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Impairment of executive function induced by hypertension in the rhesus monkey (Macaca mulatta).

The effects of chronic, untreated hypertension on executive function were investigated in a nonhuman primate model of hypertensive cerebrovascular disease. Executive function was assessed with the Conceptual Set-Shifting Task (CSST). a task adapted from the human Wisconsin Card Sorting Test (WCST). Like the WCST, the CSST requires abstraction of a stimulus set, followed by a series of set shifts. Performance on the CSST by 7 young adult monkeys (Macaca mulatta) with surgically induced hypertension was compared with that of 6 normotensive monkeys. The hypertensive group was significantly impaired relative to the normotensive group in abstraction and set shifting. Although the neural basis of this impairment is unclear, evidence from studies with humans and monkeys suggests that the prefrontal cortex may be the locus for this effect of hypertension.

Animals↗

Spatial reversal as a measure of executive functioning in children with autism.

The purpose of this experiment was to compare the executive functioning performance of children with autism with chronological- and verbal-matched controls in a spatial-reversal task. Three groups of children participated in this experiment. One group was identified as having autism (7 boys), the 2nd group contained 7 typically developing children (6 boys, 1 girl) who were matched to the 1st group based on their verbal performance, and the 3rd group contained 7 typically functioning children (6 boys, 1 girl) matched to the 1st group based on chronological age. Each group was given a spatial-reversal task containing 2 problems. In the 1st problem, children selected a toy on a particular side in a pair. In the 2nd problem, the contingencies were reversed such that children were to choose the toy on the opposite side. Children with autism generally performed worse than comparison groups as indicated by their overall higher rate of errors. However, these results must be qualified by considering the performance for each problem: Errors for the children with autism were infrequent during the 1st problem but increased in the 2nd, whereas errors for comparison children showed the opposite pattern. When these results from the spatial-reversal task were interpreted from the perspective of hypothesis-testing theory, the executive functioning deficiency of children with autism was found to involve the selection and testing of stereotypic response sets that were not likely to be revised or changed flexibly according to feedback from the environment or the demands of the task.

Autistic Disorder↗

Acquisition and short-term retention of inhaler techniques require intact executive function in elderly subjects.

BACKGROUND: patients with dementia are almost invariably unable to use any form of inhaler. Some elderly patients are unable to learn to use a metered dose inhaler or Turbohaler despite a normal abbreviated mental test score. Studies have shown that in many people this is due to unrecognised cognitive impairment and/or dyspraxia. The executive domains of cognition are particularly important in planning and sequencing; it might be expected therefore that disordered frontal (executive) function could be a predictor of poor inhaler technique in subjects with no overt features of dementia. OBJECTIVE: to explore the relationship between cognitive, and executive, function and the ability to acquire metered dose inhaler and Turbohaler technique in old age. DESIGN: a prospective randomised observational study with blinded evaluation. SUBJECTS: 30 inhaler-naive inpatients (21 female) with a mean age of 85 (range 75-94) and having a normal (8-10) abbreviated mental test score. METHODS: subjects received standardised metered dose inhaler and Turbohaler training and were scored on an analogue scale (for metered dose inhaler) or for competence (Turbohaler) the following day. The Mini-Mental State Examination and EXIT25 (for executive function) were performed by separate observers. RESULTS: significant correlation was found between the metered dose inhaler score and Mini-Mental State Examination (r 0.540, P<0.002) and EXIT25 (r -0.702, P<0.0001). Threshold effects emerged for the metered dose inhaler in that 18/19 with a competent score compared to 2/11 scored as incompetent had a Mini-Mental State Examination of >23 (P<0.01) and 19/19 compared to 0/11 had an EXIT25 of <15 (P<0.01). Similarly, for the Turbohaler 21/21 of the competent subjects had a Mini-Mental State Examination of >23 compared with 3/9 incompetent subjects (P<0.01), with 21/21 competent compared with 0/9 incompetent having an EXIT25 <15 (P<0.01). CONCLUSION: acquisition and short-term retention of metered dose inhaler and Turbohaler techniques is unlikely to be successful in frail elderly people who have an abnormal Mini-Mental State Examination and/or EXIT25 test. The latter test, when abnormal, is probably the superior predictor of inability to learn inhaler techniques.

