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Sensitivity to reward and punishment and the prefrontal cortex in major depression.

BACKGROUND: Patients with major depressive disorder (MDD) show neuropsychological impairments, including deficient executive functions and altered sensitivity to reward and punishment. METHODS: Executive functions (Wisconsin Card Sorting Test, WCST) and contingency learning based on the cumulative effect of reward and punishment (Iowa Gambling Test, IGT) were assessed in 30 medicated patients with unipolar MDD and in 20 healthy control volunteers. In the classic ABCD version of the IGT, advantageous decks are characterized by immediate small reward but even smaller future punishment. In the modified EFGH version, advantageous decks are characterized by immediate large punishment but even larger future reward. RESULTS: Patients with MDD were impaired in the WCST and in the ABCD version of the IGT but showed normal performances on the EFGH task. Depression, but not executive dysfunctions, significantly predicted performances on the EFGH task: less severe depressive symptoms were associated with better performances on the EFGH task. LIMITATIONS: The sample size was small and only few neuropsychological tests were used. Unmedicated patients were not assessed. Individual personality style, response strategies, and behavioral impulsivity were not investigated. CONCLUSIONS: Medicated patients with MDD show altered sensitivity to reward and punishment: immediate large reward enhanced related response patterns even when the strategy was disadvantageous and immediate large punishment did not prohibit related response patterns. Impairments in emotional decision-making were not a pure consequence of executive dysfunctions.

Adult↗

Contextual abnormalities of saccadic inhibition in children with attention deficit hyperactivity disorder.

Abnormalities of executive function are observed consistently in children with attention-deficit hyperactivity disorder (ADHD), and it is hypothesised that these arise because of disruption to a behavioural inhibition system. Executive and inhibitory functions were compared between unmedicated and medicated children with ADHD (combined type), age-matched healthy children and healthy adults. Executive functions were measured using a test of spatial working memory shown previously to be sensitive to ADHD and to stimulant medication. Inhibitory functions were measured using an ocular motor paradigm that required individuals to use task context to control the release of fixation. Context was set according to the probability that a target would appear at either of the two locations. In one block, targets appeared on 80% of trials. In the other block, targets appeared on 20% of trials. The ability to control the release of fixation was inferred from the fixation offset effect (FOE), or the difference in saccade latency when the current fixation is offset 200 ms prior to the onset of the saccade target (gap condition), compared with when there is no offset (overlap condition). Although the healthy children made more errors on the spatial working memory task than the healthy adults, there was no difference between the two groups in their ability to control fixation using context. Both showed a larger FOE when target probability was low. As expected, the unmedicated ADHD group made more errors on the spatial working memory test than the healthy children, although spatial working memory performance was normal in the medicated ADHD group. However, both the unmedicated and medicated ADHD groups were unable to modulate the FOE according to context, and this was due to their inability to voluntarily inhibit saccades when there was a low target probability. These data suggest that the context-based modulation of fixation release is not controlled by the same systems that control executive function. Furthermore, deficits in executive function and inhibitory control appear independent in children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

Somatotopic mapping of the human primary sensorimotor cortex during motor imagery and motor execution by functional magnetic resonance imaging.

The human primary sensorimotor cortex was investigated for somatotopic organization during motor imagery (IM) which was compared to motor execution (EM). Block designed BOLD (blood oxygen level dependent)-functional magnetic resonance imaging at 1.5 Tesla was applied in 14 right handed volunteers during imagined and executed tongue, finger and toe movements. BOLD-clusters were assessed for anatomically correct sensorimotor localization. Euklidian coordinates, relative signal change and correlation to the applied reference function were determined. Statistical means were calculated. IM recruited somatotopically organized primary sensorimotor representations of the precentral gyrus that reflected the homunculus and overlapped in part with EM representations. Mean BOLD-signals ranged from 1.93 to 3.18% for EM, and from 0.73 to 1.47% for IM. The results support the hypothesis that the primary sensorimotor cortex is active during IM and that IM and EM share common functional circuits.

Adult↗

Negative symptoms and specific cognitive impairments as combined targets for improved functional outcome within cognitive remediation therapy.

