R. D. Rogers

COSTS OF A PREDICTABLE SWITCH BETWEEN SIMPLE COGNITIVE TASKS

In an investigation of task-set reconfiguration, participants switched between 2 tasks on every 2nd trial in 5 experiments and on every 4th trial in a final experiment. The tasks were to classify either the digit member of a pair of characters as even/odd or the letter member as consonant/vowel. As the response-stimulus interval increased up to 0.6 s, the substantial cost to performance of this predictable task-switch fell: Participants could partially reconfigure in advance of the stimulus. However, even with 1.2 s available for preparation, a large asymptotic reaction time (RT) cost remained, but only on the 1st trial of the new task. This is attributed to a component of reconfiguration triggered exogenously, i. e., only by a task-relevant stimulus. That stimuli evoke associated task-sets also explains why RT and switch costs increased when the stimulus included a character associated with the currently irrelevant task.

Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms.

We used a novel computerized decision-making task to compare the decision-making behavior of chronic amphetamine abusers, chronic opiate abusers, and patients with focal lesions of orbital prefrontal cortex (PFC) or dorsolateral/medial PFC. We also assessed the effects of reducing central 5-hydroxytryptamine (5-HT) activity using a tryptophan-depleting amino acid drink in normal volunteers. Chronic amphetamine abusers showed sub-optimal decisions (correlated with years of abuse), and deliberated for significantly longer before making their choices. The opiate abusers exhibited only the second of these behavioral changes. Importantly, both sub-optimal choices and increased deliberation times were evident in the patients with damage to orbitofrontal PFC but not other sectors of PFC. Qualitatively, the performance of the subjects with lowered plasma tryptophan was similar to that associated with amphetamine abuse, consistent with recent reports of depleted 5-HT in the orbital regions of PFC of methamphetamine abusers. Overall, these data suggest that chronic amphetamine abusers show similar decision-making deficits to those seen after focal damage to orbitofrontal PFC. These deficits may reflect altered neuromodulation of the orbitofrontal PFC and interconnected limbic-striatal systems by both the ascending 5-HT and mesocortical dopamine (DA) projections.

Emotional bias and inhibitory control processes in mania and depression

BACKGROUNDnDespite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. The disinhibited behaviour characteristic of mania and evidence that subgenual prefrontal cortex is differentially activated in mania and depression both suggest that dissociable deficits will emerge on tasks that require inhibitory control and are subserved by ventromedial prefrontal cortex.nnnMETHODSnManic patients and controls undertook computerized neuropsychological tests of memory and planning ability. In addition, manic and depressed patients were directly compared with controls on a novel affective shifting task that requires inhibitory control over different components of cognitive and emotional processing.nnnRESULTSnManic patients were impaired on tests of memory and planning. Importantly, affective shifting performance of manic patients differed from that of depressed patients. Manic patients were impaired in their ability to inhibit behavioural responses and focus attention, but depressed patients were impaired in their ability to shift the focus of attention. Depressed patients exhibited an affective bias for negative stimuli, and we believe this to be the first demonstration of an affective bias for positive stimuli in manic patients.nnnCONCLUSIONSnObserved impairments on tests of memory and planning suggest a global pathology for mania consistent with previous profiles for this disorder and similar to established profiles for depression. The results on the affective shifting task demonstrate the presence of mood-congruent bias and dissociable components of inhibitory control in mania and depression. Against a background of memory and planning impairments in the two groups, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.

Probabilistic learning and reversal deficits in patients with Parkinson's disease or frontal or temporal lobe lesions : possible adverse effects of dopaminergic medication

Three groups of patients with Parkinsons disease (PD) - mild, unmedicated (UPD), mild, medicated (MPD) and severe, medicated (SPD) - and patients with lesions of the frontal lobe (FLL) or temporal lobe (TLL) were compared with matched controls on the learning and reversal of probabilistic and two-pair concurrent colour discriminations. Both of the cortical lesion groups showed reversal deficits, with no increase in perseverative responding. The UPD group, although impaired on a spatial recognition task, showed intact discrimination learning and reversal; the MPD and SPD patients showed non-perseverative reversal impairments on both reversal tasks. Two hypotheses - based on disease severity and possible deleterious effects of medication - are offered to explain the reversal impairments of the PD patients and the results are discussed in terms of the role of dopamine in reward-based learning.

