Marijuana Cues, Arousal and the Central Autonomic Network

描述（由申请人提供）：本申请是对PAR-09-073的回应，旨在促进两名成瘾研究人员进入功能性磁共振成像（fMRI）领域。目前，我们正在表征心血管唤醒对情绪和食欲视觉线索的反应的时刻变化。由于线索反应性和药物渴望在激励酒精和药物寻求，使用和治疗后复发中的基本作用，该研究重点具有重大的公共卫生意义。自主神经系统（ANS）功能的内脏变化通过广泛的ANS和中枢神经系统（CNS）互连和压力感受器反射显著地有助于情绪唤起的现象体验。然而，控制线索反应性的动态机制的理解已经被概念化ANS功能与它们在其中操作的神经系统隔离所阻碍。我们寻求应用神经生理学系统的方法来表征如何在功能，调节方面的情绪唤醒响应环境线索的个体内的变化是集成在ANS和CNS。具体目标是获得功能磁共振成像方法和分析方面的专业知识，并将此专业知识应用于研究调节心血管对药物提示反应的动态神经系统。作为概念验证，实验合并心理生理学和神经影像学的方法，提出了作为功能磁共振成像和连接分析的学习工具（目标1），并检查实质性差异的综合大脑和心血管系统响应大麻相关的图片线索在定期大麻用户相比，匹配的控制谁不使用大麻（目标2）。使用3特斯拉的磁铁收集线索暴露期间的功能磁共振成像数据，并使用大脑连接分析来检查参与唤醒调制的大脑区域之间的激活扩散。三个大脑区域（内侧前额叶皮层，杏仁核，脑干）的激活和连接将定量地与心血管调制的图论连接模型。如果成功，该应用将产生（1）初步支持一种新的方法，其中ANS反应性可以动态连接（以随时间变化的方式，而不是作为相关性）与调节线索反应性的神经系统，（2）关于三个脑区域中的激活如何与对线索的心血管反应的压力反射调节相互关联的新知识，以及（3）转化研究的基础，旨在评估改善特定心血管功能的生物反馈干预是否可用于影响控制对药物提示的唤醒的大脑系统的抑制。 公共卫生相关性：环境中的线索，例如看到有人吸烟，可以产生强烈的情绪反应，增加易感个体寻求或使用所选药物的可能性，即使在禁欲期之后。情绪唤起的内脏体验是对药物线索反应的重要组成部分。该应用程序旨在描述自主神经系统如何与大脑一起工作，以控制对大麻线索的内脏反应。

DESCRIPTION (provided by applicant): This application is in response to PAR-09-073 to facilitate the entry of two addiction researchers into the area of functional magnetic resonance imaging (fMRI). We are currently characterizing moment-to-moment changes in cardiovascular arousal in response to emotionally-valenced and appetitive visual cues. This research focus is of substantial public health significance due to the fundamental role of cue reactivity and drug craving in motivating alcohol and drug seeking, use, and relapse following treatment. Visceral changes in autonomic nervous system (ANS) functions contribute significantly to the phenomenal experience of emotional arousal through extensive ANS and central nervous system (CNS) interconnections and the baroreflex. Yet, understanding of dynamic mechanisms that control cue reactivity has been hampered by conceptualizing ANS functions in isolation from the neural system(s) within which they operate. We seek to apply a neurophysiological systems approach to characterize how intra-individual changes in functional, regulatory aspects of emotional arousal in response to environmental cues are integrated across the ANS and CNS. The specific aims are to gain expertise in fMRI methodology and analysis, and to apply this expertise to study a dynamic neural system that modulates cardiovascular response to drug cues. As proof-of-concept, an experiment merging psychophysiological and neuroimaging methodologies is proposed as a fMRI and connectivity analysis learning vehicle (Aim 1) and to examine substantive differences in integrated brain and cardiovascular system response to marijuana-related picture cues in regular marijuana users compared to matched controls who do not use marijuana (Aim 2). fMRI data during cue exposure will be gathered using a 3-Tesla magnet, and the spread of activation between brain regions involved in arousal modulation will be examined using brain connectivity analysis. Activation and connectivity of three brain regions (medial prefrontal cortex, amygdala, brain stem) will be quantitatively linked to cardiovascular modulation within a graph theoretical connectivity model. If successful, this application will yield (1) preliminary support for a new approach wherein ANS reactivity can be linked dynamically (in a time-varying manner, not as a correlation) to neural systems that modulate cue reactivity, (2) new knowledge about how activation in three brain regions interrelates with baroreflex modulation of cardiovascular response to cues, and (3) the groundwork for translational research aimed at evaluating whether biofeedback interventions that improve specific cardiovascular functions can be used to affect inhibition in brain systems that control arousal in response to drug cues. PUBLIC HEALTH RELEVANCE: Cues in the environment, such as the sight of someone smoking, can produce a powerful emotional reaction that increases the likelihood that susceptible individuals will seek or use a drug of choice, even following periods of abstinence. The visceral experience of emotional arousal is an important component of reactivity to drug cues. This application seeks to characterize how the autonomic nervous system works together with the brain to control visceral response to marijuana cues.