Abstract
INTRODUCTION: People with post-stroke aphasia (PSA) exhibit significant interindividual variability attributed to distinctive network disruption patterns across individuals. This complexity limits the effectiveness of conventional one-size-fits-all brain stimulation approaches, but to date no individualized tACS targeting on functional network was studied in PSA. This two-phase study aimed to investigate the immediate network-modulation and language-facilitation effects of dual-site in-phase tACS utilizing a novel individualized targeting method based on individual's EEG dysfunctome. METHODS: In the first phase, network-based linear regression was used to identify aphasia-severity-predictive dysfunctome from the speech-production EEG data of 15 Cantonese-speaking people with aphasia (PWA). Individualized stimulation targets were determined using two targeting principles. Restoration-based targeting aims to restore a target edge which is centralized within the target dysfunctome but weakly-connected in the individual, whereas enhancement-based targeting selects a strongly-connected target edge. The second phase involved a single-session double-blinded sham-controlled trial with the same group to evaluate the immediate effects of dual-site 7-Hz 1-mA tACS under four conditions: Restoration In-phase (RI), Enhancement In-phase (EI), Enhancement Anti-phase (EA), and Sham (SH). RESULTS: In the first phase, we explored a range of frequency bands and EEG tasks and identified a left frontal-temporal theta network under divergent naming task that significantly predicted aphasia severity. The single-session clinical trial in the second phase demonstrated that RI condition produced increases in the target node strength, global network properties, and divergent naming performance, which were absent in sham and the other two real stimulation conditions. DISCUSSION: This was the first-of-its-kind dysfunctome-based data-driven individualized tACS demonstrated immediate neuromodulatory effects in PSA. The findings suggest that EEG dysfunctome can help pinpointing effective individualized targets for tACS to promote clinically-beneficial functional reorganization. Despite limited generalizability due to the small sample, this methodology holds significant potential for application in longer-term treatment and other network-based disorders.