Number Of Perseverative Errors Research Articles

Vulnerability for autism traits in boys and men with an extra X chromosome (47,XXY): The mediating role of cognitive flexibility

The XXY chromosomal pattern (Klinefelter syndrome, KS) has been associated with specific effects on physical, neurobiological, endocrinological and psychological development. This study was focused on the described risk for autism in KS, and the cognitive mechanisms that mediate this risk. Our aim was to assess whether autistic features in KS result from impairments in executive functioning, more specifically difficulties in cognitive flexibility.In total, 71 boys and men with KS and 61 non-clinical controls participated in the study. Autistic features were assessed using the Autism-spectrum Quotient (AQ). Mental flexibility was measured using the Wisconsin Card Sorting Test (WCST).The level of autism traits was significantly increased in the KS group, the effect size for total AQ score was 1.6. The KS group also showed significantly more difficulties in cognitive flexibility, as indicated by and increased number of perseverative (but not non-perseverative) errors in the WCST. This effect was independent of intellectual functioning, age or testosterone supplements. Within the KS group, the number of perseverative errors was significantly (positively) correlated with total AQ score.Our findings suggest that KS can be associated with dysfunctions in mental flexibility, and that individuals with more mental flexibility problems also have more autism traits. This insight is relevant for diagnosis, prevention and treatment of severe problems in individuals with KS. Implications also extend beyond this specific syndrome. As executive dysfunctions in KS have also been linked to ADHD symptoms and thought disorder, this could be a shared mechanism contributing to overlap in symptoms and comorbidity between different psychiatric conditions.

Response Perseveration in Stimulant Dependence Is Associated with Striatal Dysfunction and Can Be Ameliorated by a D2/3 Receptor Agonist

Compulsivity is a hallmark of drug addiction and in animal models is measured by consecutive incorrect responses to a previously rewarded stimulus during reversal learning. The aim of this study was to measure behavioral and neural markers of compulsivity in stimulant-dependent individuals and to test whether these markers could be modulated by treatment with drugs targeting the dopamine system. In a randomized, double-blind, placebo-controlled, crossover design, stimulant-dependent individuals (SDIs; n = 18) and healthy volunteers (n = 18) received single doses of dopamine D(2/3) receptor antagonist (amisulpride, 400 mg) and agonist (pramipexole, 0.5 mg) drugs. To examine compulsivity and its dopaminergic modulation more generally, patients with obsessive-compulsive disorder (OCD; n = 18) were also included in the study. SDIs made significantly more perseverative responses to the previously correct stimulus immediately following reversal, compared with both healthy volunteers and patients with OCD. Across all participants, the number of perseverative errors was negatively correlated with functional activation in right fronto-striato-parietal networks-in particular, the right caudate nucleus. In SDIs, perseveration-related caudate activation was abnormally reduced in the placebo condition, but the dopamine D(2/3) agonist pramipexole normalized both perseverative responding and related activation of the right caudate. Perseveration during reversal learning was associated specifically with stimulant dependence rather than with compulsive behaviors more generally. The beneficial effects of a dopamine agonist drug challenge on both behavior and associated brain activation in SDIs may indicate new avenues for pharmacologic treatment in stimulant dependence.

The Contribution of Set Switching and Working Memory to Sentence Processing in Older Adults

This study evaluates the involvement of switching skills and working-memory capacity in auditory sentence processing in older adults. The authors examined 241 healthy participants, aged 55 to 88 years, who completed four neuropsychological tasks and two sentence-processing tasks. In addition to age and the expected contribution of working memory, switching ability, as measured by the number of perseverative errors on the Wisconsin Card Sorting Test, emerged as a strong predictor of performance on both sentence-processing tasks. Individuals with both low working-memory spans and more perseverative errors achieved the lowest accuracy scores. These findings are consistent with compensatory accounts of successful performance in older age.

