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Neurocognitive functioning in recently abstinent, cocaine-abusing schizophrenic patients.

PURPOSE: This report examined a broad range of cognitive functioning in a group of recently abstinent, cocaine-abusing schizophrenic patients (CA + SZ). METHODS: Measures of selective and sustained attention, learning and memory, and executive functioning were administered to CA + SZ patients within 72 h of last cocaine use. A comparison group of non-substance-abusing schizophrenic patients (SZ) presenting for inpatient psychiatric treatment were also examined in an identical time frame. We hypothesized that the neurobiological impact of cocaine abuse and acute abstinence would cause CA + SZ to manifest deficits in all domains of cognitive functioning relative to non-abusing SZ patients. RESULTS: Results revealed that CA + SZ displayed significant memory impairment relative to their non-abuser SZ counterparts. No group differences, however, were detected on any other neurocognitive measure. CA + SZ were able to selectively process digit strings during the presence and absence of distracting stimuli, sustain attention, and perform executive functions at performance levels equal to their non-abuser SZ counterparts. IMPLICATIONS: These results are consistent with many past studies that have found CA + SZ patients to manifest memory impairment but have relatively well preserved functioning in other cognitive domains. The results are discussed in terms of the biological concomitants of cocaine abuse and acute abstinence in schizophrenia.

Adult↗

Developmental impact of frontal lobe injury in middle childhood.

Executive function of frontal lobe systems, like intelligent behavior, appears to demonstrate two major features: it is adaptive and goal-directed. Disruption of executive function following injury to the frontal lobes in childhood might be predicted to impact the trajectory of normal cognitive, behavioral, and social development. Case studies of two children injured at different ages showed the primary developmental impact to involve the behavioral and social realms. While cognitive development may be suspected to also be considerably influenced, assessment of changes in cognitive abilities by traditional psychometric means was found to be problematic. Psychometric changes were found to occur over a prolonged period of time, emphasizing the importance of documenting observations and chronicling postinjury events.

Brain Injuries↗

Neuropsychological evaluation of late-onset post-radiotherapy encephalopathy: a comparison with vascular dementia.

It is known that radiotherapy (RT) may cause cerebral injury. The most frequent neurotoxic effect of RT at any age is diffuse cerebral injury. Brain injury by therapeutic irradiation has traditionally been classified according to its time of onset into acute, early delayed, and late forms. The latter is not reversible. The neurocognitive sequelae of cranial irradiation can be mediated through vascular injury. Because the pathologic changes are most profound in the white matter, we compared a group of patients treated by RT (n=34) with a group of patients affected by subcortical vascular dementia (sVaD, n=34). Patients with a total radiation does <35 cGy did not show any sign of cognitive impairment. All the patients with a total irradiation dose >45 cGy did show profound cognitive and behavioural alteration. The patients who received a total dose of brain radiation comprised between 35 and 45 cGy did show slowness of executive function, and profound alterations of frontal functions, such as attention focusing, mentation control, analogical judgement and insight. The patients who suffered from the consequences of RT had slowness of executive functions, and profound alterations of frontal functions, such as attention focusing, mentation control, analogical judgement and insight, similar to those obtained by the patients suffering from subcortical vascular dementia. High dose RT might result in a severely demented, bedridden patient, who "has been cured" from his primary disease, the brain tumour. This constellation demands serious consideration before RT is given.

Adult↗

Slowed lexical access is uniquely associated with positive and disorganised symptoms in schizophrenia.

INTRODUCTION: This study addressed the relationship of both semantic priming and slowed lexical access to the symptoms of schizophrenia, and evaluated their association with other neurocognitive deficits. METHODS: 57 outpatients with schizophrenia and 20 nonpsychiatric control subjects performed a lexical decision semantic priming task (LDT), and a brief neuropsychological battery. The schizophrenia group was also assessed with an extended Positive and Negative Symptom Scale. RESULTS: As expected, the schizophrenia group had significantly slower reaction times (RTs) than the control group, and poorer performance on most neuropsychological tasks. Both groups exhibited semantic priming effects in both automatic and controlled processing conditions; these effects were not significantly different between groups. RT was unrelated to age, illness duration, GAF scores, or neuroleptic dose; controlled semantic priming effects were related to illness duration only. RT to real word targets (but not to nonwords) on the LDT was significantly correlated with positive and disorganised, but not negative symptoms. The neurocognitive correlates of RT slowing were: full-scale IQ and verbal fluency, but not attention; working memory; episodic memory retrieval; executive function, or manual speed. Both controlled semantic priming effects as well as the difference between controlled and automatic priming effects were related to executive functions in general. Severity of symptoms in the three major symptom groups was generally unassociated with impairment on the neuropsychological battery. The associations of RT slowing to positive and disorganised symptoms remained even after controlling for each of the above clinical and neurocognitive measures. CONCLUSIONS: These findings suggest that in schizophrenia, slowed lexical access is uniquely related to positive and disorganised symptoms. This relationship is not accounted for by more general cognitive deficits, overall illness severity, or generalised effects of symptoms on cognitive function. This relationship may reflect a specific impairment in the access to semantic memory.

