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Chronological age, but not FMRP levels, predicts neuropsychological performance in girls with fragile X syndrome.

The effect of FMRP levels and chronological age on executive functioning, visual-spatial abilities ,and verbal fluency tasks were examined in 46 school-age girls with fragile X syndrome (FXS). Results indicated that FMRP levels were not predictive of outcome on the neuropsychological tests but that performance on the executive functioning task tended to worsen with chronological age. This age effect was not observed on the tests of visual-spatial abilities or verbal fluency. These data indicate that relative deficits in executive functioning in girls with FXS become more pronounced with age. In contrast, the relative deficits in spatial and verbal abilities of these girls did not appear to increase with age, suggesting that these abilities may be spared.

Adolescent↗

Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers.

N-methyl-D-aspartate (NMDA) receptor antagonists have been demonstrated to induce schizophrenia-like symptoms and cognitive impairment in humans. The NMDA receptor has been strongly implicated in memory, but research to date on the effects of NMDA antagonists has examined only some aspects of human memory functions. This study used a double-blind, placebo-controlled, independent groups design with 54 healthy volunteers to examine the effects of infusions of two doses (0.4, 0.8 mg/kg) of the NMDA antagonist ketamine upon the five human memory systems, aspects of executive functioning and schizophrenia-like and dissociative symptoms. Ketamine produced a dose-dependent impairment to episodic and working memory and a slowing of semantic processing. Ketamine also impaired recognition memory and procedural learning. Attention, perceptual priming and executive functioning were not affected following the drug. In addition, ketamine induced schizophrenia-like and dissociative symptoms, which were not correlated with the cognitive measures. These data suggest that, in humans, ketamine produces a selective pattern of impairments to working, episodic, and procedural memory but not to perceptual priming, attention or aspects of executive functioning.

Adolescent↗

Neuropsychological correlates of reality distortion in schizophrenic patients.

The present study aims at exploring the relationship between content-related aspects of delusions and hallucinations in schizophrenia and the basic domains of cognition, controlling for the other clinical and demographic variables that could produce bias in the interpretation of the results. Seventy stable schizophrenic patients were evaluated through psychiatric assessment and a neuropsychological battery including tests on attention, memory, perceptual-motor speed and executive functions. We found that the severity of negative symptoms was strongly correlated with poor performance in almost all domains of cognitive functions, while only the attentional deficit was correlated with positive symptoms. The relationships between different cognitive domains and specific types of delusions and hallucinations showed that thought insertion, guilt, grandiose, religious and somatic delusions were associated with impairment in different cognitive functions (verbal and visual memory, attention and executive functions). Voices arguing and tactile hallucinations were correlated to delay-recall memory function. Our results suggest that no specific cognitive pattern is associated with typical-content delusions and hallucinations. On the basis of our findings, cognitive impairments associated with delusions and hallucinations, as measured by our battery, seem not to play a central role in the genesis and the maintenance of these symptoms, suggesting a more complex model of pathogenesis.

Adult↗

Neuropsychological correlates of ADHD symptoms in preschoolers.

The authors examined the neuropsychological status of 22 preschoolers at risk for attention-deficit/hyperactivity disorder (ADHD) and 50 matched control children, using measures of nonverbal working memory, perceptual and motor inhibition, and memory for relative time. All tasks included paired control conditions, which allowed for the isolation of discrete executive function constructs. Group differences were evident on several measures of neuropsychological functioning; however, after accounting for nonexecutive abilities, no deficits could be attributed to specific functions targeted by the tasks. Performance on executive measures was not related to objective indices of activity level or ratings of ADHD symptoms. Yet, the fact that at-risk preschoolers were highly symptomatic casts doubt on whether executive function deficits and/or frontostriatal networks contribute etiologically to early behavioral manifestations of ADHD.