Perseverative errors on the Wisconsin Card Sorting Test and brain perfusion imaging in mild Alzheimer's disease

The Wisconsin Card Sorting Test (WCST) has long been used to investigate deficits in executive function in humans. The majority of studies investigating deficient WCST performance focused on the number of categories achieved (CA) and the number of perseverative errors of the Nelson type (PEN). However, there is insufficient evidence that these two measures reflect the same neural deficits. Twenty AD patients with high PEN scores, and 20 age- and sex-matched AD patients with low PEN scores were selected. All 40 subjects underwent brain SPECT, and the SPECT images were analyzed by Statistical Parametric Mapping. No significant differences were found between high and low PEN score groups with respect to years of education, Addenbrooke's Cognitive Examination scores, and Mini-Mental State Examination scores. However, higher z scores for hypoperfusion in the bilateral rectal and orbital gyri were observed in the high PEN score group compared with the low PEN score group. Our results suggest that functional activity of the bilateral rectal and orbital gyri is closely related to PEN scores on a modified WCST (mWCST). The PEN score on a mWCST might be a promising index of dysfunction of the orbitofrontal area among patients with mild AD.

Reference Data for the Ruff Figural Fluency Test Stratified by Age and Educational Level

The Ruff Figural Fluency Test (RFFT) was developed to avoid the difficulties that were encountered in earlier tests of figural fluency. Although the test characteristics of the RFFT seem to be good and it is a valuable addition to neuropsychological assessments, reference data are still scarce. To this aim, we required 2,404 community dwelling persons in Groningen, the Netherlands to perform the RFFT. All 1,651 persons with a complete RFFT and known educational level formed the reference sample. Their age ranged from 35 to 82 years and their educational level from primary school to university grade. Ninety-six percent of the persons were of Western European descent. All tests were analyzed by two independent examiners and subsequently three measures were calculated: number of unique designs, number of perseverative errors and error ratio. The main finding was that performance on the RFFT was dependent on age and educational level. This was not only observed in older persons but also in young and middle-aged persons. Reference data for the three RFFT measures are presented in groups of five years of age ranging from 35–39 years to 75 years or older.

Executive dysfunction in chronic cocaine users: An exploratory study

Introduction Chronic cocaine use is associated with some executive deficits. We assessed executive functions using ecologically valid tests in chronic cocaine users. Objectives To investigate the relationship between executive deficits and three measures of severity of cocaine use: years of use, quantity used, and frequency of use. Methods Twenty-four cocaine users were compared with twenty-seven community controls. We used Student's t-test and Chi-squared to compare means and categorical variables, respectively. Linear regression analyses for the adjusted comparative analysis between cases and controls, and severity of cocaine use among cocaine users were performed. Results Chronic cocaine users performed worse on measures of attention and working memory (Forward and Backward Digit Span, p < .001), set-shifting abilities (difference score between the Trail Making B and A, TMB-A, p = .006), cognitive test of mental flexibility and response inhibition (Rule Shift Cards) ( p < .001), and prefrontal functioning (Wisconsin Card Sorting Test, WCST, p = .023) than controls. Years of cocaine use were associated with deficits in the Backward Digit Span ( p = .041; CI 95%: −.760 to −.002), the TMB-A ( p = .026; CI 95%: .687 to 9.761), the Zoo Map ( p = .034; CI 95%: −.480 to −.021), and the Rule Shift Cards ( p = .006; CI 95%: −.836 to −.164), among others. Quantity of cocaine use was associated with executive deficits measured by the Forward Digit Span ( p = .007; CI 95%: −.727 to −.133), the TMB-A ( p = .021; CI 95%: 5.304–57.945), and the number of perseverative errors in the WSCT ( p = .002; CI 95%: −10.654 to −2.800). Frequency of cocaine was associated with deficits in the Backward Digit Span ( p = .042; CI 95%: −1.548 to −.030). Conclusions Chronic use of cocaine is associated with executive deficits, which may influence patients’ functionality, prognosis, and therapeutic failure.

