Initial unilateral exposure to deep brain stimulation in treatment-resistant depression patients alters spectral power in the subcallosal cingulate
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Background. High-frequency Deep Brain Stimulation (DBS) of the subcallosal cingulate (SCC) region is an emerging strategy for treatment-resistant depression (TRD). In this study, we examined changes in SCC local field potentials (LFPs). LFPs were recorded from the DBS leads following transient, unilateral stimulation at the neuroimaging-defined optimal electrode contact. The goal was to identify a putative electrophysiological signal of target engagement measurable during implantation. Methods. Fourteen consecutive patients underwent bilateral SCC DBS lead implantation. LFP recordings were collected from all electrodes during randomized testing of stimulation on each DBS contact (eight total). Analyses evaluated changes in spectral power before and after 2 minutes of unilateral stimulation at the contacts that later facilitated antidepressant response, as a potential biomarker of optimal contact selection in each hemisphere. Results. Lateralized and asymmetric power spectral density changes were detected in the SCC with acute unilateral SCC stimulation at those contacts subsequently selected for chronic, therapeutic stimulation. Left stimulation induced broadband ipsilateral decreases in theta, alpha, beta and gamma bands. Right stimulation effects were restricted to ipsilateral beta and gamma decreases. These asymmetric effects contrasted with identical white matter stimulation maps used in each hemisphere. More variable ipsilateral decreases were seen with stimulation at the adjacent ‘suboptimal’ contacts but changes were not statistically different from the ‘optimal’ contact in either hemisphere despite obvious differences in impacted white matter bundles. Change in theta power was, however, most robust and specific with left-sided optimal stimulation, which suggested a putative functional biomarker on the left with no such specificity inferred on the right. Conclusion. Hemisphere specific oscillatory changes can be detected off of the DBS lead with acute intraoperative testing at contacts that later engender antidepressant effects. Our approach defined potential target engagement signals for further investigation, particularly left-sided theta decreases following initial exposure to stimulation. More refined models combining tractography, bilateral SCC LFP, and cortical recordings may further improve the precision and specificity of these putative biomarkers. It may also optimize and standardize the lead implantation procedure and provide input signals for next generation closed-loop therapy and/or monitoring technologies for TRD.
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Intraoperative shifts in mood in direct response to effective stimulation have been described.
“This has been described in intraoperative shifts in mood in direct response to effective stimulation [108].”
From Deep brain stimulation for depression. (2022) · cites this paper as [108]
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Elias, G. J. B., Iskin, S. A., Beyn, M. E., Omere, U., Rizvi, S. J., Ceniti, A. K., Boutet, A., Voineskos, D., Kennedy, S. H., Lozano, A. M., et al. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2025.05.009 · Cited by 5 · see citing works
Pallidal beta power is associated with depression in Parkinson’s disease
Johnson, K. A., Coutinho, P. B., Kenney, L. E., Wong, J. K., Hilliard, J. D., Foote, K. D., Bowers, D., Pontone, G. M., & de Hemptinne, C. (2026) · npj Parkinson s Disease · doi:10.1038/s41531-026-01264-4 · Cited by 4 · see citing works
Liang, Y., Lai, M.-L., Chiu, F., Tseng, H.-Y., Lo, Y., Li, S., Chang, C.-W., Chen, P.-C., & Chen, Y. (2023) · Biosensors · doi:10.3390/bios13020265 · Cited by 4 · see citing works
Reservoir-based Tracking (TRAKR) For One-shot Classification Of Neural Time-series PatternsPreprint
