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PubMed2006

Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism.

BACKGROUND: Autism is a neurodevelopmental disorder affecting sociocommunicative behavior, but also sensorimotor skill learning, oculomotor control, and executive functioning. Some of these impairments may be related to abnormalities of the caudate nuclei, which have been reported for autism. METHODS: Our sample was comprised of 8 high-functioning males with autism and 8 handedness, sex, and age-matched controls. Subjects underwent functional MRI scanning during performance on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI) effects were identified as interregional blood oxygenation level dependent (BOLD) signal cross-correlation, using the caudate nuclei as seed volumes. RESULTS: In the control group, fcMRI effects were found in circuits with known participation of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits). Although in the autism group fcMRI effects within these circuits were less pronounced or absent, autistic subjects showed diffusely increased connectivity mostly in pericentral regions, but also in brain areas outside expected anatomical circuits (such as visual cortex). CONCLUSION: These atypical connectivity patterns may be linked to developmental brain growth disturbances recently reported in autism and suggest inefficiently organized functional connectivity between caudate nuclei and cerebral cortex, potentially accounting for stereotypic behaviors and executive impairments.

Journal Article↗

PubMed2003

Impact of executive dysfunctions on episodic memory abilities in patients with ruptured aneurysm of the anterior communicating artery.

Executive and memory dysfunctions are among the most frequently reported deficits following a ruptured aneurysm of the anterior communicating artery (ACoA). In order to study the impact of the dysexecutive syndrome on episodic and semantic memory, the data obtained from 59 ACoA patients were examined retrospectively. All patients were assessed on a variety of episodic memory tests (Rey Auditory-Verbal Learning Test, Rey Complex Figure Test, Weschler Memory Scale), semantic memory (verbal fluency), and standardized tests of executive functions (Trail Making Test, Maze tests, Wisconsin Card Sorting Test). There was a strong positive correlation between executive dysfunction and retrieval difficulties in episodic and semantic memory tasks. Comparisons of subgroups of patients with high and low frontal lobe functioning on delayed recall and recognition revealed a significant group X condition interaction in addition to significant group and condition main effects. ACoAs patients with low frontal lobe functioning were particularly deficient in free recall (immediate and delayed) while recognition was equally well preserved in the two subgroups. Neither subgroup presented with an abnormal forgetting over time suggesting a retrieval deficit rather than a true retention impairment.

Adult↗

PubMed2001

Associations between apolipoprotein E phenotype, glucose metabolism and cognitive function in men. An explorative study in a population sample.

AIMS: To investigate the associations of the apolipoprotein E phenotype (apoE) and disturbed glucose metabolism with cognitive function in a random population sample. METHODS: A cross-sectional study was conducted, in which 528 men aged 54 or 60 years were recruited randomly from a larger population-based sample of 1516 men. A subject was defined as having abnormal glucose tolerance (AGT), if he had a clinical diagnosis of diabetes, with either dietary or oral antidiabetic treatment or showed impaired glucose tolerance in an oral glucose tolerance test. The subjects were divided into three groups according to apolipoprotein E phenotypes: (a) E2/4, E3/4 or E4/4 (apoE E4); (b) E 3/3 (apoE E3); and (c) E2/2 or E2/3 (apoE E2). Memory function was examined using a word-list learning with Buschke's selective reminding method and test. Executive functions were assessed with the Trail Making Test A and B. RESULTS: Those subjects with apoE E2 and abnormal glucose metabolism demonstrated the worst cognitive executive control compared to other groups. Simple cognitive speed did not differ between the groups. CONCLUSIONS: The exploratory analyses revealed that subjects with apoE E2 allele and AGT had worse glycaemic control and cognitive executive control compared to other groups. Different apolipoprotein phenotypes together with impaired glucose tolerance may have different cumulative adverse effects on age-related cognitive performance. Some subgroups of subjects may be especially vulnerable to cognitive impairment.

Apolipoprotein E3↗

PubMed2006

[What place can the health executive hold in the internal contract process?].

