Executive function in tourette's syndrome and obsessive–compulsive disorder

Psychological Medicine, 2005, 35, 571–582.
Executive function in Tourette’s syndrome L A U R A H. W A T K I N S 1, B A R B A R A J. S A H A K I A N 2*, M A R Y M. R O B E R T S O N 4, D A V I D M. V E A L E 4, R O B E R T D. R O G E R S 3,5, K A T H R Y N M. P I C K A R D 1 , M I C H A E L R. F. A I T K E N 3 A N D T R E V O R W. R O B B I N S 3 1 MRC Cambridge Centre for Brain Repair, Departments of 2 Psychiatry and 3 Experimental Psychology, University of Cambridge, Cambridge, UK ; 4 Department of Psychiatry and Behavioural Sciences, Royal Free and University College School of Medicine, University of London ; UK ; 5 Department of Psychiatry, Background. Cognitive performance was compared in the genetically and neurobiologically relateddisorders of Tourette’s syndrome (TS) and obsessive–compulsive disorder (OCD), in three domainsof executive function : planning, decision-making and inhibitory response control.
Method. Twenty TS patients, twenty OCD patients and a group of age- and IQ-matched normalcontrols completed psychometric and computerized cognitive tests and psychiatric rating scales.
The cognitive tests were well-characterized in terms of their sensitivity to other fronto-striatal dis-orders, and included pattern and spatial recognition memory, attentional set-shifting, and a Go/No-go set-shifting task, planning, and decision-making.
Results. Compared to controls, OCD patients showed selective deficits in pattern recognitionmemory and slower responding in both pattern and spatial recognition, impaired extra-dimensionalshifting on the set-shifting test and impaired reversal of response set on the Go/No-go test. Incontrast, TS patients were impaired in spatial recognition memory, extra-dimensional set-shifting,and decision-making. Neither group was impaired in planning. Direct comparisons between the TSand OCD groups revealed significantly different greater deficits for recognition memory latency andGo/No-go reversal for the OCD group, and quality of decision-making for the TS group.
Conclusions. TS and OCD show both differences (recognition memory, decision-making) and simi-larities (set-shifting) in selective profiles of cognitive function. Specific set-shifting deficits in theOCD group contrasted with their intact performance on other tests of executive function, such asplanning and decision-making, and suggested only limited involvement of frontal lobe dysfunction,possibly consistent with OCD symptomatology.
usually develop in adolescence (Freeman, 1992).
Tourette’s syndrome (TS) is a neurodevelop- Despite the quite different clinical profiles of mental condition characterized by motor and these two disorders, there is good evidence for vocal tics that typically develop at 5–7 years genetic linkage between them (State et al. 2003).
of age (APA, 1994 ; Robertson, 1994, 2000).
TS and half of OCD cases are thought to be Obsessive–compulsive disorder (OCD) sufferers inherited in autosomal dominant fashion, with a single (as yet unidentified) locus for trans-mission, but with incomplete penetrance and * Address for correspondence : Professor Barbara Sahakian, variable phenotype (Pauls & Leckman, 1986 ; Department of Psychiatry (Box 189), University of Cambridge, Eapen et al. 1993 ; Pauls et al. 1995 ; Leckman Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK.
Both disorders are thought to have a neuro- biological basis in the frontal cortex and basal test results [values are mean (standard deviation)] ganglia. Changes in regional cerebral blood flow(rCBF) and metabolism have been observed in TS patients, particularly in the ventral striatum, lateral orbito-frontal cortex (OFC) and the an- terior cingulate gyrus (ACG) (Braun et al. 1993 ; for review see Weeks et al. 1996 ; Leckman et al.
1997). Dopaminergic abnormalities observed in TS (Devinsky, 1983 ; Leckman et al. 1997) suggest an imbalance in the interactions of the striatum. Similarly, many studies have found abnormal rCBF or metabolism in OCD : with the OFC, ACG and caudate nucleus typically showing overactivity (for review, see Saxena Disruption to fronto-striatal circuitry leads to impairment in tasks requiring executive Upper panel : PVIQ, predicted pre-morbid verbal IQ ; MMSE, Mini Mental-State Examination ; BDI, Beck Depression Inventory.
Lower panel : Arithmetic, arithmetic subtest of Wechsler Adult decision-making, i.e. tasks requiring higher level Intelligence Scale ; Pattern, pattern recognition memory test ; Spatial, cognition and optimization of complex cogni- spatial recognition memory test ; RT, correct response latency ; N.S.,not significant ; Statistic, statistical difference.
tive performance (Tranel et al. 1994 ; Robbins,1996). Thus, whilst spatial working memory andplanning tasks strongly involve dorsolateral issues. First, it provides a direct comparison prefrontal cortex (DLPFC) circuitry (Alexander between the two disorders, to test the hypothesis et al. 1986 ; see Robbins, 1996, for review ; Baker that a common genetic basis and similar neuro- et al. 1996 ; Owen et al. 1996 ; Bechara et al.
biological background would lead to similar 1998), decision-making between options with cognitive deficits. Second, we tested the hypoth- variable degrees of rewarding and punishing esis that the cognitive deficits seen in these two feedback relies on circuitry of the OFC (Bechara disorders would be more similar to those seen et al. 1998 ; Rahman et al. 1999 ; Rogers et al.
in other disorders that disrupt the OFC circuitry 1999, 2000). Go/No-go and reversal paradigms to a greater extent than the DLPFC circuitry have also long been known to be sensitive to (e.g. mild frontal-variant fronto-temporal de- frontal dysfunction, particularly in the OFC mentia) than to conditions that preferentially region (Iversen & Mishkin, 1970 ; Butters et al.
disrupt the DLPFC rather than OFC circuitry 1973 ; Drewe, 1975 ; Petrides, 1986 ; Rolls et al.
