Intradimensional/extradimensional Research Articles

Exploring the development of attentional set shifting in young children with a novel Intradimensional/Extradimensional shift task

Attentional set shifting is a core part of cognition, allowing quick and flexible adaption to new demands. The study of its development during early childhood has been hampered by a shortage of measures not requiring language. This article argues for a revival of the Intradimensional/Extradimensional (ID/ED) shift task by presenting a new nonverbal version of the task (Shifting Tray task). Children (N = 95 3- to 5-year-olds; 49 girls; predominantly European White) were presented with pairs of trays, each filled with a substrate and an upside-down cup on top, and were asked to find stickers. In the pre-switch phase, children learned (through trial and error) which dimension (substrate or cup) was predictive of the rewards. In the post-switch phase, all stimuli were exchanged. For children in the intradimensional shift condition, the dimension predictive of the sticker was the same as the one predictive in the pre-switch phase. For children in the extradimensional shift condition, the previously irrelevant dimension was now relevant. Results showed that most 3-year-olds were able to switch, and older children did not outperform younger children. The easy and flexible nature of the task allows researchers to investigate the impact of labels and instructions and to use it in cross-cultural and comparative research.

THE ROLE OF COGNITIVE CONTROL AND RUMINATION IN PREDICTING DEPRESSION AMONG ADOLESCENTS WITH INTERNALIZING DISORDERS

Given the high prevalence of internalizing disorders among adolescents, it is necessary to define the factors affecting the development and course of psychopathology. Nolen Hoeksema demonstrated the effect of rumination on the development of various forms of psychopathology in adults, while recent data suggest that cognitive control may be a factor underlying this relationship. The aim of this study is to investigate the relation between cognitive control impairments and symptoms of depression through rumination in adolescents suffering from internalizing psychiatric disorders. The study included 100 adolescents of both genders diagnosed with internalizing psychiatric disorders at the Unit for Child and Adolescent Psychiatry at University Hospital Center Osijek. During psychodiagnostic assessment, subjects completed Youth self report, CANTAB Intra-dimensional/extra-dimensional (IED) task, The Ruminative Response Scale, and Beck Depression Inventory-II. The results indicate a clinically significant level of internalizing symptoms and a clinically and subclinically high level of depressive symptoms. The results also show a high positive correlation between internalizing symptoms, rumination, and depressive symptoms, as well as a positive correlation between female gender and internalizing symptoms, rumination, and depressive symptoms. Significant predictors of depression are female gender and rumination while cognitive control has not been detected as a significant predictor. The results of the study emphasize the importance of rumination in the prediction of depressive symptoms in internalizing psychiatric disorders among adolescents and, accordingly, the importance of rumination as a clinical variable in terms of implications in the prevention and treatment of internalizing psychopathology.

Preliminary evidence for the phosphodiesterase type-4 inhibitor, roflumilast, in ameliorating cognitive flexibility deficits in patients with schizophrenia.

Background:Cognitive flexibility deficits are present in patients with schizophrenia and are strong predictors of functional outcome but, as yet, have no pharmacological treatments.Aims:The purpose of this study was to investigate whether the phosphodiesterase type-4 inhibitor, roflumilast, can improve cognitive flexibility performance and functional brain activity in patients with schizophrenia.Methods:This was a within-subject, randomised, double-blind, placebo-controlled, three-period crossover study using a version of the Intradimensional/Extradimensional (ID/ED) task, optimised for functional magnetic resonance imaging (fMRI), in 10 patients with schizophrenia who were scanned after receiving placebo, 100 µg or 250 µg roflumilast for 8 consecutive days. Data from an additional fMRI ID/ED study of 18 healthy participants on placebo was included to contextualise the schizophrenia-related performance and activations. The fMRI analyses included a priori driven region of interest (ROI) analysis of the dorsal frontoparietal attention network.Results:Patients on placebo demonstrated broad deficits in task performance compared to the healthy comparison group, accompanied by preserved network activity for solution search, but reduced activity in left ventrolateral prefrontal cortex (VLPFC) and posterior parietal cortex for attentional set-shifting and reduced activity in left dorsolateral prefrontal cortex (DLPFC) for reversal learning. These ROI deficits were ameliorated by 250 µg roflumilast, whereas during solution search 100 µg roflumilast reduced activity in the left orbitofrontal cortex, right DLPFC and bilateral PPC, which was associated with an improvement in formation of attentional sets.Conclusions:The results suggest roflumilast has dose-dependent cognitive enhancing effects on the ID/ED task in patients with schizophrenia, and provides sufficient support for larger studies to test roflumilast’s role in improving cognitive flexibility deficits in this clinical population.