Journal Article↗

[Contribution of ecological evaluation of executive disorders in multiple sclerosis].

INTRODUCTION: Multiple sclerosis (MS) is a major cause of neurological disability among young adults. The cognitive disorders are the second cause of alteration of quality of life after physical handicap and are often responsible for loss of social-occupational adaptability. The prevalence of cognitive disorders is 40 to 65%. The alteration of executive functions predominates whereas instrumental functions are generally preserved. The assessment of these disorders is often underestimated by the usual battery of neuropsychological tests. However, the link between psychometric results and executive difficulties of daily life is uncertain. OBJECTIVES: To evaluate the sensitivity of an ecological test compared to standard psychometric tests in assessment of executive disorders in MS. METHODS: Twenty subjects with clinically definite MS were matched for age, sex and pre-morbid intellectual level with control subjects. A battery of neuropsychological and ecological tests was applied to all subjects. The performances on these tests formed a global score of executive function (SFE). The "paper and pencil" multiple errands test was used as the ecological test to examine planning and goal-oriented behavior. We also assessed fatigue and depression with the Fatigue Severity Scale and the Beck Depression Inventory. RESULTS: There was no significant differences between MS patients and controls in neuropsychological executive tests, except for verbal fluencies (p=0.01). The performances were significantly decreased in the MS group for the multiple errands test (p=0.01). 75% of MS subjects have a pathological score for this test. There was a significant link between the performances with this test and SFE (p=0.009). CONCLUSIONS: Executive disorders are underestimated in MS. However, we suggest that an ecological approach is more reliable than standard neuropsychological tests to estimate the cognitive difficulties in daily life in MS subjects. The results of our study favor further research to ascertain the usefulness of ecological assessment in MS.

Adult↗

Low socioeconomic status and disability in old age: evidence from the InChianti study for the mediating role of physiological impairments.

BACKGROUND: Low socioeconomic status (SES) has been associated with increased risk of disability in later life. The purpose of this study was to determine if SES has an impact on mobility functioning and to explore which physiological impairments are also associated with SES and may explain its relationship with mobility. METHODS: The study sample consisted of 1025 individuals aged 65 years or older residing in the Chianti area (Italy). Number of years of education was used as an indicator of SES. Mobility functioning was assessed using gait speed (400 m) and the Short Physical Performance Battery (SPPB). Mobility-related physiological impairments were assessed with tests of executive functioning, nerve conduction velocity, muscle power, hip-ankle range of motion, Ankle-Brachial Index, and visual acuity. Linear regression models were used to study the association between number of years of education and mobility and to estimate the contribution of each of the selected physiological impairments to this association. RESULTS: Adjusting for age and sex, slower gait speed (1.16 vs 1.26 m/s, p <.0001) and lower SPPB scores (9.55 vs 10.11, p =.006) were seen in persons with < or =5 years of total education compared with those persons with >5 years of total education. Leg power and executive function decreased the strength of the association between educational level and gait speed by more than 15%. Controlling for all selected impairments (full model) decreased the education-gait speed association by 49%. Low education continued to be significantly associated with gait speed (p <.01). Adjusting for all physiological impairments substantially reduced the low education-SPPB score association by 100%, and this association was no longer significant. CONCLUSIONS: Low SES is related to multiple physiological impairments, which explain a large amount of the association between education and gait limitations. Further work must be done to understand the mechanisms whereby low SES translates into the impairments that play an important role in mobility.

Age Factors↗

The effects of anterior lesions on performance on a story comprehension test: left anterior impairment on a theory of mind-type task.

