Fundamental subcortical mechanisms of affective processing

 描述(申请人提供)：50%-66%的癌症死亡可以通过行为改变来预防。越来越多的证据表明，与情绪、压力和痛苦相关的一系列基本的情感心理过程影响着行为选择，促进了健康的选择或促进了不健康的选择，并有能力影响成功生存的关键方面。虽然情感和癌症相关决策之间的联系正在变得众所周知，但这项研究在很大程度上仍然是描述性的。对这些联系的机械性理解受到一个主要障碍的阻碍：情感处理背后的神经回路在很大程度上仍然没有得到充分的说明。另一个阻碍进展的因素是，情感科学的子领域，包括压力、情绪和疼痛，在很大程度上是相互独立的研究，尽管它们作为心理学概念存在着巨大的重叠。历史上的分歧对使用情感过程改善癌症相关决策构成了关键障碍，但研究人员倾向于专注于外围和中枢情感生物标志物，而不是同时研究它们，这加剧了这种分歧。我们的目标是将情感过程的亚域统一到一个共同的神经框架中，以皮质下脑干区域为中心，这些区域是已知与情感过程密切相关的区域，特别是中脑导水管周围灰质(PAG)，非人类动物研究表明，PAG是控制自主神经输出、止痛反应和情绪、疼痛和应激过程中其他生理反应的关键中枢。人类的情感研究主要依赖于非侵入性的神经成像技术，但以前的工作中这些技术的空间分辨率太小，无法检查脑干，特别是PAG及其与任何程度的特异性的连接性。我们已经在7特斯拉开发了一种超高场磁共振成像程序来克服这个问题。在具体目标1中，我们将使用7T成像环境中的解剖、弥散加权和静息状态(任务无关)功能连接来绘制脑干的结构和功能连接，重点是皮质下和皮质网络中的PAG。在具体目标2中，我们将考察这些脑干网络在引起压力、疼痛和情绪体验的任务中的功能组织，以从统一的神经科学角度评估这三个情感过程的结构效度，并进一步检验这些脑干网络如何通过工作记忆任务参与执行功能。最后，在探索的目标中，我们将检验外周生理测量(例如心率变异性、皮肤电导、呼吸频率)在多大程度上中介脑干网络结构/活动与每个情感领域的行为反应之间的关系。我们在R01年末的主要成果是情感过程的工作神经理论，癌症研究人员可以使用该理论来研究情感对癌症相关决策的影响。

 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.