Personalized Adaptive Cortical Electro-stimulation (PACE) in Treatment-Resistant Depression

Treatment-resistant depression (TRD) is a leading cause of premature death. For decades investigators have assessed the clinical efficacy of direct brain stimulation for TRD. Outcomes have been inconsistent due to imprecise brain targeting. Minimally invasive Personalized Adaptive Cortical Electro-stimulation (PACE) uses fMRI-based precision functional mapping (PFM) to target patient-specific network anomalies with brain surface electrodes. We utilized this novel technology in an n-of-1 study to treat a 44-year-old man (TRD-1) with over 30 years of severe unipolar depression. PFM revealed a 400% expansion in cortical area of the Salience Network (SN) and a 25% reduction in default mode (DMN) and frontoparietal (FP) networks compared to a group average controls. Stimulation paddles were implanted targeting patient-specific SN, DMN, and FP networks. Postoperative stimulation testing (within 24h) revealed immediate electrode-specific mood and cognition responses that matched the underlying functional networks. Stimulation parameters were iteratively optimized using ‘Bayes Tuning’ based on patient feedback. TRD-1’s suicidal ideations ceased within 7 weeks. Full remission of symptoms was achieved within 9 months and maintained at 30 months. PACE therapy appears to be a scalable, safe, and cost-effective approach to treat TRD.