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PubMed1999

Neuropsychological characteristics and test behaviors of boys with early onset conduct problems.

School-age children and adolescents with conduct problems typically exhibit deficits in verbal IQ, language abilities, and executive functions. This study examined the extent to which this pattern was evident in a clinic group of preschool boys with early onset conduct problems who met criteria for oppositional defiant disorder (ODD) with and without attention deficit hyperactivity disorder (ADHD). A 2nd question focused on the strength of relation between clinic boys' uncooperative or inattentive test behaviors and their test performance. As expected, the clinic boys showed a neuropsychological profile highly similar to the one found in older conduct problem populations. Verbal tests distinguished clinic from matched comparison boys even after controlling for observers' ratings of disruptive behavior during testing. Clinic boys with ODD and ADHD had lower verbal and executive function scores than clinic boys with ODD alone. After general vocabulary knowledge and test behavior were controlled, clinic boys were found to have poorer vocabularies for describing affective states than comparison group boys.

Age of Onset↗

PubMed1998

Cognitive dysfunction in patients with pituitary tumour who have been treated with transfrontal or transsphenoidal surgery or medication.

OBJECTIVE: This study was carried out to examine the neuropsychological status of patients treated for pituitary tumour by transfrontal surgery, transphenoidal surgery or medical treatment only, with or without radiotherapy. DESIGN AND MEASUREMENTS: Three groups of 23 patients who had been treated for pituitary tumour were compared with 23 healthy controls on a range of neuropsychological measures. The surgical patients were also subdivided into two groups and compared. The neuropsychological measures were standardized psychological tests designed to assess aspects of attention, memory and executive function. PATIENTS: The patients were those who had been treated with transfrontal surgery (n = 23), transsphenoidal surgery (n = 23) and medication only (n = 23). The groups did not differ with respect to age, education or premorbid ability level as assessed by the National Adult Reading Test. All participants were free of known sources of cognitive impairment other than pituitary tumour. RESULTS: Comparison of the four groups revealed that nearly half of the transfrontal, one-third of the transsphenoidal and one-quarter of the non-surgical group had three or more neuropsychological tests scores below the 10th percentile compared to less than 5% of the controls. Impairments in memory and executive function were found in both surgical groups. The non-surgical patients appeared to have problems only on tasks requiring high levels of cognitive processing. Differences were found between the two surgical groups with respect to the severity of the cognitive impairment, the transfrontal patients having more severe impairment than the transsphenoidal. No significant negative effects on cognitive functioning were associated with radiotherapy; however, transfrontal surgery patients who had not been treated with radiotherapy were found to be more impaired than other patients. This was thought to be related to radical surgery. CONCLUSIONS: Many patients with treated pituitary tumour suffer significant cognitive impairment. The severity and nature of impairment differs between treatment groups, although the cause of this could not be addressed by this study. Recommendations are made for future research and clinical practice.

Adult↗

PubMed2001

Supervisory attentional system in patients with focal frontal lesions.

The aim of this study was to re-examine the hypothesis of a link between frontal cortex and the Supervisory Attentional System (SAS; Shallice, 1988). Contrary to previous studies that examined patients with lesions extending beyond the frontal lobes (Shallice, 1982; Burgess & Shallice, 1996a, 1996b), SAS or executive functions were evaluated in a group of patients with strict frontal lesions. Three tasks (Tower of London -TOL-, Hayling and Brixton tests) designed to assess specific SAS processes (planning, inhibition and abstraction of logical rules respectively) were administered. In the TOL test, although frontal patients were slower than control participants, the two groups did not differ in their ability to solve problems. Furthermore, the two groups did not differ in terms of performance in the Hayling and Brixton tests either. These results are discussed in terms of the SAS model and are compared to those observed by Shallice (1982) and Burgess & Shallice (1996a, 1996b). Additionally, the issue of the neural subtract of executive functions is addressed.

Adult↗

PubMed2006

Andersen-Tawil syndrome: definition of a neurocognitive phenotype.

