PRESp-rTMS: a biomarker-based PREScription for personalized repetitive Transcranial Magnetic Stimulation for stroke patients with upper extremity motor impairment.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising noninvasive treatment for upper extremity motor impairment in people with stroke. However, response variability underscores the need for tools to support more personalized and effective rTMS planning.

Objectives: Implement a biomarker-based PREScription for personalized rTMS (PRESp-rTMS) in stroke patients with upper extremity motor impairment and verify its effectiveness.

Methods: In this randomized, triple-blind, single-center trial, 20 people with stroke, aged 18-80 years and presenting upper extremity motor impairment, were enrolled and assigned to either a control group receiving standard low-frequency rTMS (s-rTMS) on the non-lesioned hemisphere or a personalized rTMS (p-rTMS) group guided by the PRESp-rTMS algorithm, based on neurophysiological and clinical biomarkers. The p-rTMS group received one of four protocols, each targeting specific frequencies on a single or both hemispheres. The primary outcome was the mean difference in the Fugl-Meyer Assessment for the Upper Extremity (ΔFMA-UE). Secondary outcomes included the Functional Independence Measure, Box and Block Test, Trunk Control Test, and Modified Ashworth Scale.

Results: Compared to the s-rTMS group (ΔFMA-UE = 4.9 ± 1.4; mean ± SD), the p-rTMS group demonstrated a larger improvement in upper extremity motor impairment (ΔFMA-UE = 11.8 ± 2.9; p < 0.01; Cohen's D = 3.2, 95% CI = 2.15-3.90). No significant differences were found for secondary outcomes, although very large effect sizes favored the p-rTMS group.

Conclusions: Using the PRESp-rTMS algorithm results in greater improvements in upper extremity motor impairment in people with stroke compared to the standard rTMS protocol.