Trait affective differences influence behavioral flexibility in virtual spatial and non-spatial discrimination tasks

Affect and cognitive control processes are closely related, however, most studies have assessed state affect or affective disorders. The current study investigates the relationship between individual differences in trait affectivity and flexibility in spatial navigation and stimulus discrimination tasks. Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and the Positive and Negative Affectivity Scale (PANAS) were given to 82 participants followed by an intradimensional/extradimensional (ID/ED) set-shifting task in which navigation was reinforced based on visual stimuli colocalized with a goal or based on the spatial location of the goal. Higher BDI and NA predicted greater trials-to-criteria during ED shift, but not initial learning or ID shifting. Participants who failed to meet criteria during either ID or ED set-shifting (N = 16) had significantly higher scores for NA, BDI, and BAI compared to individuals who successfully met criterion (N = 56) with this relationship being primarily observed in males. The current findings indicate that negative affectivity is associated with poor performance in behavioral flexibility.

Sex Differences in Cognitive Flexibility and Resting Brain Networks in Middle-Aged Marmosets

Sex differences in human cognitive performance are well characterized. However, the neural correlates of these differences remain elusive. This issue may be clarified using nonhuman primates, for which sociocultural influences are minimized. We used the marmoset (Callithrix jacchus) to investigate sex differences in two aspects of executive function: reversal learning and intradimensional/extradimensional (ID/ED) set shifting. Stress reactivity and motor function were also assessed. In agreement with human literature, females needed more trials than males to acquire the reversals. No sex differences in ED set shifting or motivational measures were observed. The findings suggest enhanced habit formation in females, perhaps due to striatal estrogenic effects. Both sexes showed increased urinary cortisol during social separation stressor, but females showed an earlier increase in cortisol and a greater increase in agitated locomotion, possibly indicating enhanced stress reactivity. Independent of sex, basal cortisol predicted cognitive performance. No sex differences were found in motor performance. Associations between brain networks and reversal learning performance were investigated using resting state fMRI. Resting state functional connectivity (rsFC) analyses revealed sex differences in cognitive networks, with differences in overall neural network metrics and specific regions, including the prefrontal cortex, caudate, putamen, and nucleus accumbens. Correlations between cognitive flexibility and neural connectivity indicate that sex differences in cognitive flexibility are related to sex-dependent patterns of resting brain networks. Overall, our findings reveal sex differences in reversal learning, brain networks, and their relationship in the marmoset, positioning this species as an excellent model to investigate the biological basis of cognitive sex differences.

Effects of lesions of the subthalamic nucleus/zona incerta area and dorsomedial striatum on attentional set-shifting in the rat

Patients with Parkinson’s disease (PD) show cognitive impairments, including difficulty in shifting attention between perceptual dimensions of complex stimuli. Inactivation of the subthalamic nucleus (STN) has been shown to be effective in ameliorating the motor abnormalities associated with striatal dopamine (DA) depletion, but it is possible that STN inactivation might result in additional, perhaps attentional, deficits. This study examined the effects of: DA depletion from the dorsomedial striatum (DMS); lesions of the STN area; and the effects of the two lesions together, on the ability to shift attentional set in the rat.In a single session, rats performed the intradimensional/extradimensional (ID/ED) test of attentional set-shifting. This comprises a series of seven, two-choice discriminations, including acquisitions of novel discriminations in which the relevant stimulus is either in the currently attended dimension (ID) or the currently unattended dimension (ED shift) and reversals (REVs) following each acquisition stage.Bilateral lesions were made by injection of 6-hydroxydopamine (6-OHDA) into the DMS, resulting in a selective impairment in reversal learning. Large bilateral ibotenic acid lesions centered on the STN resulted in an increase in trials to criterion in the initial stages, but learning rate improved within the session. There was no evidence of a ‘cost’ of set-shifting – the ED stage was completed in fewer trials than the ID stage – and neither was there a cost of reversal learning. Strikingly, combined lesions of both regions did not resemble the effects of either lesion alone and resulted in no apparent deficits.

