Brain Responses to Propofol in Advance of Recovery from Coma and Disorders of Consciousness: A Preliminary Study.

Rationale: Predicting recovery of consciousness in unresponsive, brain-injured individuals has crucial implications for clinical decision-making. Propofol induces distinctive brain network reconfiguration in the healthy brain as it loses consciousness. In patients with disorders of consciousness, the brain network's reconfiguration to propofol may reveal the patient's underlying capacity for consciousness. Objectives: To design and test a new metric for the prognostication of consciousness recovery in disorders of consciousness. Methods: Using a within-subject design, we conducted an anesthetic protocol with concomitant high-density EEG in 12 patients with a disorder of consciousness after a brain injury. We quantified the reconfiguration of EEG network hubs and directed functional connectivity before, during, and after propofol exposure and obtained an index of propofol-induced network reconfiguration: the adaptive reconfiguration index. We compared the index of patients who recovered consciousness 3 months after EEG (n = 3) to that of patients who did not recover or remained in a chronic disorder of consciousness (n = 7) and conducted a logistic regression to assess prognostic accuracy. Measurements and Main Results: The adaptive reconfiguration index was significantly higher in patients who later recovered full consciousness (U value = 21, P = 0.008) and able to discriminate with 100% accuracy whether the patient recovered consciousness. Conclusions: The adaptive reconfiguration index of patients who recovered from a disorder of consciousness at 3-month follow-up was linearly separable from that of patients who did not recover or remained in a chronic disorder of consciousness on the single-subject level. EEG and propofol can be administered at the bedside with few contraindications, affording the adaptive reconfiguration index tremendous translational potential as a prognostic measure of consciousness recovery in acute clinical settings.

Brain network motifs are markers of loss and recovery of consciousness.

Motifs are patterns of inter-connections between nodes of a network, and have been investigated as building blocks of directed networks. This study explored the re-organization of 3-node motifs during loss and recovery of consciousness. Nine healthy subjects underwent a 3-h anesthetic protocol while 128-channel electroencephalography (EEG) was recorded. In the alpha (8-13 Hz) band, 5-min epochs of EEG were extracted for: Baseline; Induction; Unconscious; 30-, 10- and 5-min pre-recovery of responsiveness; 30- and 180-min post-recovery of responsiveness. We constructed a functional brain network using the weighted and directed phase lag index, on which we calculated the frequency and topology of 3-node motifs. Three motifs (motifs 1, 2 and 5) were significantly present across participants and epochs, when compared to random networks (p < 0.05). The topology of motifs 1 and 5 changed significantly between responsive and unresponsive epochs (p-values < 0.01; Kendall's W = 0.664 (motif 1) and 0.529 (motif 5)). Motif 1 was constituted of long-range chain-like connections, while motif 5 was constituted of short-range, loop-like connections. Our results suggest that anesthetic-induced unconsciousness is associated with a topological re-organization of network motifs. As motif topological re-organization may precede (motif 5) or accompany (motif 1) the return of responsiveness, motifs could contribute to the understanding of the neural correlates of consciousness.

Brain network motif topography may predict emergence from disorders of consciousness: a case series.

Neuroimaging methods have improved the accuracy of diagnosis in patients with disorders of consciousness (DOC), but novel, clinically translatable methods for prognosticating this population are still needed. In this case series, we explored the association between topographic and global brain network properties and prognosis in patients with DOC. We recorded high-density electroencephalograms in three patients with acute or chronic DOC, two of whom also underwent an anesthetic protocol. In these two cases, we compared functional network motifs, network hubs and power topography (i.e. topographic network properties), as well as relative power and graph theoretical measures (i.e. global network properties), at baseline, during exposure to anesthesia and after recovery from anesthesia. We also compared these properties to a group of healthy, conscious controls. At baseline, the topographic distribution of nodes participating in alpha motifs resembled conscious controls in patients who later recovered consciousness and high relative power in the delta band was associated with a negative outcome. Strikingly, the reorganization of network motifs, network hubs and power topography under anesthesia followed by their return to a baseline patterns upon recovery from anesthesia, was associated with recovery of consciousness. Our findings suggest that topographic network properties measured at the single-electrode level might provide more prognostic information than global network properties that are averaged across the brain network. In addition, we propose that the brain network's capacity to reorganize in response to a perturbation is a precursor to the recovery of consciousness in DOC patients.