8/3/2019 pillon 1996

1/9

P e r g a m o n 0028-3932(95)00086-0Neuropsychologia, V ol . 34 , N o . 1 , pp . 77 85 , 1996C o p y r i g h t 1 9 9 6 E l s e v i er S c i en c e L tdP r i n t e d i n G r e a t B r i t a i n . A l l r i g h t s r e se r v e d0 0 2 8 - 3 9 3 2 / 9 6 $ 1 5 . 0 0 + 0 . 0 0

M e m o r y f o r s p a t i a l l o c a t i o n i s a f f e c t e d i nP a r k i n s o n ' s d i s e a s eB E R N A R D P I L L O N , S T E P H A N E E R TL E , B E R N A R D D E W E E R , M A R I E S A R A Z I N ,Y V E S A G I D a n d B R U N O D U B O I S

I N S E R M U 289 and F6d+rat ion de Neuro logie , H6p i ta l de la Salp~tr i+re , 47 Bouleva rd de l 'H6p i ta l , 75651 Par is Cedex 13 , Franc e(Received 13 February 1995; accepted 8 M ay 1995)

Ab s t r a c t - - Ar e the s t r ia to - f ronta l neu ronal c i rcui ts impl ica ted in learning of i tem-spec ific spat ia l coord inates? To answer th isques t ion, we compared the per formance of 20 pat ients with Parkinson 's d isease to tha t of 14 controls matched for age , g lobalcogni t ive ef f ic iency and mo od, on a v isuo-spatia l learning task with l i t tle involvemen t of mo tor an d co ns truc t ive func t ions , a l lowingcontrol of encoding and compar ison of f ree recal l , cued recal l and recogni t ion. Compared to controls , pa t ients showed a severememory impairment for v isuo-spat ia l locat ion of p ic tures , contras t ing with re la t ive p reservat ion of verbal memory , and milddiff iculties in perceptiv e visuo -spatial and executive functions. Th ese results implicate s tr ia to-fro ntal neur ona l circuits in me m ory forspat ia l locat ion.Ke y W ords: Park inso n's disease; visuo-spatial learning; verbal learning; executive functions; visuo-spa tial func tions.

I n t r o d u c t i o nV e r b a l l e a r n i n g i s a f f e c t e d a f t e r f r o n t a l l o b e l e s i o n s ,p a r t i c u l a r l y w h e n i t r e q u i r e s t h e e l a b o r a t i o n a n dm a i n t e n a n c e o f e n c o d i n g a n d r e t ri e v a l st r at e g ie s a n dt h e i n h i b i t i o n o f i n t e r f e r e n c e s [ 1 8, 3 6] . T h e s a m em e m o r y p r o c e s s e s a r e a t r i s k i n P a r k i n s o n ' s d i s e a s e( P D ) , g i v e n t h e a n a t o m i c a l a n d f u n c t i o n a l r e l a t i o n sb e t w e e n b a s a l g a n g l i a a n d p r e f r o n t a l c o r t e x [ 1 , 9 , 3 9 ] . I na g r e e m e n t w i t h t h i s h y p o t h e s i s , n o n d e m e n t e d P Dp a t i e n t s , w h i l e s h o w i n g c o n s i d e r a b l e e v i d e n c e o f p r e -s e r v e d m e m o r y f u n c t i o n s , a r e i m p a i r e d o n a s u b g r o u po f t a s k s t h a t i m p l i c a t e i n t e r n a l l y d e v e l o p e d s t r at e g i e s ,t e m p o r a l o r g a n i z a t i o n a n d s o u r c e a l l o c a t i o n , a n di n h i b i t i o n o f c o m p e t i n g s t i m u l i [ 6, 4 0 ].V i s u o - s p a t i a l l e a r n i n g h a s b e e n l e s s s t u d i e d a n dc o n t r a d i c t o r y re s u l t s h a v e b e e n f o u n d . O n t h e o n eh a n d , p a t i e n t s w i t h f r o n t a l l o b e l e s i o n s [2 6 ] o r P D [ 40 ,4 2 ] e x h i b i t d i f f ic u l t i es i n e s t a b l i s h i n g a n d m a i n t a i n i n ga r b i t r a r y l i n k s b e t w e e n s t i m u l i a n d t h e i r l o c a t i o n i nc o n d i t i o n a l a s s o c i a t i v e l e a r n i n g t a s k s . O n t h e o t h e rh a n d , p a t i e n t s w i t h f r o n t a l l o b e l e s i o n s [ 3 7 ] o r P D [ 7 ]s h o w n o r m a l r e c a ll o f o b j e c t o r p i c t u r e l o c a ti o n s . T h i sd i s c r e p a n c y u n d e r l in e s t h e c o n s i d e r a b l e i m p o r t a n c e o ft h e l e a r n i n g s i t u a t i o n f e a t u r e s a n d o f t h e r e q u i re dp r o c e s s e s .T h e a i m s o f t h e p r e s e n t s t u d y w e r e : (1 ) to f u r t h e re v a l u a t e v i s u o - s p a t i a l m e m o r y i n n o n d e m e n t e d P D

p a t i e n t s, u s i n g a t a s k t h a t a l lo w s c o n t r o l o f e n c o d i n g( i n o r d e r t o l i m i t t h e i n f lu e n c e o f n o n s p e c i f i c a t t e n t i o n a ld i s o r d er s ) , a n d c o m p a r i s o n o f f r e e re c a ll , c u e d r e c a l l a n dr e c o g n i t i o n ; ( 2 ) t o c o m p a r e v e r b a l a n d v i s u o - s p a t i a ll e a r n i n g ; ( 3 ) to a s s e s s t h e i n f l u e n c e o f e x e c u t i v ef u n c t i o n s , a t t e n t i o n a l c o n t r o l , a n d p e r c e p t i v e v is u o -s p a t ia l f u n c t i o n s o n v i s u o - sp a t i a l m e m o r y p e r f o r m a n c e .

A s P D p a t i e n t s a r e i m p a i r e d i n t a s k s r e q u i r i n g s e l f -i n i t i a t e d p r o c e s s e s a n d d i s p l a y m o r e s e v e r e l e a r n i n gd e f i c i t s f o r n o n s e m a n t i c a l l y r e l a t e d i t e m s t h a n f o rs e m a n t i c a l l y r e l a t e d i t e m s [ 3 9 , 4 0 ] , w e h y p o t h e s i z e dt h a t v i s u o - s p a t i a l l e a r n i n g w o u l d b e m o r e s e v e r e l yi m p a i r e d t h a n v e r b a l l e a r n i n g .

S u b j e ct s a n d M e t h o d sSubjects

Th e diagnosis o f PD was established on th e basis o f (1) theexis t ence of e i th e r ak ine to - r ig id s y nd r ome o r r e s t ing t r em or o rbo th , w i th a good r e s p ons e to l ev od op a t r ea tmen t th a tremained present a t the t ime of evaluat ion; (2) exc lus ion ofp a r k ins on ian s y nd r omes r e s ul t ing f r om c h r on ic ad m in i s tr a t ionof neu r o lep t ic s and f r om o th e r neu r od egene r a t iv e d i s o rd e r s ,such as multiple system atrophy, progressive supranuclearpalsy , and cor t icobasal degenera t ion. None of the 20 pat ientsinc luded in the s tudy was demented ( score > 27 on the Fols te inMin i - Men ta l S ta t e E xam ina t ion [ 1 3 ] ; s c o r e > 1 3 0 on th e

77

8/3/2019 pillon 1996

2/9

78 B. Pil lon e t a l . / M e m o r y for spatial location is affected in Park ins on' s diseaseMattis Deme ntia Rati ng Scale [23]) or depressed (score < 18on the Mo ntgome ry an d Asberg Depression R ating Scale [24]).The duration of the disease (mean_+S.E.M.) was 8.1_+1.3years. The mean Hoehn and Yahr [17] stage was 2.5 + 0.2. Themean mo tor disability score, assessed under levodopa therapywith the Unified Parkinson's Disease Rating Scale [12], was18.1 + 2. I. All patients were being treated with levodopa (meandaily dose: 630.3__+87.4) associated with a p eriphera l do pa-decarboxylase inhibitor. Mean score of autonomy, evaluatedon the Activities of Daily Living Scale [34], was 83.0+ 2.7%.The control group consisted of 14 subjects withoutneuro logic or psychiatric disease. They did no t significantlydiffer f rom patients with PD for age (62.4___2.0 years inpat ien ts vs 64.3 3.3 in co ntro ls), level of ed uca tion (11.0 ___0.6years of school in patients vs 11.4_+0.8 in controls), premorbidverbal level (IQ=122.4+1.8 in patients vs 120.8-+3.5 incontrols on Beauregard's test [2 ], which holds despiteintellectual deterioration), Mini-Mental State Examination(28.9_+0.3 in patients vs 29.2-+0.3 in controls). MattisDeme ntia Rat ing Scale (138.9___0.9 in patien ts vs 141.1-+0.7in controls) and Montgomery and Asberg Depression RatingScale (8.1_+1.3 in patients vs 5.8-+1.2 in controls) scores.Informed consent was obtained from every subject after thenature of the procedure had been fully explained.

