Deficient inhibition underlies salience network hyperactivity in stress and anxiety

抑制不足是压力和焦虑中显着网络过度活跃的基础

基本信息

批准号：
10559649
负责人：
Wen Li
金额：
$ 18.63万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10559649
关键词：
Adopted Amygdaloid structure Anterior Anxiety Arousal Automobile Driving Biological Assay Biological Markers Brain Clinic Clinical Coupling Disease susceptibility Disinhibition Dorsal Electroencephalography Electrophysiology (science)Equilibrium Etiology Exhibits Experimental Designs Frequencies Functional disorder Galvanic Skin Response Graph Hyperactivity Insula of Reil Intervention Laboratories Link Maintenance Measures Mediating Mediation Mental Health Mental disorders Methodology Modeling Moods Neural Inhibition Neurobiology Neurophysiology - biologic function Parietal Lobe Pathologic Pathology Periodicity Persons Physiological Play Prefrontal Cortex Process Research Rest Role Schizophrenia Signal Transduction Societies Source Stimulus Stress anxious autism spectrum disorder cingulate cortex cognitive neuroscience comorbidity cost frontal lobe functional magnetic resonance imaging/electroencephalography insight network dysfunction neural neural network neuromechanism neuropsychiatric disorder neuropsychiatry noninvasive brain stimulation novel novel therapeutics response sensory gating trait transmission process

项目摘要

ABSTRACT Decades of research notwithstanding, there remains an urgent need to uncover the neurobiology of stress and anxiety and develop effective biomarkers for these conditions. The salience network (SN), a major intrinsic neural network anchored in the frontal lobe, consistently exhibits hyperactive functioning in stress and anxiety. This SN hyperactivity has been recognized as a novel brain network pathology, but its underlying mechanism remains elusive. EEG alpha (8-12 Hz) oscillations, dominating intrinsic neural rhythmic activity, play a critical role in cortical inhibition. Particularly, prevalent posterior-to-frontal (P→F) alpha projection (i.e., alpha directional connectivity) transmits alpha inhibitory influence from the occipitoparietal cortex (a primary alpha source) to the frontal lobe. By driving bottom-up cortical inhibition and gating sensory propagation that triggers the SN, alpha P→F connectivity can serve to downregulate the SN. Prominently featured in “thalamocortical dysrhythmia” or “oscillopathy” models of neuropsychiatric disorders, alpha dysrhythmia (particularly, deficient alpha P→F connectivity) has been increasingly observed in stress and anxiety, motivating our hypothesis that deficient alpha P→F connectivity underlies SN hyperactivity in stress and anxiety. Leveraging an integrative methodology of simultaneous EEG-fMRI combined with experimental anxiety induction via stress exposure, this project (N = 140) will establish a mechanistic role of alpha P→F hypoconnectivity in the genesis and maintenance of SN hyperactivity in stress and anxiety. This discovery will further identify an accessible, low-cost EEG biomarker for SN hyperactivity and for stress and anxiety in general. Finally, this discovery will isolate a new treatment target that is highly responsive to non-invasive brain stimulation (NIBS), motivating an R01 to normalize alpha P→F connectivity as a novel intervention for stress and anxiety.

抽象的尽管进行了数十年的研究，但仍然迫切需要揭示神经生物学压力和焦虑并开发针对这些情况的有效生物标志物显着网络（SN），一个主要的内在神经网络始终锚定在额叶，表现出过度活跃的功能这种 SN 过度活跃已被认为是一种新型的大脑网络病理学，但是其根本机制仍然难以捉摸。 EEG α（8-12 Hz）振荡，主导内在神经节律活动，在特别是，普遍存在的后额叶 (P→F) α 投射（即 α 方向性）连接性）传输来自枕顶叶皮质（主要 α 源）的 α 抑制影响通过驱动自下而上的皮质抑制和触发的门控感觉传播。 SN、α P→F 连接可以起到下调 SN 的作用。神经精神疾病的“丘脑皮质节律障碍”或“振荡病”模型，α节律障碍（特别是α P→F连接缺陷）在压力和焦虑中越来越多地被观察到，激发了我们的假设：α P→F 连接的缺陷是 SN 在压力和压力下过度活跃的基础焦虑。利用同步 EEG-fMRI 与实验相结合的综合方法通过压力暴露诱导焦虑，该项目（N = 140）将建立阿尔法的机械作用 P→F 低连接性在压力和焦虑中 SN 过度活跃的发生和维持中。这一发现将进一步确定一种可获取的、低成本的脑电图生物标志物，用于 SN 过度活跃和压力最后，这一发现将分离出一个高度敏感的新治疗靶点。到非侵入性脑刺激 (NIBS)，激励 R01 将 alpha P→F 连接正常化为针对压力和焦虑的新颖干预措施。