d t o r e c o r d t h e eye movements. The r e c o r d i n g t e c h n i q u e s of t h e p r e s e n t s t u d y c e r t a i n l y d i f f e r s f r o m t h a t u s e d i n P e t i t e t a l . (1971) who u s e d c o r n e a l l e n s e s . T h i s s t u d y , however, overcame many of t h e p r o b l e m s a s s o c i a t e d w i t h p r e v i o u s r e p o r t s i n m e a s u r i n g eye t r a c k i n g d e f i c i e n c e s by u s i n g s t a n d a r d i z e d r e c o r d i n g p r o c e d u r e s and a n a l y s e s t h a t have been shown t o be r e l i a b l e and v a l i d i n d i c a t o r s o f t r a c k i n g a b i l i t y ; as w e l l as by t e s t i n g a l a r g e r g r o u p o f s u b j e c t s a t - r i s k on a v a r i e t y of t r a c k i n g t a s k s . I t i s p o s s i b l e t h a t s u b j e c t v a r i a b i l i t y e x e r t e d an e f f e c t on t h e s a c c a d i c d u r a t i o n and a m p l i t u d e m e a s u r e s , as 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 were t h e most d i f f i c u l t f o r t h e s u b j e c t s t o p e r f o r m . An a l t e r n a t e e x p l a n a t i o n c o u l d be t h a t SPEM d e f i c i t s a r e t h e f i r s t t o a p p e a r 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 of c h o r e i c s u b j e c t s . One argument a g a i n s t t h i s i s t h a t t h e s a c c a d i c eye t r a c k i n g s y s t e m r e q u i r e s g r e a t e r p r e c i s i o n and a c c u r a c y t o . f u n c t i o n t h a n t h e smooth p u r s u i t t r a c k i n g s y s t e m b e c a u s e t h e f o r m e r i n v o l v e s h i g h v e l o c i t i e s . F u r t h e r s t u d y would be r e q u i r e d t o d e t e r m i n e t h e v a l i d i t y of t h i s s t a t e m e n t . 79 As c o n c e r n s t h e e l e c t r o d e r m a l m e a s u r e s , i t i s a p p a r e n t t h a t t h e d a t a do not s u p p o r t t h e h y p o t h e s e s g e n e r a t e d by a r e v i e w of t h e 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 and s k i n c o n d u c t a n c e r e s p o n s i v i t y . The a t - r i s k and t h e H u n t i n g t o n groups, gave as many r e s p o n s e s as d i d t h e normal c o n t r o l g r o u p when p r e s e n t e d w i t h an a r r a y of a u d i t o r y s t i m u l i w h i c h i n c l u d e d e i g h t s o f t (85 db) t o n e s , t w e l v e l o u d (105 db) t o n e s , a dog b a r k i n g and a t e l e t y p e . In a d d i t i o n , when r e s p o n s e a m p l i t u d e was examined, no d i f f e r e n c e s i n t h e s i z e 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 was e v i d e n t , between t h e t h r e e g r o u p s . A l t h o u g h t h e r e were no 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 n SCR a m p l i t u d e , t h e H u n t i n g t o n g r o u p gave s m a l l e r r e s p o n s e s t o t h e two s e t s of t o n e s as w e l l a s t o t h e dog and t h e t e l e t y p e s o u n d s . The mean r e s p o n s i v i t y o f t h e a t - r i s k g r o u p f e l l between t h e mean s c o r e s f o r t h e c o n t r o l s and t h e H u n t i n g t o n g r o u p s . W h i l e t h e r e were no 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 , t h e p a t t e r n o f 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 was as e x p e c t e d . The c o m p a r a b i l i t y o f t h e s e SCR measures r e s t e d i n p a r t on t h e su b j e c t s . ' t o n i c s k i n c o n d u c t a n c e l e v e l s , s i n c e h i g h SCLs a r e l i n k e d t o l a r g e r SCRs and t o a s l o w e r h a b i t u a t i o n r a t e . The a n a l y s e s o f SCL i n d i c a t e d t h a t a l l g r o u p s e x h i b i t e d s i m i l a r t o n i c l e v e l s . The r a t e o f h a b i t u a t i o n was c o m p a r a b l e i n t h e t h r e e g r o u p s . T h e r e was no 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 a t - r i s k g r o u p w o u l d c o n t a i n a g r e a t e r p e r c e n t a g e of f a s t 80 h a b i t u a t o r s t h a n t h e c o n t r o l g r o u p . The H u n t i n g t o n s u b j e c t s were not f a s t h a b i t u a t o r s , as w o u l d have been e x p e c t e d from e a r l i e r r e s e a r c h f i n d i n g s . The H u n t i n g t o n s u b j e c t s i n f a c t were t h e s l o w e s t t o h a b i t u a t e t o t h e l o u d t o n e s , a l t h o u g h t h e i r r a t e of h a b i t u a t i o n was 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 from t h e r a t e s of t h e two o t h e r g r o u p s . A g r e a t e r number o f t r i a l s t o h a b i t u a t i o n has been l i n k e d t o b r a i n - d a m a g e d p o p u l a t i o n s i n some s t u d i e s but not i n o t h e r s ( S t e r n & J a n e s , 1973). The slow h a b i t u a t i o n o f t h e s u b j e c t s t o t h e l o u d t o n e s may have e n s u e d b e c a u s e t h e l o u d t o n e s were l o u d enough t o p r o v o k e s t a r t l e r e a c t i o n s o r l a r g e r r e s p o n s e a m p l i t u d e s t h a n what would n o r m a l l y be e x p e c t e d . An e x a m i n a t i o n o f t h e h a b i t u a t i o n r a t e s o f t h e g r o u p s r e v e a l e d t h a t t h e s u b j e c t s t o o k on a v e r a g e 3.43 t o 6.66 t o n e t r i a l s , t o h a b i t u a t e t o t h e l o u d t o n e s . T h i s i s l o n g e r , f o r example, t h a n t h e HC s u b j e c t s i n t h e O scar-Berman & Gade (1980) s t u d y . The H u n t i n g t o n s u b j e c t s who t o o k p a r t i n t h e p r e s e n t r e s e a r c h a r e however n o t t r u l y c o m p a r a b l e t o t h e s u b j e c t s s e e n by Lawson o r by O s c a r - Berman & Gade. The l a t t e r two s t u d i e s b o t h examined h o s p i t a l i z e d HC p a t i e n t s . In a d d i t i o n , t h e Lawson r e s e a r c h s u b j e c t s were t a k i n g m e d i c a t