Exploring Neurobiological Effects of Intermittent Theta-Burst Stimulation on the Left Cerebellum for Post-stroke Unilateral Neglect: A Preliminary Transcranial Magnetic Stimulation-Electroencephalography Investigation

Unilateral neglect (UN) is a frequent consequence of stroke, for which effective therapeutic interventions are yet to be definitively established. This study aims to assess the therapeutic potential of intermittent theta-burst stimulation (iTBS) applied to the contralesional cerebellum in reducing UN symptoms. Additionally, it seeks to clarify the neurophysiological mechanisms involved, thereby supporting the development of future personalized treatment strategies for the UN. Twenty patients diagnosed with UN were recruited and randomly allocated to either an iTBS treatment group or a sham stimulation group. Both groups received their respective interventions over ten consecutive days. Clinical behavioural assessments were performed pre- and post-treatment. Concurrently, transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) data were collected to assess alterations in cortical excitability and brain network connectivity. Patients receiving iTBS exhibited statistically significant improvements in both the line cancellation (p = 0.002) and star cancellation tasks (p = 0.003). Moreover, iTBS was associated with increased cortical excitability and enhanced signal propagation within the lesioned parietal cortex. Specifically, significant increases in the P60 and N100 components were observed in the iTBS group (P60, p < 0.001; N100, p = 0.002). Cumulative excitability metrics revealed significant improvements within the iTBS group over time intervals of 25-80 ms (p = 0.007) and 25-275 ms (p = 0.025). At the network level, the iTBS group showed early-stage increases in ipsilesional frontoparietal connectivity, followed by later stage enhancements between the contralesional occipital and ipsilesional frontal regions, as well as between the ipsilesional frontal and central parietal regions. These results suggest a pivotal role of cerebellar iTBS in modulating brain network connectivity. The findings of this study suggest that iTBS can mitigate symptoms of UN and, as demonstrated through TMS-EEG analyses, significantly influence cortical excitability and functional brain network connectivity in patients with UN. Stimulation of the contralesional cerebellum not only enhanced excitability in the ipsilesional parietal cortex but also facilitated neural network reorganisation by augmenting frontoparietal connectivity. These outcomes underscore the potential of iTBS as a therapeutic intervention for the UN. Future research should focus on validating the long-term efficacy of iTBS and exploring its broader applicability across varied patient populations. Clinical trial number: ChiCTR2400080086, Xuanwu Hospital, Capital Medical University.