Attention Deficit Disorder with Hyperactivity↗

Improvement in neuropsychological performance following surgical treatment for obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is characterized by snoring and apnea during sleep leading to decreased oxygen saturation and disturbed sleep, excessive daytime sleepiness and neuropsychological disturbances. This study investigates cognitive neuropsychological abilities in a group of 53 OSAS patients before and after treatment with uvulopalatopharyngoplasty. General intellectual ability, verbal learning and memory as well as executive functioning were measured at baseline and 6 months postoperatively. After surgery there were significant improvements in verbal learning and memory (mean change -39, SD 57.3, p < 0.001), recall (mean change -24.3, SD 39.3, p < 0.001) and executive functioning (as assessed by percentage of errors on the Wisconsin Card Sorting Test; mean change -9.1, SD 15.7, p < 0.001). These improvements were in accordance with improvements in the degree of sleep apnea, the oxygen desaturation index (mean change -9.7, SD 15.9, p < 0.001) and arterial minimum oxygen saturation (mean change 4.5%, SD 10.2%, p < 0.01). Surgical treatment seems to improve verbal learning, memory and recall and executive functions in parallel with better oxygenation in OSAS.

Humans↗

Cognitive function in euthymic bipolar I disorder.

Recent reports have suggested the presence of persistent cognitive impairments in patients diagnosed with Bipolar Disorder even after prolonged euthymic phases. In this work, various domains of cognitive function were examined in asymptomatic patients diagnosed with Bipolar I Disorder (BDI) in comparison with healthy subjects. Fifteen otherwise healthy BDI patients with a prior history of psychosis during mania completed a neuropsychological testing battery after a prolonged asymptomatic remission. Their scores were compared to those of individually matched healthy subjects with unpaired two-tailed t-tests at P<0.01. Relationships between cognitive performance measures and clinical variables related to illness severity were also examined with Pearson correlations, P<0.05. We detected poorer performance on measures of verbal learning, executive functioning and motor coordination in BDI patients compared to control volunteers. Scores on tests of executive functioning were negatively correlated with the number of episodes of mania and depression. Social and occupational scores were also associated with a poorer performance on measures of verbal learning and executive function. Euthymic BDI patients, therefore, demonstrate reductions in specific cognitive domains even after prolonged asymptomatic phases. Some of these deficits appear to be associated with a more severe course of illness and poorer social and occupational functioning.

Adult↗

Characteristics and correlates of cognitive functioning following bone marrow transplantation.

Patients who undergo bone marrow transplantation (BMT) often report cognitive problems following treatment. This study used cognitive tests and a self-report measure of subjective cognitive complaints to determine (1) the rate of objective cognitive impairment in a sample of 65 BMT patients, and (2) the correspondence of patients' cognitive complaints to their actual cognitive performance. At 6 months following BMT, patients were assessed in seven cognitive domains--attention, verbal learning, verbal memory, visual memory, simple executive function, complex executive function, and psychomotor speed. Cognitive complaints were likewise assessed. In all, 51% had at least mild impairment (-1 standard deviation (s.d.) below published norms) in one or more cognitive domains, with 28% demonstrating moderate-to-severe impairment (-2 s.d.). Older patients and patients with lower IQ were more likely to score in the impaired range on objective cognitive tests, with males and the less educated showing trends toward scores in the impaired range. Younger patients made significantly more cognitive complaints. Total cognitive complaints were unrelated to average cognitive performance, and complaints in specific cognitive domains were largely unrelated to objective performance on corresponding domains. Findings suggest that patients who complain about their cognitive performance following BMT differ from those who experience actual deficits.

Bone Marrow Transplantation↗

Effects of abstinence and relapse upon neuropsychological function and cerebral glucose metabolism in severe chronic alcoholism.

Prolonged excessive consumption of alcohol has been associated with a variety of cognitive disorders accompanied by neuropathological and neurochemical abnormalities of the brain, particularly in the frontal lobes. Studies with positron emission tomography (PET) have shown decreased local cerebral metabolic rates for glucose (lCMRglc) in frontal regions, with correlated abnormalities on neuropsychological tests sensitive to executive functioning. This investigation was designed as a pilot study to examine the effects of abstinence and relapse in patients with severe chronic alcoholism studied longitudinally with PET and with neuropsychological evaluation to assess both general and executive functioning. Six patients, including 4 who remained relatively abstinent and 2 who relapsed following their initial evaluation, were studied twice, with inter-evaluation intervals ranging from 10 to 32 months. The patients who remained abstinent or who had minimal alcohol use showed partial recovery of lCMRglc in two of three divisions of the frontal lobes and improvement on neuropsychological tests of general cognitive and executive functioning, whereas the patients who relapsed had further declines in these areas. These results, although based upon a relatively small number of subjects, provide preliminary support for at least partial recovery of metabolic and cognitive functioning in individual patients who abstain from alcohol.

