19 Salas Milagros - Snowden

Neuropsychologia 41 (2003) 688701

Social cognition in frontotemporal dementia and Huntingtons diseaseJ.S. Snowden a,, Z.C. Gibbons a, A. Blackshaw a, E. Doubleday a, J. Thompson a,b,

D. Craufurd b, J. Foster c, F. Happ d, D. Neary aa Cerebral Function Unit, Greater Manchester Neuroscience Centre, Hope Hospital, Salford M6 8HD, UK

b University Department of Medical Genetics, St. Marys Hospital, Manchester M13, UKc Department of Psychology, University of Western Australia, Crawley, Perth, WA 6009, Australia

d Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, Kings College, London, UKReceived 19 February 2002; received in revised form 2 October 2002; accepted 2 October 2002

Abstract

Frontotemporal dementia (FTD) and Huntingtons disease (HD) are degenerative disorders, with predominant involvement, respectivelyof frontal neocortex and striatum. Both conditions give rise to altered social conduct and breakdown in interpersonal relationships,although the factors underlying these changes remain poorly defined. The study used tests of theory of mind (interpretation of cartoonsand stories and judgement of preference based on eye gaze) to explore the ability of patients with FTD and HD to interpret social situationsand ascribe mental states to others. Performance in the FTD group was severely impaired on all tasks, regardless of whether the testcondition required attribution of a mental state. The HD group showed a milder impairment in cartoon and story interpretation, and normalpreference judgements. Qualitative differences in performance were demonstrated between groups. FTD patients made more concrete,literal interpretations, whereas HD patients were more likely to misconstrue situations. The findings are interpreted as demonstratingimpaired theory of mind in FTD, as one component of widespread executive deficits. In HD the evidence does not suggest a fundamentalloss of theory of mind, but rather a tendency to draw faulty inferences from social situations. It is concluded that social breakdown in FTDand HD may have a different underlying basis and that the frontal neocortex and striatum have distinct contributions to social behaviour. 2002 Elsevier Science Ltd. All rights reserved.

Keywords: Frontotemporal dementia; Huntingtons disease; Social cognition, theory of mind; Behaviour

1. Introduction

Frontotemporal dementia (FTD) and Huntingtons disease(HD) are degenerative brain disorders that affect frontostri-atal systems. FTD is a predominantly neocortical disorder,characterised by radical alterations in personality, emotions,and social, interpersonal conduct [12,25,35,44,46,47,56].Behavioural changes include disinhibition, tactlessness, andloss of social proprieties [12,37,44,45,47]. Cognitive assess-ment typically shows deficits predominantly in frontal ex-ecutive functions [47,57], indicating deficits in abstraction,problem solving, attention, mental set shifting, sequencing,and mental generation of information. Patients are not clin-ically amnesic, although formal memory test performanceis often inefficient, attributed to executive impairments.

Neuroimaging [48,62] and pathological studies [41]of FTD demonstrate severe frontal and anterior temporal

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E-mail address: [email protected] (J.S. Snowden).

neocortical atrophy, which may be largely confined to or-bital regions, or (particularly with progression of disease)more widespread extending into anterior cingulate and dor-solateral frontal cortex. Modest pathological changes in thestriatum reflect the emergence of striatal neurological signsusually relatively late in the disease course.

Huntingtons disease (HD) is a predominantly subcor-tical disorder, distinguished clinically by its characteristicinvoluntary movements [30]. Patients social conduct isaltered, albeit less profoundly than in FTD, and there isfrequently severe breakdown in interpersonal relationships.Patients are often described as self-centred, lacking in sym-pathy and empathy, and mentally inflexible, sometimes withfixed ideas, which may not be consistent with the prevailingview or available evidence. As in FTD deficits have beenreported in the processing of emotions [23,32,59]. Cog-nitive changes are predominantly in the realm of frontalexecutive function [14], although generally less marked indegree than in FTD, and memory impairment is ascribedto inefficient encoding and retrieval strategies rather than aprimary failure of retention.

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Pathological [40,63] and structural neuroimaging [6,38]studies of HD have demonstrated marked atrophy of cau-date and putamen, which form the dorsal part of the stria-tum or neostriatum. This is present even in the early stagesof disease [4], and has been reported in some studies inpre-symptomatic individuals who carry the HD mutation [5].Some frontal neocortical atrophy may also occur later in thedisease course [7], assumed to be at least partly (althoughnot necessarily exclusively) secondary to striatal differenti-ation [40].

Thus, FTD and HD represent complementary disordersin which there is a virtual, although not exclusive, doubledissociation with respect to the distribution of degenerativechange within the frontal neocortex and striatum. FTD andHD thus provide ideal models for the study of frontal-striatalfunction. The striatum has traditionally been recognised forits importance in the domain of motor functioning, in theexecution of learned motor plans [42]. Conditions such asHD attest to its crucial role also in cognition. The identifi-cation of parallel and segregated frontal-subcortical circuits,distinguished by their areas of origin in the frontal cortex[3,43], has led to the notion that the striatum is intimatelylinked functionally to the cerebral cortex. The assumptionis that analogous cognitive deficits may arise from disrup-tion at different levels (i.e. frontal cortical or striatal) of thecircuit.

Commonalities between FTD and HD with respect to theprominence of behavioural changes and pattern of cognitivedeficits are thus unsurprising. Nevertheless, it cannot be in-ferred that deficits underlying FTD and HD are identical.Executive tasks make multiple demands, so that test scoresmay mask fundamental differences in the reason for fail-ure. Similarly, disordered social behaviour might have dif-ferent underlying substrates. Comparative studies of FTDand HD ought to clarify the nature of change in each con-dition. Moreover, in view of the predominance of frontalneocortical changes in FTD and of striatal changes in HD,such studies provide the potential for improving knowledgeof the relative contributions of the frontal lobes and striatumin behaviour and cognition.

