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

项目总结/摘要 焦虑是精神疾病的常见症状，与生活质量下降有关， 损伤然而，尽管焦虑症广泛流行，但现有的焦虑症治疗方法仍然有限。我 我的职业目标是成为一名学术精神病学家和神经科学家，专注于神经回路的基础 人类大脑中焦虑的各个方面，目的是开发有针对性的新疗法。 先前的研究表明，前岛叶皮层是一个更大的皮质边缘焦虑的关键节点， 网络，“它调解焦虑的各个方面。它是全球受影响最严重的地区之一， 所有的焦虑症，经常在焦虑相关的任务研究中观察到。尽管有大量的 岛叶皮层在严重精神疾病中的潜在作用， 焦虑仍然不清楚。具有高密度记录的颅内电生理标测提供了独特的 是研究高时空分辨率孤岛网络的一种有前途的方法。迄今为止，没有 使用iEEG在焦虑相关症状的背景下研究岛叶神经生理学的研究。 在我们的初步研究中，我们发现了初步证据，表明不同光谱带中的岛叶活动与 焦虑的维度我们还发现了刺激前额叶可以引起 自我报告的焦虑与活动向下游皮质边缘结构的传播有关。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 岛状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 一种基于任务的方法来识别焦虑相关症状和行为的孤立表示， 颅内记录。目的2测试岛叶活动对焦虑相关症状和下游症状的作用。 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 在高级信号处理，情感神经科学和生物统计学方面的额外培训。我严格的训练 计划和专家指导团队将为我提供必要的经验，成为一个完全独立的 研究人员能够将先进的系统神经科学方法引入基本的心理健康研究。

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.