Cerebellar Theta-Burst Stimulation Induces Distinct Functional Connectivity Patterns in Post-Stroke Aphasia: A Randomized Controlled Trial.

Abstract

Background Recent studies have identified the right cerebellar Crus I (rCrus I) as a promising target for rTMS in improving language rehabilitation. However, it remains unclear whether continuous theta burst stimulation (cTBS) over the rCrus I improves language outcomes in patients with subacute post-stroke aphasia (PSA). Objective To determine whether inhibitory cTBS over rCrus I improves language recovery in PSA and to explore underlying functional connectivity (FC) mechanisms. Methods Fifty-one PSA patients were randomized to receive either real cTBS (n = 25) or sham stimulation (n = 26) over rCrus I (10 sessions, 2 weeks) combined with speech-language therapy (SLT). Language assessments (WAB-AQ, BNT, BDAE) and resting-state fMRI were conducted before and after the intervention. Results Both groups showed significant language improvement post-intervention. No significant interaction was found for WAB-AQ ( P = .058), but a significant interaction was observed for repetition ( P = .034), favoring cTBS. Resting-state fMRI showed altered connectivity between rCrus I and right temporo-occipital regions, with FC changes negatively correlated with language gains in the cTBS group. Exploratory subgroup analyses identified 2 distinct FC response patterns (FC-increase and FC-decrease), indicating heterogeneous cerebello-cortical and intra-cerebellar connectivity modulation across participants. Conclusions Cerebellar cTBS did not confer a significant overall benefit on language recovery in PSA, but selectively improved repetition performance, suggesting domain-specific effects. Functional imaging indicated that rCrus I-centered connectivity changes were associated with behavioral outcomes, with marked inter-individual variability. These findings support a modulatory role of cerebellar cTBS on language networks, warranting further validation in larger, well-powered studies. Trial registration This trial was registered under the China Clinical Trial Registry (Registration No. ChiCTR2100049828).