Traditional executive tasks do not capture the full range ofabnormalities in FTD and HD and may be a relatively poorpredictor of the patients functioning in daily life. Indeed,some patients with FTD, in whom the pathology is confinedto the orbital regions of the frontal lobes, perform relativelywell on conventional executive tasks, despite impairedjudgement and gross breakdown in their social conduct indaily life [39,57]. Such a finding is consistent with reportsthat lesions of the orbital frontal lobes may give rise tosevere breakdown in social behaviour in the context of nor-mal executive functioning [15,16,54]. In HD, disorganisedbehaviour and breakdown in interpersonal relationships indaily life are often prominent clinical features, outweighingchanges in neuropsychological test performance. There areat least two factors that are likely to contribute to the relativeinsensitivity of traditional tests to some of the changes in

FTD and HD. Traditional neuropsychological tests are struc-tured and typically require a constrained set of responses.By contrast, everyday life situations are open-ended, andrequire self-generated structure and organisation. Secondly,traditional tests are impersonal, whereas everyday life in-volves social interaction. Neuropsychological tasks that areboth open-ended and involve interpretation of social scenar-ios are likely to be particularly informative in FTD and HDbecause they mirror the daily life situations in which FTDand HD patients so dramatically fail. They may also havethe potential to reveal fundamental differences between FTDand HD.

Recent years have seen an accumulation of literature onsocial cognition [1,2]. A core component of social function-ing is the capacity to attribute independent mental states toothers and to predict other peoples behaviour on the ba-sis of their mental states, a capacity known as theory ofmind [9,36,51]. There is a growing body of evidence fromboth neuroimaging [10,18,20,21,27] and brain lesion studies[24,29,53,60,61] that the frontal lobes have a pivotal role intheory of mind. However, to date there have been no directcomparisons in performance on tests of social cognition be-tween patients with predominantly frontal neocortical andpredominantly striatal pathology.

Clinical observation of patients with FTD and HD leadsto the prediction that performance on tests that require inter-pretation of event scenarios is likely to differ. FTD patientstypically lack insight into the change in their own behaviourand appear oblivious of the effects that their behaviour hason others, leading to the prediction that such patients showa genuine loss of theory of mind. By contrast, at clinical in-terview HD patients may make pertinent and insightful re-marks about the effects of their illness on a close relative(e.g. It is hard on my husband having to do everything forme. He must get very fed up). Such apparent cognisanceof others mental states leads to the prediction that socialbreakdown in HD arises for reasons other than a primaryinability to ascribe mental states to others. In FTD, a pur-ported problem in theory of mind is unlikely to be exclusive.FTD patients commonly show concreteness of thought. Aconcrete interpretation of events would be expected to bemanifest in a general difficulty in the interpretation of socialscenarios, even when they do not depend on attribution ofmental states.

The present study investigates the ability of FTD andHD patients to interpret social situations and explores bymeans of error analysis possible differences between thetwo groups. The study involved four tasks drawn from theliterature on social cognition that have been used to addresstheory of mind. The tasks differ with respect to their levelof difficulty. The cartoon and story tasks (tasks 13) makerelatively great mental demands on the patient raising thepossibility that they may exceed the capabilities of some pa-tients for reasons that have little to do with social cognitionper se. The judgement of preference task (task 4) examinesthe capacity for mental state attribution while minimising

690 J.S. Snowden et al. / Neuropsychologia 41 (2003) 688701

executive demands. It was predicted that FTD patientswould show a general impairment, compared to normal, intheir ability to interpret situations, but that this should beparticularly pronounced when attribution of mental statesis required. It was anticipated that HD patients would showimpaired performance relative to normal, but to a lesser ex-tent than FTD. It was predicted, however, that HD patientswould not show a disproportionate impairment in tasksdependent upon mental state attribution compared to tasksinvolving interpretation of non-social scenarios. The pat-tern of performance ought to clarify the nature of patientsdeficits more precisely and may help to identify factors thatcontribute to the breakdown in social functioning in FTDand HD.

2. Methods

2.1. Participants

Two patient groups and a normal control group took partin the study. Informed written consent was obtained fromparticipants and/or their next of kin. The study was grantedapproval by the local Ethics Committee.

2.1.1. Frontotemporal dementia (FTD)The FTD group comprised 13 consecutive patients, 9 men

and 4 women, referred to a Neurology Department Special-ist Dementia Clinic who met clinical criteria for FTD [46].Diagnosis was based on historical information, neurolog-ical examination and neuropsychological assessment, andsupported by structural (magnetic resonance) and functional(single photon emission computerised tomography) brainimaging. The presenting feature in all cases was personal-ity change and all patients had demonstrable frontal exec-utive impairments on cognitive evaluation. Patients were inthe mild to moderate stages of the disease, and were phys-ically well. Neurological examination was entirely normalin 10 patients. The remaining three patients showed a milddegree of limb rigidity. Neuroimaging showed changes pre-dominantly in orbital frontal cortex in nine patients, andwidespread frontal lobe changes in the remaining four pa-tients. Demographic information and clinical features areshown in Table 1. The patients had a mean Mini MentalState Examination (MMSE) [19] score of 22. The table alsoshows scores on category and letter fluency tests [58] (total

Table 1Demographic, clinical and neuropsychological characteristics

Group Number Male:female Age (years) Durationillness

MMSE Animalsper minute

F wordsper minute

WCSTcategories

FTD 13 9:4 60 (7) 3 (2) 22 (6) 12 (4) 6 (5) 1.4 (1.9)HD 13 5:8 50 (7) 6 (3) 25 (3) 14 (4) 8 (4) 5.5 (0.9)Control 18 8:10 49 (23) n/a (n/a) n/a (n/a) n/a (n/a) n/a (n/a) n/a (n/a)The data represent mean (S.D.).

number of animals and words beginning with F generated in1 min) and the number of categories achieved in the modi-fied version of the Wisconsin Card Sorting test [49]. The lowscores highlight the presence of frontal executive deficits inthe FTD group.

2.1.2. Huntingtons disease (HD)The HD group consisted of 13 consecutive patients, 5

males and 8 females, attending a regional HD clinic. In all,the presence of HD had been confirmed by genetic testingand all showed the characteristic choreiform movement dis-order, and cognitive changes associated with the disorder.Patients had a mean Total Functional Capacity score [55] of9.5 indicating that they were in the mild to moderate stagesof disease. They had a mean motor deficit score of 26/124,range 555, as measured by the Unified Huntingtons Dis-ease Rating Scale (UHDRS) [31], consistent with mild tomoderate disease. Six patients were taking prescribed med-ications for the treatment of mood changes, particularlyirritability. The remaining seven patients were on no medi-cation. No imaging data were available. A definitive diagno-sis of HD can be made on the basis of the clinical featuresand genetic test, so that neuroimaging was not clinicallyjustified.

