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Visuospatial processing and the function of prefrontal-parietal networks in autism spectrum disorders: a functional MRI study.

OBJECTIVE: Individuals with autism spectrum disorders typically have normal visuospatial abilities but impaired executive functioning, particularly in abilities related to working memory and attention. The aim of this study was to elucidate the functioning of frontoparietal networks underlying spatial working memory processes during mental rotation in persons with autism spectrum disorders. METHOD: Seven adolescent males with normal IQ with an autism spectrum disorder and nine age- and IQ-matched male comparison subjects underwent functional magnetic resonance imaging scans while performing a mental rotation task. RESULTS: The autism spectrum disorders group showed less activation in lateral and medial premotor cortex, dorsolateral prefrontal cortex, anterior cingulate gyrus, and caudate nucleus. CONCLUSIONS: The finding of less activation in prefrontal regions but not in parietal regions supports a model of dysfunction of frontostriatal networks in autism spectrum disorders.

Adolescent↗

Understanding obsessive-compulsive disorder: focus on decision making.

Current approaches to obsessive-compulsive disorder (OCD) have suggested that neurobiological abnormalities play a crucial role in the etiology and course of this psychiatric illness. In particular, a fronto-subcortical circuit, including the orbitofrontal cortex, basal ganglia and thalamus appears to be involved in the expression of OCD symptoms. Neuropsychological studies have also shown that patients with OCD show deficits in cognitive abilities that are strictly linked to the functioning of the frontal lobe and its related fronto-subcortical structures, such as executive functioning deficits and insufficient cognitive-behavioral flexibility. This article focuses on decision making, an executive ability that plays a crucial role in many real-life situations, whereby individuals choose between pursuing strategies of action that involve only immediate reward and others based on long-term reward. Although the role of decision-making deficits in the evolution of OCD requires further research, the collected findings have significant implications for understanding the clinical and behavioral heterogeneity that characterizes individuals with OCD.

Brain↗

Executive and mnemonic functions in early Huntington's disease.

Eighteen patients with early Huntington's disease were compared with age- and IQ-matched control volunteers on tests of executive and mnemonic function taken from the Cambridge Neuropsychological Test Automated Battery. Tests of pattern and spatial recognition memory, spatial span, spatial working memory, spatial planning and visual discrimination learning/attentional set shifting were employed. These tests have previously been found to be sensitive to the later stages of Huntington's disease. Patients with early Huntington's disease were found to have a wide range of cognitive impairments encompassing both visuospatial memory and executive functions, a pattern distinct from those seen in other basal ganglia disorders. In contrast to patients with more advanced Huntington's disease, early Huntington's disease patients were not impaired at simple reversal learning, but were impaired at performing an extradimensional shift (EDS). The results will be discussed in relation to the hypothesized neuropathological staging of Huntington's disease and to the anatomical connectivity of the striatum.

Adult↗

Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI.

Gradient echo T2*-weighted MRI has high sensitivity in detecting cerebral microbleeds, which appear as small dot-like hypointense lesions. Microbleeds are strongly associated with intracerebral haemorrhage, hypertension, lacunar stroke and ischaemic small vessel disease, and have generated interest as a marker of bleeding-prone microangiopathy. Microbleeds have generally been considered to be clinically silent; however, since they are located in widespread cortical and basal ganglia regions and are histologically characterized by tissue damage, we hypothesized that they would cause cognitive dysfunction. We therefore studied patients with microbleeds (n = 25) and a non-microbleed control group (n = 30) matched for age, gender and intelligence quotient. To avoid the confounding effects of coexisting cerebrovascular disease, the groups were also matched for the extent of MRI-visible white matter changes of presumed ischaemic origin, location of cortical strokes, and for the proportion of patients with different stroke subtypes (including lacunar stroke). A battery of neuropsychological tests was used to assess current intellectual function, verbal and visual memory, naming and perceptual skills, speed and attention and executive function. Microbleeds were most common in the basal ganglia but were also found in frontal, parieto-occipital, temporal and infratentorial regions. There was a striking difference between the groups in the prevalence of executive dysfunction, which was present in 60% of microbleed patients compared with 30% of non-microbleed patients (P = 0.03). Logistic regression confirmed that microbleeds (but not white matter changes) were an independent predictor of executive impairment (adjusted odds ratio = 1.32, 95% confidence interval 1.01-1.70, P = 0.04). Patients with executive dysfunction had more microbleeds in the frontal region (mean count 1.54 versus 0.03; P = 0.002) and in the basal ganglia (mean 1.17 versus 0.32; P = 0.048). There was a modest correlation between the number of microbleeds and the number of cognitive domains impaired (r = 0.44, P = 0.03). This study provides novel evidence that microbleeds are associated with cognitive dysfunction, independent of the extent of white matter changes of presumed ischaemic origin, or the presence of ischaemic stroke. The striking effect of microbleeds on executive dysfunction is likely to result from associated tissue damage in the frontal lobes and basal ganglia. These findings have implications for the diagnosis of stroke patients with cognitive impairment, and for the appropriate use of antihypertensive and antiplatelet treatments in these patients.

