Target identification and contact selection are known contributors to variability in efficacy across different clinical indications of deep brain stimulation surgery. A retrospective analysis of responders to subcallosal cingulate deep brain stimulation (SCC DBS) for depression demonstrated the common impact of the electrical stimulation on a stereotypic connectome of converging white matter bundles (forceps minor, uncinate fasciculus, cingulum and fronto-striatal fibers). To test the utility of a prospective connectomic approach for SCC DBS surgery, this pilot study used the four-bundle tractography ‘connectome blueprint’ to plan surgical targeting in 11 participants with treatment-resistant depression. Before surgery, targets were selected individually using deterministic tractography. Selection of contacts for chronic stimulation was made by matching the post-operative probabilistic tractography map to the pre-surgical deterministic tractography map for each subject. Intraoperative behavioral responses were used as a secondary verification of location. A probabilistic tract map of all participants demonstrated inclusion of the four bundles as intended, matching the connectome blueprint previously defined. Eight of 11 patients (72.7%) were responders and 5 were remitters after 6 months of open-label stimulation. At one year, 9 of 11 patients (81.8%) were responders, with 6 of them in remission. These results support the utility of a group probabilistic tractography map as a connectome blueprint for individualized, patient-specific, deterministic tractography targeting, confirming retrospective findings previously published. This new method represents a connectomic approach to guide future SCC DBS studies.
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We acknowledge Mary Kelley, PhD (Rollins School of Public Health, Emory University) for her collaboration and input in data management. We also acknowledge Angela Noecker (Biomedical Engineering, Case Western Reserve University) for assistance in the development of tractography models. We thank the collaboration of the research staff: Sinéad Quinn, Kelsey Hagan, Morgan Woody, Lydia Denison, as well as the patients and their families.
P Riva-Posse and KS Choi contributed equally to the design, data analysis, preparation of the manuscript.
PE Holtzheimer reported serving as a paid consultant to St Jude Medical. RE Gross reported receiving grants from Medtronic, Neuropace and MRI Interventions, honoraria from Medtronic Inc and MRI Interventions; and serving as a paid consultant to St Jude Medical, Medtronic, Neuropace, MRI Intervantions, Neuralstem and SanBio. CC McIntyre is a paid consultant for Boston Scientific Neuromodulation, and is a shareholder in the following companies: Surgical Information Sciences; Autonomic Technologies; Cardionomic; Enspire DBS; Neuros Medical. HS Mayberg has a consulting agreement with St Jude Medical, which has licensed her intellectual property to develop SCC DBS for the treatment of severe depression (US 2005/0033379A1). Medtronic and St Jude Medical Corp develop products related to the research described in this article. The terms of these arrangements have been reviewed and approved by Emory University in accordance with their conflict of interest policies. The remaining authors declare no conflict of interest.
Hope for Depression Research Foundation, Dana Foundation, NIH R01MH102238 (PI: Cameron McIntyre). The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Supplementary Information accompanies the paper on the Molecular Psychiatry website
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Riva-Posse, P., Choi, K., Holtzheimer, P. et al. A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression. Mol Psychiatry 23, 843–849 (2018). https://doi.org/10.1038/mp.2017.59
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