Patient demographics and clinical data are shown inTable 1. They were younger than the FTD patients (t =3.5, P < 0.002), commensurate with the younger onsetage of HD, and they had been clinically symptomatic forlonger (t = 2.2, P = 0.04), consistent with the more pro-tracted course of HD. The HD group did not differ fromthe FTD group with respect to MMSE or category andletter fluency scores. However, performance was less im-paired on the Wisconsin Card Sorting test, as measuredby the greater number of categories achieved (t = 10.7,P < 0.0001).

2.1.3. ControlsThe control group consisted of 18 people who were

spouses of participants in the patient groups. All werehealthy individuals who had no history of neurologicaldisease, head injury or alcohol abuse. The control groupcovered a wider distribution of ages than the two patientgroups (Table 1), reflecting the fact that they were drawnfrom the spouses of both groups. The mean difference inage between controls and the two patient groups did notreach statistical significance.


2.2. Task 1: single cartoon abstraction

2.2.1. MaterialsThe materials, taken from Happ et al. [28], consisted of

12 humorous cartoons. In six, designated mental cartoons,the humour related to a cartoon characters mistaken beliefor deception, so that humour appreciation required inferenceof a persons mental state. In one cartoon, for example, aman is shown cuddling a young woman who is sitting onhis lap, while, with his free hand, he is tapping a ping-pongball with a bat. The humour lies in the fact that an olderwoman sitting in the adjacent room, within earshot but outof view of the couple, is deceived into believing that the manis playing table tennis, whereas in reality he is otherwiseoccupied. In six cartoons, designated physical and matchedfor difficulty with the mental cartoons, the humour relatedto physical properties or anomalies in the cartoon and did notrequire inference of a persons mental state. For example, inone cartoon, a line of musicians is shown entering the stagedoor, each carrying a musical instrument case. One manhas no head, but is carrying a head-shaped instrument case.Illustrative examples of cartoons are given by Happ [28].

2.2.2. ProcedureThe cartoons were presented in randomised order, in ac-

cordance with Happ et al. [28], and subjects were asked todescribe what was funny about each. Responses were tran-scribed verbatim and the time taken to respond was recorded.Subjects were prompted with anything else? to encour-age as full a response as possible. Cartoons remained in fullview until their response was complete.

2.2.3. ScoringPerformance accuracy was measured using the scoring

system devised by Happ et al. [28]. Three points wereawarded for a full and explicit explanation, two points fora partial or implicit explanation, one point for reference torelevant parts of the cartoon, but without further explanationand zero for patently incorrect responses including omis-sions. Examples of the marking criteria are given in Happet al. [28]. Scores for each test item were summated, yield-ing a total maximum score of 18 (6 3) for each of the twocartoon types.

Errors, defined as responses yielding a less than per-fect score, were further classified as follows: (i) omissions(dont know responses), (ii) concrete responses (itemisa-tion of elements without integration), (iii) descriptions (re-sponses limited to a description of the cartoon, involvingintegration of elements but no inferences that go beyondthe cartoons content), (iv) misconstructions (responses thatgo beyond a description of the cartoons contents but in-volve drawing faulty inferences) and (v) partial responses(responses that involve correct inferences but are incompleteor implicit rather than explicitly stated). Accuracy measuresand error classification were rated independently by fourraters, who were blinded to clinical diagnosis. The ratings

used in the analyses were based on a consensus from thefour raters.

In addition to accuracy measures and error classification,the total number of words contained in each response, andthe number of action verbs (e.g. walking, pushing) and men-tal state verbs (e.g. thinking, expecting) were calculated.Word and verb counts were calculated by a single author(ZG), and verified by two others. Calculations were madeblind to diagnosis.

2.3. Task 2: cartoon pairs

2.3.1. MaterialsThe materials, taken from Happ et al. [28], consisted of

10 cartoon pairs, one of which was humorous and the otherwas not, having had the key humorous element replaced.Five of the humorous cartoons were of a mental type, inthat appreciation of the humour depended on understandingof a cartoon characters ignorance, false belief or act ofdeception. Five humorous cartoons were of a physical type,in that the humour was based on physical properties of thecartoon and did not require inferences about a charactersmental state. Illustrative examples of cartoon pairs are givenby Happ [28].

2.3.2. ProcedureCartoon pairs were presented side by side in accordance

with Happ et al [28], with the leftright order beingcounter-balanced across items. Subjects were asked to se-lect which cartoon of the pair they considered to be thefunny one. Accuracy of selection and time to respond wererecorded. Subjects were then asked to describe why thecartoon was funny. As in the previous task, subjects werecued with anything else? to elicit as full a response aspossible. Cartoons remained in full view until the responsewas complete. Responses were scored as for task 1, in termsof accuracy measure, error types and word and verb count.

2.4. Task 3: story comprehension

2.4.1. MaterialsThe materials were drawn from Happ et al. [28] and had

originally been adapted from a study of theory of mind inautism [26]. They consisted of 16 short passages, 8 of whichwere of a mental-type and 8 physical. The mental sto-ries involved false belief, acts of deception, bluff and doublebluff and were followed by questions that required an in-ference about a characters thoughts, feelings or intentions.The physical stories involved logical or practical situations,and although the stories also contained people, questions re-quired inferences about physical causation or logical conse-quence and not about a characters mental state.

2.4.2. ProcedureParticipants were asked to read each passage silently, as

described by Happ [28], and to inform the examiner when


they had done so, following which a question related tothe passage would be asked. Subjects were advised to ab-sorb as much of the information contained in the passageas possible, as they would be unable to refer back to thepassage later. When participants indicated that they had as-similated the story the page was turned to reveal the ques-tion, which was read aloud to them. The question, but notthe story, remained in front of the subject during their re-sponse. Mental and physical stories were blocked and pre-sented in counter-balanced order, in accordance with Happet al. [28]. The examiner recorded the time taken to studythe passage and the answers given.

The standardised scoring scheme devised by Happ et al.[28] was adopted. Answers were credited with two pointsfor correct answers that gave a full and explicit account,one point for partial or implicit answers and no points forincorrect responses. Examples of stories and of the scoringcriteria are given in Happ et al. [28].

In addition, a classification scheme was devised to char-acterise the nature of errors, similar to that used in the car-toon tasks. Errors were recorded as omissions (dont knowresponses), concrete responses (reiterations of parts of thepassage), descriptions (responses limited to a description ofthe story, without drawing inferences), and misconstructions(bizarre or incorrect inferences). As for the cartoon tasks,the total number of words, the number of action verbs, andthe number of mental state verbs contained in each responsewere calculated.