Adult↗

Effects of executive impairments on maladaptive explanatory styles in substance abusers: clinical implications.

Our study examined the relation between neuropsychological impairment of executive functions and explanatory styles, according to the Abramson model of learned helplessness in humans, in a sample of substance abusers. Thirty-eight polysubstance abusers were assessed during an abstinence period using a selective neuropsychological battery for the evaluation of the executive functions, as well as the Attributional Style Questionnaire (ASQ) for the assessment of the three dimensions of explanatory style: Internality-Externality, Stability-Instability and Globality-Specificity. Multiple regression analyses showed significant relationships among performance on different neuropsychological tasks sensitive to executive functions and characteristic cognitive styles. The results showed the performance on cognitive flexibility and response inhibition tasks is directly related to making more internal attributions for positive situations, and inversely related to the appearance of more stable attributions for negative events. Likewise, adequate performance on working memory tasks was related to development of more global attributions for failures. These results are partially congruent with the learned helplessness model and particularly relevant for the clinical management of substance abusers and the success on the treatment and rehabilitation of these subjects.

Adult↗

The three attentional networks: on their independence and interactions.

The present investigation was aimed to the study of the three attentional networks (Alerting, Orienting, and Executive Function) and their interactions. A modification of the task developed by Fan, McCandliss, Sommer, Raz, and Posner (2002) was used, in which a cost and benefit paradigm was combined with a flanker task and an alerting signal. We obtained significant interactions as predicted. The alerting network seemed to inhibit the executive function network (a larger flanker-congruency effect was found on trials where an alerting signal had been previously presented). The orienting network influenced the executive function network in a positive way (the flanker effect was smaller for cued than for uncued trials). Finally, alertness increased orienting (the cueing effect was bigger after the alerting signal). This last result, taken together with previous findings, points to an influence in the sense of a faster orienting under alertness, rather than a larger one. These results offer new insight into the functioning of the attentional system.

Adolescent↗

Context-sensitive cognitive-behavioural supports for young children with TBI: a replication study.

OBJECTIVE: To replicate an investigation of the effects of a multi-component cognitive-behavioural intervention on the challenging behaviour of two young children with growing behavioural concerns after TBI. EXPERIMENTAL DESIGN: Single-subject reversal designs used to document the effects of the combined behavioural, cognitive and executive function intervention on the following dependent variables: frequency and intensity of aggressive behaviours, amount of work accomplished. PARTICIPANTS: Two young children with escalating behaviour problems after TBI. INTERVENTION: Integrated components of positive behaviour supports, cognitive supports (e.g. graphic organizers) and an executive function routine (goal-plan-do-review). RESULTS: Reduced frequency and intensity of challenging behaviours; increased quantity of work completed. CONCLUSIONS: Positive replication of previous single-subject experiments demonstrating the potential for successfully treating behaviour disorders in young children with TBI using a support-oriented intervention that combines behavioural, cognitive and executive function components.

Brain Injuries↗

[Short- and long-term consequences of prenatal exposure to cannabis].

OBJECTIVE: Cannabis is one of the most commonly used drugs by pregnant women. The objective of this review of literature was to examine the association between cannabis use during pregnancy and effects upon growth, cognitive development (memory, attention, executive functions...) and behavior of newborns, children and teenagers. MATERIAL AND METHODS: We searched for articles indexed in the medline database from 1970 to 2005. The following terms were used in the literature search: cannabis/marijuana, pregnancy, fetal development, newborn, prenatal exposure, neurobehavioral deficits, cognitive deficits, executive functions, cannabinoids, reproduction. Most of the articles were published in English. RESULTS: Cannabis use during pregnancy is related to diverse neurobehavioral and cognitive outcomes, including symptoms of inattention, impulsivity, deficits in learning and memory, and a deficiency in aspects of executive functions. It seems difficult to identify complications, such as lower birth weight, only attributable to cannabis as opposed to the multiple perinatal complications associated with tobacco smoking. CONCLUSION: In addition to alcohol and cigarettes, information should be given to women about the potentially harmful effects on fetal development, newborns, children and teenagers of smoking cannabis. Therefore, it seems necessary to develop prevention programs on this subject.

