A functional brain network to detect and predict consciousness recovery

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

I am a Neurocritical Care Neurologist at the University of Pennsylvania (Penn), aiming to become an independent investigator with expertise in functional neuroimaging and disorders of consciousness (DoC) after brain injury. I have previously used functional magnetic resonance imaging to identify a novel brain network potentially associated with consciousness in humans – termed the arousal-awareness integration network (AAIN) – and have collected preliminary data to suggest that AAIN dysfunction may serve as a final common pathway in the pathophysiology of DoC after brain injury. My long-term career goal is to better understand the network dysfunction that characterizes DoC across etiologies of brain injury, and to target this pathophysiology with novel diagnostic, prognostic, and therapeutic strategies. The goals of this project are to use novel approaches to clarify the physiologic relevance of network connectivity in DoC, and to evaluate the AAIN's association with consciousness and consciousness recovery. In patients with acute brain injury in the intensive care unit, the proposed research will prospectively investigate: (1) the extent to which network connectivity reflects the dynamic level of consciousness (`state'), versus recovery potential (`fate') by determining how connectivity changes with alterations in consciousness; (2) whether AAIN connectivity, relative to other networks, is associated with state of consciousness, which will help clarify which network is most fundamental to consciousness; and (3) whether AAIN connectivity, relative to other networks, is associated with the future recovery of consciousness, which may help guide families in high-stakes decisions about continuing or withdrawing life-sustaining treatment. This project could advance our understanding of consciousness while facilitating the development of a novel clinical biomarker for consciousness detection and prognostication. My career development plan leverages the expertise of leaders in the field to acquire skills in advanced neuroimaging (advised by primary mentor, Dr. John Detre), clinical research in DoC (advised by co-mentor, Dr. Brian Edlow), and rigorous statistical approaches to the prognostication of consciousness recovery (advised by co-mentor, Dr. Jonathan Elmer). At Penn, I will benefit from a unique environment and unparalleled resources, with access to a robust infrastructure for neuroimaging research, a state-of-the-art MRI scanner that is dedicated to research and embedded within the neurocritical care unit, and an innovative clinical program that specializes in DoC. This project, along with the associated mentorship and training plan, will provide me with the knowledge and expertise necessary to develop an independent career in DoC research.