title: Sensory and motor cortex function contributes to symptom severity in spinocerebellar ataxia type 6.
abstract: Spinocerebellar ataxia type 6 (SCA6) is a genetic disease that causes degeneration of Purkinje cells, and recent evidence points to degeneration of Betz cells in the motor cortex. The relation between functional activity of motor cortex and symptom severity during a hand-grip motor control in vivo has not yet been investigated. This study explored both functional changes in the sensorimotor cortex and cerebellar regions and structural alterations in the cerebellum for SCA6 patients as compared to age-matched healthy controls using a multimodal imaging approach (task-based fMRI, task-based functional connectivity, and free-water diffusion MRI). Further, we tested their relation with the severity of ataxia symptoms. SCA6 patients had reduced functional activity in the sensorimotor cortex, supplementary motor area (SMA), cerebellar vermis, and cerebellar lobules I-VI (corrected P < 0.05). Reduced task-based functional connectivity between cortical motor regions (i.e., primary motor cortex and SMA) and cerebellar regions (i.e., vermis and lobules I-VI) was found in SCA6 (corrected P < 0.05). SCA6 had elevated free-water values throughout the cerebellum as compared with controls (corrected P < 0.05). Importantly, reduced functional activity in the sensorimotor cortex and SMA and increased free-water in the superior cerebellar peduncle and cerebellar lobule V were related to more severe symptoms in SCA6 (all pairs: R2≥ 0.4 and corrected P < 0.05). Current results demonstrate that impaired functional activity in sensorimotor cortex and SMA and elevated free-water of lobule V and superior cerebellar peduncle are both related to symptom severity, and may provide candidate biomarkers for SCA6.
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, P.O. Box 118205, Gainesville, FL, 32611-8205, USA.
authors.forename: Nyeonju
authors.initials: N
authors.lastname: Kang
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, P.O. Box 118205, Gainesville, FL, 32611-8205, USA.
authors.forename: Evangelos A
authors.initials: EA
authors.lastname: Christou
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, P.O. Box 118205, Gainesville, FL, 32611-8205, USA.
authors.forename: Roxana G
authors.initials: RG
authors.lastname: Burciu
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, P.O. Box 118205, Gainesville, FL, 32611-8205, USA.
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Chung
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, P.O. Box 118205, Gainesville, FL, 32611-8205, USA.
authors.forename: Jesse C
authors.initials: JC
authors.lastname: DeSimone
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, P.O. Box 118205, Gainesville, FL, 32611-8205, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Ofori
authors.affiliation: Department of Neurology, University of Florida, Gainesville, USA.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
authors.affiliation: Department of Neurology, University of Florida, Gainesville, USA.
authors.forename: Sankarasubramon H
authors.initials: SH
authors.lastname: Subramony
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, P.O. Box 118205, Gainesville, FL, 32611-8205, USA. vcourt@ufl.edu.|Department of Neurology, University of Florida, Gainesville, USA. vcourt@ufl.edu.|Department of Biomedical Engineering, University of Florida, Gainesville, USA. vcourt@ufl.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Vaillancourt
mesh_terms: D000368:Aged; D001931:Brain Mapping; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D018737:Hand Strength; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D066191:Sensorimotor Cortex / Q000473:pathology* / Q000503:physiopathology*; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*
keywords: Diffusion MRI; Free-water; Functional MRI; Spinocerebellar ataxia type 6; Task-based functional connectivity