Negative symptoms and poor cognition are both associated with poor functional outcome in schizophrenia. This poor functional outcome has been attributed to poor cognition rather than any independent contribution from symptoms. Identifying target cognitive processes and mechanisms that predict community function, and possible moderator effects of negative symptoms, will allow the development of cognitive remediation programs that are successful in improving functional outcome. A referred sample of 53 in- and outpatients with schizophrenia with general cognitive impairment (including 28 with severe negative symptoms) and 22 healthy controls, balanced for premorbid IQ, were compared cross sectionally on measures of community shopping skills, executive function, and working memory. Across the groups, there were direct relationships between community functioning and specific executive functions, and there were interactions between group membership and the types of associations found. Working memory was independently associated with accurate community functioning only in people with schizophrenia and negative symptoms. This association was not due to the sole presence of working memory impairment or just to negative symptoms. Poor community function is predicted both by specific cognitive impairments that are prominent in people with negative symptoms and through the moderating effect of negative symptoms on the working memory-community function relationship. This may reflect a synergistic association between symptoms and cognition: negative symptoms arise from cognitive impairment but also impact detrimentally on working memory functioning. Both cognitive processes and negative symptoms should be targeted in cognitive remediation to effect the greatest change in community functions.

Adult↗

Executive dysfunction in early Alzheimer's disease.

Twenty five patients with probable mild Alzheimer's disease were assessed for deficits in executive functioning and the impact of these deficits on performance in other neuropsychological domains. The Wisconsin card sorting test, the release from proactive interference paradigm, the verbal fluency test, and the Stroop test were adopted to classify patients with (AD+) and without (AD-) executive deficits. Seven of the patients showed an impairment in executive function (AD+), defined as a performance below the cut off score in at least two of these tests. There were no significant differences in clinical assessments, demographic features, or other cognitive functions between patients. Executive dysfunction may be an early additional feature in a subgroup of patients with mild Alzheimer's disease. Impairment on frontal lobe tests does not seem to be related to the severity or duration of disease, or to a different pattern of impairment in other cognitive domains.

Aged↗

Levodopa slows prosaccades and improves antisaccades: an eye movement study in Parkinson's disease.

BACKGROUND: The integrity of frontal systems responsible for voluntary control and their interaction with subcortical regions involved in reflexive responses were studied in patients with Parkinson's disease (PD). Previous studies have shown that patients with PD have impaired executive function, including deficits in attention, motor planning and decision making. METHODS: Executive function was measured through eye movements: reflexive (stimulus driven) prosaccades and voluntary (internally guided) antisaccades. Patients with advanced idiopathic PD, off and on their optimal levodopa therapy, were tested on a prosaccade and an antisaccade task and compared with matched controls. RESULTS: Levodopa significantly increased response time for reflexive prosaccades and reduced error rate for voluntary antisaccades. CONCLUSIONS: Consistent with our proposed model, patients with PD in the medicated state are better able to plan and execute voluntary eye movements. These findings suggest levodopa improves function of the voluntary frontostriatal system, which is deficient in PD.

Aged↗

Neuropsychological profile in patients with schizotypal personality disorder or schizophrenia.

Neuropsychological impairments have been consistently reported in patients with schizophrenia. As little is known whether subjects with schizotypal personality disorder exhibit neurocognitive dysfunction similar to that in schizophrenia, we assessed the neuropsychological profile of 15 subjects with schizotypal personality disorder and compared it with that for 15 patients with schizophrenia and for 15 psychiatrically normal volunteers. All participants were administered a standard neuropsychological battery assessing language ability, spatial ability, visuomotor function, verbal memory, visual memory, auditory attention, visual attention, and executive function. Performance on most of the cognitive domains was impaired in patients with schizotypal personality disorder but less than patients with schizophrenia. Specifically, impairment in verbal memory and visuomotor ability in patients with schizotypal personality disorder and patients with schizophrenia were comparable, while patients with schizophrenia performed worse on the test of executive function than did patients with schizotypal personality disorder. As a whole, cognitive deficits in patients with schizotypal personality disorder were qualitatively similar to, but quantitatively milder than, those for patients with schizophrenia. The results suggest that cognitive abilities related to frontotemporal lobe function are disturbed across these schizophrenia-spectrum disorders.

