Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children.

BACKGROUND: Executive function deficits have been reported repeatedly in children with Attention Deficit Hyperactivity Disorder (ADHD). Stimulant medication has been shown to be effective in improving cognitive performance on most executive function tasks, but neuropsychological tests of executive function in this population have yielded inconsistent results. Methodological limitations may explain these inconsistencies. This study aimed to measure executive function in medicated and non-medicated children with ADHD by using a computerized battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), which is sensitive to executive function deficits in older patients with frontostriatal neurological impairments. METHODS: Executive function was assessed in 30 children with ADHD: 15 were stimulant medication naive and 15 were treated with stimulant medication. These two groups were compared to 15 age, sex and IQ matched controls. RESULTS: The unmedicated children with ADHD displayed specific cognitive impairments on executive function tasks of spatial short-term memory, spatial working memory, set-shifting ability and planning ability. Impairments were also seen on spatial recognition memory and delayed matching to sample, while pattern recognition memory remained intact. The medicated children with ADHD were not impaired on any of the above executive function tasks except for deficits in spatial recognition memory. CONCLUSIONS: ADHD is associated with deficits in executive function. Stimulant medication is associated with better executive function performance. Prospective follow-up studies are required to examine these effects.     

Specific Neuropsychological Deficits in Schizophrenic Patients with Preserved Intellectual Function

Although a wide range of cognitive deficits have been demonstrated in schizophrenia, it is not clear whether specific deficits stand out from general intellectual decline. Separate cases have been made for selective impairments in mnemonic and in executive function but these remain unconfirmed. A common problem in studies of schizophrenia is heterogeneity of deficits and Shallice, Burgess, and Frith (1991) have addressed this by using a single case study approach. The present study used the CANTAB battery of neuropsychological tests to examine cognitive performance in a small group of schizophrenic patients with preserved intellectual function. This test battery allows a componential analysis of performance, and its neurological validation may enable specific neurobiological hypotheses to be addressed. Twelve schizophrenic patients with current IQ greater than 90 and within 10 points of premorbid IQ were assessed on tests of visuospatial memory, spatial working memory, planning, and attentional set-shifting. Their performance was compared to that of 12 matched controls. The patient group, as a whole, was impaired on all tasks but the pattern of impairment varied across individuals. Consistently, severe deficits were seen on tests of delayed matching to sample and attentional set-shifting. These deficits are compared to those seen in patients with unipolar depression, who showed similar deficits in delayed matching to sample but not set-shifting, and are considered in terms of common cognitive mechanisms and possible neural substrates.     

Early discrimination reversal learning impairment and preserved spatial learning in a longitudinal study of Tg2576 APPsw mice

To understand the relationship between amyloid-beta and cognitive decline in Alzheimer's disease, we evaluated cortical and hippocampal function in a transgenic mouse model of amyloid over-expression in Alzheimer's disease, the Tg2576 mouse. Tg2576 mice and their non-transgenic littermates were assessed at both 6 and 14 months of age in a battery of cognitive tests: attentional set-shifting, water maze spatial reference memory and T-maze working memory. Spatial reference memory was not affected by Tg status at either age. Working memory was only affected by age, with 6-month-old mice performing better than 14-month-old ones. Older mice were also significantly impaired on reversal learning and on the intra- and extra-dimensional shift in attentional set-shifting. A significant transgene effect was apparent in reversal learning, with Tg2576 mice requiring more trials to reach criterion at 6 months old. These data indicate that the effects of normal aging in C57B6xSJL F1 mice are most pronounced on putative frontal cortex-dependent tasks and that increasing Abeta load only affects discrimination reversal learning in our study.     

Neuropsychological functioning in stimulant-naive boys with hyperkinetic disorder

BACKGROUND: Although children with hyperkinetic disorder and/or attention deficit hyperactivity disorder (ADHD) show disordered executive neuropsychological functioning, the nature of these changes remains controversial. Additionally, impairments in non-executive neuropsychological functioning have been relatively unexplored. Here, the authors describe the neuropsychological functioning of a sample of stimulant drug-naive boys with hyperkinetic disorder on a battery of neuropsychological tasks sensitive to impairments of both executive and non-executive functions. METHOD: Seventy-five stimulant drug-naive boys meeting diagnostic criteria for ICD-10 hyperkinetic disorder were compared with 70 healthy developing controls matched for age but not IQ on computerized tests of neuropsychological functioning from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a Go/No-Go inhibition task. RESULTS: Boys with hyperkinetic disorder exhibited impairments on tasks with a prominent executive component--working memory, planning, strategy formation, attentional set-shifting and on a reaction time task. However, they were also impaired on tasks without prominent executive components--pattern and spatial recognition, spatial span, delayed matching to sample and paired associates learning. Contrary to predictions, no impairment was observed on the Go/No-Go inhibition task. CONCLUSIONS: Medication-naive boys with hyperkinetic disorder displayed a broad range of neuropsychological impairments. Deficits were demonstrated on tasks with and without prominent executive components. Impairments were not confined to tasks dependent upon frontostriatal functioning, cannot wholly be explained by deficits in inhibitory control, nor can they be attributed to intelligence or previous exposure to stimulant medication.     