Adolescent↗

Visual and auditory event-related potentials in sporadic amyotrophic lateral sclerosis.

OBJECTIVES: To investigate the relationship between amyotrophic lateral sclerosis (ALS) and cognitive function by means of oddball event-related potentials (ERPs) and to determine the usefulness of this methodology in the cognitive status assessment of physically disabled patients. METHODS: Visual and auditory oddball ERPs were recorded in 16 consecutive sporadic ALS patients. A comprehensive battery of neuropsychological (NP) tests assessed intelligence, executive functions, attention, memory, word fluency, visuo-motor and visual-constructive skills. RESULTS: All patients performed visual and auditory ERPs and 75% of cases showed abnormal N200 and/or P300 waves. Ten patients (62.5%) carried out the entire psychometric evaluation with significant impairment on tests of executive function and attention. A significant correlation between delayed visual (P<0.04) and auditory (P<0.04) P300 latency and impaired NP tests was found. CONCLUSIONS: In agreement with literature data, our findings confirm the hypothesis of cognitive impairment in ALS patients especially on attention and executive functions suggesting a more extensive degeneration beyond the motor areas. ALS causes severe physical disabilities and such a condition may interfere with NP testing. Thus, the P300 seems to be a useful tool for the assessment of cognition and attention when severe physical deficits are present.

Adult↗

Relationship of indicators of neuropathology, psychopathology, and effort to neuropsychological results in patients with epilepsy or psychogenic non-epileptic seizures.

Previous research suggests epilepsy and psychogenic non-epileptic seizure (PNES) patients do not show consistent group differences on neuropsychological measures. However, both groups of patients show decreased neuropsychological performance when compared to a normal population (Cragar, Berry, Fakhoury, Cibula, & Schmitt, 2002). Swanson, Springer, Benbadis, and Morris (2000) have suggested epilepsy patients show decreased neurocognitive functioning due to neuropathology whereas PNES patients show decreased neurocognitive functioning due to psychopathology. Effort has also been implicated as an important factor in neuropsychological test results in general (Green, 2003). The purpose of this study was to investigate the relationships of medical history variables (e.g., duration of disorder), neuropathology, psychopathology, and effort to neuropsychological findings in epilepsy and PNES patients. Neuropsychological functioning was divided into six domains: intelligence, memory, language, executive functions, visual-spatial, and motor. Results indicated that medical history variables were related to intellectual, memory, language, and motor functioning. Psychopathology was associated with all cognitive domains except executive functioning. Effort was related to intellectual, memory, language, visual-spatial, and motor functioning. Neuropathology and diagnosis were related only to memory.

Adult↗

Clinicometabolic dissociation of cognitive functions and social behavior in frontal lobe lesions.

OBJECTIVE/BACKGROUND: Case studies suggest a dissociation between cognitive functions that have been impaired after damage to the dorsolateral prefrontal cortex and social skills disturbed when the ventromedial prefrontal areas are affected. Because this dissociation had not been confirmed in a clinical setting, clinicometabolic correlations were sought in 13 patients with various lesions of the prefrontal cortex. DESIGN/METHODS: The clinical assessment included extensive testing of executive functions and evaluation of behavioral abnormalities based on an informant questionnaire. Regional cerebral glucose metabolism (rCMRGlu) was measured with [l8F] fluorodeoxyglucose ([18F] FDG) and 31-slide high-resolution PET. RESULTS: Executive-function test performance was significantly correlated with rCMRGlu in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9, 45, 46, and 47) and anterior cingulate cortex (Brodmann's areas 24 and 32). Behavioral scores were significantly correlated with rCMRGlu in the frontopolar (Brodmann's area 10) and orbitofrontal cortex (Brodmann's areas 11, 12, 13, and 14). CONCLUSION: These results show that impaired executive functions and serial skill deficits are associated with distinct metabolic patterns in patients with frontal lobe pathology. In agreement with activation studies in normal subjects, our data suggest the existence of a modular organization of the frontal cortex in humans, as previously reported in nonhuman primates.

Adult↗

Neuropsychological profiles of adolescents with ADHD: effects of reading difficulties and gender.