(e.g. mild Huntington’s disease, see Lawrence & 1994 ; Godefroy et al. 1996 ; Dias et al. 1996) and provide measures of inhibitory controlmechanisms that may well be disturbed in such Despite its proposed fronto-striatal neuro- pathology, studies of complex task performance Permission for this study was obtained from the in TS are sparse and findings in OCD have Local Research Ethics Committee and all sub- proved inconsistent. This study, therefore, com- jects gave written informed consent. The patient pared performance in the domains of atten- tional control, planning and decision-making in patients and 20 age- and IQ-matched control patients with TS and OCD using neuropsycho- subjects (Table 1). TS patients were diagnosed logical tools that have been well-characterized and recruited by MMR from the out-patient in terms of their sensitivity to other fronto- clinic at the National Hospital for Neurology striatal disorders. This is, thus, perhaps the first detailed neuropsychological comparison of made on the basis of interview and completion these groups. The study addresses two main of the National Hospital Interview Schedule Cognition in Tourette’s syndrome and OCD (Robertson & Eapen, 1996). OCD patients were Ten patients were unmedicated, eight were Priory Hospital or an OCD support group.
taking SSRIs (five taking paroxetine, two taking Subjects who scored below 24 on the Mini- fluoxetine and one taking sertraline), one was taking a tricyclic antidepressant (clomipramine) excluded (Folstein et al. 1975), as were those and one was taking both a monoamine oxidase with a history of neurological or psychiatric inhibitor (moclobemide) and an antipsychotic conditions other than those under study [except (trifluoperazine). The mean score on the Yale– depression and attention deficit hyperactivity Brown Obsessive–Compulsive Scale (YBOCS ; disorder (ADHD)]. Twenty control subjects Goodman et al. 1989) was 19.3 (S.D.=14.3).
were recruited by advertisement in Cambridgeand chosen to match the patient groupsaccording to age, pre-morbid IQ and gender ratio. Severity of depression was assessed using The background psychometric tests were as the Beck Depression Inventory (BDI ; Beck et al.
follows : MMSE, National Adult Reading Test 1961) and severity of ADHD in TS patients was [NART ; Nelson, 1982, to provide an estimate assessed using the Attention Deficit Scale for of pre-morbid verbal IQ (PVIQ)], letter fluency Adults (ADSA ; Triolo & Murphy, 1996).
(Benton, 1968), semantic fluency and finallythe arithmetic subtest from the Wechsler Adult Intelligence Scale (WAIS ; Wechsler, 1981). The Six patients were unmedicated, 10 were taking fluency and arithmetic tests were included as a single medication and the remaining four were examples of ‘ standard ’ tests of executive func- taking more than one medication. Antipsy- tion, the arithmetic test assessing working- chotic medications were the most frequent : four patients were taking sulpiride, six were taking haloperidol, three were taking pimozide, two portable microcomputer fitted with a Datalux were taking risperidone and one was taking touch-sensitive screen, which was positioned clonidine. One patient was taking an anti- approximately 0.5 m from the subject. Three muscarinic drug (benzoptropine), three were taking a selective serotonergic reuptake inhibi- tor (SSRI) (fluoxetine) and one was taking a benzodiazepine (lormetazepam). The mean Yale Global Tic Severity Scale (YGTSS ; Leckman et al. 1989) was 43.5 [standard deviation (S.D.)= 19.3] out of 100 ; this scale assesses motor and vocal tics and their impact on daily activities.
puterized tests was counterbalanced.
After exclusion of patients with distinct co-morbid OCD by the clinician, all remaining candidates were pre-screened with the Leyton This test of discrimination learning assesses Obsessional Inventory (LOI ; Cooper, 1970 ; the ability to selectively attend to and set-shift Snowdon, 1980) ; those who scored outside the normal range were not tested. The mean LOI dimensions (Downes et al. 1989). Measures were score of the 20 TS patients included in the study number of subjects passing each stage, errors was 11.1 (S.D.=6.1), which is comparable to and latency at the intra-dimensional (ID) and the means obtained by Cooper (1970) of 8.7 (S.D.=5.6) for male controls (n=40) and 11.4(S.D.=6.7) for female controls (n=60). TSpatients scored a mean of 153.6 ( One-touch Tower of London (one-touch TOL) the ADSA, which is within 1 S.D. of the norma- This is a spatial planning test, involving plan- tive mean of 141. Three patients scored greater ning a sequence of moves to achieve a goal than 2 S.D. from the normative mean, indicating arrangement of coloured balls without moving the balls (Owen et al. 1995). Measures were the proportion of perfect solutions and latency to age, MMSE score or predicted PVIQ [largest F(2, 57)=1.54, p=0.22], although the groupsdiffered in mean (square-root-transformed) BDI scores F(2, 55)=24.75] TS patients had higher This test of decision-making and risk-taking BDI scores than did the OCD or control groups has previously been described by Rogers et al.
[smaller t(55)=5.03], who did not differ signifi- (1999). Main measures were the latency to make a decision, the proportion of decisions with the As the patient groups were not completely most likely outcome and the mean percentage matched for age and sex ratio, care was taken to ensure this did not confound interpretation.
All subsequent ANOVAs were conducted both with gender and age as predictors (fixed factor, This test examines the ability to attend and and covariate respectively). If these factors had respond to relevant targets while inhibiting no significant effects (Ff1.0), they were dis- responses to distractors (McLean et al. 2004).
carded from the model ; thus, hypotheses on the Measures were response, latencies, correct target group factor are tested on the observed means presses or ‘ hits ’, misses and false-positive errors.
only. Otherwise, both full and restricted models Switch blocks (blocks on which the response were analysed (observed and estimated marginal contingencies are reversed from the previous means), and the more conservative of the two block) can be compared to non-switch blocks.
p values obtained was used for each hypothesistest on the group factor.
