Functional magnetic resonance imaging (fMRI) has been broadly employed to map large-scale brain dynamics in healthy and diseased populations. Withal its high spatial localization and accessibility to deep brain structures, fMRI suffers from several key limitations, including its vulnerability to systemic physiology and inaccessibility to various neuromodulatory processes, that hinder its use in deciphering the fundamental neurophysiological basis of large-scale brain dynamics. The innovation of this proposal lies in the addition to fMRI of concurrent PET imaging, a modality with higher neuronal specificity and accessibility to a myriad of metabolic and neurochemical processes, to address the essential limitations of fMRI, being an indirect marker of neural activity. Functional PET (fPET) is a recently innovated technique with the potential to track functionally relevant metabolic changes. Specifically, we will first pioneer an analytical framework to link large-scale brain dynamics with concurrent fPET signals; then as a first application, employ this framework to illuminate the neuronal changes linked with naturalistic arousal fluctuations and the metabolic underpinnings of complex network behavior. The outcomes of this proposal will lay the foundation for a long-term independent research program that employs this novel multi-modal technique to probe various neuronal, vascular, energetic and neuromodulatory mechanisms underlying large-scale brain dynamics, and ultimately identifies how disruption of any facets of these mechanisms leads to various pathological syndromes. This candidate has in-depth training in signal processing, statistics, state-of-the-art fMRI and concurrent EEG/fMRI methodology. With additional training in advanced PET methodology, multi-modal integration, neuroscience as well as clinical translational research skills enabled by this grant mechanism, she will be well versed to begin an independent career focusing on 1) developing analytical toolsets to facilitate the application of advanced neuroimaging techniques; and 2) integrating multi- faceted functional information to investigate the biophysical underpinnings of large-scale brain functional dynamics in health and disease.
