Corticospinal imbalance following major upper limb amputation is transiently modulated by continuous theta burst stimulation

Objective: Major upper limb amputation (mULA) induces neuroplastic changes that can impact neurorehabilitation and prosthetic control. Previous literature suggested heightened corticospinal excitability (CE) in the hemisphere contralateral to the amputation (CLH). This interhemispheric imbalance in CE might represent a maladaptive process. We aimed to assess baseline CE in individuals with chronic mULA and the acute effects of continuous theta burst stimulation (cTBS) applied to the primary motor cortex (M1) contralateral to the amputation. Methods: Thirteen adults with chronic transradial or transhumeral mULA underwent electrophysiological assessments before and after unilateral cTBS. CE was measured through motor-evoked potential (MEP) amplitudes at baseline, 5 and 10 min post-stimulation. Linear mixed models assessed the effects of Hemisphere (contralateral vs ipsilateral), Time (baseline, 5, 10 min), and their interaction. Results: Group-level analyses indicated higher MEP amplitudes in the CLH compared with the ipsilateral hemisphere. cTBS was associated with a transient reduction of MEP amplitudes in the stimulated CLH at 5 minutes, with partial recovery at 10 minutes, leading to a temporary attenuation of interhemispheric asymmetry. Conclusions: These findings suggest that cTBS may transiently modulate CE in chronic mULA, with effects that appear restricted to the stimulated hemisphere. Significance: This study provides preliminary evidence of interhemispheric asymmetry in CE after mULA and indicates that cTBS could represent a potential tool to modulate it. Further studies are needed to establish robustness and clinical relevance.