Disruption of posteromedial large-scale neural communication predicts recovery from coma

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.

Multimodal study of default‐mode network integrity in disorders of consciousness

“…In the favorable scenario of low or no movement, rs-fMRI seems to have high sensitivity to DMN activity; however, a sizable proportion of cases, especially MCS patients, move during scanning (see Supplementary Table 3), curtailing the diagnostic potential of this technique. 22 We hypothesize that rs-fMRI might be useful for detecting cases where additional diagnostics or increased rehabilitation efforts may be motivated in light of possible conversion to MCS. Here, to accurately represent clinical reality, we chose to include all patients who could be scanned and a posteriori, blinded to the clinical data, we removed those most affected by movement.…”

“…7 Key advances in understanding DOC have come from 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). 18,19,21 Recently, it has been shown that preservation 18 (14)(15)(16)(17)(18)(19)(20)(21)(22) Etiology is reported as traumatic/vascular/anoxic (No.). 2,[8][9][10] Recent studies have confirmed that metabolic integrity can disentangle VS/UWS from MCS patients with good accuracy and predict clinical outcome.…”

“…2,[8][9][10] Recent studies have confirmed that metabolic integrity can disentangle VS/UWS from MCS patients with good accuracy and predict clinical outcome. 22 Although in some domains rs-fMRI is capable of attaining rather high diagnostic accuracy levels, [23][24][25] its clinical value in DOC remains unclear. Resting-state functional MRI (rs-fMRI) reveals multiple cortical networks of synchronized activity.…”

“…[16][17][18][19][20][21] In MCS, the DMN is somewhat stronger than in VS/UWS, but severely impaired compared to healthy subjects. 18,19,21 Recently, it has been shown that preservation (14)(15)(16)(17)(18)(19)(20)(21)(22) Etiology is reported as traumatic/vascular/anoxic (No.). Age, disease duration, and CRS-R scores are given as median (range).…”

Degrees of functional connectome abnormality in disorders of consciousness

“…Thus, in Wu et al (), functional connectivity strength patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. Along the same lines, Silva et al () showed that the correlation between posterior cingulate cortex and medial prefrontal cortex (also part of the DMN) in comatose patients predicted the Coma Recovery Scale‐Revised (CRS‐R) score 3 month after the scanning. More recent studies have also found disrupted connectivity in resting‐state networks other than the DMN (Demertzi et al, ).…”