Adult↗

Neuropsychological performance in adult attention-deficit hyperactivity disorder: meta-analysis of empirical data.

Attention-deficit hyperactivity disorder (ADHD) is increasingly recognized not only in children but also in adults. Neuropsychological tests are important tools to quantify the attentional and/or cognitive deficits of patients compared to controls. The present meta-analysis integrates 24 empirical studies reporting results of at least one of 50 standard neuropsychological tests comparing adult ADHD patients with controls. The 50 tests were categorized into the following 10 functional domains: verbal ability, figural problem solving, abstract problem solving, executive function, fluency, simple attention, sustained attention, focused attention, verbal memory, figural memory. For each domain a pooled effect size d' was calculated. Complex attention variables and verbal memory discriminated best between ADHD patients and controls. Effect sizes for these domains were homogeneous and of moderate size (d' between 0.5 and 0.6). In contrast to results reported in children, executive functions were not generally reduced in adult ADHD patients.

Adolescent↗

[Selective attention deficit in schizophrenia].

OBJECTIVE: To evaluate the cognitive deficits which have been linked with schizophrenia, particularly those related to selective attention from a neurocognitive point of view. DEVELOPMENT: We present a concept of attention consistent with a system of control of information processing composed of a group of neurone networks which carry out specific functions. Some functions are related to visual orientation, while others are involved in executive functions which are at the root of many cognitive skills. The convergence of data from behaviour studies and those made available by neuroimaging techniques have facilitated the identification of neuroanatomical areas responsible for these functions. Thus, the posterior parietal lobe, superior colliculus and pulvinar nucleus of the thalamus are responsible for directing visual attention to different spatial locations. The singular cortex, parts of the medial prefrontal area and supplementary motor area will be involved in executive functions. The question arises as to whether schizophrenia is related to a general attention deficit or to specific deficits linked to the different attention neurone networks. In the studies reviewed attention tasks for the evaluation of facilitatory and inhibitory functions related to the different attention networks were used. CONCLUSIONS: The studies showed that schizophrenic patients present deficits in inhibitory mechanisms which depend on the executive attention network. These results may contribute to a better understanding of the cognitive problems which occur in schizophrenia and also to design more effective strategies for the treatment of this disorder.

Attention↗

Comparative neuropsychological function in obsessive-compulsive disorder and schizophrenia with and without obsessive-compulsive symptoms.

Executive function deficits are seen in both schizophrenia and obsessive-compulsive disorder (OCD), but research suggests that dorsolateral prefrontal (DLPF) dysfunction is associated with schizophrenia and orbitofrontal (OBF) dysfunction is associated with OCD. As part of a comprehensive neuropsychological assessment, the Bechara Gambling Task (BGT) was used to assess OBF function and the Wisconsin Card Sorting Test (WCST) was used to assess DLPF function among three groups: 26 individuals with schizophrenia/schizoaffective disorder with obsessive-compulsive symptoms (SCZ+), 28 individuals with schizophrenia/schizoaffective disorder without obsessive-compulsive symptoms (SCZ-), and, 11 individuals with OCD. It was predicted that the SCZ+ group and the OCD group would show impairments in OBF function, as compared to the SCZ- group, and that the SCZ+ and SCZ- groups would show impairments in DLPF function, as compared to the OCD group. It was also predicted that the SCZ+ group would perform more poorly than the SCZ- and OCD groups in a number of other cognitive domains. Contrary to expectation, no divergence between groups was seen on tests of executive function. Instead, there was a statistical trend for the SCZ+ and SCZ- groups, when combined, to perform worse than individuals with OCD on the measure of OBF. Although not significant at the designated alpha level, the profile results showed that the SCZ+ group performed slightly below the OCD and SCZ- groups across nearly all neuropsychological domains.

Adult↗

Approaches to cognitive remediation of neuropsychological deficits in schizophrenia: a review and meta-analysis.

