Imaging brainstem, thalamic, and hypothalamic dynamics in human sleep

About This Grant

Project Abstract Sleep is essential for brain function and health. Over 50 million Americans have sleep disorders, and disrupted sleep causes impairments in attention and cognition. Furthermore, over the long term, disrupted sleep raises the risk of neurological and psychiatric disorders, including Alzheimer's disease, anxiety, and depression. Identifying the brain circuit activity that regulates healthy sleep in humans is a key step needed to enable understanding and addressing sleep disorders. However, the subcortical brain regions thought to regulate sleep have not yet been imaged with high spatial precision in the human brain during sleep, limiting our understanding of how these networks contribute to modulating sleep architecture and vigilance levels. This project will use advanced neuroimaging technologies to map the subcortical (including brainstem, thalamic, and hypothalamic) circuit activity underlying sleep-wake states in humans. We will employ high spatiotemporal resolution 7T fMRI and precise individual-level analysis strategies to distinguish activity in individual nuclei, in combination with simultaneous EEG using a novel net that allows for use at ultra-high magnetic field strengths. We will identify the circuit activity underlying the descent into non-rapid eye movement (NREM) sleep, and the activity pattern that underlies arousals from sleep. Furthermore, we will investigate which subsets of these circuits are linked to distinct EEG rhythms that appear during increasingly deep stages of NREM sleep. We will then test which dynamics are predictive of sleep depth and sensory responses in cortical networks. Finally, we will determine whether this sleep-associated activity is overlapping or distinct from the activity patterns that underlie fluctuations in vigilance and microsleeps that impair daytime cognition, using a sustained attention task. Overall, these studies will identify the subcortical activity dynamics that underlie sleep and vigilance levels in the human brain, providing new insight into the intricate networks that regulate sleep architecture in humans. This knowledge will provide an essential scientific foundation for understanding the circuits that are involved in disrupted sleep and vigilance states, and identifying potential targets for clinical populations.