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PubMed2006

Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a brief review and hypothesis.

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity. Adenylate cyclase-activating VNs including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) act as hormones, neurotransmitters, neuroregulators, immune modulators and neurotrophic substances. They and their receptors are potentially immunogenic. VNs are widely distributed in the body particularly in the central and peripheral nervous systems and have been identified in the gut, adrenal gland, blood cells, reproductive system, lung, heart and other tissues. They have a vital role in maintaining cardio-respiratory function, thermoregulation, memory, concentration and executive functions such as emotional responses including social cues and appropriate behaviour. They are co-transmitters for a number of neurotransmitters including acetylcholine and gaseous transmitters, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system against toxic assault as well as being important in the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of certain fatigue-related syndromes based on loss of immunological tolerance to these VNs or their receptors following infection, other events or de novo resulting in significant pathophysiology possibly mediated via CpG fragments and heat shock (stress) proteins. These conditions extend the public health context of autoimmunity and VN dysregulation and have implications for military medicine where radiological, biological and chemical agents may have a role in pathogenesis. Possible treatment and prevention options are considered.

Animals↗

PubMed1999

The relative influences of symptoms, insight, and neurocognition on social adjustment in schizophrenia and schizoaffective disorder.

Impaired insight and neurocognitive deficits are commonly seen in schizophrenia. No study to date, however, has documented the relative influences of insight deficits, neurocognitive functioning, and psychotic symptoms on overall social adjustment in this population. This was done in a cohort of individuals recovering from acute exacerbations. Forty-six individuals with schizophrenia or schizoaffective disorder were recruited upon discharge from an inpatient unit. Symptom levels, neurocognitive functioning (information processing, memory, and executive functioning), and symptom awareness were documented, and social adjustment was assessed in three domains: treatment compliance, social behavior, and subjective quality of life. Cross-sectional data from initial assessments are reported. Sequential linear regression analyses identified differential associations between illness characteristics and outcome domains. Treatment compliance was most influenced by insight; social behavior deficits were associated with thought disorder and neurocognitive (working memory and visuo-spatial) impairments; and quality of life was associated with mood disturbances. Outcome is multidimensional in schizophrenia, and there are differential patterns of associations between illness characteristics and domains of social adjustment. Studies such as this can guide clinicians in determining the most appropriate treatments for specific individuals and should also guide researchers in efforts to clarify the processes that underlie treatment response and recovery in schizophrenia.

Adult↗

PubMedDate not supplied

Association between attitude toward medication and neurocognitive function in schizophrenia.

OBJECTIVES: A patient's attitude toward medication is important for medication adherence, which is a key determinant of outcome in schizophrenia. This study examined the association between attitude toward antipsychotic medication and clinical status, particularly neurocognitive function, in patients with schizophrenia. METHOD: Ninety-two patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for schizophrenia participated in this study. The attitudes of the subjects toward medication were evaluated using the Drug Attitude Inventory (DAI). Clinical characteristics, including psychiatric symptoms and side effects of medication were evaluated. Neurocognitive function was measured using the Mini Mental State Examination and a computerized battery consisting of the Digit Span Test, Verbal Learning Test, Continuous Performance Test, Wisconsin Card Sorting Test, Finger Tapping Test, and Trail Making Test, parts A and B. The associations between attitude toward medication and neurocognitive function and clinical characteristics were analyzed. RESULTS: The scores on the DAI were not significantly correlated with the clinical characteristics, such as psychopathology, subjective well-being, or neuroleptic-induced extrapyramidal side effects. Instead, the scores on the DAI were significantly correlated with the learning index and delayed free recall on the Verbal Learning Test, the number of categories completed on the Wisconsin Card Sorting Test, and omission and commission errors on the Continuous Performance Test; the scores were not significantly correlated with measures on the Mini Mental State Examination, Digit Span Test, Finger Tapping Test, or Trail Making Test. CONCLUSIONS: Our findings indicate that a patient's attitude toward medication is associated with neurocognitive function. Specifically, verbal learning memory, executive functioning, and sustained attention were associated with attitude toward medication.

