Clinical and electrophysiological outcomes of deep TMS over the medial prefrontal and anterior cingulate cortices in OCD patients

Background Obsessive Compulsive Disorder (OCD) is a chronic and disabling disorder with poor response to pharmacological treatments. Converging evidences suggest that OCD patients suffer from dysfunction of the cortico-striato-thalamo-cortical (CSTC) circuit, including in the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC). Objective To examine whether modulation of mPFC-ACC activity by deep transcranial magnetic stimulation (DTMS) affects OCD symptoms. Methods Treatment resistant OCD participants were treated with either high-frequency (HF; 20 Hz), low-frequency (LF; 1 Hz), or sham DTMS of the mPFC and ACC for five weeks, in a double-blinded manner. All treatments were administered following symptoms provocation, and EEG measurements during a Stroop task were acquired to examine changes in error-related activity. Clinical response to treatment was determined using the Yale-Brown-Obsessive-Compulsive Scale (YBOCS). Results Interim analysis revealed that YBOCS scores were significantly improved following HF (n = 7), but not LF stimulation (n = 8), compared to sham (n = 8), and thus recruitment for the LF group was terminated. Following completion of the study, the response rate in the HF group (n = 18) was significantly higher than that of the sham group (n = 15) for at least one month following the end of the treatment. Notably, the clinical response in the HF group correlated with increased Error Related Negativity (ERN) in the Stroop task, an electrophysiological component that is attributed to ACC activity. Conclusion HF DTMS over the mPFC-ACC alleviates OCD symptoms and may be used as a novel therapeutic intervention. Notwithstanding alternative explanations, this may stem from DTMS ability to directly modify ACC activity.