i o n t o c o n t r o l f o r c h o r e i c movements. The r e s u l t s o f t h e p r e s e n t s t u d y d e p a r t as w e l l f r o m t h a t r e p o r t e d by Lawson (1981) i n t e r m s o f t h e r e s u l t s o b t a i n e d w i t h t h e a t - r i s k s u b j e c t s . The m e t h o d o l o g i c a l p r o c e d u r e s employed i n t h e Lawson s t u d y were n o t s t r i c t l y c o m p a r a b l e t o 81 t h o s e p r o c e d u r e s u s e d i n t h e p r e s e n t s t u d y as Lawson t e s t e d s u b j e c t s on p o r t a b l e p o l y g r a p h equipment i n t h e i r homes. Such f i e l d s t u d i e s c a n n o t c o n t r o l f o r e x t r a n e o u s v a r i a b l e s s u c h as room t e m p e r a t u r e and h u m i d i t y w h i c h a r e known t o a f f e c t b o t h SCL and SCR m e a s u r e s . T h e r e were fewer a t - r i s k s u b j e c t s who n e v e r r e s p o n d e d t o t h e t o n e s t h a n t h e r e were c o n t r o l s u b j e c t s who were n o n r e s p o n d e r s . A t h i r d of b o t h t h e H u n t i n g t o n and t h e c o n t r o l s u b j e c t s d i d n o t r e s p o n d t o t h e l o u d t o n e s ; t h i s i s u n u s u a l i n t h a t l o u d e r t o n e s a r e more l i k e l y t o e l i c i t a r e s p o n s e t h a n s o f t e r t o n e s . T h i s f i g u r e i s a l s o much h i g h e r t h a n t h e 7% base r a t e o f n o n r e s p o n d e r s t h a t has been f o u n d i n c o n t r o l p o p u l a t i o n s . I a c o n o e t a l . , (1983) have however f o u n d t h a t 24% of t h e i r c o n t r o l s u b j e c t s were n o n r e s p o n d e r s t o a s e r i e s o f s e v e n t e e n t o n e s . A p l a u s i b l e e x p l a n a t i o n f o r s u c h a r e s u l t i s t h a t t h e r e was an e f f e c t of t h e i n s t r u c t i o n s g i v e n t o t h e s u b j e c t s on t h e i r r e s p o n s i v i t y . S u b j e c t s were t o l d t o i g n o r e t h e t o n e s and g i v e n b r i e f r e l a x a t i o n i n s t r u c t i o n s b e f o r e t h e t o n e s were p r e s e n t e d t o them. T h i s a t t e m p t t o c o n t r o l f o r 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 t h e s i g n i f i c a n c e s u b j e c t s a s s i g n t o e s s e n t i a l l y m e a n i n g l e s s t o n e s may have dampened r e s p o n s i v i t y as s u b j e c t s p o s s i b l y d i d i n d e e d r e l a x and i g n o r e t h e t o n e s . I a c o n o & L y k k e n ( 1 9 8 3 ) , i n a r e c e n t s t u d y on t h e r o l e of i n s t r u c t i o n s on 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 p o r t s u b j e c t s r e q u i r e d t o i g n o r e t o n e s as t h e y h e a r d a t a p e d s t o r y gave fewer t o n e - 82 e l i c i t e d r e s p o n s e s and t h a t t h e s e were of s m a l l e r m a g n i t u d e t h a n t h o s e r e s p o n s e s g i v e n by s u b j e c t s w i t h n e u t r a l i n s t r u c t i o n s o r s u b j e c t s r e q u i r e d t o a t t e n d c a r e f u l l y t o t h e s t o r y . Thus t h e need t o c o n t r o l f o r t h e s i g n i f i c a n c e s u b j e c t s a s s i g n e d t o t h e t o n e s may have l e d t o more a t t e n u a t e d r e s p o n s e s . T h i s does not e x p l a i n why t h e r e were more n o n r e s p o n d e r s t o t h e l o u d t o n e s i n p a r t i c u l a r . Nor does i t e x p l a i n why more a t - r i s k s u b j e c t s were r e s p o n d i n g . T h i s c u r i o u s f i n d i n g was l i m i t e d i n i n t e r e s t i n t h e s e n s e t h a t t h e r e were a f t e r a l l no 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 n e i t h e r r e s p o n s i v i t y o r i n t e r m s of a c t u a l numbers of n o n r e s p o n d e r s . W h i l e l a t e r a l i t y was not a f o c u s of t h i s r e s e a r c h , i t was i n t e r e s t i n g t o n o t e t h a t t h e r e were no 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 h a n d s . The g r o u p s were e q u a l l y r e s p o n s i v e i n b o t h h ands. R e s e a r c h w i t h c o n t r o l and o t h e r p s y c h i a t r i c o r b r a i n - damaged p o p u l a t i o n s have o c c a s i o n a l l y f o u n d t h a t e l e c t r o d e r m a l a c t i v i t y i s g r e a t e r i n t h e r i g h t hand ( B e l l , M e d n i c k , G o t t e s m a n , & S e r g e a n t , 1976). T h i s s t u d y gave no s u p p o r t f o r g r e a t e r e l e c t r o d e r m a l a c t i v i t y i n t h e r i g h t hand. S u b j e c t s gave SCRs o f s i m i l a r a m p l i t u d e t o t h e dog and t h e t e l e t y p e . Group d i f f e r e n c e s were n o t s i g n i f i c a n t even t h o u g h t h e i n s t r u c t i o n s i m m e d i a t e l y p r i o r t o t h e o n s e t o f t h e two sounds r e q u i r e d s u b j e c t s t o pay c l o s e a t t e n t i o n as t h e y would be r e q u i r e d t o i d e n t i f y t h e sounds once t h e y were t e r m i n a t e d . The sounds were i n c l u d e d i n t h e s t u d y so t h a t a c o m p a r i s o n o f 83 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 c o u l d be made as t h e y r e s p o n d e d f i r s t t o a s e t o f m e a n i n g l e s s s t i m u l i ( t o n e s ) and t h e n t o a s e t of m e a n i n g f u l s t i m u l i ( f a m i l i a r s o u n d s ) . No e l u c i d a t i o n o f t h e r e l a t i o n between meaning and a t t e n t i o n — a s measured by e l e c t r o d e r m a l i n d i c e s - - c a n be made from t h e r e s u l t s of t h e p r e s e n t s t u d y . T h i s seems u n f o r t u n a t e s i n c e a t t e n t i o n a l d e f i c i t s have been f o u n d i n c h o r e i c s u b j e c t s i n th e p a s t . The p r e s e n t r e s e a r c h does not c o n t r i b u t e a d d i t i o n a l i n f o r m a t i o n a s t o t h e r o l e of a t t e n t i o n a l p r o