Carlos R Hernandez-Castillo1, Víctor Galvez2, Roberto E Mercadillo3, Rosalinda Díaz4, Petra Yescas5, Leticia Martinez5, Adriana Ochoa5, Luis Velazquez-Perez6, Juan Fernandez-Ruiz2,4,7. 1. Consejo Nacional de Ciencia y Tecnología-Cátedras-Instituto de Neuroetologia, Universidad Veracruzana, México. 2. Programa de Doctorado en Neuroetología, Universidad Veracruzana, México. 3. Cátedras CONACYT, Área de Neurociencias, Depto. de Biología de la Reproducción, Universidad Autónoma Metropolitana-Unidad Iztapalapa, México. 4. Laboratorio de Neuropsicología, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México. 5. Departamento de Neurogenética y Biología Molecular, Instituto Nacional de Neurología y Neurocirugía. Manuel Velasco Suarez, México. 6. Centro para la Investigación y Rehabilitación de las Ataxias Hereditarias, Cuba. 7. Facultad de Psicología, Universidad Veracruzana, México.
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.
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 SCA2patients 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 SCA2patients 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.
Authors: Shriya S Srinivasan; Greta Tuckute; Jasmine Zou; Samantha Gutierrez-Arango; Hyungeun Song; Robert L Barry; Hugh M Herr Journal: Sci Transl Med Date: 2020-12-09 Impact factor: 17.956
Authors: G Olivito; M Cercignani; M Lupo; C Iacobacci; S Clausi; S Romano; M Masciullo; M Molinari; M Bozzali; M Leggio Journal: Neuroimage Clin Date: 2017-03-25 Impact factor: 4.881
Authors: Carlos R Hernandez-Castillo; Victor Galvez; Roberto Mercadillo; Rosalinda Diaz; Aurelio Campos-Romo; Juan Fernandez-Ruiz Journal: PLoS One Date: 2015-08-11 Impact factor: 3.240