title: Early Cerebellar Network Shifting in Spinocerebellar Ataxia Type 6.
abstract: Spinocerebellar ataxia 6 (SCA6), an autosomal dominant degenerative disease, is characterized by diplopia, gait ataxia, and incoordination due to severe progressive degeneration of Purkinje cells in the vestibulo- and spinocerebellum. Ocular motor deficits are common, including difficulty fixating on moving objects, nystagmus and disruption of smooth pursuit movements. In presymptomatic SCA6, there are alterations in saccades and smooth-pursuit movements. We sought to assess functional and structural changes in cerebellar connectivity associated with a visual task, hypothesizing that gradual changes would parallel disease progression. We acquired functional magnetic resonance imaging and diffusion tensor imaging data during a passive smooth-pursuit task in 14 SCA6 patients, representing a range of disease duration and severity, and performed a cross-sectional comparison of cerebellar networks compared with healthy controls. We identified a shift in activation from vermis in presymptomatic individuals to lateral cerebellum in moderate-to-severe cases. Concomitantly, effective connectivity between regions of cerebral cortex and cerebellum was at its highest in moderate cases, and disappeared in severe cases. Finally, we noted structural differences in the cerebral and cerebellar peduncles. These unique results, spanning both functional and structural domains, highlight widespread changes in SCA6 and compensatory mechanisms associated with cerebellar physiology that could be utilized in developing new therapies.
authors.affiliation: Department of Anatomy and Neurobiology.
authors.forename: M I
authors.initials: MI
authors.lastname: Falcon
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Gomez
authors.affiliation: Department of Anatomy and Neurobiology.
authors.forename: E E
authors.initials: EE
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Neurobiology.
authors.forename: A
authors.initials: A
authors.lastname: Shereen
authors.affiliation: Department of Anatomy and Neurobiology Department of Neurology, UC Irvine School of Medicine, Irvine, CA 92697, USA.
authors.forename: A
authors.initials: A
authors.lastname: Solodkin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001931:Brain Mapping; D002531:Cerebellum / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D011698:Pursuit, Smooth / Q000502:physiology; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D014796:Visual Perception / Q000502:physiology; D066127:White Matter / Q000000981:diagnostic imaging / Q000503:physiopathology
keywords: DTI; eye movements; fMRI; spinocerebellar ataxia; vermis