Biomedical subjects

B J Sahakian

Publications and source records attributed to B J Sahakian.

At least 19 recordsLinked to original sources

PubMed2006

Changes over time in cognitive and structural profiles of head injury survivors.

Survivors of traumatic head injury often suffer chronic cognitive deficits. Considerable evidence implicates the cholinergic system in these deficits. Recently, we reported cognitive and structural abnormalities in a cohort of head injured survivors consistent with this hypothesis [see Salmond, C. H., Chatfield, D. A., Menon, D. K., Pickard, J. D., & Sahakian, B. J. (2005). Cognitive Sequelae of Head Injury: Involvement of Basal Forebrain and associated structures. Brain, 128(1), 189-200]. The stability of the cognitive and structural MRI profiles was investigated in a longitudinal study. Twenty-one survivors of moderate-severe head injury completed two comprehensive neuropsychological assessments and two structural MRI scans at least six months apart. A cohort of controls also completed these investigations. The results revealed that the cognitive and structural profiles are relatively stable from six months post-injury forward up to 3 years post-injury. Deficits in memory, attention and reaction time were found, with relative preservation of working memory, consistent with abnormalities in the cholinergic system. These findings suggest that cholinergic enhancers may be an effective treatment for cognitive deficits post-head injury in survivors up to three years post-injury.

Adolescent↗

PubMed2006

Impaired dimensional selection but intact use of reward feedback during visual discrimination learning in Parkinson's disease.

It has been suggested that Parkinson's disease (PD) impairs the ability to learn on the basis of reward or reinforcing feedback i.e., by trial-and-error. In many learning tasks, particular 'dimensions' of stimulus information are relevant whilst others are irrelevant; therefore, efficient performance depends on identifying the dimensions of these 'compound' stimuli and selecting the relevant dimension for further processing. We investigated the ability of patients with PD, as well as patients with Huntington's disease and patients with frontal or temporal lobe lesions, to learn visual discriminations which required either a number of associations to be learned concurrently (the 'eight-pair' task) or the selection of information from compound stimuli (the 'five-dimension' task), both tasks being learned by trial-and-error. None of the basal ganglia disorder patient groups was impaired on the eight-pair task, militating against a crucial role for these brain structures in trial-and-error learning per se. Patients with mild, medicated PD, but not unmedicated PD patients, were impaired at identifying all five feature dimensions in the five-dimension task, implying dopaminergic 'overdosing' of the ability to analyse compound stimuli in terms of their component dimensions. Temporal lobe lesion patients performed similarly, suggesting that the temporal lobe may be the site of the medication overdose effect. Patients with severe, medicated PD were impaired at compound discrimination learning on the five-dimension task in the absence of an underlying impairment in identifying component stimulus dimensions; this pattern resembled that seen in Huntington's disease and frontal lobe lesion patients, implying that fronto-striatal circuitry is involved in the formation of rules based upon selected stimulus dimensions.

Adult↗

PubMed2006

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.

Adolescent↗

PubMed2006

Cognitive reserve in neuropsychiatry.

BACKGROUND: The idea that superior cognitive function acts as a protective factor against dementia and the consequences of head injury is well established. Here we suggest the hypothesis that cognitive reserve is also important in neuropsychiatric disorders including schizophrenia, bipolar disorder and depression. METHOD: We review the history of passive and active models of reserve, and apply the concept to neuropsychiatric disorders. Schizophrenia is used as an exemplar because the effects of premorbid IQ and cognitive function in this disorder have been extensively studied. RESULTS: Cognitive reserve may impact on neuropsychiatric disorders in three ways: by affecting the risk for developing the disorder, in the expression of symptoms within disorders, and in patients' functional outcome. Cognitive failure below a certain threshold may alone, or in combination with common psychiatric symptoms, produce neuropsychiatric syndromes. CONCLUSIONS: Consideration of cognitive reserve may considerably improve our understanding of individual differences in the causes and consequences of neuropsychiatric disorders. For these reasons, the concept of cognitive reserve should be incorporated in future studies of neuropsychiatric disorder. It may be possible to enhance cognitive reserve through pharmacological or non-pharmacological means, such as education, neurocognitive activation or other treatment programmes.

