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  • Title: Functional connectivity changes related to cognitive and motor performance in spinocerebellar ataxia type 2.
    Author: Hernandez-Castillo CR, Galvez V, Mercadillo RE, Díaz R, Yescas P, Martinez L, Ochoa A, Velazquez-Perez L, Fernandez-Ruiz J.
    Journal: Mov Disord; 2015 Sep; 30(10):1391-9. PubMed ID: 26256273.
    Abstract:
    BACKGROUND: Several neuropathological studies in spinocerebellar ataxia type 2 (SCA2) have revealed significant atrophy of the cerebellum, brainstem, sensorimotor cortex, and several regions in the frontal lobe. However, the impact of the neurodegeneration on the functional integration of the remaining tissue is unknown. To analyze the clinical impact of these functional changes, we correlated the abnormal functional connectivity found in SCA2 patients with their scores in clinical scales. To obtain the functional connectivity changes, we followed two approaches. In one we used areas with significant cerebellar gray matter atrophy as anchor seeds, and in the other we performed a whole-brain data-driven analysis. METHODS: Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Voxel-based morphometry and resting-state functional magnetic resonance imaging (fMRI) were done to analyze structural and functional brain changes. Independent component analysis and dual regression were used for intrinsic network comparison. Significant functional connectivity differences were correlated with the behavioral scores. RESULTS: Seed-based analysis found reduced functional connectivity within the cerebellum and between the cerebellum and frontal/parietal cortices. Cerebellar functional connectivity increases were found with parietal, frontal, and temporal areas. Intrinsic network analysis found a functional decrease in the cerebellar network, and increase in the default-mode and fronto-parietal networks. Further analysis showed significant correlations between clinical scores and the abnormal functional connectivity strength. CONCLUSION: Our findings show significant correlations between functional connectivity changes in key areas affected in SCA2 and these patients' motor and neuropsychological impairments, adding an important insight to our understanding of the pathophysiology of SCA2.
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