Differential performance on tasks of affective processing and decision-making in patients with Panic Disorder and Panic Disorder with comorbid Major Depressive Disorder

BACKGROUND: Neuropsychological studies have provided evidence for deficits in psychiatric disorders, such as schizophrenia and mood disorders. However, neuropsychological function in Panic Disorder (PD) or PD with a comorbid diagnosis of Major Depressive Disorder (MDD) has not been comprehensively studied. The present study investigated neuropsychological functioning in patients with PD and PD + MDD by focusing on tasks that assess attention, psychomotor speed, executive function, decision-making, and affective processing. METHODS: Twenty-two unmedicated patients with PD, eleven of whom had a secondary diagnosis of MDD, were compared to twenty-two healthy controls, matched for gender, age, and intelligence on tasks of attention, memory, psychomotor speed, executive function, decision-making, and affective processing from the Cambridge Neuropsychological Test Automated Battery (CANTAB), Cambridge Gamble Task, and Affective Go/No-go Task. RESULTS: Relative to matched healthy controls, patients with PD + MDD displayed an attentional bias toward negatively-valenced verbal stimuli (Affective Go/No-go Task) and longer decision-making latencies (Cambridge Gamble Task). Furthermore, the PD + MDD group committed more errors on a task of memory and visual discrimination compared to their controls. In contrast, no group differences were found for PD patients relative to matched control subjects. LIMITATIONS: The sample size was limited, however, all patients were drug-free at the time of testing. CONCLUSIONS: The PD + MDD patients demonstrated deficits on a task involving visual discrimination and working memory, and an attentional bias towards negatively-valenced stimuli. In addition, patients with comorbid depression provided qualitatively different responses in the areas of affective and decision-making processes.     

Impaired cognition and decision-making in bipolar depression but no 'affective bias' evident

BACKGROUND: Depression is usually the predominant affective state in bipolar disorder. There are few studies, with discrepant views, examining the extent of cognitive impairment in patients with bipolar depression. To our knowledge, there are no previous studies examining decision-making ability or whether there is an affective attentional bias in bipolar depression. METHOD: We ascertained 24 depressed bipolar I patients from acute psychiatric hospital wards and out-patient clinics and 26 age- and IQ-matched healthy controls. Using computerized tests we evaluated their performance on 'neutral' (non-emotional) cognitive tasks (i.e. memory, attention and executive function) and on novel tasks of emotional cognition (i.e. the decision-making task and the affective go/no-go task). RESULTS: Accuracy measures were significantly impaired on tests of visual and spatial recognition and attentional set-shifting in bipolar depression compared with age- and IQ-matched controls. The quality of decision-making was also significantly impaired in the patients. A mood-congruent attentional bias for 'sad' targets was not evident on the affective go/no-go task. CONCLUSIONS: We found widespread evidence of significant cognitive impairment and impaired quality of decision-making in symptomatically severe depressed bipolar patients. This cognitive impairment may contribute to difficulties with daily living, decision-making and the ability to engage and comply with psychological and drug treatments.     

Impairment of olfactory identification in obsessive-compulsive disorder

BACKGROUND: Olfactory identification ability has been associated with processing in the orbitofrontal cortex (OFC), an area that has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). Although olfactory sensitivity is normal in patients with OCD, no study has investigated olfactory identification in this disorder. METHODS: A group of 20 subjects with OCD and 23 age- and education-matched controls performed a standardized test of olfactory identification. They also performed computerized tests of spatial memory span, spatial working memory and spatial recognition memory that have been shown previously to be sensitive to cognitive deficits in patients with OCD. RESULTS: Performance on the olfactory identification task, spatial recognition task and spatial span task was significantly worse in the OCD group than controls. CONCLUSIONS: While impairment in spatial cognition is consistent with previous studies of OCD, its significance for brain-behaviour models of OCD is unclear. However, the finding of abnormal olfactory identification in patients with OCD is consistent with the hypothesis that there is a disruption to processing at the level of the OFC in the disorder.     