Adolescent↗

PubMed2006

Postsurgical outcome in pediatric patients with epilepsy: a comparison of patients with intellectual disabilities, subaverage intelligence, and average-range intelligence.

PURPOSE: Intellectual disabilities are often associated with bilateral or diffuse morphologic brain damage. The chances of becoming seizure free after focal surgery are therefore considered to be worse in patients with intellectual disabilities. The risk of postoperative cognitive deficits could increase because diffuse brain damage lowers the patient's ability to compensate for surgically induced deficits. Several studies in adult patients have indicated that IQ alone is not a good predictor of postoperative cognitive and seizure outcome. Our study evaluated this subject in children and adolescents. METHODS: Pediatric patients with intellectual disabilities (IQ < or = 70), subaverage intelligence (IQ between 71 and 85), or average-range intelligence (IQ > 85) were matched according to several clinical and etiologic criteria to determine the influence of IQ (N = 66). RESULTS: No dependency of seizure outcome, postoperative cognitive development, and behavioral outcome on the IQ level was found. All groups slightly improved in attention while memory functions tended to decrease and executive functions were stable. School placement remained unchanged for the majority of patients. Between 67 and 78% were seizure free 1 year after surgery (Engel outcome class I). CONCLUSIONS: IQ alone is not a good predictor of postoperative outcome in pediatric patients with epilepsy. As with patients of average-range intelligence, the decision to operate on patients with a low level of intelligence should depend on the results of the presurgical diagnostics. If the results of the neuropsychological examination indicate diffuse functional impairment, this should not hinder further steps, if all other findings are consistent.

Achievement↗

PubMed1996

Neuropsychological assessment of dementia: state of the art.

A comprehensive neuropsychological examination includes an assessment of both cognitive functions and personality characteristics. In order to evaluate dementia, the patient's present as well as the premorbid functioning has to be assessed, which is performed by means of tests, behavioral observations, rating scales, and inquiries. These methods are used for diagnostic purposes, for differential diagnostics, follow-up studies, and for evaluation of treatment effects. Recent research has shown that neuropsychological methods have a high sensitivity and specificity in detection of dementia, utilizing measures of episodic memory. For staging of dementia, episodic memory as well as other cognitive functions are necessary. The effectiveness of dementia differentiation by means of neuropsychological methods varies from quite good regarding frontal lobe degeneration to less good regarding cerebrovascular dementias, probably due to the variation in site, extent, number, and temporal characteristics of the lesion. Future development is required regarding methods for evaluation of premorbid functioning, instruments for assessment of executive functions, and personality characteristics in dementia. Furthermore, brain-behavior studies are needed to learn more about the relation between neuropsychological measures vs neuropathology, neurochemistry, and neuroimaging.

Aged↗

PubMed2006

Estrogen, cognitive function and negative symptoms in female schizophrenia.

The aim of this study was to evaluate the relationship of serum reproductive hormone levels with cognitive function and negative symptoms in schizophrenic women during the follicular phase of the menstrual cycle. Thirty-five women with chronic schizophrenia who had minimal positive symptoms participated in this study. We evaluated the correlation of serum reproductive hormone levels with the Scale for the Assessment of Negative Symptoms (SANS) and cognitive function tests such as the Immediate Visual Recognition Scale, Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Tests A and B, and Digit Symbol Test. The patients were divided into two subgroups (low estradiol group and normal estradiol group) using the normal serum reference range for estradiol. Significant correlation between SANS subcategories, such as Alogia and Attention Impairment, and estradiol were found. Moreover, significant relationships between the estradiol level and the Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Test B and Digit Symbol Test were observed. In the low estradiol group, the SANS scores, except for Anhedonia-Asociality and Avolition-Apathy, were significantly higher than those in the normal estradiol group. Patients in the low estradiol group had a significantly lower performance in the cognitive function tests, except Visual Recognition Scale, when compared to patients in the normal estradiol group. These results suggest that for schizophrenic women of reproductive age, lower levels of estrogen are associated with more severe negative symptomatology as well as reduced performance in cognitive function, especially verbal performance and executive functioning.