2.5. Task 4: judgement of preference

2.5.1. MaterialsThe task was based on one described previously by

Baron-Cohen et al. [8] and involved the ability to judge

Fig. 1. Example of stimuli used in task 4 involving judgement of preference.

preference based on eye gaze. Unlike the previous tasksit involved a structured, forced-choice, rather than anopen-ended response. The materials consisted of 48 A4-sizecards presented in landscape format, each showing the car-toon outline of a face, positioned centrally and four colouredpictures of items belonging to a single category (e.g. ap-ple, strawberry, banana, pineapple) one in each of the fourcorners of the card. The eye gaze of the face (upper-left,lower-left, upper-right or lower-right) was directed towardsone of the four pictures. Across the 48 items, six object cat-egories were used: cartoon characters, fruits, bakery items,houses, jumpers, and cars, each category having eight exem-plars. For the first 24 test items (arrow condition), a heavyblack arrow was also present, which pointed to one of thepictures other than that towards which the faces eye gazewas directed. The remaining 24 cards (neutral condition)were a duplicate of the first 24, with the exception that noarrow was present. The direction of eye gaze and the arrowposition was pseudo-random, occurring in each of the fourpositions an equal number of times across the stimulus set.An example of the test stimuli is shown in Fig. 1.

2.5.2. ProcedureEach card was presented individually, using a blocked pre-

sentation, the arrow condition being presented first. Partici-pants were instructed to point to the one of the four pictureson the card that the central face likes best. Responses wererecorded on a score sheet by the examiner. Participants werenot given feedback about their choices. On completion of thetask, participants whose responses did not accord with thedirection of eye gaze of the cartoon face were re-presentedwith the stimuli and asked to point to the picture that theface is looking at. They were also shown the four pictureson a card devoid of face and arrow and asked to indicate


which one of the four was their personal favourite. Choiceswere recorded. The control looking at task was not ad-ministered to all subjects. The preference task was judged tobe so easy that it was expected to present no difficulty to anormal adult. Given that a correct judgement of preferenceimplied knowledge of the item being looked at it seemedsuperfluous, and perhaps slightly insulting, to ask also for alooking at judgement. Nevertheless, the looking at taskwas deemed critical for those people who had difficulty onthe judgement task, to distinguish specific problems in men-tal state attribution from general problems in attention orother executive function.

The arrow condition and neutral condition were scoredseparately, each item being credited one point if the patientspicture selection accorded with the direction of eye gaze ofthe central face. Errors in the arrow condition were coded asarrow if the participant had incorrectly selected the picturecorresponding to the direction of the arrow, favourite if theparticipant had incorrectly chosen their personal favourite,perseveration if the participant pointed to the same itemposition as their immediately preceding response, andrandom if an incorrect choice did not fit into any of theabove error types. The errors made in the neutral conditionwere coded as above, but without the arrow error type.

3. Results

3.1. Task 1: single cartoon abstraction

3.1.1. Time taken to respondThe patient groups did not differ significantly in terms

of the time taken to respond for either mental or physicalcartoons.

Fig. 2. Mean accuracy scores for single cartoon interpretation (task 1) as a function of cartoon type.

3.1.2. Performance accuracyFig. 2 illustrates the mean scores for the cartoon explana-

tions across groups and cartoon types. A repeated measuresANOVA showed a main effect of group (F(2, 41) = 17.3,P < 0.0001), but no effect of cartoon type, nor group bycartoon-type interaction. Post hoc Tukey analyses showedthat controls performed significantly better than both FTD(P < 0.0001) and HD patients (P = 0.004). There was atrend towards better performance in HD compared to FTD(P = 0.09).

3.1.3. Error typeA preliminary examination of error patterns showed that

error type was not influenced by cartoon type, so analy-ses of errors were based on a summation from both men-tal and physical cartoons. FTD patients made significantlymore omissions (t = 2.7, d.f. 29, P = 0.01) and concreteresponses (t = 4.1, d.f. 29, P < 0.0001) than the con-trol group, and more concrete responses (t = 2.7, d.f. 24,P = 0.01) than the HD group. In contrast, the HD pa-tients made more misconstruction errors than both the con-trol (t = 3.9, d.f. 29, P = 0.001) and the FTD (t = 3.8,d.f. 4, P = 0.001) groups. When they made errors, controlsubjects were more likely than the HD (t = 3.7, d.f. 29,P = 0.001) and the FTD (t = 4.0, d.f. 29, P < 0.0001)groups to produce partially correct responses. The follow-ing are examples of responses to the ping-pong cartoon,described in Section 2.2.1, in which a man deceives anolder woman in the adjacent room into believing that he isplaying table tennis by tapping a ping-pong ball while hecuddles his younger female companion. An FTD patientsconcrete response consisted of: Hes bouncing the ball onthe table. An HD patients misconstruction response con-sisted of: Theyre having a bit of nooky while the wifes


sat in there. Shes thinking At least hes leaving me alone.Peace!.

3.1.4. Word and verb countA repeated measures ANOVA comparing the number of

words per response elicited by the three groups for the twotypes of cartoon revealed a main effect of cartoon type(F(1, 39) = 12.6, P = 0.001), but no effect of group norgroup by cartoon type interaction. Mental cartoons elicitedlengthier responses than physical cartoons.

A repeated measures ANOVA comparing the number ofaction verbs produced by the three groups for the two cartoontypes showed no main effect of group, but a small effect ofcartoon type (F(1, 41) = 7.0, P = 0.01). More action verbswere produced for physical than for mental cartoons. Therewas no interaction effect of group by cartoon type.

A repeated measures ANOVA comparing the number ofmental state verbs produced showed a main effect of group(F(2, 41) = 7.9, P = 0.001), a main effect of cartoon type(F(1, 41) = 63.0, P < 0.0001), and an interaction effect ofgroup by cartoon type (F(2, 41) = 9.5, P < 0.0001). Posthoc analyses showed that FTD patients produced signifi-cantly fewer mental state verbs than controls (P = 0.001).Other group comparisons were non-significant. As expected,mental cartoons elicited more mental state verbs than phys-ical cartoons. The interaction effect resulted from a smallerdisparity in number of mental state verbs for the two cartoontypes in the FTD group (t = 2.1, P = 0.06) compared tothe HD group (t = 4.9, P < 0.0001) and controls (t = 7.1,P < 0.0001).