EXPLORING COMORBID OBSESSIVE-COMPULSIVE DISORDER AND ALCOHOL USE DISORDER USING NEUROPSYCHOLOGICAL TOOLS: A PRELIMINARY ANALYSIS

abstract By investigating neuropsychological profiles in patients with obsessive-compulsive disorder (OCD) and OCD with alcohol use disorder (OCD+AUD), focusing on tasks of behavioural inhibition, attentional set-shifting and decision-making, we aimed to elucidate factors contributing to compulsive behaviour. Consenting patients (n=24) were recruited from outpatient clinics and attributed to DSM-IV OCD (n=14) or OCD+AUD (n=10) groups. Healthy controls with no relevant family history (n= 15) were identified through established databases and public advertisement. We used the Barratt Impulsiveness Scale (BIS) to assess behavioural impulsivity, the Stop-Signal Task for motor response inhibition, the Intradimensional-Extradimensional (ID-ED) Set-Shift Task for attentional flexibility and the Cambridge Gamble Task (CGT) for decision-making. Analysis of co-variance was used to test for group differences, controlling for depression (Montgomery-Asberg Depression Rating Scale) and anxiety (State-Trait Anxiety Inventory), for which both patient groups scored significantly higher (p When we co-varied for anxiety and depression, both patient groups showed poorer attentional flexibility on the ID-ED task than controls (p=.01, with large effect size). Motor response inhibition (SST) did not differ between groups, however the OCD+AUD group showed poorer attentional inhibition than both other groups on the attentional subscale of BIS (p=.001). The quality of CGT decision-making was also significantly poorer in the OCD+AUD group than in the pure OCD group and controls (p=.05). Interestingly, significantly higher (p Although our interpretations are limited by small sample size, it appears the impairment in decision-making, set-shifting and attentional impulsivity observed in OCD+AUD may be attributable to between-group differences in intelligence. There is some evidence that lower premorbid IQ may be linked with AUD, specifically in those patients with a strong family history of AUD. On the other hand, questions have been raised as to the validity of the NART as a specific measure of premorbid IQ in AUD. Future such studies should pay close attention to measuring to premorbid intelligence and its relationship with neurocognitive performance.

Attentional Set-Shifting Paradigm in the Rat.

The attentional set-shifting task (ASST) is the rat version of the intra-dimensional/extra-dimensional (ID/ED) test and was developed fifteen years ago. Damage to the medial frontal cortex results in a failure to "unlearn" old contingencies, i.e., impairs ED set shifting. As such, the task measures cognitive flexibility that can be compromised both in schizophrenia and depression as well as in animal models of these diseases.

Guanfacine enhances inhibitory control and attentional shifting in early abstinent cocaine-dependent individuals.

Attenuation of adrenergic drive and cognitive enhancement, via stimulation of alpha2 pre- and post-synaptic receptors, may selectively enhance executive performance in early abstinent cocaine-dependent individuals. As these cognitive processes underpin important treatment-related behaviors, the alpha2 agonist, guanfacine HCl, may represent an effective pharmaco-therapeutic intervention. Twenty-five early abstinent cocaine-dependent individuals were administered a battery of neurocognitive tasks on entry into treatment (baseline) and again following 3 weeks of either placebo or guanfacine treatment (up to 3 mg). Tasks included: Stop Signal, Stroop, 3-Dimentional Intra-dimensional/Extra-dimensional (IDED) task, Spatial Working Memory (SWM), Paired Associates Learning (PAL), Verbal Fluency and the Rey Auditory Verbal Learning Test (RAVLT). Compared with placebo, the guanfacine group demonstrated attenuated anxiety and negative affect as well as improved performance on selective executive tests. This included fewer directional errors on the stop signal task, fewer errors on the extra-dimensional shift component of the IDED task and better attentional switching during verbal fluency. Guanfacine did not improve strategic working memory or peripheral memory. Guanfacine improves selective cognitive processes which may underlie salient treatment-related regulatory behaviors. Alpha2 agonists may therefore represent important agents for cocaine dependence.

A longitudinal examination of neuropsychological and clinical functioning in boys with attention deficit hyperactivity disorder (ADHD): improvements in executive functioning do not explain clinical improvement