Adult↗

PubMed2002

Testing the efficiency and independence of attentional networks.

In recent years, three attentional networks have been defined in anatomical and functional terms. These functions involve alerting, orienting, and executive attention. Reaction time measures can be used to quantify the processing efficiency within each of these three networks. The Attention Network Test (ANT) is designed to evaluate alerting, orienting, and executive attention within a single 30-min testing session that can be easily performed by children, patients, and monkeys. A study with 40 normal adult subjects indicates that the ANT produces reliable single subject estimates of alerting, orienting, and executive function, and further suggests that the efficiencies of these three networks are uncorrelated. There are, however, some interactions in which alerting and orienting can modulate the degree of interference from flankers. This procedure may prove to be convenient and useful in evaluating attentional abnormalities associated with cases of brain injury, stroke, schizophrenia, and attention-deficit disorder. The ANT may also serve as an activation task for neuroimaging studies and as a phenotype for the study of the influence of genes on attentional networks.

Adult↗

PubMed2004

Effects of transcutaneous electrical nerve stimulation (TENS) on cognition, behavior, and the rest-activity rhythm in children with attention deficit hyperactivity disorder, combined type.

OBJECTIVE: The aim of this study was to examine the effects of transcutaneous electrical nerve stimulation (TENS) on cognition, behavior, and the rest-activity rhythm in children with attention deficit hyperactivity disorder, combined type (ADHD-CT). METHODS: Twenty-two children diagnosed with ADHD-CT received TENS treatment during 6 weeks, 2 times 30 min a day. Neuropsychological tests were administered to assess cognition, parent/teacher behavioral rating scales were used to measure behavior, and actigraphy was used to assess the rest-activity rhythm. RESULTS: TENS appeared to have a moderate beneficial influence on cognitive functions that load particularly on executive function. There was also improvement in behavior as measured by parent/teacher behavioral rating scales. Moreover, motor restlessness during sleep and motor activity during the day decreased by TENS. CONCLUSIONS: The effects of TENS in children with ADHD are modest but encouraging and warrant further research.

Adolescent↗

PubMed2000

Cognitive deficits associated with sleep apnea syndrome: a proposed neuropsychological test battery.

Numerous studies have assessed a wide range of cognitive deficits associated with obstructive sleep apnea syndrome (OSAS). The comparison of these various results, however, is hampered by the fact that different studies employ different neuropsychological tests, even when assessing the same function. The aim of this paper is to present a standardized neuropsychological test battery for the evaluation of OSAS patients. Following a description of the general characteristics of OSAS, we review the main cognitive functions reported as being impaired in OSAS patients. These include general intellectual functioning, attentional functioning, memory and learning abilities, executive functions, and motor performance. Based on this review, we propose a test battery designed to cover these cognitive processes while taking into account the time constraints present in most research and clinical centers. In addition to providing a comprehensive neuropsychological evaluation of OSAS patients, the proposed test battery should facilitate the comparison of results from different laboratories.

Adolescent↗

PubMed2001

Cognitive function in adolescents and young adults in complete remission from benign childhood epilepsy with centro-temporal spikes.

