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PubMed2005

Frontal glucose hypometabolism in abstinent methamphetamine users.

Changes in relative regional cerebral glucose metabolism (rCMRglc) and their potential gender differences in abstinent methamphetamine (MA) users were explored. Relative rCMRglc, as measured by (18)F-fluorodeoxyglucose positron emission tomography, and frontal executive functions, as assessed by Wisconsin card sorting test (WCST), were compared between 35 abstinent MA users and 21 healthy comparison subjects. In addition, male and female MA users and their gender-matched comparison subjects were compared to investigate potential gender differences. MA users had lower rCMRglc levels in the right superior frontal white matter and more perseveration and nonperseveration errors in the WCST, relative to healthy comparison subjects. Relative rCMRglc in the frontal white matter correlated with number of errors in the WCST in MA users. In the subanalysis for gender differences, lower rCMRglc in the frontal white matter and more errors in the WCST were found only in male MA users, not in female MA users, relative to their gender-matched comparison subjects. The current findings suggest that MA use causes persistent hypometabolism in the frontal white matter and impairment in frontal executive function. Our findings also suggest that the neurotoxic effect of MA on frontal lobes of the brain might be more prominent in men than in women.

Adult↗

PubMed2005

The sensitivity and specificity of the Middlesex Elderly Assessment of Mental State (MEAMS) for detecting cognitive impairment after stroke.

The aim of the study was to assess the sensitivity and specificity of the MEAMS (Golding, 1989) for detecting cognitive impairment after stroke. Stroke patients admitted to hospital received a cognitive screening assessment, the MEAMS, and a detailed cognitive assessment. The information obtained from the detailed assessment was summarised in a structured written report. From the conclusions in these reports, patients were classified as "impaired" or "not impaired" in perception, memory, executive function and language. The sensitivity and specificity of the MEAMS subtests and the overall number of tests passed were determined in relation to the presence of impairment, as given in the overall conclusion of the written reports. There were 30 stroke patients, aged 58 to 92 (mean 75.80, SD 7.94) years. Of these, 17 were men and 13 were women. The sensitivity of the MEAMS subtests ranged from 11% to 100% and the specificity ranged from 69% to 100%. The sensitivity of the overall MEAMS score was 52% and the specificity was 100%, using a cut-off score of 3 or more fails to indicate impairment. Three subtests, Orientation, Naming and Unusual views had 81% sensitivity and 50% specificity for detecting problems in language, perception or memory. The MEAMS was not a sensitive screen for overall cognitive impairment or for memory, perceptual, language, or executive function problems after stroke, but it was specific. Although screening for cognitive impairment is important, the MEAMS is not recommended as the sole method, as it produces an unacceptably high false negative rate. Three subtests (Orientation, Naming and Unusual views) had 81% sensitivity and 50% specificity for detecting cognitive problems in language, perception or memory after stroke.

Aged↗

PubMed2006

Basal ganglia-thalamocortical circuitry disruptions in schizophrenia during delayed response tasks.

BACKGROUND: Schizophrenia is characterized by executive functioning deficits, presumably mediated by prefrontal cortex dysfunction. For example, schizophrenia participants show performance deficits on ocular motor delayed response (ODR) tasks, which require both inhibition and spatial working memory for correct performance. METHODS: The present functional magnetic resonance imaging (fMRI) study compared neural activity of 14 schizophrenia and 14 normal participants while they performed ODR tasks. RESULTS: Schizophrenia participants generated: 1) more trials with anticipatory saccades (saccades made during the delay period), 2) memory saccades with longer latencies, and 3) memory saccades of decreased accuracy. Increased blood oxygenation level-dependent (BOLD) signal changes were observed in both groups in ocular motor circuitry (e.g., supplementary eye fields [SEF], lateral frontal eye fields [FEF], inferior parietal lobule [IPL], cuneus, and precuneus). The normal, but not the schizophrenia, group demonstrated BOLD signal changes in dorsolateral prefrontal regions (right Brodmann area [BA] 9 and bilateral BA 10), medial FEF, insula, thalamus, and basal ganglia. Correlations between percentage of anticipatory saccade trials and BOLD signal changes were more similar between groups for subcortical regions and less similar for cortical regions. CONCLUSIONS: These results suggest that executive functioning deficits in schizophrenia may be associated with dysfunction of the basal ganglia-thalamocortical circuitry, evidenced by decreased prefrontal cortex, basal ganglia, and thalamus activity in the schizophrenia group during ODR task performance.

