Mixed-Frequency rTMS Rapidly Modulates Multiscale EEG Biomarkers of Excitation-Inhibition Balance in Autism Spectrum...

Background: Repetitive transcranial magnetic stimulation (rTMS) is an established neuromodulatory method, yet its multiscale neurophysiological effects in autism spectrum disorder (ASD) remain insufficiently characterized. Recent EEG analytic advances-such as spectral parameterization, long-range temporal correlation (LRTC) assessment, and connectivity modeling-enable quantitative evaluation of excitation-inhibition (E/I) balance and network organization. Objective: This study aimed to examine whether an eight-session, EEG-guided mixed-frequency rTMS protocol-combining inhibitory 1 Hz and excitatory 10 Hz trains individualized to quantitative EEG (qEEG) abnormalities-produces measurable changes in spectral dynamics, temporal correlations, and functional connectivity in a pediatric ASD case. Methods: An 11-year-old right-handed female with ASD (DSM-5-TR, ADOS-2) underwent resting-state EEG one week before and four months after intervention. Preprocessing used a validated automated pipeline, followed by spectral parameterization (FOOOF), detrended fluctuation analysis (DFA), and connectivity analyses (phase-lag index and Granger causality) in MATLAB (2023b). No inferential statistics were applied due to the single-case design. The study was conducted at Cosmos Healthcare (London, UK) with in-kind institutional support and approved by the Atlantic International University IRB (AIU-IRB-22-101). Results: Post-rTMS EEG showed (i) increased delta and reduced theta/alpha/beta power over central regions; (ii) steeper aperiodic slope and higher offset, maximal at Cz, suggesting increased inhibitory tone; (iii) reduced Hurst exponents (1-10 Hz) at Fz, Cz, and Pz, indicating decreased long-range temporal correlations; (iv) reorganization of hubs away from midline with marked Cz decoupling; and (v) strengthened parietal-to-central directional connectivity (Pz→Cz) with reduced Cz→Pz influence. Conclusions: Mixed-frequency, EEG-guided rTMS produced convergent changes across spectral, aperiodic, temporal, and connectivity measures consistent with modulation of cortical E/I balance and network organization. Findings are preliminary and hypothesis-generating. The study was supported by in-kind resources from Cosmos Healthcare, whose authors participated as investigators but had no influence on analysis or interpretation. Controlled trials are warranted to validate these exploratory results.