c e s s e s a s measured by t h e 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 i n c e t h e g r o u p s were n o t d i f f e r e n t . I f a n y t h i n g t h i s s t u d y g i v e s l i t t l e s u p p o r t f o r t h e n o t i o n t h a t c h o r e i c s u b j e c t s a r e h y p o a r o u s e d , even t h o u g h t h e mean r e s p o n s i v i t y f o r t h e HC s u b j e c t s was t h e l o w e s t o f t h e t h r e e g r o u p s . T h i s f i n d i n g i s p e r h a p s a r e s u l t of t h e i n c l u s i o n o f c h o r e i c s u b j e c t s i n an e a r l i e r r a t h e r t h a n i n a more a d v a n c e d s t a g e o f H u n t i n g t o n ' s c h o r e a . A l i m i t a t i o n of t h e p r e s e n t s t u d y was t h e s m a l l sample s i z e of c h o r e i c s u b j e c t s . A l a r g e r sample s i z e w ould have had g r e a t e r power t o d i s c r i m i n a t e t h e g r o u p s 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 f o l l o w - u p s t u d y c o u l d i n c l u d e as w e l l , a g r e a t e r v a r i e t y of s t i m u l i t o p r e s e n t t o s u b j e c t s . An i n t e r e s t i n g a d d i t i o n would have been t h e use o f m e a n i n g f u l words, or phonemes as were u s e d i n t h e Lawson (1977) r e s e a r c h . Lawson's c o n c l u s i o n s r e g a r d i n g t h e f a s t h a b i t u a t i o n o f h e r H u n t i n g t o n s u b j e c t s were d e r i v e d from t h e r e s p o n s e s t h e s e s u b j e c t s gave 84 to verbal stimuli (phonemes) and not to neutral tone or sound st imuli. 85 R e f e r e n c e s Andre-Thomas M., A b e l y X., A j u r i a g u e r r a J . de, & E u l i e r L. ( 1 9 4 5 ) . T r o u b l e s d ' e l e v a t i o n des g l o b e s o c u l a i r e s dans un c a s de c h o r e e de H u n t i n g t o n . [ D i f f i c u l t i e s e n c o u n t e r e d i n r a i s i n g t h e o c u l a r g l o b e s i n a c a s e o f H u n t i n g t o n ' s c h o r e a ] . Revue N e u r o l o g i q u e , 77, 248-250. A v a n z i n i , G., G i r o t t i , F., C a r a c e n i , T., & S p r e a f i c o , R. ( 1 9 7 9 ) . O c u l o m o t o r d i s o r d e r s i n H u n t i n g t o n ' s c h o r e a . J o u r n a l o f N e u r o l o g y , N e u r o s u r g e r y and P s y c h i a t r y , 42, 581 — 589. B a c h - y - R i t a , P. ( 1 9 7 4 ) . S t r u c t u r a l - f u n c t i o n a l c o r r e l a t i o n s i n eye m u s c l e f i b e r s : Eye m u s c l e p r o p r i o c e p t i o n . In G. L e n n e r s t r a n d & P. B a c h - y - R i t a ( E d s . ) , B a s i c Mechanisms o f O c u l a r M o t i l i t y . P r o c e e d i n g s o f t h e Wenner-Gren I n t e r n a t i o n a l Symposium S e r i e s : V o l . 24 (pp. 9 1 - 1 0 8 ) . S t o c k h o l m : Pergamon P r e s s . B a l o h , W.R., & H o n r u b i a , V. (1976) R e a c t i o n t i m e and a c c u r a c y of t h e s a c c a d i c eye movements of n o r m a l s u b j e c t s i n a m o v i n g - t a r g e t t a s k . A v i a t i o n , S p ace, and E n v i r o n m e n t a l M e d i c i n e , 47, 1165-1167. B a l o h , W.R., L a n g h o f e r , L., H o n r u b i a , V., & Yee, R.D. ( 1 9 8 0 ) . O n - l i n e a n a l y s i s of eye movements u s i n g a D i g i t a l c o m p u t e r . A v i a t i o n , S p ace, and E n v i r o n m e n t a l M e d i c i n e , 47, 563-567. B a r b e a u , A., C h a s e, T.N., & P a u l s o n , G.W. ( E d s . ) . ( 1 9 7 3 ) . A d v a n c e s i n n e u r o l o g y : V o l . 1. H u n t i n g t o n ' s c h o r e a 1872- 1972. New Y o r k : Raven P r e s s . B a r o , F. ( 1 9 7 3 ) . A n e u r o p s y c h o l o g i c a l a p p r o a c h t o e a r l y d e t e c t i o n o f H u n t i n g t o n ' s c h o r e a . In A. B a r b e a u , T.N. C h a s e , & G.W. P a u l s o n ( E d s . ) , A d v a n c e s i n n e u r o l o g y : V o l . 1 . H u n t i n g t o n ' s c h o r e a 1872-1972 (pp. 3 2 9 - 3 3 5 ) . New Y o r k : Raven P r e s s . Beck, A.T., Ward, C.H., M e n d e l s o n , M., Mock, J . , & E r b a u g h , J . ( 1 9 6 1 ) . An i n v e n t o r y f o r m e a s u r i n g d e p r e s s i o n . A r c h i v e s of G e n e r a l P s y c h i a t r y , 4, 561-571. B e l l , B., M e d n i c k , S.A., G o t t e s m a n , I . I . , & S e r g e a n t , J . ( 1 9 7 7 ) . E l e c t r o d e r m a l p a r a m e t e r s i n male t w i n s . In S.A. Mednick & K.O. C h r i s t i a n s e n ( E d s . ) , B i o s o c i a l b a s e s of c r i m i n a l b e h a v i o r (pp. 2 1 7-225). New Y o r k : G a r d n e r P r e s s . 86 Bernstein, A.S., Taylor, K.W., & Weinstein, A. 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N e u r o n a l m o d els and t h e o r i e n t i n g r e f l e x . In M.A. B r a z i e r ( E d . ) , The C e n t r a l N e r v o u s System and B e h a v i o r . New Y o r k : Macy. S p i e l b e r g e r , CD.. G o r s u c h , R.L., & L u s h e n e , R.E. ( 1 9 7 0 ) . M a n u a l : 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 . P a l o A l t o : C o n s u l t i n g P s y c h o l o g i s t s P r e s s . S t a r r , A. ( 1 9 6 7 ) . A d i s o r d e r o f r a p i d eye movements i n H u n t i n g t o n ' s c h o r e a . B r a i n , 90, 545-564. S t e r n , J.A., & J a n e s , C L . ( 1 9 7 3 ) . P e r s o n a l i t y and p s y c h o p a t h o l o g y . I n W.F. P r o k a s y & D.C. R a s k i n ( E d s . ) , E l e c t r o d e r m a l a c t i v i t y i n p s y c h o l o g i c a l r e s e a r c h ( p p . 283- 3 4 6 ) . New Y o r k : Academic P r e s s . 