Altered static and dynamic spontaneous brain activity patterns in spinocerebellar ataxia type3 patients

Spinocerebellar ataxia type 3 (SCA3) is characterized by extensive supra- and infra-tentorial brain injuries, beginning in the pre-symptomatic stage. However, the alterations and evolution of spontaneous brain activity in SCA3 patients remain poorly understood.

This study aimed to investigate the abnormal brain activity of SCA3, classified it into distinct patterns, and explored the association between spontaneous brain activity in affected regions and clinical variables.

Ninety-nine SCA3 patients (76 sym- and 23 pre-SCA3 patients, mean age: 39.97 ± 10.83y; 28.74 ± 7.99y) and 49 healthy controls underwent 3.0T MRI and acquired T1 and resting-state functional MRI images. The static and dynamic amplitude of low-frequency fluctuation (s/dALFF) and regional homogeneity (s/dReHo) were used to estimate local brain activity alterations.

SCA3 patients exhibited significantly abnormal spontaneous brain activities in multiple regions, classified into four patterns (P < 0.001). Patterns 1 and 2 were found in the pre-symptomatic stage, involving the right opercular part of inferior frontal gyrus, right rolandic operculum, right insula, right angular gyrus, right crus I of cerebellar hemisphere and left superior frontal gyrus. Pattern 3 emerged in symptomatic SCA3, with expanded involvement of supra- to infra-tentorial regions. Pattern 4 showed increased activity in the right cerebellar lobule IX. Negative correlations were found between sReHo value in the right anterior cingulate cortex with the disease duration and severity (P ≤ 0.04).

SCA3 patients exhibit different patterns of brain activity damage at different stages. These findings provide new insight into brain dysfunction in SCA3 and suggest potential imaging markers for disease staging and monitoring.