Auditory Event-Related "Global Effect" Predicts Recovery of Overt Consciousness

Pauline Perez, Mélanie Valente, Bertrand Hermann, Jacobo Sitt, Frédéric Faugeras, Sophie Demeret, Benjamin Rohaut, Lionel Naccache, Pauline Perez, Mélanie Valente, Bertrand Hermann, Jacobo Sitt, Frédéric Faugeras, Sophie Demeret, Benjamin Rohaut, Lionel Naccache

Abstract

Objective: To explore whether the presence of an event-related potential (ERP) "global effect" (GE+)-that corresponds to a correlate of conscious processing in the local-global auditory task-predicts behaviorally overt consciousness recovery in a large cohort of patients suffering from disorders of consciousness (DOC). Methods: We conducted a prospective study on all DOC patients evaluated during the 2009-2018 period. Behavioral examination included Coma Recovery Scale-Revised (CRS-R) scores and bedside high-density EEG recordings. Consciousness recovery was evaluated at 6 months by a structured phone interview. The predictive value of a GE+ was calculated both on survivors and on all patients. Results: A total of 236 patients with a documented outcome and technically valid EEG recordings could be included. Among them, 66 patients had a GE+ status (28%). Presence of GE+ predicted behaviorally overt consciousness recovery in survivors with high specificity (Sp = 84%) and high positive predictive value (PPV = 80%) but with low sensitivity (Se = 35%) and low negative predictive value (NPV = 42%). Positive likelihood ratio (LR+) of GE+ was superior to LR+ of initial clinical status and of ERP effect indexing unconscious auditory processing [local effect (LE)]. Interpretation: Our results demonstrate that the presence of a bedside ERP GE+ is highly predictive of behaviorally overt consciousness recovery in DOC patients, regardless of the delay, of behavioral status, and of the etiology of brain dysfunction. However, the absence of this effect is not a reliable predictor of negative outcome. This study provides Class III evidence that the presence of an ERP "global effect" predicts consciousness recovery in DOC patients.

Keywords: EEG–electroencephalogram; critical care; disorder of consciousness (DOC); evoked potential; prognosis.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Perez, Valente, Hermann, Sitt, Faugeras, Demeret, Rohaut and Naccache.

Figures

Figure 1
Figure 1
Flowchart.
Figure 2
Figure 2
Global field power (GFP) of survivors according to their global effect (GE)(+/–) and local effect (LE)(+/–) status. GFP was computed from mean event-related potentials (ERPs) of deviant (red) and standard (blue) conditions and was plotted with a confidence interval at 95% (shaded areas), respectively, in GE+ patients (N = 40; see upper left panel), GE- patients (N = 103; see lower left panel), LE+ patients (N = 86; see upper right panel), and LE- patients (N = 57; see lower right panel). This figure is only shown to illustrate mean ERP patterns: (i) responses to each of the five sounds, (ii) contingent negative variation (CNV) component visible as a ramping ongoing slope in particular in the GE+ group, (iii) mismatch negativity (MMN)-P3a for LE+, and (iv) late P3b component in the GE+ group. No statistical test was calculated given that patients were selected for the corresponding category at the single-subject level statistics.
Figure 3
Figure 3
Repartition of patients' outcomes according to their initial clinical state and to global effect (GE) (upper figure) and to local effect (LE) (lower figure) presence. GE was a specific predictor of consciousness recovery in survivors. Note the few GE+ patients with a bad outcome (8/51 = 16%; see upper middle orange dots) contrasting with a higher proportion of LE+ patients with a bad outcome (23/51 = 45%; see lower middle orange dots). Inversely, LE was a sensitive predictor of consciousness recovery. The proportion of LE+ patients who recovered consciousness was larger than the proportion of GE+ with a good outcome (63/92 = 68 vs. 32/92 = 35%; see rightmost upper and lower orange dots).
Figure 4
Figure 4
Outcome of global effect (GE)+ and GE– surviving patients. Outcome of GE- patients (left panel) represents each patient by a black segment connected to the patient's initial behavioral status [vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS)–, MCS+, exit-MCS (EMCS)] and to the patient's behavioral outcome (same categories) at 6 months. Outcome of GE+ patients is represented using a similar method in the right panel. Note in particular that all MCS+/GE+ surviving patients recovered overt behavioral evidence of consciousness.

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