Defining critical white matter pathways mediating successful subcallosal cingulate deep brain stimulation for treatment-resistant depression
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Background Subcallosal cingulate white matter (SCC) deep brain stimulation (DBS) is an evolving investigational treatment for depression. Mechanisms of action are hypothesized to involve modulation of activity within a structurally defined network of brain regions involved in mood regulation. Diffusion tensor imaging was used to model white matter connections within this network to identify those critical for successful antidepressant response.Methods Preoperative high-resolution magnetic resonance imaging data, including diffusion tensor imaging, were acquired in 16 patients with treatment-resistant depression, who then received SCC DBS. Computerized tomography was used postoperatively to locate DBS contacts. The activation volume around the contacts used for chronic stimulation was modeled for each patient retrospectively. Probabilistic tractography was used to delineate the white matter tracts traveling through each activation volume. Patient-specific tract maps were calculated using whole-brain analysis. Clinical evaluations of therapeutic outcome from SCC DBS were defined at 6 months and 2 years.Results Whole-brain activation volume tractography demonstrated that all DBS responders at 6 months (n = 6) and 2 years (n = 12) shared bilateral pathways from their activation volumes to 1) medial frontal cortex via forceps minor and uncinate fasciculus; 2) rostral and dorsal cingulate cortex via the cingulum bundle; and 3) subcortical nuclei. Nonresponders did not consistently show these connections. Specific anatomical coordinates of the active contacts did not discriminate responders from nonresponders.Conclusions Patient-specific activation volume tractography modeling may identify critical tracts that mediate SCC DBS antidepressant response. This suggests a novel method for patient-specific target and stimulation parameter selection.
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In a retrospective analysis of initial open-label SCC DBS data, a confluence of white matter bundles was identified near but not always overlapping the notional SCC target; when all three bundles were captured within the inferred DBS electric field, patients responded, while non-responders lacked engagement of at least one bundle.
“In a retrospective analysis of their initial open-label data, they identified a confluence of white matter bundles that was near, but did not always overlap, the notional SCC target (Riva-Posse et al. 2014). When all three bundles were captured within the (inferred) DBS electric field, patients responded, but non-responders lacked engagement of at least one bundle.”
From Deep brain stimulation for psychiatric disorders: From focal brain targets to cognitive networks (2021) · cites this paper as Riva-Posse et al. 2014
Recent studies suggest maximal clinical efficacy of subcallosal cingulate cortex DBS is directly correlated with the specific white matter tracts affected rather than anatomic location of stimulation as defined by traditional gray-white matter landmarks.
“Recent studies suggest maximal clinical efficacy of SCC DBS is directly correlated with the specific white matter tracts affected rather than anatomic location of stimulation as defined by traditional gray-white matter landmarks [6].”
From Deep brain stimulation for depression. (2022) · cites this paper as [6]
Bilateral stimulation of all four white matter tracts appears necessary for a full response in SCC DBS.
“bilateral stimulation of all four white matter tracts appears required to achieve a full response [6].”
From Deep brain stimulation for depression. (2022) · cites this paper as [6]
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Predictors of hypomania during ventral capsule/ventral striatum deep brain stimulation
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- Authors
- Riva-Posse, P., Choi, K. S., Holtzheimer, P. E., McIntyre, C. C., Gross, R. E., Chaturvedi, A., Crowell, A. L., Garlow, S. J., Rajendra, J. K., & Mayberg, H. S.
- Affiliations
- Georgia Institute of Technology (US)
- Dartmouth College (US)
- Case Western Reserve University (US)
- Emory University (US)
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 76
- Issue
- 12
- Pages
- 963-969
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4487804
- OpenAlex
- W2072296702
- Cited by
- 460
- References
- 53
- Citations by year
- 2026: 27 · 2025: 30 · 2024: 34 · 2023: 42 · 2022: 37 · 2021: 52 · 2020: 40 · 2019: 38 · 2018: 44 · 2017: 41 · 2016: 32 · 2015: 34 · 2014: 9
- FWCI
- 25.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 NS059736)
- Dana Foundation
- Stanley Medical Research Institute
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- treatment-resistant depression, white matter tracts, antidepressant response prediction, cingulum, uncinate fasciculus, forceps minor, medial frontal cortex, cingulate cortex, subcortical nuclei
- MeSH terms
- Corpus Callosum, Female, Gyrus Cinguli, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Male, Deep Brain Stimulation, Diffusion Tensor Imaging, Depressive Disorder, Treatment-Resistant, White Matter
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