The current context of cost control relative to health expenditures forces hospitals to wonder about their management style. Therefore, the question of the efficiency of the health system is raised. Would the formalization by contract bring the beginnings of an answer? This is what its growing development within numerous public health establishments leads one to suppose, thus signing an evolution towards some new "medical and administrative" governance. Through this article, I therefore suggest to you a questioning on the essence of the contractual method, its stakes, its limits and especially a projective approach on the consequences of this management method considering the "health executive" function. As the stake in this reflection is to highlight the fact that if the health executive has a place acknowledged in the internal formalization by contract, its competence will constitute an increase in value in the contractual process. Indeed, this questioning seems important to me and this, all the more as the ordinance dated May 2, 2005 including "various arrangements relative to the functioning of public health establishments and modifying the public health code", stipulates that public hospitals should resort to the method of internal formalization by contract in setting up centres of activity and this, at the latest, before December 31, 2006.

Contract Services↗

PubMed2002

Planning and problem solving skills following focal frontal brain lesions in childhood: analysis using the Tower of London.

Problem solving skills were investigated in children with focal lesions using the Tower of London test (TOL; Shallice, 1982). The scoring procedure was elaborated from previous studies to delineate separate processes contributing to overall performance in children. Thirty-one children with focal frontal pathology, 18 children with focal pathology in other brain regions (extra-frontal), 17 children with generalized pathology and 38 healthy children participated in the study. Results suggest a distributed network for problem solving skills, particularly cognitive flexibility and goal setting skills. Within the frontal group, children with lesions involving the right pre-frontal cortex had greatest problems with self-regulation, with rule breaks most common among this group. As these skills develop relatively early in comparison to other aspects of executive function, right pre-frontal regions may play a particularly important role in the development of executive skills in childhood, with damage to these regions rendering children vulnerable to a range of cognitive and social deficits.

Adolescent↗

PubMedDate not supplied

[Anoxic encephalopathy. Clinical description, prognosis and neuroimaging].

OBJECTIVES: To describe the clinical profile (neuropsychological, psychopathological, functional and neuroimaging), as well as the evolution of patients with anoxic encephalopathy. PATIENTS AND METHODS: Nine patients with anoxic encephalopathy attending our Service were included in the study. All patients were assessed with a broad range of neuropsychological tests, checklists of psychopathological symptoms, and several functional scales. A CT/MRI or a positron emission tomography (PET) were performed in five patients. Five patients were admitted to a multidisciplinary rehabilitation program. RESULTS: All patients showed problems in orientation, executive functions, verbal learning an immediate and long-term verbal memory, in association with diffuse cognitive changes in other functions. Psychopathologically, all patients showed apathy-indifference, and eight subjects showed anosognosia. All subjects have an important dependence in daily activities. CT/MRI were normal or showed subcortical changes whereas the PET showed a predominantly cortical hypometabolism with specific patterns. There were no significant improvements after rehabilitation in treated patients. CONCLUSION: In the absence of a unique clinical profile, our patients with anoxic encephalopathy showed similarities in their symptoms (diffuse cognitive deficits with predominance of amnesic and executive impairments; presence of apathy and anosognosia; complete functional dependence; and poor response to the rehabilitation). Functional neuroimaging could be a useful tool for a better understanding of these encephalopathies.

Adolescent↗

PubMed2002

Correlation of regional proton magnetic resonance spectroscopic metabolic changes with cognitive deficits in mild Alzheimer disease.

CONTEXT: The staging of Alzheimer disease (AD) dementia could be improved by a neurometabolic analysis using magnetic resonance spectroscopy. OBJECTIVE: To examine the correlation between regional cerebral metabolic alterations measured by proton magnetic resonance spectroscopy and neuropsychological dysfunctions in patients with early AD. DESIGN: A case-control study. SETTING: University hospital neurology clinic and radiology department. PARTICIPANTS: A cohort of 14 patients with mild AD and 14 control subjects paired for age and sex. INTERVENTIONS: Single-voxel proton magnetic resonance spectroscopic brain examination (60 minutes) and a comprehensive battery of psychometric tests (2 hours). MAIN OUTCOME MEASURES: Metabolite ratios relative to unsuppressed water were calculated for magnetic resonance spectroscopic metabolites (N-acetylaspartate, choline, creatine-phosphocreatine, and myo-inositol) in the medial temporal lobes (MTLs), parietotemporal cortices (PTCs), and frontal cortices of both hemispheres. Correlations were examined between metabolic changes in an area and psychometric scores of its known regional function: MTL and verbal memory, PTC and language and visuoconstructional abilities, and frontal cortices and executive functions. RESULTS: A significant reduction of N-acetylaspartate/water (H2O) in the left MTL and of choline/H2O in both MTLs, as well as a significant increase of myo-inositol/H2O in the right PTC were observed. Metabolic alterations in the left MTL were correlated with a loss of verbal memory, in the left PTC with language impairment, and in the right PTC with a loss of visuoconstructional abilities in the group with AD. CONCLUSION: These findings are consistent with regional distribution of neuropathologic changes and cognitive symptoms characterizing early phases of AD, and with the pattern of lateralization of normal brain function.

