Exploring functional and structural connectivity disruptions in spinocerebellar ataxia type 3: Insights from gradient analysis.

Aims: Spinocerebellar Ataxia Type 3 (SCA3) is a rare genetic ataxia that impacts the entire brain and is characterized as a neurodegenerative disorder affecting the neural network. This study explores how alterations in the functional hierarchy, connectivity, and structural changes within specific brain regions significantly contribute to the heterogeneity of symptom manifestations in patients with SCA3. Methods: We prospectively recruited 51 patients with SCA3 and 59 age‐and sex‐matched healthy controls. All participants underwent comprehensive multimodal neuroimaging and clinical assessments. In SCA3 patients, an innovative approach utilizing gradients in resting‐state functional connectivity (FC) was employed to examine atypical patterns of hierarchical processing topology from sensorimotor to supramodal regions in the cerebellum and cerebrum. Coupling analyses of abnormal FC and structural connectivity among regions of interest (ROIs) in the brain were also performed to characterize connectivity alterations. Additionally, relationships between quantitative ROI values and clinical variables were explored. Results: Patients with SCA3 exhibited either compression or expansion within the primary sensorimotor‐to‐supramodal gradient through four distinct calculation methods, along with disruptions in FC and structural connectivity coupling. A comprehensive correlation was identified between the altered gradients and the clinical manifestations observed in patients. Notably, altered fractional anisotropy values were not significantly correlated with clinical variables. Conclusion: Abnormal gradients and connectivity in the cerebellar and cerebral cortices in SCA3 patients may contribute to disrupted motor‐to‐supramodal functions. Moreover, these findings support the potential utility of FCG analysis as a biomarker for diagnosing SCA3 and assessing treatment efficacy. [ABSTRACT FROM AUTHOR]