No abstract

There is an increasing demand for alternate-form neuropsychological tests that can be used in clinical trials with little risk of direct practice effect. Although the Brief Visuospatial Memory Test (BVMT) includes six equivalent alternate forms, its administration is limited to an immediate and 25-min delayed free-recall trial. We now present a revised version of the BVMT called the Brief Visuospatial Memory Test-Revised (BVMT-R) that includes three learning trials, a 25-min delayed recall trial, and a delayed yes/no recognition task. A new scoring system, which accounts for the location of test stimuli as well as the accuracy of recall, is also introduced. Using these new administration and scoring procedures, we administered the BVMT-R to 261 neuropsychiatric patients and 456 normal healthy adults. The results indicated that the test has excellent interform reliability, and the construct and criterion-related validity of the test were supported in studies using clinical samples. Although the BVMT-R is not without its limitations, the test's brevity and alternate-form capacity make it a valuable instrument for serial neuropsychological assessments.We recently presented a newly developed, multiple-form test of Visuospatial memory called the Brief Visuospatial Memory Test (BVMT;. Modeled after the Visual Reproduction subtest of the Wechsler Memory Scales (Russell, 1975;1988;Wechsler 1945Wechsler , 1987, the test was created to provide a quick means of assessing visual memory, using multiple test forms. In its original version, the BVMT required patients to reproduce as many figures as possible from an array of six figures, which was presented for 10 s. A delayed recall trial was administered 25 min after the immediate recall trial. Our results demonstrated that the six BVMT forms are equivalent in difficulty and that the recall scores discriminate brain-injured patients from normal controls.

We present a multivariate alternative to the voxel-based morphometry (VBM) approach called source-based morphometry (SBM), to study gray matter differences between patients and healthy controls. The SBM approach begins with the same preprocessing procedures as VBM. Next, independent component analysis is used to identify naturally grouping, maximally independent sources. Finally, statistical analyses are used to determine the significant sources and their relationship to other variables. The identified “source networks,” groups of spatially distinct regions with common covariation among subjects, provide information about localization of gray matter changes and their variation among individuals. In this study, we first compared VBM and SBM via a simulation and then applied both methods to real data obtained from 120 chronic schizophrenia patients and 120 healthy controls. SBM identified five gray matter sources as significantly associated with schizophrenia. These included sources in the bilateral temporal lobes, thalamus, basal ganglia, parietal lobe, and frontotemporal regions. None of these showed an effect of sex. Two sources in the bilateral temporal and parietal lobes showed age-related reductions. The most significant source of schizophrenia-related gray matter changes identified by SBM occurred in the bilateral temporal lobe, while the most significant change found by VBM occurred in the thalamus. The SBM approach found changes not identified by VBM in basal ganglia, parietal, and occipital lobe. These findings show that SBM is a multivariate alternative to VBM, with wide applicability to studying changes in brain structure.

Changes in cognitive functioning often result from traumatic brain injury (TBI) and predict other important aspects of psychosocial recovery. Despite this pivotal role, no quantitative review of cognitive functioning across the spectrum of TBI severity has been reported. We therefore conducted a meta-analysis of 39 mostly cross-sectional studies of the cognitive effects of mild head injury (MHI) and moderate-severe TBI from the acute phase through long-term follow-up. The studies reported 48 comparisons of patients (n = 1716) and control subjects (n = 1164). Averaged across all follow-up periods, the effect of moderate-severe TBI (weighted mean Cohen's d = -0.74) was more than three times the effect of MHI (weighted mean d = -0.24) on overall cognitive functioning. Further, the natural logarithm of the follow-up interval correlated very strongly with estimates of d among patients with MHI, but less so among those with moderate-severe TBI. In short, findings from published research suggest that overall cognitive functioning recovers most rapidly during the first few weeks following MHI, and essentially returns to baseline within 1-3 months. Cognitive functioning also improves during the first two years after moderate-severe TBI, but remains markedly impaired even among patients tested > 2 years post-injury.

The present investigation examined the validity of the revised Hopkins Verbal Learning Test (HVLT-R). In a principal components analysis with varimax rotation, measures of new learning and delayed recall loaded on a single factor distinguishable from measures related to general cognitive function and visual memory. The HVLT-R also correlated most strongly with other tests of verbal memory and relatively weakly with a test of general intelligence. Group comparisons showed that normal controls performed better than age- and education-matched patients with probable Alzheimer's disease (AD) or vascular dementia (VaD). Discriminant function analyses and Bayesian statistics revealed high classification accuracies for dementia patients versus controls. When scores on the HVLT-R and other neuropsychological tests were subjected to discriminant function analyses, performance on the HVLT-R delayed recognition task was found to be the most useful in discriminating patients with AD from those with VaD. We conclude that the HVLT-R is a valid test of verbal learning and memory that is best suited for use with elderly patients suspected of dementia.

In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [11 C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.

Lesch-Nyhan disease (LND) is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit over-production of uric acid, along with a characteristic neurobehavioural syndrome that includes mental retardation, recurrent self-injurious behaviour and motor disability. Prior studies involving relatively small numbers of patients have provided different conclusions on the nature of the motor disorder. The current study includes the results of a multi-centre international prospective study of the motor disorder in the largest cohort of patients studied to date. A total of 44 patients ranging from 2 to 38 years presented a characteristic motor syndrome that involved severe action dystonia superimposed on baseline hypotonia. Although some patients also displayed other extrapyramidal or pyramidal signs, these were always less prominent than dystonia. These results are compared with a comprehensive review of 122 prior reports that included a total of 254 patients. Explanations for the differing observations available in the literature are provided, along with a summary of how the motor disorder of LND relates to current understanding of its pathophysiology involving the basal ganglia.

Background Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives. Methods We investigated resting state functional MRI (fMRI) in 70 schizophrenia and 64 psychotic bipolar probands, their respective first-degree relatives (N = 70 and 52) and 118 healthy subjects. We used independent component analysis (ICA) to identify components representing various resting state networks and assessed spatial aspects of functional connectivity within all networks. We first investigated group differences using five-level, one-way analysis of covariance (ANCOVA), followed by post-hoc t-tests within regions displaying ANCOVA group differences and correlation of such functional connectivity measures with symptom ratings to examine clinical relationships. Results Seven different networks revealed abnormalities (five-level one-way ANCOVA, family-wise error correction p < 0.05): (A) fronto-occipital, (B) midbrain/cerebellum, (C) frontal/thalamic/basal ganglia, (D) meso/paralimbic, (E) posterior default mode network, (F) fronto-temporal/paralimbic and (G) sensorimotor networks. Abnormalities in networks B and F were unique to schizophrenia probands only. Furthermore, abnormalities in networks D and E were common to both patient groups. Finally, networks A, C and G showed abnormalities shared by probands and their relative groups. Negative correlation with Positive and Negative Syndrome Scale (PANSS) negative and positive scores were found in regions within network C and F respectively, and positive correlation with PANSS negative scores was found in regions in network D among schizophrenia probands only. Conclusion Schizophrenia, psychotic bipolar probands and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes.