Repetitive transcranial magnetic stimulation normalizes cerebrocerebellar loop functional connectivity in spinocerebellar ataxia type 3: a synthetic control study

Background Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disorder characterized by ataxia; structural and functional damage to the cerebrocerebellar loop play key roles in its pathology. However, effective treatments for SCA3 remain limited. Repetitive transcranial magnetic stimulation (rTMS) modulates cortical plasticity. Here, we investigated the utility of rTMS in SCA3 treatment. Methods This study included 25 confirmed SCA3 patients and 33 age- and sex-matched healthy volunteers as controls. The Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS) were used to assess the severity of clinical symptoms in the SCA3 group. Both groups completed neuropsychological evaluations and underwent brain magnetic resonance imaging (MRI) before and after treatment. MRI data were preprocessed using DPABI software to analyze changes in functional connectivity strength, both at the stimulation target and across the whole brain, in SCA3 patients before and after multi-target rTMS therapy based on the cerebrocerebellar loop. Results After multi-target rTMS treatment, SARA ( p  < 0.001) and ICARS ( p  < 0.001) scores in SCA3 patients were significantly reduced, whereas Montreal Cognitive Assessment ( p  < 0.001) scores showed a substantial improvement in cognitive performance. Functional connectivity strengths between the paracentral lobule and cerebellum, and between the cerebellar vermis and paracentral lobule, decreased in SCA3 patients after treatment, gradually approaching levels observed in healthy controls. Discussion A multi-target rTMS treatment strategy targeting the cerebrocerebellar loop may significantly improve motor and cognitive functions in SCA3 patients by effectively regulating functional connectivity within this circuit.