Neuropsychological as se s smentBesides the expe rimental procedure of visuo-spatial learning,the neuropsychological examination included tests of verballearning, and of executive and visuo-spatial functions.Visuo-spatial learning tes t . The procedure was as similar aspossible to that of the Gr ober and Buschke's test [16] used forverbal learning (see below). The material included 16 familiarpictures of Snodgrass and Vandervart [38] and a 29.7 x 21 cmmatrix, with 16 squares divided into 4 groups of 4 squares.Each group of squares differed from the others by its own

spatial configuration (for instance, pictures were arranged insquare in one configuration and in cross in another one), inorder to limit interferences between groups of pictures.Spat ia l encod ing was run for one group of 4 pictures at atime. On the first presentation, 4 pictures were located in theleft top configuration of the matrix, while the 3 otherconfigurations were empty. Fo ur pictures were presented onindividual cards one by one to the subject, who was asked topoint to the corresponding picture on the matrix and toremember its exact location. Once the location of the 4presented pictures had been shown by the subject, the entireprocedure was repeated to reinforce encoding. Then the samewhole matrix, without any picture, was presented to thesubject, who was asked to show the exact location of the 4pictures presented again one by one in the same order. If therewas any error, the same group of pictures was presented againand the encoding procedure was run again for that (those)picture(s), until a correct location was obtained at immediatecued recall. The same procedure was followed for the 3 othergroups of pictures in a predetermined order. The "spatialencoding score" (from 0 to 16) was determined by the numb erof pictures correctly located at the first trial on immediate cuedrecall.The " r ecall phas e" of the 16 locations included 3 trials, eachpreceded by 20 sec of coun ting backward to obtai n recall fromsecondary memory. On each trial, the subject was presentedfor 2 min with the empty matrix and asked to spontaneouslyrecall which picture was in each square. Then, all pictures thatthe subject had not correctly located at free recall, but onlythese pictures, were presented again for cued recall, one byone, and the subject was invited to select the correct location.The items failed at cued recall were selectively reminded, the

examiner showing the correct location of the picture. The"spatial learning free recall score" (from 0 to 48) wasdetermined by the total number of pictures correctly evokedand located on the matrix during the 3 trials ("trial spatial freerecall scores", from 0 to 16 on each trial). The "spa tial learni ngtotal recall score" (from 0 to 48) was determined by thenumber of pictures correctly located on the matrix at free orcued recall during the three trials ("trial spatial total recallscores", from 0 to 16 on each trial). Given the procedure,where cued recall is tested only for items that are notspontaneously evoked, a cued recall score alone would notbe a valid index, since a subject with near perfect free recallwould have a very poor cued recall score. In contrast, a subjectwith very low free recall could have a near perfect cued recallscore. Because of these methodolo gical constr aints , the"learning total recall score" is actually the best evaluation ofcued recall, since it is the sum of all correctly evoked items,either at free recall or at cued recall, and since the itemsspontaneously evoked at free recall would presuma bly be (atleast for most of them) also correctly evoked at cued recall. Inagreement with this interpretation, the "learning total recallscore" may be normal even when free recall is very poor [27,28]. Pictures correctly evoked at free recall, but incorrectlylocated, were added to the pictures correctly located in order togive a "picture evocation score"; they were also added to thepictures incorrectly located at cued recall in a "spatialinterferences score". "Delayed spatial free recall" and "de-layed spatial total recall" scores were also measured after a 15min delay.At the "recogni t ion phase" , after delayed recall, each picturewas presented at 3 different locations: the correct one (thenumber of correct responses yielded a "spatial correctrecognition score"), an incorrect one but in the sameconfiguration of 4 squares (the number of errors yielded a"proximal incorrect recognition score"), and an incorrect onein a different configuration (the number of errors yielded a"distant incorrect recognition score"). The or der of present ionwas randomly predetermined for each picture and eachlocation. The patient had to say if the presented picture wasor was no t correctly located.Verbal l earning." Grober and Bus chke 's t e s t. The 16 to-be-learned words, b elonging to 16 different semantic categories,and which were not prototypical of these categories, werepresented to the sub ject on 4 different cards, 1 card w ith 4words at a time. In this modified vers ion of the task [11], weused only printed words and n ot verbally labeled pictures as inthe original procedure.The " e nc od ing ph as e " was controlled by asking the subject topoint to and read aloud each word (e.g. grapes) when itscategory cue was verbally provided (e.g. "Which is the fruit?").When all 4 words on a card were correctly read, the card wasremoved and immediately cued recall was tested, in the sameorder as for identification, by providi ng each category cue.Whenever the subject was unable to recall a given item inresponse to its cue, the procedure of po inting and reading wasperform ed again for this (these) item(s), and cued recall wastested again, until the correct answer was obtained at cuedrecall. Once immed iate cued recall was comple ted for a g roupof 4 words, the next set of 4 words was presented. The "verbalencoding score" (from 0 to 16) was determined by the n umbe rof words correctly evocated on the first trial at immediate cuedrecall.T he " r e c a ll phas e " of the 16 words included 3 trials, eachpreceded by 20 sec of counting backward to o btain recall fromsecondary memory. Each trial consisted of an extended periodof free recall (up to 2 rain), immediat ely followed by cued recallfor those items not retr ieved at free recall. Items missed at cuedrecall were selectively reminded by the examiner, who orallygave the correct response, which was repeated by the subject.

8/3/2019 pillon 1996

3/9

B. P i l lon e t a l . /M em ory fo r spa t i a l l oca t ion i s a f fec ted in Park inso n ' s d i sease 79The "verba l l ea rn ing f ree reca l l s core" ( f rom 0 to 48 ) wasde t e r m i n e d b y t he n u m b e r o f w o r ds t o t a l co r r e c t ly e vo k e ddur ing the 3 t r i a l s . The "verba l l ea rn ing to t a l reca l l s core"( f r o m 0 t o 48) w a s de t e r m i n e d b y t he n u m b e r o f w o r dscor rect ly evok ed a t f ree o r cued reca ll . Thi s index wouldp r o v i de t he b e s t e s ti m a t e o f t he a m o u n t o f in f o r m a t i o n e a chs u b j e c t w a s a b l e t o e n co d e a n d r e t ri e ve [ 16 ] . " D e l a ye d ve r b a lf ree reca l l " and "de layed verba l to t a l reca l l " s cores were a l someasured a f t e r a 15 min de lay .A t t h e "recognition phase", af t e r de layed reca l l , 48 wordsw e r e p r es e n t e d : t he 16 co r r e c t o n e s ( t he n u m b e r o f co r r e c tresponses y i e lded a "verba l cor rect recogni t ion s core" ) , 16s e m a n t i c d i s t ra c t o r s ( t he n u m b e r o f e r r o r s y ie l de d a " ve r b a lsemant i c incor rect recogni t ion s core" ) , and 16 neu t ra ld i s t r a c t o rs ( t he n u m b e r o f e r ro r s y i e l de d a " ve r b a l n e u t r a li n co r r e c t r e co g n i t i o n s co r e " ) .Complementary tests. Tes t s o f execu t ive funct ions includedthe s impl i fi ed vers ion of t he Wiscons in C ard Sor t ing Tes t [25 ],verba l f luency t es ts ( fo r ca t eg ory f luency, t he names o f an imal si n 1 m i n a n d t he S u pe r m a r k e t s u b t e s t o f the M a t t i s D e m e n t i aR a t i n g Sca l e ; f o r pho n e m i c f l u e n cy , w o r ds b e g i n n i n g w i t h"M " and "D " , fo r 1 min each [3 ] ) , and a g raphic s er ies [21] .Behaviora l abnormal i t i e s (prehens ion , imi t a t ion and u t i l i za -t ion behaviors ; i ne r t i a , i ndi f fe rence) observed in pa t i en t s wi thfron tal lobe les ion s [20] were also assessed, us ing a scale withpreci se s t eps rang ing f rom 4 (normal behavior ) to 0 (verysevere abnorm al i ty) . F or ins t ance , t he s core o f imi t a t ionbehavior was : (4) i f t he pa t i en t was perplexed by theexam iner ' s a rb i t ra ry ges tures ; (3 ) i f t he pa t i en t a sked i f hehad to imi t a t e ; (2 ) i f t he pa t i en t imi t a t ed , b u t s top ped wh enasked by th e exam iner no t to imi t a t e ; (1) i f t he pa t i en t im i t a t edaga in a f t e r a sh or t d i s t rac t ing per iod: (0 ) i f t he pa t i en tcon t inued to imi t a t e , despi t e he ( she) was sa id no t to do so .F r o m t he pe r f o r m a n ce a t t he s e b e ha v i o r a l e va l u a t i o n s , a" f r o n t a l b e ha v i o r s co r e " ( f r o m 0 t o 2 0 ) w a s ca l cu l a t e d . F r o mthe per formance on a l l t he t asks s ens i t i ve to f ron ta l l obedys f u n c t i o n , a " g l o b a l f r o n t a l s co r e " ( f r o m 0 t o 6 0 ) w a sdef ined [30] ; t h i s s core has been shown to be re l a t ed to f ron ta lhyp o m e t a b o l i s m i n p r o g r e s s i ve s u p r a n u c l e a r pa l s y [ 5 ] . G i ve nt he po t e n t i a l r o l e o f co n t r o l o f a t t e n t i o n i n v i s u o - s pa t i alm e m o r y , w e a dd e d t he S t r o o p t e s t [ 15] , w h i ch e s t i m a t es t heinhib i t ion of in te r fe rences , and th e Odd M an Out t e s t [31],