Brain↗

PubMed2005

Profile of neurocognitive impairments associated with female in-patients with anorexia nervosa.

BACKGROUND: Although many studies have reported impairments of neurocognitive performance in patients with anorexia nervosa (AN), these have involved a wide range of assessment methods and some findings are inconsistent. METHOD: Twenty-five female in-patients with a DSM-IV diagnosis of AN, identified from three units specializing in the treatment of eating disorders, volunteered for the study. Twenty-five non-clinical control subjects were recruited, matched for age, gender and estimated IQ. Subjects were assessed with a range of computer-administered neurocognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), which has been validated in many studies of neuropsychiatric disorders. RESULTS: The patient group showed significant but moderate impairments (i.e. less than one standard deviation below the mean performance of the control group) on tests of spatial recognition memory, a planning task and rapid visual information processing, while a subgroup of patients (n = 14) showed greater degrees of impairments on at least one of these tests. The degrees of impairments did not correlate with body mass index (BMI). No impairments were observed on tests of spatial span, pattern recognition memory, spatial working memory, matching-to-sample, paired associates learning and set-shifting. CONCLUSIONS: The findings, in relation to a mean BMI of 15.3, are compatible with, in general, subtle impairments in neurocognition in AN. However, in those patients with relatively severe degrees of impairments, these may have adverse effects on complex tasks of social and occupational functioning. Further research is needed on the nature of relevant causal mechanisms, including the effects of potentially confounding variables.

Adolescent↗

PubMed2005

Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity.

RATIONALE: Reduced serotonin neurotransmission is implicated in disorders of impulse control, but the involvement of serotonin in inhibitory processes in healthy human subjects remains unclear. OBJECTIVES: To investigate the effects of an acute manipulation of serotonin and genotype at a functional polymorphism in a gene coding for the serotonin transporter (5-HTT) on an established measure of response inhibition. METHODS: Serotonin function was reduced by the acute tryptophan depletion (ATD) procedure in a double-blind, crossover design in 42 healthy subjects. The Stop Signal Task (SST) was administered 5-7 h after drink administration. The influences of 5-HTT polymorphism, gender and trait impulsivity were investigated. RESULTS: ATD was associated with significant depletion of plasma tryptophan levels but did not increase the stop signal reaction time in comparison to the balanced (placebo) amino acid mixture. Subjects possessing the short allele of the 5-HTT polymorphism were not more impulsive on the SST than subjects homozygous for the long allele under placebo conditions and were not disproportionately sensitive to the effects of ATD. There was no effect of gender or trait impulsivity on ATD-induced change. CONCLUSIONS: We find no support for the involvement of brain serotonin neurotransmission in this form of inhibitory control in healthy human subjects.

Adolescent↗

PubMed2005

Abnormal frontal activations related to decision-making in current and former amphetamine and opiate dependent individuals.

RATIONALE: There is converging evidence for impairments in decision-making in chronic substance users. In the light of findings that substance abuse is associated with disruptions of the functioning of the striato-thalamo-orbitofrontal circuits, it has been suggested that decision-making impairments are linked to frontal lobe dysfunction. We sought to investigate this possibility using functional neuroimaging. METHODS: Decision-making was investigated using the Cambridge Risk Task during H2(15)O PET scans. A specific feature of the Risk Task is the decisional conflict between an unlikely high reward option and a likely low reward option. Four groups, each consisting of 15 participants, were compared: chronic amphetamine users, chronic opiate users, ex-drug users who had been long-term amphetamine/opiate users but are abstinent from all drugs of abuse for at least 1 year and healthy matched controls without a drug-taking history. RESULTS: During decision-making, control participants showed relatively greater activation in the right dorsolateral prefrontal cortex, whereas participants engaged in current or previous drug use showed relatively greater activation in the left orbitofrontal cortex. CONCLUSION: Our results indicate a disturbance in the mediation by the prefrontal cortex of a risky decision-making task associated with amphetamine and opiate abuse. Moreover, this disturbance was observed in a group of former drug users who had been abstinent for at least 1 year.

Adult↗

PubMed2005

Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices.

