THE BAROREFLEX MECHANISM: TRANSLATION TO AUD TREATMENT AND PROGNOSTIC MODELS

描述（申请人提供）：大脑和心脏之间的双向交流在思想，情感和行为中的至关重要性已经被人们所知超过100年，但这一知识对酒精使用障碍（AUD）的治疗几乎没有影响。一位职业生涯中期的翻译临床科学家修改了K24的应用，通过翻译一种新的神经心脏信号模型，（称为压力反射[BAR]模型）用于AUD的行为干预。研究目标是完善和测试干预措施的基础上，她的基础研究支持酒吧作为一个积极的行为改变机制。影响BAR机制的干预措施增加了大脑和心血管系统之间的反馈。这个K24的总体假设是，增强BAR功能将增加对酒精的行为灵活性，如减少饮酒，预防复发，减少抑郁症和其他积极的心理社会结果所证明的。第一个具体目标是使用来自四个正在进行的临床试验的数据来评估两个已建立的（有氧运动，冥想）和一个新的（心率变异性生物反馈）干预措施的有效性，并确定BAR是否是每个干预措施的共同作用机制。第二个目的是检查治疗反应者与没有反应的人相比是否表现出不同的神经连接模式。第三个探索性目标是使用临床、心血管和神经指标建立预后模型，以预测哪些人最有可能从针对BAR机制的干预措施中获益。遗传指标是否可以改善预测也将被探索的职业发展目标是移动候选人的病人为导向的研究计划从早期到后期阶段的临床翻译。培训目的是获得随机临床试验的设计，实施和分析方面的专业知识，使用神经影像学和神经心脏工具区分治疗应答者与非应答者，以及应用非线性灵敏度和不确定性分析构建多水平预后模型。拟议的研究和职业发展战略将提供一个独特的培训机会，为五个上升的初级教师和一个研究生在转化临床科学，情绪调节和酒精使用障碍的共同利益。学员们为团队带来了独特的背景和合作，包括情绪失调和人际暴力的临床精神病理学，心理生理学和运动科学，神经影像学和遗传学。研究和培训里程碑的实现将通过年度会议报告、同行评议的出版物和以患者为导向的研究资助申请来正式衡量。

DESCRIPTION (provided by applicant): The critical importance of two-way communication between the brain and the heart during thought, emotion, and behavior has been known for over 100 years, but this knowledge had little impact on alcohol use disorder (AUD) treatment .This revised K24 application by a mid-career translational clinical scientist addresses this gap by translating a new model of neurocardiac signaling (called the baroreflex [BAR] model) into behavioral interventions for AUDs. The research goal is to refine and test interventions based on her basic research supporting the BAR as an active behavioral change mechanism. Interventions that affect the BAR mechanism increase feedback between the brain and cardiovascular system. The overarching hypothesis of this K24 is that enhancing BAR functioning will increase behavioral flexibility towards alcohol as evidenced by reduced drinking, relapse prevention, decreased depression, and other positive psychosocial outcomes. The first specific aim is to use data from four ongoing clinical trials to evaluate the efficacy of two established (aerobic exercise, meditation) and one new (heart rate variability biofeedback) intervention and determine whether the BAR is a common mechanism of action in each intervention. The second aim is to examine whether treatment responders show different patterns of neural connectivity compared to those who do not respond. The third exploratory aim is to build prognostic models using clinical, cardiovascular, and neural indicators to predict which persons are most likely to benefit from interventions that target the BAR mechanism. Whether genetic indicators can improve prediction will also be explored the career development goal is to move the Candidate's patient oriented research program from early to late stage clinical translation. Training aims are to gain expertise in the design, conduct, and analysis of randomized clinical trials, the use of neuroimaging and neurocardiac tools to differentiate treatment responders versus non-responders, and the application of nonlinear sensitivity and uncertainty analysis to build a multi-level prognostic model. The proposed research and career development strategy will provide a unique training opportunity for five rising junior faculty and one graduate student with shared interests in translational clinical science, emotion regulation, and alcohol use disorders. The mentees bring to the team unique backgrounds and collaborations in the clinical psychopathology of emotional dysregulation and interpersonal violence, psychophysiology and exercise science, neuroimaging, and genetics. Attainment of research and training milestones will be gauged formally from yearly conference presentations, peer-reviewed publications, and patient-oriented research grant submissions.