which eva lua tes s e t - shi f t ing and se t -main tenance . Vi suo-spa t i a l pe rcept ive funct ions were s tudied wi th t es t s o f Fo rmD i s c r i m i n a t i o n a n d L i n e O r i e n t a t i o n [ 4 ] .Statistical analyses. L e a r n i n g s co r e s w e r e co m pa r e d b y t w o -w a y A N O V A s , w i t h g r o u p a s a b e t w e e n - s u b j e c t s f a c t o r(pa t i en t s vs con t ro l s ) and type of l ea rn ing (p i c tu re loca t ionsvs w o r ds ) a s a w i t h i n - s u b j e c t f a c t o r . O n e - w a y A N O V A s w e r eu s e d f o r post hoc a n a l y s e s a n d co m pl e m e n t a r y t e s t s , w i t hn o n pa r a m e t r i c t e s ts w he n r e q u i re d b y va r i a n ce he t e r o g e n e i ty .Given the num ber o f com par i sons , t he s t a t i s ti ca l s ign if i canceleve l was de te rmined a t P < 0 .01. W i thin-g roup in t e r re l a t ionsw e r e a n a l yz e d b y m e a n s o f l i n e a r co r r e la t i o n s .

R e s u l t sL e a r n i n g t e s t s

R e s u l t s s h o w e d a r e l a ti v e l y s p e ci fi c i m p a i r m e n t o fp a t i e n t s f o r t h e " s p a t i a l l e a r n i n g f r e e r e c a l l " , t h e" s p a t i a l l e a r n i n g t o t a l r e c a l l " , t h e " s p a t i a l i n t e r f e r -e n c e s " , t h e " s p a t i a l d e l a y e d f r e e re c a l l " , t h e " s p a t i a ld e l a y e d t o t a l r e c a l l " a n d t h e " s p a t i a l c o r r e c t r e c o g n i -t i o n " s c o r e s ( T a b l e 1 , F i g s 1 a n d 2 ) .

E n c o d i n g s c o r e s . A t w o - w a y A N O V A w i th g ro u p s( p a t i en t s v s c o n t r o l s ) a s b e t w e e n f a c t o r a n d t y p e s o fl e a r n i n g ( " s p a t i a l e n c o d i n g s c o r e " v s " v e r b a l e n c o d i n gs c o r e " ) a s w i th i n f a c t o r s h o w e d n o g r o u p e f fe c t ( F (1 ,3 2 ) = 3 . 0 , P = 0 . 0 9 ) , n o t y p e o f l e a rn i n g e f fe c t ( F (1 ,3 2 ) = 1 . 7 , P = 0 . 2 1 ) a n d n o i n t e ra c t i o n b e t w e e n g r o u pa n d t y p e o f l e a r n i n g ( F ( 1, 3 2 ) = 1 .2 , P = 0 . 2 9 ) . T h e r e -f o r e, t h e p a t ie n t s s h o w n o s p e c if ic i m p a i r m e n t a te n c o d i n g p i c t u r e l o c a t i o n s .

L e a r n i n g f r e e r e c a l l s c o r e s . A t w o - w ay A N O V A w i t hg r o u p ( p a t i e n ts v s c o n t r o l s ) a s b e t w e e n f a c t o r a n d t y p eo f l e a r n i n g ( " s p a t i a l l e a r n i n g f r e e r e c a ll s c o r e " v s" v e r b a l l e a r n i n g f r ee r e c al l s c o r e " ) a s w i t h i n f a c t o r

Table 1 . Learn ing t es ts . In t e ract io n be tween grou ps and typ es o f l ea rn ing e ffect s was search ed for byt w o - w a y A N O V A s , b u t n o t ca l cu l a te d f o r t he l a s t t w o s co r e s, g i ven t he a b s e n ce o f va r i a n ce i ncon t ro l s ' ve rba l pe r form ance . N S: no t s ign if ican t. NC : no t ca l cu la t edSpa t i a l Verba l In t e rac t ion

E n c o d i n g s c o rePatients 15.2__+0.4 14.7 + 0.3 NSCo ntr ols 15.6 _+ 0.1 15.6 + 0.1Learn ing f ree reca l l s corePat ie nts 12.6 + 1.8"1" 25.2 + 1.5 P < 0.0005C on tro ls 29.9 __+2.7 29.3 + 1.5Learn ing to t a l reca l l s corePa tien ts 39.0 __+1.6" t 46.0 + 0.4 P < 0.003C on tro ls 46.3___ 0.5 47.2_+ 0.3Delayed f ree reca l l s coreP a t ie n ts 6 . 5 + 0 . 7 " t 9 . 2 + 0 . 5 P < 0 . 0 0 0 1C on tro ls 13.6 + 0.6* 10.5 + 0.6Delayed to t a l reca l l s corePa tien ts 12.9 __+ .6* t 15.7 + 0.1 N CC on tro ls 15.7 _+ 0.2 16.0 _+ 0.0C o r r e c t r e co g n i t i o n s co r ePat ie nts 12.9 _ 0 .6 *t 15.9 _+ 0.1 N CCo ntr ols 15.6 _+ 0.2 16.0 + 0.0

*Sign i f i can t d i f fe rence (P < 0 .01) w i th verba l l ea rn ing .tS ign i f i c an t d i f ference (P < 0 .01) w i th con t ro l s .

8/3/2019 pillon 1996

4/9

80 B. Pillon et al./Memory for spatial loc ation is affected in Pa rkinso n's disease

1614 .12 .1 0

8

642

Controls

o#

PD

- , , ! : -

1 2 3 D 1 2 3 DFig. 1. Visuo-spatial learning in patients with Parkinson'sdisease (PD) a nd controls. Perform ance at the three trials (1, 2,3) and delayed (D) recall . Dashed l ine indicates free recall ;solid line, total recall. Significant difference between patientsand cont rols: *(P