3.1.5. Frequency analysisThe frequency with which overall performance accuracy

scores were superior or inferior in the mental comparedto the physical cartoon condition was calculated for eachgroup and frequency values were submitted to a Signtest. FTD patients were significantly more likely to per-form worse in the mental than the physical condition(two-tailed test P < 0.01), whereas other groups showedno significant bias.

3.2. Task 2: cartoon pairs

3.2.1. Choice of cartoon pairThe number of correct choices made by the three groups

for mental and physical cartoons is shown in Table 2. Arepeated measures ANOVA comparing the number of correct

Table 2Correct selection of forced-choice cartoons

Group Mental cartoons Physical cartoons

FTD 3.2 (1.8) 1.8 (1.3)HD 4.1 (1.2) 3.4 (1.2)Control 4.6 (0.5) 4.6 (0.7)The data represent mean (S.D.).

choices for the two cartoon types showed a main effect ofgroup (F(2, 41) = 19.6, P < 0.0001), and cartoon type(F(1, 41) = 11.9, P = 0.001), and an interaction effect ofgroup by cartoon type (F(2, 41) = 3.9, P = 0.03). Posthoc analyses revealed that controls were significantly moreaccurate than the FTD patients (P < 0.0001), and there wasa trend towards greater accuracy of controls compared to HDpatients (P = 0.07). HD patients made more correct choicesthan FTD patients (P = 0.002). More correct choices weremade for mental than physical cartoons, particularly in thepatient groups compared to controls.

3.2.2. Time taken to respondA repeated measures ANOVA showed no difference in

response times in the three groups and there was no effectof cartoon type on response time.

3.2.3. Accuracy of interpretationFig. 3 illustrates scores for the three groups across car-

toon types. A repeated measures ANOVA showed a maineffect of group (F(2, 41) = 21.4, P < 0.0001), but noeffect of cartoon type or group by cartoon-type interaction.Post hoc analyses showed that controls performed signifi-cantly better than both FTD (P < 0.0001) and HD patients(P = 0.007). HD patients achieved higher scores than FTDpatients (P = 0.01).

3.2.4. Error typeA preliminary examination of error patterns showed that

error type was not influenced by cartoon type, so analysesof errors were based on a summation from both mental andphysical cartoons. FTD patients made more omission andsingle element concrete responses than HD patients (t = 2.2,d.f. 23, P = 0.04; t = 3.4, d.f. 23, P = 0.003, respectively)and controls (t = 3.3, d.f. 28, P < 0.003; t = 3.8, d.f. 28,P = 0.001, respectively). HD patients, by contrast, mademore misconstruction errors than FTD patients (t = 3.7, d.f.23, P = 0.001) and controls (t = 4.2, d.f. 29, P < 0.0001).Control subjects made significantly more partially correctresponses than both FTD (t = 4.3, d.f. 29, P < 0.0001),and HD patients (t = 2.3, d.f. 29, P = 0.03).

3.2.5. Word and verb countA repeated measures ANOVA showed that the groups did

not differ in terms of the number of words contained in theirresponses. There was also no effect of cartoon type on lengthof response and no interaction effect.

A repeated measures ANOVA comparing the number ofaction verbs produced by the three groups showed a small ef-fect of group (F(2, 41) = 4.1, P = 0.02). FTD patients pro-duced fewer overall action words than controls (P = 0.03).There was no main effect of cartoon type. There was howeveran interaction effect of group by cartoon type (F(2, 41) =6.9, P = 0.003), reflecting the fact that whereas control sub-jects tended to produce more action verbs for physical thanmental cartoons, the HD group showed the reverse effect.


Fig. 3. Mean accuracy scores for forced-choice cartoon interpretation (task 2) as a function of cartoon type.

A repeated measures ANOVA comparing the number ofmental state verbs produced by the three groups showeda main effect of group (F(2, 41) = 4.6, P = 0.02), andof cartoon type (F(1, 41) = 25.0, P < 0.0001), and aninteraction effect of group by cartoon type (F(2, 41) =3.8, P = 0.03). Post hoc analyses revealed that FTDpatients produced fewer mental state verbs than con-trols (P = 0.01). As expected more mental state verbswere produced for mental than for physical cartoons, butthe difference was proportionally smaller for the FTDgroup.


scores were superior or inferior in the mental comparedto the physical cartoon condition was calculated for eachgroup and frequency values were submitted to a Sign test.Control subjects were significantly more likely to per-form worse in the mental than the physical condition(two-tailed test P < 0.02), whereas the patient groupsshowed no significant bias.

3.3. Task 3: story comprehension

3.3.1. Time taken to respondA repeated measures ANOVA comparing the time to re-

spond by the three groups for the two story types showeda main effect of group (F(2, 27) = 4.1, P = 0.03), but noeffect of story type or interaction effect. HD patients wereslower to respond than FTD patients (P = 0.04), and tendedto be slower than control subjects (P = 0.06). No othergroup comparisons were significant.

3.3.2. AccuracyFig. 4 shows accuracy scores for the story comprehen-

sion test in the three groups for the two story types. A re-peated measures ANOVA showed a main effect of group(F(2, 30) = 19.3, P < 0.0001), but no effect of story typeor interaction effect. Control subjects performed better thanboth FTD (P < 0.0001) and HD patients (P = 0.01), andHD patients performed better than FTD patients (P = 0.01).

3.3.3. Error typeFTD patients were more likely than controls to make

omission errors (t = 2.4, d.f. 22, P = 0.03), concrete re-sponses (t = 4.1, d.f. 22, P < 0.0001) and description re-sponses (t = 5.2, d.f. 22, P < 0.0001). FTD patients alsomade more concrete responses (t = 2.1, d.f. = 13, P =0.05) and description responses (t = 3.0, d.f.13, P = 0.01)than HD patients. HD patients showed a trend towards moremisconstruction errors than the control group (t = 1.9, d.f25, P = 0.07). Control subjects were more likely than FTDpatients to make partially correct responses (t = 3.6, d.f.22, P = 0.002).

3.3.4. Word and verb countThere was no difference in the overall number of words

per response produced by each of the three groups and lengthof response was not influenced by story-type.

A repeated measures ANOVA comparing the number ofaction verbs produced by the three groups showed no effectof group, story type, or interaction effect of group by storytype.