BACKGROUND: Executive function, particularly behavioral inhibition, has been implicated as a core deficit specific to Attention-Deficit/Hyperactivity Disorder (ADHD) whereas rapid naming has been implicated as a core deficit specific to reading disabilities (RD). Females may be less impaired in executive function although adolescent females with ADHD have yet to be studied. METHOD: Neuropsychological profiles of four adolescent groups aged 13-16 with equal female representation were investigated: 35 ADHD, 12 RD, 24 ADHD+RD, and 37 normal controls. A semi-structured interview (K-SADS-PL), the Conners Rating Scales and the Ontario Child Health Study Scales were used to diagnose ADHD. RD was defined as a standard score below 90 on at least one of the following: Reading or Spelling of the WRAT3 or Word Attack or Word Identification of the WRMT-R. The WISC-III, Rapid Automatized Naming, Stroop and Stop tasks were used as measures of cognitive and executive function. RESULTS: The two ADHD groups (ADHD, ADHD+RD) showed deficits in processing speed, naming of objects, poor behavioral inhibition and greater variability in reaction times whereas the two RD groups (RD, RD+ADHD) showed verbal working memory deficits and slower verbal retrieval speed. Only the comorbid group was slower with naming of numbers and colors and had slower reaction times. Regression analyses indicated that incongruent color naming (Stroop) and variability in go reaction time were the best predictors of hyperactive/impulsive ADHD symptoms whereas variability in go reaction time and processing speed were the best predictors of inattentive ADHD symptoms. Speed of letter naming and verbal working memory accounted for the most variability in composite achievement scores. No gender differences were found on any of the cognitive tests. CONCLUSIONS: This study challenges the importance of behavioral inhibition deficits in ADHD and that naming deficits are specific to RD. Further investigation into cognitive deficits in these groups is required.

Adolescent↗

Effect of aging on stimulus-reward association learning.

The flexible learning of stimulus-reward associations when required by situational context is essential for everyday behavior. Older adults experience a progressive decline in several cognitive functions and show deficiencies in neuropsychological tasks requiring flexible adaptation to external feedback, which could be related to impairments in reward association learning. To study the effect of aging on stimulus-reward association learning 20 young and 20 older adults performed a probabilistic object reversal task (pORT) along with a battery of tests assessing executive functions and general intellectual abilities. The pORT requires learning and reversing associations between actions and their outcomes. Older participants collected fewer points, needed more trials to reach the learning criterion, and completed less blocks successfully compared to young adults. This difference remained statistically significant after correcting for the age effect of other tests assessing executive functions. This suggests that there is an age-related difference in reward association learning as measured using the pORT, which is not closely related to other executive functions with respect to the age effect. In human aging, structural alterations of reward detecting structures and functional changes of the dopaminergic as well as the serotonergic system might contribute to the deficit in reward association learning observed in this study.

Adult↗

Treatment response in late-onset depression: relationship to neuropsychological, neuroradiological and vascular risk factors.

BACKGROUND: Late-onset depressive disorder is associated with white matter lesions and neuropsychological deficits that in some studies are linked to a poorer outcome for depression. Some white matter lesions may be vascular in origin. This study investigated the relationship between response or non-response to antidepressant monotherapy and neuropsychological function, structural brain measures and vascular factors. METHOD: This was a case control study. Fifty patients with late-onset major depressive disorder (29 who were responders to antidepressant monotherapy and 21 who were not) were compared with 35 non-depressed control subjects. Measures included assessment of vascular risk factors, neuropsychological testing and a magnetic resonance imaging (MRI) scan. RESULTS: After adjustment for depressed mood and medication at evaluation, both patient groups had significantly more impairment compared to control subjects on verbal learning tasks involving immediate or delayed recall. Patients who did not respond to antidepressant monotherapy had significantly poorer performance than controls on tests involving visuospatial ability, language, word recognition and tests of executive function, whereas there were no differences between control subjects and responders. On two tests of executive function (verbal fluency and the Stroop test) non-responders scored significantly worse than responders. There were no significant group differences on MRI measures of atrophy or of white matter lesions apart from a higher periventricular hyperintensity score in non-responders compared to controls. There were no group differences on measures of vascular disease. CONCLUSION: The results lend support to the emerging evidence that resistance to treatment in late-onset depression may be associated with impaired executive function. Subtle cerebrovascular mechanisms may be involved.

Age of Onset↗