8/3/2019 pillon 1996

5/9

B. Pillon e t a l . /M em ory for spatial location is affected in Park inson 's disease 81(1 ) a h igh ly s i gn i f i can t d i f fe rence i n p a t i en t s b e tween" s p a t i a l l e a r n i n g t o t a l r e c a ll s c o r e " a n d " v e r b a l l e a r n in gt o t a l r e c a ll s c o r e " , w h i c h w a s h i g h e r ( F ( 1, 1 9 ) = 2 2 . 2 ,P < 0 . 0 0 01 ) , c o n t r a s t i n g w i t h ( 2) n o d i f f e re n c e b e t w e e nt h e s e s c o r e s i n c o n t r o l s ( F (1 , 1 3 ) = 1 . 9 , P = 0 . 1 8 ) .T h e r e f o r e , t h e g r o u p b y t y p e o f l e a r n i n g i n t e r a c t i o nw a s m a i n l y d u e t o a s p e c i fi c de f i c it o f p a t i e n t s o n t h e" s p a t i a l l e a r n i n g t o t a l r e c a l l s c o r e " . T h i s d e f i c i t w a sc o n f i r m e d b y t h e " s p a t i a l i n t e r fe r e n c e s c o r e " w h i c h w a ss ign i f i can t l y h igh e r i n p a t i en t s (20.4___3.0) t h a n i nc o n t r o l s ( 2. 5_ _ _1 .2 ; F ( 1 , 3 2 ) = 2 2 . 8 , P < 0 . 0 0 0 1 ) . I ns p i te o f t h i s d e f ic i t , t h e l e a r n i n g c u r v e o f p a t i e n t s f o rp i c t u r e l o c a t i o n s ( F i g . 1 ) w a s i d e n t i c a l t o t h a t o fc o n t r o l s , a s i n d i c a t e d b y a t w o - w a y A N O V A w i t hg r o u p s a s b e t w e e n f a c t o r a n d " t r i a l s p a t i a l t o t a l r e c a l ls c o r e s " a s w i t h i n f a c t o r w i t h r e p e a t e d m e a s u r e s ,s h o w i n g a s i g n i f i c a n t g r o u p e f f ec t ( F ( 1, 3 2 ) = 1 6 . 4 ,P < 0 . 0 0 0 3 ) , a m a r g i n a l r e p e a t e d m e a s u r e e ff e c t ( F (2 ,6 4 ) = 3 . 7 , P < 0 . 0 3 ) , b u t n o i n t e r a c t i o n b e t w e e n g r o u p sa n d r e p e a t e d m e a s u r e s ( F (2 , 6 4 ) = 0 . 3 , P = 0 . 7 2 ) .

D e l a y e d f r e e r e c a ll s c o r es . A t w o - w a y A N O V A w i thg r o u p ( p a t i e n t s v s c o n t r o l s ) a s b e t w e e n f a c t o r a n d t y p eo f l e a r n i n g ( " d e l a y e d s p a t i a l f r ee r e c a ll s c o r e " v s" d e l a y e d v e r b a l f r e e r e c a ll s c o r e " ) a s w i t h i n f a c t o rs h o w e d a g r o u p e f f e ct ( F (1 , 3 2 ) = 4 2 . 5 , P = 0 . 0 0 0 1 ) , n oty p e o f l e a r n ing e f fec t (F (1 , 32 ) = 0 .28 , P = 0 .60 ) , bu t ag r o u p b y t y p e o f l e a r n i n g i n t e r a c t i o n ( F ( 1 , 3 2 ) = 26 . 8,P < 0 . 0 0 0 1 ) . P o s t h o c a n a l y s e s o f t h e g r o u p e f f e c ts h o w e d : ( 1) a h i g h l y s i g n i f i c a n t e f fe c t o n " d e l a y e ds p a t i a l fr e e r e c a ll s c o r e " ( F (1 , 3 2 ) = 5 5 . 5 , P < 0 . 0 0 0 1 ) ,b u t ( 2) n o e f f e c t o n " d e l a y e d v e r b a l f r e e r e c a ll s c o r e "(F (1 , 32) = 3 .0 , P = 0 .09) . P o s t h o c a n a l y s e s o f t h e t y p eo f l e a r n i n g e f f e c t s h o w e d : ( 1 ) a h i g h l y s i g n i f i c a n td i f f e r e n c e i n p a t i e n t s b e t w e e n " d e l a y e d s p a t i a l f r e er e c a ll s c o r e " a n d " d e l a y e d v e r b a l f r e e r e c a ll s c o r e " ,wh ic h was h ig h e r (F (1 , 1 9 )= 9 .5 , P < 0 .007 ) ; (2 ) a h igh lys i g n i f i c a n t d i f f e r e n c e b e t w e e n t h e s e s c o r e s i n c o n t r o l s( F ( 1 , 1 3 ) = 4 3 . 1 , P = 0 . 0 0 0 1 ) . T h e r e f o r e , t h e g r o u p b yt y p e o f l e a r n i n g in t e r a c t i o n r e s u l t e d f r o m b o t h a s p ec i fi cd e f i c i t o f p a t i e n t s o n t h e " d e l a y e d s p a t i a l f r e e r e c a l ls c o r e " a n d a b e t t e r p e r f o r m a n c e o f c o n t r o ls o n " d e l a y e ds p a t i a l fr e e re c a l l s c o r e " t h a n o n " d e l a y e d v e r b a l f re ereca l l s co re " .

D e l a y e d t o t a l r e c a l l s c o r e s . T h e " d e l a y e d v e r b a l t o ta lr e c a ll s c o r e " o f c o n t r o l s w a s p e r f e c t. G i v e n t h e a b s e n c eo f v a r i a n c e o n t h i s s c o r e , o n l y n o n p a r a m e t r i c t e s t s w e r eu s e d f o r a n y c o m p a r i s o n i n c l u d i n g v e r b a l p e r f o r m a n c ea n d c o n t r o l s . T h e g r o u p e f f e c t w a s m a r g i n a l l y s i g n i fi c a n to n t h i s s c o r e (z = 2 . 2, P < 0 . 03 ; M a n n - W h i t n e y U t e s t) ,b u t w a s h i g h l y s i g n i f i c a n t o n t h e " d e l a y e d s p a t i a l t o t a lr e c a ll s c o r e " ( F ( 1, 3 2 ) = 1 7 .0 , P < 0 . 0 0 0 2 ) . T h e t y p e o fl e a r n i n g e f f e c t w a s h i g h l y s i g n i f i c a n t in p a t i e n t s , w i t h alower s p a t i a l s co re (F (1 , 1 9 ) = 25 .7 , P < 0 .0001 ) , bu t wasn o t s i g n if i c an t i n c o n t r o l s ( z = l . 6 , P = 0 . 1 1 o n t h eW i l c o x o n s i g n e d - r a n k t e s t ) .

R e c o g n i t i o n s c o r e s . T h e " c o r r e c t r e c o g n i t i o n v e r b a ls c o r e " o f c o n t r o l s w a s p e r f e c t. G i v e n t h e a b s e n c e o fv a r i a n c e o n t h i s s c o r e , o n l y n o n p a r a m e t r i c t e s t s w e r e

u s e d i n t h e r e l a t e d c o m p a r i s o n s . T h e g r o u p e f f e c t w a sn o t s i g n if i ca n t o n t h is s c or e ( z = 0 . 8 , P = 0 . 4 2 ; M a n n -W h i t n e y U t e s t ), b u t w a s h i g h l y s i g n i fi c a n t o n t h e" c o r r e c t r e c o g n i t i o n s p a t i a l s c o r e " ( F ( 1 , 3 2 ) = 1 5. 1,P < 0 . 0 0 0 5 ) . T h e t y p e o f l e a r n i n g ef f e c t w a s h i g h l ys i g n i fi c a n t i n p a t i e n t s , w i t h a l o w e r s p a t i a l s c o r e ( F ( 1,1 9 ) = 2 7 . 8 , P < 0 . 0 0 0 1 ) , b u t w a s n o t s i g n i fi c a n t i nc o n t r o l s ( z = 1 .9 , P = 0 . 0 6 o n t h e W i l c o x o n s i g n e d - r a n kt e st ) . T h i s s p e c if i c s p a t i a l i m p a i r m e n t o f p a t i e n t s , e v e n a tr e c o g n i t i o n , w a s c o n f i r m e d b y t h e n u m b e r o f f a l s ea l a rm s a t r e c o g n i ti o n , b o t h f o r t h e " p r o x i m a l i n c o r r e c trecog n i t i on sco re" (1 .1 +0 .3 i n p a t i e n t s v s 0 .0+__0 .0 i nc o n t r o l s ; z = 3. 05 , P < 0 . 00 2 ; M a n n - W h i t n e y U t e s t ) a n dt h e " d i s t a l i n c o r r e c t r e c o g n i t i o n s c o r e " ( 0 . 9 + 0 . 2 i np a t i en t s v s 0 .0 _ 0 .0 i n con t ro l s ; z = 3 .05 , P < 0 .002) .