Aged↗

A review and critique of the process approach in neuropsychological assessment.

This paper surveys the process approach literature with an emphasis on higher level cognitive functions like attention and concentration, learning and memory, and problem solving and executive functioning. In particular, it discusses organizational strategies and kinds of errors found on a variety of tests as well as behavioral, situational, and interpersonal issues as they relate to test procedures. It critiques the process approach and suggests future directions.

Cognition↗

Cognitive functioning in adolescents with schizophrenia spectrum disorders.

In contrast to studies of cognitive functioning in adults with schizophrenia, there has been a relative paucity of studies assessing adolescents with schizophrenia. We investigated cognitive functioning in 22 adolescents with schizophrenia spectrum disorders compared with 30 healthy adolescents. The patient group demonstrated impaired performance on all of the functions investigated except sustained attention. Against the background of this broad impairment, executive function and psychomotor speed were the most impaired, sustained attention was spared, while preattentional processing, early visual information processing, visual long-term memory, auditory short-term memory and working memory emerged as relative deficits. The study shows that adolescents with schizophrenia spectrum disorders demonstrate a similar pattern of cognitive functioning to adults in all areas, except sustained attention.

Adolescent↗

Neuropsychological impairment and quality of life in obstructive sleep apnea.

Although clinical experience has suggested for more than two decades that OSA is associated with impairment of cognition, emotional state, and quality of life and that treatment with nasal CPAP produces significant improvements in these areas, sound empirical evidence to support this view, especially regarding treatment outcome, has been lacking. More recent investigations have begun to provide this support from randomized, adequately controlled studies. These assessments suggest that some degree of cognitive dysfunction is associated with OSA. The effects are most apparent in the severe cases, whereas results in mild cases are more equivocal. Reported impairments include global intellectual dysfunction and deficits in vigilance, alertness, concentration, short- and long-term memory, and executive and motor function. Considerable discrepancy exists across studies with respect to type and degree of dysfunction, however. Disturbances in general intellectual function and executive function show strongest correlations with measures of hypoxemia. Not unexpectedly, alterations in vigilance, alertness, and, to some extent, memory seem to correlate more with measures of sleep disruption. Although many inadequately controlled investigations have demonstrated reversibility of most or all of these deficits with effective treatment, more recent placebo-controlled studies have raised doubts regarding whether the observed changes are truly a function of treatment. This issue requires further systematic exploration with adequate controls and step-wise analysis of treatment duration effects. A similar set of considerations exists with respect to the relationship between psychological disturbance, primarily depression, and OSA. Although several studies suggest significant depression in these patients, the results are mixed. Placebo-controlled treatment trials fail to demonstrate consistently a difference in mood improvement between active treatment groups and controls, although several methodologic considerations suggest that these results should be interpreted with caution. Numerous investigations leave little doubt about the issue of quality of life impairment among persons with OSA. Further characterization of impairment, particularly in areas specific to this population, will provide clearer understanding of the problem. Preliminary investigations of treatment response in controlled studies indicate significantly greater improvement of quality of life in response to CPAP. Although patients with OSA commonly report disturbances in cognitive and psychological function and general quality of life, the increased rates of obesity, hypertension, diabetes, cardiovascular disease, medication use, and related psychosocial complications present a host of potential etiologies that might explain the impairments noted. There can be little doubt that these covariants do, in some cases, contribute to neuropsychological dysfunctions. It is essential that future studies continue to define those disturbances that are specific to OSA, the relationship between levels of severity and impairment, the role of treatment in reversing these dysfunctions, and the correlation between test results and significant day-to-day social and occupational functional impairment.

Clinical Trials as Topic↗

Cognitive functioning of adult survivors of cerebral hypoxia.

