Biomedical subjects

Barbara J Sahakian

Publications and source records attributed to Barbara J Sahakian.

At least 19 recordsLinked to original sources

PubMed2006

Questionnaire ratings of attention-deficit/hyperactivity disorder (ADHD) in adults are associated with spatial working memory.

OBJECTIVE: Data related to brain function may have the potential to improve the reliability and validity of assessments for the aetiologically and clinically heterogeneous syndrome of attention-deficit/hyperactivity disorder (ADHD). This study investigated associations between questionnaire assessments of behavioural features of adults with ADHD and an aspect of neurocognitive performance which has been reported to be impaired in adults with ADHD. METHODS: Fifty-nine adult patients with a DSM-IV diagnosis of ADHD, and their informants, completed questionnaires related to aspects of severity of ADHD. Associations were examined between questionnaire ratings and performance on a computer-administered task of spatial working memory (SWM). RESULTS: Correlations between ratings of ADHD and SWM indicated moderate but significant correlations for patients' ratings, but not for informants' ratings. Also, patients who reported a past history of 'self-harm' (N=33) had a significantly worse mean performance on both measures of SWM (p=0.004, 0.003). CONCLUSIONS: The results indicate that aspects of impulsivity, i.e. self-ratings of 'emotive' behaviour (involving rapid response to stimuli and marked reactivity of mood) and of past 'self-harm', show relatively strong associations with SWM performance in adults selected on the basis of an ADHD diagnosis. A profile of neurocognitive performances may have a role in the assessment of ADHD.

Adult↗

PubMed2006

Association between response inhibition and working memory in adult ADHD: a link to right frontal cortex pathology?

BACKGROUND: We sought to assess the relationship between response inhibition and working memory in adult patients with attention-deficit/hyperactivity disorder (ADHD) and neurosurgical patients with frontal lobe damage. METHODS: The stop-signal reaction time (SSRT) test and a spatial working memory (SWM) task were administered to 20 adult patients with ADHD and a group of matched controls. The same tasks were administered to 21 patients with lesions to right frontal cortex and 19 patients with left frontal lesions. RESULTS: The SSRT test, but not choice reaction time, was significantly associated with search errors on the SWM task in both the adult ADHD and right frontal patients. In the right frontal patients, impaired performance on both variables was correlated with the volume of damage to the inferior frontal gyrus. CONCLUSIONS: Response inhibition and working memory impairments in ADHD may stem from a common pathologic process rather than being distinct deficits. Such pathology could relate to right frontal-cortex abnormalities in ADHD, consistent with prior reports, as well as with the demonstration here of a significant association between SSRT and SWM in right frontal patients.

Adult↗

PubMed2006

A neuropsychological comparison of obsessive-compulsive disorder and trichotillomania.

BACKGROUND: Obsessive-compulsive disorder (OCD) and trichotillomania (compulsive hair-pulling) share overlapping co-morbidity, familial transmission, and phenomenology. However, the extent to which these disorders share a common cognitive phenotype has yet to be elucidated using patients without confounding co-morbidities. AIM: To compare neurocognitive functioning in co-morbidity-free patients with OCD and trichotillomania, focusing on domains of learning and memory, executive function, affective processing, reflection-impulsivity and decision-making. METHOD: Twenty patients with OCD, 20 patients with trichotillomania, and 20 matched controls undertook neuropsychological assessment after meeting stringent inclusion criteria. RESULTS: Groups were matched for age, education, verbal IQ, and gender. The OCD and trichotillomania groups were impaired on spatial working memory. Only OCD patients showed additional impairments on executive planning and visual pattern recognition memory, and missed more responses to sad target words than other groups on an affective go/no-go task. Furthermore, OCD patients failed to modulate their behaviour between conditions on the reflection-impulsivity test, suggestive of cognitive inflexibility. Both clinical groups showed intact decision-making and probabilistic reversal learning. CONCLUSIONS: OCD and trichotillomania shared overlapping spatial working memory problems, but neuropsychological dysfunction in OCD spanned additional domains that were intact in trichotillomania. Findings are discussed in relation to likely fronto-striatal neural substrates and future research directions.

