Direct Intracranial Electrophysiological Mapping of Insular Circuits for Anxiety in the Human Brain

人脑焦虑岛叶回路的直接颅内电生理图测

• 批准号: 10318646
• 负责人: Andrew Moses Lee
• 金额: $ 20.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10318646
• 关键词: Address; Affective; Anterior; Anxiety; Anxiety Disorders; Aversive Stimulus; Behavior; Biological Markers; Biometry; Brain; Clinical; Code; Data; Dimensions; Electric Stimulation; Electroencephalography; Electrophysiology (science); Emotional; Epilepsy; Excision; Extinction (Psychology); Face; Facial Expression; Feeling; Frequencies; Goals; Human; Image; Impairment; Implant; Individual; Insula of Reil; Interoception; Intervention; Intractable Epilepsy; Link; Maps; Measurement; Mediating; Mental Health; Mental disorders; Mentors; Methods; Modeling; Monitor; National Institute of Mental Health; Neurosciences; Operative Surgical Procedures; Patient Self-Report; Patients; Pattern; Pharmaceutical Preparations; Physiological; Pilot Projects; Population; Prevalence; Process; Psychiatrist; Quality of life; Reporting; Research; Research Personnel; Resolution; Role; Seizures; Shock; Signal Transduction; Social Functioning; Structure; Symptoms; Testing; Training; Work; advanced system; affective neuroscience; anxiety spectrum disorders; anxiety states; anxiety treatment; associated symptom; base; career; common symptom; comorbidity; conditioned fear; density; diagnostic criteria; experience; improved; meetings; multimodality; negative affect; neural circuit; neural network; neurophysiology; neuroregulation; new therapeutic target; novel; novel strategies; relating to nervous system; response; self-reported anxiety; severe mental illness; signal processing; spatiotemporal; temporal measurement; theories

PROJECT SUMMARY/ABSTRACT Anxiety is a common symptom across psychiatric disorders and is associated with worse quality of life and impairment. However, the existing treatments for anxiety remain limited despite its widespread prevalence. My career goal is to become an academic psychiatrist and neuroscientist focused on the neural circuits underlying various dimensions of anxiety in the human brain with the aim of developing targeted novel therapeutics. Previous studies suggest that the anterior insular cortex is a critical node within a larger corticolimbic `anxiety network,' which mediates various dimensions of anxiety. It is one of the most heavily implicated regions across all anxiety disorders and frequently observed in anxiety-related task studies. Despite the large body of evidence implicating the insular cortex across serious mental illness, the underlying role of insular circuits in anxiety remains unclear. Intracranial electrophysiological mapping with high density recordings offers a unique and promising method to study insular networks with high spatiotemporal resolution. To date, there are no studies that have investigated insular neurophysiology in the context of anxiety-related symptoms using iEEG. In our pilot studies, we found preliminary evidence that insular activity in distinct spectral bands correlates with dimensions of anxiety. We also found evidence that stimulation of the anterior insula can elicit an increase in self-reported anxiety associated with propagation of activity to downstream corticolimbic structures. This proposal builds upon these preliminary findings to validate our model that distinct spatiotemporally overlapping insular circuits mediate specific anxiety-related processes through coordinate oscillatory activity. Aim 1 utilizes a task-based approach to identify insular representations of anxiety-related symptoms and behaviors using intracranial recordings. Aim 2 tests the role of insular activity on anxiety-related symptoms and downstream corticolimbic networks using direct electrical stimulation. To address these research goals, I will need additional training in advance signal processing, affective neuroscience, and biostatistics. My rigorous training plan and expert mentoring team will provide me with the experience necessary to become a fully independent investigator able to bring advanced systems neuroscience approaches to basic mental health research.

项目概要/摘要 焦虑是精神疾病的常见症状，与生活质量较差和 损害。然而，尽管焦虑症普遍存在，但现有的治疗方法仍然有限。我的 职业目标是成为一名学术精神病学家和神经科学家，专注于潜在的神经回路 人类大脑中焦虑的各个方面，旨在开发有针对性的新型疗法。 先前的研究表明，前岛叶皮质是更大的皮质边缘“焦虑”中的关键节点 网络”，它调节焦虑的各个方面。它是全球受影响最严重的地区之一 所有焦虑症，并在与焦虑相关的任务研究中经常观察到。尽管身体庞大 有证据表明岛叶皮质在严重精神疾病中的作用，岛叶回路在精神疾病中的潜在作用 焦虑仍不清楚。具有高密度记录的颅内电生理图提供了独特的 以及研究具有高时空分辨率的岛屿网络的有前途的方法。迄今为止，还没有 使用 iEEG 调查焦虑相关症状背景下的岛神经生理学的研究。 在我们的试点研究中，我们发现了初步证据，表明不同光谱带中的岛活动与 焦虑的维度。我们还发现有证据表明刺激前岛叶可以引起 自我报告的与下游皮质边缘结构活动传播相关的焦虑。这 该提案建立在这些初步发现的基础上，以验证我们的模型，即不同的时空重叠 岛回路通过协调振荡活动介导特定的焦虑相关过程。目标1利用 基于任务的方法来识别焦虑相关症状和行为的岛状表征 颅内记录。目标 2 测试岛叶活动对焦虑相关症状及其下游的作用 使用直接电刺激的皮质边缘网络。为了实现这些研究目标，我需要 高级信号处理、情感神经科学和生物统计学方面的额外培训。我的严格训练 计划和专家指导团队将为我提供成为完全独立的人所需的经验 研究人员能够将先进的系统神经科学方法引入基础心理健康研究。