Executive functions in young males with fragile X syndrome in comparison to mental age-matched controls: baseline findings from a longitudinal study

The performance of 54 boys with fragile X syndrome (FXS), ages 7 to 13 years, was compared to that of a group of typically developing boys who were matched on mental age (MA) and ethnicity across multiple measures of executive function (EF). Boys with FXS varied in their ability to complete EF measures, with only 25.9% being able to complete a set-shifting task and 94.4% being able to complete a memory for word span task. When compared to the control group, and controlling for MA and maternal education, boys with FXS showed significant deficits in inhibition, working memory, cognitive flexibility/set-shifting, and planning. No group differences were observed in processing speed. Mental age significantly impacted performance on working memory, set-shifting, planning, and processing speed tasks for both groups. In boys with FXS, MA significantly predicted performance on working memory and set-shifting tasks. Our findings suggest that deficits in EF in boys with FXS are not solely attributable to developmental delays but, rather, present as a true array of neurocognitive deficits.     

强迫症的认知执行功能研究

本文着重回顾了强迫症患者在注意、记忆、模式转换和组织策略等方面的认知执行功能的表现，提出各研究之间结果所存在的分歧，主要与测验的选用，患者状态的控制（用药、病程）有关。脑影像学的结果指出强迫症患者的认知执行功能障碍很可能与额叶-纹状体回路功能失调有关。建议对强迫症患者执行功能的研究尽量选用测查内容更为细化的测验。     

The role of learned irrelevance in attentional set-shifting impairments in Parkinson's disease

In this study, the cognitive and neurochemical factors underlying learned irrelevance, one of the mechanisms thought to be responsible for attentional set-shifting deficits in Parkinson's disease (PD), were investigated. In a visual discrimination learning task, the extent to which a target dimension was irrelevant prior to an extra-dimensional shift was varied. Twenty patients with PD and 22 healthy participants performed the task twice, with patients tested on and off L-dopa. The patients made more errors than control participants in the condition in which the target dimension was completely irrelevant prior to the extradimensional shift, but not when it was partially reinforced. Moreover, L-dopa had no effect on the patients' task performance, despite improving their working memory. These results confirm that learned irrelevance is a significant factor in accounting for attentional set-shifting deficits in patients with PD, although unlike other executive impairments in this group, the phenomenon appears to be unrelated to their central dopaminergic deficit.     

A meta-analytic review of Wisconsin Card Sorting Test and verbal fluency performance in obsessive-compulsive disorder

Introduction. Abnormalities in associative frontostriatal circuits are often associated with obsessive-compulsive disorder (OCD), leading many researchers to predict that executive dysfunction should be particularly pronounced. However, deficits on putative tests of this construct have not consistently been identified. Methods. The present study used quantitative techniques to integrate results from 32 studies that assessed OCD patients' performance on tests of phonemic fluency, semantic fluency, and/or the Wisconsin Card Sorting Test (WCST). Results. As has been found for patients with focal frontal (but not focal nonfrontal) cortical lesions, relative to healthy controls OCD patients were comparably impaired on tests of phonemic and semantic fluency (r s =.33 and.37, respectively). However, in contrast to patients with focal frontal lobe injuries, fluency deficits did not qualify as differential deficits relative to psychomotor speed. Moreover, although a prominent view in the literature is that set-shifting is particularly compromised, the WCST was less sensitive to the presence of OCD than phonemic and semantic fluency, and also failed to qualify as a differential deficit. Conclusions. For patients with OCD, deficits on tests of verbal fluency and the WCST do not appear to reflect executive dysfunction, but are instead consistent with a more generalised cognitive impairment.     

A deficit in attentional set-shifting of violent offenders

BACKGROUND: Recent brain imaging studies suggest that proneness to violence and antisocial behaviour may be associated with dysfunction of the prefrontal cortex. The present study. therefore, examined aspects of prefrontally guided executive functions in a group of criminal violent men. METHODS: Violent offenders undergoing forensic psychiatric examination by court order undertook computerized tasks for planning, visual working memory and attentional set-shifting from the Cambridge Neuropsychological Test Automated Battery. Their performance was compared to that of subjects with marginal mental retardation and normal controls. RESULTS: Violent offenders performed well on tasks for spatial and figurative working memory, as well as on a test for planning. A marked impairment was observed in the attentional set-shifting task: offenders made significantly more errors than the other groups when required to shift attention from one perceptual dimension to another. Reversal learning was also deficient. Correlational analyses within the offender group revealed that poor performance on the perceptual shift problem was associated with fewer errors in tasks for working memory and planning. CONCLUSIONS: The present results suggest that violent offenders show dual impairments in inhibitory cognitive control. First, they are deficient in shifting attention from one category to another. Secondly, the ability to alter behaviour in response to fluctuations in the emotional significance of stimuli is compromised. These deficits might constitute cognitive reflections of the biological prefrontal alterations observed in this group of people.     