Developmental and genetic influences on prefrontal function in adolescents: A longitudinal twin study of WCST performance

Adolescence is characterized by a relative immaturity of the prefrontal cortex and associated cognitive control functions, which is hypothesized to be a major contributing factor to high-risk behaviors. However, little is known about the role of genetic and environmental factors in frontal brain development during adolescence. Here we examined heritability of performance on the Wisconsin Card Sorting Test (WCST), an established neuropsychological measure of prefrontally mediated executive functioning, in a longitudinal sample of adolescent twins (n=747) tested at ages 12 and 14. WSCT performance significant improved with age as indicated by a decrease in the number of perseverative errors (p<0.001), which was paralleled by an increase in heritability in females (19% at age 12 and 49% at age 14) and shared environmental influences in males (non-significant at age 12 and 34% at age 14). The results suggest increasing influence of familial factors on frontal executive functioning during adolescence, as well as gender differences in the relative role of genetic and environmental factors.

The Role of Switching, Inhibition and Working Memory in Older Adults' Performance in the Wisconsin Card Sorting Test

ABSTRACT The Wisconsin Card Sorting Test (WCST) is considered a typical executive test. However, several interesting questions are still open as to the specific executive processes underlying this task. In the present study, we explored how local and global switching, inhibition and working memory, assessed through the Number–Letter, the Stop Signal and the Reading Span tasks, relate to older adults' performance in the WCST. Results showed that older adults' performance variability in the number of perseverative errors was predicted by the local switch component of the Number–Letter task. Results also showed age-related differences in inhibition, working memory and global switching, while local switching resulted largely spared in aging. This study provides evidence that switching abilities may contribute to performance of older adults in the WCST. It also provides initial evidence suggesting that switching processes, associated with local switch costs, are involved in performance on the WCST, at least in older adults.

Inhibition of the norepinephrine transporter improves behavioral flexibility in rats and monkeys

RationalePoor cognitive control, including reversal learning deficits, has been reported in children with attention deficit hyperactivity disorder, in stimulant-dependent humans, and in animal models of these disorders; these conditions have each been associated with abnormal catecholaminergic function within the prefrontal cortex.ObjectivesIn the current studies, we sought to explore how elevations in extracellular catecholamine levels, produced by pharmacological inhibition of catecholamine reuptake proteins, affect behavioral flexibility in rats and monkeys.Materials and methodsAdult male Long–Evans rats and vervet monkeys were trained, respectively, on a four-position discrimination task or a three-choice visual discrimination task. Following systemic administration of pharmacological inhibitors of the dopamine and/or norepinephrine membrane transporters, rats and monkeys were exposed to retention or reversal of acquired discriminations.ResultsIn accordance with our a priori hypothesis, we found that drugs that inhibit norepinephrine transporters, such as methylphenidate, atomoxetine, and desipramine, improved reversal performance in rats and monkeys; this was mainly due to a decrease in the number of perseverative errors. Interestingly, the mixed dopamine and norepinephrine transporters inhibitor methylphenidate, if anything, impaired performance during retention in both rats and monkeys, while administration of the selective dopamine transporter inhibitor GBR-12909 increased premature responses but did not alter reversal learning performance.ConclusionsOur results suggest that pharmacological inhibition of the membrane norepinephrine, but not membrane dopamine, transporter is associated with enhanced behavioral flexibility. These data, combined with earlier reports, may indicate that enhanced extracellular catecholamine levels in cortical regions, secondary to norepinephrine reuptake inhibition, improves multiple aspects of inhibitory control over responding in rats and monkeys.

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

A dysfunction of the fronto-striatal loop has been associated with obsessive-compulsive disorder (OCD). Functional imaging studies suggest that reversal learning is affected by deficits in fronto-striatal brain areas and thus should be impaired in patients with OCD. The authors compared patients with OCD and healthy comparison subjects on a reversal learning task. Correlation analyses and group comparisons showing prolonged reaction times of different response parameters are associated with increasing severity of compulsions. The reversal learning task has been shown to be associated with ventral fronto-striatal brain activation by functional magnetic resonance imaging (fMRI) in healthy comparison subjects. The purpose of this article is to suggest that the reversal learning task can be used as a neuropsychiatric measurement of the ventral fronto-striatal dysfunction in OCD.