93 S t e r n , J.A., Bremer, D.A., & M c C l u r e , J . ( 1 9 7 4 ) . A n a l y s i s of eye movements and b l i n k s d u r i n g r e a d i n g : E f f e c t s o f V a l i u m . P s y c h o p h a r m a c o l o g i a , 40, 171-175. Thompson, R.F., B e r r y , S.D., R i n a l d i , P.C., & B e r g e r , T.W. ( 1 9 7 8 ) . H a b i t u a t i o n and t h e o r i e n t i n g r e f l e x : The d u a l - p r o c e s s t h e o r y r e v i s i t e d . In H.D. Kimmel, E.H. Van O l s t , & J . F . O r l e b e k e ( E d s . ) , The o r i e n t i n g r e f l e x i n humans (pp. 2 1 - 6 0 ) . H i l l s d a l e , N . J . : Lawrence E r l b a u m A s s o c i a t e s V e n a b l e s , P.H. ( 1 9 7 7 ) . The e l e c t r o d e r m a l p h y s i o l o g y of s c h i z o p h r e n i c s and c h i l d r e n a t r i s k f o r s c h i z o p h r e n i a : C u r r e n t c o n t r o v e r s i e s and d e v e l o p m e n t s . S c h i z o p h r e n i a B u l l e t i n , 3, 28-48. von Noorden, G.K., & P r e z i o s i , T . J . ( 1 9 6 6 ) . Eye movement r e c o r d i n g s i n n e u r o l o g i c a l d i s o r d e r s . A r c h i v e s of O p t h a l m o l o g y , 76, 162-171. W e x l e r , N.S. ( 1 9 7 9 ) . P e r c e p t u a l - m o t o r , c o g n i t i v e and e m o t i o n a l c h a r a c t e r i s t i c s of p e r s o n 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 . In T.N. Chase, N.S. W e x l e r , & A. B a r b e a u ( E d s . ) , A d v a n c e s i n N e u r o l o g y : V o l . 23. H u n t i n g t o n ' s d i s e a s e (pp. 257-271) . New Y o r k : Raven P r e s s . W i l k i n s o n , I . , Kime, R., & P u r n e l l , M. ( 1 9 7 4 ) . A l c o h o l and human eye movement. B r a i n , 97, 785-792. W i l s o n , R.S., & G a r r o n , D.C. ( 1 9 7 9 ) . C o g n i t i v e and a f f e c t i v e a s p e c t s of H u n t i n g t o n ' s d i s e a s e . In T.N. C h a s e, N.S. W e x l e r & A. B a r b e a u ( E d s . ) , A d v a n c e s i n n e u r o l o g y : V o l . 23. H u n t i n g t o n ' s d i s e a s e (pp. 193-203). New Y o r k : Raven P r e s s . W i n e r , B . J . ( 1 9 7 1 ) . S t a t i s t i c a l p r i n c i p l e s i n e x p e r i m e n t a l d e s i g n ( I n t e r n a t i o n a l S t u d e n t E d i t i o n ) . T o k y o : M c G r a w - H i l l Kogakusha L t d . 94 R e f e r e n c e L i s t W i l l i a m G. 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. 95 APPENDIX A Huntington's Disease Family Research Project at the University of B r i t i s h Columbia At the University of B r i t i s h Columbia, we are conducting a study that w i l l aid in predicting who w i l l develop Huntington's Disease. We are taking this opportunity to inform you and your family members of this project and encourage your pa r t i c i p a t i o n . For nearly the past 10 years in research currently funded by the Medical Research Council of Canada, we have been s t r i v i n g to identify b i o l o g i c a l signs that can be used to predict who w i l l succumb to severe psychiatric and neurologi- cal disorders. Our goal is to develop techniques that w i l l aid in the diagnosis, treatment, and prevention of these diseases. We know that heredity plays an important role in il l n e s s e s which affect the brain and nervous system. We are combining this knowledge with recent findings that certain b i o l o g i c a l responses, which broadly tap brain functioning, are also genetically influenced. In other words, with regard to Huntington's Disease, we know HD i s a genetically-determined neurological i l l n e s s . We also know that certain b i o l o g i c a l responses which give a global picture of how the brain works are genetically influenced. Our plan i s to put these pieces of information together to determine i f we can use the genetically-determined brain responses to predict who has the HD gene. As you probably know* previous attempts to identify the HD gene prior to the onset of symptoms have been unsuccessful. You may wonder what we are doing d i f - ferently that leads us to be optimistic. Most of this unsuccessful research has focused on a few chemicals found i n sp e c i f i c areas of the brain that are believed to play a role in HD. However, the brain i s very complex and involves the in t e r - action of many chemicals, nerves, and groups of c e l l s . Investigations based on a single brain chemical cannot begin to tap these i n t r i c a c i e s and could easily overlook factors important in the development of HD. Our measures, on the other hand, tap the general functioning of the brain and depend on a l l the parts of the brain working together in a normal way. If any one function of the brain i s impaired, this impairment might show up in the general type of readings we take. Not much research has been done with the measures we w i l l be using; what l i t t l e has been done has produced some encouraging findings, which require further study. In this project, we w i l l be monitoring your brain waves, eye movements, and the amount of sweating in your fingertips while you watch flashing l i g h t s , l i s t e n to sounds, and follow moving li g h t s with your eyes. To make these measurements, we w i l l attach sensing devices (electrodes) to your skin. Our procedures do not involve pain or discomfort; most people who volunteer find participation in our tests interesting. This project has been approved by the UBC committees that monitor research with human subjects and has been reviewed by the Huntington's Society of Canada and i t s B.C. chapter. S t r i c t c o n f i d e n t i a l i t y of a l l information collected w i l l , of course, be maintained. We are looking for two separate groups of individuals who come from families in which there i s HD. The f i r s t consists of persons who are in the early stages of the disease. That i s , people who are a) currently working or b) able to cook and do other household work or c) drive their cars. The second and largest group consists of individuals who are the children or descendants of a parent with HD and who are themselves t o t a l l y symptom-free. From this group, we are forming two subgroups: At-risk persons aged 25 and over and at-ris k individuals under age 24. Parental consent w i l l be required for participants under age 16. 