Brain dynamics of behavioral state transitions across sleep and wakefulness

Virtually every organism with a nervous system must enter a reversible state of quiescence, namely sleep, to maintain brain function. Sleep contributes to major aspects of cognition - including mood, attention, learning, memory, and decision making - and almost all neuropsychiatric disorders are associated with altered sleep. Though this state of decreased arousal is crucial for health and life quality, much remains unknown about how the brain traverses through high and low arousal states. To address this question, we systematically evaluated the relationship between brain activity and arousal state from two angles. First, we centered on the moment that behavioral responsiveness returns with awakening and delineated how activity unfolds in key brain networks during this state switch. Then, we reversed our analysis approach and zoomed into moments that brain activity changed, investigating how behavioral arousal state fluctuates with intrinsic brain-wide dynamics that are prevalent in restfulness and light sleep. Awakening from sleep reflects a profound transformation in neural activity and behavior. The thalamus is a key controller of arousal state, but whether its diverse nuclei exhibit coordinated or distinct activity at transitions in behavioral arousal state is unknown. Using fast functional magnetic resonance imaging (fMRI) at ultra-high field (7 Tesla), we measured sub-second activity across thalamocortical networks and within nine thalamic nuclei to delineate these dynamics during spontaneous transitions in behavioral arousal state. We discovered a stereotyped sequence of activity across thalamic nuclei and cingulate cortex that preceded behavioral arousal after a period of inactivity, followed by widespread deactivation. These thalamic dynamics were linked to whether participants subsequently fell back into unresponsiveness, with unified thalamic activation reflecting maintenance of behavior. These results provide an outline of the complex interactions across thalamocortical circuits that orchestrate behavioral arousal state transitions, and additionally, demonstrate that fast fMRI can resolve sub-second subcortical dynamics in the human brain. In light sleep and drowsiness, the brain exhibits low-frequency oscillations that are linked to changes in arousal state. It is unknown if specific spatiotemporal properties of these infraslow brain dynamics have functional relevance for arousal state. To address this gap in knowledge, we used fast fMRI to capture brain-wide activity while subjects performed a simple, self-paced behavioral task and transitioned in and out of behavioral unresponsiveness. We found that behavioral arousal state fluctuates with ongoing, infraslow fMRI activity. We determined that specific spatiotemporal features (magnitude, frequency, and propagation dynamics) are linked to various arousal state dynamics. We found that larger-amplitude, slower, peaks with greater lags across the brain were more likely to be associated with a change in arousal state than smaller-amplitude, faster, more tightly coupled activations across the brain. We found that peak magnitude was directly coupled to greater transitions in arousal state, and that frequency was coupled to baseline arousal state levels. Additionally, we found that thalamic and global peaks may contribute differently to behavioral arousal state transitions. Therefore, peaks in infraslow fMRI activity are linked to behavior and electroencephalography (EEG) rhythms in a state-dependent manner, with changes in behavior and EEG rhythms occurring more strongly in peaks with specific features. This study reveals functional differences in oscillatory blood oxygen level dependent (BOLD) signal activity linked to drowsiness and light sleep. Overall, this work elucidates key brain dynamics that underlie changes in arousal state, providing a foundational understanding of the basic network mechanisms underlying transitions between active behavior and unresponsiveness.

Author dc:creator

• Setzer, Beverly

Advisor dc:contributor.advisor

• Lewis, Laura D.

• Neurosciences

Language dc:language.iso

en_US

Handle dc:identifier.uri

https://hdl.handle.net/2144/51775

OAI identifier oai:identifier

oai:open.bu.edu:2144/51775