||5U01CA193632-03 Interpret this number
||Fundamental Subcortical Mechanisms of Affective Processing
DESCRIPTION (provided by applicant): Between 50-66% of deaths caused by cancer could be prevented through behavioral modification. Accumulating evidence points towards a family of basic, affective psychological processes related to emotion, stress, and pain that influence behavioral choices, facilitating healthful choices or promoting unhealthful choices, and that have the capacity to influence key aspects of successful survivorship. While the links between affect and cancer-related decision making are becoming well-known, the research remains largely descriptive. A mechanistic understanding of these links is hampered by a major barrier: the neural circuitry underlying affective processing is still largely underspecified. A further barrierto progress is that subdomains of affective science including stress, emotion, and pain, have largely been studied independently of one another even though they overlap tremendously as psychological constructs. The historical divides that pose a critical barrier to using affective processes to improve cancer-related decision-making are exacerbated by a tendency for researchers to focus either on peripheral and central biomarkers of affect, but not to study them simultaneously. Our goal is to unify subdomains of affective processes into a common neural framework centered on subcortical brainstem regions that are known to be critically involved in affective processes, with a particular emphasis on the periaqueductal gray (PAG) which non-human animal research shows is a critical hub controlling autonomic output, analgesic responses, and other physiological responses during emotion, pain, and stress. Affective research in humans relies primarily on non-invasive neuroimaging techniques, but the spatial resolution of these techniques in prior work has been too small to examine the brainstem and particularly the PAG and its connectivity with any degree of specificity. We have developed an ultra-high field magnetic resonance imaging procedure at 7 Tesla that overcomes this problem. In Specific Aim 1, we will map the structural and functional connectivity of the brainstem, with a focus on the PAG, within subcortical and cortical networks using anatomical, diffusion weighted, and resting state (task-independent) functional connectivity within a 7T imaging environment. In Specific Aim 2, we will examine the functional organization of these brainstem networks across tasks that evoke stress, pain, and emotional experience to assess the construct validity of these three affective processes from a unified neuroscience perspective, and we further examine how these brainstem networks participate in executive function using a working memory task. Finally, in the Exploratory Aim, we will examine the extent to which peripheral physiological measurements (e.g., heart rate variability, skin conductance, respiratory rate) mediate the relation between brainstem network structure / activity and behavioral responses in each affective domain. Our main deliverable at the end of this R01 is a working neural theory of affective processes that can be used by cancer researchers to study the influence of affect on cancer-related decision making.