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

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...

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Main Authors: Aaron E. L. Warren, Marina Raguž, Helen Friedrich, Frederic L. W. V. J. Schaper, Jordy Tasserie, Samuel B. Snider, Jian Li, Melissa M. J. Chua, Konstantin Butenko, Maximilian U. Friedrich, Rohan Jha, Juan E. Iglesias, Patrick W. Carney, David Fischer, Michael D. Fox, Aaron D. Boes, Brian L. Edlow, Andreas Horn, Darko Chudy, John D. Rolston
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61988-4
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author Aaron E. L. Warren
Marina Raguž
Helen Friedrich
Frederic L. W. V. J. Schaper
Jordy Tasserie
Samuel B. Snider
Jian Li
Melissa M. J. Chua
Konstantin Butenko
Maximilian U. Friedrich
Rohan Jha
Juan E. Iglesias
Patrick W. Carney
David Fischer
Michael D. Fox
Aaron D. Boes
Brian L. Edlow
Andreas Horn
Darko Chudy
John D. Rolston
author_facet Aaron E. L. Warren
Marina Raguž
Helen Friedrich
Frederic L. W. V. J. Schaper
Jordy Tasserie
Samuel B. Snider
Jian Li
Melissa M. J. Chua
Konstantin Butenko
Maximilian U. Friedrich
Rohan Jha
Juan E. Iglesias
Patrick W. Carney
David Fischer
Michael D. Fox
Aaron D. Boes
Brian L. Edlow
Andreas Horn
Darko Chudy
John D. Rolston
author_sort Aaron E. L. Warren
collection DOAJ
description 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 analyses 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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spelling doaj-art-e0e16a46953740ee944d85ca6dfa3e692025-08-20T04:03:02ZengNature PortfolioNature Communications2041-17232025-07-0116111610.1038/s41467-025-61988-4A human brain network linked to restoration of consciousness after deep brain stimulationAaron E. L. Warren0Marina Raguž1Helen Friedrich2Frederic L. W. V. J. Schaper3Jordy Tasserie4Samuel B. Snider5Jian Li6Melissa M. J. Chua7Konstantin Butenko8Maximilian U. Friedrich9Rohan Jha10Juan E. Iglesias11Patrick W. Carney12David Fischer13Michael D. Fox14Aaron D. Boes15Brian L. Edlow16Andreas Horn17Darko Chudy18John D. Rolston19Department of Neurosurgery, Mass General Brigham, Harvard Medical SchoolDepartment of Neurosurgery, Dubrava University HospitalCenter for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical SchoolAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Mass General Brigham, Harvard Medical SchoolCenter for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Mass General Brigham, Harvard Medical SchoolAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical SchoolEastern Health Clinical School, Monash UniversityPerelman School of Medicine, University of PennsylvaniaCenter for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical SchoolDepartments of Neurology, Pediatrics, and Psychiatry, Carver College of Medicine, University of IowaAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical SchoolCenter for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Dubrava University HospitalDepartment of Neurosurgery, Mass General Brigham, Harvard Medical SchoolAbstract 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 analyses 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.https://doi.org/10.1038/s41467-025-61988-4
spellingShingle Aaron E. L. Warren
Marina Raguž
Helen Friedrich
Frederic L. W. V. J. Schaper
Jordy Tasserie
Samuel B. Snider
Jian Li
Melissa M. J. Chua
Konstantin Butenko
Maximilian U. Friedrich
Rohan Jha
Juan E. Iglesias
Patrick W. Carney
David Fischer
Michael D. Fox
Aaron D. Boes
Brian L. Edlow
Andreas Horn
Darko Chudy
John D. Rolston
A human brain network linked to restoration of consciousness after deep brain stimulation
Nature Communications
title A human brain network linked to restoration of consciousness after deep brain stimulation
title_full A human brain network linked to restoration of consciousness after deep brain stimulation
title_fullStr A human brain network linked to restoration of consciousness after deep brain stimulation
title_full_unstemmed A human brain network linked to restoration of consciousness after deep brain stimulation
title_short A human brain network linked to restoration of consciousness after deep brain stimulation
title_sort human brain network linked to restoration of consciousness after deep brain stimulation
url https://doi.org/10.1038/s41467-025-61988-4
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