Aged↗

PubMed2003

A specific deficit in context processing in the unaffected siblings of patients with schizophrenia.

BACKGROUND: Understanding the biological basis of complex, heritable illnesses such as schizophrenia is facilitated by sensitive and functionally specific measures of intermediate processes. Context processing is a theoretically motivated construct associated with executive function. Impairments in this process have been associated with dysfunction of the prefrontal cortex. In the present study, we evaluated whether a specific deficit in context processing could be associated with the unexpressed genetic liability to schizophrenia. METHODS: Twenty-four patients with schizophrenia, 24 unaffected siblings and 36 control subjects completed a version of the AX task with (1) a condition that required context processing and (2) an expectancy condition in which intact context processing could lead to errors. RESULTS: Patients and unaffected siblings performed relatively worse in the context processing condition, whereas controls performed relatively worse in the expectancy condition. A double dissociation between siblings and controls (F = 9.5, P<.005) constituted strong evidence of a specific deficit in context processing associated with a familial or genetic liability to schizophrenia. Preliminary evidence of high diagnostic efficiency was also noted (specificity, 38%; and sensitivity, 100%). CONCLUSIONS: Context processing deficits have been associated with dorsolateral prefrontal cortex dysfunctions in schizophrenia. Such a dysfunction may occur even when genetic liability to schizophrenia is unexpressed clinically. The present method of demonstrating a double dissociation may be a useful approach to exploring endophenotypes related to specific cognitive and neural processes that can be measured in ways sensitive to subtle group differences.

Adult↗

PubMed2005

Spatial cognition in autism spectrum disorders: superior, impaired, or just intact?

The profile of spatial ability is of interest across autism spectrum disorders (ASD) because of reported spatial strengths in ASD and due to the recent association of Asperger's syndrome with Nonverbal Learning Disability. Spatial functions were examined in relation to two cognitive theories in autism: the central coherence and executive function (EF) theories. Performance on spatial tasks, EFs, and global/local processing was compared in children with ASD and controls. While the ASD group had faster reaction times on the Embedded Figures task, spatial performance was intact, but not superior, on other tasks. There was no evidence for impairments in EF or in processing global/local information, therefore contradicting these two theories. The implications of these results for these two theories are discussed.

Adolescent↗

PubMed2006

Pharmacogenetic tools for the development of target-oriented cognitive-enhancing drugs.

The identification of the anatomical and physiological substrates involved in the regulation of the dorsolateral prefrontal cortex function in humans provided the basis for the understanding of mechanisms involved in cognitive and executive function under normal as well as pathological conditions. In this context, substantial evidence indicates that alterations in monaminergic function in the dorsolateral prefrontal cortex significantly contributes to the cognitive impairments present in schizophrenia, attention deficit disorders, and other neuropsychiatric conditions. The development of a number of compounds that selectively increase extracellular dopamine (DA) concentrations in the dorsolateral prefrontal cortex but not in subcortical areas by either blocking its metabolism or reuptake, or increasing its release, or that directly activate postsynaptic DA-1 receptor mechanisms provided powerful pharmacotherapeutic tools to mitigate the cognitive deficits brought about by the dopaminergic alterations of the prefrontal cortex. More recently, the findings that polymorphisms of the catecholamine-O-methyl-transferase gene may also modify the effect of these drugs on the prefrontal cortex points toward a more specific genotype-based neuropsychopharmacology for the treatment of cognitive deficits in schizophrenia as well as in a number of other neuropsychiatric conditions. The ability of these compounds to increase DA load selectively in the frontal cortex and not on subcortical systems allows a targeted intervention without the stimulant-like effects observed with older drugs used to treat those conditions.

Benzhydryl Compounds↗

PubMed2006

Cognitive functions in carotid artery disease before endarterectomy.

