Abstract
Objective: We hypothesize that the major consciousness deficit observed in coma is due to the breakdown of long-range neuronal communication supported by precuneus and posterior cingulate cortex (PCC), and that prognosis depends on a specific connectivity pattern in these networks.
Methods: We compared 27 prospectively recruited comatose patients who had severe brain injury (Glasgow Coma Scale score <8; 14 traumatic and 13 anoxic cases) with 14 age-matched healthy participants. Standardized clinical assessment and fMRI were performed on average 4 ± 2 days after withdrawal of sedation. Analysis of resting-state fMRI connectivity involved a hypothesis-driven, region of interest–based strategy. We assessed patient outcome after 3 months using the Coma Recovery Scale–Revised (CRS-R).
Results: Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with PCC, globally notwithstanding etiology. The functional connectivity strength between PCC and medial prefrontal cortex (mPFC) was significantly different between comatose patients who went on to recover and those who eventually scored an unfavorable outcome 3 months after brain injury (Kruskal-Wallis test, p < 0.001; linear regression between CRS-R and PCC-mPFC activity coupling at rest, Spearman ρ = 0.93, p < 0.003).
Conclusion: In both etiology groups (traumatic and anoxic), changes in the connectivity of PCC-centered, spontaneously synchronized, large-scale networks account for the loss of external and internal self-centered awareness observed during coma. Sparing of functional connectivity between PCC and mPFC may predict patient outcome, and further studies are needed to substantiate this potential prognosis biomarker.
GLOSSARY
- BOLD=
- blood oxygen level–dependent;
- CRS-R=
- Coma Recovery Scale–Revised;
- DMN=
- default-mode network;
- FDR=
- false discovery rate;
- mPFC=
- medial prefrontal cortex;
- PCC=
- posterior cingulate cortex;
- PMC=
- posteromedial cortex;
- PreCu=
- precuneus;
- ROI=
- region of interest;
- SMG=
- supramarginal gyrus;
- TBI=
- traumatic brain injury
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by INSERM.
Supplemental data at Neurology.org
- Received April 8, 2015.
- Accepted in final form August 10, 2015.
- © 2015 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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