Attention deficit hyperactivity disorder (ADHD) often, but not always, persists into adulthood. Investigations of the associations between clinical and biological markers of persistence can shed light on causal pathways. It has been proposed that compensatory improvements in executive neuropsychological functioning are associated with clinical improvements. This is the first study to test this hypothesis prospectively. The clinical and neuropsychological functioning of 17 boys with ADHD (mean age 10.45 years at time 1; 14.65 years at time 2) and 17 typically developing (TYP) boys (mean age 10.39 years at time 1; 14.47 years at time 2) was tested on two occasions, 4 years apart. This was done using a battery of standardized neuropsychological tests that included tasks with high and low executive demands. Clinical improvements were observed over time. Neuropsychological performance improvements were also evident, with ADHD boys developing with a similar pattern to TYP boys, but with a developmental lag. Whilst there was an association between reduced symptoms and superior performance at retest for one task with a high executive demand (spatial working memory), this was not seen with two further high executive demand tasks [Stockings of Cambridge and intra-dimensional extra-dimensional (ID/ED) set shifting]. Also, there was no association between change in executive functioning and change in symptoms. Baseline performance on the ID/ED set-shifting task predicted better clinical outcome. Only change in performance on the low executive demand delayed matching-to-sample task predicted better clinical outcome. These data highlight the importance of longitudinal measurements of cognition, symptoms and treatment response over time in children and adolescents with ADHD.

Set shifting and reversal learning in borderline personality disorder

People with BPD have been shown in some studies to have structural deficits in regions of the prefrontal cortex. A sensitive test of prefrontal cortex function is the intra-dimensional/extra-dimensional (IDED) set shifting task. This study sought to examine whether people with BPD demonstrate impaired performances on extra-dimensional shift (EDS) and reversal learning aspects of this task similar to those seen in conditions such as schizophrenia and bipolar affective disorder. Twenty subjects with BPD and 21 healthy control subjects were administered the IDED task from the Cambridge Neuropsychological Test Automated Battery cognitive test battery. EDS and reversal learning errors were compared between the groups using repeated measures ANOVAs. There was no significant difference between the BPD and control participants in EDS or reversal learning on the IDED task or in stage of the task completed. There was a medium effect size difference (Cohen's d = 0.4) for simple reversal learning and small effect sizes for reversal learning (Cohen' d = 0.17) and IDED shift stages (Cohen's d = 0.2 and -0.3 respectively). Participants with BPD in this study did not show statistically significant deficits in EDS or reversal learning, although small to medium effect sizes were found. These findings distinguish them from sufferers of schizophrenia and bipolar affective disorder and are in keeping with the idea that BPD is a distinct condition with discrete neuropathological processes.

Executive Functioning in People With Obsessive-Compulsive Personality Traits: Evidence of Modest Impairment

Investigations of executive dysfunctions among people with obsessive-compulsive personality disorders (OCPD) have yielded inconsistent results. The authors speculate that obsessive-compulsive personality traits (OCPT) from a nonclinical population may be associated with specific executive dysfunctions relative to working memory, attentional set-shifting, and planning. A sample consisting of 79 adults (39 females, 40 males) was divided into high and low scorers on the Personality Diagnostic Questionnaire-4 (PDQ-4; Hyler, 1994). In addition, these participants were interviewed using the SCID-II (First, Spitzer, Gibbon & Williams, 1997) to confirm the presence of symptoms of obsessive-compulsive personality. Participants completed a battery of executive tasks associated with the Cambridge Neuropsychological Test Automated Battery (CANTAB), including Spatial Working Memory, Intradimensional/Extradimensional (ID/ED), Attentional Set-Shifting, and Stockings of Cambridge. Also, self-report measures of executive functions as well as of anxiety and depressive symptoms were administered. The analysis of covariance revealed significant differences between participants with OCPT and controls on the Spatial Working Memory tasks, ID/ED tasks, Stockings of Cambridge, and the Dysexecutive Questionnaire (DEX). Nevertheless, there were no significant differences in the number of problems solved in minimum movements. These results suggest that executive dysfunctions are present in people with prominent OCPT and that there is a high convergence between clinical and ecological measures of executive functions in people with obsessive personality traits.

Cognitive dysfunction in childhood-onset pathologic skin picking

ObjectiveThere has been little research examining cognitive correlates of childhood-onset pathologic skin picking. MethodsOf 50 subjects with Pathological Skin Picking (PSP), 24 (48%) (mean age 32.3±12.2 years; PSP onset at 7.67±2.54 years; 87.5% female) reported onset of skin picking before age 11 years. These subjects were compared to 26 subjects with later onset of picking after age 11 years (mean age 34.2±14.5 years; PSP onset 18.04±9.51 years; 92.3% female) on measures of symptom severity, comorbidity, and social functioning. Both groups undertook cognitive assessments using the Stop-signal task (assessing response impulsivity) and the Intra-dimensional/Extra-dimensional (ID/ED) Set Shift task (assessing cognitive flexibility). ResultsThere were no significant clinical differences based on age of PSP onset. Early and later onset PSP showed significantly prolonged stop-signal reaction times (i.e., worse inhibition) versus healthy controls, but, contrary to our hypothesis, only the later onset patients manifested significantly elevated errors on the set-shifting task versus controls (i.e., cognitive inflexibility: total errors corrected and errors for the extradimensional shift stage). ConclusionThese results indicate overlapping clinical features and impulse dyscontrol between early and later onset PSP, but heterogeneity with respect to set-shifting dysfunction. Future work should explore possible subgroups in PSP and whether age of onset and cognitive functioning is predictive of treatment outcomes.