Adult↗

PubMedDate not supplied

When the central executive lets us down: schemas, attention, and load in a generative working memory task.

Participants were asked to generate a single sequence of numbers in between two bounds. By varying the requested sequence length and way in which the question is posed, this paradigm enables assessment of the contributions to central executive functioning of schema, focus of attention, and load. With sequences of three or four numbers, a quarter of the sample failed fully to comply with the instructions. They generated an incorrect number of numbers or went outside the specified bounds. With sequences of six numbers, more than half of the sample infringed one or more of the constraints. Participants consistently generated sequences with particular generic properties. The overall frequency and patterns of infringements suggest that a substantial proportion of participants focused their conceptual attention on sequence content and often neglected the problem of how thelength and boundary constraints were going to be evaluated either before or during response delivery.

Attention↗

PubMed2005

Double-blind, placebo-controlled study of modafinil for fatigue and cognition in schizophrenia patients treated with psychotropic medications.

OBJECTIVE: To assess the effects of modafinil on fatigue, symptoms, attention, working memory, and executive functioning in schizophrenia patients treated with psychotropic medications. METHOD: Twenty-four patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder (10 men and 14 women) were randomly assigned to modafinil up to 200 mg a day (N = 13) or placebo (N = 11) as an adjunct therapy in an 8-week, double-blind, placebo-controlled study. Data were collected from May 18, 2001 to September 11, 2003. RESULTS: Four subjects terminated the study early, including one because of worsening of psychosis during the first week taking modafinil. In the modafinil (N = 10) and placebo (N = 10) groups, fatigue improved significantly over time (p < .01), but there were no differences between groups on changes in fatigue, positive and negative symptoms, or cognition. CONCLUSION: Fatigue improved in both groups, and there were no differences between groups on changes in fatigue, symptoms, attention, working memory, or executive functioning. Lack of differences between groups may be due to small sample size or possible regression to the mean in the placebo group.

Adult↗

PubMed2002

Apathy in Parkinson's disease.

OBJECTIVE: To assess apathy in patients with Parkinson's disease and its relation to disability, mood, personality, and cognition. METHODS: Levels of apathy in 45 patients with Parkinson's disease were compared with a group of 17 similarly disabled patients with osteoarthritis. Additional neuropsychiatric data were collected concerning levels of depression, anxiety, and hedonic tone. Personality was assessed with the tridimensional personality questionnaire. Cognitive testing included the mini-mental state examination, the Cambridge examination of cognition in the elderly, and specific tests of executive functioning. RESULTS: Patients with Parkinson's disease had significantly higher levels of apathy than equally disabled osteoarthritic patients. Furthermore, within the Parkinson sample, levels of apathy appear to be unrelated to disease progression. The patients with Parkinson's disease with the highest levels of apathy where not more likely to be depressed or anxious than those with the lowest levels of apathy, though they did show reduced hedonic tone. No differences in personality traits were detected in comparisons between patients with Parkinson's disease and osteoarthritis, or between patients in the Parkinson group with high or low levels of apathy. As a group, the patients with Parkinson's disease tended not to differ significantly from the osteoarthritic group in terms of cognitive skills. However, within the Parkinson's disease sample, the high apathy patients performed significantly below the level of the low apathy patients. This was particularly evident on tests of executive functioning. CONCLUSIONS: Apathy in Parkinson's disease is more likely to be a direct consequence of disease related physiological changes than a psychological reaction or adaptation to disability. Apathy in Parkinson's disease can be distinguished from other psychiatric symptoms and personality features that are associated with the disease, and it is closely associated with cognitive impairment. These findings point to a possible role of cognitive mechanisms in the expression of apathy.

Activities of Daily Living↗

PubMed2004

Random number generation in patients with symptomatic and presymptomatic Huntington's disease.