Prefrontal dysfunction in depressed patients performing a complex planning task : a study using positron emission tomography

INTRODUCTIONnPatients with unipolar depression show impaired performance on the Tower of London planning task. Positron emission tomography, which has previously identified resting state blood flow abnormalities in depression, was used to investigate neural activity associated with performance of this task in depressed patients and normal controls.nnnMETHODSnSix patients with unipolar depression and six matched controls were scanned while performing easy and hard Tower of London problems in a one-touch computerized paradigm and while performing a perceptuomotor control task.nnnRESULTSnThe patients in this study showed an expected task-related performance deficit compared with normal subjects. In normal subjects, the task engaged a network of prefrontal cortex, anterior cingulate, posterior cortical areas and subcortical structures including the striatum, thalamus and cerebellum. Depressed patients failed to show significant activation in the cingulate and striatum; activation in the other prefrontal and posterior cortical regions was significantly attenuated relative to controls. Crucially, patients also failed to show the normal augmentation of activation in the caudate nucleus, anterior cingulate and right prefrontal cortex associated with increasing task difficulty.nnnCONCLUSIONSnThese findings provide evidence for cingulate, prefrontal and striatal dysfunction associated with impaired task performance in depression. The present results are consistent with a central role of cingulate dysfunction in depression as well as suggesting impaired frontostriatal function.

Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour

Abstractu2002Rationale: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. Objectives and methods: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the α1/α2 agonist, clonidine (1.5 µg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. Results: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. Conclusions: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.

Decision-making cognition in mania and depression

BACKGROUNDnDespite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. Recent work has suggested that differences may emerge on cognitive tasks requiring affective processing, such as decision-making. The present study sought to compare decision-making cognition in mania and depression in order to clarify the current profiles of impairment for these disorders and to contribute to our more general understanding of the relationship between mood and cognition.nnnMETHODSnMedicated manic patients, depressed patients, and normal healthy controls completed a computerized decision-making task. All subjects were asked to win as many points as possible by choosing outcomes based on variably-weighted probabilities and by placing bets on each decision.nnnRESULTSnBoth patient groups were impaired on this task, as evidenced by slower deliberation times, a failure to accumulate as many points as controls and suboptimal betting strategies. Manic, but not depressed, patients made suboptimal decisions--an impairment that correlated with the severity of their illness.nnnCONCLUSIONSnThese findings are consistent with a growing consensus that manic and depressed patients are characterized by significant impairments in cognitive and particularly executive, functioning. Furthermore, the distinct patterns of observed impairment in manic and depressed patients suggests that the nature and extent of cognitive impairment differ between these two groups. Viewed in the context of other recent studies, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.

Neuropsychological evidence of a relatively selective profile of temporal dysfunction in drug-free MDMA ("ecstasy") polydrug users.

HeadingAbstractn Rationale. Experimental evidence has shown that 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) can act as a serotonergic neurotoxin in laboratory animals. The serotonin system predominantly innervates frontal and limbic regions of the brain and has been associated with consolidatory learning and mnemonic processes in humans.n Objectives. The aim of the present study was to investigate the cognitive neuropsychological profile of drug-free ecstasy users by employing a selection of tasks previously associated with lesion or neurodegenerative damage to the temporal lobe or fronto-striatal regions.n Methods. The study comprised 40 participants: 20 ecstasy polydrug users and 20 polydrug users who had never taken ecstasy.n Results. Ecstasy users were significantly impaired on a recognition task for complex visual patterns and spatial working memory, as a function of task difficulty rather than systematic search strategy. They also showed a trend towards impairment on several learning paradigms. Ecstasy users remained relatively unimpaired on most measures associated with prefrontal functioning, with the exception of verbal fluency letter generation.n Conclusions. Initial cognitive deficits in ecstasy polydrug users may be more apparent in tasks known to be sensitive to temporal functioning.

Executive function in Tourette's syndrome and obsessive-compulsive disorder

BACKGROUNDnCognitive performance was compared in the genetically and neurobiologically related disorders of Tourettes syndrome (TS) and obsessive-compulsive disorder (OCD), in three domains of executive function: planning, decision-making and inhibitory response control.nnnMETHODnTwenty TS patients, twenty OCD patients and a group of age- and IQ-matched normal controls completed psychometric and computerized cognitive tests and psychiatric rating scales. The cognitive tests were well-characterized in terms of their sensitivity to other fronto-striatal disorders, and included pattern and spatial recognition memory, attentional set-shifting, and a Go/No-go set-shifting task, planning, and decision-making.nnnRESULTSnCompared to controls, OCD patients showed selective deficits in pattern recognition memory and slower responding in both pattern and spatial recognition, impaired extra-dimensional shifting on the set-shifting test and impaired reversal of response set on the Go/No-go test. In contrast, TS patients were impaired in spatial recognition memory, extra-dimensional set-shifting, and decision-making. Neither group was impaired in planning. Direct comparisons between the TS and OCD groups revealed significantly different greater deficits for recognition memory latency and Go/No-go reversal for the OCD group, and quality of decision-making for the TS group.nnnCONCLUSIONSnTS and OCD show both differences (recognition memory, decision-making) and similarities (set-shifting) in selective profiles of cognitive function. Specific set-shifting deficits in the OCD group contrasted with their intact performance on other tests of executive function, such as planning and decision-making, and suggested only limited involvement of frontal lobe dysfunction, possibly consistent with OCD symptomatology.

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

BACKGROUNDnRepeated, 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.nnnMETHODnForty-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.nnnRESULTSnThe 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.nnnCONCLUSIONSnThese 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.