Deconstructing the temporal and multi-level influences of the baroreflex mechanism on alcohol use behaviors

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Abstract This Independent Scientist Award application, in response to PAR-14-045, seeks to extend understanding of the baroreflex (the heart-brain feedback loop) as a malleable physiological mechanism of behavior change. Its significance stems from the central role that physiological reactions to environmental and internal cues play in instigating ‘automatic’ alcohol use behaviors despite conscious motives to remain abstinent, and the far- reaching public health impact that would arise from optimizing methods to interrupt these ‘automatic’ behaviors. Its innovation derives from a career development and research plan that bridges AUD treatment- based mechanisms of change research with NIH’s broad science of behavior change platform. Specifically, the proposed, and highly integrated, career development and research components focus on conceptual/analytical training and studies to deconstruct the baroreflex mechanism in terms of its temporal nature (in-the-moment versus across time) and its multi-level influence on biology (heart/brain), cognition (attention), and behavior (alcohol use). The ultimate goal is to bring the scientific evidence for how the baroreflex acts to affect behavior change in line with growing evidence of its clinical utility. The proposed career development activities span three domains: ecological momentary assessment (EMA) analytic strategies, attention theory and tasks, and neuroimaging tools and methodologies, to increase understanding of how behavioral flexibility towards alcohol is managed across cardiovascular and neural systems, and how disruption to the integration of these systems can disrupt attention, leading to a loss of adaptive flexibility and the persistence of AUDs. The first research aim uses EMA strategies to examine the temporal relationship between in-the-moment physiological changes and physiological, psychological and substance use changes that occur daily and weekly during treatment. In doing so, it provides direct insight into changes in baroreflex activation on short time scales and under real world conditions when resonance breathing is used in response to triggers outside the treatment context. The second research aim uses experimental studies to examine the ability of baroreflex activation to alter in-the- moment as well as longer-term (pre- to post-treatment) attentional processing via its influence on neural and cardiac signaling. Thus, it tests whether attention, measured from cognitive test performance as well as physiological and fMRI BOLD reactivity, mediates the influence of baroreflex activation on behavioral control. The research plan is designed as an efficient add-on to R01 AA023667, “Project IMPACT: In-the-Moment Protect from Automatic Capture by Trigger”, a randomized clinical trial that delivers a baroreflex-based intervention as an adjunct to treatment-as-usual for alcohol and drug use disorders in women with young children (through April 2019). If successful, the proposed research will serve as a springboard for understanding the relation of the baroreflex to cognitive processing, cardiac and neural activity, and to the often unpredictable success of current empirically supported behavioral treatments for AUD.