Frontal release signs and cognition in people with schizophrenia, their siblings and healthy controls

Frontal release signs, a subset of neurological soft signs, are common in schizophrenia. To explore the relationship between frontal release signs and neuropsychological tests of frontal lobe function in people with schizophrenia, their siblings and healthy controls. Neuropsychological tests and frontal release signs were measured in a cohort of index cases (n=302), their siblings (n=240) and healthy controls (n=346). The mean total score of frontal release signs was 1.5 (s.d.=1.58) in the schizophrenia group, 0.54 (s.d.=0.92) for siblings and 0.42 (s.d.=0.77) for controls. Schizophrenia group scores were greater than healthy control or sibling cohort scores (P < 0.0001), which did not differ. In all three cohorts, right grasp reflex scores positively correlated with number of perseverative errors on the Wisconsin Card Sort Task (P < 0.05). In the schizophrenia group, frontal release signs scores showed an inverse correlation with IQ (R=-0.199, P < 0.0005). Our findings of relationships between frontal release signs and cognitive assays of cortical dysfunction and the increased frequency of these signs in people with schizophrenia implicate a cortical origin for these clinical signs and evidence of frontal lobe dysfunction in this disorder.

Performance on the Wisconsin Card Sorting Test in schizophrenia and genes of dopaminergic inactivation (COMT, DAT, NET)

The aim of the study was to test an association between polymorphisms of genes connected with dopaminergic inactivation in prefrontal cortex [catechol- O-methyltransferase (COMT), dopamine transporter (DAT), norepinephrine transporter (NET)], and performance on the Wisconsin Card Sorting Test (WCST), in schizophrenic patients. The number of perseverative errors (WCST-P), non-perseverative errors (WCST-NP), completed corrected categories (WCST-CC), conceptual level responses (WCST-%CONC) and set to the first category (WCST-1st CAT) were measured. Genotyping was done for the Val108(158)Met polymorphism of the COMT gene (79 patients), the 3′UTR VNTR polymorphism of the DAT gene (124 patients) and the 1287 A/G polymorphism of the NET gene (63 patients). Male schizophrenic patients with Val/Val genotype of COMT obtained better results on WCST-P, while female patients had worse results on the WCST-NP compared with the remaining genotypes. There was a slight trend for patients with the A9/A9 genotype of DAT and with the A/A genotype of NET to perform better on some domains of the WCST, compared with other genotypes. A limitation to the interpretation of results could be small number of patients studied as well as variable psychopathological state and medication during cognitive testing.

A heart rate analysis of developmental change in feedback processing and rule shifting from childhood to early adulthood

Over the course of development, the ability to switch between different tasks on the basis of feedback cues increases profoundly, but the role of performance monitoring remains unclear. Heart rate indexes can provide critical information about how individuals monitor feedback cues indicating that performance should be adjusted. In this study, children of three age groups (8–10, 12–14, and 16–18 years) performed a rule change task in which sorting rules needed to be detected following positive or negative feedback. The number of perseverative errors was lower for 16- to 18-year-olds than for 8- to 10-year-olds, and 12- to 14-year-olds performed at an intermediate level. Consistent with previous findings, heart rate slowed following feedback indicating a rule change, and the magnitude of slowing was similar for all age groups. Thus, 8- to 10-year-olds are already able to analyze feedback cues. In contrast, 12- to 14-year-olds and 16- to 18-year-olds, but not 8- to 10-year-olds, showed heart rate slowing following performance errors, suggesting that with age children are increasingly able to monitor their performance online. Performance monitoring may therefore be an important contributor to set-shifting ability.

Prefrontal cognition in schizophrenia and bipolar illness in relation to Val66Met polymorphism of the brain‐derived neurotrophic factor gene

The measures of prefrontal cognition have been used as endophenotype in molecular-genetic studies. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive functions and in the pathogenesis of major psychoses. This study investigates the relationship between Val66Met polymorphisms of the BDNF gene and prefrontal cognitive function in 129 patients with schizophrenia and 111 patients with bipolar mood disorder. Cognitive tests included the Wisconsin Card Sorting Test (WCST), with such domains as number of perseverative errors, non-perseverative errors, completed corrected categories, conceptual level responses, and set to the first category, and the N-back test, where mean reaction time and percent of correct reactions were measured. Genotyping for Val66Met BDNF polymorphism was done by polymerase chain reaction method. In schizophrenia, no relationship between Val66Met polymorphism of the BDNF gene and the results of the WCST was observed. Patients with Val/Val genotype had a higher percentage of correct reactions in the N-back test than those with the remaining genotypes. Bipolar patients with Val/Val genotype obtained significantly better results on three of five domains of the WCST. No relationship between BDNF polymorphism and the results of the N-back test was found in this group. A limitation to the results could be variable psychopathological state and medication during cognitive testing and lack of Hardy-Weinberg equilibrium in schizophrenia group. Val66Met polymorphism of the BDNF gene may be associated with cognitive performance on the WCST in bipolar mood disorder but not in schizophrenia. An association of this polymorphism with performance on the N-back test in schizophrenia and not in bipolar illness may suggest that in schizophrenia, the BDNF system may be connected with early phases of information processing.

