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PubMed2026

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n = 38) or sham stimulation (n = 36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0 mA, 20 min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74 ± 2.76 vs. sham: 2.69 ± 2.69; t = 4.799, p < 0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p < 0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p < 0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

Humans↗

PubMed2007

'Prefrontal' cognitive performance of healthy subjects positively correlates with cerebral FDOPA influx: an exploratory [18F]-fluoro-L-DOPA-PET investigation.

Dopamine neurotransmission influences those cognitive processes, which are generally regarded as prefrontal cortical functions. In previous positron-emission-tomography (PET) studies, net blood-brain clearance of [18F]-fluoro-l-DOPA (FDOPA) correlated with impaired cognitive performance in patients with Parkinson's disease or schizophrenia. We hypothesized that FDOPA influx also correlates with performance of cognitive tasks associated with prefrontal functioning in healthy volunteers. The net blood-brain clearance of FDOPA (K(in)(app)) was mapped in a group of 11 healthy volunteers and calculated in striatal volumes-of-interest. The Wisconsin-Card-Sorting-Test (WCST), Stroop-Test, Trail-Making-Test (TMT-A/B), and Continuous-Performance-Test (CPT-M) had been administered previously to the same subjects. No correlation of K(in) (app) with perseverative errors in WCST or age could be found. However, there were significant positive correlations between the magnitude of K(in)(app) in caudate nucleus, putamen, and midbrain with performance of the TMT-B, CPT-M, and the Stroop test. Highest correlations were found between the time needed to perform the Stroop interference task and the K(in)(app) of striatal areas (Caudate nucleus: -0.780, P = 0.005; putamen: -0.870, P < 0. 001). Thus, the present findings reveal a strong correlation between dopamine synthesis capacity in striatum of healthy volunteers and performance of cognitive tasks linked to the prefrontal cortex.

Adult↗

PubMed2004

Incomplete improvement of visuo-motor deficits in patients with minimal hepatic encephalopathy after liver transplantation.

Previous studies have suggested reversibility of minimal hepatic encephalopathy in patients with liver cirrhosis after liver transplantation (LT), however, this topic is controversially discussed. We investigated this issue in a prospective study on liver cirrhotic patients listed for LT. Patients were investigated before and after liver transplantation (on average 21 months later) using a neuropsychological test battery which measured visuo-constructive and visuo-motor ability, verbal fluency, and memory function. To assess visuo-motor and visuo-constructive functions, we performed 4 tests: Rey Complex Figure Test copy, trail making tests A and B, and digital symbol test. The average percentile score of the tests, arbitrarily named the visuo-motor and visuo-constructive performance score (VMCP), was calculated. After LT, the patients did not demonstrate a significant increase of VMCP (P =.29) and additionally showed significantly lower VMCP score (P =.041) compared to control group. Analysis of individual responses showed that only 7 of 14 patients improved their VMCP values after LT. These data indicate that the cirrhosis-associated visuo-motor deficits subside or disappear only in some of the patients after LT, whereas a significant number of patients show no improvement of the visuo-motor and visuo-constructive function. We concluded that monitoring of cognitive and visuo-motor functioning is important for the post-transplant rehabilitation of patients with liver cirrhosis.

Cognition Disorders↗

PubMed1987

Neuropsychologic deficits and the risk for alcoholism.

The importance of genetic factors in alcoholism has prompted a search for trait or vulnerability markers of a predisposition toward this disorder. Responding to the diverse and at times persistent neuropsychologic impairments observed in alcoholics, several laboratories have documented possible neurocognitive deficits in young men with alcoholic biologic fathers. This paper begins with a review of this complex, and at times contradictory, literature and then presents original data comparing 24 sons of alcoholic fathers with 24 control subjects matched on demography and drinking histories. Among the present sample of students and working men aged 18 to 25 years, the sons of alcoholics demonstrated no significant levels of impairment on the Category Test, the Trail Making Test Part B, Body Sway, Word REcall, or the Missing Digit Test. Taken together with the literature, these negative findings call into question whether any specific array of neurocognitive or psychomotor test results will in the near future prove to be clinically relevant general markers of a risk for alcoholism.

Adult↗

PubMed2005

Long-term neuropsychological impact of brief occupational exposure to organic solvents.