A repeated measures ANOVA comparing the number ofmental state verbs produced by the three groups showed


Fig. 4. Mean accuracy scores for story interpretation (task 3) as a function of story type.

no main effect of group, but a main effect of story type(F(1, 30) = 56.2, P < 0.0001), and a trend towards aninteraction effect of group by story type (F(2, 30) = 3.1,P = 0.06). More mental state verbs were elicited for mentalthan for physical stories, but this increase was smaller forthe FTD group than the other groups.


scores were superior or inferior in the mental compared tothe physical story condition was calculated for each groupand frequency values were submitted to a Sign test. No groupshowed a statistical bias towards better performance for oneor other story type.

3.4. Task 4: determining preference from eye gaze

3.4.1. AccuracyFig. 5 shows mean accuracy scores for each group,

when a distracting arrow was present and absent. A re-peated measures ANOVA showed a main effect of group(F(2, 39) = 5.5, P = 0.008), but no effect of condi-tion (arrow versus no arrow), and no interaction effect ofgroup by condition. Post hoc analyses showed that FTDpatients made more errors than both HD patients (P =0.03) and controls (P = 0.01). HD patients did not differfrom controls and performance in both approached ceilinglevels.

3.4.2. Error typesIn view of the rarity of errors made by the HD and con-

trol groups, their responses were not subjected to analysis oferror type. In the FTD group incorrect responses were dom-inated by favourite errors, which accounted for 71% of all

incorrect responses (patients selected their personal favouritepicture disregarding eye gaze). Although a relatively highnumber of incorrect responses (39%) accorded with the di-rection of the arrow, in the majority of these instances theresponse also corresponded to the patients favourite pic-ture, so that the basis for the correct choice was ambiguous.The lack of a statistical effect of condition (arrow presentversus arrow absent), implying that the presence of the ar-row had no overall effect on performance accuracy, suggeststhat incorrect choices were largely being made on the ba-sis of personal favourite and not arrow direction. One singleFTD patient appears to represent an exception to this generalrule. In the arrow condition 20 of his 22 incorrect responsescorresponded to the arrow direction. Perseverations of a sin-gle response position and random errors were rare in allpatients.

3.4.3. Judgement of eye directionThree of the FTD patients had exhibited chance level

performance in the judgement of preference task. Theseindividuals were subsequently asked to indicate which ofthe four items the cartoon face was looking at. Two FTDpatients had no difficulty carrying out the looking at taskand scored, respectively 100 and 92% correct, comparedwith performance, respectively of 21 and 17% correct inthe preference task. These differences in performancefor the like and look at tasks were highly signifi-cant (McNemar test 2 = 17.1, P < 0.001; 2 = 16.1,P < 0.001 for the two patients, respectively). By contrastthe third patient persisted in selecting her own personalfavourite item, disregarding the direction of eye gaze ofthe cartoon face. Her accuracy score of 25% correct wasunchanged from her chance level score in the preferencetask.


Fig. 5. Mean score for judgement of preference (task 4) as a function of the presence or absence of a distractor arrow.

Table 3Correlation between social cognition and standard executive test scores

Social task Executive task

Category fluency (n = 12) Letter fluency (n = 13) WCST categories (n = 11)(a) FTD

Task 1 (single cartoons) 0.58 0.62 0.57Task 2 (forced-choice cartoons) 0.69 0.53 0.75Task 3 (stories) 0.13 0.01 0.58Task 4 (preference judgement) 0.28 0.36 0.20

(b) HDTask 1 (single cartoons) 0.38 0.04 0.09Task 2 (forced-choice cartoons) 0.37 0.02 0.08Task 3 (stories) 0.73 0.38 0.11Task 4 (preference judgement) 0.37 0.28 0.71 P < 0.05. P < 0.001.

3.5. Relationship of performance on social cognition andstandard executive tests

For each of the four social cognition tasks a total per-formance accuracy score was calculated. In the case of thecartoon and story tasks, this involved summating accuracyscores for the mental and physical conditions. In the case ofthe judgement of preference task scores for the arrow and noarrow conditions were summated. The relationship betweentotal accuracy scores and performance on the category flu-ency (animals generated in one minute), letter fluency (Fwords generated in one minute) and Wisconsin Card Sortingtest (WCST) was examined.

Table 3 shows the correlation between performance onthe experimental tasks and standard executive tests. Modestrelationships were found but these were not consistent acrosstasks or for the two groups.

3.6. Relationship of FTD performance to distributionof frontal atrophy

Nine FTD patients showed predominant orbitofrontal ab-normalities on neuroimaging, whereas four patients showedwidespread frontal lobe changes, extending into dorsolateralfrontal cortex. Patients with widespread changes performedworse that those with more circumscribed changes on thecartoon and story tasks (P < 0.05) but not the preferencetask.

4. Discussion

Both FTD and HD groups were impaired relative to con-trols in their interpretation of humorous cartoons and storyvignettes. The FTD group was more severely affected than


the HD group, consistent with the grosser social breakdownand executive failure demonstrable in FTD.

Previous investigations using the same cartoon and storymaterials have shown a disproportionate impairment onthe mental compared to the physical conditions in patientsfollowing right hemisphere stroke [28] and in a patientfollowing frontal lobe surgery [29]. The dissociation wasinterpreted as demonstrating impairments in theory of mindassociated respectively with right hemisphere and frontallobe lesions. It was predicted that FTD patients would showa similar disproportionate impairment for mental comparedto physical items, whereas HD patients would show no suchdissociation. The findings were not entirely in accordancewith prediction. Both patient groups were essentially com-parably impaired for the two types of test material, poorerscores for mental compared to physical material beingdemonstrated in FTD only in task 1.

Analysis of error responses provides clues to the basisfor the lack of dissociation, whilst also drawing attention toimportant qualitative differences between FTD and HD. Inthe FTD group, the largest proportion of errors for the car-toon tasks were omissions and concrete responses. Patientsreported not knowing what was funny about cartoons and ei-ther failed to produce a response, or itemised elements with-out further explanation (e.g. Theres a car, theres a child).Thus, not only did patients fail to go beyond the contents ofthe cartoon and draw inferences they also failed to integrateelements of the cartoon into a thematic narrative. Failuresoccurring at this relatively low-order level of cognition in-evitably applied equally to mental and physical test material.These concrete-type responses contrasted strikingly with theerrors of control subjects, which largely constituted partialresponses: responses that were insufficiently detailed or in-ferences were implicit rather than explicitly stated. Controlstypically did draw inferences, going beyond the literal ele-ments of the cartoon.