Adult↗

PubMed2006

Differences in orbitofrontal activation during decision-making between methadone-maintained opiate users, heroin users and healthy volunteers.

OBJECTIVE: Previously, we reported that opiate users enrolled in methadone treatment made 'risky' choices on a decision-making task following a loss of points compared with heroin users and healthy volunteers. One possible explanation for this behaviour is that methadone users were less sensitive to punishment on immediately preceding unsuccessful trials. METHODS: We sought to explore this finding from a neural perspective by performing a post hoc analysis of data from a previous [see text] positron emission tomography study. We restricted the analysis to the opiate groups and controls, assessing differences between opiate users on methadone and those on heroin. RESULTS: We found significant over-activation in the lateral orbitofrontal cortex (OFC) in methadone users compared with both heroin users and controls concomitant with the greatest overall tendency to 'play risky'. Heroin users showed significant under-activation in this area compared with the other two groups whilst exhibiting the greatest overall tendency to 'play safe'. Correlational analysis revealed that abnormal task-related activation of the left OFC was associated with the dose of methadone in methadone users and with the duration of intravenous heroin use in heroin users. 'Playing safe' following a loss of points was also negatively correlated with the activation of pregenual anterior cingulate and insula cortex in controls, but not in opiate users. CONCLUSION: Our findings suggest that the interplay between processes involved in integrating penalty information for the purpose of response selection may be altered in opiate users. This change was reflected differentially in task-related pattern of OFC activation depending on the opiate used.

Adult↗

PubMed2006

The effect of polymorphism at the serotonin transporter gene on decision-making, memory and executive function in ecstasy users and controls.

RATIONALE: 3, 4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a popular drug of abuse known to result in depletions of the serotonin (5-HT) system. A number of studies have reported that ecstasy users differ from controls on a variety of measures of cognitive function. However, the literature is not consistent and many negative findings were also reported. One reason for such inconsistency might be interindividual variance in vulnerability to the deleterious effects of ecstasy due to a number of factors, both genetic and environmental. OBJECTIVES: To investigate the hypothesis that carriers of the s allele at the 5-HT transporter gene-linked polymorphic region (5-HTTLPR), which was associated with reduced serotonergic neurotransmission relative to the l allele, would be most vulnerable to the effects of ecstasy on cognitive function. METHODS: We assessed memory, decision-making, and executive function in ecstasy users and controls, stratifying by genotype at the 5-HTTLPR. RESULTS: We observed that the 5-HTTLPR genotype groups differed on a number of measures in both the ecstasy users and the controls. While performing a risky decision-making task, ss and ls controls attended to differences in the probability of winning chosen gambles to a greater extent than the ll controls. However, this difference was dramatically attenuated in the ss ecstasy users. Furthermore, independent of ecstasy use, volunteers of the ss genotype outperformed the ll genotype on a visual planning task. CONCLUSIONS: The results are consistent with the hypothesis that cognitive impairment in ecstasy users may depend on genetic variation at the 5-HTTLPR.

Case-Control Studies↗

PubMed2006

The effects of acute tryptophan depletion and serotonin transporter polymorphism on emotional processing in memory and attention.

