Differential Effects of Continuous Theta Burst Stimulation over the Bilateral and Unilateral Cerebellum on Working Memory

Recent functional MRI studies have implicated the cerebellum in working memory (WM) alongside the prefrontal cortex. Some findings indicate that the right cerebellum is activated during verbal tasks, while the left is engaged during visuospatial tasks, suggesting cerebellar lateralization in WM function. The cerebellum could be a potential target for non-invasive brain stimulation (NIBS) to enhance WM function in cognitive disorders. However, the comprehensive influence of cerebellar lateralization on different types of WM and the effect of stimulation over the unilateral or bilateral cerebellum remain uncertain. This study was to investigate the cerebellum's functional lateralization and its specific impact on various aspects of WM in a causal manner using unilateral or bilateral cerebellar continuous theta burst stimulation (cTBS), a form of inhibitroy NIBS. Twenty-four healthy participants underwent four sessions of cTBS targeting the left, right, or bilateral Crus I of the cerebellum, or a sham condition, in a controlled cross-over design. WM performance was assessed pre- and post-stimulation using neuropsychological tests, including the 3-back task, spatial WM task, and digit span task. Results indicated that cTBS over the bilateral and right cerebellum both led to a greater improvement in 3-back task performance compared to sham stimulation. Additionally, active cTBS over the bilateral cerebellum yielded better performance in the spatial WM task than sham stimulation. However, no significant differences were observed between stimulation conditions for the auditory digit span task. This study may provide novel causal evidence highlighting the specific involvement of the right and bilateral cerebellum in various types of WM. Specifically, the right cerebellum appears crucial for updating and tracking 3-back WM content, while spatial WM processes require the coordinated engagement of both cerebellar hemispheres.