In the HD group, a large proportion of errors in the car-toon tasks were of the description type: a full and inte-grated commentary on the contents of each cartoon wasprovided but without drawings inferences beyond the phys-ical contents. Such errors occurred to some extent in allgroups and were of no differentiating value. Of more theo-retical interest is the presence of misconstruction errors. Fora substantial proportion of items HD patients did draw in-ferences that went beyond the physical contents of the car-toon. They abstracted and formulated hypotheses, includinghypotheses about a characters feelings or belief. However,those inferences deviated from the conventional interpreta-tion. For example, the usual interpretation of the ping-pongcartoon described in Section 2.2.1 is that the man is deceiv-ing the older woman into thinking he is playing table ten-nis. The response Theyre having a bit of nooky while thewifes sat in there. Shes thinking At least hes leaving mealone. Peace! suggests a diametrically opposite response:the older woman is not deceived. Such eccentric interpreta-tions constituted a trademark of HD, in that they occurred

at least once in all but one of the HD patients, yet werevirtually absent in other groups. Group differences cannotbe explained in terms of notional differences in severity ofimpairment between FTD and HD. Misconstruction errorsdid not occur even in relatively high-functioning FTD pa-tients, whose overall level of accuracy on the cartoon testswas comparable to that of HD subjects. They cannot, more-over, be attributed to scoring bias, because responses wereevaluated blind to diagnosis. The tendency to misconstruecut across stimulus type, being present both for mental andphysical cartoon types.

A similar pattern of errors occurred for the story task.FTD patients were more likely than other groups to giveconcrete responses, reiterating parts of the story withoutdrawing inferences. By contrast, there was a trend for HDpatients to make misconstruction errors, drawing faultyinferences from stories. Controls were more likely to givepartially correct responses. Thus, the findings suggest aconsistent pattern of performance regardless of the natureof the stimulus material.

The cartoon and story tasks are both relatively demand-ing. Concrete responses in FTD patients might potentiallyhave arisen due to task complexity: the requirement to in-tegrate information and draw inferences might simply haveimposed too great a mental executive demand on the patient.General executive deficits may have masked more specificdeficits in mental state attribution. The face test is importantin that it is undemanding, requiring no active mental manip-ulation or integration of information and it can be achievedby children as young as 3 years. Participants merely pointto one of four pictures that the cartoon face prefers, prefer-ence being determined by direction of eye gaze. Neverthe-less, FTD patients as a group showed an impaired ability tocarry out the task, frequently disregarding eye gaze direc-tion and basing their selection of preference on their ownpersonal favourite. The fact that at least some patients hadno difficulty determining which item the face was lookingat suggests that failures on preference judgement could notbe ascribed to executive deficits such as inability to attendto the test stimuli. Moreover, all patients complied with thetask when asked for their personal preference suggesting thatfailures are unlikely to be secondary to comprehension im-pairment. Expression of personal preference might be con-strued as constituting a pre-potent response that the patientis no longer able to override or inhibit and is consistent withthe impairments in response inhibition typical of frontal lobedysfunction. However, the concrete mode of response, basedon their own personal preference, is compatible also withthe notion that FTD patients have an egocentric world-viewin which they fail to recognise or attribute to others a mentalstate that differs from their own. Such an interpretation isconsistent with relatives reports that FTD patients are obliv-ious to the feelings and needs of others. FTD patients, unlikechildren with autism [8], were not typically greatly influ-enced by the presence of an arrow, suggesting that externalenvironmental stimuli were a less potent factor in guiding


responses than patients own internal mental state. However,there was an exception to this general rule. Responses in oneFTD patient consistently corresponded to the arrow direc-tion, highlighting heterogeneity within the FTD population.

HD patients had no difficulty on the preference judge-ment task. This is consistent with earlier findings that theycould draw inferences about another persons emotions,thoughts or beliefs and with clinical observations that HDpatients make pertinent and insightful remarks about theeffects of their illness on a close relative. Nevertheless,insight demonstrated at a cognitive level, is frequently notmatched by commensurately considerate, sympathetic orempathic behaviour in the patients daily life. There is amismatch between what the patient says and does. HD pa-tients show alterations in the processing of emotion [23,59]and one possibility is that HD patients lack of sympathyand empathy arises more at an emotional than a cognitivelevel. In any event, it cannot be attributed to an inability perse to attribute mental states. By contrast, FTD patients existin an egocentric world, in which they do not ascribe inde-pendent mental states to others, a factor likely to contributeto their loss of capacity for sympathy and empathy.

If HD patients can infer mental states in others but FTDpatients cannot then this should be reflected in the numberof mental state terms used in interpreting cartoons and sto-ries. Consistent with prediction HD patients did not differfrom controls with respect to the number of mental termsused. Conversely, FTD patients produced significantly fewermental state terms, despite a comparable overall length of re-sponses. This may partly reflect patients tendency to itemiseelements, without integration into a coherent narrative. In-deed, on the cartoon pairs task FTD patients showed a re-duction in the number of action verbs as well as mental stateverbs. Nevertheless, a significant reduction in action verbswas demonstrated on a single task only, whereas a reductionin mental state verbs was a more pervasive finding. This dis-parity suggests that at least one contribution to FTD patientspoor test performance is a failure to engage in mentalisingand in the attribution of mental states to others. It is of rel-evance that a SPECT imaging study [10] demonstrated ac-tivation of orbitofrontal cortex in subjects required to judgewhether words represented mental state terms. All the FTDpatients in the present study had demonstrable involvementof orbitofrontal cortex on MR and SPECT imaging.