Participants with unilateral anterior or posterior lesions were compared to a healthy group on a theory of mind-type task that involved explaining the words or actions of story characters in a series of brief vignettes. Participants also carried out a set of non-social neuropsychological tests. Those with left anterior brain lesions (n=6) showed impairment relative to those with right anterior (n=13), left (n=4) and right (n=8) posterior lesions and healthy participants (n=60) in story comprehension, and their errors commonly involved failure to make non-literal interpretations. The left anterior lesion participants also showed impairment on some measures of executive function. The implications of the findings for our understanding of impairments in story comprehension after brain injury are discussed in terms of models of executive function and theory of mind.

Adult↗

Making working memory work: a computational model of learning in the prefrontal cortex and basal ganglia.

The prefrontal cortex has long been thought to subserve both working memory (the holding of information online for processing) and executive functions (deciding how to manipulate working memory and perform processing). Although many computational models of working memory have been developed, the mechanistic basis of executive function remains elusive, often amounting to a homunculus. This article presents an attempt to deconstruct this homunculus through powerful learning mechanisms that allow a computational model of the prefrontal cortex to control both itself and other brain areas in a strategic, task-appropriate manner. These learning mechanisms are based on subcortical structures in the midbrain, basal ganglia, and amygdala, which together form an actor-critic architecture. The critic system learns which prefrontal representations are task relevant and trains the actor, which in turn provides a dynamic gating mechanism for controlling working memory updating. Computationally, the learning mechanism is designed to simultaneously solve the temporal and structural credit assignment problems. The model's performance compares favorably with standard backpropagation-based temporal learning mechanisms on the challenging 1-2-AX working memory task and other benchmark working memory tasks.

Algorithms↗

Prevalence, course, and risk factors for executive impairment in patients hospitalized on a general medicine service.

The purpose of this study was to determine the prevalence, course, and risk factors for executive impairment in patients hospitalized on a general medicine service. One hundred patients were administered the Executive Interview (EXIT25), the Executive Clock Drawing Task (CLOX), and the Mini-Mental State Examination at admission and discharge. Fifty-two percent of the patients at admission and 56% at discharge had scores indicating impairment on at least one measure of executive function. Median scores on every measure improved during hospitalization. Older patients and those with a cardiac or gastrointestinal disorder were more likely to have executive impairment. The prevalence of executive impairment on general medicine services is high. Although improvement in executive function occurs during hospitalization, many patients remained impaired.

Cognition Disorders↗

The Frontal Assessment Battery (FAB): normative data from an Italian sample and performances of patients with Alzheimer's disease and frontotemporal dementia.

The Frontal Assessment Battery (FAB) is a short neuropsychological tool aiming to assess executive functions at the bedside. Two-hundred and thirty-six normal controls were administered the FAB and three other tasks assessing attentional and executive functions. The FAB was also administered to 28 patients suffering from mild Alzheimer's disease (AD, n. 15 subjects) or frontotemporal dementia (FTD, n. 13 subjects). The FAB showed good concurrent and discriminant validity and high internal consistency. Test-retest and inter-rater reliability were fairly good. A multiple regression analysis showed a significant positive effect of education and a negative effect of age. Cut-off values of non-parametric distribution were computed. A difference on FAB scores within dementia patients was observed, with subjects with FTD performing worse than patients suffering from AD.

Adult↗

On testing the face validity of planning/problem-solving tasks in a normal population.

Clinically, tests of executive functions tend to be chosen on face validity. If such tests are to be used to evaluate a clinical population, their ability to measure executive functions should be reliably demonstrated in a normal population. In order to investigate the reliability of such tests, a sample of 130 normal adults (74 women, 56 men) ages 17 to 55 years were administered 4 tests purporting to measure planning/problem-solving: the Tower of London Test, the Six Element Test, the Twenty Questions Test, and the Rey Complex Figure Test. A structural equation modeling approach provided by the LISREL 8 program was used to evaluate three models hypothesized to explain the relationship among the test variables and the latent construct of planning/problem-solving. An adequate model was unable to be estimated, thus raising questions about the meaning of the latent construct planning/problem-solving and the psychometric structure of the Tower of London Test.

Adolescent↗

Electroencephalographic cordance patterns distinguish exceptional clinical responders with fibromyalgia to individualized homeopathic medicines.