A cognitive comparison of pathological skin picking and trichotillomania

Objective Pathological Skin Picking (PSP) and Trichotillomania (TTM) share overlapping comorbidity and phenomenology. The extent to which these disorders share a common cognitive phenotype, however, has yet to be examined. This study sought to compare inhibitory control processes in individuals with PSP or TTM. Methods Thirty-one subjects with PSP (mean age 31.2 ± 12.5 years; 93.5% female), 39 subjects with TTM (mean age 35.9 ± 10.7 years; 87.2% female), and 33 matched controls (mean age 31.9 ± 9.9 years; 72.7% female) undertook cognitive assessments using the Stop-Signal Task (assessing response impulsivity) and the Intra-dimensional/Extra-dimensional (ID/ED) Set Shift task (assessing cognitive flexibility). Groups were matched for age, gender, race/ethnicity, and education. Results PSP was associated with significantly impaired stop-signal reaction times but intact ID/ED cognitive flexibility compared to controls. TTM occupied an intermediate position in terms of stop-signal reaction times between controls and PSP but did not differ significantly from either group on the ID/ED Set Shift Task. Conclusion These results replicate the finding of impaired inhibitory control in PSP but suggest TTM may be heterogeneous with respect to such impairment. Future work should explore possible subgroups in TTM and whether cognitive variables are predictive of treatment outcomes.

A neurocognitive comparison of cognitive flexibility and response inhibition in gamblers with varying degrees of clinical severity

As a behavioral addiction with clinical and phenomenological similarities to substance addiction, recreational and pathological gambling represent models for studying the neurobiology of addiction, without the confounding deleterious brain effects which may occur from chronic substance abuse. A community sample of individuals aged 18-65 years who gamble was solicited through newspaper advertising. Subjects were grouped a priori into three groups (no-risk, at-risk, and pathological gamblers) based on a diagnostic interview. All subjects underwent a psychiatric clinical interview and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Subjects with a current axis I disorder, history of brain injury/trauma, or implementation or dose changes of psychoactive medication within 6 weeks of study enrollment were excluded. A total of 135 no-risk, 69 at-risk and 46 pathological gambling subjects were assessed. Pathological gamblers were significantly older, and exhibited significant deficiencies in motor impulse control (stop-signal reaction times), response speed (median 'go' trial response latency) and cognitive flexibility [total intra-dimensional/extra-dimensional (IDED) errors] versus controls. The finding of impaired impulse control and cognitive flexibility was robust in an age-matched subgroup analysis of pathological gamblers. The no-risk and at-risk gambling groups did not significantly differ from each other on task performance. Impaired response inhibition and cognitive flexibility exist in people with pathological gambling compared with no-risk and at-risk gamblers. The early identification of such illness in adolescence or young adulthood may aid in the prevention of addiction onset of such disabling disorders.

Adolescent rats show cognitive rigidity in a test of attentional set shifting

As neuropsychiatric disorders such as schizophrenia, attention deficit disorder, and mood disorders all impact executive function and are likely to be diagnosed prior to adulthood, it is important to understand the normal ontogeny of executive function. Previous behavioral research has shown that adolescents' executive function is different than that of adults. In the present study, we use a previously validated cognitive test, the intradimensional/extradimensional (ID/ED) set-shifting task, to assess attentional set shifting and reversal learning in adolescent and adult, male, Long-Evans rats. These data suggest that adolescent rats are more cognitively rigid than adult rats and have impairments in the shifting, but not formation, of an attentional set. Adolescent rats are also more susceptible to distraction than adult rats when an irrelevant stimulus dimension is introduced as part of a complex stimulus. Moreover, we find that attentional set shifting becomes adult-like at an earlier age than reversal learning. As these functions are mediated by distinct prefrontal subregions, that is, the prelimbic and orbitofrontal cortices, respectively, we hypothesize that prefrontal cortical subregions show slightly different developmental trajectories.