C o m p l e m e n t a r y t e s t sR e s u l t s s h o w e d i n p a t i e n t s a m i l d d y s e x e c u t i v es y n d r o m e a n d a m i l d i m p a i r m e n t i n v i s u o - s p a t i a lp e r c e p t i v e f u n c t i o n s ( T a b l e 2 ).T h e p e r f o r m a n c e o f t h e t w o g r o u p s s i g n i f i c a n t lyd i f f e re d f o r ( 1) t h e n u m b e r o f p e r s e v e r a t i o n s a t t h eW i s c o n s i n C a r d S o r t i n g T e s t ( F ( 1 , 3 2 ) = 6 . 6 , P = 0 . 0 1 ) ;( 2) t h e f r o n t a l b e h a v i o r s ( F (1 , 3 2 ) = 2 5 . 8 , P < 0 . 0 0 0 1 ) ;

( 3) t h e g l o b a l f r o n t a l sc o r e s ( F (1 , 3 2 ) = 8 . 4 , P < 0 . 0 0 7 ) ;( 4) t h e t h i r d tr i a l o f t h e O d d M a n O u t T e s t ( F ( 1,3 2 ) = 7 . 5 , P < 0 . 0 1 ) . T h e r e w a s a l s o a t r e n d f o r a l o w e rp e r f o r m a n c e o f p a t i e n t s f o r ( 1 ) t h e g r a p h i c s e ri es ( F ( 1 ,32 ) = 4 .2 , P < 0.05 ) ; (2 ) t h e S t roo p i n t e r fe renc e cond i t i o n( F (1 , 3 2 ) = 4 . 2 , P < 0 . 0 5 ) ; ( 3) t h e t o t a l s c o r e o f th e O d dM a n O u t T e s t ( F (1 , 3 2 ) = 5 .4 , P < 0 . 0 5 ) ; ( 4) t h e s h if t i n gs c o r e ( t o t a l m i n u s f i rs t t r ia l ) o f th e O d d M a n O u t T e s t( F ( 1, 3 2 ) = 6 . 2 , P < 0 . 0 2 ) ; ( 5) t h e l i n e o r i e n t a t i o n t e s t( F ( I , 3 2 ) = 4 . 7 , P < 0 . 0 5 ) . T h e r e w a s n o s i gn i fi c a nt

Table 2 . Com plementary tes tsPat ients Controls

Wisconsin CSTCriteria 4.8 + 0.4 5.6 + 0.3Perseverations 2.9_+ 0.6* 0.9 + 0.3Lexical fluencyCa tego ry 46.2_+ 2.9 49.5 _+ 3.3L ett er 25.2 +__1.8 30.8 __.2. 9G rap hic series 8.7 _ 0.5 9.8 ___0.1Fro ntal behaviors 18.0 + 0.3* 19.7 + 0.2Fr on tal score 51.1 +__1.8" 57.4 + 1.2Stroop testN am ing 63.7 ___3.1 73.6 -+ 3.1Interfe renc e 32.2 -+ 2.5 40.3 _+3.1O d d M a n O u t1 8.5-+0.4 8.9_+0.32 7.8 +0 .5 8.9_+0.53 7.5__+0.5* 9.2_+ 0.34 8.4 +0 .4 9.3_+0.3Shiftin g 23.6 _+ 1.2 27.4_+ 0.8Lin e ori enta tion 22.6 ___1 . 0 2 5 . 4 _ + 0 . 7Fo rm discrimination 28.8___0.7 30.1 _+0.5*Significant difference (P < 0.01) with controls.

8/3/2019 pillon 1996

6/9

82 B. Pillon et al./Memory for spatial loc ation is affected in Pa rkins on's diseased i f f e r e n c e b e t w e e n p a t i e n t s a n d c o n t r o l s f o r ( 1 ) t h en u m b e r o f c r i te r ia a c h i e v e d a t t h e W i s c o n s in C a r dS or t i n g T es t ; (2 ) ca t e go ry f l uency ; (3 ) l e t te r f l uency , and( 4 ) f o r m d i s c r i m i n a t i o n .

Analyses of correlationsControls. Ver ba l f ree reca l l was s i gn i f i can t l y co r re -l a te d w i t h a g e ( r = - 0 . 7 9 , P < 0 . 0 1 ) . V i s u o - s p a ti a l f r ee

r e c al l w a s s i g n i f i c a n t l y c o r r e l a t e d w i t h a g e ( r = - 0 . 7 0 ,P < 0 .01 ) , g loba l f ro n t a l s co re ( r = 0 .57 , P < 0 .05 ) , S t roopi n t er f e re n c e c o n d i t i o n s c or e ( r = 0 . 5 9 , P < 0 . 0 5 ) , O d dM a n O u t t o t a l s c o r e ( r = 0 . 7 6 , P < 0 . 0 1 ) a n d s h i ft i n gs c o r e ( r - - 0 . 7 2 , P < 0 . 0 1 ) . V e r b a l a n d v i s u o - s p a t i a l f r e er e c a ll s c o r e s w e r e n o t s i g n i f ic a n t l y c o r r e l a t e d .Patients. V e r b a l f r e e r e c a ll w a s s i g n i f ic a n t l y c o r r e l a t e dw i th a ge ( r = - 0 . 5 4 , P < 0 . 0 5 ) a n d th e p h o ne m i ce v o c a t i o n o f w o r d s b e g i n n i n g w i t h " M " ( r = 0 . 5 4 ,P < 0 . 0 5 ) . V i s u o - s p a t i a l f r e e r e c a l l w a s n o t s i g n i f i c a n t l yc o r r e l a t e d w i t h a n y o t h e r v a r i a b le . D u r a t i o n o f d i se a s e ,m o t o r d i s a b il i ty ( H o e h n a n d Y a h r [ 17 ]) , a n d a u t o n o m yo f d a i l y l i v i n g s c o r e s w e r e n o t s i g n i f ic a n t l y c o r r e l a t e dwi th v e rba l o r v i suo- sp a t i a l f ree reca l l s co re s .

D i s c u s s i o nT h e s e v e re i m p a i r m e n t o f v is u o - s p a t i a l le a r n i n go b s e r v e d i n n o n d e m e n t e d P D p a t i e n t s c o n s t i t u t e s t h e

m a i n r e s u lt o f t h is s t u d y . C o m p a r e d t o c o n t r o l s , p a ti e n t sh a d a l o w e r p e r f o r m a n c e o n f r e e r e ca l l, t o t a l r e c al l , a n de v e n r e c o g n i t i o n . A s w e c a r e f u l ly m a t c h e d p a t i e n t s a n dc o n t r o l s f o r a g e , e d u c a t i o n a l le v e l, p r e m o r b i d v e r b a l I Q ,g l o b a l i n t e l l e c tu a l e f f ic i e n c y a n d m o o d , s u c h g l o b a lf a c t o r s c a n n o t a c c o u n t f o r t h e s p e c i f i c d i f f i c u l t i e so b s e r v e d i n p a t i e n t s .A v i s u o - s p a t i a l d e f i c i t m a y i n t e r v e n e i n t h i s v i s u o -s p a ti a l m e m o r y i m p a i r m e n t , s i n ce p a t ie n t s h a d a l o w e rp e r f o r m a n c e t h a n c o n t r o l s o n t h e L i n e O r i en t a t i o n T e s t,o n e o f t h e f e w t as k s t h a t d i s t in g u i s h n o n d e m e n t e d P Dp a t i e n t s f r o m n o r m a l s u b j e c ts [ 1 4 , 1 9 ] . A v i s u o - s p a t i a ld e fi c it c a n n o t f u l ly e x p la i n t h e m e m o r y i m p a i r m e n t ,h o w e v e r , s i n c e P D p a t i e n t s e x h i b i t e d a " s p a t i a l e n -c o d i n g s c o r e " s i m i l a r t o t h a t o f c o n t r o l s . M o r e o v e r , n os i g n i f ic a n t c o r r e l a t i o n w a s f o u n d b e t w e e n v i s u o - s p a t i a lm e m o r y p e r f o r m a n c e a n d s c o r e s o n p e r c e p t i v e v i s u o -sp a t i a l t e s t s .A g e n e ra l iz e d m e m o r y d y s f u n c t i o n d o e s n o t s e e m t ob e a p l a u s i b l e e x p l a n a t i o n f o r t h e d e f i c i t i n v i s u o - s p a t i a lm e m o r y , g i v en t h e n e a r n o r m a l p e r f o r m a n c e o f p a t ie n t si n t h e v e r b a l m e m o r y t e s t t h a t i n v e s t i g a t e s t h e s a m em e m o r y p r o c e s s e s ( f r e e a n d c u e d r e c a l l a n d r e c o g n i -t i o n ) . T h e r e l a ti v e p r e s e r v a t i o n o f v e rb a l m e m o r y i n t h ep re sen t s t ud y i s su rp r i s i ng , s i nce v e rba l f ree reca l l i su s u a l l y i m p a i r e d i n P D , e v e n a t a n e a r l y s t a g e o f t h ed i s e a s e , w h e n p a t i e n t s a r e n o t y e t t r e a t e d b y l e v o d o p a[ 8 ] . S u c h a d e f i c i t , h o w e v e r , m a i n l y a p p e a r s i n v e r b a l