9 7 i A A r» r» • x APPENDIX B M.A.P. Project U.B C./C.V M.H.S./W.H.O. Why do some people develop physical and mental disorders while others do not? Even in a s i n g l e family, where people share common heredity and l i f e s t r e s s e s , i t is d i f f i c u l t to understand why only c e r t a i n family members seem vulnerable to such i l l n e s s e s . Only through research can we learn more about these d i s o r d e r s and the role genetic and s o c i a l f a c t o r s play in t h e i r development. With the help of grants from the Medical Research Council and Health and Welfare Canada, the Family P r a c t i c e Unit is cooperating with s c i e n t i s t s at the U n i v e r s i t y of B r i t i s h Columbia who are studying these problems in depth. This p r o j e c t is part of a major i n t e r n a t i o n a l c o l l a b o r a t i v e e f f o r t sponsored by the World Health Organization. In order to successfu1 1y complete our p r o j e c t , we need information from normal volunteers because i t enables us to compare f i n d i n g s from f a m i l i e s with i l l members to normal f a m i l i e s such as yours. Only in th i s way can we hope to discover the causes and best ways of t r e a t i n g severe medical d i s o r d e r s . Who is e l i g i b l e ? Anyone in good he a l t h , between the ages of 15 and 5^ , who has never been treated and whose cl o s e r e l a t i v e s (parents, brothers, s i s t e r s , c h i l d r e n ) have never been treated for a severe p s y c h i a t r i c d i s o r d e r or for alcohol or drug abuse. The ordinary s t r e s s , depression, or anxiety which almost a l l of us experience from time to time is not considered a severe p s y c h i a t r i c d i s o r d e r and would not make you i n e l i g i b l e to p a r t i c i p a t e . In a d d i t i o n , a p a r t i c i p a n t should not be s u f f e r i n g from a long-term physical i l l n e s s or have v i s i o n problems that cannot be corrected by glass e s . Since we are studying f a m i l i e s , f o r purposes of comparison, we would l i k e members of your family over age 15 to p a r t i c i p a t e as w e l l . What would you do as a volunteer f o r our study? Arrangements would be made f o r you to v i s i t with us at UBC during your free time to provide some interview information and take some simple perceptual tests in our laboratory. Most people f i n d our procedures i n t e r e s t i n g ; there is nothing about our tasks that is s t r e s s f u l , embarassing or p a i n f u l . You need not be concerned about how well you perform because there is no such thing as doing badly on these tasks. We are merely c o l l e c t i n g information. A l l aspects of your p a r t i c i p a t i o n w i l l be kept s t r i c t l y c o n f i d e n t i a l . What do you get out of i t ? The main thing is simply the s a t i s f a c t i o n of knowing you have contributed to a very important research p r o j e c t . In a d d i t i o n , we w i l l provide every volunteer with $20 once a l l the tests are completed. This means we w i l l a l s o pay $20 to every member of your family who decides to p a r t i c i p a t e . F i n a l l y , we w i l l be happy to share the r e s u l t s of this p r o j e c t with you should you be i n t e r e s t e d . If you are i n t e r e s t e d , please complete the attached forms and leave them with the c l i n i c r e c e p t i o n i s t . By completing this form, you are under no o b l i g a t i o n to p a r t i c i p a t e ; you are merely expressing your i n t e r e s t . A member of the M.A.P. p r o j e c t w i l l be contacting you to discuss the pr o j e c t and provide an opportunity to answer any questions that you might have. Please feel free to take thi s information sheet with you; j u s t leave the attached forms. For further information, please contact Dr. V e r i t e Livingstone or Ms. Rosemary Grant, R.N. of the Fairmount Family P r a c t i c e C l i n i c or Dr. Neil Kyle of the M.A.P. p r o j e c t Thank you for considering our request. 98 APPENDIX C INTAKE QUESTIONNAIRE 1. Have you ever r e c e i v e d treatment f o r an emotional or p s y c h i a t r i c i l l n e s s ? I I No • Yes Nature of problem What kind of treatment ( i n c l u d i n g m e d i c a t i o n , h o s p i t a l i z a t i o n ) 2. Have your mother, f a t h e r , b r o t h e r s , s i s t e r s , o r c h i l d r e n ever r e c e i v e d treatment f o r an emotional or p s y c h i a t r i c i l l n e s s ? I I No 1 | Yes Nature of r e l a t i v e ' s problem Re 1 a t i ve Treatment 3. Have you ever had a d r i n k i n g problem or has anyone ever suggested that you had a d r i n k i n g problem? • • No Yes Treatment A. Have your mother, f a t h e r , b r o t h e r s , s i s t e r s , or c h i l d r e n ever had a d r i n k i n g problem? • • No Yes Who Extent Treatment 5. Do you have any d i s o r d e r a f f e c t i n g your b r a i n or s p i n a l c o r d , long-term pain disorder, o r long-term p h y s i c a l d i s o r d e r (e.g. e p i l e p s y , c h r o n i c back p a i n , a r t h r i t i s , diabetes. • h y p e r t e n s i o n , m u l t i p l e s c l e r o s i s , s t r o k e , e t c . ) No • Yes Spec i fy 6. Oo you have any problems with your eyes or v i s i o n ? • No | 1 Yes S p e c i f y C o r r e c t e d by g l a s s e s ? | j N q • Yes 99 APPENDIX D MAP PROJECT CONSENT FORM I h a v e ' b e e n - a s k e d " t o : p a r t i c i p a t e i n a . s t u d y i n : w h i c h : ray b o d y ' s r e s p o n s e s w i l l b e - r e c o r d e d : w h i l e I p e r f o r m s e v e r a l s i m p l e t a s k s - . T h e s e - t a s k s , i n c l u d e c o m f o r t a b l y r e l a x i n g 1 w h i l e - l i s t e n i n g , t o b r i e f t o n e s , , w a t c h i n g b r i e f f l a s h e