Introduction: Treatment-resistant depression (TRD) is a major contributor to disability and premature mortality. Precision Cortical Stimulation (pCS), guided by fMRI-based Precision Functional Mapping (PFM) and adaptive Bayesian optimization, offers a tailored approach for individuals with severe depression. We tested this method in a 44-year-old male patient with a 30-year history of severe unipolar TRD and comorbid PTSD. PFM revealed a significant expansion of the Salience Network (SN) and reduced coverage of the default mode (DMN) and frontoparietal (FPN) networks. Four stimulation paddles were placed to target these regions with patient-specific precision. Initial postoperative testing indicated immediate positive responses in mood and cognition, with further optimization using Bayesian tuning over 9 months leading to complete remission. This remission was sustained for 21 months post-optimization. Our findings suggest that multi-target pCS, coupled with Bayesian tuning, offers a promising and scalable approach for treating TRD by precisely modulating relevant cortical networks.
Methods: Precision Functional Mapping (PFM) identified targeted brain networks in a TRD patient (NCT04124341). Four electrode paddles were implanted using neuronavigation. Stimulation parameters were optimized through Bayesian adaptive tuning based on patient feedback. Mood and cognition were tracked using the Montgomery–Åsberg Depression Rating Scale (MADRS) and 24-item Hamilton Depression Rating Scale (HDRS-24).
Results: Immediate improvements were observed in mood and cognitive clarity following initial stimulation. Full remission was achieved by 9 months and sustained through 21 months. The targeted modulation of SN, DMN, and FPN showed that specific network engagement correlated with treatment efficacy.
Conclusion : This case highlights the potential of PFM-guided pCS with adaptive tuning as a personalized intervention for TRD. Targeting expanded SN and associated networks may be critical in achieving lasting remission. Future studies should explore the efficacy of pCS in larger TRD populations, aiming to develop individualized neuromodulation protocols that address the unique neural alterations in TRD patients.
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