Electroencephalographic connectivity predicts clinical response to repetitive transcranial magnetic stimulation in patients with insomnia disorder

BACKGROUND: Accumulating evidence suggests that low frequency repetitive transcranial magnetic stimulation (rTMS), which generally decreases cortical excitability and remodels plastic connectivity, improves sleep quality in patients with insomnia disorder. However, the effects of rTMS vary substantially across individuals and treatment is sometimes unsatisfactory, calling for biomarkers for predicting clinical outcomes. OBJECTIVE: This study aimed to investigate whether functional connectivity of the target network in electroencephalography is associated with the clinical response to low frequency rTMS in patients with insomnia disorder. METHODS: Twenty-five patients with insomnia disorder were subjected to 10 sessions of treatment with 1 Hz rTMS over the right dorsolateral prefrontal cortex. Resting-state electroencephalography was collected before rTMS. Pittsburgh Sleep Quality Index, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Mini-Mental State Exam were performed before and after rTMS treatment, with a follow-up after one month. Electroencephalographic connectivity was measured by the power envelope connectivity at the source level. Partial least squares regression identified models of connectivity that maximally accounted for the rTMS response. RESULTS: Scores of Pittsburgh Sleep Quality Index, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale were decreased after rTMS and one-month later. Baseline weaker connectivity of a network in the beta and alpha bands between a brain region approximating the stimulated right dorsolateral prefrontal cortex and areas located in the frontal, insular, and limbic cortices was associated with a greater change in Pittsburgh Sleep Quality Index and Hamilton Depression Rating Scale following rTMS. CONCLUSIONS: Low frequency rTMS could improve sleep quality and depressive moods in patients with insomnia disorder. Moreover, electroencephalographic functional connectivity would potentially be a robust biomarker for predicting the therapeutic effects.