Investigating repetitive transcranial magnetic stimulation-induced interhemispheric changes in stroke: a transcranial...

Interhemispheric imbalance after stroke impedes motor recovery. Although repetitive transcranial magnetic stimulation (rTMS) shows therapeutic potential, the neural mechanisms underlying its effects-particularly on cortical excitability and interhemispheric interaction-remain unclear. Understanding these mechanisms is essential for optimizing personalized neuromodulation strategies in stroke rehabilitation.

To explore how low-frequency rTMS facilitates motor recovery post-stroke, especially in regulating interhemispheric inhibition (IHI), functional connectivity, and cortical excitability, we used a multimodal approach that included paired-pulse TMS, functional near-infrared spectroscopy (fNIRS), and motor outcomes.

A total of 27 patients with stroke were randomized to receive 2 weeks of either real ( $n=14$ ) or sham ( $n=13$ ) 1 Hz rTMS over the contralesional primary motor cortex (M1). Paired-pulse TMS was used to measure IHI and laterality quotient (LQ), whereas fNIRS was used to measure resting-state functional connectivity (RSFC). Clinical scales were also used to assess behavioral-level motor functioning.

Compared with the sham group, rTMS significantly modulated IHI, as evidenced by a reduction in inhibitory drive from the stimulated contralesional M1 to ipsilesional M1 (mean difference = 15.57%, $p=0.048$ ). In parallel, RSFC analysis revealed decreased connectivity from contralesional M1 to ipsilesional premotor and supplementary motor areas [ $F\left(\mathrm{2,50}\right)=7.704$ , $p=0.006$ , false discovery rate-corrected]. Between-group comparisons further showed greater LQ improvements in the rTMS group than in the sham group. Changes in selected neurophysiological measures were significantly correlated with improvements in upper limb motor function.

We showed that low-frequency rTMS promotes motor recovery after stroke by rebalancing cortical excitability and reducing maladaptive connectivity patterns. The integration of TMS and fNIRS provides converging evidence for rTMS-induced cortical plasticity and highlights the potential of these tools for guiding personalized neuromodulation strategies in stroke rehabilitation.