This case series describes the cognitive functioning of 10 individuals who were briefly exposed to a mixture of organic solvents as a result of an industrial accident. Data were obtained 10 years after the exposure on measures of intellect, memory, attention, and executive functioning, using standardised neuropsychological measures including WAIS III, WMS III, Hayling and Brixton Tests, The Trail Making Test, Controlled Oral Word Association, Rey-Osterrieth Complex Figure Test, and The Speed and Capacity of Language-Processing Test. The group performed in the average range across the majority of measures but deficits (z > 1.0 S.D.) were observed on tests that measure speed of information processing, memory, attention, and verbal fluency. Discrepancy scores between the NART and the WAIS suggest subtle but statistically significant decline in performance IQ following solvent exposure.

Accidents, Occupational↗

PubMed2006

Improving the ecological validity of executive functioning assessment.

The current study investigated ways to improve the ecological validity of the neuropsychological assessment of executive functioning through the formal assessment of compensatory strategies and environmental cognitive demands. Results indicated that the group of executive functioning tests (i.e., Trail Making Test, Wisconsin Card Sorting Test, Stroop, and Controlled Oral Word Association Test) accounted for 18-20% of the variance in everyday executive ability as measured by the Dysexecutive Questionnaire and Brock Adaptive Functioning Questionnaire. The addition of extra-test variables significantly increased the variance in everyday executive ability accounted for. The current study adds to the literature on the ecological validity of executive functioning assessment by highlighting the importance of extra-test variables when trying to understand the complex relationship between cognitive testing and real world performance.

Activities of Daily Living↗

PubMed2005

Executive function and memory in posttraumatic stress disorder: a study of Bosnian war veterans.

The present study assessed neuropsychological functions related to attention, executive function and everyday memory in a group of men with a diagnosis of combat-related posttraumatic stress disorder (PTSD). Twenty Bosnian male combat veterans with a diagnosis of PTSD were tested using the Sustained Attention to Response Task, the Hayling Sentence Completion Test, the Trail Making Test, Rivermead Behavioral Memory Test and Wechsler Adult Intelligence Scale (verbal scales). Their performance was compared with age- and IQ-matched male war veterans with no PTSD. The study disclosed pervasive cognitive impairments with large effect sizes pertaining to attention, working memory, executive function, and memory. The effects did not appear to be attributable to alcohol abuse, loss of consciousness, or educational level. We speculate that, in the present group of combat veterans, PTSD was associated with dysfunction of a higher-level attentional resource which in turn affected the activity in other systems concerned with memory and thought.

Adult↗

PubMed2005

Clinical significance of extrapyramidal signs in patients with cirrhosis.

BACKGROUND/AIMS: Extrapyramidal signs have been described in cirrhosis and there is little information about their clinical significance. The aims of this study have been to investigate the relationship between extrapyramidal signs and cognitive impairment, and what is their influence on quality of life. METHODS: 46 patients with cirrhosis were evaluated for cognitive impairment with psychometric tests (Trail-Making Test part A, Grooved-Pegboard, Block-Design, Oral Symbol Digit and Stroop Test) and cognitive evoked potentials (P300). Extrapyramidal signs were evaluated using the UPDRS scale. Health-related quality of life (HRQL) was measured using SF-36 scale and the Chronic Liver Disease Questionnaire (CLDQ). RESULTS: Twenty-two patients had extrapyramidal signs, and these patients scored worse in all psychometric tests, except Block-Design. Patients with extrapyramidal signs also showed a longer P300 latency. Moreover, patients with extrapyramidal signs had the worst score in all the HRQL scales used. A multivariate analysis disclosed that the only variable showing an independent relationship to the mental component summary of SF-36 and with CLDQ was UPDRS score. CONCLUSIONS: We have found a clear relationship between the presence of extrapyramidal signs and cognitive impairment. Moreover, patients with extrapyramidal signs have worse scores in quality of life scales.

Basal Ganglia Diseases↗

PubMed2006

Efficacy and tolerability of OROS methylphenidate in Korean children with attention-deficit/hyperactivity disorder.