Cognitive impairment in remission in bipolar affective disorder

BACKGROUND: Although the traditional view of bipolar affective disorder is that the majority of patients have full remission between episodes, recent evidence suggests that residual cognitive deficits are present. The aim of this study was to determine whether memory and executive deficits were present in a well-defined clinically remitted group of patients. METHODS: This was a case-control study of bipolar patients in remission (N = 18). Subjects had to fulfil stringent clinical criteria for inclusion into the study and had to have been in remission for at least 4 months. Subjects also had no history of substance dependence. The cognitive battery examined memory and executive function. RESULTS: Patients in excellent clinical remission and who reported good social adaptation showed imipairment on tests of visuospatial recognition memory. Accuracy on four tests of executive function was not impaired in patients in remission compared with controls, although response latency on these executive tests was still impaired. CONCLUSIONS: As our group and others have shown, patients with mania and unipolar depression show generalized impairment on tests of memory and executive function. In comparison, this study has demonstrated that patients in remission show a relatively specific impairment in memory with recovery of accuracy measures on executive function task. The increased response latency on the executive tasks suggests a possible small residual impairment. These findings suggest that in netIroanatomical terms, more posterior cortical function (temporal lobe) has not improved but there is at least some recovery of frontal lobe function in remission.     

Neurocognitive deficits in decision-making and planning of patients with DSM-III-R borderline personality disorder

BACKGROUND: Repeated, self-damaging behaviour occurring in the context of borderline personality disorder (BPD) may reflect impairments in decision-making and planning cognition. However, there has been no systematic neuropsychological examination of these particular cognitive functions in patients diagnosed with BPD. Such investigations may improve our understanding of the possible role of brain dysfunction in BPD and improve the characterization of the psychological difficulties associated with this disorder. METHOD: Forty-two psychiatric patients with a diagnosis of DSM-III-R BPD (41 of whom gave a history of self-harm), without a history of specified 'psychoses' or current major affective disorder, were clinically assessed before completing computerized tasks of decision-making and planning previously shown to be sensitive to frontal lobe dysfunction, and tests of spatial and pattern visual recognition memory previously shown to be sensitive to frontal lobe damage and temporal lobe damage respectively. The performance of the BPD patient group was compared with that of a non-clinical control group consisting of 42 subjects. RESULTS: The performance of the BPD patients on the decision-making task was characterized by a pattern of delayed and maladaptive choices when choosing between competing actions, and by impulsive, disinhibited responding when gambling on the outcome of their decisions. BPD patients also showed impairments on the planning task. There was no evidence of impaired visual recognition memory. Additional analyses suggested only limited effects of current medication and history of previous substance use disorder. CONCLUSIONS: These findings suggest that BPD is associated with complex impairments in dissociable cognitive processes mediated by circuitry encompassing the frontal lobes. These impairments may mediate some of the behavioural changes evident in BPD. Further work is needed to examine the specificity of these findings.     

Reconsidering the Gospel According to Group Studies: A Neuropsychological Case Study Approach to Schizophrenia

Individual patterns of performance on tests of: visual perception, language, executive function, memory, and face-processing, were examined in 10 schizophrenic patients who were preselected for having current WAIS IQ and premorbid NART IQ scores in the normal range. Although the patients showed some heterogeneity in the type, pervasiveness, and degree of cognitive impairment, a majority had severely impaired verbal recall and familiar face-naming. This contrasted with the low incidence and severity of impairment on tests of executive function, visual recall, recognition memory, naming, and unfamiliar faceprocessing. Contrasts between individual patients indicated that verbal recall and executive performance are independent in some patients and that memory appears to be the core deficit. The profile of impaired and preserved cognitive function revealed some important dissimilarities from the pattern that has emerged from group studies. Finally, face-naming correlated highly with the learning of unrelated paired associates, confirming a similarity with neurological patients who have person name anomia. It is suggested that both deficits might reflect a problem with learning ''meaninglessness'' associations; this interpretation is discussed with reference to a deficit at the level of the Supervisory Attentional System (Shallice, 1988).     

Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability

BACKGROUND: Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia. METHOD: Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses. RESULTS: Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance. CONCLUSION: The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.     

Neuropsychological performance of OCD patients before and after treatment with fluoxetine: evidence for persistent cognitive deficits

BACKGROUND: There is an ongoing debate about the nature of executive dysfunction that accompanies obsessive-compulsive disorder (OCD). One reason for this may be that state-related factors, such as use of medication or co-morbid symptoms, confound with task performance. This study tried to isolate trait- from state-dependent cognitive impairments by examining variability of cognition following treatment. METHOD: Nineteen OCD patients were tested on the Cambridge Neuropsychological Test Automated Battery (CANTAB) before and after treatment with fluoxetine. Their pattern of performance was compared to the one observed in healthy volunteers (N = 24). RESULTS: OCD patients displayed impairments in planning ability, spatial memory and motor speed that persisted after clinical improvement. With treatment, OCD performance diverged from that of controls on measures of focused attention and strategic ability. However, these effects were rather mild as they did not entail a significant deterioration of performance within the OCD sample. CONCLUSIONS: Our data suggest that cognitive impairments in OCD are not secondary to symptoms and therefore form a trait feature of the disorder. The nature of the deficits refers to a chronic dysfunction of the dorsolateral-striatal circuit. The minor effects of treatment on task performance is in line with recent evidence that serotonin mediates cognitive functions of orbitofrontal cortex to a greater extent than those associated with dorsolateral prefrontal regions.     

Distinct manifestations of executive dysfunction in aged rats

Different components of executive function such as working memory, attention, and cognitive flexibility can be dissociated behaviorally and mechanistically; however, the within-subject influences of normal aging on different aspects of executive function remain ill-defined. To better define these relationships, young adult and aged male F344 rats were cross-characterized on an attentional set-shifting task that assesses cognitive flexibility and a delayed response task that assesses working memory. Across tasks, aged rats were impaired relative to young; however, there was significant variability in individual performance within the aged cohort. Notably, performance on the set-shifting task and performance at long delays on the delayed response task were inversely related among aged rats. Additional experiments showed no relationship between aged rats' performance on the set-shifting task and performance on a hippocampal-dependent spatial reference memory task. These data indicate that normal aging can produce distinct manifestations of executive dysfunction, and support the need to better understand the unique mechanisms contributing to different forms of prefrontal cortical-supported executive decline across the lifespan.     

Executive function,memory, and learning in Tourette's syndrome

Young people with Tourette's syndrome (TS) alone, TS plus attention-deficit/hyperactivity disorder (+ADHD), or TS plus obsessive-compulsive disorder (+OCD) were compared with a healthy control group on a set of measures of executive functioning, memory, and learning. The TS-alone group was impaired on one executive measure involving inhibition and strategy generation but did not differ significantly from the healthy control group on other measures. The TS+ADHD group showed impairment on several executive measures. There was no evidence of impairment in implicit aspects of memory and learning for any of the TS groups. The findings are discussed in terms of the frontostriatal hypothesis of TS and the contribution of comorbid symptomatology.     

Memory and executive functioning in obsessive-compulsive disorder: a selective review

BACKGROUND: The neurocognitive deficits that underlie the unique features of obsessive-compulsive disorder (OCD) are not yet completely understood. This paper reviews the main neuropsychological findings in memory and executive functioning in this disorder, and examines a number of challenges facing this area of research. METHOD: A selective review of the neuropsychological literature on OCD was conducted using MEDLINE and drawing on literature known to the authors. RESULTS: The neuropsychological profile of OCD appears to be one of primary executive dysfunction. Although memory functioning may be affected, these deficits appear secondary to an executive failure of organizational strategies during encoding. On tasks of executive functioning patients with OCD demonstrate increased response latencies, perseveration of responses, and difficulties utilizing feedback to adapt to change. LIMITATIONS: A statistical meta-analysis was not performed and only the cognitive domains of memory and executive functioning were examined. CONCLUSIONS: Given the prominence of chronic doubt and indecision in clinical settings, it is surprising that decision making as a cognitive construct as related to OCD has not received greater attention in the neuropsychological literature. On the basis of emerging literature we suggest that it is a potential area of dysfunction and one that warrants further investigation as it may assist in enhancing our understanding of the pathophysiology of OCD.