LAUSR

For patients with severe brain injuries in the intensive care unit (ICU), consciousness can be present in the absence of purposeful responses on bedside examination. If consciousness goes undetected, clinicians can render an inaccurate, pessimistic prognosis, increasing the risk that life-sustaining therapy is withdrawn for a patient who had the potential for neurological recovery. Withdrawal of life-sustaining therapy is a leading cause of death in ICU patients with severe traumatic brain injury and hypoxic–ischemic injury, and early re-emergence of consciousness is a primary determinant of decisions regarding withdrawal of life-sustaining therapy. Detection of consciousness in the ICU thus has time-sensitive, lifeor-death consequences. The prognostic relevance of early detection of consciousness in the ICU has been demonstrated primarily using behavioral examination. The first signs of reemergence of consciousness are typically visual fixation, gaze tracking, and pain localization, but multiple confounders limit the behavioral examination, including pain, immobility from polytrauma, and disruption of central or peripheral motor pathways. Furthermore, patients may require continuous sedation or tolerate only brief, intermittent examinations owing to elevations in intracranial pressure, ventilator dyssynchrony, or bronchospasm. To circumvent these limitations, advanced electrophysiologic and neuroimaging tests have been developed to detect covert consciousness (ie, cognitive motor dissociation), which is present in approximately 15% of patients whose behavioral examination suggests a vegetative state (also known as unresponsive wakefulness syndrome). Task-based electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) protocols initially developed for patients with subacute-to-chronic disorders of consciousness (DoC) are now being deployed in the ICU for patients with acute DoC. The recent observation that early detection of covert consciousness using task-based EEG predicts 1-year functional recovery suggests that covert consciousness has similar prognostic relevance to overt consciousness in the ICU. Nonetheless, task-based EEG and fMRI protocols pose substantial cognitive demands on critically ill patients, as evidenced by high false-negative rates in patients who are able to follow commands on behavioral examination but not on task-based EEG or fMRI. Even in healthy volunteers, the false-negative rate for task-based EEG and fMRI motor imagery protocols (ie, “imagine opening and closing your hand”) is as high as 25%. This high false-negative rate raises the possibility that consciousness might evade detection by behavioral examination and task-based EEG or fMRI protocols in some critically ill patients. Moreover, task-based EEG and fMRI require infrastructure and personnel that are currently unavailable at most hospitals, limiting their clinical utility and generalizability. The cognitive demand, high false-negative rate, and limited generalizability of task-based protocols provide motivation for the ground-breaking study by Sokoliuk and colleagues published in this issue of Annals of Neurology. The authors developed an EEG protocol that probes language function under passive stimulation, free of any task instruction. Specifically, the EEG protocol interrogates electrophysiologic responses to three levels of stimulus integration (single words, phrases, and whole sentences) according to frequency tagging in spectral EEG decomposition space. Crucially, all supra-single word information was removed from the stimuli (eg, there is no prosody effect related to phrase or sentence structure) to isolate the syntactico-semantic level of integration. This hierarchical language EEG protocol was performed in 28 critically ill patients with severe traumatic brain injury who were unresponsive on bedside examination. The key finding of the study is that EEG responses to language in the ICU were correlated with 3and 6-month outcomes, as assessed by the Glasgow Outcome Scale-Extended. The EEG responses accounted for variance in outcomes beyond that accounted for by standard clinical predictors, such as the Glasgow Coma Scale score and head computed tomography scan. These results provide initial