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A human brain network linked to restoration of consciousness after deep brain stimulation

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Warren, Aaron E. L., Raguž, Marina, Friedrich, Helen, Schaper, Frederic L. W. V. J., Tasserie, Jordy, Snider, Samuel B., Li, Jian, Chua, Melissa M. J. +12 more·2025·Nature Communications
DOI 10.1038/s41467-025-61988-4PMC PMC12279989

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Abstract

Disorders of consciousness are characterized by severe impairments in arousal and awareness. Deep brain stimulation is a potential treatment, but outcomes vary-possibly due to differences in patient characteristics, electrode placement, or the specific brain network engaged. We describe 40 patients with disorders of consciousness undergoing deep brain stimulation targeting the thalamic centromedian-parafascicular complex. Improvements in consciousness are associated with better-preserved gray matter, particularly in the striatum. Electric field modeling reveals that stimulation is most effective when it extends below the centromedian nucleus, engaging the inferior parafascicular nucleus and the adjacent ventral tegmental tract-a pathway that connects the brainstem and hypothalamus and runs along the midbrain-thalamus border. External validation analyzed show that effective stimulation engages a brain network overlapping with disrupted patterns of brain activity observed in two independent cohorts with impaired consciousness: one with arousal-impairing stroke lesions and the other with awareness-impairing seizures. Together, these findings advance the field by informing patient selection, refining stimulation targets, and identifying a brain network linked to recovery that may have broader therapeutic relevance across consciousness-impairing conditions.

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  • Related findings have been reported in nonhuman primates and in patients with disorders of consciousness treated with deep brain stimulation, although substantial technical and ethical challenges remain.

    “Related findings have been reported in nonhuman primates (Tasserie et al., 2022) and in patients with disorders of consciousness treated with deep brain stimulation (Warren et al., 2025), although substantial technical and ethical challenges remain, emphasizing the potential interest of this theoretical framework.”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Warren et al., 2025

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Cited by

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Authors
Warren, A. E. L., Raguž, M., Friedrich, H., Schaper, F. L. W. V. J., Tasserie, J., Snider, S. B., Li, J., Chua, M. M. J., Butenko, K., Friedrich, M. U., Jha, R., Iglesias, J. E., Carney, P. W., Fischer, D., Fox, M. D., Boes, A. D., Edlow, B. L., Horn, A., Chudy, D., & Rolston, J. D.
Affiliations
  • Brigham and Women's Hospital (US)
  • University Hospital Dubrava (HR)
  • Harvard University (US)
  • Florey Institute of Neuroscience and Mental Health (AU)
  • University of Pennsylvania (US)
  • University of Iowa (US)
  • University of Zagreb (HR)
Corresponding author
  • Warren, Aaron E. L.
  • Rolston, John D.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-07-21
Volume
16
Issue
1
Pages
6721-6721
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-61988-4
PMC
PMC12279989
OpenAlex
W4412537699
Cited by
18
References
3
Citations by year
2026: 14 · 2025: 4
FWCI
10.96
Type
journal article
Language
en
Update notices
correction (2025-08-14)
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Massachusetts General Hospital
  • Massachusetts Institute of Technology
  • University of Pennsylvania
  • EU Joint Programme – Neurodegenerative Disease Research
  • Neurocritical Care Society
  • Deutsche Forschungsgemeinschaft (R01MH130666, 1R01NS127892-01, TRR-295, UM1NS132358, 424778381)
  • Hrvatska Zaklada za Znanost (CSF-IP-2020-02-4308, IP-2020-02-4308, IP-2020-02)
  • National Institutes of Health (1rf1ag080371-01a1, 2020-02, 1rf1mh123195-01)
  • National Institute on Aging (RF1 AG080371, R01AG070988)
  • National Institute of Mental Health (R21MH126271, RF1 MH123195, UM1MH130981, R01MH130666, R01MH113929)
  • National Institute of Neurological Disorders and Stroke (R21NS123813, UH3NS109557, R01NS138257, R01NS127892, K23NS136745, K23NS136767, UM1NS132358)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (DP2HD101400)
Topics
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
Keywords
disorders of consciousness, deep brain stimulation, centromedian-parafascicular complex, thalamus, striatum, electric field modeling, arousal, awareness, stroke, seizures, brain networks, patient selection, stimulation targets
MeSH terms
Adult, Aged, Brain, Consciousness, Consciousness Disorders, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Deep Brain Stimulation, Gray Matter

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