Internally and externally driven arousal changes in neural activity and hemodynamics - PROJECT SUMMARY/ABSTRACT Our level of arousal influences almost all of the cognitive and behavioral abilities that allow us to engage with our environment. A variety of terminology has been used to describe arousal-related changes in cognition, including wakefulness, internal state, engagement, and alertness. Despite this ambiguity, it is clear that arousal is a global phenomenon that affects brain activity, systemic physiology, and behavior. Arousal deficits in behavior and systemic markers, such as heart rate and pupil diameter, are present in many neurologic disorders, including Alzheimer’s, schizophrenia, and attention deficit disorder. In order to use these non-invasive systemic measures of arousal as diagnostic markers, we need to understand how arousal level influences brain activity in neurotypical cognition and in turn leads to changes in behavior. The goal of this proposal is to investigate changes in brain activity that occur with fluctuations in arousal level. Specifically, we will study slow changes in simultaneously measured cortical neural population activity and cerebral hemodynamics. We will track arousal level using pupil diameter and heart rate. Our overarching hypothesis is that we can link minute-to-minute arousal fluctuations with slow changes in neural population activity and cerebral hemodynamics. In the first aim, we will study internally driven variations in arousal level that occur over hours and across the circadian cycle. In the second aim, we will probe arousal level using an external stimulus to assess whether we can modulate arousal- linked drifts in neural population activity and hemodynamics. Our strategy to record simultaneous population activity and hemodynamic changes in context of systemic parameters and behavior will allow us to comprehensively probe arousal-related changes and integrate arousal effects across the brain, body, and behavior. Results from this proposal will help to understand how deviations in arousal, measured via behavior and systemic physiology, could serve as biomarkers of changes in global brain activity that are present in neurologic disorders. This proposal will be completed in the interdisciplinary and collaborative training environment of Carnegie Mellon University and its Center for the Neural Basis of Cognition that consists of a large community of neuroscientists and engineers investigating brain activity underlying cognition and brain disorders. Under the guidance of Dr. Matt Smith, an expert in systems neuroscience, and Dr. Jana Kainerstorfer, an expert in biomedical optics, this proposal will provide me with a multimodal skill set in electrophysiology, optics, and psychophysics to probe cognitive function. These skills will help me progress towards my goal of becoming a physician scientist studying the interaction between the brain, systemic physiology, and behavior to identify biomarkers of cognitive disorders.