Chronic intracranial neural dynamics forecast treatment response and therapeutic engagement during deep brain...

Clinical improvement following psychiatric neuromodulation often requires weeks to months, creating prolonged uncertainty during treatment optimization. Neural biomarkers could reduce this uncertainty by forecasting treatment outcome, providing early evidence of therapeutic engagement, and objectively tracking clinical response. We analyzed nearly 120,000 patient-hours of chronic intracranial recordings from 24 patients undergoing ventral capsule/ventral striatum deep brain stimulation for treatment-resistant obsessive-compulsive disorder. Before stimulation initiation, circadian neural features distinguished eventual responders from non-responders. Within the first two weeks of therapy, reductions in neural predictability differentiated eventual responders from non-responders and correlated with the magnitude of subsequent symptom improvement, months before stable clinical response was achieved. During chronic treatment, neural predictability tracked clinical response state. Together, these findings establish a framework for neural biomarkers spanning the course of DBS therapy: forecasting treatment response before stimulation, detecting early therapeutic engagement after activation, and longitudinally monitoring clinical response.