Benign childhood epilepsy with centrotemporal spikes (BECTS) is a frequent, benign childhood epilepsy with a good prognosis. However, neuropsychological deficits have been reported during its active phase. In this study, we evaluate the long-term neuropsychological consequences of this reputedly benign epilepsy, particularly the relation between paroxysmal abnormalities and cerebral language lateralization. The neuropsychological outcomes concerning both overall cognitive and lateral hemispheric functions were studied in twenty-three adolescents and young adults in total recovery from BECTS, in thirty-three controls without any significant past neurological history and in ten adolescents and young adults with complete resolution of generalized idiopathic epilepsy (childhood absence epilepsy or CAE). Language lateralization was evaluated using classical neuropsychological procedures (dichotic listening tasks, dual-task procedure). No difference was seen in the three populations with respect to overall cognitive function: memory, language and the executive functions. Although the Performance IQ was lower in patients in remission from CAE, the results were within normal limits. However, qualitative analysis of the dual-task procedure suggested a different organizational pattern for cerebral language in adolescents and young adults in remission from BECTS as compared to controls and patients in remission from CAE. The different organization in cerebral pattern in BECTS patients appeared to be related to the initial epileptic focus as determined by the EEG and/or the sleep-recording. We discuss the relationship between the presence of paroxysmal anomalies in childhood and subtle functional lateralized hemispheric abnormalities in adulthood.

Adolescent↗

PubMedDate not supplied

[Pragmatic impairments following traumatic brain injury].

OBJECTIVE: To describe how cognitive impairments contribute to the loss of communicative competence after traumatic brain injury (TBI), what instruments can be used to evaluate the pragmatic skills and which therapeutic approaches may be used to improve or compensate for this deficit. DISCUSSION: We present a detailed bibliographic review on the topic that shows how certain functions (namely, memory, attention and executive functions) interact with communication skills, both expressive and comprehensive. The pragmatic approaches for cognitive-communicative TBI impairments are allow to count typical difficulties that are described (difficulty with topic selection, turn-taking initiation, ability to respond or give indirect requests, ability to meet the informational needs of the listener, appropriateness of utterances within conversation, etc). Next a general outline of the assessment and treatment of is provided, including several strategies based on recovery and functional adaptation and compensation. CONCLUSIONS: Given the huge influence of communicative skills on social and vocational integration, it is crucial to obtain a better understanding of the interaction between cognitive functions and communicative skills. Therefore, we need to devise assessment protocols specifically designed for Spanish speakers as well as new therapeutic approaches to increase the life quality of this population. The specific approaches to improve narrative, procedural and conversational discourse must divide from the components of the pragmatic competence and promote the cooperative participation of the teamwork who attend to the patient.

Attention↗

PubMed2006

[Support of working life of persons with schizophrenia].

The aim of this study was to review the theories and methodologies for helping persons with schizophrenia to gain employment because working is one of the important factors for normalizing lives. The rate of employment among schizophrenics is determined by several factors including the unemployment rate of the nation, the date, sampling method and so on. However, persons with schizophrenia generally have had a lower employment rate around 20%, calculated as the rate of competitive employment compared to other psychiatric disorders both in the U.S. and Japan. Because traditional vocational rehabilitation did not lead to a good vocational outcome, supported employment has been developed over the last 20 years. Many studies clarified that supported employment led to a better outcome in the competitive employment, especially "Individual Placement and Support (IPS)". The systematic review of the Cochrane database, the Treatment Guideline of Schizophrenia of APA, and the PORT Treatment Guideline of Schizophrenia recommended the use of supported employment. Supplementary programs such as cognitive rehabilitation have been recently developed because psychiatric symptoms and social functioning were not improved and income and tenure of employment were not sufficient, even with supported employment. Cognitive functioning, attention, learning, memory, and executive functioning were verified to have influences on vocational functioning in many studies, and cognitive rehabilitation with supported employment was verified to improve vocational outcome. Six evidence based technologies of vocational rehabilitation were discussed. Vocational rehabilitation centers, day treatment centers aiming at competitive employment, and NPOs for employment of disabled persons are recommended as good clinical models of evidence based vocational rehabilitation. Professionals of the same agency in these models help people concerning both working and independent living, which is one of the important principles of IPS. Finally, we discussed several issues about methodologies and social framework which need further research and social agreement.