Polymorphism at the serotonin transporter linked polymorphic region (5-HTTLPR) has been associated with neuroticism, increased risk for affective disorders and greater vulnerability to mood change following serotonin (5-HT) depletion. The aim of the present study was to investigate whether the cognitive effects of 5-HT depletion were differentially affected by genotype at the 5-HTTLPR polymorphism, using neuropsychological measures of memory and attention. We utilized the acute tryptophan depletion (ATD) technique to temporarily reduce 5-HT synthesis in two groups of healthy volunteers pre-selected on the basis of 5-HTTLPR genotype, 15 of the ll genotype and 15 of the ss genotype, in a double-blind, placebo-controlled crossover design. As expected, ATD resulted in a robust reduction in plasma tryptophan concentration in both genotype groups. However, the genotype groups differed in terms of the effect of ATD on cognitive performance. The ss genotype group showed impaired verbal recall following depletion, while episodic memory was unimpaired by ATD in the ll genotype group. Averaging across depletion condition, the ss genotype group outperformed the ll genotype group on tests of episodic memory and attention. Neither group was significantly affected by ATD on measures of emotional state. These data confirm previous reports that ss individuals are particularly vulnerable to 5-HT depletion, but extend these findings to the cognitive domain. The unexpected finding that ss volunteers showed improved memory and attention relative to ll volunteers suggests a possible evolutionary advantage to possession of the s allele, which may offset the disadvantage of vulnerability to depression following stressful life events.

Adult↗

PubMed2006

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.

Adult↗

PubMed2006

Noradrenergic modulation of working memory and emotional memory in humans.

RATIONALE: Noradrenaline (NA) is implicated in arousal. Working memory is dependent upon prefrontal cortex, and moderate levels of NA are thought to facilitate working memory whereas higher levels during extreme stress may impair working memory and engage more posterior cortical and sub-cortical circuitry. The NA system also influences emotional memory via modulation of the amygdalae and related mediotemporal structures. NA dysfunction and abnormalities in arousal-dependent memory functions are evident in a variety of neuropsychiatric illnesses. OBJECTIVES: The authors provide a concise overview of pharmacological studies that have investigated effects of selective NA manipulations on working memory and emotional memory functions in healthy human volunteers. MATERIALS AND METHODS: Selection of relevant peer-reviewed publications was based on a PubMed search. RESULTS: Studies to date indicate that: (1) the beta-blocker propranolol impaired working and emotional memory, (2) clonidine frequently impaired working memory, and (3) reboxetine, a selective noradrenaline reuptake inhibitor, enhanced emotional memory for positive material. CONCLUSIONS: Improved understanding of coupling between NA, cortico-subcortical circuitry and human mnemonic functions will suggest novel therapeutic directions for the treatment of neuropsychiatric conditions, such as attention deficit hyperactivity disorder and post-traumatic stress disorder. Future research directions are discussed in relation to neuroimaging techniques, functional central nervous system polymorphisms and study designs.

Adrenergic Agonists↗

PubMed2006

Serotonin transporter polymorphism mediates vulnerability to loss of incentive motivation following acute tryptophan depletion.

The serotonin (5-HT) system is implicated in incentive motivational processes. The present study utilized the acute tryptophan depletion (ATD) procedure to investigate the effect of temporarily lowering 5-HT synthesis on motivation in healthy volunteers, stratifying the results by allelic variation at the serotonin transporter gene (5-HTTLPR). ATD resulted in a robust reduction in plasma tryptophan concentration. Consistent with a previous study, ATD attenuated motivationally speeded action on the Cued-Reinforcement Reaction Time task. The present investigation revealed that this effect was restricted to volunteers of the ss genotype, whereas ll volunteers exhibited intact motivationally speeded action following ATD (treatment x reinforcement probability x genotype interaction: F1,26=5.8, p=0.024). Furthermore, tryptophan availability to the brain was correlated positively with motivationally speeded action following ATD in the ss genotype group (rho13=0.71, p=0.006), whereas this correlation was negative in the ll genotype group (rho14=-0.60, p=0.023). This is the first study to suggest that allelic variation at the 5-HTTLPR mediates motivational responses to ATD in healthy volunteers. These data indicate that the s allele at the 5-HTTLPR may confer risk for depression via its effect on incentive motivational processing, and highlight the importance of genetic variation in determining individual responses to pharmacological treatments.

Adult↗

PubMed2006

Neurochemical modulation of response inhibition and probabilistic learning in humans.

