A Day in the Life of the Human Brain: Investigating the Dynamic Interrelationship Between Brain, Cognition, Behavior, and Physiology - Summary/Abstract Whether we are fatigued from a teleconference call, eager to read a book, energetic and ready to start our day or tired and preparing for sleep, anxious or happy, in the real world key neurocognitive processes and moods fluctuate over minutes-to-hours. Hunger, circadian rhythms, hormone levels, blood sugar, heart rate, body temperature, all fluctuate at the mesoscopic timescale of minutes-to-hours modulating how we respond to the world. For example, the response of the brain to the odor of fresh cookies just out of the oven is different when one is hungry versus for someone who just ate. These state fluctuations also influence why the same event will trigger pathological symptoms at some times, but not others, in individuals with neurological or psychiatric disorders. Despite the critical importance of interrelated brain, cognitive, behavioral, and physiological fluctuations at the timescale of minutes-to-hours in the real world, nearly everything we know about human brain function mostly comes from highly controlled experiments lasting milliseconds-to-seconds, or longitudinal studies from months-to-years. This has left a critical gap in scientific knowledge regarding the dynamics of brain, cognitive, behavioral, and physiological interactions at the timescale of minutes-to-hours in real world settings. To fill this gap, we will develop a platform for measuring and analyzing brain activity, cognitive states, behavior, and physiology leveraging the unique opportunity to record multiday neural activity during natural behavior in the real world in individuals undergoing the surgical treatment for epilepsy. We will integrate cutting- edge wearable and artificial intelligence technology for rich behavioral and physiological monitoring along with neural network and dynamical systems learning approaches. We will rigorously quality control and validate this platform to ensure the highest quality data. We will also perform a bioethics study to develop a paradigm that addresses the unique privacy concerns that arise in using ubiquitous measurements for real-world neuroscience in this participant population. In the R33 phase of this project, we will then use this platform to examine how brain, cognitive, behavioral, and physiological interrelationships fluctuate with circadian rhythms and relate to brain network excitability. Given the ubiquity of circadian rhythms across the brain and body, their influence on cognition and behavior, and their relationship with many neurological and psychiatric disorders, the R33 study has broad implications for both our understanding of the brain and for potential treatment strategies for many disorders. For example, knowing when brain networks are in high or low excitability states can suggest windows of opportunity for maximally beneficial clinical interventions. The development of this integrated brain, cognitive, behavioral, and physiological measurement and analysis platform in the R61 phase of this project will open up new neuroscientific and translational research opportunities. The studies on circadian rhythms and brain network excitability in the R33 phase will lead to new understanding of these important neurobiological processes and provides insights with broad clinical and translational implications.
