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: R 2 ≥ 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.
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Acknowledgments
The authors would like to thank the participants and their families for their time and commitment to this research. This work was Supported by the National Institutes of Health (R01 NS075012, R01 NS058487, R21 NS093695, and T32 NS082168).
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429_2016_1263_MOESM1_ESM.tif
Supplementary material 1 Supplementary Data Fig. 1. Functional activity for control and SCA6 groups during a hand-grip force control. Data are thresholded at P < 0.005 (cluster size correction using the AFNI’s 3dClustSim, providing a corrected P < 0.05). Warm (yellow) colors indicate where BOLD (blood oxygen level-dependent) activity was positive. C: contralateral hemisphere, I: ipsilateral hemisphere (TIFF 1741 kb)
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Kang, N., Christou, E.A., Burciu, R.G. et al. Sensory and motor cortex function contributes to symptom severity in spinocerebellar ataxia type 6. Brain Struct Funct 222, 1039–1052 (2017). https://doi.org/10.1007/s00429-016-1263-4
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DOI: https://doi.org/10.1007/s00429-016-1263-4