l e a r n i n g o f n o n s e m a n t i c a l l y r e l a te d i t e m s , a s i n t h e R e yA u d i t o r y V e r b a l L e a r n i n g T e s t [ 3 9 ] , o r i n t a s k sr e q u i r i n g a s e l f - e l a b o r a t e d s t r a t e g y o f s e m a n t i c c l u s -t e r i n g , s u c h a s t h e C a l i f o r n i a V e r b a l L e a r n i n g T e s t [ 6 ,4 0 ], w h e r e a s i t m a y b e p a r t l y a l l e v i a te d i n m o r e e x p l ic i t lys e m a n t i c a l l y o r g a n i z e d t a s k s , a s i n l o g i c a l m e m o r y [ 39 ].T h e s e m a n t i c c o n t r o l o f e n c o d i n g , p r o v i d e d b y t h ep r o c e d u r e o f G r o b e r a n d B u s c h k e , li k el y a c c o u n t s f o rt h e p re se rv a t i on o f v e rba l f ree reca l l . T h i s re s u l t d i f fe r sf r o m t h a t o f d e m e n t e d P D p a t i en t s , w h o s e v e r b a l f re ereca l l i s s ev e re ly d i s t u rbed , wh i l e t o t a l r e ca l l andr e c o g n i t i o n a r e p r e s e r v e d [ 2 7 ] . S u c h a d i f f e r e n c e isp r e s u m a b l y r e l a t e d t o t h e f a c t t h a t t h e f r o n t a l l o b e - l i k ed y s func t i on , imp l i ca t ed i n t h e re t r i ev a l d e f i c i t [27 ] , i sm o r e p r o m i n e n t i n d e m e n t e d t h a n i n n o n d e m e n t e d P Dp a t i en t s [29 ] .A f a c t o r o f t a s k c o m p l e x i t y m i g h t i n t e r v e n e , b e c a u s ei n t h e v i s u o - s p a t i a l l e a r n i n g t a s k , a t t e n t i o n i s d i v i d e db e t w e e n t h e p i c t u r e a n d i ts l o c a t i o n , b o t h o f w h i c h h a v et o b e r e c a l l e d . T h e r e w a s , h o w e v e r , n o d i f f e r e n c eb e t w e e n v e r b a l a n d v i s u o - s p a t i a l l e a r n i n g i n c o n t r o l s ,e x c e p t f o r d e l a y e d f r e e r e c a l l w h i c h w a s a c t u a l l y b e t t e ri n t h e v i s u o - s p a t i a l c o n d i t i o n . F u r t h e r m o r e , n o d i f f e r -e n c e h a s b e e n f o u n d b e t w e e n p a t i e n t s a n d c o n t r o l s i n ad u a l t a s k c o n d i t i o n , i n w h i c h s u b j e c t s w e r e i n i t i a l l yi n s t r u c t e d t o r e m e m b e r t h e l o c a t i o n o f e a c h i t e m a s w e lla s e s t im a t ing i t s s i ze [7] .I t m i g h t a l s o b e a r g u e d t h a t a d e c r e a s e d f r e e r e c a l lf o r p i c t u r e s m a y a c c o u n t f o r t h e d e f i c i t o f p i c t u r e sl o c a t i o n , b e c a u s e a d i s s o c i a t i o n h a s b e e n o b s e r v e db e t w e e n i m p a i r e d v e r b a l e v o c a t i o n o f p i c t u r e s a n dc o r r e c t s p a t i a l l o c a t i o n o f t h e s a m e i t e m s , a t l e a s t a tc u e d r e c a l l [ 7 ]. N e v e r t h e l e s s , i n o u r s t u d y t h e l o c a t i o nd e f i c i t p e r s i s t e d e v e n w h e n w e t o o k i n t o a c c o u n t t h en u m b e r o f s p o n t a n e o u s l y e v o k e d p i c t u r e s , s i n c e t h ep e r c e n ta g e o f c o r r e c t ly l o c a t e d u p o n s p o n t a n e o u s l ye v o k e d p i c t u r e s w a s a b o u t 3 6 % l o w e r i n p a t i e n t s t h a ni n c o n t r o l s .T a k e n t o g e t h e r , o u r d a t a s u g g e s t t h a t t h e i m p a i r e dp e r f o r m a n c e o f n o n d e m e n t e d P D p a t i e n ts m a y r e s ul tf r o m a p r i m a r y d e f i c i t i n m e m o r y f o r s p a t i a l l o c a t i o n s .S u c h a c o n c l u s i o n i s c o n s i s t e n t w i t h t h e p r e s e n c e o fi n t e r fe r e n c e s b e t w e e n p i c t u r e l o c a t i o n s a t f r e e a n d c u e dr e c a l l , a n d w i t h t h e p e r s i s t e n c e o f t h e l o c a t i o n d e f i c i te v e n a t r e c o g n i t i o n , e i t h e r i n t e r m s o f h i t s o r f a l s ea l a r m s . W h i c h f a c t o r s c o u l d c o n t r i b u t e t o t h e s p a t i a ll o c a t i o n m e m o r y d e f ic i t ? A r e t r ie v a l d e f i c i t, i n r e l a t i o nw i t h d e f i c i e n t r e s e a r c h i n m e m o r y s e l f - e l a b o r a t e ds t r a t e g y , i s u s u a l l y p r o p o s e d t o i n t e r p r e t t h e d i s s o c i a -t i o n s b e t w e e n i m p a i r e d f r e e r e c a l l a n d n o r m a l o r n e a rn o r m a l t o t a l r e c a ll a n d r e c o g n i t i o n , o b s e r v e d i n p a t i e n t sw i t h p r e d o m i n a n t l y s u b c o r t ic a l n e u r o d e g e n e r a t i v e d i s -e a s es [ 2 2 , 2 7 , 28 ]. T h e f a c t t h a t t h e v i s u o - s p a t i a l m e m o r yd e f i c it w a s m u c h m o r e s e v e r e a t f r e e r e c a ll t h a n a t t o t a lr e c a l l o r r e c o g n i t i o n f a v o r s t h i s h y p o t h e s i s . T h e d e f i c i tp e r s i s t e d , h o w e v e r , i n t h e l a s t c o n d i t i o n s , s u g g e s t i n gt h a t t h i s e x p l a n a t i o n c a n n o t b y i t s e l f a c c o u n t f o r t h eo v e r a l l d e f i c it e n c o u n t e r e d i n P D p a t i e n t s .

8/3/2019 pillon 1996

7/9

B. Pillon et al./Memory for spatial location is affected in Parkinson's disease 83A s to rage de f ic i t i s un l ike ly , because the le a rn ingcurves we re s imi la r in pa t ien t s and con t ro l s , andbecause , in bo th g roups , v i suo- spa t ia l f r ee r eca l l wass l igh t ly be t te r a f te r the de lay . Some au thor s havep r o p o s e d a n e n c o d i n g d e f ic i t i n n o n d e m e n t e d P Dpa t ien t s to a ccoun t fo r ve rba l l e a rn ing impa i rmen t [6 ,4 0 ] . T h i s h y p o t h e s i s m a y a p p e a r i n a p p r o p r i a t e t oexpla in the v i suo- spa t ia l l e a rn ing de f ic i t , g iven thenorm a l " sp a t ia l encod ing score s" o f pa t ien t s . I t r ema insposs ib le , howeve r , tha t a s e l f - e labora ted encodings t ra tegy i s su f f ic ien t to pe rmi t norma l ma in tenance o ft h e s p a t i al l o c a t i o n o f 4 p i c t u r e s i n w o r k i n g m e m o r y ,bu t in su f f ic ien t to co r rec t ly encode and ma in ta in 16spa t ia l loca t ions in long- te rm memory .Such a de f ic i t o f encoding se l f - e labora ted s t r a tegymight expla in the d i f f e rence be tween the pre sen t da taa n d t h o s e o f a p r e v i o u s s t u d y s h o w i n g n o r m a l c u e dreca l l of spa t ia l loca t ions [7] . In the la t te r s tudy, a l l to-