OBJECTIVES: To characterize initial central nervous system responses to olfactory administration of homeopathic remedies as biomarkers for subsequently exceptional, simillimum-like clinical outcomes at a systemic level (i.e., both locally and globally). DESIGN: Double-blinded, randomized, placebo-controlled clinical trial. SETTING: A private homeopathic clinic in Phoenix, AZ, and a university laboratory in Tucson, AZ. PATIENTS: Sixty-two (62) persons with physician-confirmed fibromyalgia (FM) (mean age, 49 years; 94% women) enrolled; 53 completed the 3-month assessment visit. Exceptional responders (n = 6, 23% of active treatment group; none on placebo) were those with improvements in the top one-third for both tender point pain and global health ratings after 3 months. INTERVENTION: Patients took daily oral doses of treatment solution in LM (1/50,000 dilution) potency (active group received individualized remedy; placebo group received plain solvent). Dependent measures: Baseline and 3-month difference scores for initial prefrontal electroencephalographic alpha frequency cordance (EEG-C, a correlate of functional brain activity) during 16 pairs of randomized, double-blinded bottle sniffs (treatment minus control solutions). RESULTS: Exceptional responders versus other patients exhibited significantly more negative initial EEG-C difference scores at prefrontal sites. Right prefrontal cordance findings correlated with subsequently reduced pain (r = 0.85, p = 0.03), better global health (r =-0.73, p = 0.10), and trait absorption (genetically determined ability to focus attention selectively and fully) (r = 0.91, p = 0.012). CONCLUSIONS: These observations suggest prefrontal EEG-C as an early biomarker of individualized homeopathic medicine effects in patients with FM who later exhibit exceptional outcomes. Prefrontal cortex controls executive function, including ability to redirect attention. Interactions between executive function, absorption, and the simillimum remedy could facilitate exceptional responses.

Adult↗

Developmental gene network analysis.

The developmental process is controlled by the information processing functions executed by the cis-elements that regulate the expression of the participating genes. A model of the network of cis-regulatory interactions that underlies the specification of the endomesoderm of the sea urchin embryo is analyzed here. Although not all the relevant interactions have yet been uncovered, the model shows how the information processing functions executed by the cis-regulatory elements involved can control essential functions of the specification process, such as transforming the localization of maternal factors into a domain-specific program of gene expression; refining the specification pattern; and stabilizing states of specification. The analysis suggests that the progressivity of the developmental process is also controlled by the cis-regulatory interactions unraveled by the network model. Given that evolution occurs by changing the program for development of the body plan, we illustrate the potential of developmental gene network analysis in understanding the process by which morphological features are maintained and diversify. Comparison of the network of cis-regulatory interactions with a portion of that underlying the specification of the endomesoderm of the starfish illustrates how the similarities and differences provide insights into how the programs for development work and how they evolve.

Animals↗

Neurocognitive function in antisocial personality disorder.

Recent neuroimaging studies and neuropsychological test findings support the contention that prefrontal dysfunction is associated with psychopathic personality traits and antisocial behavior. However, conflicting results have arisen regarding performance on measures of frontal executive function. We administered a neuropsychological test battery consisting of measures sensitive to frontal lobe dysfunction and a battery of personality questionnaires and clinical scales sensitive to antisocial personality disorder (APD) subjects presenting with prominent psychopathic personality features and matched control subjects. We also monitored the subjects' electrodermal activity during the presentation of emotionally charged stimuli. APD subjects showed greater neuropsychological deficits on measures sensitive to orbitofrontal dysfunction in comparison to control participants. Moreover, APD subjects were electrodermally hyporesponsive to aversive stimuli relative to control group members. APD subjects did not demonstrate performance deficits on classical tests of frontal executive function. Participants also underwent clinical assessment. As expected, APD subjects were less conscientious, self-reproaching, guilt-prone, and socially anxious than matched control subjects. Moreover, the scores indicated that APD subjects were more venturesome and uninhibited relative to control subjects. Contrary to expectations, APD subjects and community control subjects did not differ on a self-report measure of sensitivity to specific phobic situations.

Antisocial Personality Disorder↗

Androgen-responsive aspects of cognition in girls with Turner syndrome.

