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

摘要 这个独立科学家奖的申请，在响应PAR-14-045，旨在扩大理解， 压力感受器反射（心-脑反馈回路）作为行为改变的可塑性生理机制。其 重要性源于对环境和内部线索的生理反应在其中发挥的核心作用 煽动“自动”酒精使用行为，尽管有意识的动机保持禁欲，和远- 达到公共卫生的影响，将产生优化方法，以中断这些“自动” 行为。它的创新源于职业发展和研究计划，将AUD治疗- 基于改变研究的机制与NIH的行为改变平台的广泛科学。具体而言是 拟议的高度一体化的职业发展和研究部分侧重于概念/分析 训练和研究，以解构压力感受器反射机制的时间性质（在那一刻 及其对生物学（心脏/大脑）、认知（注意力）和行为的多层次影响 （酒精使用）。最终的目标是为压力反射如何影响行为提供科学证据 随着越来越多的证据表明其临床实用性而改变。拟议的职业发展活动涵盖 三个领域：生态瞬时评估（EMA）分析策略，注意力理论和任务， 神经成像工具和方法，以增加对酒精行为灵活性的理解 是在心血管和神经系统中进行管理的，以及这些系统的整合如何受到破坏， 可能会扰乱注意力，导致适应灵活性的丧失和AUD的持续性。第一研究 aim使用EMA策略来检查即时生理变化之间的时间关系 以及治疗期间每天和每周发生的生理、心理和物质使用变化。在 这样做，它提供了直接洞察的变化，压力反射激活在短时间尺度和下真实的 当共振呼吸用于响应治疗环境之外的触发时的世界条件。的 第二个研究目的是使用实验研究来检查压力反射激活的能力， 瞬间以及长期（治疗前至治疗后）注意力处理通过其对神经和 心脏信号因此，它测试了注意力，从认知测试的表现以及 生理和fMRI BOLD反应性，介导压力反射激活对行为控制的影响。 该研究计划被设计为R 01 AA 023667“项目影响：当前”的有效附加内容 保护免受触发自动捕获”，一项随机临床试验，提供了一个基于压力反射的 干预作为年轻女性酒精和药物使用障碍常规治疗辅助手段 儿童（2019年4月）。如果成功，拟议的研究将作为跳板， 了解压力感受器反射与认知过程、心脏和神经活动的关系， 目前经验支持的AUD行为治疗的成功率通常不可预测。

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.