be - loca ted p ic tu re s we re pre sen ted s imul taneous ly a tt h e e n c o d i n g p h a s e . T h i s p r o c e d u r e a l l o w e d t h e p a t i e n tt o s p o n t a n e o u s l y s c a n t h e w h o l e m a t r i x , t o a u t o m a t i c -a l ly encode mul t ip le a s soc ia t ive l inks be tween theprec i se to -be - loca ted p ic tu re and a l l the o the r s , andto e labora te a g loba l r epre sen ta t ion o f p ic tu re loca t ionsin the ma t r ix . Th e mul t ip l i ca t ion o f v i sua l cue s , thei m p l i c i t c o n s t r u c t i o n o f a n e x t e r n a l l y g u i d e d w h o l erepre sen ta t ion , and the s imi la r i ty o f con tex t a t theencoding a nd re t r ieva l s tages [41] pre sum ably con t r ib -u ted to norm a l pe r fo rmanc e o f pa t ien t s . In con t ra s t , inour s tudy , we l im i ted the s imul taneous pre sen ta t ion a tencoding to 4 p ic tu re s and reduced the con tex tua ls imi la r i ty be tween encoding and re t r ieva l ( ex tended to16 p ic tu re loca t ions ) .The hyp o the s i s o f a de f ic it in s e l f - e labora teds t r a teg ie s a t bo th the encoding and re t r ieva l s tagesrece ive s some suppor t f rom the mi ld dysexecu t ives y n d r o m e o b s e r v e d i n p a t i e n t s a t t h e W i s c o n s i n C a r dSor t ing Tes t , g loba l f ron ta l s co re , S t roop in te r fe rencec o n d i t i o n a n d O d d M a n O u t T e s t . T h i s i n t e r p r e t a t i o ni s fu r the r sugges ted by the s ign i f ican t co r re la t ionsbe tween f ree r eca l l pe r fo rmance and score s on te s t so f execu t ive func t ions and a t ten t iona l con t ro l ob se rvedin aged norma l sub jec t s . Howeve r , s t i l l o the r f a c to r sma y in te rvene , g iven the d i sappea rance o f the secor re la t ions in pa t ien t s , the h igh n um ber o f in te r fer -ences be tween spa t ia l loca t ions a t f r ee and cued reca l l ,and the pe r s i s tence o f bo th mis se s and fa l se a la rms a tr ecogn i t ion . A s ou t l ined by Sch ac te r [33 ] , " f ron ta lr eg ions p lay a ma jo r ro le in the segmenta t ion andorgan iza t ion o f on-go ing expe r ience in to d i s t inc tiveun i t s tha t a re d i s c r iminab le f rom one ano the r" . Thisf ron ta l r e la ted proces s , r e fe r red to a s "con tex tua lc h u n k i n g " , w o u l d i n t e r v e n e i n t e m p o r a l a n d s p a t i a lb u t n o t i n i t e m m e m o r y . I n a g r e e m e n t w i t h t h i si n t e r p r e t a t i o n , a r e c e n t s t u d y h a s d e m o n s t r a t e d t h a t" o b j e c t l o c a t i o n i n e l d e rl y a d u l t s w a s d e p e n d e n t o n t h ev isua l d i s t inc t iveness o f the con tex t in which theo b j e c ts t o - b e - r e m e m b e r e d w e r e p l a c e d " [ 35 ].

C o n c l u s i o nRecen t s tud ie s impl ica ted the s t r i a to - f ron ta l dys func-t ion assoc ia ted w ith P D [10] in def ic i ts of f ree reca l l [22 ,27, 28] , encoding se lf -e labora ted s tra tegies [6 , 40] , anda l so o f temp ora l o rgan iza t ion o f memor ie s [32 , 40 , 42] .S t r ia to - f ron ta l c i r cu i ts m ight a l so spec i f i ca lly in te rvenei n s p a t ia l l o c a t i o n m e m o r y , a n o t h e r a s p e c t o f c o n t e x tu a lremember ing [33 ] , a s sugges ted by the r e su l t s o f thepre sen t s tudy . This wou ld expla in the sub jec t ive f ee l ingo f s p at i al d i s o r i e n t at i o n t h a t n o n d e m e n t e d p a r k i n s o n i a npa t ien t s may expre s s .

Acknowledgments--Florence Calicis, Chantal Wyns and Mar-tial Van Der Linden permitted use of their French adaptationof the Grober and Busch ke Test . Mart ia l Van Der Lindenhelped us to critically examine a previous version o f the visuo-spatial learning test.

R e f e r e n c e s1 . Alexande r , G. E . , De Long , M. R . and S t r ick , P . L .Pa ra l le l o rgan iza t ion o f func t iona l ly segrega tedc i r cu i t s l ink ing ba sa l gang l ia and cor tex . Ann. Rev.Neurosci. 9, 357-381, 1986.2 . Beaurega rd , D. Le Test Des Automatismes Verbaux,Edi t ions Sc ien t if iques e t Psycho techn iques , I s sy-le s -Moul ineaux , France , 1971 .3 . Ben ton , A. L . D i f fe ren t ia l behav io ra l e f fec t s inf ron ta l lobe d i sea se . Neuropsychologia 6, 53-60,1968.4 . B e n t o n A . L . , H a m s h e r , K . , V a r n e y , N . R . a n dSpreen , O. Contributions to NeuropsychologicalAssessment, Oxford Unive r s i ty Pre s s , Oxford , 1983 .5 . Blin , J ., Baro n, J . C . , Dub ois , B. , Pi l lon, B . ,C a m b o n , H . , C a m b i e r , J . a n d A g i d , Y . P o s i t r o ne m i s s i o n t o m o g r a p h y s t u d y i n p r o g r e s s i v e s u p r a -n u c l e a r p a l s y : b r a i n h y p o m e t a b o l i c p a t t e r n a n dc l in ico -me tabo l ic co r re la t ions . Arch. Neurol. 4 7 ,747-752, 1990.6 . Buytenhu i j s , E . L . , Be rge r , H. J . , Van Spaendonck ,K . P . , H o r s t i n k , M . W . , B o r m , G . F . a n d C o o l s , A .R . Memory and lea rn ing s t r a teg ie s in pa t ien t s wi thPa rk inson ' s d i sea se . Neuropsychologia 32 , 335 -342 ,1994.7 . Coo pe r , J . A . and Saga r , H. J . Inc iden ta l an din ten t iona l r e ca l l in Pa rk inson ' s d i sea se : an accoun tbased on d imin ished a t ten t iona l r e source s . J. Clin.Exp. Neuropsychol. 15, 713-731, 1993.8 . Coope r , J . A . , Saga r , H. J . , Jo rdan , N. , Ha rvey , N.S . and Su l l ivan E . Cogn i t ive impa i rmen t in ea r ly ,un t rea ted Pa rk inson ' s d i sea se and i t s r e la t ionsh ip tomotor d i sab i l i ty . Brain 114, 2095-2122, 1991.9 . Dubois , B. , Boiler , F. , Pi l lon, B. and Agid, Y.Cogn i t ive de f ic i t s in Pa rk inson ' s d i sea se . InHandbook of Neuropsychology, F. Bo i le r and J .Gra fman (Edi to r s ) , Vo l . 5 , pp . 195 -240 . E l sev ie r ,A m s t e r d a m , 1 9 9 1 .10 . Dubo is , B . and P i l lon , B . B iochemica l co r re la te s o fc o g n i t i v e c h a n g e s a n d d e m e n t i a i n P a r k i n s o n ' s

8/3/2019 pillon 1996

8/9

84 B. Pillo n et al . /Memory for spatial location is affected in Parkinson's diseasedisease . In Park i n son ' s Di sease Neurobehav i o ra lAspec t s , S . J . H u b e r a n d J . L . C u m m i n g s(Edi to r s ) , pp . 178 -198 . Oxford Unive r s i ty Pre s s ,Oxford , 1992 .11 . E rg i s , A. M. , Van Der L inden , M. and Dewee r , B .L ' e x p l o r a t i o n d e l a m t m o i r e 6 p i s o d i q u e d a n s l am a l a d i e d ' A l z h e i m e r d t b u t a n t e a u m o y e n d ' u n e6preuve de r ap pe l ind ic& Revue de Neuropsycho l ogi e4, 47-68, 1994.1 2 . F a h n , S . , E l t o n , R . L . a n d U P D R S D e v e l o p m e n tCom mit tee . U n i f ied Pa rk in son ' s d i sea se r a t ingscale. In Recen t Deve l opmen t s i n Park i n son ' sDisease, S . F a h n , C . D . M a r s d e n , D . C a l n e a n dM. Golds te in (Edi to r s ) , Vo l . 2 , pp . 153 -163 ; 293 -3 0 4 . M c M i l l a n H e a l t h c a r e I n f o r m a t i o n , F l o r h a mP a r k , N Y , 1 9 8 7 .13 . Fo ls te in , M. F . , Fo ls te in , S . E . and McHugh, P . R .Min i -men ta l s ta te : a p rac t i ca l me thod fo r g rad ingthe cogn i t ive s ta tus o f pa t ien t s fo r the c linic ian . J .Psych i a t r . Res . 12, 189-198, 1975.