Restorative effects of carotid endarterectomy (CEA) on cognitive functioning in patients with severe atherosclerotic disease presuppose the existence of cognitive deficits prior to the intervention. Thorough examination of this premise received only minor attention. The present study assessed symptomatic and asymptomatic patients with severe unilateral or bilateral stenosis of the carotid arteries one day before CEA. Healthy volunteers with similar demographic characteristics served as control subjects. Patients overall showed decreased functioning on tests of attention, verbal and visual memory, verbal fluency, and psychomotor speed and executive functioning, even after correction for the effects of mood. Simple motor skills and visuospatial functioning were not affected. Patients grouped according to presence and type of previous clinical symptoms and severity of contralateral stenosis only slightly differed from each other. The findings leave open the potential of improving cognitive function after CEA.

Aged↗

PubMedDate not supplied

From perception to action: temporal integrative functions of prefrontal and parietal neurons.

The dorsolateral prefrontal cortex (DPFC) and the posterior parietal cortex (PPC) are anatomically and functionally interconnected, and have been implicated in working memory and the preparation for behavioral action. To substantiate those functions at the neuronal level, we designed a visuomotor task that dissociated the perceptual and executive aspects of the perception-action cycle in both space and time. In that task, the trial-initiating cue (a color) indicated with different degrees of certainty the direction of the correct manual response 12 s later. We recorded extracellular activity from 258 prefrontal and 223 parietal units in two monkeys performing the task. In the DPFC, some units (memory cells) were attuned to the color of the cue, independent of the response-direction it connoted. Their discharge tended to diminish in the course of the delay between cue and response. In contrast, few color-related units were found in PPC, and these did not show decreasing patterns of delay activity. Other units in both cortices (set cells) were attuned to response-direction and tended to accelerate their firing in anticipation of the response and in proportion to the predictability of its direction. A third group of units was related to the determinacy of the act; their firing was attuned to the certainty with which the animal could predict the correct response, whatever its direction. Cells of the three types were found closely intermingled histologically. These findings further support and define the role of DPFC in executive functions and in the temporal closure of the perception-action cycle. The findings also agree with the involvement of PPC in spatial aspects of visuomotor behavior, and add a temporal integrative dimension to that involvement. Together, the results provide physiological evidence for the role of a prefrontal-parietal network in the integration of perception with action across time.

Animals↗

PubMed2004

Neurobehavioral correlates of sleep-disordered breathing in children.

The effects of sleep-disordered breathing (SDB) on neurobehavioral function were examined in two matched groups of children from the general population. Thirty-five children with polysomnographically confirmed SDB were matched for ethnicity, age, gender, maternal educational attainment, and maternal smoking, to healthy children with no evidence of SDB. Children with SDB had significantly lower mean scores on the Differential Ability Scales for General Conceptual Ability (similar to IQ) and for the Non-verbal Cluster. On the neuropsychology assessment battery (NEPSY), children with SDB scored significantly lower than the control group on the attention/executive function domain and two subtests within that domain, one measuring visual attention and the other executive function. In addition, children with SDB scored significantly lower than the controls on one subtest from the NEPSY language domain: Phonological Processing. This subtest measures phonological awareness, a skill that is critical for learning to read. No differences in behavior, as measured by the Child Behavior Checklist (CBCL) or the Conners' Parent Rating Scale, were found between the two groups. Using a novel algorithm to assess sleep pressure, we found that children with SDB were significantly sleepier than controls. Furthermore, total arousal index was negatively correlated with neurocognitive abilities, suggesting a role for sleep fragmentation in pediatric SDB-induced cognitive dysfunction.

Aptitude↗

PubMedDate not supplied

A single-photon emission computed tomography imaging study of driving impairment in patients with Alzheimer's disease.

Single-photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination (MMSE). Driving impairment in Alzheimer's disease is related to changes in cortical function which vary according to the severity of the disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the MMSE that are weighted toward left-hemisphere-based verbal tasks.

Activities of Daily Living↗

PubMed2005

Neuropsychological functioning in early- and late-onset obsessive-compulsive disorder.

Significant relationships have been noted between age of onset and demographics, clinical characteristics, and cerebral metabolic activity in obsessive-compulsive disorder (OCD). The authors investigated whether patients with early (N=21) and late (N=17) onset OCD differ with respect to neuropsychological functioning. Results revealed that the late onset OCD group obtained poorer scores on measures of executive function and auditory attention than the early onset group. Late onset OCD was also associated with poorer visual memory relative to healthy comparison subjects. These findings suggest that early and late onset OCD may be the result of at least partially differing neurobiological mechanisms.