What should clinical neuropsychologists look out for when asked to assess someone with hypoxic brain damage? To determine whether there are typical cognitive profiles of hypoxic patients, all referrals for a neuropsychological assessment made to the author over a period of 16 years were scanned to identify those with a primary diagnosis of cerebral hypoxia as recorded in the hospital notes. From a total sample of 567 patients, 18 (3.17%) had sustained primary cerebral hypoxia from a variety of causes including carbon monoxide poisoning, cardiac arrest, anaesthetic accident, respiratory failure following a pulmonary embolus, hanging and drowning. Not surprisingly, in view of the different degrees of brain damage, the cognitive functioning of the 18 patients was variable, with the greatest number showing deficits of memory and executive functioning (n = 6). Three presented with an amnesic syndrome; two with memory, executive and visuospatial deficits; and three with visuospatial or visuoperceptual problems without severe memory impairments. The remaining four patients were very severely impaired intellectually (VSI), with widespread cognitive deficits precluding the use of neuropsychological assessment procedures designed for adults.

Adolescent↗

Development and validation of the Subjective Awareness of Neuropsychological Deficits Questionnaire for Children (SAND-C).

Although lowered awareness of abilities has been associated with poorer outcome in adults with neurological compromise, a dearth of research exists examining whether lowered awareness exists in younger populations. Using findings from recent literature and expert opinion, a 47-item Subjective Awareness of Neuropsychological Deficits Questionnaire for Children (SAND-C) was created to assess awareness of cognitive functioning in 6 domains (attention, psychomotor, visual-spatial, language, memory, and executive functioning). Confirmatory factor analysis (CFA) of the SAND-C was conducted on a sample consisting of 365 healthy children and 48 children with epilepsy. The SAND-C was found to have strong reliability. Factor analysis confirmed the a priori 6 factor model, but the 6-factor model was only marginally better than a more parsimonious 1-factor solution. Post-hoc exploratory factor analyses indicate that the SAND-C may measure more constructs for adolescents than for younger children. The difference between younger and older children may reflect developmental changes in metacognitive awareness and abstraction about their own abilities.

Adolescent↗

Cognitive function in patients with Parkinson's disease undergoing stereotaxic thalamotomy.

OBJECTIVE: To determine whether thalamotomy leads to cognitive disturbances in patients with Parkinson's disease. METHODS: A total of 53 patients with Parkinson's disease undergoing stereotaxic ventrolateral thalamotomy for tremor and rigidity were tested for cognitive functions before and after surgery. The cognitive functions investigated involved visuospatial perception and memory. verbal memory, attention shift, and executive functions including set maintenance and shift. A neuropsychological test battery was used that contained the Wisconsin card sorting test, Street completion test, Stroop test, a dichotic memory listening test, and a facial recognition test. RESULTS: Clinically, a good or moderately good effect on parkinsonian symptoms was obtained in 50 patients. The neuropsychological investigations showed that the patients were impaired compared with healthy age matched control subjects on most tests, showing slight improvement postoperatively on verbal memory and visuospatial perception. No major differences were found between tests before and after operation, and there were no significant differences between patients undergoing surgery in the right or in the left thalamus. CONCLUSION: The study indicates that ventrolateral thalamotomy does not reduce the cognitive capacity in this group of patients.

Adult↗

Differentiation of vascular dementia from AD on neuropsychological tests.

BACKGROUND: The concept of vascular dementia (VaD) is currently in a state of evolution. Memory impairment is emphasized as a primary criterion, reflecting the influence of AD on the concept of dementia. We have systematically reviewed whether the nature of neuropsychological dysfunction is distinct in AD and VaD, and whether similar defining criteria for the concept of dementia in both disorders can be supported. METHODS: We searched five bibliographic databases (Medline, Biological Abstracts, EMBASE, PsychINFO, PsychLIT) for research articles in which VaD and AD had been compared using neuropsychological tests and that met criteria for scientific merit. RESULTS: Of the 45 studies, 18 were excluded because of inadequacies, and the remaining 27 were analyzed. There were a number of similarities of dysfunction between VaD and AD. However, when matched for age, education, and severity of dementia, VaD patients had relatively superior function in verbal long-term memory and more impairment in frontal executive functioning compared with AD patients. Interpretation of the results is limited by uncertainty in diagnostic criteria for VaD, possible inclusion bias due to use of clinical diagnosis alone, possible overlap of AD and VaD, and the methodologic shortcomings of some studies. CONCLUSIONS: The neuropsychological differentiation of VaD from AD was consistent with the different neuroimaging findings in the two disorders, and argues for differential criteria for the definition of the syndromes. The simple application of Alzheimer's dementia criteria to VaD, with the inclusion of cerebrovascular disease etiology, may not be sufficient to capture the uniqueness of VaD.

