Circuit-based neuromodulation for obsessive–compulsive disorder: a systematic review, meta-analysis, and translational case study

BACKGROUND: Obsessive-compulsive disorder (OCD) remains refractory to conventional pharmacological and psychotherapeutic treatments in a substantial proportion of patients. Neuromodulation has emerged as a promising intervention, but optimal neural circuit targets remain unclear. This systematic review and meta-analysis aimed to evaluate the efficacy of invasive and non-invasive neuromodulation for OCD using a circuit-based framework and to translate these findings into clinical practice. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials investigating neuromodulation for OCD. PubMed/MEDLINE, Web of Science, and the Cochrane Library were searched from database inception to December 2023. Eligible studies included adult patients with a primary diagnosis of OCD receiving invasive or non-invasive neuromodulation, with symptom outcomes assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Random- or fixed-effects meta-analyses were performed using mean differences or standardized mean differences, depending on heterogeneity. The review was registered in PROSPERO (CRD42024518326). RESULTS: Twenty-seven randomized controlled trials involving 868 patients met inclusion criteria. Overall, neuromodulation significantly reduced OCD symptoms compared with control conditions. Circuit-based subgroup analyses indicated that modulation of the fronto-limbic circuit-primarily via invasive deep brain stimulation-was associated with the largest and most consistent Y-BOCS improvements, while sensorimotor, dorsal cognitive, and ventral affective circuits also demonstrated significant but more heterogeneous effects. Invasive neuromodulation showed greater efficacy than non-invasive approaches. These findings informed a translational multi-target deep brain stimulation case, demonstrating clinically meaningful symptom improvement (Y-BOCS decreased from 25 to 16 after 6 months). LIMITATIONS: Heterogeneity across non-invasive studies, short follow-up durations, and limited circuit-specific data constrain interpretation of long-term and symptom-domain-specific effects. CONCLUSIONS: This systematic review, meta-analysis, and case study suggest that circuit-based neuromodulation-particularly targeting the fronto-limbic circuit-may offer the most consistent benefit for treatment-refractory OCD. Larger, longer-term, and circuit-informed trials are needed to optimize individualized neuromodulation strategies.