Cognition↗

PubMedDate not supplied

Associations between phenylalanine-to-tyrosine ratios and performance on tests of neuropsychological function in adolescents treated early and continuously for phenylketonuria.

Phenylketonuria (PKU) is a genetic disorder characterized by hyperphenylalaninemia. Treatment involves dietary phenylalanine restriction to prevent mental retardation. Because phenylalanine is involved in tyrosine synthesis and tyrosine is a catecholamine precursor, low tyrosine may lead to brain dopamine deficiencies. Because dopamine is involved in the modulation of prefrontally orchestrated executive functions, deficiencies may lead to executive impairments. Despite treatment, impairments in executive cognitive functions have been reported in young children with PKU. Outcome beyond middle childhood has not been extensively investigated. In this study, PKU-affected adolescents (N = 18) with normal-range IQ scores completed neuropsychological tests, and their performance was compared with unaffected peers (N = 16) and chronically ill controls (N = 17). Results demonstrated that the overall performance of the PKU group did not differ from that of the other two groups, but that performance of the PKU proband was associated with phenylalanine and tyrosine levels, and most strongly with phenylalanine-to-tyrosine ratios at several points in development. These findings provide a preliminary test of the dopamine hypothesis of PKU as it applies to adolescents and young adults.

Adolescent↗

PubMed2006

Alterations in working memory as a function of leukoaraiosis in dementia.

Dementia research suggests executive dysfunction is best understood within the context of disease-specific neuropathology. Leukoaraiosis (LA) results in executive dysfunction yet little is known about its impact on specific aspects of working memory (WM). This study aimed to investigate the relationship between MRI LA severity and WM in dementia. A visual rating scale was used to assign patients with dementia into groups with minimal-mild LA (Low LA; n=34) and moderate-severe LA (High LA; n=32). A modified Digit Span Backward Task consisting of 3-, 4-, and 5-span trials measured specific components of WM. Short-term storage and rehearsal in WM were assessed by the total number of digits reported regardless of recall order (ANY-ORDER; e.g., 47981 recalled '18943', score=4). Mental manipulation in the form of disengagement and temporal re-ordering was assessed by the total number of digits recalled in correct position (SERIAL-ORDER; e.g., 47981 recalled '18943', score=3). There was no difference between LA groups on ANY-ORDER comparisons. The High LA group obtained lower SERIAL-ORDER scores than the Low LA group. Stepwise regression analyses were conducted that first entered MMSE scores then composite z-scores reflecting executive functioning, language and memory. ANY-ORDER performance variance was explained solely by dementia severity. SERIAL-ORDER performance variance was further explained by executive dysfunction. Results suggest that high degrees of LA do not interfere with immediate (digit) recall but do interfere with disengagement and temporal re-ordering. LA may disconnect the frontal lobes from subcortical and cortical structures that form the neuronal networks critical for these WM functions.

Aged↗

PubMed2002

The neuropsychology of antisocial personality disorder.

BACKGROUND: The literature on executive function in antisocial populations is unclear due to variation in diagnostic criteria and variation in the inclusion of healthy control comparison groups. Some studies suggest prototypical psychopathy is associated with specific deficits in ventromedial prefrontal (VMPFC) function rather than dorsolateral prefrontal (DLPFC). Meta-analytical studies, however, suggest that antisocial personality disorder may be associated with a broader range of executive deficits. This study assessed DLPFC and VMPFC function in antisocial personality disorder subjects and controls using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a Go/NoGo task respectively. METHODS: All subjects were screened for Axis I pathology, substance misuse and prescribed medication. The performance of 29 subjects with antisocial personality disorder DSM-IV and 20 male right-handed controls (matched for age and IQ) on the neuropsychological test battery was compared. RESULTS: Subjects with antisocial personality disorder displayed impairments on DLPFC executive function tasks of planning ability and set shifting. Impairments were also seen in VMPFC Go/NoGo tasks and in visual memory tasks. CONCLUSIONS: Antisocial personality disorder is associated with a broad range of deficits in DLPFC and VMPFC function. Future studies need to examine relationships between the interpersonal and behavioural components of antisocial personality disorder and neuropsychological function.