Aged↗

Executive function and verbal working memory in adolescents with closed head injury (CHI).

The relationship between executive function (EF) and working memory (WM) was studied in eight adolescents with closed head injury (CHI) and eight controls, matched for age, gender and socioeconomic status (SES). A cognitive-linguistic test (Scales of Cognitive Ability for Traumatic Brain Injury, SCATBI) was used to group CHI participants by seventy. EF was tested with a measure of daily functioning (Pro-Ex) and WM was tested with a recognition memory task (RMT). When all subject test data were grouped, a positive linear correlation was found for the Pro-Ex and the RMT. A strong-to-moderate positive correlation was found for components of the EF measure and the RMT. Severity of injury influenced test performance for both the EF and WM measures, with a significance between group effects found on the RMT task. Results indicate a relationship between executive function and working memory, severity of injury and test performance and the need to assess EF of CHI adolescents with a measure of daily functioning.

Activities of Daily Living↗

Tests of executive functioning predict scores on the MacAndrew Alcoholism Scale.

1. Previous work reported that tests of executive functioning (EF) predict the risk of alcoholism in subject populations selected for a "high density" of a family history of alcoholism and/or the presence of sociopathic traits. The current experiment examined the ability of EF tests to predict the risk of alcoholism, as measured by the MacAndrew Alcoholism Scale (MAC), in outpatient subjects referred to a general neuropsychological testing service. 2. Sixty-eight male and female subjects referred for neuropsychological testing were assessed for their past drinking histories and administered the Wisconsin Card Sorting Test, the Wechsler Adult Intelligence Scale-Revised, the Trails (Part B) Test, and the MAC. Principal Components analysis (PCA) reduced the number of EF tests to two measures, including one that loaded on the WCST, and one that loaded on the Similarities, Picture Arrangement, and Trails tests. Multiple hierarchical regression first removed the variance from demographic variables, alcohol consumption, and verbal (i.e., Vocabulary) and non-verbal (i.e., Block Design) IQ, and then entered the executive functioning factors into the prediction of the MAC. 3. Seventy-six percent of the subjects were classified as either light, infrequent, or non-drinkers on the Quantity-Frequency-Variability scale. The factor derived from the WCST on PCA significantly added to the prediction of risk on the MAC (p = .0063), as did scores on Block Design (p = .033). Relatively more impaired scores on the WCST factor and Block Design were predictive of higher scores on the MAC. The other factors were not associated with MAC scores. 4. These results support the hypothesis that decrements in EF are associated with risk factors for alcoholism, even in populations where the density of alcoholic behaviors are not unusually high. When taken in conjunction with other findings, these results implicate EF test scores, and prefrontal brain functioning, in the neurobiology of the risk for alcoholism.

Adult↗

Executive functions in young children with autism.

The executive dysfunction hypothesis of autism has received support from most studies of older people with autism; however, studies of young children have produced mixed results. Two studies are presented that compare the performance of preschoolers with autism (mean = 51 months/4.3 years of age) to a control group matched on age, and verbal and nonverbal ability. The first study (n = 18 autism and 17 control) found no group differences in performance on 8 executive function tasks (A not B, Object Retrieval, A not B with Invisible Displacement, 3-Boxes Stationary and Scrambled, 6-Boxes Stationary and Scrambled, and Spatial Reversal), but did find that children with autism initiated fewer joint attention and social interaction behaviors. The second (longitudinal) study of a subset of the children (n = 13 autism and 11 control) from the first study found that neither groups' performance on Spatial Reversal changed significantly over the course of a year. The results of these studies pose a serious challenge to the executive dysfunction hypothesis of autism.

Attention↗

Executive functions in dyslexia.

This study focused on executive functions in dyslexia. A group of 43 heavily-affected young dyslexics, divided into two groups based on the results of a receptive language test, and 20 non-dyslexic controls, were tested with a Dichotic Listening Test, the Stroop Color Word Test and the Wisconsin Card Sorting Test. The dyslexic subjects demonstrated significant impairment on all tasks, but with different patterns of impairment according to the subgrouping. The subgroups were equally impaired on the Dichotic Listening Test, but differed on the Stroop and the Wisconsin Tests. The data support a hypothesis suggesting executive problems in dyslexia, depending on receptive language skills.

