Journal
NEUROLOGY
Volume 87, Issue 23, Pages 2427-2434Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000003404
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Funding
- Howard Hughes Medical Institute
- Parkinson's Disease Foundation
- NIH [S10RR023043, K23NS083741, R01HD069776, R01NS073601, R01NS085477, R21MH099196, R21NS082870, R21NS085491, R21HD07616, R25NS065743, R25NS070682, T32 HL007901, P01HL095491]
- Academy of Neurology/American Brain Foundation
- Sidney R. Baer, Jr. Foundation
- Harvard Catalyst
- Belgian National Funds for Scientific Research
- European Commission
- James McDonnell Foundation
- European Space Agency
- Mind Science Foundation
- French Speaking Community Concerted Research Action [ARC-06/11-340]
- Public Utility Foundation Universite Europeenne du Travail
- Fondazione Europea di Ricerca Biomedica
- University and University Hospital of Liege
- Center for Integrative Neuroscience
- Max Planck Society
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Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness.
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