Motor Response Variability Reflects Recovery Potential After Stroke: A Transcranial Magnetic Stimulation Study

BACKGROUND: Stroke recovery is highly heterogeneous, and predictive neurophysiological markers of motor outcome are still needed. Although transcranial magnetic stimulation-derived motor evoked potentials (MEPs) are widely used to assess corticospinal integrity, their trial-to-trial variability remains poorly explored and has largely been interpreted as noise rather than a source of clinically relevant information. METHODS: In this prospective longitudinal observational study, we investigated MEP peak-to-peak amplitude and amplitude variability in 77 patients with subacute stroke assessed at baseline (T0, early subacute phase) and after a 2-month high-intensity daily rehabilitation program (T1), alongside 10 age- and sex-matched healthy controls. MEPs were recorded from both hemispheres at rest. Clinical outcomes were evaluated using the Fugl-Meyer Upper Extremity scale and a Motor Recovery Index. RESULTS: Seventy-seven patients with subacute stroke (mean age, 68.5±12.7 years; 41.6% women) and 10 age- and sex-matched healthy controls (mean age, 73.9±4.3 years; 40.0% women) were included. At T0, MEP amplitude was lower in the affected than in the unaffected hemisphere (0.16±0.02 versus 0.38±0.01 mV; P =5.42×10 −10 ), as was MEP variance (0.013±0.002 versus 0.038±0.003 mV 2 ; P =8.43×10 − 12 ). Regarding T1, MEP amplitude increased over time in the affected hemisphere (0.21±0.02 mV; P =0.01), whereas MEP variance remained unchanged ( P =0.55). Importantly, baseline MEP amplitude was strongly associated with motor status at follow-up (Fugl-Meyer Upper Extremity scale at T1; P =9.52×10 − 9 ), but not with the degree of recovery. In contrast, baseline MEP variability was significantly associated with both motor outcome (Fugl-Meyer Upper Extremity scale at T1; P =2.76×10 − 7 ) and the Motor Recovery Index ( P =0.009), indicating a specific link with recovery potential. CONCLUSIONS: These findings reveal a dissociation between MEP amplitude and variability, suggesting that they capture complementary aspects of corticospinal function. Although amplitude reflects the current functional state of motor pathways, variability appears to index network flexibility and adaptive capacity. MEP variability may, therefore, represent a novel neurophysiological biomarker for predicting motor recovery and guiding personalized rehabilitation strategies after stroke.