Deficient inhibition underlies salience network hyperactivity in stress and anxiety

摘要 尽管经过了几十年的研究，仍然迫切需要揭示神经生物学 压力和焦虑，并为这些条件开发有效的生物标志物。突出网络（SN）， 一个主要的内在神经网络锚定在额叶，一贯表现出过度活跃的功能， 压力和焦虑这种SN过度活跃被认为是一种新的大脑网络病理学， 其基本机制仍然难以捉摸。 EEG α（8-12 Hz）振荡，支配内在神经节律活动，在以下方面起关键作用： 皮层抑制特别是，普遍的后额叶（P→F）α投影（即，阿尔法方向 连接）从枕顶皮层（主要的α源）传递α抑制影响 到额叶通过驱动自下而上的皮层抑制和门控感觉传播， SN，α P→F连接性可用于下调SN。突出表现在 神经精神障碍的“丘脑皮质节律障碍”或“神经病”模型，α节律障碍 （特别是，缺乏α P→F连接）已经越来越多地在压力和焦虑中观察到， 激发了我们的假设，即缺乏α P→F连接是压力下SN过度活跃的基础， 焦虑 利用同步EEG-fMRI结合实验的综合方法 通过压力暴露诱导焦虑，本项目（N = 140）将建立α的机械作用 P→F低连接在应激和焦虑中SN过度活跃的发生和维持中的作用这 这一发现将进一步确定一种可获得的、低成本的用于SN多动和应激的EEG生物标志物 和焦虑。最后，这一发现将分离出一种新的治疗靶点，这种靶点具有高度反应性 到非侵入性脑刺激（NIBS），激励R 01将α P→F连接正常化， 压力和焦虑的新干预。

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.