Mapping and Manipulating Circuits for Emotion and Cognition in Anxiety and Depression

绘制和操纵焦虑和抑郁情绪和认知的回路

• 批准号: 8817396
• 负责人: Amit Etkin
• 金额: $ 84.59万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-05 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8817396
• 关键词: Affect; Amygdaloid structure; Anterior; Anxiety; Bilateral; Brain; Brain Mapping; Brain region; Chronically Ill; Clinical; Cognition; Data; Development; Diagnostic and Statistical Manual of Mental Disorders; Disease; Emotions; Enrollment; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Human; Image; Imagery; Impairment; Individual; Intervention; Lateral; Left; Link; Maps; Mental Depression; Methods; Modeling; Moods; Neural Pathways; Neurons; Outcome Study; Participant; Pathway interactions; Patients; Pattern; Pharmaceutical Preparations; Physiologic pulse; Post-Traumatic Stress Disorders; Psychopathology; Publishing; Recording of previous events; Regulation; Research; Research Domain Criteria; Role; Science; Site; Specificity; Symptoms; Syndrome; Time; Trauma; Validation; Work; base; brain behavior; brain pathway; clinically significant; cognitive neuroscience; depressive symptoms; design; emotion regulation; evidence base; executive function; innovation; insight; neuroimaging; neuromechanism; novel; post-traumatic stress; programs; public health relevance; repetitive transcranial magnetic stimulation; response

DESCRIPTION (provided by applicant): At present, the ability to apply or develop neurocircuitry-based treatments founded on cognitive neuroscience is still extremely limited for two fundamental reasons: 1) conventional neuroimaging studies provide information on correlations between brain and behavior, but not how activity in one brain region directly drives activation or inhibition in another. To understand the causal relationships between different brain regions or networks, it is necessary to exert direct experimental control over specific brain regions and simultaneously image the consequences on other brain regions or networks. We refer to this as a "causal circuit map." Consequently, 2) it is unknown which specific neural pathways within these causal circuit maps are abnormal and which are intact in patients, and how particular clinical factors such as trauma exposure impact these brain pathways. It would be of fundamental theoretical and practical importance for implementing a future circuit-targeting neuromodulatory intervention to know, for example, whether stimulation should be directed to intact pathways or to abnormal ones (with a goal of normalizing dysfunction). Without causal circuit mapping, target identification and validation for future neuromodulatory treatments, such as repetitive transcranial magnetic stimulation (rTMS), will remain as trial-and-error guesswork. An additional limitation of prior studies on mood/anxiety-related disorders is that the DSM does not capture the full spectrum of clinically-significant negative affect symptomatology, including the role of trauma in clinical syndromes beyond post-traumatic stress. Our primary focus in this proposal is therefore to delineate for the first time the causal circuit maps relevant for impairments in emotion regulation (ER) and executive function (EF) in a broad range of chronically ill patients with high negative affect symptoms, consistent with the aims of the Research Domain Criteria Project (RDoC). Prior work on high negative affect disorders with correlational imaging has found abnormalities across multiple nodes in several well-defined large-scale neuronal networks. However, unlike these prior correlational studies, we propose to employ a causal circuit mapping neuroimaging approach to achieve an unprecedented level of specificity with regard to which causal brain pathways are intact and which are abnormal. Here we provide this casual map by direct brain activation using non-invasive single pulse excitatory TMS (spTMS), combined with visualization of network effects using concurrent functional magnetic resonance imaging (fMRI). The targets for spTMS/fMRI are cortical regions within well-defined large-scale networks relevant to ER/EF (eight bilateral prefrontal sites as well as one control site), thus systematically linking causal maps to circuit-level models of the illnesses A successful outcome from this study would be directly useful in guiding how and where to target existing long-term neuromodulatory interventions, and lay the groundwork for the development of novel methods.

描述（由申请人提供）：目前，应用或开发基于认知神经科学的基于神经回路的治疗的能力仍然非常有限，原因有两个：1）常规神经成像研究提供了关于大脑与行为之间相关性的信息，但没有提供一个大脑区域的活动如何直接驱动另一个大脑区域的激活或抑制。为了了解不同的大脑之间的因果关系， 因此，如果我们要对特定的脑区或网络进行直接的实验控制，并同时对其他脑区或网络的结果进行成像，就有必要。我们称之为“因果电路图”。“因此，2）尚不清楚这些因果电路图中哪些特定的神经通路是异常的，哪些是完整的，以及特定的临床因素如创伤暴露如何影响这些大脑通路。这将是一个基本的理论和实践的重要性，为实现未来的电路靶向神经调节干预，以了解，例如，刺激是否应该被引导到完整的通路或异常的（以正常化功能障碍的目标）。如果没有因果电路映射，未来神经调节治疗的目标识别和验证，如重复经颅磁刺激（rTMS），将仍然是试错猜测。先前关于情绪/焦虑相关障碍的研究的另一个限制是DSM没有捕获临床显著的负面影响心理学的全部谱，包括创伤在创伤后应激以外的临床综合征中的作用。因此，我们在这项建议中的主要重点是首次描绘与情绪调节（ER）和执行功能（EF）障碍相关的因果电路图，这些障碍与广泛的具有高负性情绪症状的慢性病患者有关，这与研究领域标准项目（RDoC）的目标一致。先前对高负性情感障碍与相关成像的研究发现，在几个定义明确的大规模神经元网络中的多个节点存在异常。然而，与这些先前的相关性研究不同，我们建议采用因果电路映射神经成像方法，以达到前所未有的特异性水平，其中因果脑通路是完整的，哪些是异常的。在这里，我们提供了这个休闲地图的直接大脑激活使用非侵入性单脉冲兴奋性TMS（spTMS），结合可视化的网络效应，使用并发功能磁共振成像（fMRI）。spTMS/fMRI的目标是与ER/EF相关的明确定义的大规模网络中的皮质区域（8个双侧前额叶部位和1个对照部位），从而系统地将因果图与疾病的回路水平模型联系起来。这项研究的成功结果将直接有助于指导如何以及在何处靶向现有的长期神经调节干预，并为新方法的发展奠定基础。