This study evaluated the efficacy and tolerability in the initiation treatment of Concerta (OROS methylphenidate HCl) in Korean children with Attention-Deficit/Hyperactivity Disorder (AD/HD). One hundred and nineteen children with AD/HD were entered into a multi-center, open-label, four-week trial. The dosage of Concerta was adjusted by the investigators based on symptoms and safety assessments performed on a weekly basis. The safety of the drug and its efficacy for attention, behavior, and cognitive function were assessed. The primary outcome measures for efficacy were the Parent and Teacher IOWA Conners Rating Scales, Peer Interaction Items, and the Clinical Global Impression Scale. Cognitive tests (Continuous Performance Test, Matched Familiar Figure Test, Verbal Fluency Test, and Trail Making Test) were included as the secondary outcome measures. In most participants, OROS methylphenidate was well tolerated. There were significant improvements in attention, behavior, and function as measured by parents, teachers, and investigators. The benefit of the initiation of OROS methylphenidate in children with AD/HD was shown on the cognitive tests as well. These data provide support for the benefit of the once-daily methylphenidate preparation, Concerta in the treatment of Korean children with AD/HD. Children were initiated safely in this short-term trial, and its effectiveness was evident in the behavioral, as well as neuropsychological measurements.

Adolescent↗

PubMed2004

Concurrent validity of the stroke drivers screening assessment.

OBJECTIVE: To determine the concurrent validity of the Stroke Drivers Screening Assessment (SDSA). DESIGN: Comparison of the SDSA with criterion standards. SETTING: Subjects' homes in the community in the United Kingdom. PARTICIPANTS: Ninety-three stroke patients (age range, 22-83y) who were referred for assessment of fitness to drive or who had been driving before their stroke. Participants were assessed a median of 5 months post stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients were assessed on the SDSA and tests of visuospatial ability (Visual Object and Space Perception [VOSP] Battery), executive abilities (Stroop Neuropsychological Screening Test, Trail-Making Test [TMT], Cognitive Estimates Test [CET]), and visual memory (Recognition Memory Tests [RMT], Verbal Descriptions of Road Signs [VDRS]). RESULTS: The SDSA subtests all correlated significantly with the Stroop test (P<.001) and TMT (P<.001), which suggests that they measure executive abilities and attention. The SDSA Dot Cancellation (DC) also correlated significantly with the VDRS (P<.01). The SDSA Square Matrices (SM) test correlated significantly with the VOSP cube analysis (P< or =.01) and the RMT faces subtest (P<.001), which suggests that the SM test also measures visuospatial abilities and visual memory. The SDSA Road Sign Recognition (RSR) test also correlated significantly with the VOSP cube analysis (P<.05), which suggests that the RSR test also measures visuospatial abilities. Factor analysis produced a 2-factor solution with DC time, SM compass, and RSR all loading on factor 1, together with the Stroop and TMT. This factor was interpreted as "executive abilities and attention." The RMT faces subtest and CET loaded onto a second factor. CONCLUSIONS: The SDSA seems to measure predominantly attention and executive abilities, which have previously been shown to be important determinants of safety to drive. This may account for the high predictive validity of the SDSA.

Adult↗

PubMed1999

Neuropsychological profiles of FMR-1 premutation and full-mutation carrier females

The present French-German investigation of fragile-X syndrome (fra-X) was undertaken to disentangle genetic from environmental effects on cognitive performance as assessed with the following measures: Wechsler Adult Intelligence Scale-Revised (WAIS-R), Wisconsin Card Sorting Test, Trail-Making Test, Tower of Hanai, Verbal Fluency Test, Stroop Test, short-term and consolidation memory, and the d2 task. Groups with different genotypes (n = 11 mothers with a full mutation in the FMR-1 gene of fra-X children; n = 65 mothers with a premutation in the FMR-1 gene of fra-X children; n = 18 siblings of these mothers with normal CGG repeats) and with different psychosocial stressors from fra-X families (n = 14 siblings with a premutation but without affected children of their own) were examined. A group of mothers of non-fra-X autistic children (n = 39) formed an external control group. Previous findings were replicated concerning cognitive performance of FMR-1 full-mutation carrier mothers, who were characterized by lower overall IQ and poorer performance than the group of mothers with the FMR-1 premutation in verbal and performance subtests of the WAIS-R, tests of executive-frontal lobe functioning, and tests of sustained attention. Carriers of the FMR-1 premutation, whether they were mothers of affected children or not,performed in a similar way on all neuropsychological tasks to the intrafamilial control group without CGG amplification. On the basis of these results, it is concluded that there is no neuropsychological evidence of reduced cognitive performance of FMR-1 premutation carriers compared with performance of two control groups with normal CGG repeats. Furthermore, the psychosocial burden of raising fra-X children does not exert an environmental effect on neuropsychological test performance.

Journal Article↗

PubMed2003

Neuropsychological-neurophysiological alterations and brain atrophy in cirrhotic patients.

