Mixed-Frequency rTMS Rapidly Modulates Multiscale EEG Biomarkers of Excitation–Inhibition Balance in Autism Spectrum Disorder: A Single-Case Report

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.