Adolescent↗

PubMed2000

Atypical dementia and spastic paraplegia in a patient with primary lateral sclerosis and numerous necortical beta amyloid plaques: new disorder or Alzheimer's disease variant?

Primary lateral sclerosis (PLS) and hereditary spastic paraplegia (HSP) are clinically similar disorders in which progressive lower limb spasticity and corticospinal tract degeneration are characteristic. We report the occurrence of progressive spastic paraplegia and frontal systems dementia in a patient with postmortem features of PLS combined with moderate Alzheimer-like changes in neocortex and hippocampus. This combination of clinical and neuropathologic findings has not been described in PLS or HSP and varies from other cases in which spastic paraplegia, dementia, and Alzheimer neuropathology occurred concurrently. This 69-year-old woman developed spastic quadriplegia and dementia over 12 years. Left leg weakness progressed over 7 years to paraplegia, then quadriplegia by age 68. Sensory and cerebellar function were preserved and fasciculations were absent. Dementia characterized by concrete thinking, perseveration, and impaired executive function appeared in the seventh year and remained relatively stable until 6 months before death at age 69. Degeneration of the lateral corticospinal and dorsal spinocerebellar tracts confined to the spinal cord was evident at postmortem examination. Brain stem, midbrain, and cerebellum were normal. Numerous beta/A4 amyloid positive diffuse plaques (10-15/200x field) were apparent in neocortex, and neurofibrillary tangles immunopositive for paired helical filament were detected in hippocampus. This case broadens the spectrum of disorders associated with Alzheimer neuropathologic changes. The relationship between PLS, HSP, and Alzheimer's disease requires further study.

Aged↗

PubMed2000

Differential effects of cocaine and cocaine alcohol on neurocognitive performance.

OBJECTIVE: To investigate the dose-related effects of cocaine with or without alcohol use on the CNS by measuring performance on neurobehavioral tests. BACKGROUND: Chronic use of cocaine is associated with persistent decrements in cognitive function that are most pronounced in heavy users. Specific neurobehavioral deficits in areas such as executive function and impulsivity would make it difficult for the cocaine abuser to discontinue using drugs. Because alcohol is often used in conjunction with cocaine, the CNS effects of alcohol when taken with cocaine deserve further investigation. METHOD: The authors evaluated the dose-related effects of cocaine and alcohol use on performance in a variety of neuropsychological tests after 1 to 3 days of abstinence and again after 4 weeks of abstinence. Fifty-six chronic cocaine abusers who had used cocaine during the past 24 to 48 hours volunteered to perform a battery of neuropsychological tests on two separate occasions during a period of enforced abstinence. In addition to using cocaine, most of the volunteers consumed alcohol. Approximately half of the participants consumed more than 10 alcohol-containing drinks per week. RESULTS: After controlling for the effects of age, sex, and intelligence on performance, the authors found dose-related associations between neurobehavioral performance and cocaine dose and alcohol dose. When the influences of cocaine and alcohol on neurobehavioral performance were taken separately, cocaine and alcohol each selectively affected performance on different neurobehavioral tests after 1 to 3 days of abstinence, with these effects persisting after 4 weeks of abstinence. CONCLUSION: The concomitant use of cocaine and alcohol may have additive negative effects on the brain as compared to the use of only one of these two substances.

Adult↗

PubMed2005

Effect of catechol-O-methyltransferase val158met genotype on attentional control.

The cingulate cortex is richly innervated by dopaminergic projections and plays a critical role in attentional control (AC). Evidence indicates that dopamine enhances the neurophysiological signal-to-noise ratio and that dopaminergic tone in the frontal cortex is critically dependent on catechol-O-methyltransferase (COMT). A functional polymorphism (val158met) in the COMT gene accounts for some of the individual variability in executive function mediated by the dorsolateral prefrontal cortex. We explored the effect of this genetic polymorphism on cingulate engagement during a novel AC task. We found that the COMT val158met polymorphism also affects the function of the cingulate during AC. Individuals homozygous for the high-activity valine ("val") allele show greater activity and poorer performance than val/methionine ("met") heterozygotes, who in turn show greater activity and poorer performance than individuals homozygous for the low-activity met allele, and these effects are most evident at the highest demand for AC. These results indicate that met allele load and presumably enhanced dopaminergic tone improve the "efficiency" of local circuit processing within the cingulate cortex and thereby its function during AC.

Adult↗

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