Characterizing vigilance in fMRI data and its relation to age-related cognitive impairment.

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PROJECT SUMMARY/ABSTRACT Magnetic resonance imaging (MRI) is a powerful non-invasive tool for imaging brain activity that allows for investigating the dynamically changing activity patterns and structure that give rise to human brain function and dysfunction. Functional MRI (fMRI) signal variations linked with vigilance states, and the subcortical-cortical networks that underlie these fluctuations in vigilance, are being increasingly recognized as fMRI signals of interest both for neuroscience and in studying disease. However, vigilance has been largely ignored in routine fMRI studies, despite the fact that subjects tend to fall asleep in the scanner and certain patient populations may be susceptible to fatigue or daytime sleepiness. More precisely characterizing the role of vigilance in disease, and its effects in fMRI data, could be key for developing imaging biomarkers as well as improving treatment. My doctoral work thus far, (Aim 1.1) developed a method for extracting a vigilance metric, based on fMRI data alone, using a vigilance-related activity pattern built from correlations between simultaneous fMRI-EEG in healthy young adults. For my F99 phase, I will (Aim 1.2) investigate whether a state-of-the-art image acquisition/processing method, multi-echo independent component analysis (ME-ICA), improves the correspondence between fMRI signal and EEG signal, and whether using the ME-ICA approach improves sensitivity in detecting subcortical arousal networks. Finally, I will (in Aim 1.3) attempt to distinguish between mild cognitive impaired (MCI) patients and healthy aging controls by leveraging fMRI-based vigilance as a biomarker. By comparing vigilance fluctuations and functional connectivity differences in vigilance network regions of interest, we seek to understand the role of vigilance in early-stage Alzheimer’s disease. The proposed project will help the candidate, Sarah Goodale; achieve her career goal of becoming an independent investigator at the forefront of aging neuroimaging at a research-focused institution. This project provides cutting-edge research training in EEG and fMRI analysis and advanced statistical methods. Further, the proposed studies will provide professional and technical training to prepare the candidate to successfully transition the postdoctoral (K00) phase. The postdoctoral laboratory will extend Sarah’s training to incorporate structural imaging to characterize the impact of structural degeneration on functional networks with respect to age-related cognitive decline. Vanderbilt University is an ideal environment to achieve these goals as it (1) encourages collaboration, (2) has state-of-the-art technical resources to perform cutting-edge research, and (3) contains renowned faculty that encourage training, mentorship, and the development of aspiring researchers. The complete plan proposed for both the F99 and K00 phases is designed to develop an independent neuroimaging scientist prepared for a successful postdoctoral position and transition to an aging focused career, with an ultimate goal of becoming an independent tenured investigator.