Psychometric performance has been reported to be related to brain atrophy in cirrhotics, but the relationship between brain atrophy and EEG findings is still unknown. The aim of this study was to ascertain the relationship among brain atrophy, EEG, and cognitive performance in cirrhotics. Sixty-eight cirrhotics (age = 55 +/- 10 years; males-66%) underwent psychometric evaluation (Symbol Digit Test, Trail Making Test-Part A, Scan test), EEG recording and spectral analysis (S-EEG), and brain CT scan. Central brain atrophy was ascertained by the following indexes of brain atrophy: the Evans' index, the bicaudate index, the cella media index, the bifrontal index, and the ventricular index; cortical brain atrophy by the sulci index. The severity of liver failure was assessed by the Child-Pugh score: 18% of patients were Child-Pugh Class A, 50% Class B, and 32% Class C. Central and cortical atrophies were found to be correlated with age, but not with the Child-Pugh score. Psychometric performance and the EEG mean dominant frequency (MDF) were found to be correlated with brain atrophy. Multivariate analysis showed that a poor psychometric performance was independently predicted by EEG slowing (MDF: p < 0.01) and by central brain atrophy (cella media index: p < 0.01). In conclusion, brain atrophy was associated with a poor psychometric performance and EEG alterations in cirrhosis. Both brain atrophy and EEG alterations independently predicted cognitive dysfunction in cirrhotic patients.

Adult↗

PubMed2003

Cognitive dysfunction and health-related quality of life in long-term liver transplant survivors.

Although several studies have investigated short-term effects of liver transplantation on cognitive function and health-related quality of life, there have been no studies looking at long-term effects. Patients who received a single liver transplant at St James's University Hospital (Leeds, UK) before October 1, 1991, were invited to participate in this cross-sectional study. Cognitive function was assessed using the Mini-Mental State Examination, the Rey Auditory Verbal Learning Test, trail-making tests, the Stroop test, and the Benton Visual Retention Test. Anxiety and depression were documented using the Hospital Anxiety and Depression Scale. Health-related quality of life was assessed using the EuroQol. Twenty-five healthy volunteers acted as controls. Thirty-six patients had undergone transplantation before October 1, 1991. Thirteen patients (36%) had died, 6 patients had received more than one transplant, 2 patients did not speak English, and 3 patients did not want to participate, leaving 12 patients included in the study. Patients scored significantly lower on measures of health-related quality of life than healthy controls, but there were no differences in levels of anxiety or depression. Patients scored significantly lower than controls across a wide range of cognitive functions, suggesting global cognitive impairment. We show that patients who survive for more than 10 years after liver transplantation have significant cognitive dysfunction and poor health-related quality of life. Whether these patients never return to normal after transplantation or whether they experience an increased rate of decline in cognitive function and health-related quality of life is uncertain and requires further study.

Aged↗

PubMed1999

Practice effects on commonly used measures of executive function across twelve months.

Fifty men (age M = 32.50; education M = 14.98 years) were administered the Wisconsin Card Sorting Test (WCST), Ruff Figural Fluency Test (FFT), Verbal Concept Attainment Test (VCAT) Trail Making Test, Parts A and B (TMT), and F-A-S Verbal Fluency at baseline and 12 months later. WCST, FFT, and VCAT scores improved significantly over a 12-month interval. In contrast, TMT and F-A-S scores did not change. Level of intellectual ability failed to moderate the effect of previous testing upon performance. Suggestions concerning the use of these measures in longitudinal research designs and clinical follow-up examinations are offered, and reliable change indices concerning these measures are included.

Adult↗

PubMed1977

The relationship of perceptual field orientation to measures of cognitive functioning and current adaptive abilities in alcoholics and nonalcoholics.

The present study investigated the influence of perceptual field orientation, as measured by the Group Embedded Figures Test (GEFT), on cognitive functioning among alcoholics and nonalcoholics. The subjects were classified as field dependent, intermediate, or field independent based upon their GEFT scores. Cognitive function was assessed by the Wechsler-Bellevue Intelligence Scale as well as the Category Test. Tactual Performance Test, and Trail Making Tests of the Halstead-Reitan Neuropsychological Test Battery. Three primary findings emerged. First, the alcoholics appeared to be significantly impaired on measures of abstraction, problem solving, and adaptive abilities relative to nonalcoholics. Second, a direct relationship was found between GEFT scores and level of cognitive function within both alcoholic and nonalcoholic samples, with field-dependent subjects evidencing the most impaired performance. Third, the level of perceptual field orientation accounted for a large portion of the variance between the alcoholic and nonalcoholic samples, with field-independent alcoholics performing at a level comparable to or greater than other nonalcoholic subroups on a number of the cognitive variables. These results provide validational support for the GEFT and indicate that field orientation may be a relevant variable in the assessment of cognitive function in both alcoholics and nonalcoholics.