Treatment of a first episode of psychotic illness with quetiapine: An analysis of 2 year outcomes

Background The first episode of a psychotic disorder provides a unique opportunity to initiate optimal treatment but when a new medication becomes available, little data exist to guide the appropriate use in this population. Objectives The objectives were to determine the optimal doses and titration of quetiapine for this group and to measure outcomes (including symptom response, social functioning, mood alterations, motor symptoms, metabolic parameters and cognitive functioning) over 2 years of treatment with quetiapine. Design Thirty nine subjects with a first episode of psychosis referred to the Nova Scotia Early Psychosis Program in Halifax, Canada, were invited to participate in this study. Standardized clinical, laboratory, and neuropsychological assessments were performed at baseline and following treatment with quetiapine at intervals out to 2 years. Results Quetiapine was effective in treating the psychotic and mood symptoms while not causing extra-pyramidal signs or symptoms (EPSS). Pre-existing motor dysfunction improved. No anticholinergic medications were required. Several domains of cognitive function also improved (sustained attention, the number of perseverative errors, visuomotor speed and sequencing, verbal fluency and verbal memory). Weight gain was observed along with increases in cholesterol levels but there was no glucose dysregulation. Conclusions The results of this two year, naturalistic study of people with a first episode of psychosis indicated that quetiapine was well tolerated and effective for this population. Significant improvements in cognitive functioning also provided evidence for potential longer-term benefits of early and optimal treatment with this agent. However, monitoring metabolic parameters, as recommended for other atypicals, is likely prudent.

An association study of dopamine receptors polymorphisms and the Wisconsin Card Sorting Test in schizophrenia

Dopamine (DA), an important neurotransmitter in prefrontal cortex (PFC), is involved in the pathogenesis of schizophrenia. The aim of the study was to test an association between common polymorphism of genes for DA receptors DRD1, DRD2, DRD3, DRD4, and performance on the Wisconsin Card Sorting Test (WCST), measuring various functions of PFC, in 138 schizophrenic patients. Patients with G/G genotype of DRD1 tended to obtain worse results in all domains of WCST compared to patients with remaining genotypes, particularly for number of completed corrected categories, and trials to set the first category. A relationship was also found in female patients between DRD2 polymorphism and number of perseverative errors, while no association between WCST results and DRD3 or DRD4 polymorphism was observed in patients studied. The results may suggest an association between DRD1 gene polymorphism and performance on PFC test in schizophrenia. Also, the gender-dependent role of DRD2 in this process may be presumed.

Ralentissement cognitif dans le vieillissement : fonctions exécutives et apprentissage procédural lors d'une tâche informatisée de labyrinthe