Diffusion tensor imaging (DTI) provides a unique insight into the cellular integrity of the brain. While conventional magnetic resonance imaging underestimates the extent of pathology following closed head injury, diffusion-weighted imaging has been shown to more accurately delineate the extent of cerebral damage. There have only been a few case studies of DTI in chronic head injury survivors. This study used DTI to investigate changes in anisotropy and diffusivity in survivors of head injury at least 6 months after their injury. The relationship between cognition and diffusion abnormality was also investigated. The voxel-based analysis revealed significant bilateral decreases in anisotropy, in major white matter tracts and association fibers in the temporal, frontal, parietal and occipital lobes. Statistically significant increases in diffusivity were also found in widespread areas of the cortex. A significant positive correlation was found between diffusivity and impairment of learning and memory in the left posterior cingulate, left hippocampal formation and left temporal, frontal and occipital cortex. The common pattern of abnormality despite heterogeneous injury mechanism and lesion location in the group suggests that these cellular changes reflect secondary insults. The importance of diffusion abnormalities in head injury outcome is emphasized by the significant correlation between a learning and memory index and diffusivity in areas known to subserve this cognitive function.

Adolescent↗

PubMed2005

Imaging of cerebral blood flow and metabolism in brain injury in the ICU.

The heterogeneity of the initial insult and subsequent pathophysiology has made both the study of human head injury and design of randomised controlled trials exceptionally difficult. The combination of multimodality bedside monitoring and functional brain imaging positron emission tomography (PET) and magnetic resonance (MR), incorporated within a Neurosciences Critical Care Unit, provides the resource required to study critically ill patients after brain injury from initial ictus through recovery from coma and rehabilitation to final outcome. Methods to define cerebral ischemia in the context of altered cerebral oxidative metabolism have been developed, traditional therapies for intracranial hypertension re-evaluated and bedside monitors cross-validated. New modelling and analytical approaches have been developed.

Animals↗

PubMed2005

The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers.

Obsessive compulsive disorder (OCD) is a highly debilitating neuropsychiatric condition with estimated lifetime prevalence of 2-3%, more than twice that of schizophrenia. However, in contrast to other neuropsychiatric conditions of a comparable or lesser prevalence, relatively little is understood about the aetiology, neural substrates and cognitive profile of OCD. Despite strong evidence for OCD being familial, with risk to first-degree relatives much greater than for the background population, its genetic underpinnings have not yet been adequately delineated. Although cognitive dysfunction is evident in the everyday behaviour of OCD sufferers and is central to contemporary psychological models, theory-based studies of neurocognitive function have yet to reveal a reliable cognitive signature, and interpretation has often been confounded by failures to control for co-morbidities. The neuroimaging findings in OCD are amongst the most robust reported in the psychiatric literature, with structural and functional abnormalities frequently reported in orbitofrontal cortex, anterior cingulate cortex, and caudate nucleus. In spite of this, our relative lack of understanding of OCD neurochemical processes continues to impede progress in the development of novel pharmacological treatment approaches. Integrating the neurobiological, cognitive, and clinical findings, we propose that OCD might usefully be conceptualised in terms of lateral orbitofrontal loop dysfunction, and that failures in cognitive and behavioural inhibitory processes appear to underlie many of the symptoms and neurocognitive findings. We highlight existing limitations in the literature, and the potential utility of endophenotypes in overcoming these limitations. We propose that neurocognitive indices of inhibitory functions may represent a useful heuristic in the search for endophenotypes in OCD. This has direct implications not only for OCD but also for putative obsessive-compulsive spectrum conditions including attention deficit hyperactivity disorder, Tourette's syndrome, and trichotillomania (compulsive hair pulling).

Animals↗

PubMed2005

Effects of methylphenidate on cognition and apathy in normal pressure hydrocephalus: a case study and review.