BACKGROUND: The Andersen-Tawil syndrome (ATS) is a potassium ion channelopathy caused by mutations in the KCNJ2 gene. It is characterized by periodic paralysis, cardiac arrhythmias, and distinctive features; the effect of KCNJ2 mutations on the CNS has never been studied. OBJECTIVE: To define a potential CNS phenotype in ATS using standardized methods. METHODS: Ten subjects with KCNJ2 mutations and their unaffected siblings were evaluated at the University of California San Francisco General Clinical Research Center. A comprehensive battery of neurocognitive tests was administered to ATS subjects and their unaffected siblings, followed by pairwise analysis of the resultant differences in scores. An EEG was obtained for all ATS subjects. RESULTS: There was no EEG evidence of subclinical seizure activity in any subject. ATS subjects universally had more school difficulties than their siblings, despite similar IQ between the two groups. On formal neurocognitive testing, there was no difference between ATS subjects and their siblings on tests of verbal and visual memory. Assessment of executive functioning revealed ATS subjects scored 1.93 points lower than their siblings on tests of Design Fluency (95% CI -3.46, 0.01; p = 0.052) and made 1.9 more errors (95% CI 0.46, 2.54; p = 0.005). Subjects with ATS scored an average of 5 points lower than their siblings on tests of matrix reasoning (95% CI -8.67, -1.33; p = 0.008). On tests of general ability, ATS subjects achieved much lower scores than their siblings, with an average difference of 9.13 points for reading (95% CI -12.46, 3.21; p = 0.056) and 23.4 points for mathematics (95% CI -42.53, -4.22; p = 0.017). CONCLUSION: Mutations in KCNJ2 are associated with a distinct neurocognitive phenotype, characterized by deficits in executive function and abstract reasoning.

Adolescent↗

PubMed1995

Regional cerebral blood flow measured by 99mTc-HMPAO SPECT differs in subgroups of Alzheimer's disease.

Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might have impact in patients' response to different treatment strategies. We designed a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To identify AD subtypes, we performed a cluster analysis including performance on memory, language, visuospatial, praxic, and executive functions. The rCBF measured by 99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35 patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex-matched healthy cognitively intact controls. AD patients were at the early stage of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6). The cluster analysis revealed two AD subgroups: AD1 (N = 12) and AD2 (N = 23). The subgroups did not differ in age, sex, or global clinical severity as assessed by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally impaired memory. The AD2 group was inferior to the AD1 group on verbal, visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF ratios in the temporal and parietal cortices and the amygdala compared to controls. The AD2 group differed from controls in the rCBF ratios of frontal, temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients, the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several significant correlations were found between decreases rCBF ratios and impairment of memory and other cognitive functions. In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity.

Aged↗

PubMed2002

Spatial working memory performance in patients with schizoaffective psychosis versus schizophrenia: a tale of two disorders?

We explored the relationship between schizophrenia and schizoaffective disorder by comparing the two patient groups in terms of their performance on measures of executive functioning (spatial working memory and Wisconsin Card Sorting Test). Patients with schizophrenia (N=34) and those with schizoaffective disorder (N=23) performed significantly poorer than community controls (N=30). However, the schizoaffective and schizophrenia groups did not differ from each other in terms of working memory accuracy or mean response latencies. Similarly, the two patient groups did not differ in terms of the number of categories achieved or number of perseverative errors on the Wisconsin Card Sorting Test. Among the patients, working memory accuracy was associated with number of WCST perseverative errors and number of categories achieved, though working memory performance was not associated with number of WCST nonperseverative errors. These findings indicate that both schizophrenia and schizoaffective disorder are associated with executive functioning deficits. The findings are discussed in the context of the ongoing debate regarding the conceptualization of schizoaffective disorder.

Adult↗

PubMed2000

Trail making test, part B as a measure of executive control: validation using a set-switching paradigm.

Recent controversy surrounds the use of the Trail Making Test as a measure of cognitive flexibility, given that the Trail Making Test, Part B (TMT-B) also differs from Part A (TMT-A) in factors of motor control and perceptual complexity. The present study compared performance in the TMT and a set-switching task in order to test the assumption that cognitive flexibility is captured in TMT-B performance. Set-switching tasks have low motor and perceptual selection demands, and therefore provide a clearer index of executive function. In this study, participants made category judgments for digits, letters, or symbols across a series of trials, and performance for consecutive same-task trials was compared with task-switch trials. Results of the set-switching task indicated significant switch cost, but only for the situation of task alternation (e.g., an ABA series), suggesting that task-set inhibition may play a role in this effect. Alternating-switch cost was significantly correlated with TMT-B performance, especially with the TMT-B to TMT-A ratio (B/A). Cost for alternating switches was especially large for participants with B/A ratio > 3. These results provide direct evidence that the B/A ratio of performance in the TMT provides an index of executive function.

