Ipsilateral inhibitory rTMS restores interhemispheric motor cortex balance and reduces phantom limb pain: an exploratory longitudinal nTMS mapping study.

Abstract

Phantom limb pain (PLP) is a debilitating condition associated with maladaptive neuroplastic changes following limb amputation. The prevailing neuromodulatory approach targets the deafferented contralateral motor cortex, yet interhemispheric imbalance is increasingly recognized as a central pathophysiological feature of PLP. We investigated whether inhibitory repetitive transcranial magnetic stimulation (rTMS) applied to the ipsilateral (unaffected) hemisphere could reduce PLP and induce measurable normalization of interhemispheric cortical asymmetry. Two individuals with traumatic right upper-limb amputation and severe PLP underwent a longitudinal study comprising a four-week baseline phase, an inhibitory 1 Hz rTMS intervention targeting the ipsilateral motor cortex, and a five-week follow-up phase. Serial navigated transcranial magnetic stimulation (nTMS) motor mapping of both hemispheres was performed before and after the intervention. A principal component analysis (PCA)-based spatial projection and Gaussian kernel regression pipeline was developed to quantify motor map area, center of gravity (CoG), mean motor evoked potential (MEP) amplitude, and signal amount bilaterally. Both participants demonstrated clinically meaningful PLP reductions (66% and 33% relative decreases on the Visual Analog Scale [VAS]), sustained across the five-week follow-up. Serial nTMS mapping revealed enlarged residual limb motor representations in the affected hemisphere at baseline. Following rTMS, cortical area of the triceps representation in the affected hemisphere decreased by 67% and 61% in the two participants respectively, with concurrent normalization of interhemispheric differences in both representation area and signal amount. CoG shifts were modest (mean 3.28 mm), indicating focal map consolidation rather than wholesale topographic reorganization. These findings offer novel neurophysiological evidence suggesting that inhibitory rTMS targeting the ipsilateral motor cortex reduces PLP while concurrently normalizing interhemispheric motor map asymmetry. The results are consistent with a callosal disinhibition mechanism, whereby ipsilateral inhibition may facilitate adaptive reorganization of the deafferented hemisphere. The novel PCA-based bilateral mapping pipeline introduced here provides a quantitative framework for future controlled trials.