PROJECT SUMMARY Sleep is an important behavior for humans and many other species, impacting mood, cognition, and waste clearance in the brain. Receiving sufficient sleep requires the brain to undergo widespread changes in stereotyped sleep cycles, going between rapid eye movement (REM) sleep and non-REM (NREM) sleep. This important sleep structure is established by several deep brain regions, together known as the ascending arousal network (AAN). Regions within the AAN connect to each other and much of the brain, releasing neuromodulators diffusely throughout. Although research in rodents has separately shown that regions of the AAN regulate transitions between sleep-wake states, how this network modulates arousal state in humans and how these regions coordinate to do so remains unknown. The small size of the regions of the AAN and other technical limitations have limited direct measurement of the human AAN; however, advancements in magnetic resonance imaging (MRI) at ultra-high magnetic fields has improved the spatiotemporal resolution of functional MRI (fMRI), positioning us to study human AAN control of arousal states. The ultimate objective of this study is to identify the functional role of the human AAN in supporting arousal states, through maintenance of arousal states and transitions between sleep-wake states. To do so, I will employ simultaneous electroencephalography (EEG) and functional MRI while human subjects sleep in the MRI scanner for a four-hour scan. We will bring in subjects around their typical bedtime and during the resting scan they will be instructed to close their eyes while we track behavioral responsivity and electrophysiological arousal state. To improve the spatial resolution of our fMRI scans, we have created a high spatial resolution functional sequence which more closely matches the smallest cross-sectional dimensions of regions of the AAN. In aim 1, our goal is to identify the response profile and intrinsic dynamics of the AAN during prolonged periods of wake and sleep, as well as at transitions between states. In aim 2, our goal is to identify the impact of sleep on sensory processing and how the regions of the AAN modulate the impact of sensory stimuli on arousal state. To assess this, the same experimental setup will be used as in aim 1 while presenting a high-intensity visual stimulus to probe sensory processing across arousal states. From aim 2 we will be able to understand stimulus-locked responses of the AAN and visual areas during sleep-wake states, as well as assess how activity in these regions may maintain or change arousal states. Throughout this project, Mr. Cicero will be sponsored and mentored by several personnel with expertise in simultaneous EEG-fMRI, brainstem circuits, thalamocortical neural dynamics, and ultra-high field MRI. The research training will be taking place across Boston University’s Graduate Program in Neuroscience. Massachusetts Institute of Technology’s Research Laboratory of E...