Stimulation-induced modulation of fronto-limbic responses to threat

刺激诱导的额叶边缘对威胁反应的调节

• 批准号: 10646799
• 负责人: Adam M Goodman
• 金额: $ 22.28万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646799
• 关键词: Alabama; Amygdaloid structure; Anxiety; Anxiety Disorders; Area; Behavior; Behavioral; Brain; Clinical Research; Clinical Trials; Cognition; Cognitive; Cues; Data; Disease; Electric Stimulation; Electrodes; Electroencephalography; Emotional; Emotions; Epilepsy; Equipment and supply inventories; Evaluation; Functional Magnetic Resonance Imaging; Functional disorder; Future; Galvanic Skin Response; Goals; High Prevalence; Human; Implant; Individual; Investigation; Knowledge; Laboratories; Learning; Link; Measurement; Measures; Mediating; Memory; Mental Depression; Mental Health; Modeling; Moods; Neurobiology; Operative Surgical Procedures; Patients; Persons; Pharmaceutical Preparations; Physiologic pulse; Physiological; Prefrontal Cortex; Prevalence; Process; Public Health; Regulation; Research; Research Personnel; Research Project Grants; Resistance; Resources; Seizures; Severities; Stimulus; Symptoms; Techniques; Testing; Training; Universities; Work; anxiety symptoms; behavior measurement; behavioral response; brain behavior; comorbidity; conditioned fear; conditioning; emotion regulation; expectation; experience; experimental study; information processing; network dysfunction; neural; neural circuit; neurobehavioral; neuroregulation; novel; perceived stress; power analysis; randomized, clinical trials; response; success; therapy development; tool; trait; treatment center; treatment trial

PROJECT SUMMARY/ABSTRACT There are bidirectional neurobiological links between anxiety and epilepsy. However, the specific processes linking these conditions remain unclear. Stereo-electroencephalography (sEEG) is a critical tool for localizing the ictal onset zone in patients with treatment-resistant epilepsy (TRE) undergoing evaluation for resective surgery and provide an ideal approach to study the disruptions in the distributed networks that underlie this link. Further, investigation of these circuits and their causal impact on human behavior and cognition is possible through the delivery of electrical stimuli via the already implanted sEEG electrodes. The proposed work will assess anxiety-related disruptions in emotion regulation neurocircuitry using sEEG and test how stimulation to dorsomedial prefrontal cortex modulates the underlying networks in TRE. Completion of the proposed work will provide a causal understanding of the link between fronto-limbic network functions, anxiety, and epilepsy. The knowledge gained from this study will be applied to the field of mental health research to identify critical network nodes related to anxiety and demonstrate that this circuit can be modulated by electrical stimulation. The central hypothesis is that TRE is associated with disruption in the function of the fronto-limbic network (i.e., prefrontal cortex; amygdala), and in turn, this dysfunction disrupts healthy emotion regulation resulting in anxiety symptoms (Aim 1). Further, stimulation of dorsomedial prefrontal regions will directly influence anticipatory regulation of amygdala responses to threat (Aim 2). These aims will be accomplished in the context of a formal research plan, supported by a team of researchers with relevant expertise. Additionally, the data generated during the R21 effort will gather the preliminary data required for a competitive R01 randomized clinical trial application. The University of Alabama at Birmingham offers state-of-the-art research expertise and resources that will also serve to prepare this proposal for success. Specifically, the proposed work will utilize advanced sEEG recording and stimulation techniques, including functional connectivity and behavioral measures of emotion processes, one of the nation’s top epilepsy research and treatment centers, and a dynamic network of clinical research expertise, cores, and laboratories.

项目概要/摘要 焦虑和癫痫之间存在双向神经生物学联系，但具体过程却不同。 这些情况之间的联系仍不清楚。立体脑电图（sEEG）是定位的关键工具。 接受切除评估的难治性癫痫 (TRE) 患者的发作区 手术并提供了一种理想的方法来研究其背后的分布式网络的中断 此外，对这些回路及其对人类行为和认知的因果影响的调查正在进行中。 通过已经植入的 SEEG 电极传递电刺激是可能的。 这项工作将使用 SEEG 评估与焦虑相关的情绪调节神经回路中断，并测试如何 对背内侧前额叶皮层的刺激可调节 TRE 的基础网络。 拟议的工作将提供对额叶边缘网络功能、焦虑、 从这项研究中获得的知识将应用于心理健康研究领域。 识别与焦虑相关的关键网络节点，并证明该电路可以通过以下方式调节 核心假设是 TRE 与大脑功能的破坏有关。 额边缘网络（即前额皮质；杏仁核），反过来，这种功能障碍会破坏健康的情绪 此外，刺激背内侧前额叶区域会导致焦虑症状（目标 1）。 直接影响杏仁核对威胁反应的预期调节（目标 2）。 这些目标将在研究人员团队的支持下在正式研究计划的背景下实现 此外，R21 工作期间生成的数据将收集初步数据。 阿拉巴马大学伯明翰分校的竞争性 R01 随机临床试验申请所需。 提供最先进的研究专业知识和资源，也将有助于准备该提案 具体来说，拟议的工作将利用先进的 sEEG 记录和刺激技术， 包括情绪过程的功能连接和行为测量，这是美国顶尖的研究之一 癫痫研究和治疗中心，以及临床研究专业知识、核心和技术的动态网络 实验室。