Alzheimer Disease↗

[Assessment of frontal functions in psychiatric patients during maintenance electroconvulsive therapy].

INTRODUCTION: Previous studies on adverse cognitive effects of electroconvulsive therapy (ECT) have not found any significant alteration of the frontal functions after an acute treatment course. This study aims to assess frontal executive functions in psychiatric patients during maintenance electroconvulsive therapy (M-ECT). SUBJECTS AND METHODS: Thirty two patients treated with M-ECT and 29 psychiatric patients never treated with ECT were evaluated with neuropsychological tests that assessed the following frontal functions: work memory, planning, cognitive flexibility, attention, visuomotor velocity, verbal abstract reasoning and phonetic verbal fluency. RESULTS: Multivariate global analysis did not detect significant frontal function tests differences between both groups. The M-ECT group only scored significantly lower on the FAS test, a test that measures phonetic verbal fluency. A significant correlation between number of previous ECT sessions and performance in the FAS was found. CONCLUSIONS: The M-ECT patient group presented a phonetic verbal fluency alteration that may also be associated to the previous number of ECT sessions. No significant differences in the other frontal functions were detected.

Bipolar Disorder↗

Early cognitive changes and nondementing behavioral abnormalities in Parkinson's disease.

Early cognitive changes in patients with PD are often subtle and influenced by factors that interact with the disease process, including age of disease onset, medication, and the specific constellation of motor symptoms. These factors notwithstanding, ample evidence exists that specific cognitive changes occur early in the course of PD. This evidence does not imply that cognitive deficits are pervasive during the early stages. To the contrary, they are usually subtle and often difficult to detect without formal neuropsychological testing. Executive-function deficits are the most frequently reported cognitive problems and, given that executive skills are an integral part of many tasks, it follows that subtle difficulties may be seen on a wide range of cognitive measures, particularly in working memory and visuospatial dysfunction, two areas that rely heavily on executive skills. Whereas apraxia and language processing deficits occur infrequently, subtle changes in olfaction and contrast sensitivity have also been repeatedly observed. Finally, depressive symptoms are also common in the early stages of the disease. The significance of the early behavioral changes and their prognostic implications are largely unknown. Prospective studies are needed to understand the longitudinal course of early cognitive changes to determine whether they remain as circumscribed impairments or represent a precursor to a more widespread dementia.

Age of Onset↗

Brain potentials related to self-generated and external information used for performance monitoring.

OBJECTIVE: Humans need to supervise and adjust their own behavior by means of an error detection and correction system as well as by using externally available information. The purpose of the present study was to compare the electrophysiological effects related to self-generated internal and to external (feedback) information used for performance monitoring. METHODS: Fourteen young normal subjects learned to associate each of several line-drawings with either a left-hand or right-hand response. In the experiment proper multi-channel ERPs were obtained time-locked to (a) the line-drawings, (b) the button-press, and (c) subsequent feedback stimuli. Feedback was either affirmative, negative, or equivocal. Event-related potentials were quantified and statistically evaluated using standard methodology. RESULTS: Response-locked ERPs showed a typical error-related negativity (ERN) for erroneous responses. ERPs to negative and equivocal feedback stimuli contained a negativity with a more posterior distribution than that of the ERN, which occurred earlier and had a higher peak amplitude in the equivocal condition. Dipole modeling suggests that this feedback-related negativity is generated by medial prefrontal and posterior cingulate cortex areas. CONCLUSIONS: Different brain systems support the use of internal and external information necessary for performance monitoring and modification. SIGNIFICANCE: The flexible use of internal and external information for performance control is a core executive function. The delineation of the corresponding brain correlates will further our understanding of executive dysfunction in neurological disorders.

Adult↗

Functional MRI of task switching in children with Specific Language Impairment (SLI).

The objective of this study was to examine executive functioning in children with Specific Language Impairment (SLI) using functional MRI. Six children with SLI and seven control children participated in this study and received a task-switching paradigm. No specific deficit in executive control was observed at the behavioral level in children with SLI. However, the neuroimaging data did show remarkable differences between the SLI and control children. The children with SLI recruited frontal and cingulate areas, normally associated with executive control, even when the task did not require them in the children without SLI. This might indicate that the task was more demanding for the SLI group and that compensatory mechanisms were engaged for successful task performance.