A number of studies have demonstrated dissociations inperformance on theory of mind and traditional frontal exec-utive tasks [11,17,24,29,34,39,52], interpreted as evidencefor the independence of theory of mind and executive skills.Nevertheless, it is reasonable to suppose that executive im-pairments will have a secondary impact on performance ontheory of mind tasks, and some studies have found a relation-ship between performance on the two types of tasks [13,53].In one study [13] patients with left anterior lesions, like FTDpatients in the present study, failed to make non-literal inter-pretations, a finding ascribed to their tendency to attend onlyto the most salient aspect of the relevant information. The

authors argued that impaired executive function provided asufficient explanation of the impaired story comprehensionperformance, without the need to invoke an additional the-ory of mind impairment. Nevertheless, they acknowledgedthe possibility that there may be two routes to impairmentin theory of mind tasks, arising from disruption either tobroader executive processes or to specific theory of mindability. We would adopt such a view. The FTD group wasnot disproportionately impaired for social than for physicalcartoons and stories compared to controls, and FTD patientsshowed worse performance for social compared to physicalstimuli only on task 1, suggesting that general executive im-pairments contribute substantially to test performance. In-deed, poorer overall performance was generally seen in thosepatients with widespread frontal lobe atrophy. Nevertheless,the relationship between performance on social cognitionand standard executive tests was relatively modest and notsystematic across tasks. Moreover, on the preference judge-ment task some FTD patients failed to ascribe preference,yet had no difficulty reporting direction of eye gaze. Thetwo tasks (Which one does he like? versus Which oneis he looking at?) make comparable demands on attentionand differ only with respect to the need for mental stateattribution. Performance differences provide evidence for aspecific impairment in theory of mind. We would argue thatFTD patients have a genuine impairment in theory of mind,but that in many patients, in whom frontal lobe atrophy issevere and widespread this constitutes only one of a varietyof deficits. General executive impairments will have an in-evitable impact on performance on theory of mind tasks andmay mask more specific deficits in theory of mind. Deficitsin theory of mind independent of executive function mightbe expected early in the course of disease when patholog-ical change is relatively confined to orbitofrontal regions[57]. Later in the disease course, with extension of pathol-ogy into dorsolateral regions, the picture will be increasinglycoloured by additional executive deficits. Complementaryfindings and anatomical interpretation come from a studyof the relationship between empathy, which requires the ca-pacity to appreciate anothers thoughts and feelings, andcognitive flexibility, as measured by conventional executivetasks [22]. Differences between findings in the present studyand another study of FTD patients [24], in which impair-ments were demonstrated on theory of mind but not controltasks, are likely to be attributed to differences in severity.The patients in the latter study had a substantially highermean MMSE score than the present FTD patients (27 ver-sus 22) and performed better on the WCST (4.4 versus 1.4categories), suggesting that they were at an earlier stages intheir illness.

HD patients in the present study showed little convincingevidence of deficits in theory of mind. Nevertheless patientsperformed abnormally on tasks requiring interpretation ofsituations. Their tendency to make misconstruction errorshas a resonance with their functioning in daily life. Relativesreports suggest that people with HD sometimes interpret


events and social interactions in ways that do not accord withthe norm. It is possible that their tendency to misconstruemay underlie or at least contribute to the fixed ideation andintransigence that are characteristic of some people withHD. The relatively weak correlation between performanceon social cognition and standard executive tasks exemplifiesthe fact that the problems encountered by HD patients inopen-ended tasks (and indeed normal social situations) maynot be adequately reflected in standard executive tests.

We have interpreted differences between FTD and HD asreflecting the fact that FTD is largely a frontal neocorticaldisorder and HD a disorder of the striatum. However, in dis-orders that affect frontostriatal circuitry a common assump-tion is that analogous deficits will arise regardless of the levelof the circuit at which disruption occurs. Why then shouldFTD and HD be qualitatively different? If FTD and HD in-volve different striatofrontal circuits[3,43] then might thisexplain qualitative differences? FTD is thought to progressin an orbital-to-dorsolateral direction [57], whereas the dor-sal to ventral striatal progression in HD [63] suggests thereverse. Nevertheless, differential involvement of circuits isan unlikely explanation. The classification of frontostriatalcircuits [50] and the extent to which they are parallel [33]is itself not without controversy. Moreover, the FTD groupincluded patients both with a relatively circumscribed or-bitofrontal atrophy and with widespread frontal atrophy, pre-sumably involving each of the dorsolateral, orbitofrontal andanterior cingulate loops, yet none showed an HD-like pat-tern of error response. Furthermore, poor performance onexecutive tasks has characteristically been associated withdorsolateral frontal lobe pathology [43], yet it was the FTDpatients who performed the more poorly on these tasks sug-gesting dorsolateral frontal dysfunction at least as great asin HD. In FTD frontal cortical grey and white matter arecomparably affected [41], whereas in HD there is imaging[7] and pathological [40] evidence of a disproportionate in-volvement of white matter. In FTD maximal loss of neu-rones occurs in the superficial layers II and III, resultingprimarily in loss of cortico-cortical connections, whereas inHD pyramidal neurones in deeper layers V and VI, whichsubserve cortico-subcortical projection fibres, are most in-volved. We would suggest that the key distinction underly-ing performance differences is that FTD involves primarilyfrontal neocortex and its cortico-cortical afferents whereasHD is a disorder of the striatum and its cortico-subcorticalconnections.

The study highlights the value of open-ended tasks involv-ing interpretation of social situations, in exploring deficitsarising from disorders of the frontostriatal system. The find-ings suggest that, despite superficial similarities in the pat-tern of cognitive disorder and altered social conduct in FTDand HD, qualitative differences exist in the nature of un-derlying deficits. In FTD there is a loss of theory of mindbut that additional executive deficits colour patients per-formance on theory of mind tasks. In HD there is no con-vincing evidence of a loss of theory of mind. Future studies

need to address the qualitative characteristics of performancein laboratory-based and real-life social situations to clarifymore precisely the basis for social breakdown in FTD andHD.

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Social cognition in frontotemporal dementia and Huntington's diseaseIntroductionMethodsParticipantsFrontotemporal dementia (FTD)Huntington's disease (HD)Controls

Task 1: single cartoon abstractionMaterialsProcedureScoring

Task 2: cartoon pairsMaterialsProcedure

Task 3: story comprehensionMaterialsProcedure

Task 4: judgement of preferenceMaterialsProcedure

ResultsTask 1: single cartoon abstractionTime taken to respondPerformance accuracyError typeWord and verb countFrequency analysis

Task 2: cartoon pairsChoice of cartoon pairTime taken to respondAccuracy of interpretationError typeWord and verb countFrequency analysis

Task 3: story comprehensionTime taken to respondAccuracyError typeWord and verb countFrequency analysis

Task 4: determining preference from eye gazeAccuracyError typesJudgement of eye direction

Relationship of performance on social cognition and standard executive testsRelationship of FTD performance to distribution of frontal atrophy

DiscussionReferences

Documents

19 Salas Milagros - Snowden