Data were analysed using SPSS version 11.0.1 (SPSS Inc., 2001). Comparisons of the means of Results of the background neuropsychological the three groups were via analysis of variance tests are shown in the lower rows of Table 1. The (ANOVA). Standard transformations of each three groups did not differ on WAIS arithmetic, subject’s mean score (Howell, 1997) were used category fluency or letter fluency (F<1), nor on to increase homogeneity of variance when this response latency in the motor screening task assumption was untenable (p<0.10, Levene’s [F(2, 53)=2.40, p=0.10]. Significant main effects of group were observed on both (arcsine-trans- Significant main effects were investigated by formed) accuracy and (logarithmic-transformed) Fisher’s LSD test (protected t procedure for latencies for the spatial and pattern recognition three means), to give a strict control of maxi- memory tasks [smallest F(2, 53)=3.43]. The mum family-wise error rate, and a significance OCD patients were slower than the other groups level of 0.05 is used throughout. Where par- to respond in both tasks [smaller t(53)=2.12]; ametric analyses were unsuitable, data were response latencies were similar for TS and analysed using the likelihood ratio method controls (t<1). The two patient groups did not (Kullback, 1968 ; Robbins, 1977) or Mann– differ in accuracy of performance on either task [larger t(53)=1.33, p=0.19] ; OCD patientswere less accurate than controls at the patternrecognition task, and TS patients were less ac- curate than controls on both tasks [smaller For five subjects, one of the tests was not com- pleted successfully, and these data are missingfrom the analyses : BDI (two patients in the OCD group) ; Go/No-go (one OCD) ; decision- making task (one TS) ; TOL (one TS).
For purposes of analysis, subjects were scoredas to whether they successfully completed all phases, or whether they failed before or after One-way ANOVAs revealed no significant dif- starting the ED shift phase. Likelihood-ratio ferences between the three groups in terms of analyses confirmed that a higher proportion of Cognition in Tourette’s syndrome and OCD response latencies on these two key dimen- sional shift stages is possible by contrasting model as a repeated-measures factor. However,estimates of mean population differences in performance will be slightly conservative, as the worst performing subjects in the patient groupsdid not contribute to these stages.
The groups differed in overall error rates the ED shift phase [F(1, 53)=45.95], and there was a significant interaction between these two factors [F(2, 53)=4.21]. Separate analysis of thetwo stages confirmed the pattern seen in pass/ fail data. Whilst there were no group differences in errors at the ID shift stage [F<1], there was asignificant effect of group upon error rates at the ED shift stage [F(2, 55)=4.73)], with both patient groups making more errors than controls [smaller t(53)=2.24]. The two patient groups did not differ in ED shift error rates (t<1).
Response latencies (logarithm-transformed) were similar for all groups, and stages, with no interaction [largest F(1, 49)=1.68, p=0.20].
Attentional set-shifting test. –#–, TS ; –%–, OCD ; –m–, The results of this test are shown in Table 2.
control. (a) Percentage of subjects passing each stage, shown as a Separate ANOVAs were performed, contrast- cumulative attrition curve. OCD patients and controls performedsimilarly up to the intra-dimensional reversal (IDR) stage, but sig- ing (arcsine-transformed) proportion of trials nificantly more OCD patients failed at the extra-dimensional shift correct first attempt, and (logarithmic-trans- (EDS) stage than controls. (b) Mean errors at intra-dimensional shift(IDS) and EDS stages of the attentional set-shifting test. Data are formed) mean latency to first response for the included for all subjects who attempted both stages, regardless of three groups, with trial difficulty as a within- outcome on the EDS stage. Both TS patients and OCD patients subject factor. There was a main effect of diffi- made disproportionately more errors at the EDS stage comparedwith the matched control group. Error bar=1 standard error of the culty on both measures [smaller F (4, 208)= mean (S.E.M.). (c) Mean correct response latencies. There were no 31.66], but they did not interact with group significant differences, although the OCD patients tended to be slow.
reversal ; CDr, superimposed compound discrimination/reversal ; groups to take longer and make fewer correct IDSr, intra-dimensional shift/reversal ; EDSr, extra-dimensional first responses were non-significant [larger shift/reversal. Note that for (b) and (c) performance at the EDris disconnected from the EDS stage, as a number of patients failed at the EDS, and therefore did not attempt the EDr.
patients than controls failed to complete all The proportion of trials on which subjects chose stages [x2(2)=7.51], as shown in Fig. 1a. The the most likely outcome were 95.9, 98.1 and tendency of TS patients to be more likely than 98.6 % for the TS, OCD and control groups OCD patients to fail prior to the EDS phase was respectively. With half or more of the subjects non-significant [x2(1)=1.99, p=0.27].
in each group scoring 100 %, these data cannot Error rates and response latencies for those be made suitable for parametric analyses.
subjects who attempted the ED shift stage of the task are shown in Fig. 1(b, c). Because all sub- groups differed [x2(2)=6.65], Mann–Whitney jects who undertook the ID shift stage also tests confirming that OCD patients and controls undertook the ED shift stage (20 controls, 19 chose similarly well (ZU=0.53) and that TS OCD, 17 TS), comparison of group errors and patients chose the more likely outcome less Performance on psychological tests (values are untransformed cell means) % Bet, mean percentage of points staked on trials on which the more likely outcome was chosen. % First, mean percentage of problems on which the correct response was chosen first. Analysis revealed no significant differences between groups on these measures.
frequently than did the other groups (smaller methods do not allow estimation of the contri-bution of age and sex to these differences.
The mean choice latency and bet sizes for this task are shown in Table 2. Analysis of the (logarithm-transformed) choice latency and the mean percentage bet size was performed by separate ANOVA models with ratio condition included as a within-subject factor. Ratio sig- nificantly influenced bet size [F(3, 156)=31.10], but not choice latency (F<1). Crucially, neither measure was influenced by group, nor were there any grouprratio interactions (all F ’s<1).
Mean change in percentage false alarm rate between switch and non-switch trials for the three groups in the Go/No-go task.
Error bars represent 2 S.E.D., estimated from the error term of for the Very few targets were missed : 0.7, 0.9 and 1.0 % grouprswitch interaction in an ANOVA, using harmonic mean n.
of targets for TS, OCD and control groups Means and error bars calculated from untransformed values.
respectively. These data are unsuitable forparametric analysis ; Kruskal–Wallis analysis in Fig. 2. OCD patients had a significantly revealed no effect of group upon omission errors greater switch cost (increase in false-positive [x2(2)=1.16, p>0.5]. Somewhat higher pro- errors following switch blocks) than did TS portions of non-targets were responded to (false- patients [t(56)=2.43], which was also margin- positive errors) : 11.8, 8.3 and 7.4 of targets for ally greater than controls [t(56)=1.95, p=0.055].