General slowing of performance speed is a common finding associated with normal aging. However, which aspects of information processing are playing a major role in this decline are not well understood. Impairment in maze learning has been shown in patients with neurological disorders. Hippocampal bilateral lesions are associated mith larger deficits and interfere with both storage and retrieval of spatial information. Frontal lesions also produce similar effects and are characterized by perseverative errors. Reduced working memory has also been implicated in cognitive aging and is reflected in difficulties encountered in the execution of a task in real time when alterning between encoding and retrieval of information. A computerized maze learning task (Groton Maze Learning Task, GMLT) was developed specifically to determine the extent to which perseverative behaviors, working memory difficulties or other factors are implicated in the cognitive slowing generally observed in aging. Two groups of right-handed subjects (20 young adults: M =22.6; SD =1.54; 19 older adults: M =64; SD3 =0.93) were compared looking at speed of learning and perseverative errors. Subjects were also assessed on tasks of procedural learning (Tower of Toronto), working memory (Paced Auditory Serial Addition Test; PASAT), and four subtests of the Wechsler Memory Scale-III (logical memory, faces, paired associates, family pictures) with immediate and delayed recall. With respect to the GMLT, subjects were required to find the correct path through a hidden maze by pressing on the computer’s touchscreen to move to the location of their choice. After practice trials, all subjects underwent ten consecutive trials followed, ten minutes later, by one last trial. Results of interest showed significant differences between the two groups in the time needed to complete all trials and in the number of perseverative errors. More specifically, the older subjects made more perseverative errors and were slower in learning the maze. In addition, a canonical correlation analysis was performed to determine the relationship between maze learning and the cognitive systems involved (executive function, working memory, procedural learning). The analysis revealed a canonical variate explaining 49% of the total variance, showing that the number of perseverative errors and number of moves on the Tower of Toronto test are the main components principally implicated in the performance of subjects on the GMLT. We conclude that the tendency for healthy elderly adults to make perseverative errors while completing the learning trials, often related to frontal-lobe dysexecutive syndromes, may also be associated with normal aging. It is suggested that the poorer monitoring of errors and/or the inhibition of a choice in response to new information observed in the elderly accounts, at least in part, for the overall finding of slowed information processing speed.

Modified Card Sorting Test: Normative Data

The Modified Card Sorting Test (MCST), a shortened version of the Wisconsin Card Sorting Test, proposed by Nelson in 1976 is a neuropsychological test that is widely used in clinical settings for the evaluation of executive functions in patients with focal, traumatic and degenerative brain diseases. Despite its frequent use, normative data for the MCST are scant. The aim of this study was to collect normative data for the MCST on a sample including 248 healthy individuals ranging from 20 to 90 years of age and equally distributed for education level and sex (124 males and 124 females). Performance on the MCST was scored by computing the number of categories achieved by a participant, and the number of perseverative errors. Multiple regression analyses revealed a significant effect of age and education on the number of categories and perseverative errors but no effect of sex. Cut-off scores were then determined and equivalent scores computed for both the number of categories and the perseverative errors. The availability of normative data for the MCST will be very valuable in clinical settings for testing patients with focal, traumatic and degenerative brain diseases. The use of reference norms will permit a better characterisation of a patient’s impaired and spared abilities.

The validity and reliability of chinese frontal assessment battery in evaluating executive dysfunction among Chinese patients with small subcortical infarct.

Frontal Assessment Battery (FAB) is a valid and reliable screening test for evaluating executive dysfunction among whites with frontal and subcortical degenerative lesions. We studied the properties of a Chinese version of FAB (CFAB) in evaluating executive dysfunction among Chinese stroke patients with small subcortical infarct. Concurrent validity was evaluated using Wisconsin Card Sorting Tst (WCST) and Mattis Dementia Rating Scale-Initiation/Perseveration Subset (MDRS I/P) among 41 controls and 30 stroke patients with small subcortical infarct. Discriminant validities of CFAB and its subitems were compared with those of Mini-Mental State Examination (MMSE). Internal consistency, test-retest, and interrater reliability of CFAB were evaluated. The CFAB had low to good correlation with various executive measures: MDRS I/P (r = 0.63, p < 0.001), number of category completed (r = 0.45, p < 0.001), and number of perseverative errors (r = -0.37, p < 0.01) of WCST. Among the executive measures, only number of category completed had significant but small contribution (6.5%, p = 0.001) to the variance of CFAB. A short version of CFAB using three items yielded higher overall classification accuracy (86.6%) than that of CFAB full version (80.6%) and MMSE (77.6%). Internal consistency (alpha = 0.77), test-retest reliability (rho = 0.89, p < 0.001), and interrater reliability (rho = 0.85, p < 0.001) of CFAB were good. Although CFAB is reliable, it is only moderately valid in evaluating executive dysfunction among Chinese stroke patients with small subcortical infarct. The clinical use of CFAB in the evaluation of executive dysfunction among this group of patients cannot be recommended at this stage.