Analysis of Variance↗

The effects of reward and punishment contingencies on decision-making in multiple sclerosis.

Many patients with multiple sclerosis (MS) show cognitive and emotional disorders. The purpose of this study is to evaluate the role of contingency learning in decision-making in young, non-depressed, highly functioning patients with MS (n=21) and in matched healthy controls (n=30). Executive functions, attention, short-term memory, speed of information processing, and selection and retrieval of linguistic material were also investigated. Contingency learning based on the cumulative effect of reward and punishment was assessed using the Iowa Gambling Test (IGT). 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 revealed that patients with MS showed significant dysfunctions in both versions of the IGT. Performances on neuropsychological tests sensitive to dorsolateral prefrontal functions did not predict and did not correlate with the IGT scores. These results suggest that patients with MS show impaired performances on tasks designed to assess decision-making in a situation requiring the evaluation of long-term outcomes regardless of gain or loss, and that this deficit is not a pure consequence of executive dysfunctions.

Adult↗

Characteristics of minimal hepatic encephalopathy.

The term minimal hepatic encephalopathy refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy. Use of this term emphasizes the fact that the entity of hepatic encephalopathy is a single syndrome with quantitatively distinct features relating to severity. The absence of clinical evidence of hepatic encephalopathy is key to the diagnosis and can only be determined by a detailed assessment of the patients' history and a comprehensive neurological assessment of consciousness, cognitive, and motor function. The neuropsychological features of minimal hepatic encephalopathy point to a disorder of executive functioning, particularly selective attention and psychomotor speed, but other abnormalities may be observed. Alterations in electrophysiological variables have been described; endogenous evoked potentials are, in principle, more likely to reflect the presence of minimal hepatic encephalopathy, since they reflect cognitive phenomena rather than mere stimulus conduction but the specificity of the changes observed is unclear at present. Changes have also been described in the execution of diadochokinetic movements and in the capacity to discriminate flickering light, both of which may have diagnostic potential. The changes observed in cerebral blood flow and metabolism in SPET, PET, and 1H and 31P MRS studies reflect the pathogenic process that underlies the condition rather than providing diagnostic information. Similarly, the morphological brain abnormalities identified in this population, including mild brain oedema, hyperintensity of the globus pallidus and other subcortical nuclei observed in cerebral MR studies, and the central and cortical atrophy observed in neural imaging studies, are unlikely to have diagnostic utility. The presence of minimal hepatic encephalopathy is not without clinical consequence; it has a detrimental effect on health-related quality of life, the ability to perform complex tasks such as driving, and on outcome.

Brain↗

Post-stroke depression, executive dysfunction and functional outcome.

The early diagnosis of vascular cognitive impairment has been challenged and executive control function has been suggested to be a rational basis for the diagnosis of vascular dementia. We sought to examine the correlates of executive dysfunction in a well-defined stroke cohort. A group of 256 patients from a consecutive cohort of 486 patients with ischaemic stroke, aged 55-85 years, was subjected to a comprehensive neuropsychological examination 3-4 months after ischaemic stroke and 188 of them in addition to detailed psychiatric examination. Basic and complex activities of daily living (ADLs) (bADLs and cADLs) post-stroke were assessed. The DSM-III-R criteria were used for the diagnosis of the depressive disorders. Altogether 40.6% (n=104) of the patients had executive dysfunction. The patients with executive dysfunction were older, had lower level of education, were more often dependent, did worse in bADLs and cADLs, had more often DSM-III dementia, had worse cognition as measured by Mini Mental State Examination (MMSE) and were more depressed as measured by the BECK depression scale, but not with the more detailed psychiatric evaluation. They had more often stroke in the anterior circulation and less often in the posterior circulation. The independent correlates of executive dysfunction were cADLs (OR 1.1, 95% CI 1.03-1.16), each point of worsening in cognition by MMSE (OR 1.7, 95% CI 1.42-1.97) and stroke in the posterior circulation area (OR 0.4, 95% CI 0.18-0.84). Clinically significant executive dysfunction is frequent after ischaemic stroke and is closely connected with cADLs and to overall cognitive status but could be distinguished from depression by detailed neuropsychological examination. Executive measures may detect patients at risk of dementia and disability post-stroke.

Activities of Daily Living↗