TS, OCD and control groups respectively.
TS patients were no more or less influenced by Analysis of these (arcsine-transformed) data was conducted with block type (switch ornon-switch) as a repeated-measures factor. This revealed the expected effect of switch, in that The results from the patient groups were further subjects made significantly more false-positives analysed to investigate the effects of medi- on switch blocks [F(1, 56)=36.78]; any tendency cation on patient performance. Antipsychotic- for the groups to differ in overall false-positive medicated TS patients were significantly more rate was not significant [F(2, 56)=2.32, p>0.1].
accurate on the spatial recognition memory test Critically, the detrimental effect of switch on [U=13.5, p<0.05] than TS patients who were error rates was significantly influenced by sub- not taking antipsychotic medication but none of ject group [F(2, 56)=3.30]; these data are shown the other core test measures differed between Cognition in Tourette’s syndrome and OCD these two groups. There were no significant dif- new information on previously unstudied as- ferences between the OCD patient group taking pects of cognitive functioning in OCD.
SSRIs and the unmedicated OCD patients on By contrast to their intact verbal fluency, arithmetic performance, planning and decision-making, OCD patients were selectively im-paired at the ED shift stage of the attentional set-shifting test. Three previous studies of OCD(Veale et al. 1996 ; Purcell et al. 1997 a, 1998) This study is the first systematically to compare have analysed the data for this test differently a broad range of ‘ frontal ’ executive functions in by using trials to criterion (rather than errors TS and OCD. Overall, the results clearly show to criterion) to index rule learning and Purcell qualitative similarities in cognitive performance et al. (1997 a, 1998) did not compare the ID between TS and OCD with some differences and ED shift stages directly. Veale et al. (1996) in the exact form and degree of deficits. This found gradual attrition throughout the test profile was particularly evident for the tests of stages, but their OCD group were mostly in- inhibitory control where both groups were sig- nificantly impaired on the shifting component clinically disabled or had a higher degree of co-morbidity than the current group, probably group more significantly so) and at the extra- resulting in fewer patients attempting the ED shift stage, thus reducing the power of detect- attentional-set formation and shifting task. TS ing differences in attentional set-shifting per se.
patients showed a non-significant tendency to From Veale et al. (1996) and the current study have more difficulties with the stages earlier it appears that ED shift performance in OCD than the extra-dimensional shift. Thus the OCD depends on severity ; less clinically impaired group, in particular, showed impressive evidence OCD patients (present group) are impaired of selectivity of deficits at the shifting stages selectively at the ED shift stage, whereas sev- erely affected in-patients show attrition at attentional set-shifting tests. For the tests of earlier stages. It is relevant to compare the recognition memory, again both groups were performance of depressed unipolar patients of impaired, however, with some differences, for similar age, where there has been little con- example the OCD patients had significantly sistent evidence to support an ED shifting slowed response latencies. Both groups had deficit (Purcell et al. 1997 b ; Elliott et al. 1998 ; spared executive function, in terms of perform- Sweeney et al. 2000), although this may depend ance on conventional tests of verbal fluency on factors such as the severity of depressive and working memory (WAIS arithmetic), the TOL test of planning and decision-making tests.
The clear-cut nature of the deficits of the However, the TS group did show a small deficit in quality of decision-making. These profiles of other stages, thus suggests a selective deficit in cognitive impairment are striking, given the cognitive flexibility in this group, probably not close genetic relationship between the two con- due to depressed mood, but consistent with the ditions and additional similarities of under- hypothesis that some of the tendency towards lying neuropathology (for review, see Leckman compulsive modes of behaviour and ruminative et al. 1997 ; Saxena et al. 1998). This discussion tendencies arises from a generalized impair- focuses on the cognitive profiles of the two ment in inhibitory function at the cognitive patient groups, particularly with respect to their level that normally allows adaptive shifting be- relationship to clinical symptoms, and impli- tween different actions and thoughts. Further cations for the neuroanatomical bases of these support for this view can be found in the significant deficits by the OCD group in theswitching of the Go/No-go reversal task.
Whilst the OCD group neither made signifi- The data for the OCD group help to resolve cantly more false-positive errors overall than inconsistencies in the literature and also provide controls, nor had a particular difficulty in the challenging situation of withholding respond- et al. 1997 a, 1998 ; Schmidtke et al. 1998). Use ing to a non-target subsequent to a response of the one-touch TOL in this study has avoided to the previous target (which is impaired in the potential confounds of online monitoring Huntington’s disease patients ; Watkins, L., of (and possibly ruminating over) performance unpublished observations), the OCD group did (Goel & Grafman, 1995), allowing confirmation respond excessively to the previously rewarded of intact planning ability in OCD, which con- stimulus category (i.e. they perseverated) when trasts markedly with the impairments seen in required to reverse response categories on depressed patients of similar age (Elliott et al.
switch blocks. This reversal is somewhat akin to tests of simple alternation, in which subjects The OCD patients were also unimpaired on a must reverse reward contingencies on each test of decision-making in which they had to trial, and which are very sensitive to OCD select from and ‘ bet ’ on outcomes with dif- (Abbruzzese et al. 1995 ; Gross-Isseroff et al.
fering probabilities. Although they exhibited 1996 ; Cavedini et al. 1998). Behavioural pro- some slowing in deliberation time, this was not significant, and contrasts with the slow- paradigms have been particularly associated ing observed in depression. OCD patients are with the ventro-lateral prefrontal region, from also unimpaired in accuracy on probabilistic studies with non-humans (e.g. Iversen & reasoning tasks (Volans, 1976 ; Fear & Healy, Mishkin, 1970 ; Butters et al. 1973), patients with frontal lobe damage (Aron et al. 2003) Although the robust impairment we observed and using functional imaging in healthy hu- in visual recognition memory on this test may mans (Kawashima et al. 1996 ; Casey et al.
