Cognitive impairment in MS: Impact of white matter integrity, gray matter volume, and lesions.
ABSTRACT OBJECTIVE: To investigate whether extent and severity of white matter (WM) damage, as measured with diffusion tensor imaging (DTI), can distinguish cognitively preserved (CP) from cognitively impaired (CI) multiple sclerosis (MS) patients. METHODS: Conventional MRI and DTI data were acquired from 55 MS patients (35 CP, 20 CI) and 30 healthy controls (HC). Voxelwise analyses were used to investigate fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity of a WM skeleton. Regional gray matter volume was quantified and lesion probability maps were generated. RESULTS: Compared to HCs, decreased FA was found in 49% of the investigated WM skeleton in CP patients and in 76% of the investigated WM in CI patients. Several brain areas that showed reduced FA in both patient groups were significantly worse in CI patients, i.e, corpus callosum, superior and inferior longitudinal fasciculus, corticospinal tracts, forceps major, cingulum, and fornices. In CI patients, WM integrity damage was additionally seen in cortical brain areas, thalamus, uncinate fasciculus, brainstem, and cerebellum. These findings were independent of lesion location and regional gray matter volume, since no differences were found between the groups. CONCLUSION: CI patients diverged from CP patients only on DTI metrics. WM integrity changes were found in areas that are highly relevant for cognition in the CI patients but not in the CP patients. These WM changes are therefore thought to be related to the cognitive deficits and suggest that DTI might be a powerful tool when monitoring cognitive impairment in MS.
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ABSTRACT: Visual perception of body motion is vital for everyday activities such as social interaction, motor learning or car driving. Tumors to the left lateral cerebellum impair visual perception of body motion. However, compensatory potential after cerebellar damage and underlying neural mechanisms remain unknown. In the present study, visual sensitivity to point-light body motion was psychophysically assessed in patient SL with dysplastic gangliocytoma (Lhermitte-Duclos disease, WHO grade I) to the left cerebellum before and after neurosurgery, and in a group of healthy matched controls. Brain activity during processing of body motion was assessed by functional MRI. Alterations in underlying cerebro-cerebellar circuitry were studied by psychophysiological interaction (PPI) analysis. Visual sensitivity to body motion in patient SL before neurosurgery was substantially lower than in controls, with significant improvement after neurosurgery. Functional MRI in patient SL revealed a similar pattern of cerebellar activation during biological motion processing as in healthy participants, but located more medially, in the left cerebellar lobules III and IX. As in normalcy, PPI analysis showed cerebellar communication with a region in the superior temporal sulcus, but located more anteriorly. The findings demonstrate a potential for recovery of visual body motion processing, likely mediated by topographic shifts within the corresponding cerebro-cerebellar circuitry induced by damage to the cerebellum. The outcome is of importance for further understanding of cerebellar plasticity and neural circuits underpinning visual social cognition.Cortex 10/2014; · 6.04 Impact Factor
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ABSTRACT: Neuropsychological deficits constitute enduring trait-like features in bipolar disorder (BD), and persist in euthymia. White matter (WM) abnormalities are one of the most consistently reported findings in neuroimaging studies of BD. We hypothesized that neuropsychological performances could correlate with WM integrity in a sample of bipolar patients in core WM tracts. Seventy-eight patients affected by BD were evaluated for verbal memory, working memory, psychomotor coordination, executive functions, attention and information processing, and verbal fluency through the Brief Assessment of Cognition in Schizophrenia. White matter integrity was evaluated using DTI and tract-based spatial statistics with threshold free cluster enhancement (p>0.949). We observed that cognitive performances in attention and information processing, working memory, executive functions and psychomotor coordination were associated with DTI measures of WM integrity in several association fibres: inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, cingulum bundle, corpus callosum, and corona radiata. The drug treatments administered during the course of the illness could have influenced DTI measures and neurocognitive function. Other limitations include issues such as generalizability due to the lack of a control group, possible undetected past comorbidities, population stratification, and the presence of a 28% of patients which previously experienced delusions. This is the first study to use a validated cognitive battery to investigate the principal cognitive domains in BD. Our data confirm the importance of WM integrity as a neurobiological underpinning of cognitive deficits. Copyright © 2014 Elsevier B.V. All rights reserved.Journal of Affective Disorders 12/2014; 174C:342-352. · 3.76 Impact Factor
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ABSTRACT: Background: Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast “connectometry” approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS. Methods: We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast “connectometry” by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores. Results: In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, P < 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage. Conclusion: Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.Human Brain Mapping 11/2014; · 6.92 Impact Factor