Intrinsic fMRI functional architecture differentiates single patients after severe brain injury

Abstract

Background: Resting state acquisitions are by definition appropriate to assess non-communicating subjects. We here assessed the clinical relevance of systems-level resting state fMRI in patients with disorders of consciousness with the aim to promote single-patient diagnostics. Methods: Seventy three patients in minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS) and coma were scanned in 3 different centers. The main analysis was performed on the dataset coming from one centre (Liège, 51 patients; 26 MCS, 19 VS/UWS, 6 coma; 16 traumatic, 32 non-traumatic, 3 mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised (CRS-R) was congruent with positron emission tomography scanning. Using a multiple-seed correlation approach, group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks. Between-group inferential statistics and machine learning were used to identify each network’s capacity to discriminate between patients in MCS and VS/UWS. Data from 22 patients independently scanned in two other centres (Salzburg: 10 MCS, 5 VS/UWS; New York: 5 MCS, 1 VS/UWS, 1 emerged from MCS) were used to validate the classification with the indetified features. Results: CRS-R total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. Although all networks had a high discriminative capacity (>80%) for separating patients in MCS and VS/UWS, the auditory network was ranked the most highly. Specifically, bilateral auditory and visual cortices of the auditory network were more functionally connected in patients in MCS compared to VS/UWS. Connectivity values in these three regions discriminated congruently 20 out of 22 independently assessed patients. Conclusions: These findings highlight the significance of preserved multisensory integration and top-down processing in minimal consciousness which are seemingly supported by auditory-visual crossmodal connectivity, and promote the clinical utility of the resting paradigm for single-patient diagnostics