Adult↗

PubMed2005

The neuropsychopharmacology of attention-deficit/hyperactivity disorder.

More than three decades of research has attempted to elucidate the neuropsychopharmacology of attention-deficit/hyperactivity disorder (ADHD). Stimulants, a principle treatment for the disorder, act on the norepinephrine (NE) and dopamine (DA) systems; this has led to a long-standing hypothesis of catecholamine dysfunction in ADHD. Animal studies show a clear role for NE and DA in the modulation of executive functions, which are often disturbed in persons with ADHD. Nonstimulant agents that are effective in the treatment of ADHD tend to affect the NE system, whereas those affecting only DA, or those that affect neither catecholamine, are less potent in reducing ADHD symptoms. Studies of the effects of NE and DA peripheral metabolites by ADHD pharmacotherapies show acute increases in levels of these catecholamines; however, their long-term turnover may be reduced. Imaging studies suggest stimulants increases DA levels in the brain, whereas some animal models of ADHD are more consistent with excessive DA activation in the disorder. Ultimately, ADHD therapy may modify activity in the NE and DA systems to a more optimal level, thus improving responses to environmental stimuli and enhancing working memory and executive function.

Animals↗

PubMed2002

Adult age differences in strategy use during verbal fluency performance.

This study investigated adult age differences in strategy use during verbal fluency performance among 60 older and 60 younger adults. Clustering and switching, strategic components of fluency, were investigated as predictors of performance along with cognitive processes thought to underlie these strategies, namely verbal ability, speed of processing and executive function (strategic planning, performance monitoring, etc.). Two measures of verbal fluency were used: initial and excluded letter (words produced not containing a designated letter). These tasks both require search for words based on a phonemic cue but are thought to reflect a differential reliance on strategic retrieval search processes for successful performance. The number of clusters produced accounted for age differences in excluded, but not initial, letter fluency. Performance on both fluency tasks was associated with the number of clusters and switches participants produced and initial letter fluency was associated with cluster size for older adults and a ratio index of effective search for both age groups. In general, both fluency tasks relied on verbal ability and articulation speed, and excluded letter fluency performance relied more on speed and executive function than did initial letter fluency, especially for older adults.

Adolescent↗

PubMed2002

Clock face drawing in children with attention-deficit/hyperactivity disorder.

The clock drawing test has been found to be sensitive to visual-spatial perception, graphomotor skills, verbal reasoning, and executive functioning in adult patient populations, as well as frontal lobe maturation in normal children. Our study is among the first to assess the use of clock drawing as a neuropsychological measure in the pediatric population. Participants included 41 children with attention-deficit/hyperactivity disorder (ADHD) and 41 normal controls, ages 6-12 years, matched for age, gender, and handedness. Conceptualization of time and construction of the clock face were assessed separately using a scoring system normed on school-age children in an earlier study. Children with Predominantly Inattentive Type were found to perform similarly to those with Combined Type of ADHD. However, children with ADHD, regardless of subtype, performed significantly poorer than controls. Qualitative analysis of performance revealed errors that were subsequent to poor planning during task execution, consistent with executive dysfunction commonly present in children with ADHD. Further, multiple regression analysis demonstrated that a neuropsychological measure of executive functioning was predictive of clock construction performance in children with ADHD. Constructional praxis and receptive vocabulary also were predictive of clock construction ability. Implications of these findings are discussed.

Journal Article↗

PubMed2006

Cognitive remediation therapy for outpatients with chronic schizophrenia: a controlled and randomized study.

Cognitive Remediation Therapy (CRT) is a novel rehabilitation approach designed to improve neurocognitive abilities such as attention, memory and executive functioning. The aim of the present study is to evaluate the effect of CRT on neurocognition, and secondarily on symptomatology and psychosocial functioning. Cognitive Behavioural Therapy (CBT) was used as a control condition because it aims to improve emotional problems and positive symptoms, focusing on modification of maladaptive beliefs and schemas, but neurocognition is not targeted. A total of 40 chronic patients with DSM-IV schizophrenia disorder were randomly assigned for 4 months to one of two treatment groups: CRT or CBT. Repeated assessments were conducted before and after the treatments and at the end of a follow-up period of 6 months. Additionally, a method to establish reliable change was calculated from a separate sample of 20 schizophrenic patients who were under standard medication without any kind of psychological treatment. Results showed that CRT produced an overall improvement on neurocognition (Mean effect size=0.5), particularly in verbal and nonverbal memory, and executive function. CBT showed the expected treatment effect on general psychopathology (anxiety and depression) but produced only a slight non-specific improvement in neurocognition (Working Memory). Furthermore, patients receiving CRT showed improvement in social functioning, demonstrating that cognitive improvements are clinically meaningful. These gains were still present at the 6 month follow-up.