A review and critique of the literature pertaining to the use of cognitive remediation techniques in patients with schizophrenia is presented. The review is organized into three sections, according to the neuropsychological deficit targeted for remediation: 1) executive-function, 2) attention, and 3) memory. With regards to executive-function, despite an initial report suggesting that Wisconsin Card Sorting Test performance cannot be remediated, subsequent studies suggest that performance can be improved on a variety of dependent measures including perseverative errors, categories achieved, and conceptual level responses. These observations were confirmed by a meta-analytic investigation that revealed large mean effects sizes (d+ = 0.96) for these studies. Effect sizes were homogenous across discrepant remediation strategies and dependent measures. With regards to attention, serial scanning can be improved with instruction and reinforcement, whereas there is mixed evidence suggesting that practice-based attention drills can improve performance on measures of sustained attention in schizophrenia. With regards to memory, relatively simple semantic and affective elaborate encoding strategies elevates verbal list-learning memory in patients with schizophrenia to levels consistent with controls. A similar encoding procedure, combined with vigilance training, produces substantial improvement in social cue recognition. Avenues for future research are discussed.

Attention↗

Construct overlap in resource theories of memory aging. Commentary.

This article evaluates the conceptual status of working memory, processing speed, executive function and sensory function as mediational constructs to explain memory aging. The main difficulty for these mediational constructs is that they may not be independent. Mediational constructs may overlap with each other or with the dependent variable due to theoretical, substantive or methodological reasons. It is argued that sensory function has an advantage over processing speed, working memory and executive function as a mediational construct because it is non-cognitive. The problem of construct overlap is relevant to both cross-sectional and longitudinal studies. Further research is required to evaluate the relative importance of mediational constructs in theories of memory aging, general intellectual aging and dementia.

Aging↗

Lateralization in individuals with high-functioning autism and Asperger's disorder: a frontostriatal model.

Neurobiological and behavioural studies of possible left hemisphere dysfunction in autism have generated conflicting results. Left hemisphere dysfunction may manifest in autism only in tasks that invoke executive functions. Moreover, left hemisphere dysfunction may underpin autism but not Asperger's disorder. We thus aimed to systematically investigate reports of anomalous lateralization in individuals with high-functioning autism and Asperger's disorder. Two of the tasks were sensitive to executive dysfunction: a serial choice reaction-time task and a Posner-type paradigm; the remaining tasks instead investigated aspects of perceptual lateralisation. Compared with age- and IQ-matched controls, the autism group displayed deficiencies in right hemispace (and by implication, left hemisphere) performance on both executive function tasks; however, this group demonstrated normal lateralization effects on the nonexecutive, visual-perceptual tasks. In contrast, the Asperger's disorder group showed similar laterality effects to their age- and IQ-matched controls on both executive and nonexecutive function tasks. The etiological relevance of this neurobehavioral dissociation between high-functioning autism and Asperger's disorder was discussed; in particular, it was suggested that the period where dominance shifts from right to left hemisphere is important in whatever process might dictate the emergence of either autism or Asperger's disorder.

Adolescent↗

A deficit in shifting attention present in high-functioning autism but not Asperger's disorder.

The aim of this study was to examine executive functioning, in particular, attentional set-shifting deficits in high-functioning autism (n = 12) and Asperger's disorder (n = 12). A large or global digit composed of smaller or local digits was presented during each trial. The participants indicated the presence of 1s or 2s by pressing the appropriate button. These targets could appear globally or locally Relative to IQ, sex and age matched controls, reaction time to global targets in individuals with autism was retarded when the previous target appeared locally. This deficiency in shifting from local to global processing, however, was not observed in individuals with Asperger's disorder. The theoretical and neurobiological significance of this dissociation in executive functioning in these clinically related disorders was explored.

Adolescent↗

The serotonin 5-HT2A receptors antagonist M100907 prevents impairment in attentional performance by NMDA receptor blockade in the rat prefrontal cortex.

