Functional connectivity alterations in spinocerebellar ataxia type 10: insights from gray matter atrophy

Abstract

Spinocerebellar ataxia type 10 (SCA10) is a rare, inherited neurological disease caused by an expansion of the non-coding ATTCT pentanucleotide repeat in the ATAXIN 10 gene. It is characterized by cerebellar ataxia and epilepsy. Previous research has demonstrated extensive white and gray matter degeneration, particularly in the cerebellum. However, the impact of the SCA10 mutation on functional connectivity (FC) remains unexplored. This study aimed to characterize intrinsic FC changes in SCA10 patients and their relationship to clinical manifestations. Structural and resting-state Magnetic Resonance Imaging (MRI) were obtained from 26 SCA10 patients and 26 control subjects. Voxel-based morphometry (VBM) and seed-ROI and Independent Components Analysis (ICA) were performed to identify cerebral atrophy and FC changes respectively. Additionally, correlation analyses were conducted between FC changes and scores from the Scale for the Assessment and Rating of Ataxia (SARA) and the Montreal Cognitive Assessment (MoCA). In SCA10 patients, VBM analysis revealed extensive gray matter loss in motor cortices and the cerebellum. FC analysis identified significant FC changes originating from seed-ROIs in the right cerebellar VI and left precentral gyrus. Furthermore, group comparison using ICA components showed that SCA10 patients exhibited higher FC in the sensorimotor and cerebellar functional networks. Moreover, the average Blood Oxygen Level Dependent (BOLD) signal within the cerebellar network negatively correlated with MoCA scores. In summary, SCA10 patients exhibited enhanced FC in brain regions that displayed gray matter atrophy, underscoring the impact of SCA10 degeneration on resting state networks and induction of potential maladaptive FC compensatory mechanisms.

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