Post-stroke cortical oscillatory activity is frequently disrupted, characterized by increased low-frequency oscillation and reduced high-frequency oscillation, which are associated with stroke severity and motor dysfunction. γ-tACS has the potential to entrain brain oscillations and enhance motor performance in healthy individuals, yet evidence in stroke patients is still limited.

This randomized, double-blind, sham-controlled pilot study enrolled 42 patients with post-stroke upper-limb motor impairment. Participants were randomly assigned to either the γ-tACS group or the sham-tACS group. High-definition tACS was applied over the M1 hotspot (70 Hz, 2 mApeak to peak, 20 min/session) for 10 sessions, once daily, in addition to conventional rehabilitation. The primary outcome was the Fugl–Meyer Assessment-Upper Extremity (FMA-UE). Secondary outcomes included the Modified Barthel Index (MBI) and resting-state EEG measures, including spectral power, power-ratio indices, and functional connectivity.

 A total of 42 participants were included in this trial (γ-tACS, n=21; sham-tACS, n=21), and the baseline characteristics were comparable between groups. FMA-UE improved in both groups, but the improvement was greater in γ-tACS group (ΔFMA-UE=4.64±4.55, P=0.039, 95%CI=[0.154, 5.799]), whereas between-group differences in MBI improvement were not significant. Baseline EEG showed ipsilesional–contralesional asymmetry, with higher delta power, lower alpha power and elevated deltaalpharatio (DAR), deltabetaratio(DBR), and (delta+theta)/(alpha+beta) raio (DTABR) on the ipsilesional side. After treatment, γ-tACS reduced ipsilesional delta power and lowered DBR and DTABR. Greater reductions in delta power and DTABR were associated with greater improvement in FMA-UE. In addition, γ-tACS increased ipsilesional beta-band connectivity (FC3–-C3 wPLI), and this increase was also associated with motor improvement. 

Compared with sham-tACS, γ-tACS applied over the ipsilesional M1 improved upper-limb motor function in patients with stroke. These clinical improvements were accompanied by restored oscillatory balance and enhanced network connectivity. Quantitative EEG parameters may serve as useful biomarkers for tracking neurophysiological changes and treatment response during stroke recovery.