Quantifying the axonal pathways directly stimulated in therapeutic subcallosal cingulate deep brain stimulation

• Type of Material: Article
• Authors: Bryan Howell, Case Western Reserve University; Ki Choi, Emory University; Ki Seung Gunalan, Case Western Reserve University; Justin Rajendra, NIMH; Helen Mayberg, Emory University; Cameron C. McIntyre, Case Western Reserve University
• Language: English
• Date: 2019-02-15
• Publisher: Wiley Periodicals Inc.
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2018 Wiley Periodicals, Inc.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/hbm.24419
• Title of Journal or Parent Work: Human Brain Mapping
• Volume: 40
• Issue: 3
• Start Page: 889
• End Page: 903
• Grant/Funding Information: National Institute of Mental Health, Grant/Award Number: R01 MH102238; National Institute of Neurological Disorders and Stroke, Grant/Award Number: F32 NS096839; National Institutes of Health, Grant/Award Numbers: T32 EB004314, TL1 TR000441, T32 GM007250, UH3 NS103550; Dana Foundation; Hope for Depression Research Foundation;; U.S. Department of Education, Grant/Award Number: GAANN P200A100112
• Keywords: PET FINDINGS; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging; Neurosciences; SYSTEM; TRACTOGRAPHY; pathway activation; WHITE-MATTER; SUBCORTICAL PROJECTIONS; MAJOR DEPRESSION; computational model; Life Sciences & Biomedicine; connectomic; Neuroimaging; Science & Technology; MODELS; OUTCOMES; ROBUST; CORTEX
• Research Categories: Biology, Neuroscience

Abstract

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is an emerging experimental therapy for treatment-resistant depression. New developments in SCC DBS surgical targeting are focused on identifying specific axonal pathways for stimulation that are estimated from patient-specific computational models. This connectomic-based biophysical modeling strategy has proven successful in improving the clinical response to SCC DBS therapy, but the DBS models used to date have been relatively simplistic, limiting the precision of the pathway activation estimates. Therefore, we used the most detailed patient-specific foundation for DBS modeling currently available (i.e., field-cable modeling) to evaluate SCC DBS in our most recent cohort of six subjects, all of which were responders to the therapy. We quantified activation of four major pathways in the SCC region: forceps minor (FM), cingulum bundle (CB), uncinate fasciculus (UF), and subcortical connections between the frontal pole and the thalamus or ventral striatum (FP). We then used the percentage of activated axons in each pathway as regressors in a linear model to predict the time it took patients to reach a stable response, or TSR. Our analysis suggests that stimulation of the left and right CBs, as well as FM are the most likely therapeutic targets for SCC DBS. In addition, the right CB alone predicted 84% of the variation in the TSR, and the correlation was positive, suggesting that activation of the right CB beyond a critical percentage may actually protract the recovery process.