Random number generation (RNG), which involves producing lists of numbers at random, requires response selection and inhibition, which are aspects of executive function mediated by the frontal lobe. This study examined RNG performance in a group of mild to moderate Huntington's disease (HD) patients, asymptomatic gene-positive HD patients, and controls. The HD symptomatic group was significantly less random in their choices than controls. The gene-positive asymptomatic HD patients also showed a tendency toward abnormal RNG measures compared with controls, although this did not reach statistical significance after correction for multiple comparisons. However, analyzing the HD group as a whole showed that the frequency of errors, preferential selection of favorite numbers, and counting in 1's correlated significantly with the degree of symptom severity. Furthermore, counting in 1's correlated with degree of vulnerability to symptoms. A subset of patients and controls were retested 6 months later, and all RNG measures showed high correlations over time, highlighting the robust reliability of this test. The data therefore suggest that RNG is a useful, brief and reliable test of executive function and may be of value in studies investigating the longitudinal effects of disease-modifying treatment in HD.

Adult↗

PubMed2002

Reduced cognitive abilities in lead-exposed men.

OBJECTIVES: Since it is still controversial whether-low-to moderate long-term lead exposure below current threshold values causes neurobehavioural deficits in adults, we investigated executive functions of the prefrontal cortex, attention, and visuospatial and visuomotor functioning in lead-exposed subjects. METHODS: Forty-seven lead-exposed subjects with a mean blood lead (PbB) level of 30.8 microg/100 ml and 53 non-lead-exposed aged-matched subjects (PbB: 4.32 microg/100 ml) with the same socio-economic background were investigated. Both groups were also matched on verbal intelligence. Neuropsychological tests were done by the modified Wisconsin card sorting test, block design test, visual recognition test, simple reaction time, choice reaction and digit symbol substitution. Lead exposure was assessed by current and cumulative measures. RESULTS: While there were significant differences in the results of the Wisconsin, block design and visual recognition tests, no differences were found in simple reaction time, choice reaction and digit symbol substitution. Significant correlations existed between current exposure and cognitive deficits. No correlation was found between cumulative exposure measures and cognitive parameters. CONCLUSIONS: Our results show that PbB below 70 microg/100 ml reduce neurobehavioural abilities, particularly visuospatial abilities and executive functions referring to the prefrontal cortex. As neurobiological substrate of the prefrontal dysfunction, glutamatergic system disturbances are discussed.

Adult↗

PubMed2005

Stroop interference task and single-photon emission tomography in anorexia: a preliminary report.

OBJECTIVE: The aim of this preliminary study was to investigate the physiologic substrate of executive function in anorexia nervosa (AN) by assessing the relation between brain perfusion and Stroop interference task (SIT). METHOD: The classical SIT test and brain single-photon emission tomography (SPET) were evaluated in 16 AN females (mean age = 23.69 +/- 8.68 years; mean body mass index [BMI] = 16.19 +/- 1.53 kg/m2). The relation between the two examinations was searched by statistical parametric mapping (SPM 99) with a height threshold of p = .001. RESULTS: An abnormally low or a borderline SIT value was found in 25% of patients. A significant correlation between the SIT score and brain perfusion was found in the superior frontal gyrus of both hemispheres (Brodmann's area [BA] 6 in both hemispheres and BA 8 in the right hemisphere). No correlation was found in the anterior cingulate gyrus. CONCLUSION: BA 6 and BA 8 and the anterior cingulate are believed to be the basis of both error detection and immediate correction. Activity of BA 6 and BA 8 reflects this executive task in AN patients as well, whereas the lack of correlation in the anterior cingulate may suggest its blunted activity in AN patients, similarly to what is shown in other conditions characterized by impaired executive function, such as patients with depression, patients with schizophrenia, and abstinent drug abusers. However, these findings should still be quoted as preliminary, given some limitations of the study design, such as the lack of a control group, and the unfeasibility of controlling some relevant confounding variables, such as psychiatric comorbidity, medication, and the time interval between examinations, mainly deriving from the relatively few patients studied.

Adolescent↗

PubMed2006

[Dopamine system genes interaction and neurocognitive traits in patients with schizophrenia, their relatives and healthy controls from general population].