s o f l i g h t , a n d w a t c h i n g a s p o t o f l i g h t m o v e b a c k a n d , f o r t h on; , as s c r e e n a n d . a t t e m p t i n g to-- p r o d u c e s i m i l a r - m o v e m e n t s ; b y t u r n i n g , a k n o b b a c k a n d f o r t h . T h e r e s p o n s e s o f my b o d y t h a t w i l l b e r e c o r d e d i n c l u d e my eye= m o v e m e n t s , h e a r t b e a t , , b r a i n w a v e s : , a n d t h e - a c t i v i t y o f - m y s w e a t . - g l a n d s ' . T o m a k e t h e s e r e c o r d i n g s , . s e n s o r s w i l l b e a t t a c h e d t o r my a r m s , l e g s , a n d h e a d , , b u t n o d i s c o m f o r t o r d a n g e r t o ; m y s e l f i s , i n v o l v e d " . . I n : a n o t h e r p a r t o f t h i s - s t u d y a t d r o p o f o i l s i m i l a r t o ; c o o k i n g ; o i l w i l l b e p l a c e d o n my s k i n n e a r e a c h o f my f i n g e r - n a i l s a n d at p h o t o g r a p h o f my s k i n w i l l b e m a d e . I u n d e r s t a n d t h a t t h e s e t e s t s w i l l n o t i n f l u e n c e my m e d i c a l c a r e - o r t r e a t m e n t , a n d t h a t a l l t h e i n f o r m a t i o n o b t a i n e d - i n t h i s p r o j e c t w i l l b e k e p t c o n f i d e n t i a l a n d u s e d ? o n l y , f o r t h e * p u r p o s e s o f f t h i s , s t u d y - By- s i g n i n g , - t h i s * f o r m , . I; a g r e e - t o - p a r t i c i p a t e , , a l t h o u g h L r e a l i z e - T.-am f r e e r t o w i t h d r a w f r o m , t h i s , s t u d y a t : a n y t i m e 1 , w i t h o u t p r e j u d i c e * t o c u r r e n t a n d . f u t u r e c a r e " a n d - t r e a t m e n t - w i t n e s s s i g n a t u r e p r i n t n a m e date I.D. number APPENDIX E Parental Consent Form I, , parent/guardian of NAME agree to l e t my son/daughter NAME OF VOLUNTEER UNDER 16 participate i n the Huntington's disease family research project at UBC. 101 APPENDIX F NAME: DATE: Please pick out the statement in the groups below which best describes the way you f e e l today, that i s , right now. Indicate your answer by c i r c l i n g your choice. do not f e e l sad. f e e l blue or :sad; am blue or sad a l l the time and I can't snap out of i t . am so sad or unhappy that i t i s quite painful, am so sad or unhappy that I can't stand i t . am not pa r t i c u l a r l y pessimistic or discouraged about the future, f e e l discouraged about the future, f e e l I have nothing to look forward to. f e e l that I won't ever get over my troubles. fee l that the future i s hopeless and that things cannot improve, do not f e e l l i k e a f a i l u r e . f e e l that I have f a i l e d more than the average person, f e e l I have accomplished very l i t t l e that i s worthwhile or that means anything. I look back on my l i f e , a l l I can see i s a l o t of f a i l u r e , f e e l X am a complete f a i l u r e as a person (parent, husband, wife). am not p a r t i c u l a r l y d i s s a t i s f i e d , f e e l bored most of the time, don't enjoy things the way I used' to. I don't get satisfaction out of anything anymore. don't f e e l p a r t i c u l a r l y guilty, f e e l bad or unworthy a good part of the time. f e e l quite guilty.. f e e l bad or unworthy p r a c t i c a l l y a l l the time now. feel as though I am very bad or worthless. don't f e e l that I am being punished, have a feeling that something bad may happen to me. f e e l I am being punished or w i l l be punished, f e e l I deserve' to be punished, want to be punished. don't f e e l disappointed in myself, am disappointed in myself, don't l i k e myself, am disgusted with myself, hate myself. don't f e e l I am any worse than anybody else, am c r i t i c a l of myself for my weaknesses or mistakes, blame myself for my faults. blame myself for everything bad that happens, don't have any thoughts of harming myself. have thoughts of harming myself but I would not carry them out. f e e l I would be better off dead. f e e l my family would be better off i f I were dead, have definite plans about committing suicide, would k i l l myself i f I could. A. 0 r . 1 I : 2a I , 2b I ; 3 I J B. 0 I •'; l a I : 2a X : 2b X : 3 I-.: C. 0 I 1 I 2a I 2b As 3 I D. 0 I l a I lb I 2 X E. 0 I • 1 I 2a I 2b I 3 I F. 0 I 1 I 2 I 3a i : 3b I G. 0 I l a I lb X 2 X 3 I H. 0 I 2 I 2 X 3 I I. 0 X 1 I 2a X 2b I 3a X 3b I 1 0 2 APPENDIX F - 2 - J. 0 I don' t cry any. more than usual. 1 I cry more now than I used to. 2 I cry a l l the time now; I can't stop i t . 3 I used to be able to cry but now I can't cry at a l l even though I want to. K. 0 I am no more irritated now than I ever am. 1 I feel annoyed or irritated more easily than I used to. 2 I feel irritated a l l the time. 3 I don't get irritated at a l l at the things that used to i r r i t a t e me. L. 0 I have not lost interest in other people. 1 I am less interested in other people now than I used to be. 2 I have lost most of my interest in other people and have l i t t l e feeling for them. 3 I have lost a l l my interest in other people and don't care about them at a l l . M. 0 I make decisions about as well as ever. ;l I try to put off making decisions. 2 I have great d i f f i c u l t y in making decisions. 3 I can't make any decisions at a l l any more. N. 0 I don't feel I look any worse than I used to. 1 I am worried that 1 am looking old or unattractive. 2 I feel that there are permanent changes in my appearance and they make me look unattractive. 3 I feel that I am ugly or repulsive looking. 0. 0 I can work about as well as before. l a It takes extra effort to get started at doing something. lb 1 don't work as well as I used to. 2 I have to push myself very hard to do anything. ;3 I can't do any work at a l l . P. 0 I can sleep as well as usual. '•1 I wake up more tired than I used to in the morning. 