Nmachi Anumba
BME PhD Defense Presentation

Date: 2024-03-25
Time: 1:00 pm
Location / Meeting Link: Emory HSRB-II N600 / https://emory.zoom.us/j/94562259463

Committee Members:
Dr. Shella Keilholz (advisor); Dr. David Weinshenker; Dr. Erin Buckley; Dr. Candace Fleischer; Dr. Garrett Stanley


Title: Studying The Effects of Noradrenergic Neuromodulation on the BOLD Global Signal and Quasi-Periodic Patterns in Rat rs-fMRI

Abstract:
The study of dynamically changing resting-state fMRI (rs-fMRI) signals that span multiple brain regions provides an opportunity to better understand the intrinsic contexts of large-scale communication across the brain. Two prominent examples of these whole-brain spatiotemporal patterns are the blood oxygen level dependent (BOLD) global signal and quasi-periodic patterns (QPPs). The BOLD global signal is defined as the averaged activity of the brain during a scan and its use as a nuisance regressor has been a contentious topic for years. QPPs are propagating waves of anticorrelated activity that alternate between two prominent resting-state brain networks, though their origin is unknown. Both of these signals have been shown to exhibit notable relationships with measures of arousal and vigilance. Activity of the locus coeruleus (LC), a brainstem nucleus responsible for the synthesis and release of norepinephrine, is known to play a significant role in arousal. Speculation that QPPs may originate from the activity of brainstem nuclei, in addition to findings that link the global signal to levels of arousal, led us to believe that the widespread nature of LC influence could have a significant effect on these two signals. In this work we studied the direct effects of LC activity on the BOLD global signal and QPPs in rats. This was done by first identifying a neural global signal component in a noise-controlled environment that could consequently be affected by LC neuromodulation (Aim 1). Secondly, we used optogenetic-fMRI to stimulate the LC at different frequencies and study how these varying levels of LC activity affected both the global signal and QPPs in rats (Aim 2). Both spatiotemporal signals were analyzed both through traditional methods and through the employment of complex principal component analysis (CPCA). Our findings show evidence for a neural global signal component that is distinct from noise. We also report spatially specific changes in global signal distribution under tonic LC stimulation as well as regional changes in QPP involvement under 5 Hz and 15 Hz phasic stimulation. Given that the LC is also strongly implicated in Alzheimer's disease (AD), we also used the AD rat model TgF344-AD to investigate the effects of the disease on whole-brain dynamics using CPCA, for which we show age-specific AD effects. These results show that the neuromodulatory effects of the LC norepinephrine system on large-scale spatiotemporal patterns may be small in scale and more regionally specific than initially thought.