We investigated whether 5-HT2A receptors contribute to the control of attentional performance by glutamate NMDA receptor mechanisms in the medial prefrontal cortex (mPFC). We examined the effects of NMDA receptor blockade in the mPFC on attentional performance by infusing a competitive glutamate NMDA receptor antagonist, 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) into the mPFC of rats performing a task of divided and sustained visual attention. The five-choice serial reaction time task provides indices of attentional functioning (% correct responses), executive control (measured by anticipatory and perseverative responses) and speed. A dose of 10 ng CPP injected bilaterally into the mPFC increased anticipatory and perseverative responding; 50 ng reduced accuracy. Increasing the stimulus duration alleviated the CPP-induced accuracy deficit but did not reduce its effects on anticipatory and perseverative responses. CPP at 50 ng caused motor hyperactivity whereas lower doses had no effect. [R-(+)-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol] (M100907) (M100907), a 5-HT2A receptor antagonist, injected subcutaneously at 10 and 40 microg/kg, had no effect on accuracy but dose dependently reversed the impairment induced by 50 ng CPP. Both doses of M100907 completely abolished CPP-induced anticipatory but not perseverative over-responding. At the dose of 40 microg/kg M100907 reversed CPP-induced motor hyperactivity. This study provides evidence that the prefronto-cortical glutamate NMDA system may make an important contribution to the control of attention and executive functions. It also indicates that 5-HT2A receptors may serve to optimize attentional selectivity and improve some aspects of executive control.

Animals↗

Cognitive rehabilitation in the elderly: effects on strategic behavior in relation to goal management.

Executive functions are highly sensitive to the effects of aging and other conditions affecting frontal lobe function. Yet there are few validated interventions specifically designed to address executive functions, and, to our knowledge, none validated in a healthy aging sample. As part of a large-scale cognitive rehabilitation randomized trial in 49 healthy older adults, a modified Goal Management Training program was included to address the real-life deficits caused by executive dysfunction. This program emphasized periodic suspension of ongoing activity to establish goal hierarchies and monitor behavioral output. Tabletop simulated real-life tasks (SRLTs) were developed to measure the processes targeted by this intervention. Participants were randomized to two groups, one of which received the intervention immediately and the other of which was wait-listed prior to rehabilitation. Results indicated improvements in SRLT performance and self-rated executive deficits coinciding with the training in both groups. These gains were maintained at long-term follow-up. Future research will assess the specificity of these effects in patient groups.

Aged↗

The course of neurocognitive functioning in high-grade glioma patients.

We evaluated the course of neurocognitive functioning in newly diagnosed high-grade glioma patients and specifically the effect of tumor recurrence. Following baseline assessment (after surgery and before radiotherapy), neurocognitive functioning was evaluated at 8 and 16 months. Neurocognitive summary measures were calculated to detect possible deficits in the domains of (1) information processing, (2) psychomotor function, (3) attention, (4) verbal memory, (5) working memory, and (6) executive functioning. Repeated-measures analyses of covariance were used to evaluate changes over time. Thirty-six patients were tested at baseline only. Follow-up data were obtained for 32 patients: 14 had a follow-up at 8 months, and 18 had an additional follow-up at 16 months. Between baseline and eight months, patients deteriorated in information-processing capacity, psychomotor speed, and attentional functioning. Further deterioration was observed between 8 and 16 months. Of 32 patients, 15 suffered from tumor recurrence before the eight-month follow-up. Compared with recurrence-free patients, not only did patients with recurrence have lower information-processing capacity, psychomotor speed, and executive functioning, but they also exhibited a more pronounced deterioration between baseline and eight-month follow-up. This difference could be attributed to the use of antiepileptic drugs in the patient group with recurrence. This study showed a marked decline in neurocognitive functioning in HGG patients in the course of their disease. Patients with tumor progression performed worse on neurocognitive tests than did patients without progression, which could be attributed to the use of antiepileptic drugs. The possibility of deleterious effects is important to consider when prescribing antiepileptic drug treatment.

Adult↗

[Functional anatomy of the third ventricle. Neuropsychological data].

The functional structures surrounding the third ventricle explain the occurrence of neuropsychological disorders when a tumor develops in this area. The functional environment of the third ventricle is involved in memory, motor executive control, endocrine and vegetative regulations. The types of memory deficit, the behavioural and emotional regulations, the interhemispheric transfer, and the regulation of executive functions are analyzed and correlated to the concerned anatomical structures. The review of the literature collected few specific considerations in neuropsychological dysfunctions occurring with tumors of the third ventricle. A retrospective study was conducted in 17 patients of the national series operated on for a third ventricle lesion : long-term memory and executive functions were frequently impaired in the patients, and the deficits were underestimated by usual follow-up. More systematic utilization of preoperative and postoperative test batteries is necessary for a better evaluation of neuropsychological disorders after third ventricle surgery.

Adolescent↗