14. G irot t i , F. , Soliver i , P. , Ca re l la , F. , Pic colo, I . ,Ca f fa r ra , P . , Mus icco , M. and Ca racen i , T .D e m e n t i a a n d c o g n i t i v e i m p a i r m e n t i n P a r k i n s o n ' sdisease . J . NeuroL Neurosurg . Psych i a t . 51, 1498 -1502, 1988.15 . Go lden , C . J . S t roop C o l or and Wo rd Tes t . S toe l t ingC o m p a n y , C h i c a g o , I L , 1 9 7 8 .1 6. G r o b e r , E . a n d B u s c h k e , H . G e n u i n e m e m o r yde f ic i t s in dement ia . Dev. Neuropsychol . 3, 13-36,1987.1 7. H o e h n , M . M . a n d Y a h r , M . D . P a rk i n s o n is m :Onse t , p rogre s s ion and mor ta l i ty . Neuro l ogy 17,427-442 , 1967 .18 . Inc i sa De l la Roche t ta , A. and Mi lne r , B . S t r a teg icsea rch and re t r ieva l inh ib i t ion : Th e ro le o f thef ron ta l lobes . Neuropsycho l og i a 31, 503-524, 1993.19 . Lave rnhe , G. , Po l lak , P . , Bren ie r , F . , Ga io , J . M. ,Hommel , M. , Pe l la t , J . and Pe r re t , J . Ma lad ied 'Alzhe imer e t ma lad ie de Pa rk inson .D i f f t r e n t i a t i o n n e u r o p s y c h o l o g i q u e . Rev. Neurol .145, 24-30, 1989.20 . Lhe rmi t te , F . , P i l lon , B . and Se rda ru , M. Humanau tonomy and the f ron ta l lobes , I : Imi ta t ion andu t i li z at i o n b e h a v i o r s : A n e u r o p s y c h o l o g i c a l s t u d y o f75 pa t ients . Ann . Neuro l . 19, 326-334, 1986.21 . Lur ia , A. R . Higher Cort ical Funct ions in Man.B a s i c B o o k s I n c ., N e w Y o r k , 1 9 66 .22 . Massman , P . J . , De l i s , D. C . , Bu t te r s , N. , Levin , B .E . and Sa lmon , D. P . Are a l l subcor t i ca l dement ia sa l ike? Ve rba l l e a rn ing and memory in Pa rk inson ' sa n d H u n t i n g t o n ' s d i s e a s e p a t i e n t s . J. Clin. Exp.Neuropsycho l . 12, 729-744, 1990.23 . Ma t t i s , S . Demen t i a Ra t i ng Sca l e . P s y c h o l o g i c a lAsse s smen t Resource s Inc . , Odessa , FL, 1988 .2 4 . M o n t g o m e r y , S . A . a n d A s b e r g , M . A n e wdepre s s ion sca le de s igned to be sens i tive to change .Br. J . Psychiatry 134, 382-389, 1979.25 . Ne lson , H. E . A mod i f ied Ca rd Sor t ing Tes tsens i t ive to f ron ta l lobe de fec t . Cor tex 12 , 313 -324, 1976.26 . Pe t r ide s , M . D e f ic it s on c ondi t iona l a s soc ia t ivelea rn ing ta sks a f te r f ron ta l and tempora l lobele s ions in man . Neuropsycho l og i a 23, 601-614, 1985.

27 . P i l lon , B . , Dewee r , B . , Ag id , Y. and Dubo is , B .E x p l i c i t m e m o r y i n A l z h e i m e r ' s , H u n t i n g t o n ' s a n dPa rk inson ' s d i sea se s . Arch. Neurol . 50 , 374-379 ,1993.28 . P i l lon , B . , Dewee r , B . , Michon , A. , Ma lapan i , C . ,A g i d , Y . a n d D u b o i s , B . A r e e x p l i c i t m e m o r ydiso rde r s o f p rogre s s ive supran uc lea r p a l sy r e la tedt o d a m a g e t o s t r i a t o f r o n t a l c i r c u i t s ? C o m p a r i s o nw i t h A l z h e i m e r ' s , P a r k i n s o n ' s , a n d H u n t i n g t o n ' sdiseases . Neuro l ogy 44, 1264-1270, 1994.29 . P i l lon , B . , Dubo is , B . , P loska , A. and Agid , Y.Seve r i ty and spec i f i c i ty o f cogn i t ive impa i rmen t inAlzhe imer ' s , Hun t ing ton ' s , and Pa rk inson ' s d i s -ea se s and progre s s ive supranuc lea r pa l sy .Neuro l ogy 41, 634-643, 1991.30 . P i l lon , B . , G ou id e r -K hou ja , N. , Dew ee r , B . ,Vidha i le t , M. , Ma lapan i , C . , Dubo is , B . and Agid ,Y . N e u r o p s y c h o l o g i c a l p a t t e r n o f s t r i a t o n i g r a ld e g e n e ra t i on : C o m p a r i s o n w i t h P a r k i n s o n ' s d i s e a s eand progre s s ive supranuc lea r pa l sy . J . Neurol .Neurosurg , Psych i a r 58, 174-179, 1995.31 . R icha rds , M. , Co te , L . J . and S te rn , Y. Execu t ivefunc t ions in Pa rk inso n ' s d i sea se : Se t - sh i ft ing o r s e t -ma in tenance . J . Cl in . Exp. Neuropsychol . 15 , 266 -279, 1993.32. Sagar , H. J . , Cohen, N. J . , Sull ivan, E. V. , Corkin,S . a n d G r o w d o n , J . H . R e m o t e m e m o r y f u n c t i o n i nAlzhe imer ' s d i sea se and Pa rk inson ' s d i sea se . Brain111, 185-206, 1988.33 . Schac te r , D. L . Memory , amnes ia , and f ron ta l lobedys func t ion . Psychob i o l ogy 15, 21-36, 1987.34 . Schw ab , R . S . and Eng land , A. C . Pro j ec t iontechn iques fo r eva lua t ing su rge ry in Pa rk inson ' sdisease . In 3rd Sympos i um i n Park i n son ' s Di sease ,F. J . Gi l l ingham and I . M. Do na ld son (Edi to r s ) ,pp . 151-157 . E . & S . L iv ings tone , Edinburgh , UK,1969.35 . Sha rps , M. J . and Gol l in , E . S . Memory fo r ob j ec t sloca t ion in youn g and e lde r ly adu l ts . J . Gerontol . 42 ,336-341, 1987.36 . Sh im amura , A. P . , Janow sky , J. S . and Squ i re , L . R .W h a t i s t h e ro l e o f fr o n t a l l o b e d a m a g e i n m e m o r ydiso rde r s? In Fron ta l Lobe Funct i on andDysfunct ion , H. S . Levin , H. M. He isenbe rg andA. L . Ben ton (Edi to r s ) , pp . 173 -195 . OxfordUnive r s i ty Pre s s , Oxford , 1991 .37. Sm ith, M. L . and M ilner , B. Differentia l e ffects off ron ta l lobe le s ions on cogn i t ive e s t ima t ion andspa t ia l memory . Neuropsycho l og i a 22 , 697-705 ,1984.38 . Snodgra s s , J . G . and V ande rv a r t , M. A. As t a n d a r d i ze d s e t o f 2 6 0 p ic t u re s : N o r m s f o r n a m eagreement , f ami l ia r i ty and v i sua l complex i ty . J .E x p . P s y c h o l . , H u m a n L e a r n i n g M e m o r y 6, 174-215, 1980.39 . Taylo r , A. E . , Sa in t -Cyr , J . A . and Lang , A. E .F r o n t a l l o b e d y s f u n c t i o n i n P a r k i n s o n ' s d i s e a s e - -the co r t i ca l focus o f neos t r ia ta l ou t f low. Brain 109,845-883, 1986.40 . Taylo r , A. R . , Sa in t -Cyr , J . A . and Lang , A. E ,Memory and lea rn ing in ea r ly Pa rk inson ' s d i sea se :E v i d e n c e f o r a " f r o n t a l l o b e s y n d r o m e " . BrainCogn. 13, 211-232, 1990.

8/3/2019 pillon 1996

9/9

B. Pillonet al . /Memory for spatial location is affected in Parkinson's disease 8541. Tulving, E. and Pearlstone, Z. Availability versusaccessibility of info rmation in memory for words. J.Verb. Learn . Verb. Behav. 5, 381-391, 1966.

42. Vriezen, E. R. and Moscovitch, M. Memory fortemporal order and conditional associative learningin patients with Parkinson's disease. Neuropsycho -logia 28, 1283-1293, 1990.