Stimulation-induced modulation of fronto-limbic responses to threat

项目总结/摘要 焦虑和癫痫之间存在双向神经生物学联系。然而，具体过程 这些情况之间的联系尚不清楚。立体脑电图（sEEG）是定位的关键工具， 接受切除性评估的难治性癫痫（TRE）患者的发作起始区 手术，并提供了一个理想的方法来研究分布式网络的中断，这是基础 链接.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是 通过已经植入的sEEG电极传递电刺激是可能的。拟议 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调节TRE中的潜在网络。完成 拟议的工作将提供一个因果关系的理解之间的联系额边缘网络功能，焦虑， 和癫痫。从本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，并证明该回路可以通过以下方式进行调节： 电刺激核心假设是TRE与细胞功能的破坏有关， 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 调节导致焦虑症状（目的1）。此外，刺激背内侧前额叶区域将 直接影响杏仁核对威胁反应的预期调节（目标2）。 这些目标将在一个正式的研究计划的背景下完成，并由一个研究小组提供支持。 相关专业知识。此外，R21工作期间生成的数据将收集初步数据 竞争性R 01随机临床试验申请所需。伯明翰亚拉巴马大学 提供最先进的研究专业知识和资源，也将有助于准备这一建议， 成功具体来说，拟议的工作将利用先进的sEEG记录和刺激技术， 包括情感过程的功能连接和行为测量， 癫痫研究和治疗中心，以及临床研究专业知识，核心， laboratories.

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.