Adult↗

PubMed1996

Frontal/executive impairments in schizophrenia.

A study of frontal/executive impairments in schizophrenia is reported. Schizophrenia patients and controls were not significantly different with respect to age, sex, and premorbid IQ. The schizophrenia group demonstrated significant impairments in cognitive flexibility and forward planning, replicating results from a 1990 study by Morice. Impairment prevalence figures of 65 and 76 percent for cognitive flexibility and forward planning, respectively, were demonstrated. Several tests for short-term memory were administered. Schizophrenia patients were not found to be impaired on tests of simple, or primary, short-term memory as measured by Digits Span Forward and Words Span Forward, but they were found to be significantly impaired compared with controls on two tests of working memory, Alphabet Span and Sentence Span. Using a cutoff derived from the mean score for the controls, 65 percent of schizophrenia patients proved to be impaired on Sentence Span. A total of 16 (94%) were impaired on one or more of the three tests of executive functioning used. The effects of IQ on test results were examined, and impairment of cognitive flexibility and forward planning seemed to occur regardless of whether premorbid IQ had been preserved or had deteriorated. However, working memory impairments occurred in the subgroup of schizophrenia patients demonstrating a substantial fall in IQ from premorbid levels. The ability to process increasingly complex information was addressed by a more detailed examination of the Tower of London results. There were no differences in performance between groups for the first three levels of complexity (1-3 moves), but significant, and increasing, differences emerged for the last three levels (4-6 moves). These results were taken to support the hypothesis that schizophrenia represents a loss of, or a failure to acquire, the ability to process complex information. Impairments of executive functions that could affect complex information processing could have implications for schizophrenia rehabilitation.

Adult↗

PubMed2003

Basic neuropsychological dimensions in schizophrenia.

Neuropsychological (NP) studies in schizophrenia often require data reduction to avoid statistical type I error from multiple comparisons. Typically, this involves grouping measures into domains defined by experts a priori based on delineations validated in brain-injured but not schizophrenia samples (e.g. attention, executive functioning, memory, language visuospatial, motor). Component measures are arbitrarily selected and validity may not generalize to different samples or within the same sample over time. One solution to these problems is illustrated using neurocognitive subdomains based on recent schizophrenia literature, and validated with data from a longitudinal study (156 subjects) involving repeated NP testing (baseline--within 6 months of hospital discharge--and 6 and 18 months later). A priori subdomains were grouped and submitted to principal component analysis (PCA) at each time point. Longitudinal stability of the resulting factors was tested by computing congruency coefficients. Six stable factors were extracted having good construct, divergent and predictive validity. Five neuropsychological measures frequently studied in schizophrenia were not correlated with these factors, suggesting that they should be maintained as independent neurocognitive subdomains. Distinct factors for executive functioning, verbal memory and motor functions could not be validated; this raises concerns about conclusions of previous studies regarding the pattern, severity and correlates of specific neurocognitive functions in schizophrenia.

Adult↗

PubMed2001

Prefrontal lesions impair the implicit and explicit learning of sequences on visuomotor tasks.

OBJECTIVE: (1) To verify whether the prefrontal cortex (PFC) is specifically involved in visuomotor sequence learning as opposed to other forms of motor learning and (2) to establish the role of executive functions in visuomotor sequence learning. BACKGROUND: Visuomotor skill learning depends on the integrity of the premotor and parietal cortex; the prefrontal cortex, however, is essential when the learning of a sequence is required. METHODS: We studied 25 patients with PFC lesions and 86 controls matched for age and educational level. Participants performed: (1) a Pursuit Tracking Task (PTT), composed of a random tracking task (perceptual learning) and a pattern tracking task (explicit motor sequence learning with learning indicated by the decrease in mean root square error across trial blocks), (2) a 12-item sequence version of a serial reaction time task (SRTT) with specific implicit motor sequence learning indicated by the rebound increase in response time when comparing the last sequence block with the next random block, and (3) a neuropsychological battery that assessed executive functions. RESULTS: PFC patients were impaired in sequence learning on the pattern tracking task of the PTT and on the SRTT as compared to controls, but performed normally on the PTT random tracking task. Learning on the PTT did not correlate with learning on the SRTT. PTT performance correlated with planning functions while SRTT performance correlated with working memory capacity. CONCLUSIONS: The PFC is specifically involved in explicit and implicit motor sequence learning. Different PFC regions may be selectively involved in such learning depending on the cognitive demands of the sequential task.