Turner syndrome (TS) represents a unique, sex hormone-deficient model in which to study the biological effects of androgen treatment (replacement) on cognition in females because TS girls have gonadal dysgenesis and absent ovarian androgen and estrogen production. We investigated the effects of androgen replacement therapy in TS girls, ages 10-14 yr, on cognitive function. A total of 64 TS girls were randomized to receive oxandrolone or placebo for 2 yr. They had a cognitive evaluation of four domains (verbal abilities, spatial cognition, executive function, and working memory) at baseline, 1, and 2 yr of the study. In addition, all subjects were examined for study safety every 6 months. Three of the four domains studied did not change significantly in response to oxandrolone treatment (verbal abilities, spatial cognition, and executive function). In contrast, the working memory summary score had a significant group by time interaction. The oxandrolone-treated group demonstrated improved performance after 2 yr, compared with the placebo group (P < 0.03). Minimal or no side effects were observed. In conclusion, oxandrolone treatment for 2 yr improves working memory in adolescent girls with TS. What this degree of improvement will mean in real life terms for TS girls remains to be determined.

Anabolic Agents↗

Frontal lobe lesions and executive dysfunction in children.

OBJECTIVE: To investigate the relationship of frontal lobe lesions and neuropsychologic performance in school-aged children to determine whether damage to frontal regions results in specific cognitive sequelae. BACKGROUND: The role of the frontal lobes in executive function remains incompletely understood, particularly in children. METHOD: This retrospective study included children aged 8 to 17 with brain lesions of various etiology (n = 63) or diverse psychiatric disorders (n = 48). All were evaluated for details of neurologic and medical history and for scores on the Wechsler Intelligence Scale for Children (WISC-III) and the Wisconsin Card Sorting Test, and all but the psychiatric patients had neuroimaging scans. Five groups were analyzed--dorsolateral frontal, medial-orbital frontal, focal nonfrontal, diffuse, and psychiatric--and neuropsychologic test results were compared using a Kruskal-Wallis nonparametric analysis of variance. RESULTS: Children with damage to dorsolateral frontal regions were more impaired on the Wisconsin Card Sorting Test than those in all other groups. Comparable performance on the Wechsler scale was found in all groups, suggesting that intellectual functioning did not account for this difference. CONCLUSIONS: These data provide evidence for a prominent role of the dorsolateral frontal regions in the mediation of executive function in children. They also support the use of the Wisconsin Card Sorting Test in children as a measure of dorsolateral frontal integrity.

Adolescent↗

Association between striatal reduction and poor Wisconsin card sorting test performance in patients with schizophrenia.

Several findings support the hypothesis that the striatum is implicated in executive functions and in the modulation of goal-directed behavior, and could play a key role in the pathophysiology and in the production of symptoms and signs in schizophrenia. We have studied the relationship between the objective measures of the striatal structures, as evaluated by magnetic resonance imaging (MRI), and the Wisconsin Card Sorting Test (WCST) performance in a schizophrenic sample. Thirty-five schizophrenic patients underwent MRI scans of striatal structure and neuropsychological evaluation of executive functions by WCST. Poor WCST performers had a reduction of the left caudate nucleus and putamen, and right total striatum when compared to 24 healthy controls. Significant correlation coefficients were also observed between neuropsychological indexes and left striatal measures. The findings suggest the existence of a relationship between abnormalities of striatal structure and abnormal executive-type or organizational cognitive functions.

Adult↗

Relationship between psychopathology and cognitive functioning in schizophrenia.

The purpose of this study was to delineate the relationship between positive, negative, cognitive, depressive, and excitement symptom dimensions of schizophrenia and cognitive functioning. Fifty-eight patients with schizophrenia (DSM-IV criteria) were assessed using the Positive and Negative Syndrome Scale (PANSS) and a battery of neuropsychological tests (executive function/abstraction, verbal and spatial working memory, verbal and nonverbal memory/learning, attention, visuospatial ability, and psychomotor speed). The cognitive symptom dimension correlated with executive functions, attention, verbal memory, and spatial ability. Severity of the negative symptom dimension was related to impairment in the structure of the semantic knowledge system, verbal memory, and auditory attention. In contrast, severity of the positive symptom dimension correlated only with impairment in the structure of the semantic knowledge system, and psychomotor speed. Finally, severity of the depressive and excitement symptom dimension was not associated with cognition. Correlations between symptom dimensions and cognitive measures were at best modest. Severity of cognitive and negative symptoms was mainly correlated with deficits on executive functions, semantic memory, and verbal memory, while positive symptoms only with semantic memory. These correlations were modest, suggesting that psychopathology and cognitive deficits in schizophrenia are caused, at least partially, by distinct pathophysiological processes.

Adult↗