Project Summary Traumatic brain injury (TBI) affects 1.7 million individuals in the US each year and when TBI is severe (sTBI), nearly all survivors experience cognitive dysfunction at 6 months. Trials aimed at lowering elevated intracranial pressure (ICP) through surgery or aggressive medical therapies have failed to show benefit in functional outcome, but the measurement of ICP as a marker for secondary brain injury remains a cornerstone of modern neurocritical care. We hypothesize that elevations in ICP impact cognition, a more biologically plausible result of elevations in ICP that contribute to brain ischemia, and that measurements of ICP-related cortical dysfunction can provide more precise targets of intervention to improve cognitive dysfunction in survivors of sTBI. Dr. Foreman will use data from a large, ongoing multicenter TBI study (Transforming Research and Clinical Knowledge, or TRACK-TBI; NIH/NINDS U01 NS086090) and an embedded multicenter EEG-based study (Spreading Depolarizations II: Development and Validation of Spreading Depolarization Monitoring for TBI Management, or SD II; DOD W81XWH-16-2-0020) to examine the effects of elevated ICP on domain-specific cognitive dysfunction (Aim 1). Dr. Foreman will then use intracranial and scalp electroencephalography (EEG) to stratify ICP based on the presence of ischemic EEG changes in cortical signaling (Aim 2). This research plan will leverage the clinical research infrastructure of TRACK-TBI, the physiologic data collection of SDII, and the expertise of National Science Foundation-funded engineering partners to analyze time-locked ICP and EEG signals, defining novel physiology with the potential to individualize ICP therapy to reduce the need for surgery or aggressive medical therapies, and to improve cognitive disability in survivors of sTBI. This K23 award will establish Dr. Foreman as a clinician-scientist with expertise in 1) understanding time- series physiologic relationships in those with sTBI and 2) developing individualized physiologic targets for therapeutic intervention in order to improve clinically important outcomes, i.e. cognition after sTBI. This career development award will support Dr. Foreman?s short-term goals, including 1) a detailed understanding of cognitive outcome assessments and their application as primary endpoints in clinical and translational research; 2) acquisition of skills necessary to analyze and interpret EEG and other biological sensor data; 3) obtaining knowledge in statistical techniques necessary to link physiology with outcome. Dr. Foreman will meet these objectives under the guidance of a Mentorship Committee, including Dr. Daniel Woo (primary mentor), a federally-funded clinician-scientist and established faculty mentor; Dr. Opeolu Adeoye, an Emergency Physician and Neurointensivist with expertise in clinical research and trial design; and Dr. Jed Hartings, a neurophysiologist an international expert in intracranial EEG after sTBI. Dr. Foreman?s mentorship will also include Dr. Joel Kramer, a cognitive neuropsychologist and member of TRACK-TBI?s Outcomes Core and Dr. Jay Lee, a mechanical engineer and national leader in intelligent maintenance systems (IMS) research and algorithm development.