Cognitive functions dependent on the prefrontal cortex, such as the ability to suppress behavior (response inhibition) and to learn from complex feedback (probabilistic learning), play critical roles in activities of daily life. To what extent do different neurochemical systems modulate these two cognitive functions? Here, using stop-signal and probabilistic learning tasks, we show a double dissociation for the involvement of noradrenaline and serotonin in human cognition. In healthy volunteers, inhibition of central noradrenaline reuptake improved response inhibition but had no effect on probabilistic learning, whereas inhibition of central serotonin reuptake impaired probabilistic learning with no effect on response inhibition.

Adult↗

PubMed2006

Reflection impulsivity in current and former substance users.

BACKGROUND: Chronic drug use is associated with increased impulsivity, risky decision making, and impaired behavioral control, but the underlying mechanisms of this neurocognitive profile remain unclear. We investigated impulsive responding in the context of decision making, using a novel behavioral measure of reflection impulsivity: the tendency to gather and evaluate information before making a decision. METHODS: The Information Sampling Task was administered to current substance users dependent on amphetamines (n = 24) or opiates (n = 40), former users of amphetamines or opiates abstinent for at least 1 year (n = 24), and non-drug-using control subjects (n = 26). RESULTS: Current users of amphetamines and opiates sampled less information than control subjects and responded at a lower probability of making a correct response. Amphetamine- and opiate-dependent subjects did not differ. Reduced reflection was also apparent in the former substance users, who did not differ from the current users. Questionnaire ratings of impulsivity (on the Barratt Impulsivity Scale, version 11) were also inflated in three groups of substance users but were not significantly correlated with performance on the behavioral task. CONCLUSIONS: Reduced reflection is suggested to represent a cognitive marker for substance dependence that does not recover with prolonged abstinence and is associated with multiple drugs of abuse.

Adult↗

PubMed2006

The neuropsychology of mood disorders.

Cognitive dysfunction is central to our understanding of mood disorders in terms of patient experiences, Diagnostic and Statistical Manual of Mental Disorders criteria, and psychological models. In this article, we highlight key findings from studies that have used neuropsychological tests and functional neuroimaging techniques to explore cognitive dysfunction in patients with depression and mania. In particular, we focus on affective processing bias, abnormal response to negative feedback, and decision making. Results are discussed in the context of current conceptualizations of dysfunctional neural circuitry, and in relation to important clinical research implications.

Bipolar Disorder↗

PubMed2006

Impulsivity, reward sensitivity, and decision-making in subarachnoid hemorrhage survivors.

Subarachnoid hemorrhage (SAH) survivors often report psychosocial and emotional changes, including a diminished capacity for decision making. However, systematic investigations into the nature of the changes have been limited to those patients surviving SAH secondary to aneurysms of the anterior communicating artery. This study aimed to explore the nature of decision making in survivors of SAH secondary to aneurysms of the middle cerebral or posterior communicating artery using a series of computerized tasks. Twenty SAH survivors and 20 matched controls completed a battery of computerized decision-making tasks. These included tasks examining an individual's ability to make probabilistic choices and risk-taking behavior, as well as tasks examining aspects of impulsivity. The results revealed two key patterns of abnormal decision-making behavior in the SAH survivors: altered sensitivity to both reward and punishment, and impulsive responding. These complex deficits may contribute to difficulties in daily living resulting from apathy, poor judgment, or inhibition in SAH survivors.

Case-Control Studies↗

PubMed2006

Methylphenidate ('Ritalin') can ameliorate abnormal risk-taking behavior in the frontal variant of frontotemporal dementia.

The frontal variant of frontotemporal dementia is a significant neurological condition worldwide. There exist few treatments available for the cognitive and behavioural sequelae of fvFTD. Previous research has shown that these patients display risky decision-making, and numerous studies have now demonstrated pathology affecting the orbitofrontal cortex. The present study uses a within-subjects, double-blind, placebo-controlled procedure to investigate the effects of a single dose of methylphenidate (40 mg) upon a range of different cognitive processes including those assessing prefrontal cortex integrity. Methylphenidate was effective in 'normalizing' the decision-making behavior of patients, such that they became less risk taking on medication, although there were no significant effects on other aspects of cognitive function, including working memory, attentional set shifting, and reversal learning. Moreover, there was an absence of the normal subjective and autonomic responses to methylphenidate seen in elderly subjects. The results are discussed in terms of the 'somatic marker' hypothesis of impaired decision-making following orbitofrontal dysfunction.