To elucidate main effects of dopamine receptor D4 (DRD4) and cathecol-O-methyltransferase (COMT) genes as well as their interaction effect on neurocognitive traits, DRD4 gene polymorphisms (-809G/A, -521C/T) and the COMT gene Val158Met polymorphism, along with characteristics of verbal memory, executive functions and peculiarities of associative processes, have been studied in 150 patients with schizophrenia, 83 their relatives and 118 mentally healthy subjects without positive family history of psychosis. A main effect of -521C/T polymorphism and DRD4 (-521C/T).Vall58Met polymorphisms interaction were found for verbal fluency, carriers of the Val/Val+CC and the Met/Met+TT genotypes performing better on this task as compared to other genotypes. An interaction DRD4 (-521C/T).Val158Met effect on originality of speech associations was observed in the combined group of unaffected individuals (relatives and controls), with lower scores of the trait in those with the Met/Met+CC genotype. The COMT-DRD4 (-809G/A) interaction effect on working memory was demonstrated for patients and unaffected individuals, homozygotes for the Val and the G alleles having the best results and homozygotes for the Met and the A alleles--the worst ones. The data obtained suggest the relationship of DRD4 and COMT genes with different characteristics of executive functions but not with verbal memory.

Adult↗

PubMed2006

Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson's disease: a meta-analysis.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN DBS) is an increasingly common treatment for Parkinson's disease. Qualitative reviews have concluded that diminished verbal fluency is common after STN DBS, but that changes in global cognitive abilities, attention, executive functions, and memory are only inconsistently observed and, when present, often nominal or transient. We did a quantitative meta-analysis to improve understanding of the variability and clinical significance of cognitive dysfunction after STN DBS. METHODS: We searched MedLine, PsycLIT, and ISI Web of Science electronic databases for articles published between 1990 and 2006, and extracted information about number of patients, exclusion criteria, confirmation of target by microelectrode recording, verification of electrode placement via radiographic means, stimulation parameters, assessment time points, assessment measures, whether patients were on levodopa or dopaminomimetics, and summary statistics needed for computation of effect sizes. We used the random-effects meta-analytical model to assess continuous outcomes before and after STN DBS. FINDINGS: Of 40 neuropsychological studies identified, 28 cohort studies (including 612 patients) were eligible for inclusion in the meta-analysis. After adjusting for heterogeneity of variance in study effect sizes, the random effects meta-analysis revealed significant, albeit small, declines in executive functions and verbal learning and memory. Moderate declines were only reported in semantic (Cohen's d 0.73) and phonemic verbal fluency (0.51). Changes in verbal fluency were not related to patient age, disease duration, stimulation parameters, or change in dopaminomimetic dose after surgery. INTERPRETATION: STN DBS, in selected patients, seems relatively safe from a cognitive standpoint. However, difficulty in identification of factors underlying changes in verbal fluency draws attention to the need for uniform and detailed reporting of patient selection, demographic, disease, treatment, surgical, stimulation, and clinical outcome parameters.

Chi-Square Distribution↗

PubMed2003

Development of pro- and antisaccades in children with attention-deficit hyperactivity disorder (ADHD) and healthy controls.

To date, the investigation of the antisaccade task, a simple test of "executive functions," in children with ADHD has yielded inconsistent results. The present study aimed at contributing to this issue by (a) the investigation of a large sample of carefully diagnosed ADHD patients aged 7-15 years, and (b) the analyses of differential age effects in patients and controls. Healthy control children were pairwise matched with patients (N = 46; age = 136 +/- 24 months) for age and gender, and did not significantly differ in IQ. Horizontal pro- and antisaccades were elicited under the 200-ms gap and overlap conditions (blocks of 100 trials each). Overall, patients exhibited (a) augmented pro- and antisaccadic reaction times, (b) augmented error rates (antitasks), (c) augmented proportions of early responses (all conditions), and (d) reduced proportions of express saccades under the prosaccadic gap condition. The greater decline in anti- as compared to pro-SRT with increasing age that characterized controls was missing in patients. Confirming Barkley's (1997) neuropsychological theory of ADHD, these results altogether point to alterations in "executive functions" in ADHD patients that are presumably supported by frontal lobe structures, in particular the lateral prefrontal cortex and the frontal eye fields.

Adolescent↗

PubMed1998

Autism and visual agnosia in a child with right occipital lobectomy.

