Interactions between arousal and brain function are well established, particularly as they relate to extremes of arousal state such as fight/flight versus relaxed, awake versus asleep, and attentive versus inattentive. However, recent studies suggest far more prevalent and nuanced effects of arousal on moment-by-moment, attentive information processing in the normal and clinically affected brain. Less is known about the mechanisms responsible for these more nuanced effects. Based in part on recent studies linking arousal- mediated modulations of information processing to release of norepinephrine (NE) from neurons in the brainstem nucleus locus coeruleus (LC) to much of the rest of the brain and our own preliminary data, here we test the hypothesis that moment-by-moment changes in arousal state during attentive processing modulate coordinated neuronal dynamics within and across brain regions. Three key features of this study will substantially broaden its impact. First, we wil study the effects of fluctuations of arousal on brain function under conditions that are in widespread use in human and animal studies: an attentive individual performing a task requiring information processing and controlled behaviors over many hundreds of trials. Second, we will study coordinated neural dynamics, which are particularly susceptible to changes in brain state and can only be interpreted correctly when such influences are taken into account. Third, and perhaps most critically, we will help to identify which of several readily available, non-invasive physiological measures of arousal, including pupillometry, skin conductance responses (SCR), heart rate variability (HRV), and electroencephalography (EEG), can be used to effectively characterize ongoing effects of arousal on simultaneously measured brain activity and behavior. Specifically, we will: 1) Determine relationships between arousal measures (pupil, SCR, HRV, and EEG) and coordinated neuronal dynamics within and across several brain regions in attentive monkeys; and 2) Develop mathematical tools to relate arousal measures to patterns of coordinated neural activity within and across brain regions. Together, these Aims will improve scientific knowledge about the neural basis of these kinds of arousal effects, and provide new, practical approaches for taking these effects into account when interpreting coordinated brain activity.
The proposed work is basic research, designed to provide new insights into how moment-by-moment fluctuations in physiologically measured arousal relate to coordinated neuronal dynamics in a healthy nervous system. Thus, direct benefits to public health are intended to come in the longer term, as these new insights can be used to design new ways to diagnose and treat disorders that involve abnormal regulation of arousal (e.g., attention-deficit/hyperactivity disorder, depression, anxiety, and certain neurodegenerative disorders). .