Aged↗

PubMed2006

Profile of executive and memory function associated with amphetamine and opiate dependence.

Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices.

Adult↗

PubMed2006

Cognitive reserve as a resilience factor against depression after moderate/severe head injury.

Depression is one of the most frequently reported and distressing residual complaints in survivors of head injury. Studies investigating the pattern of neuropathology associated with depression post head injury have found little consistency. One explanation for this is that cognitive reserve "protects" against depression either through more efficient processing or more effective compensation. An alternative explanation is that previous studies have used relatively gross measures of lesion location, and variable inclusion criteria and times between scan and injury. This study explored these possibilities in a cohort of survivors of moderate-severe head injury at least 6 months post-injury. Volunteers completed neuropsychological assessments and structural magnetic resonance imaging (MRI) scans. A significant difference between depressed and non-depressed survivors was found, with higher intelligence associated with lower rates of depression. No significant anatomical differences were found between depressed and non-depressed survivors. These results suggest that premorbid intelligence may provide a resilience factor against depression in head injury survivors.

Adult↗

PubMed2006

Neuropharmacological modulation of cognition.

PURPOSE OF REVIEW: Problems relating to impulsivity, attention, and working memory occur in many neuropsychiatric disorders and represent important targets for pharmacological intervention. The purpose of this article is to review recent neuropharmacological manipulation studies in humans relating to these domains. RECENT FINDINGS: Serotonin manipulations in healthy volunteers did not affect response inhibition, a cognitive function implicated in impulsive symptoms of attention deficit hyperactivity disorder, trichotillomania, and substance abuse. Serotonin manipulations did affect performance on cognitive tests involving emotionally salient rewards and feedback, suggesting involvement of this neurochemical in affective aspects of impulsivity. Attentional deficits in attention deficit hyperactivity disorder and visuospatial neglect were ameliorated by noradrenergic drugs. Noradrenergic beta-blockade suppressed the encoding of emotionally arousing unpleasant stimuli and reduced amygdala activation in healthy volunteers, with potential implications for posttraumatic stress disorder. Dopaminergic manipulations affected aspects of working memory in healthy volunteers and in patients with Parkinson's disease, with evidence for bidirectional effects depending on baseline performance. SUMMARY: Recent findings raise exciting prospects for modulating impulsivity, attention, and working memory in a variety of neuropsychiatric disorders. Future studies should use computerized cognitive assessment, measures of functional genetic polymorphisms, and neuroimaging techniques, in order to further elucidate the neurochemical substrates of cognition and optimize treatment approaches.

Attention↗

PubMed2006

Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania.

OBJECTIVE: Problems with inhibiting certain pathological behaviors are integral to obsessive-compulsive disorder (OCD), trichotillomania, and other putative obsessive-compulsive spectrum disorders. The authors assessed and compared motor inhibition and cognitive flexibility in OCD and trichotillomania for the first time, to their knowledge. METHOD: The Stop-Signal Task and the Intradimensiona/Extradimensional Shift Task were administered to 20 patients with OCD, 17 patients with trichotillomania, and 20 healthy comparison subjects. RESULTS: Both OCD and trichotillomania showed impaired inhibition of motor responses. For trichotillomania, the deficit was worse than for OCD, and the degree of the deficit correlated significantly with symptom severity. Only patients with OCD showed deficits in cognitive flexibility. CONCLUSIONS: Impaired inhibition of motor responses (impulsivity) was found in OCD and trichotillomania, whereas cognitive inflexibility (thought to contribute to compulsivity) was limited to OCD. This assessment will advance the characterization and classification of obsessive-compulsive spectrum disorders and aid the development of novel treatments.

Adult↗