Deficient inhibition underlies salience network hyperactivity in stress and anxiety

摘要 尽管进行了几十年的研究，但仍迫切需要发现神经生物学 并针对这些情况开发出有效的生物标记物。显著网络(SN)， 定位于额叶的一个主要的内在神经网络，一直表现出过度活跃的功能 在压力和焦虑中。这种SN多动已被认为是一种新的大脑网络病理，但 其潜在机制仍然难以捉摸。 主导固有神经节律活动的脑电α(8-12赫兹)振荡在 皮质抑制。具体地，普遍的后前额(P→F)阿尔法投影(即，阿尔法方向 连通性)传递来自枕顶皮质(主要阿尔法来源)的阿尔法抑制影响 前额叶。通过驱动自下而上的皮质抑制和门控感觉传播，触发 SN，Alpha P→F连通性可用于下调SN。突出显示在 神经精神障碍的“丘脑皮质节律失常”或“振荡病”模型 (尤其是缺乏αP→F连接)在压力和焦虑中越来越多地被观察到， 支持我们的假设，即缺乏α-P-→-F连接是应激和 焦虑。 利用同步脑电-功能磁共振成像与实验相结合的综合方法 通过压力暴露诱导焦虑，这个项目(N=140)将建立阿尔法的机械作用 P-→-F低连接性在应激和焦虑状态下SN多动的发生和维持中的作用这 该发现将进一步确定一种可获得的、低成本的SN多动和压力的EEG生物标记物 以及总体上的焦虑。最后，这一发现将分离出一种高度反应的新治疗靶点 到非侵入性脑刺激(NIB)，激励R01将αP→F连接正常化为 针对压力和焦虑的新型干预措施。

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.