Motor network pre-habilitation by low-frequency repetitive transcranial magnetic stimulation. A proof-of-concept

Abstract

Background: Tumors involving motor-eloquent brain regions pose a significant surgical challenge, as maximizing resection while preserving motor function requires a delicate balance. Neuromodulation-induced cortical prehabilitation (NICP) has emerged as a potential strategy to promote functional reorganization before surgery, potentially expanding the margins of safe resection. Objective: This pilot study aimed to investigate whether accelerated, low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the right primary motor cortex (M1) could induce functional and microstructural changes in the motor network. Methods: Two healthy subjects underwent a seven-day intervention consisting of twice-daily sessions of inhibitory rTMS over the right M1 (14 sessions in total). Pre- and post-intervention imaging included resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Functional changes were assessed descriptively using seed-based and ROI-to-ROI connectivity analyses. Microstructural changes were evaluated through tract-specific comparisons of fractional anisotropy (FA). Results: Both subjects exhibited increased interhemispheric functional connectivity and strengthening of compensatory motor pathways, including the supplementary motor areas and bilateral precentral and postcentral gyri. DTI revealed tract-specific changes in FA, with evidence of microstructural modulation in regions such as the SMA, corpus callosum, and corticospinal tract. The magnitude and spatial distribution of changes varied between individuals. Conclusion: These preliminary findings provide exploratory support for the hypothesis that inhibitory rTMS can induce functional and structural reorganization of the motor network. The combined use of rs-fMRI and DTI highlights the potential of NICP as a prehabilitation strategy in neurosurgical contexts. Further studies in clinical populations are warranted.