12 I wake up 1-2 hours earlier than usual and find i t hard to get back to sleep. i3 I wake up early every day and can't get more than 5 hours sleep. q. :0 I don't get any more tired than usual. 11 I get tired more easily than I used to. 2 I get tired from doing anything. ,3 I get too tired to do anything. R. 0 My appetite is no worse than usual. ; i My appetite is not as good as i t used to be. 2 My appetite is much worse now. '3 I have no appetite at a l l now. S. 0 I haven't lost much weight, i f any, lately. 1 I have lost more than 5 pounds. ,2 I have lost more than 10 pounds. 3 I have lost more than 15 pounds. 103 APPENDIX F - 3 - 0 I am no more concerned about my health than usual. 1 I am concerned about aches and pains or upset stomach or constipation. 2 I am so concerned with how I fee l or what I f e e l that i t ' s hard to think or much else. 3 I am completely absorbed in what I f e e l . 0 X have not noticed any recent change in my interest in sex. 1 X am less interested in sex than X used to be. 2 X am much less interested in sex now. 3 X have lost interest in sex completely. 104 APPENDIX G SELF-EVALUATION QUESTIONNAIRE Developed by C. D. Spielberger, R. L. Gorsuch and R. Lushene STAI FORM X-1 NAME DATE DERECTIONS: A number of statements which people have used to describe themselves are given below. Read each state- ment and then blacken in the appropriate circle to the right of the statement to indicate how you feel right now, that is, at this moment. There are no right or wrong answers. Do not spend too much time on any one statement but give the answer which seems to describe your present feelings best. N O T  A T  A L L  S O M E W H A T  M O D E R A T E L Y  S O  V E R Y  M U C H  80 © ® ® © © ® ® ® © © ® ® •© ® ® ® © ® ® ® © ® ® ® 7. I am presently worrying over possible misfortunes © ® ® © © ® ® ® 9. I feel anxious _ _ © ® ® ® 10. I feel comfortable © ® ® ® 11. I feel self-confident © © ® © 12. I feel nervous © ® ® ® © ® ® ® 14. I feel "high strung" © ® ® ® © ® ® ® © ® ® © © ® ® ® 18. I feel over-excited and "rattled" © ® ® ® © ® ® ® © ® ® © •wS^i'. CONSULTING PSYCHOLOGISTS PRESS '^Wwr 577 College Avenue< Pal° Alt0'Call,ornia 94306 1 0 5 A P P E N D I X G SELF-EVALUATION QUESTIONNAIRE STAI FORM X-2 NAME DATE DIRECTIONS: A number of statements which people have used to describe themselves are given below. Read each state- ment and then blacken in the appropriate circle to the right of the statement to indicate how you generally feeL There are no right or wrong answers. Do not spend too much time on any one statement but give the answer which seems to describe how you generally feeL © ® © ® © ® © © 23. I feel like crying . _ _ © © © © 24. I wish I could be aa happy as others seem to be _ .... . © © © © 25. I am losing out on thinga because I can't make up my mind soon enough © © © 26. I feel rested._ © © © © 27. I am "calm, cool, and collected" . . ... © © © © 28. I feel that difficulties are piling up so that I cannot overcome them „ © © © © 29. I worry too much over something that really doesn't matter © © © © 30. I am happy _ © © © © 31. I am inclined to take things hard © © © © © © © © © © © © ©' © © ® 3fi. I feel blue . _ _ .._ © © © © © © © © 37. Some unimportant thought runs through my mind and bothers me © © © © 38. I take disappointments so keenly that I can't put them out of my mind.— © © © ® © © © © 40. I get in a state of tension or turmoil as I think over my recent concerns and © © © ® Copyright © 1968 by Charles D. Spielberger. Reproduction of this test or any portion thereof by any process without written permission of the Publisher is prohibited. 1 0 6 APPENDIX H SUBJECT ID DATE MEDICATION 1. Prescription Drugs A- Current medication Name Amount/frequency Date use began B. Most recent time subject was not taking any prescription drug Medication history since date entered above Name Amount/frequency Date use began Duration of use 2. Nonprescription Drugs Name Amount/frequency Last time used APPENDIX I Electrodermal Habituation To begin this next part of our session the f i r s t thing we want to do is check the recording equipment to make sure i t is working correctly. We would l i k e to see how your body reacts when you cough, just an ordinary cough li k e this (cough). Please cough once now ... cough again ... and one more time. Alright. Now take a deep breath and hold i t . Take a deep breath now. Hold i t , don't let any air out... OK, you can breathe normally now. OK. That's the most excitement you're going to get. During the next part of our session, we'll ask you to s i t perfectly s t i l l for about 10 minutes, so take a few moments now to get comfortable in your chair. Next, we want to measure your a b i l i t y to ignore distracting sounds while you concentrate on becoming completely relaxed. Every 30 often you w i l l hear a short tone; the tones w i l l come at unpredictable times. A l l the tones w i l l sound exactly alike. Our equipment w i l l record your body's reactions to these tones. At f i r s t y o u ' l l probably respond to them. As they are repeated you'll get used to them and soon you won't react to them at a l l . We want to see how quickly you can stop responding to these sounds. Some people can stop responding to a meaningless, distracting sound very quickly. For others, i t takes longer. We want to see how quickly you can stop responding. I t ' 8 easier to ignore something that's distracting and unimportant i f you have something else to focus your attention on. We want you to focus your attention on becoming completely relaxed. This w i l l require some concentration. One way to concentrate on relaxing, to become deeply relaxed, is to repeat over and over to your self sentences li k e "I feel deeply relaxed. My whole body is completely relaxed." This is what we want you to do while listening to the tones. Keep repeating these sentences over and over in your mind. The more you do, the more relaxed you w i l l become, and the easier i t w i l l be to ignore the tones. 