well reflect impaired temporal lobe function 1997 ; Konishi et al. 1998). The OCD patients (Owen et al. 1995), it is also possible that it in this study were impaired only when reversing reflects prefrontal cortex (PFC) dysfunction, Go/No-go contingencies, suggesting that, as there being good evidence that the more pos- well as implicating the ventro-lateral region terior OFC regions and the anterior cingulate (see Cools et al. 2002), such a deficit could be are important in visual recognition memory more closely related to the reversal deficits seen (Bachevalier & Mishkin, 1986 ; Elliott & Dolan, after ventral frontal damage (Daum et al. 1991 ; 1999 ; Frey & Petrides, 2000). The OCD patients Rolls et al. 1994 ; Dias et al. 1996). Indeed, were not significantly impaired on the spatial Rolls et al. (1994) study employed a Go/No-go recognition memory task, which, in contrast to visual pattern recognition resembles those frontal lesion patients although unimpaired on tests of spatial working memory that activate the initial Go/No-go discrimination stage, then the DLPFC (Owen et al. 1996), as well as being perseverated to the previously correct stimulus more sensitive to frontal as opposed to tem- in subsequent reversal stages ; a similar pattern poral lobe lesions in humans (Owen et al. 1995).
to that seen in the OCD patients here. The However, the OCD patients were significantly selectivity of this impairment is particularly slower on both tasks, which may reflect a speed- important as the intact Go/No-go performance error trade-off strategy that compensates effec- overall by OCD patients shows that they were tively for spatial working-memory deficits. The not impaired in global aspects of response in- lengthened latencies of the OCD patients on hibition, leading for example, to excessively the memory recognition tasks were not matched disinhibited or impulsive responding.
by significant overall slowing on the other tasks.
The deficient performance of OCD patients However, it should be pointed out that de- on tests of response inhibition contrasted pressed patients are also impaired in recognition markedly with their intact performance on other ‘ frontal ’ executive tests less dependent on in-hibitory processes. The preservation of ‘ look- ahead ’ planning accuracy in these patients is By comparison with OCD, the TS group gen- consistent with previous findings of intact ac- erally showed qualitatively similar, although curacy on TOL planning tasks and the related smaller, deficits, except for the decision-making Tower of Hanoi task (Veale et al. 1996 ; Purcell test. Such impairment was unlikely to have Cognition in Tourette’s syndrome and OCD preservation also of several aspects of fronto- TS group since neither the mean ADSA score (Triolo & Murphy, 1996) nor the mean LOI(Cooper, 1970 ; Snowdon, 1980) score were Conclusions and implications for the neural significantly different from normative data substrates of cognitive deficits in OCD and TS and neither score correlated with cognitive This study has identified a distinct profile of deficits, especially in terms of response inhi- Overall, the cognitive changes in TS were bition, in the genetically related disorders of much less clear-cut than for OCD. Over one- third of TS patients failed to complete all stages of cognitive shifting in OCD, despite intact of the attentional set-shifting test but the pattern planning and decision-making helps to resolve was one of gradual attrition, suggesting diffi- several previous discrepancies in the literature.
culties in set-formation and set-maintenance, These deficits reflect a general difficulty in shift- as well as set-shifting. The only previous study ing of set in OCD patients, which is also seen comparing performance of TS patients with in their obsessive and compulsive symptoms, matched control subjects on the Wisconsin Card perhaps resulting from impaired functioning Sorting Test found no evidence for impairment of fronto-striatal circuitry. The set-shifting im- (Sutherland et al. 1982). However, the results of pairments are consistent with dorsolateral and the current study show that some TS patients ventrolateral prefrontal dysfunction. However, have difficulties with set-shifting, and possibly such dysfunction is unlikely to be global, as performance on the TOL test, which is sensitive Possibly the most surprising finding in the to dorsolateral prefrontal dysfunction (see TS group was that of relatively intact Go/ Manes et al. 2002), was strikingly unimpaired.
No-go performance. This test was designed to detect inhibitory problems at three distinct abilities in a test also sensitive to orbito-frontal levels of behavioural regulation : general in- damage (Rogers et al. 1999), also suggests that ability to withhold responding to non-targets ; OCD patients do not suffer from global OFC inability to withhold responding to non-targets deficits either. Overall, the pattern of fronto- in the particularly taxing situation of when executive impairment in OCD is consistent non-targets directly follow targets ; and in- with the nature of their clinical symptoms, but ability to switch between response categories does not indicate generalized executive mal- on different blocks. Only for the last measure function. In comparison, TS patients showed a was there a statistically marginal tendency for similar, but less clear-cut pattern of impair- TS patients to be impaired. Ozonoff et al.
ment on tests of pattern and spatial recognition (1994) also found intact Go/No-go and Go/ memory, attentional set-formation and shift- No-go reversal in children with TS. Thus TS ing and quality of decision-making, consist- patients appear able to inhibit the well-in- ent with the genetic relationship with OCD.
tegrated responses required in the Go/No-go Their limited profile of cognitive impairments, paradigm. This indicates that tics are not a re- was not, however, simply restricted to fronto- sult of fronto-executive inhibitory dysfunction executive function, including, for example a operating at a cognitive level of response con- visual recognition memory deficit. The most trol, but instead are caused by impairments at a interesting area of relative preservation of lower level of response control, possibly striatal function in TS was for those Go/No-go test measures of impulsive, as distinct from com- The TS patients were unimpaired on the one- pulsive (switching set), modes of responding.
touch TOL, but had a minor deficit in selecting Thus, the TS patients were able to inhibit highly the most likely outcome on the decision-making pre-potent voluntary responses, although their tests. In summary, the TS patients had some syndrome is characterized by a difficulty in significant deficits in decision-making, atten- suppressing involuntary behaviour. Consistent tional set-shifting and in visual pattern and spatial recognition memory accuracy, including tested here, it is possible that this difference a test of spatial working memory, but showed results from impairments in response control mechanisms at the striatal, rather than the Bachevalier, J. & Mishkin, M. (1986). Visual recognition impairment follows ventromedial but not dorsolateral prefrontal lesions inmonkeys. Behavioural Brain Research 20, 249–261.