OBJECTIVES: Autistic disorder is a developmental handicap with an unknown neurological basis. Current neuropsychological models for autism suggest an abnormal construction of visual perceptual representation or a deficit in executive functions. These models predict cerebral lesions in the temporo-occipital or frontal regions of autistic patients. The present study aimed at studying the presence of symptoms of autism and visual agnosia in a 13 year old girl who had a right temporo-occipital cortical dysplasia that was surgically removed at the age of 7. METHODS: Neuropsychological evaluation included Wechsler and Kaufman intelligence scales, a test of word fluency, digit span, Corsi block, California verbal learning, Trail making, Benton facial recognition, Snoodgrass object recognition tests, Rivermead face learning subtest, and developmental test of visual perception. The ADI-R was used to show current and retrospective diagnosis of autistic disorder. Neuroimagery included brain MRI, single photon emission computed tomography (SPECT), and PET. RESULTS: Brain MRI showed a right occipital defect and an abnormal hyperintensity of the right temporal cortex. PET and SPECT disclosed a left frontal hypometabolism together with the right occipital defect. Neuropsychological testing showed a visual apperceptive agnosia and executive function deficits. Psychiatric study confirmed the diagnosis of autistic disorder. CONCLUSIONS: Although the possibility that autism and visual agnosia were dissociable factors in this patient cannot be excluded, the finding of both deficits supports the possibility that occipito-temporal lesions can predispose to the development of autism.

Adolescent↗

PubMed2003

Performance of girls with ADHD and comparison girls on the Rey-Osterrieth Complex Figure: evidence for executive processing deficits.

In spite of a multitude of scoring approaches, the ability of the Rey-Osterrieth Complex Figure (ROCF) to measure executive functions versus grapho-motor skill is still open to question. To clarify this issue, we examined the performance of an ethnically and socioeconomically diverse sample of preadolescent girls (ADHD-Combined, n = 93; ADHD-Inattentive, n = 47; and comparison girls, n = 88) on the ROCF, scoring both immediate copy and delayed recall performance. Girls with ADHD performed the task following a stimulant medication washout. Dependent measures were the established Developmental Scoring System variables of Organization, Accuracy, and Style, plus an operationalized and extensively detailed scoring of errors, featuring an error proportion score (EPS). The major finding is that only EPS differentiated girls with ADHD from comparison girls (a) on both immediate and delayed performance and (b) with stringent statistical control of Performance IQ, fine motor speed, and performance on the Porteus Mazes (as well as comorbidities), with effect sizes in the medium range. Perseverative errors contributed significantly to EPS. Overall, error scores on the ROCF appear to tap planning, a key executive function, and are quite sensitive to deficits in this domain for girls with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Decreased frontal white-matter integrity in abstinent methamphetamine abusers.

This study explored differences in frontal white-matter (WM) integrity between methamphetamine (MA) abusers and healthy comparison subjects using diffusion tensor imaging (DTI). Fractional anisotropy (FA) values, which indicate WM integrity, were calculated for regions-of-interest in frontal WM on diffusion tensor images of 32 MA abusers and 30 healthy comparison subjects. Frontal executive functions were also assessed by the Wisconsin Card Sorting test (WCST). MA abusers had significantly lower FA values in bilateral frontal WM at the anterior commissure-posterior commissure (AC-PC) plane and the right frontal WM 5 mm above the AC-PC plane relative to healthy comparison subjects. MA abusers had more total, perseveration and non-perseveration errors in the WCST relative to healthy comparison subjects. FA values of the right frontal WM 5 mm above the AC-PC plane negatively correlated with the number of total and non-perseveration errors in the WCST in MA abusers. In the sub-analysis for gender differences, lower FA values in frontal WM and more errors in the WCST were found only in male MA abusers, not in female MA abusers, relative to comparison subjects of the respective gender. We report that frontal WM integrity of MA abusers is compromised. This finding may also be related to impairment in frontal executive function. In addition, the neurotoxic effect of MA on frontal WM may be less prominent in women than in men, possibly due to oestrogen's neuroprotective effect.

Adult↗

PubMed1998

Conversational discourse abilities following severe traumatic brain injury: a follow-up study.