The psychostimulant methylphenidate has been previously shown to improve cognitive performance in both normal control volunteers and patient populations. In the present case study, the effects of methylphenidate on cognitive and behavioural function were examined in a single patient with idiopathic normal pressure hydrocephalus (NPH) who had undergone ventriculoperitoneal shunting. A double-blind placebo-controlled ABBA drug design was employed, with the administration of two different doses of methylphenidate followed by neuropsychological assessment on a number of psychometric tests and cognitive tasks drawn from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Methylphenidate produced a dose-dependent positive improvement in behavioural measures in the patient associated with a reduction in apathy. It also had a dose-independent enhancing effect on performance of a Spatial Recognition task. These findings require replication in a large sample of patients to determine whether methylphenidate may prove to be generally useful in enhancing cognition and reducing apathy in normal pressure hydrocephalus.

Aged↗

PubMed2005

The neuropsychology of normal pressure hydrocephalus (NPH).

Normal pressure hydrocephalus (NPH) accounts for one of the few known forms of reversible dementia. Varied aetiology and clinical presentation contribute to difficulties with early or differential diagnoses, and delayed surgical treatment may be less efficacious. Clinical neuropsychology provides a means of determining a cognitive profile for NPH, assisting in differential diagnosis, tracking the disorder's progression and assessing the efficacy of treatment. This article will review possible applications of clinical neuropsychology and propose a clinical assessment protocol for NPH.

Clinical Protocols↗

PubMed2005

Deficits in decision-making in head injury survivors.

Many survivors of head injury suffer chronic personality changes, such as increased impulsivity and a lack of insight and poor judgment. These changes are well recognized and likely to affect the ability to make decisions. However, systematic investigations into their nature have been limited. This study aims to explore the nature of decision making in head injury survivors using a computerized task. Forty-three head injury survivors and a group of 29 matched controls completed the computerized task. The task required participants to make a probability-based choice and to further qualify this choice with an associated "bet." This betting component allows an assessment of the participant's level of confidence in the decision, via the affective evaluation of its possible consequences in terms of points won or lost. The survivors were found to be slow at making the probability- based choice. Whilst at highly favorable odds, the survivors chose the most likely option in a similar manner to the controls, they chose the most likely option less often than the controls at less favorable odds. Examination of the survivors' betting behavior revealed that they responded impulsively compared to controls. This pattern of prolonged decision making and poor quality of decisions is similar to that found in patients with orbitofrontal cortex lesions, whilst impulsive betting has been associated with abnormalities of the dopamine system. These complex deficits in decision making may contribute to difficulties with poor judgment and inhibition in head injury survivors.

Adolescent↗

PubMed2004

Cognitive sequelae of head injury: involvement of basal forebrain and associated structures.

Traumatic brain injury is the most common cause of death and disability in young people and survivors often suffer from chronic cognitive deficits. From animal, post-mortem and cognitive studies, there is now increased evidence that abnormalities in the cholinergic system may be underlying some of these deficits. This study investigated this hypothesis in a group of survivors of moderate-severe head injury (n = 31). Patients completed a comprehensive neuropsychological assessment and an MRI scan. Compared with a group of controls (matched on age, sex and premorbid intelligence quotient), the patients showed deficits in sustained attention, paired associate learning and reaction time, but comparative preservation of spatial working memory. Voxel-based morphometry revealed reduced grey matter density in the head injured group in the basal forebrain, the hippocampal formation and regions of the neocortex. These cognitive and structural results are consistent with cholinergic dysfunction. These preliminary findings suggest that cholinergic enhancers may be an effective treatment of cognitive deficits post head injury.

Adult↗

PubMed2004

Characteristic neurocognitive profile associated with adult attention-deficit/hyperactivity disorder.

BACKGROUND: It is now accepted that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. However, relative to the considerable literature concerning the profile of neurocognitive deficits associated with this disorder in childhood, equivalent investigations in adult populations have been less common. The current study examined cognitive function in adults diagnosed with ADHD employing well-validated neuropsychological tasks. METHOD: Nineteen adult patients who satisfied DSM-IV criteria for ADHD and 19 matched (gender, age and verbal IQ), non-clinical control subjects were recruited. Patients were either unmedicated or had abstained from a psychostimulant medication regime for at least 24 h prior to neurocognitive assessment. A functionally wide-ranging test battery was administered. RESULTS: Relative to controls, ADHD adults performed significantly worse on spatial working memory, planning, and attentional-set shifting tests and were significantly slower to respond to target stimuli on the go/no-go task. In contrast, the two subject groups performed equivalently on decision-making and pattern/spatial recognition memory assessments. CONCLUSIONS: The demonstration of neuropsychological dysfunction in the adult ADHD cohort provides some support for the validity of this diagnosis in adulthood. In particular, there is broad consistency between the cognitive profile revealed in the current investigation and that previously demonstrated in a study of medication-naïve ADHD children. There is evidence that frontostriatal function is especially disrupted.

