Brain-Circuit Dysfunctions and Neuromodulatory Interventions in Obsessive-Compulsive Disorder: Systematic Review of Recent Clinical and Experimental Studies

Abstract Background Obsessive-compulsive disorder (OCD) is increasingly understood as a disorder of cortico-striato-thalamo-cortical (CSTC) circuit dysfunction. Hyperactivity in the orbitofrontal cortex, anterior cingulate cortex, and maladaptive striatal and thalamic connectivity contribute to intrusive thoughts and compulsive behaviors. Methodology: We conducted a systematic review of recent clinical and experimental studies investigating brain-circuit dysfunctions and neuromodulatory interventions in OCD, including deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Preclinical evidence from electrophysiological and optogenetic studies was also considered to validate circuit-based mechanisms. Results DBS demonstrated the most robust efficacy for treatment-resistant OCD, with adaptive closed-loop approaches offering enhanced personalization and reduced side effects. Non-invasive modalities such as rTMS and tDCS showed moderate improvements, with variability across studies. Integration of neuroimaging and electrophysiological biomarkers supports individualized targeting and precision psychiatry approaches. Preclinical studies confirm the causal role of CSTC hyperactivity in compulsive behaviors, reinforcing the circuit-based therapeutic framework. Conclusions Neuromodulatory interventions targeting CSTC dysfunction represent a promising strategy for OCD treatment. Continued research into adaptive stimulation technologies, biomarker-guided targeting, and combined therapeutic approaches is essential to optimize efficacy, safety, and accessibility.