Adolescent↗

Executive function in alcohol use disorder with low psychiatric comorbidity: Comparison with a non-clinical sample and predictive value for treatment outcome.

BACKGROUND: Executive functions (EF) encompass abilities such as planning, decision-making, and inhibitory control, critical for learning, establishing and maintaining behavioral change. The association between alcohol use disorder (AUD) and impairments in EF are well established. However, prior research is dominated by studies on convenience samples including individuals with severe AUD with high levels of psychiatric comorbidity, which limits generalizability. The present study therefore aimed to investigate the degree of impairment and predictive ability of EF, on alcohol consumption, among individuals with moderate AUD with low levels of psychiatric comorbidity. METHODS: Adults with moderate AUD (n&#x2009;=&#x2009;147) were recruited at three specialized addiction outpatient clinics in Stockholm, to a randomized controlled trial investigating the efficacy of two psychological treatments. Participants underwent neuropsychological testing before treatment. Eight tests from the CANTAB&#xae; battery were administered at baseline, assessing mental flexibility, sustained attention, visuospatial working memory, response inhibition, and delay discounting. Assessments of alcohol use and related symptoms were conducted at baseline, the 12- and 26-weeks follow-up. A non-clinical reference sample (n&#x2009;=&#x2009;72) completed corresponding CANTAB&#xae; tests. The two groups were compared regarding EF using descriptive statistics and t-tests, and the predictive value of EF for reduction in alcohol consumption, was investigated using multiple regression models. RESULTS: Individuals with AUD did not perform worse on any of the tests on executive function (CANTAB&#xae;) as compared to the non-clinical reference sample. Measures of EF were not significant predictors for reduction in alcohol use for the 12-week, or the 26-week follow-up. CONCLUSIONS: EFs were not impaired and were not a clinically relevant predictor of treatment outcomes in this population with AUD. Future research on EF as a predictor in AUD treatment, needs to corroborate the present findings, and include other populations, e.g., with different socio-economic backgrounds and by including other methodologies for measuring EF.

Humans↗

Is a mild deficit in executive functions in boys related to childhood ADHD or to parental multigenerational alcoholism?

A mild deficit in executive functions has been hypothesized to be associated with attention deficit hyperactivity disorder (ADHD), with externalizing problem behaviors such as conduct disorder (CD) and with the vulnerability to alcoholism in sons of multi-generational alcoholics (SOMGAs). These three categories overlap, which raises concerns about the specificity of the hypothesized associations. In the present study, measures of executive functions (EFs) were tested in seventy-six 7- to 11-year-old boys: boys with ADHD but without a family history of addiction, SOMGAs, and controls. Specific deficits in EFs were found for boys with ADHD but not for SOMGAs. The association between a deficit in EFs and attention problems remained after controlling for externalizing problem behaviors, but not for the reverse. These results suggest that a mild deficit in EFs is specifically related to ADHD and that the deficits reported in boys with CD and in SOMGAs are due to relatively high attentional problems in these groups or due to other factors such as motivation.

Alcoholism↗

Executive functions and P300 latency in elderly depressed patients and control subjects.

The authors asked whether impaired executive functioning and long P300 latency are related dysfunctions and whether they are associated with geriatric depression. A group of 25 elderly depressed patients without dementia and 20 control subjects were assessed on tasks of fluency, initiation and perseveration, the Stroop task, the Wisconsin Card Sorting Test (WCST) perseverative error score, and P300 latency. The groups' performance differed significantly on these tasks and in P300 latency. Longer latency was associated with poorer performance in both groups on all measures except WCST perseverative errors. Regardless of patients' depression status, increased P300 latency predicts poorer performance on executive function tasks requiring speeded performance.

Aged↗

Tryptophan depletion, executive functions, and disinhibition in aggressive, adolescent males.