Adult↗

PubMed2006

Performance of healthy, older adults on the Tower of London Revised: Associations with verbal and nonverbal abilities.

Neuropsychological studies suggest a subclinical impairment in executive function that occurs with normal aging. This is the first study to examine the performance of healthy older adults on the Tower of London-Revised (TOL-R), as well as the relationship between TOL-R performance and verbal and nonverbal abilities. Performance of 63 older adult participants on the TOL-R and two WAIS-III subtests was compared to that of 35 young adult college students. Group comparisons indicated age differences in TOL-R performance; however, these were eliminated after adjusting for individual differences in Matrix Reasoning performance. In the older adult groups, multiple regression analyses demonstrated that Matrix Reasoning performance was a stronger predictor of TOL-R performance than was chronological age or years of education. These results suggest that performance on the TOL-R is a psychometrically sound executive function measure for older adults and that individual differences in fluid intelligence are more predictive of performance than chronological age.

Adolescent↗

PubMed2003

Sensitivity and specificity of neuropsychological tests for mild cognitive impairment, vascular cognitive impairment and Alzheimer's disease.

BACKGROUND: Early diagnosis of dementia is important for those who might benefit from treatment. We designed a brief comprehensive neuropsychological test battery to help differentiate control subjects from patients with mild cognitive impairment (MCI) and dementia. METHOD: The battery included tests of memory, attention, executive function, speed, perception and visuospatial skills. It was administered to subjects from the OPTIMA cohort: 51 controls, 29 with MCI, 60 with 'possible' or 'probable' Alzheimer's disease (AD) (NINCDS/ADRDA) and 12 with cerebrovascular disease (CVD). Mann-Whitney U tests were used to compare performance of controls with other diagnostic groups. The sensitivity and specificity of the tests were determined using Receiver Operating Characteristic curve analyses. The effects of age, gender and years of education on test performance were determined with Spearman's rank correlations. RESULTS: The AD group performed worse than controls on all tests except an attention task. The Hopkins Verbal Learning Test and The Placing Test for episodic memory showed significant discriminative capacity between controls and other groups. Attention and processing speed tests discriminated CVD from controls. Category fluency, episodic memory tests and the CLOX test for executive function distinguished MCI from AD. Spearman's correlations showed negative associations between age and processing speed. Years of education affected performance on all tests, except The Placing Test. CONCLUSIONS: Certain neuropsychological tests have been shown to be sensitive and specific in the differential diagnosis of various types of dementia and may prove to be useful for detection of MCI.

Aged↗

PubMed2001

Oculomotor delayed response abnormalities in young offspring and siblings at risk for schizophrenia.

Individuals with schizophrenia are know to demonstrate cognitive and behavioral difficulties, particularly alterations in executive functions, including working memory. It is unclear whether these deficits reflect trait-related vulnerability to schizophrenia indicators and can be assessed by studying nonpsychotic relatives of patients with schizophrenia. In this study, we used an oculomotor delayed response (ODR) paradigm to examine spatial working memory in 37 "high-risk" child and adolescent offspring and siblings (age range=6-25 years) of patients with schizophrenia or schizoaffective disorder. Compared with 37 age- and sex-matched healthy controls (age range=6-23 years), high-risk subjects showed nonsignificantly greater errors in the ODR task at longer delay intervals. Statistical analyses suggested that performance improved with age in healthy control subjects, whereas it worsened with age in high-risk subjects. In both groups, the ODR errors were generally associated with poorer sustained attention (Continuous Performance Test: visuospatial d prime), somewhat poorer executive function (Wisconsin Card Sorting Test), and elevated Heinrichs-Buchanan neurological soft signs scores. These findings indicate the presence of spatial working memory abnormalities in individuals at risk for schizophrenia. Furthermore, these abnormalities may be progressive in nature. The ODR task is a valuable indicator of prefrontal cortical function and spatial working memory and may be a potentially valuable marker for familial risk of schizophrenia.

Journal Article↗

PubMed2006

Cognitive estimation impairment in Alzheimer disease and mild cognitive impairment.

Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance.

Aged↗