Adaptation, Psychological↗

PubMed1999

Differential patterns of executive function in children with attention-deficit hyperactivity disorder according to gender and subtype.

The present investigation examined differential patterns in executive functions of children with attention-deficit hyperactivity disorder (ADHD; no diagnosed comorbid disorders) according to subtype and gender, and identified instrumentation sensitive to executive function in children aged 6 to 12 years with ADHD. Data were obtained from 94 children diagnosed with ADHD (predominantly inattentive, n = 32, ADHD combined, n = 62), and from 28 controls. Participants with ADHD, who were unmedicated at the time of testing, were administered five tests of executive function (the Wisconsin Card Sorting Test, the Stroop Color-Word Test, the Matching Familiar Figures Test, the Trail Making Test, and the Tower of London). A two-way multivariate analysis of covariance with age as the covariate and subtype and gender as the independent variables was conducted on all of the tests administered. While children with ADHD predominantly inattentive and those with ADHD combined differed from controls, it was only the latter subtype that differed significantly in perseveration and response inhibition. The absence of diagnosed comorbidity in the children with ADHD at the time of test administration demonstrates that the impairments in executive function are clearly located in ADHD, particularly in the ADHD combined subtype, thus providing support for Barkley's proposed unifying theory of ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Phenylketonuria: no specific frontal lobe-dependent neuropsychological deficits of early-treated patients in comparison with diabetics.

Neuropsychologic studies have shown that even phenylketonuric patients treated early suffer from phenylalanine-related deficits in all age periods, from childhood to adulthood. This study was performed to determine whether phenylketonuric children show specific frontal lobe-dependent deficits when compared with diabetic patients. The comparative study included 42 phenylketonuric patients, 10 to 18 y of age [mean 14.7 (years, months), SD 2.9], and 42 diabetic patients matched for sex, age, and socioeconomic status. Patients were assessed for intelligence quotient (Culture Fair Intelligence Test), information processing (Wisconsin Card Sorting Test, Trail-Making Test), and selective (Stroop task) as well as sustained attention (Test d-2). Phenylketonuric patients had significantly poorer results than the diabetic patients. Within all tests, however, this was due to reduced performance speed, not to deficits in specific functions. Patients did not show deficits in insight and learning. The selection abilities and the sustained attention of the phenylketonuric patients were not impaired. Performance speed and blood phenylalanine levels were negatively correlated. Elevated phenylalanine levels may cause an imbalance in neurotransmitter metabolism. However, this seems to refer to a global neurotoxic effect rather than to specific effects on the dopaminergic system, which would affect specifically the activation of the frontal lobes.

Adaptation, Psychological↗

PubMed1997

Decline of frontal lobe functions in subjects with age-associated memory impairment.

OBJECTIVE: To assess frontal lobe functions of subjects with age-associated memory impairment (AAMI) and to examine whether performance on neuropsychological tests is correlated with the volume of the frontal lobes in magnetic resonance imaging. DESIGN: Cross-sectional two-group comparison. SETTING: The Memory Research Clinic of Kuopio University and the Magnetic Resonance Imaging Center of Kuopio University Hospital. PARTICIPANTS: Ninety subjects (mean age, 70.5 years), 43 with AAMI diagnosed according to National Institute of Mental Health criteria and 47 age-matched healthy controls. MEASUREMENTS: Four neuropsychological tests were used to assess frontal lobe function: Verbal Fluency Test (VFT), Modified Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Stroop Test (ST). A 1.5-T magnetic resonance imager was used for volume measurements. RESULTS: The AAMI subjects scored significantly worse on the WCST, ST, and TMT compared with controls (ANCOVA, adjusted for age and education, p < 0.05). The frontal lobe volumes did not differ between AAMI subjects and controls. CONCLUSIONS: AAMI subjects appear to be impaired not only in tests assessing memory but also in tests of executive functions. This finding agrees with previous reports suggesting a central role for frontal dysfunction in memory loss of elderly people.

Aged↗