Low serotonin has been associated with aggressive behavior and impulsivity. Executive functions (cognitive abilities involved in the initiation/maintenance of goal attainment) have also been related to aggression. We tested whether dietary depletion of tryptophan, the amino acid precursor of serotonin, would increase disinhibition (impulsivity) in aggressive male adolescents. Cognitive-neuropsychological variables predictive of disinhibition were explored. Stable aggressive and nonaggressive adolescent men received balanced and tryptophan-depleted, amino acid mixtures separately (counterbalanced, double-blind). Commission errors on a go/no-go learning task (i.e., failures to inhibit responding to stimuli associated with punishment/nonreward) measured disinhibition. Aggressive adolescent males made more commission errors as compared to nonaggressives. Lower executive functioning was significantly related to commission errors over and above conventional memory abilities. Tryptophan depletion had no effect on commission errors in the aggressive adolescents, possibly because of a ceiling effect.

Adolescent↗

Executive function and magnetic resonance imaging subcortical hyperintensities in vascular dementia.

OBJECTIVE: To determine the relation between subcortical hyperintensities (SHs) visible on magnetic resonance imaging and executive function among patients with vascular dementia. BACKGROUND: The relation between SHs and executive dysfunction is not well understood, because studies have varied widely in methodology and have produced conflicting results. METHOD: We examined the relation between SHs (expressed as a percentage of total brain volume, not including ventricular volume) and six tests of executive function in a well-defined group of 24 individuals with vascular dementia. Executive tests were divided in two groups: Attention/Speed and Abstraction/Problem Solving. Bivariate correlations were computed between individual neuropsychological variables and SHs. RESULTS: Results showed significant bivariate correlations between SHs and three of the four tests in the Attention/Speed domain. Subcortical hyperintensities shared virtually no association with performance on tests in the Abstraction/Problem-Solving domain. CONCLUSIONS: The finding that SHs are significantly associated with psychomotor slowing and attentional dysfunction is consistent with what is known about the behavioral manifestations of subcortical disease. More detailed investigations of the regional distribution of SHs as well as measures of atrophy, hypoperfusion, and hypometabolism may be necessary to accurately characterize the complex relation between vascular disease and different aspects of executive dysfunction.

Aged↗

Dissociating executive functions of the prefrontal cortex.

An analysis is provided of three distinct paradigms that have been used to study executive functions of the prefrontal cortex involving planning, self-ordered memory or attentional set-shifting. Psychological and anatomical dissociations are sought from the perspective of studies of patients with frontal lobe lesions, functional neuroimaging, psychometric studies in normal volunteers and experimental studies in non-human primates. Particular attention is paid to attempts to dissociate mnemonic from other executive capacities. Thus, patients with frontal damage are shown to have deficits in their (1) use of strategies to improve performance in a spatial working memory task and (2) capacity to make an extra-dimensional shift due to a high-order failure of inhibition in an attentional set-shifting paradigm. These results are discussed in terms of anatomical and neuropharmacological dissociations of different aspects of executive function within the prefrontal cortex shown in monkeys.

Animals↗

The unity and diversity of executive functions and their contributions to complex "Frontal Lobe" tasks: a latent variable analysis.

This individual differences study examined the separability of three often postulated executive functions-mental set shifting ("Shifting"), information updating and monitoring ("Updating"), and inhibition of prepotent responses ("Inhibition")-and their roles in complex "frontal lobe" or "executive" tasks. One hundred thirty-seven college students performed a set of relatively simple experimental tasks that are considered to predominantly tap each target executive function as well as a set of frequently used executive tasks: the Wisconsin Card Sorting Test (WCST), Tower of Hanoi (TOH), random number generation (RNG), operation span, and dual tasking. Confirmatory factor analysis indicated that the three target executive functions are moderately correlated with one another, but are clearly separable. Moreover, structural equation modeling suggested that the three functions contribute differentially to performance on complex executive tasks. Specifically, WCST performance was related most strongly to Shifting, TOH to Inhibition, RNG to Inhibition and Updating, and operation span to Updating. Dual task performance was not related to any of the three target functions. These results suggest that it is important to recognize both the unity and diversity of executive functions and that latent variable analysis is a useful approach to studying the organization and roles of executive functions.

Cognition↗

Neuropsychological executive functions and DSM-IV ADHD subtypes.