1 0 8 APPENDIX I Take a moment now to get comfortable. Close your eyes now and let your whole body start to relax. Let the day's tensions just drain out of your body. Breathe easily, i n a steady, regular way. Swallow i f you have to but try not to move any other muscles. I'm going to give you some instructions now to help you become deeply relaxed. Since I want you to concentrate on relaxing by saying things to yourself in your mind, the instructions you w i l l hear next are spoken as though you were saying them to your s e l f . After I say each sentence, repeat i t to yourself in your thoughts. Here we go. "My whole body is becoming limp and relaxed. My feet feel heavy and relaxed. My legs feel heavy and relaxed. My ankles, knees and hips feel heavy, relaxed, and comfortable. My hands feel heavy and relaxed. My arms feel heavy and relaxed. My wrists, elbows, and shoulders feel heavy and relaxed. My stomach and chest feel deeply relaxed. The muscles in my face and neck fee l heavy and relaxed. My neck, my jaw, and my forehead feel comfortable and deeply relaxed. My whole body feels completely relaxed." In a few moments we w i l l turn on a soft, r u s t l i n g noise that sounds l i k e wind in the trees or running water. Remember, the more you concentrate on relaxing the easier i t w i l l be to ignore the tones. Keep saying to yourself over and over "I feel deeply relaxed. My whole body feels heavy and relaxed." If you feel tension anywhere in your body, for example, in your jaw, keep saying to yourself "My jaw feels heavy and relaxed" u n t i l you can feel the tension melt away. Then continue to repeat to your self "I feel deeply relaxed. My whole body feels heavy and relaxed." Start saying that now. You'll know when this part of the session is over because I ' l l speak to you again. Here we go. (8 85 db tones) Continue to relax deeply. If you need to move about you can do so now, but try to stay comfortable and relaxed. We are going to to li s t e n to some 109 APPENDIX I more tones, only this time the tones w i l l be much louder than before. Once again we w i l l ask you to relax and ignore the tones. Now you've had some practice so even though the tones w i l l be louder than before, you should s t i l l be able to relax and ignore them. Remember, the more you focus your attention on becoming completely relaxed, the easier i t w i l l be to ignore the tones. Just concentrate on relaxing, keep your muscles free of tension, repeat to yourself "I feel deeply relaxed. My whole body feels heavy and relaxed". Keep repeating that to yourself. Once again, you w i l l know when this part of the session is over because I w i l l speak to you again. Here we go... (12 105 db tones) OK. We are finished with this type of task. Take a moment now to stretch and wake up... Move your arms and legs and your body. We have one more task for you, but before I explain i t to you, we'll help you s i t up in your chair. Next, we want you to l i s t e n to some different types of sounds. These sounds are recordings of things that you might hear from time to time in your everyday l i f e , like a f i r e engine siren or the sound of a jet plane. While none of the interesting sounds you w i l l hear are frightening or scarey, some are a l i t t l e unusual and you may have d i f f i c u l t y identifying them. In the last part of our session, we were measuring your a b i l i t y to ignore sounds. Now, however, we want you to do the opposite. We want you to pay close attention to these sounds. See i f you can figure out what each one i s . Listen carefully so you can decide i f a l l the sounds are different or i f some of them are the same. After we have finished with this part of our session, we w i l l ask you some questions about the sounds to see how many you were able to identify. Get comfortable now and try not to move during the rest of our session. Pay close attention to the sounds. We'll turn on the rustling noise again. Here we go. (sounds played here) Okay. We're finished with this part of the session. 110 APPENDIX J Scoring Skin Conductance Skin conductance level (SCL) and skin conductance response (SCR) are each measured in micromhos (umhos). A micromho is one millionth of a mho. A mho is the inverse or reciprocal of an ohm, which is a measure of resistance. Tonic l e v e l of skin conductance is the amount of skin conductance when a subject i s not exposed to a stimulus. Tonic l e v e l of skin conductance, or skin conductance l e v e l (SCL) i s calculated using 2 pieces of information: 1) zero suppression (zs). This is usually a whole number and indicates, in micromhos, what the conductance le v e l would be i f the pen were i n the center of the chart. If the pen ̂ s in the center of the chart, this i s the only piece of information necessary to know the l e v e l of skin conductance. To calculate skin conductance le v e l at any point on the chart, take the zero suppression and add/subtract micromhos according to the s e n s i t i v i t y settings. To calculate SCL at point X, draw a l i n e upward at point X u n t i l i t crosses the skin conductance record. Since zs = 7, the center of the chart represents 7 micromhos of con- ductance. Since s e n s i t i v i t y = .2 mv/mm, a .5 cm deflection represents 1 micromho of conductance (1 cm => 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 - — e — - • i •; 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....; •( ' -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 #£SPo/4S£ AFTER 7 Second MoT AFTelZ ^S£.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»v 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).

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