Baker, S. C., Rogers, R. D., Owen, A. M., Frith, C. D., Dolan, R. J., co-morbid feature of OCD and TS, possibly Frackowiak, R. J. & Robbins, T. W. (1996). Neural systemsengaged by planning : a PET study of the Tower of London task.
However, a recent study by McLean et al. (2004) Bechara, A., Damasio, H., Tranel, D. & Anderson, S. W. (1998).
Dissociation of working memory from decision making withinthe human prefrontal cortex. Journal of Neuroscience 18, 428–437.
battery, showed a distinctly different profile Beck, A. T., Ward, C. H., Mendelson, M., Mock, J. E. & Erbaugh, on the Go/No-go test, ADHD patients being J. K. (1961). An inventory for measuring depression. Archives slower to respond but not impaired at shifting, Benton, A. L. (1968). Different behavioral effects in frontal lobe and also being worse at planning, than their disease. Neuropsychologia 6, 53–60.
age-matched controls. Overall, these data are Braun, A. R., Stoetter, B., Randolph, C., Hsiao, J. K., Vladar, K., Gernert, J., Carson, R. E., Herscovitch, P. & Chase, T. N. (1993).
consistent with a cognitive pattern of deficits in The functional neuroanatomy of Tourette’s syndrome : an FDG- OCD that mainly appears to contribute to or PET study. I. Regional changes in cerebral glucose metabolism promote the perseverative or compulsive tend- differentiating patients and controls. Neuropsychopharmacology9, 277–291.
ency, rather than reflecting what Hollander & Butters, N., Butter, C., Rosen, J. & Stein, D. (1973). Behavioural Rosen (2000) describe as the impulsivity pole of effects of sequential and one-stage ablations of orbital prefrontal the compulsive–impulsive spectrum.
cortex in the monkey. Experimental Neurology 39, 204–214.
Cambridge Cognition (2004). CANTAB (www.camcog.com). Cam- bridge Neuropsychological Test Automated Battery. Cambridge,UK.
Casey, B. J., Trainor, R. J., Orendi, J. L., Schubert, A. B., Nystrom, L. E., Giedd, J. N., Castellanos, X., Haxby, J. V., Noll, D. C.,Cohen, J. D., Forman, S. D., Dahl, R. E. & Rapoport, J. L. (1997).
We are grateful to the participants of this study A developmental functional MRI study of prefrontal activation and their families, to Professor M. Trimble and during performance of a Go-No-Go task. Journal of Cognitive Dr E. Krishnamoorthy for help with recruiting Cavedini, P., Ferri, S., Scarone, S. & Bellodi, L. (1998). Frontal in the TS clinic and to Dr A. Rosser and Elise lobe dysfunction in obsessive-compulsive disorder and major de- DeVito for helpful discussion. This work was pression : a clinical-neuropsychological study. Psychiatry Research78, 21–28.
Cools R, Clark, L, Owen, A. M. & Robbins, T. W. (2002). Defining grant (no. 019407) and was completed within the neural mechanisms of probabilistic reversal learning using the MRC Centre for Behavioural and Clinical event-related functional magnetic resonance imaging. Journal ofNeuroscience 22, 4563–4567.
Neuroscience. L.H.A.W. was supported by the Cooper, J. (1970). The Leyton Obsessional Inventory. Psychological Huntington’s Disease Association and the Daum, I., Schugens, M. M., Channon, S., Polkey, C. E. & Gray, J. A.
unilateral temporal or frontal lobe lesions in man. Cortex 27,613–622.
Devinsky, O. (1983). Neuroanatomy of Gilles de la Tourette’s syndrome. Archives of Neurology 40, 508–514.
Dias, R., Robbins, T. W. & Roberts, A. C. (1996). Dissociation in B.J.S. and T.W.R. both consult for Cambridge prefrontal cortex of affective and attentional shifts. Nature 380, Downes, J. J., Roberts, A. C., Sahakian, B. J., Evenden, J. L., Morris, R. G. & Robbins, T. W. (1989). Impaired extra-dimen-sional Parkinson’s disease. Neuropsychologia 27, 1329–1343.
Drewe, E. A. (1975). Go-No Go learning after frontal lobe lesions in Abbruzzese, M., Ferri, S. & Scarone, S. (1995). Wisconsin Card Sorting Test performance in obsessive-compulsive disorder : no Eapen, V., Pauls, D. L. & Robertson, M. M. (1993). Evidence for evidence for involvement of dorsolateral prefrontal cortex.
autosomal dominant transmission in Gilles de la Tourette Syndrome – United Kingdom cohort study. British Journal of Alexander, G. E., Delong, M. R. & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal Elliott, R. & Dolan, R. J. (1999). Differential neural responses during ganglia and cortex [Review]. Annual Review of Neuroscience 9, performance of matching and non-matching to sample tasks at two delay intervals. Journal of Neuroscience 19, 5066–5073.
APA (1994). Diagnostic and Statistical Manual of Mental Disorders Elliott, R., McKenna, P. J., Robbins, T. W. & Sahakian, B. J. (1998).
(4th edn). American Psychiatric Association : Washington, DC.
Specific neuropsychological deficits in schizophrenic patients Aron, A. R., Fletcher, P. C., Bullmore, E. T., Sahakian, B. J. & with preserved intellectual function. Cognitive Neuropsychiatry 3, Robbins, T. W. (2003). Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nature Neuroscience 6, Elliott, R., Sahakian, B. J., McKay, A. P., Herrod, J., Paykel, E. S.
& Robbins, T. W. (1996). Neuropsychological impairment in Cognition in Tourette’s syndrome and OCD unipolar depression : the influence of perceived failure on sub- Owen, A. M., Sahakian, B. J., Semple, J., Polkey, C. E. & sequent performance. Psychological Medicine 26, 975–989.