Adult↗

PubMed2004

Impaired spatial working memory in adults with attention-deficit/hyperactivity disorder: comparisons with performance in adults with borderline personality disorder and in control subjects.

OBJECTIVE: This study investigated a previous claim that working memory may be 'particularly impaired' in adult attention-deficit/hyperactivity disorder (ADHD), compared with other psychiatric disorders which affect frontal lobe-mediated executive functions. METHOD: Performance on spatial working memory (SWM) and two additional tasks were investigated for adult patients selected on the basis of DSM-IV ADHD (n = 19), adult patients selected on the basis of borderline personality disorder (BPD) (n = 19), and non-clinical control subjects (n = 19). Groups were matched for age, verbal IQ and gender. RESULTS: Analysis of variance showed that the ADHD group had significant impairment of SWM performance relative to the non-clinical controls. Although there was a trend towards impairment in the BPD group relative to non-clinical controls, this did not reach significance. CONCLUSION: The results are consistent with the claim that aspects of working memory are 'particularly impaired' in adult ADHD. Also, the BPD group had a longer deliberation time for one of the additional tasks, compared with the ADHD group, which indicated that the patient groups may have different patterns of neuropsychological impairments.

Adult↗

PubMed2004

Neuropsychological profile of young adults with spina bifida with or without hydrocephalus.

OBJECTIVES: To determine the relative impact of hydrocephalus and spinal dysraphism in young adults on intellectual and cognitive functioning. Sub-groups of patients with congenital hydrocephalus and/or spina bifida were assessed between 1995 and 2003. The entry criteria were that individuals should have (i) intact global function, (ii) average verbal intelligence (or above), and (iii) should not have clinical depression. There were three sub-groups: patients with hydrocephalus and spina bifida, patients with hydrocephalus without spina bifida, and patients with spina bifida without hydrocephalus. METHODS: Patients were neuropsychologically assessed as part of their normal clinical assessment during their annual medical review. Each individual completed a screening battery assessing global functioning, verbal intelligence, and mood. In addition they completed additional tests including measures of emotional intelligence, memory, attention, and executive function. Results were analysed to compare the performance of the patient sub-groups and to compare them to a healthy control group. RESULTS: Patients with hydrocephalus (with or without spina bifida) were significantly impaired on the vast majority of all test scores as compared to patients with spina bifida and healthy controls. They were particularly poor on measures assessing executive function. By contrast for patients with spina bifida with no associated hydrocephalus, the significant majority of all test scores fell within the average range or above. CONCLUSIONS: The neuropsychological profile of patients with hydrocephalus is one of relative impairment and this is so whether or not spina bifida is present. In spina bifida alone, in the absence of hydrocephalus, cognitive function is relatively spared.

Adult↗

PubMed2003

Profile of cognitive progression in early Huntington's disease.

OBJECTIVE: To examine the pattern of cognitive decline in early Huntington's disease (HD). METHODS: The authors studied 61 patients with mild to moderate HD who had at least three annual neuropsychological assessments using the Core Assessment Program for Intracerebral Transplantation in Huntington's Disease short battery. A subset of 34 patients had additional neuropsychological tests, and another subset of 21 patients was assessed annually on the Cambridge Neuropsychological Test Automated Battery. Neuropsychological measures that changed significantly over time were submitted to a multiple analysis of covariance to explore associations with demographic and neurologic indices. RESULTS: Patients showed a progressive impairment in attention, executive function, and immediate memory, with timed tests of psychomotor skill being particularly sensitive to decline. In contrast, general cognition, semantic memory, and delayed recall memory were relatively unaffected. CONCLUSION: The profile of cognitive performance shows selective and progressive dysfunction of attention and executive function in patients with mild to moderate HD, consistent with frontostriatal pathology at this stage of disease.

Adult↗