Adolescent↗

PubMed2003

Lack of normal association between cerebellar volume and neuropsychological functions in first-episode schizophrenia.

OBJECTIVE: Functional neuroimaging studies have identified a role for the cerebellum in the neuropsychology of schizophrenia. Few studies, however, have examined the relationship between cerebellar size and neuropsychological functioning in schizophrenia. The authors' goal was to examine this relationship in patients and healthy comparison subjects. METHOD: Total cerebellar volume was computed from magnetic resonance images in 48 male and 33 female patients experiencing a first episode of schizophrenia and in 14 male and nine female healthy comparison subjects. Patients and comparison subjects completed a comprehensive neuropsychological assessment encompassing six domains of functioning: executive, motor, language, visuospatial, memory, and attention. A global domain of functioning was computed as the mean of these six domains. RESULTS: Larger cerebellar volume correlated significantly with better global functioning in healthy subjects but not among patients with schizophrenia; this relationship was significantly stronger in healthy subjects than in patients. Additional analyses revealed significant associations between cerebellar volume and visuospatial, executive, and memory functions in healthy volunteers but not among patients. CONCLUSIONS: The cerebellum plays a role in higher cognitive functions in healthy individuals, and normal associations between cerebellar size and function are absent in patients experiencing a first episode of schizophrenia. These findings are consistent with neurobiological models implicating the cerebellum in the pathogenesis of schizophrenia.

Adult↗

PubMed2000

Age-related differences in supervisory attentional system functions.

The authors explored the effect of age on executive functions by using 3 tasks (Tower of London, Hayling, and Brixton tests) designed to assess specific executive processes (planning, inhibition, and abstraction of logical rules) that were also sensitive to frontal dysfunction. The performance of elderly participants (n = 48) was significantly poorer than that of young participants (n = 47) in all 3 tasks. Processing speed, measured by means of a color-naming task, explained some but not all of the age-related differences. These results are discussed in terms of general and specific factors in cognitive aging.

Adaptation, Psychological↗

PubMed1997

Rapid rate transcranial magnetic stimulation--a safety study.

We assessed the safety of repeated short trains (4 stimuli) of rapid-rate transcranial magnetic stimulation (rrTMS) over the left motor cortex in 6 healthy normal subjects. rrTMS involved two separate blocks of 50 consecutive trains of 4 stimuli at a frequency of 20 Hz and an intensity of 5-10% above active motor threshold. We monitored EEG, and assessed aspects of neurological (balance, gait, two-point discrimination, blood pressure, pulse rate), cognitive (attention, memory, executive function) and motor function (speed of movement initiation and execution and manual dexterity) before and after the two blocks of rrTMS. EMG was also recorded from a number of hand, forearm and arm muscles contralateral to the site of stimulation. Two blocks of repeated rrTMS at 20 Hz and 5-10% above active motor threshold did not produce any adverse effects. Measures of neurological, cognitive and motor function showed no change following rrTMS. From the EMG recording there was evidence of increase in the amplitude of the motor evoked potentials (MEPs) recorded from the biceps in one subject during the first block of rrTMS, but this did not occur in the second block. A similar magnification of MEPs was also observed in another subject only during the second block of stimulation. When applied using parameters falling within published guidelines (Pascual-Leone et al., 1993; Pascual-Leone et al., 1994), repeated rrTMS is a relatively safe technique in healthy normal subjects. As rrTMS allows disruption of cortical function for a longer period, it has the potential of becoming a particularly useful tool for the study of cognitive function as well as sensory or motor function.

Adult↗