Personalized repetitive transcranial magnetic stimulation reduces frontal eeg complexity in patients with obsessive–compulsive disorder

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) shows therapeutic potential for obsessive-compulsive disorder (OCD). Brain entropy has recently emerged as a candidate biomarker in neuropsychiatry, yet its modulation by rTMS in OCD remains unclear. Given EEG's superior temporal resolution for capturing rapid fluctuations in neural complexity, it was used to evaluate the effects of fMRI-neuronavigated rTMS on frontal entropy and its potential as an objective treatment marker. METHODS: Resting-state EEG was recorded from 44 OCD patients and 24 healthy controls (HCs) to compute frontal entropy- and complexity-based measures, including approximate entropy (ApEn), sample entropy (SampEn), and Lempel-Ziv complexity (LZC). Patients were randomized to an active (n = 22) or sham (n = 22) rTMS group, with the active group receiving individualized 1 Hz stimulation over the right pre-supplementary motor area for 14 consecutive days. EEG was repeated post-intervention. RESULTS: At baseline, OCD patients exhibited higher frontal complexity than healthy controls across all three measures. Linear mixed-effects models consistently revealed significant main effects of time and stimulation, as well as their interaction. Bayesian and FDR-corrected analyses confirmed significant reductions in all three measures following active stimulation. Post-treatment, frontal complexity remained elevated in the sham group relative to healthy controls, whereas no such difference was observed in the active stimulation group. CONCLUSION: OCD is characterized by increased frontal neural complexity as indexed by multiple entropy- and complexity-based EEG measures. Individualized rTMS modulated these abnormalities, supporting frontal EEG complexity as a promising objective biomarker of neuromodulatory effects.