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

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 and John D. Rolston ()
Additional contact information
Aaron E. L. Warren: Harvard Medical School
Marina Raguž: Dubrava University Hospital
Helen Friedrich: Harvard Medical School
Frederic L. W. V. J. Schaper: Harvard Medical School
Jordy Tasserie: Harvard Medical School
Samuel B. Snider: Harvard Medical School
Jian Li: Harvard Medical School
Melissa M. J. Chua: Harvard Medical School
Konstantin Butenko: Harvard Medical School
Maximilian U. Friedrich: Harvard Medical School
Rohan Jha: Harvard Medical School
Juan E. Iglesias: Harvard Medical School
Patrick W. Carney: Monash University
David Fischer: University of Pennsylvania
Michael D. Fox: Harvard Medical School
Aaron D. Boes: University of Iowa
Brian L. Edlow: Harvard Medical School
Andreas Horn: Harvard Medical School
Darko Chudy: Dubrava University Hospital
John D. Rolston: Harvard Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61988-4

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