Afzal, M. F., Márton, C. D., Rich, E. L., Mayberg, H. S., & Rajan, K. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.13.464288 · Cited by 4 · see citing works
Self-citationDecoding depression during subcallosal cingulate deep brain stimulationPreprint
Tiruvadi, V., Veerakumar, A., Smart, O. L., Crowell, A. L., Riva‐Posse, P., Gross, R. E., McIntyre, C. C., Rozell, C. J., Butera, R. J., & Mayberg, H. S. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.27.501778 · Cited by 4 · see citing works
Self-citationPutting deep brain stimulation for depression in a wider perspective
Bergfeld, I. O. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30476-6 · Cited by 3 · see citing works
Connectomic Determinants of Subcallosal Cingulate Deep Brain Stimulation for Depression
Song, H. N., Choi, K. S., Kopell, B. H., Figee, M., de Bruin, J., Cha, J., Riva‐Posse, P., Boutet, A., Elias, G. J. B., Germann, J., et al. (2026) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20250449 · Cited by 2 · see citing works
Self-citationExploration of acute effects of stimulation frequency on subcallosal cingulate dynamics in SCC DBS
Fitoz, E. C., Alagapan, S., Waters, A. C., Tiruvadi, V., Veerakumar, A., Obatusin, M., Choi, K. S., Crowell, A. L., Riva‐Posse, P., Butera, R. J., et al. (2023) · International IEEE/EMBS Conference on Neural Engineering · doi:10.1109/ner52421.2023.10123785 · Cited by 2 · see citing works
Self-citationCan Deep Brain Stimulation Be a Promising Treatment for Treatment-Resistant Depression?
Nazanin, A., & Ijeuma, N. (2023) · International Journal of Depression and Anxiety · doi:10.23937/2643-4059/1710036 · Cited by 1 · see citing works
Iskin, S. A., Elias, G. J. B., Naheed, A., Pinto, J., Omere, U., Kennedy, S. H., Loh, A., Ajala, A., Santyr, B. G., Boutet, A., et al. (2025) · The Canadian Journal of Psychiatry · doi:10.1177/07067437251387573 · Cited by 1 · see citing works
The Physiologic Basis of Neuromodulation
Wilson, T. J., & Butala, A. (2024) · Advances in Psychiatry and Behavioral Health · doi:10.1016/j.ypsc.2024.05.001 · Cited by 1 · see citing works
Network Action of Subcallosal Cingulate White Matter Deep Brain StimulationPreprint
Tiruvadi, V., Choi, K. S., Waters, A. C., Tao, L., Konda, R., Ibrahim, N., Smart, O. L., Crowell, A. L., Riva‐Posse, P., Gross, R. E., et al. (2022) · medRxiv · doi:10.1101/2022.07.27.22278130 · Cited by 1 · see citing works
Self-citationFitoz, E. C., Alagapan, S., Cha, J., Choi, K. S., Figee, M., Kopell, B. H., Obatusin, M., Heisig, S., Nauvel, T., Razavilar, A., et al. (2026) · medRxiv · doi:10.64898/2026.04.13.26350107 · Cited by 1 · see citing works
Self-citationBaumann‐Vogel, H., Ineichen, C., Stieglitz, L. H., & Kawohl, W. (2023) · Praxis · doi:10.1024/1661-8157/a004047
- Authors
- Smart, O., Choi, K. S., Riva-Posse, P., Tiruvadi, V., Rajendra, J., Waters, A. C., Crowell, A. L., Edwards, J., Gross, R. E., & Mayberg, H. S.
- Affiliations
- Emory University (US)
- Georgia Institute of Technology (US)
- Corresponding author
- Smart, Otis
- ORCID
- Venue
- Frontiers in Computational Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-06-12
- Volume
- 12
- Pages
- 43-43
- ISSN
- 1662-5188 (ISSN-L)
- PMC
- PMC6008542
- OpenAlex
- W2805698000
- Cited by
- 41
- References
- 55
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 11 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 1
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Computational Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (1R01MH102238, 1R01MH106173, UH3NS103550)
- Dana Foundation
- Hope for Depression Research Foundation
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- deep brain stimulation, treatment-resistant depression, subcallosal cingulate, local field potentials, spectral power, theta band, unilateral stimulation, hemispheric lateralization, target engagement biomarkers, white matter tracts, closed-loop therapy
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