Longitudinal Reorganization of Cortical and Cerebellar Functional Networks in Spinocerebellar Ataxia Type 7

Spinocerebellar ataxia type 7 (SCA7) is a rare neurodegenerative disorder characterized by progressive cerebellar ataxia and visual impairment. Although previous neuroimaging studies have reported functional abnormalities, the longitudinal evolution of cortical and cerebellar network organization remains underexplored. We investigated longitudinal changes in resting-state functional connectivity and their clinical associations. Resting-state functional MRI was acquired from 16 individuals with SCA7 and 16 age- and sex-matched healthy controls across three visits spanning approximately 24 months. Network-to-network functional connectivity was quantified using cortical and cerebellar functional atlases, and machine-learning models were trained using functional connectivity features. SCA7 exhibited lower baseline MoCA (p = 0.045) and MMSE (p = 0.025) scores and progressive worsening of ataxia (SARA, p < 0.001). Significant Group × Visit interactions were observed for Visual–Default Mode (FDR-corrected p = 0.012) and Somatomotor–Cerebellar Dorsal Attention connectivity (FDR-corrected p = 0.038). Functional connectivity abnormalities involved cortical, cortico-cerebellar, and cerebellar networks that became more widespread at the final follow-up assessment, with the visual network emerging as the most consistently affected system across analyses. Functional connectivity abnormalities were associated with both cognitive performance (MMSE: r = − 0.62, p = 0.01) and disease severity (SARA: r = 0.589, p = 0.016). Functional connectivity features accurately classified SCA7 and healthy controls (accuracy = 96.4%, F1 = 0.969). These findings demonstrate progressive network reorganization in SCA7 and support resting-state functional connectivity as a candidate biomarker of disease-related functional alterations that warrants further investigation.