Cerebellar transcranial direct current stimulation in spinocerebellar ataxia type 3: An electric field modelling study

Objectives: To compare cerebellar transcranial direct current stimulation (tDCS)-induced electric field strengths between individuals with spinocerebellar ataxia type 3 (SCA3) and healthy controls and to identify factors that underlie the variability in field strength. Methods: MRI scans from 68 SCA3 mutation carriers spanning the disease spectrum and 37 healthy adults were used to reconstruct tetrahedral volume meshes of the head. Electric field simulations of midline cerebellar tDCS were performed with the buccinator muscle, frontopolar region, and lower neck as reference electrode positions. Eight regions of interest were defined throughout the cerebellum. Results: Simulated electric field strengths induced by cerebellar tDCS were generally lower in SCA3 mutation carriers than in healthy controls, particularly in the anterior lobe and with cephalic reference electrodes. The frontopolar montage induced the highest field strengths, while the lower neck montage caused the lowest field strengths. Skin-cerebellum distance, Scale for the Assessment and Rating of Ataxia (SARA) score, and “occipital angle” were independently associated with electric field strength. Conclusion: Skin-cerebellum distance, posterior fossa morphometry, ataxia severity, and electrode montage predict cerebellar tDCS-induced electric field strength in SCA3 mutation carriers. These results may guide the development of personalized neuromodulation protocols and inform the design of future cerebellar tDCS trials in degenerative ataxias. Significance: This study identified clinical and anatomical factors that affect cerebellar tDCS-induced field strength in individuals with the most common type of dominantly inherited ataxia worldwide.