Robbins, T. W. (1995). Visuospatial short term recognition Fear, C. F. & Healy, D. (1997). Probabilistic reasoning in obsessive- memory and learning after temporal lobe excisions, frontal lobe compulsive and delusional disorders. Psychological Medicine 27, excisions or amygdale hippocampectomy in man. Neuropsycho- Folstein, M. F., Folstein, S. E. & McHugh, P. R. (1975). Mini-mental Ozonoff, S., Strayer, D. L., McMahon, W. M. & Filloux, F. (1994).
state. Journal of Psychiatric Research 12, 189–198.
Executive function abilities in autism and Tourette syndrome : an Freeman, C. P. (1992). What is obsessive compulsive disorder ? information processing approach. Journal of Child Psychology and International Clinical Psychopharmacology 7 (Suppl. 1), 11–17.
Psychiatry, and Allied Disciplines 35, 1015–1032.
Frey, S. & Petrides, M. (2000). Orbitofrontal cortex : a key prefrontal Pauls, D. L., Alsobrook, J. P., Goodman, W., Rasmussen, S. & region for encoding information. Proceedings of the National Leckman, L. F. (1995). A family study of obsessive-compulsive Academy of Sciences USA 97, 8723–8727.
disorder. American Journal of Psychiatry 152, 76–84.
Godefroy, O., Lhullier, C. & Rousseaux, M. (1996). Non-spatial Pauls, D. L. & Leckman, J. F. (1986). The inheritance of Gilles de attention disorders in patients with frontal or posterior brain la Tourette’s syndrome and associated behaviours : evidence for autosomal dominant inheritance. New England Journal of Goel, V. & Grafman, J. (1995). Are the frontal lobes implicated in planning functions – interpreting data from the Tower of Hanoi.
Petrides, M. (1986). The effect of periarcuate lesions in the monkey on the performance of symmetrically and asymmetrically Goodman, W. K., Price, L. H., Rasmussen, S. A., Mazure, C., reinforced visual and auditory Go, No-Go tasks. Journal of Fleischmann, R. L., Hill, C. L., Heninger, G. R. & Charney, D. S.
Purcell, R., Maruff, P., Kyrios, M. & Pantelis, C. (1997 a). Cognitive Development, use, and reliability. Archives of General Psychiatry deficits in obsessive-compulsive disorder on tests of frontal-striatal function. Biological Psychiatry 43, 348–357.
Gross-Isseroff, R., Sasson, Y., Voet, H., Hendler, T., Luca-Haimovici, Purcell, R., Maruff, P., Kyrios, M. & Pantelis, C. (1997 b).
K., Kandel-Sussman, H. & Zohar, J. (1996). Alternation learning Neuropsychological function in young patients with unipolar in obsessive-compulsive disorder. Biological Psychiatry 39, major depression. Psychological Medicine 27, 1277–1285.
Purcell, R., Maruff, P., Kyrios, M. & Pantelis, C. (1998).
Hollander, E. & Rosen, J. (2000). Impulsivity. Journal of Psycho- Neuropsychological deficits in obsessive-compulsive disorder.
Archives of General Psychiatry 55, 415–423.
Howell, D. C. (1997). Statistical Methods for Psychology. Duxbury Rahman, S., Sahakian, B. J., Rogers, R. D., Hodges, J. R. & Robbins, T. W. (1999). Specific cognitive deficits in early frontal variant Iversen, S. D. & Mishkin, M. (1970). Perseverative interference in frontotemporal dementia. Brain 122, 1469–1493.
monkeys following selective lesions of the inferior prefrontal con- Robbins, T. W. (1977). A critique of the methods available for the vexity. Experimental Brain Research 11, 376–386.
measurement of spontaneous locomotor activity. In Handbook of Kawashima, R., Satoh, K., Itoh, H., Ono, S., Furumoto, S., Gotoh, R., Psychopharmacology VII (ed. L. L. Iversen and S. D. Iversen), Koyama, M., Yoshioka, S., Takahashi, T., Thakahashi, K., Yanagisawa, T. & Fukuda, H. (1996). Functional anatomy of Go/ Robbins, T. W. (1996). Dissociating executive functions of the No-Go discrimination and response selection – a PET study in prefrontal cortex. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 351, 1463–1470.
Konishi, S., Nakajima, K., Uchida, I., Sekihara, K. & Miyashita, Y.
Robertson, M. M. (1994). Gilles de la Tourette Syndrome – an (1998). No-go dominant brain activity in human inferior pre- update. Journal of Child Psychology and Psychiatry, and Allied frontal cortex revealed by functional magnetic resonance imaging.
European Journal of Neuroscience 10, 1209–1213.
Robertson, M. M. (2000). Tourette syndrome : associated conditions Kullback, S. (1968). Information Theory and Statistics. Dover Press : and the complexities of treatment. Brain 123, 425–462.
Robertson, M. M. & Eapen, V. (1996). The National Hospital Lawrence, A. & Sahakian, B. J. (1996). The neuropsychology Interview Schedule for the assessment of Gilles de la Tourette of fronto-striatal dementias. In Handbook of the Clinical Syndrome. International Journal of Methods in Psychiatric Psychology of Aging (ed. R. T. Woods), pp. 243–265. John Wiley : Rogers, R. D., Andrews, T. C., Grasby, P. M., Brooks, D. J. & Leckman, J. F., Peterson, B. S., Anderson, G. M., Arnsten, A. F. T., Robbins, T. W. (2000). Contrasting cortical and sub-cortical Pauls, D. L. & Cohen, D. J. (1997). Pathogenesis of Tourette’s activations produced by attentional-set shifting and reversal syndrome. Journal of Child Psychology and Psychiatry, and Allied learning in humans. Journal of Cognitive Neuroscience 12, Leckman, J. F., Riddle, M. A., Hardin, M. T., Ort, S. I., Swartz, Rogers, R. D., Everitt, B. J., Baldacchino, A., Blackshaw, A. J., K. L., Stevenson, J. & Cohen, D. J. (1989). The Yale Global Tic Swainson, R., Wynne, K., Baker, N. B., Hunter, J., Carthy, T., Severity Scale : initial testing of a clinician-rated scale of tic sev- Booker, E., London, M., Deakin, J. F., Sahakian, B. J. & Robbins, erity. Journal of the American Academy of Child and Adolescent T. W. (1999). Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with Manes, F., Sahakian, B. J., Clark, L., Rogers, R., Antoun, N., Aitken, focal damage to prefrontal cortex, and tryptophan-depleted nor- M. & Robbins, T. W. (2002). Decision making processes following mal volunteers : evidence for monoaminergic mechanisms. Neuro- damage to the prefrontal cortex. Brain 125, 624–639.
