From bed to bench side: Reverse translation to optimize neuromodulation for mood disorders
Open accessAbstract
The advent of neuroimaging has provided foundational insights into the neural basis of psychiatric conditions, such as major depression. Across countless studies, dysfunction has been localized to distinct parts of the limbic system. Specific knowledge about affected locations has led to the development of circuit modulation therapies to correct dysfunction, notably deep brain stimulation (DBS). This and other emerging neuromodulation approaches have shown great promise, but their refinement has been slow and fundamental questions about their mechanisms of action remain. Here, we argue that their continued development requires reverse translation to animal models with close homology to humans, namely, nonhuman primates. With a particular focus on DBS approaches for depression, we highlight the parts of the brain that have been targeted by neuromodulation in humans, their efficacy, and why nonhuman primates are the most suitable model in which to conduct their refinement. We finish by highlighting key gaps in our knowledge that need to be filled to allow more rapid progress toward effective therapies in patients for whom all other treatment attempts have failed.
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The sweet spot is in the high-frequency range of 100-150 Hz, which is also supported by animal studies.
“the sweet spot is in the high-frequency range (100-150 Hz) [103], which is also supported by animal studies [104,105].”
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Deep brain stimulation for depression.
Figee, M., Riva-Posse, P., Choi, K. S., Bederson, L., Mayberg, H. S., & Kopell, B. H. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01270-3 · Cited by 175 · see citing works
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- Authors
- Rudebeck, P. H., Rich, E. L., & Mayberg, H. S.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Mayberg, Helen S.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-12-23
- Volume
- 116
- Issue
- 52
- Pages
- 26288-26296
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6936427
- OpenAlex
- W2997594689
- Cited by
- 42
- References
- 88
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 13 · 2020: 4 · 2019: 1 · 2018: 2
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (R01MH110822)
- HHS | NIH | National Institute on Minority Health and Health Disparities (UH3NS103550)
- HHS | NIH | National Institute on Drug Abuse (K08DA039351)
- Hope for Depression Research Foundation (0000)
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- reverse translation, deep brain stimulation, major depressive disorder, mood disorders, non-human primates, animal models, limbic system, neuromodulation, translational research, treatment-resistant depression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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