Distinct tDCS montages act via dissociable lateralization mechanisms to enhance motor function in chronic stroke.

The imbalance in interhemispheric functional connectivity following stroke fundamentally impedes motor recovery. Although transcranial direct current stimulation (tDCS) effectively modulates neuroplasticity, the acute effects of distinct stimulation montages on lateralized brain networks and how these network shifts drive behavioral improvements warrant further investigation. Approach. We employed a single-blind, randomized crossover design involving 28 patients with chronic subcortical stroke. Participants received anodal, cathodal, bilateral, or sham tDCS targeting the primary motor cortex. Resting-state electroencephalography (EEG) data were acquired immediately before and after each intervention. To quantify network lateralization, we computed dynamic functional connectivity using mutual information and constructed an asymmetry index matrix. Key connectivity features were isolated via robust feature selection algorithms, classifying stimulation states and evaluating correlations with acute motor gains on the Jebsen-Taylor Hand Function Test (JTT). Main results. Network dynamics features successfully discriminated pre- versus post-intervention states with high accuracy (AUC: 0.87-0.98). All three active tDCS protocols exhibited montage-specific directional modulation. Crucially, anodal tDCS uniquely reversed contralesional network dominance, facilitating ipsilesional connectivity and shifting the interhemispheric balance toward the affected hemisphere. Conversely, cathodal and bilateral tDCS predominantly induced contralesional network inhibition, whereas sham stimulation exhibited no directional bias. Furthermore, the functional inhibition of the contralesional network (specifically at the P2-P6 connection) induced by bilateral tDCS significantly correlated with acute JTT improvements (r = 0.55, p = 0.04). Significance. This study demonstrates that distinct tDCS montages modulate stroke-induced network imbalances through dissociable lateralization mechanisms. While anodal tDCS drives ipsilesional facilitation to reverse contralesional dominance, bilateral and cathodal montages operate primarily via contralesional inhibition. These findings provide critical mechanistic insights into interhemispheric network dynamics.