The major aim of this study was to describe the conversational abilities of a group of severely injured TBI speakers, at a minimum of 2 years post-injury. The association between conversational impairment and (a) selected measures of executive function and (b) psychosocial handicap was also examined. Twenty-four members of the group of 26 severely injured TBI speakers who had initially been assessed between 3 and 6 months post-injury were reviewed at a minimum of 2 years post-injury (mean = 2 years, 10 months). At initial assessment, TBI speakers were compared with non-TBI orthopaedic patients and with a group of university students. At follow-up, however, they were compared only with the orthopaedic patients. Conversational assessment was carried out using a modified form of Damico's Clinical Discourse Analysis. As a group, the TBI speakers' conversational abilities did not improve over time. There was, however, a subgroup (n = 8) of speakers who did improve, and these could be distinguished by greater initial severity of injury and a significantly longer period of speech-language pathology intervention than the speakers who either remained the same or worsened over time. Modest associations between conversational discourse skills and measures of executive function and a measure of psychosocial handicap were identified. These findings indicate that disruptions in conversation persist into the longer term. More assiduous efforts may need to be made to (a) identify subtle discourse changes in the early months after injury and (b) engage TBI speakers in speech-language pathology services. Such services are also required over a longer time frame, in community-based models of service provision.

Adolescent↗

PubMed2005

Selected executive skills in adolescents with recent first episode major depression.

BACKGROUND: To investigate whether recent first episode major depression in adolescence is characterised by selected executive difficulties in attentional flexibility, behavioural inhibition and decision-making. METHODS: Selected executive functions were compared in adolescents with recent (past year) first episode major depression (n = 30) and community controls (n = 49). Three computerised tests within the CANTAB battery were completed by all subjects (the Intra-Dimensional, Extra-Dimensional Set-Shifting task, the Affective Go, No-Go task, and the Decision-Making task). RESULTS: Compared with controls, recently depressed cases displayed a bias towards negative stimuli with fewer errors on sad words as well as being more accurate in their responses to sad targets on the Affective Go, No-Go task. Cases also made faster decisions in the context of betting more of their available points compared to controls, as indexed by the Decision-Making task. These results were not influenced by age, gender, IQ, recent mood, severity of depression, medication or comorbidity. CONCLUSIONS: Adolescents with recent first episode major depression show greater attention towards sad stimuli and more impulsive behaviour when making decisions. They were able to switch attentional set to neutral stimuli. This study demonstrates that computerised tests for measuring executive functions can be successfully deployed in adolescents, and suggests that specific patterns of neuropsychological functions may be relatively compromised in first episode major depression. These, together with their underlying neural substrates, deserve further investigation within this age range.

Adolescent↗

PubMed2005

Subtle executive impairment in children with autism and children with ADHD.

BACKGROUND: The executive functions of inhibition, planning, flexible shifting of actions, and working memory are commonly reported to be impaired in neurodevelopmental disorders. METHOD: We compared these abilities in children (8-12 years) with high functioning autism (HFA, n = 17), attention deficit-hyperactivity disorder (ADHD, n = 21) and healthy controls (n = 32). Response inhibition was assessed using the Stroop Color and Word Test (Golden, 1978). Problem solving, set-shifting, and nonverbal memory were assessed using three tasks, respectively, from the CANTAB (Cambridge Cognition, 1996): the Stockings of Cambridge task; the Intra-Dimensional/Extra-Dimensional set-shifting task; and the Spatial Working Memory task (SWM) with tokens hidden behind 3, 4, 6, and 8 boxes. RESULTS: There were no group differences on the response inhibition, planning, or set-shifting tasks. On the SWM task, children with HFA made significantly more between-search errors compared with controls on both the most difficult problems (8-box) and on the mid-difficulty problems (6-box); however, children with ADHD made significantly more errors compared to controls on the most difficult (8-box) problems only. CONCLUSION: Our findings suggest that spatial working memory is impaired in both ADHD and HFA, and more severely in the latter. More detailed investigation is needed to examine the mechanisms that differentially impair spatial working memory, but on this set of tasks there appears to be sparing of other executive functions in these neuropsychiatric developmental disorders.

Attention Deficit Disorder with Hyperactivity↗