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.

抽象的尽管有数十年的研究，但迫切需要揭示神经生物学压力和动画以及为这些条件开发有效的生物标志物。显着网络（SN），锚定在额叶中的主要固有神经元网络，始终表现出多动功能在压力和焦虑中。这种SN多动症已被认为是一种新型的大脑网络病理学，但是它的基本机制仍然难以捉摸。 EEG Alpha（8-12 Hz）振荡，主导内在的神经元节律活性，在皮质抑制。特别是，普遍的后额 - frontal（P→F）alpha投影（即α定向连通性）从枕皮层传输α抑制作用（主要的α源）到额叶。通过推动自下而上的皮质抑制和门控感官传播 SN，Alpha P→F连接可以下调SN。突出出现神经精神疾病的“丘脑皮质心律失常”或“振荡性”模型（特别是，缺乏αP→F连接）在压力和动画中越来越多地观察到激励我们的假设，缺乏αP→F连通性是压力和焦虑。利用简单的EEG-FMRI结合实验的集成方法通过压力暴露焦虑诱导，该项目（n = 140）将建立alpha的机械作用 P→F在压力和动画中SN多动症的起源和维持中的P→f次连接性。这发现将进一步确定可访问的低成本脑电图生物标志物，用于SN多动症和压力和动画一般。最后，这一发现将隔离一个高度响应的新治疗目标进行非侵入性脑刺激（NIBS），激励R01将alpha p→F连接归一化压力和动画的新颖干预。