Project Summary/Abstract Severe traumatic brain injury (TBI) has a high mortality, largely driven by the early withdrawal of life-sustaining therapies during hospitalization. This critical decision is influenced by whether patients remain unresponsive after TBI. Current models use age, basic neurological assessment, and radiological findings as predictors of recovery. Bedside neurological examinations are examiner dependent, and often misclassify patients as unresponsive despite preserved awareness. Current approaches to predicting recovery of consciousness and functional recovery lack accuracy. Brain activation using a task-based functional magnetic resonance imaging or electroencephalogram (EEG) measure preserved awareness in clinically unresponsive patients, known as covert consciousness. Covert consciousness indicates a higher chance of recovery after acute brain injury. Most research studies examining covert consciousness have not been performed in the acute, intensive care setting (ICU) when clinicians discuss the patients’ goals of care with families. Music and spoken words are auditory stimuli to which unresponsive brain-injured patients may easily attend. Our preliminary data provide the scientific premise and the feasibility of using brain activation to music and spoken words in the ICU as a biomarker to detect covert consciousness after TBI. We hypothesize that preserved brain activation to music and spoken words may indicate preserved basic cognitive functions and subsequently predict recovery after TBI. In this study, we propose using a personalized prognostication approach shortly after severe brain injury using our assessment battery MUSICA (MUsic and Speech Induced Cerebral Activation). Our assessment battery MUSICA encompasses brain activation to [1] classical music; [2] words, phrases, and sentences; [3] congruent and incongruent sentences. Using MUSICA, we aim to identify covert consciousness in unresponsive TBI patients in the ICU (AIM 1). We will also determine if brain activation to MUSICA can be used to predict recovery after TBI (AIM 2). A total of 80 unresponsive TBI patients will be recruited from a high-volume level 1 trauma center during the ICU stay. We will test patients’ brain activation to MUSICA and compare their responses to responses from 20 healthy subjects (AIM 1). We will assess global, functional, and cognitive outcomes at 1-, 3- and 6-month follow-up to determine the predictive value of MUSICA (AIM 2). Results from this study will change the current prognostication paradigms in clinical practice after severe TBI using an electrophysiologic signature to music and spoken words.