Stereo-encephalography-guided multi-lead deep brain stimulation for treatment-refractory obsessive compulsive disorder – study design and individualized surgical targeting approach
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Introduction
Treatment-refractory obsessive-compulsive disorder (trOCD) is a complex brain network disorder that remains partially understood and may require personalized treatment strategies due to disease heterogeneity. While stereo-electroencephalography (sEEG) is standard of care for surgical epilepsy workups, its use in refractory neuropsychiatric disorders remains investigational. A multi-site, multi-stage, double-blinded, randomized crossover clinical trial is currently underway, using sEEG to guide selection of multi-nodal targets for subsequent deep brain stimulation (DBS) in the treatment of trOCD.
Objectives
To describe the study design of this ongoing clinical trial, with an emphasis on personalized surgical targeting strategies that ensure both the feasibility and precision of sEEG electrode placement, and enable adequate sampling of relevant targets in trOCD for network evaluation and modulation.
Methods
Adult patients with severe trOCD (Yale-Brown Obsessive Compulsive Scale ≥ 28) who meet eligibility criteria will be enrolled in this study. The clinical trial ( NCT05623306 ) involves three stages. In stage 1, up to 20 sEEG electrodes will be implanted in cortical and subcortical regions implicated in trOCD. Individualized probabilistic-tractography-guided target refinement will be performed for surgical planning. To ensure surgical feasibility of non-conventional surgical trajectories, patient-specific three-dimensional (3D) printed head models may be used for surgical rehearsal. Continuous and synchronous audiovisual and intracranial electroencephalographic (iEEG) recordings will be performed in the psychiatric monitoring unit. Participants undergo psychologist-led symptom provocations, brain stimulation evoked potential mapping, acute stimulation testing and cognitive tasks over a 12-day inpatient evaluation. In stage 2, up to four permanent DBS electrodes will be implanted followed by stimulation optimization for up to 52 weeks. Stage 3 involves a randomized, double-blinded cross-over phase.
Expected Outcomes
Safety, feasibility and preliminary efficacy will be assessed in this ongoing study. Primary safety endpoints include the number and type of serious adverse events. Feasibility endpoints include percentage of patients in whom OCD-relevant network or stimulation target can be identified. Treatment response will be determined by change in Y-BOCS II score between active and sham stimulation conditions. We anticipate that sEEG to guide selection of multi-nodal targets for DBS will be safe, feasible and result in clinically meaningful improvements in symptom severity and functional impairment in trOCD.
Discussion
We present the clinical protocol of sEEG-guided investigation of brain networks involved in trOCD and describe our tractography-guided surgical targeting strategy designed to optimize individualized network engagement and neuromodulation.
