Covert Speech Comprehension Predicts Recovery From Acute Unresponsive States

Abstract

Objective Patients with traumatic brain injury who fail to obey commands after sedation‐washout pose one of the most significant challenges for neurological prognostication. Reducing prognostic uncertainty will lead to more appropriate care decisions and ensure provision of limited rehabilitation resources to those most likely to benefit. Bedside markers of covert residual cognition, including speech comprehension, may reduce this uncertainty. Methods We recruited 28 patients with acute traumatic brain injury who were 2 to 7 days sedation‐free and failed to obey commands. Patients heard streams of isochronous monosyllabic words that built meaningful phrases and sentences while their brain activity via electroencephalography (EEG) was recorded. In healthy individuals, EEG activity only synchronizes with the rhythm of phrases and sentences when listeners consciously comprehend the speech. This approach therefore provides a measure of residual speech comprehension in unresponsive patients. Results Seventeen and 16 patients were available for assessment with the Glasgow Outcome Scale Extended (GOSE) at 3 months and 6 months, respectively. Outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6, p < 0.007), quantified by inter‐trial phase coherence. Linear regressions revealed that the strength of this comprehension response (beta = 0.603, p = 0.006) significantly improved the accuracy of prognoses relative to clinical characteristics alone (eg, Glasgow Coma Scale [GCS], computed tomography [CT] grade). Interpretation A simple, passive, auditory EEG protocol improves prognostic accuracy in a critical period of clinical decision making. Unlike other approaches to probing covert cognition for prognostication, this approach is entirely passive and therefore less susceptible to cognitive deficits, increasing the number of patients who may benefit. ANN NEUROL 2021;89:646–656

Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions

“…Another key consideration in future clinical trial design will be the timing of enrollment, particularly for patients with cognitive motor dissociation [ 30 ] (i.e., active command-following on task-based fMRI or EEG) or covert cortical processing [ 10 ] (i.e., passive responses to language or music on stimulus-based fMRI or EEG). Emerging evidence suggests that these two groups of patients have a better chance of long-term functional recovery than do patients without responses on task-based or stimulus-based diagnostic tests [ 26 , 234 ], which may also suggest an increased receptivity to therapeutic stimulation. Investigators will have to consider whether these patients should be analyzed as prespecified subgroups in future studies and whether a transition from unresponsiveness to cognitive motor dissociation or covert cortical processing should be defined as a favorable therapeutic response.…”

Proceedings of the First Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness

“…• Electrophysiological biomarkers can be used to detect CMD [59]. EEG can be used at the bedside to detect command-following [10,40,41,60] and covert cortical processing [44,61] in patients who do not show behavioral evidence of purposeful responses. EEG can also be used to develop biomarkers of cellular preservation that relate to outcomes, such as features within burst suppression patterns, that allow for the identification of patients with and without a chance to recover [62][63][64].…”

“…Biomarkers of covert consciousness may improve prognostic capabilities for patients with coma [10]. Similarly, biomarkers of covert cortical processing (i.e., association cortex responses to language otherwise missed by behavioral assessments) also may predict long-term functional outcomes [44]. A combination of model-based and datadriven analyses may enhance mechanistic understanding of DoC [37].…”

The search for the neural correlate of consciousness: Progress and challenges

“…Another promising approach to investigating consciousness in populations with restricted responsiveness, such as infants and patients with cerebral lesions, is the use of neural frequency tagging, which we initially developed to evaluate language capacities and access to meaning in neurotypical individuals (Ding et al, 2016). Recently, we and others have used the frequency tagging approach for both retrospective (Gui et al, 2020) and prospective (Sokoliuk et al, 2021) classification on unresponsive patients, and the results have been encouraging.…”