McLean, A., Dowson, J., Toone, B., Young, S., Bazanis, E., Robbins, Rolls, E. T., Hornak, J., Wade, D. & McGrath, J. (1994). Emotion- T. W. & Sahakian, B. J. (2004). Characteristic neurocognitive related learning in patients with social and emotional changes profile associated with adult attention-deficit/hyperactivity dis- associated with frontal lobe damage. Journal of Neurology, order. Psychological Medicine 34, 681–692.
Neurosurgery and Psychiatry 57, 1518–1524.
Nelson, H. E. (1982). National Adult Reading Test Manual. NFER : Sahakian, B. J., Morris, R. G., Evenden, J. L., Heald, A., Levy, R., Philpot, M. & Robbins, T. W. (1988). A comparative study of Owen, A. M., Doyon, J., Petrides, M. & Evans, A. C. (1996).
visuospatial memory and learning in Alzheimer-type dementia Planning and spatial working memory : a positron emission tom- and Parkinson’s disease. Brain 111, 695–718.
ography study in humans. European Journal of Neuroscience 8, Saxena, S., Brody, A. L., Schwartz, J. M. & Baxter, L. R.
obsessive-compulsive disorder. British Journal of Psychiatry ; the (ed. A. J. Friedhoff and T. N. Chase), pp. 311–322. Raven Press : Journal of Mental Sciences 173 (Suppl. 35), 26–37.
Schmidtke, K., Schorb, A., Winkelmann, G. & Hohagen, F. (1998).
Sweeney, J. A., Kmiec, J. A. & Kupfer, D. J. (2000). Neuro- Cognitive frontal lobe dysfunction in obsessive-compulsive dis- psychologic impairments in bipolar and unipolar mood disorders order. Biological Psychiatry 43, 666–673.
on the CANTAB neurocognitive battery. Biological Psychiatry 48, Schwartz, J. M. (1998). Neuroanatomical aspects of cognitive- behavioural therapy response in obsessive-compulsive disorder.
Tranel, D., Anderson, S. W. & Benton, A. (1994). Development of An evolving perspective on brain and behaviour. British Journal of the concept of ‘ executive function ’ and its relationship to the frontal lobes. In Handbook of Neuropsychology (ed. F. Boller and Snowdon, J. (1980). A comparison of written and postbox forms J. Grafman), pp. 125–148. Elsevier : Amsterdam.
of the Leyton Obsessional Inventory. Psychological Medicine 10, Triolo, S. J. & Murphy, K. R. (1996). Attention Deficit Scales for Adults (ADSA) : Manual for Scoring and Interpretation. Brunner/ SPSS Inc. (2001). SPSS version 11.0.1. Statistical Package for the Veale, D. M., Sahakian, B. J., Owen, A. M. & Marks, I. M. (1996).
State, M. W., Greally, J. M., Cuker, A., Bowers, P. N., Henegraiu, Specific cognitive deficits in tests sensitive to frontal lobe dys- O., Morgan, T. M., Gunel, M., DiLuna, M., King, R. A., Nelson, function in obsessive-compulsive disorder. Psychological Medicine C., Donovan, A., Anderson, G. M., Leckman, J. F., Hawkins, T., Pauls, D. L., Lifton, R. P. & Ward, D. C. (2003). Epigenetic ab- Volans, P. J. (1976). Styles of decision-making and probability normalities associated with a chromosome 18 (q21–q22) inversion appraisal in selected obsessional and phobic patients. British and a Gilles de la Tourette syndrome phenotype. Proceedings of Journal of Social and Clinical Psychology 15, 305–317.
the National Academy of Sciences USA 100, 4684–4689.
Wechsler, D. (1981). Manual for the Wechsler Adult Intelligence Sutherland, R. J., Kolb, B., Schoel, W. M., Whishaw, I. Q. & Scale – Revised. Psychological Corporation : New York.
Davies, D. (1982). Neuropsychological assessment of children and Weeks, R. A., Turjanski, N. & Brooks, D. J. (1996). Tourette’s adults with Tourette syndrome : a comparison with learning syndrome : a disorder of cingulate and orbitofrontal function ? disabilities and schizophrenia. In Gilles de la Tourette Syndrome Quarterly Journal of Medicine 89, 401–408.

Source: http://www.veale.co.uk/wp-content/uploads/2010/10/46-Executive-function-in-Tourettes-OCD-.pdf

Microsoft word - sordoochoafinalworkshopmedinfapp032309.doc

A PSO/ACO Approach to Knowledge Discovery in a Pharmacovigilance Context ABSTRACT at any dose is suspected to have resulted in adverse outcome in a We propose and evaluate the use of a PSO/ACO methodology for classification and rule discovery in the context of medication Given the limitations of premarketing trials, e.g. highly selected postmarketing surveillance or pharmacovigilan

12 a qi stärkende arzneien

Lehrgang Chinesische Arzneien Materia Medica 12 A Qi stärkende Arzneien ein Ausbildungskurs der Sacam Postfach 2003 • 8021 Zürich • Tel. 0844 200 200 Fax 031 332 41 12 • [email protected] • www.sacam.ch I. Qi-Schwäche (Qi Xu) Ursachen  unregelmässiges oder falsches Essen  Blutverlust  zu viel oder zu wenig Bewegung Symptome  Milz-Qi-Schwäche

Copyright ©2010-2018 Medical Science