Pretreatment spatial signature of contralesional cortical activation predicts therapeutic response to 1 Hz rTMS in post-stroke upper limb motor Recovery: A fNIRS-based biomarker study.

BACKGROUND

While 1 Hz repetitive transcranial magnetic stimulation (rTMS) targeting contralesional primary motor cortex (M1) shows promise for stroke recovery, individual response variability remains a critical challenge. Emerging evidence suggests that interhemispheric activation patterns may mediate rTMS efficacy. We investigated whether pretreatment spatial features of contralesional activation, measured by functional near-infrared spectroscopy (fNIRS), could predict response to 1 Hz rTMS.

METHODS

In this nested unmatched case-control study, 60 patients with upper limb motor impairment received 1 Hz rTMS over contralesional M1 hand area plus conventional rehabilitation for 4 weeks. Responders were defined by a ≥5-point improvement on the Upper Extremity Fugl-Meyer (UEFM) assessment. Cortical activation during affected wrist extension was recorded using fNIRS, and the Euclidean distance from the peak activation channel to the M1 hand area ("activation distance") was computed. An additional non-rTMS cohort (n=30) receiving only conventional rehabilitation was included to evaluate specificity.

RESULTS

In the rTMS cohort, responders (n=32) exhibited significantly shorter pretreatment activation distances than non-responders (n=28) (25.80±8.82 mm vs. 34.07±7.81 mm; p<0.001). Activation distance independently predicted treatment response after adjusting for baseline UEFM, time since stroke and age (adjusted OR=0.40 per 10 mm increase; 95% CI: 0.17-0.83; p=0.014). A cutoff of ≤25 mm optimally discriminated responders (response rate 86% vs. 34% for >25 mm). No association was found in the non-rTMS cohort, confirming specificity to rTMS response.

CONCLUSION

Pretreatment contralesional activation proximity to M1-assessed via fNIRS-predicts response to inhibitory rTMS, supporting its use as a biomarker for personalized neuromodulation therapy in stroke rehabilitation.