OBJECTIVE: To evaluate and compare a focused set of component neuropsychological executive functions in the DSM-IV attention-deficit/hyperactivity disorder combined (ADHD-C) and inattentive (ADHD-I) subtypes. METHOD: The Stop task, Tower of London, Stroop task, Trailmaking Test, and output speed measures were completed by 105 boys and girls aged 7-12 classified as either DSM-IV ADHD-C (n = 46), ADHD-I (n = 18), or community control (n = 41). RESULTS: Both subtypes had deficits on output speed. A group x gender interaction was observed on the Stop task: boys with ADHD-C were impaired versus boys with ADHD-I, whereas girls in the two subtypes did not differ. The ADHD-C type had a deficit in planning. Neither ADHD group had a deficit in interference control per se, although they were slower than controls on the Stroop tasks. CONCLUSIONS: ADHD-I shares neuropsychological deficits with ADHD-C in the domain of output speed; on most domains the subtypes did not differ. Neuropsychological distinctions between these ADHD subtypes may be few, depending on which domain of executive functioning is assessed, and these distinctions differ by gender. In the case of boys, the two subtypes may be distinguished by the specificity of motor inhibition deficits to ADHD-C.

Attention Deficit Disorder with Hyperactivity↗

Executive function differences in multiple system atrophy and Parkinson's disease.

The aim of the present study was to assess executive function in patients with multiple system atrophy (MSA) and Parkinson's disease (PD) looking for specific differences and considering motor disability and disease duration. Performance of 11 MSA patients was compared to that of 12 healthy controls and two groups of 12 PD patients, one matched with respect to the severity of motor symptoms and the other with respect to disease duration. Compared to healthy controls, MSA and PD patients both presented executive dysfunction but, in MSA, the impairment was more severe and diffuse. This study suggests that despite the evidence of some differences in executive function in MSA and PD, the contribution of standard neuropsychological examination to the differential diagnosis of both syndromes remains still limited.

Adult↗

The impact of deep brain stimulation on executive function in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) improves Parkinson's disease and increases frontal blood flow. We assessed the effects of bilateral DBS on executive function in Parkinson's disease patients, seven with electrodes implanted in the STN and six in the GPi. Patients were assessed off medication with stimulators off, on and off again. The groups showed differential change with stimulation on the Reitan Trail-Making test (TMT B) (STN more improved) and on some measures of random number generation and Wisconsin Card Sorting (STN improved, GPi worse with stimulation). Across the groups, stimulation speeded up responding (Stroop control trial, TMT A) and improved performance on paced serial addition and missing digit tests. Conversely, conditional associative learning became more errorful with stimulation across the two groups. In general, change in performance with stimulation was significant for the STN but not the GPi group. These results support two opposite predictions. In support of current models of Parkinson's disease, 'releasing the brake' on frontal function with DBS improved aspects of executive function. Conversely, disruption of basal ganglia outflow during DBS impaired performance on tests requiring changing behaviour in novel contexts as predicted by Marsden and Obeso in 1994.

Association Learning↗

Low-level lead exposure, executive functioning, and learning in early childhood.

The current paper presents evidence relating low-level lead exposure to impaired executive functioning in young children. Using the Shape School task, we assessed focused attention, attention switching, working memory, and the ability to inhibit automatic responses in a cohort of 170 children. Participants performed the Shape School task at both 48 and 54 months of age; the mean blood lead level was 6.49 microg/dl at 48 months. After controlling for a wide range of sociodemographic, prenatal, and perinatal variables, blood lead level was negatively associated with children's focused attention while performing the tasks, efficiency at naming colors, and inhibition of automatic responding. In addition, children with higher blood lead levels completed fewer phases of the task and knew fewer color and shape names. There was no association between blood lead and performance on the most difficult tasks, those requiring attention switching or the combination of inhibition and switching. Children's IQ scores were strongly associated with blood lead and Shape School performance, and when entered as a covariate, only color knowledge and the number of tasks completed remained significant. Results provide only weak support for impaired executive functioning, but the deficits in color knowledge may indicate a primary sensory deficit or difficulty with forming conditional associations, both implicating disruptions in dopamine system function.

Attention↗