Cigarette smoking status in pathological gamblers: Association with impulsivity and cognitive flexibility

Background While the majority of pathological gamblers are current cigarette smokers (CS), some have quit smoking (former smokers, FS) while others never smoked (never smokers, NS). The reasons for elevated smoking rates in pathological gambling are not known, but gamblers may use nicotine as a putative cognitive enhancer. This study evaluated impulsivity and cognitive flexibility in a sample of pathological gamblers with differing smoking status. Methods Fifty-five subjects with pathological gambling (CS, n = 34; FS, n = 10; NS, n = 11) underwent cognitive assessments using the Stop-Signal (SST) and Intradimensional/Extra-dimensional (ID/ED) set-shift tasks. Results CS reported less severe gambling problems than either FS or NS on the Yale Brown Obsessive Compulsive Scale modified for Pathological Gambling, and CS was associated with significantly fewer directional errors on the SST task, compared to NS. In addition, in CS, higher daily cigarette consumption was associated with fewer total errors on the ID/ED task. Conclusions The potential role of nicotine as a cognitive enhancer was supported by objective tests of impulsivity and cognitive flexibility. Human laboratory studies using nicotine challenges in pathological gambling will shed further light on this relationship.

Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study.

Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG. This study sought to examine the safety and efficacy of Memantine in PG. Twenty-nine subjects (18 females) with DSM-IV PG were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra-dimensional (ID/ED) set shift task (assessing cognitive flexibility). Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8 ± 4.3 at baseline to 8.9 ± 7.1 at study endpoint (p < 0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p < 0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p = 0.037) at study endpoint. The mean effective dose of memantine was 23.4 ± 8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility. These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

Motor inhibition and cognitive flexibility in pathologic skin picking

Individuals with pathologic skin picking (PSP) often report significant difficulty resisting the urges and drive to engage in picking behavior. Studies have shown significant inhibitory deficiencies (i.e. increased impulsivity) in subjects with other putative obsessive-compulsive spectrum disorders, such as trichotillomania, using objective tests. This study sought to assess motor inhibitory control and aspects of cognitive flexibility in a sample of individuals with PSP. Twenty subjects with PSP (mean age 33.1+/-14.3 years; 85% female) and 20 healthy controls (mean age 31.6+/-9.1 years; 85% female) underwent cognitive assessments using the Stop-signal and Intra-dimensional/Extra-dimensional (ID/ED) set-shift tasks. Groups were matched for age, gender, and education. PSP was associated with significantly impaired stop-signal reaction times but intact ID/ED cognitive flexibility compared to controls. Measures of disease severity in the PSP subjects did not covary significantly with stop-signal performance. The finding of impaired inhibitory control but intact set-shift cognitive flexibility draws remarkable parallels with findings in trichotillomania but differs from obsessive compulsive disorder. These findings have important implications for understanding potential neurobiological dysfunction in PSP, how the disorder should be classified, and suggest new potential treatment directions.

Chronic infusion of PCP via osmotic mini-pumps: A new rodent model of cognitive deficit in schizophrenia characterized by impaired attentional set-shifting (ID/ED) performance

The identification of animal disease-like models for cognitive symptoms in schizophrenia is of central importance to the successful development of pharmacological therapies for psychosis resulting in a functional outcome in patients. Executive function is one of the most severely affected cognitive domains in schizophrenia that remains inadequately treated by existing therapies. The rat attentional set-shifting (or intra-dimensional–extra-dimensional (ID/ED)) task has been developed to test executive function in rodents and successful translation of pre-clinical data into the clinical setting now depends on the identification of a predictive animal disease-like model. The present study investigates whether a continuous 14-day mini-pump infusion of the non-competitive NMDA receptor antagonist phencyclidine (PCP) leads to a deficit in the ID/ED task, and subsequently evaluates the effect of modafinil in this model.Lister hooded rats were implanted subcutaneously with osmotic mini-pumps containing saline or PCP (15mg/kg/day) for 14 days followed by a 7-day drug-free recovery phase. Rats were then tested in the ID/ED task following an acute injection of either vehicle or modafinil. PCP-treated animals displayed a selective deficit at the ED shift stage resembling that observed in schizophrenic patients. This deficit was reversed by an acute injection of modafinil. The PCP-induced impairment and its reinstatement by modafinil are quantitatively and qualitatively similar to that described earlier by our group following sub-chronic intraperitoneal PCP administration, indicative that sub-chronic PCP infusion via osmotic mini-pumps may represent an attractive alternative to the systemic administration protocols generally employed to date.