Mechanisms and Functions of Cortical Activity to Restore Behavior

项目摘要 在脑损伤后恢复意识的过程中，监测向清醒的转变是至关重要的， 麻醉，以及那些新冠肺炎幸存者改变了意识。然而，我们有一个不精确的 对神经动力学的理解与受试者醒来时的行为变化有关。我们之前的工作 研究发现，刺激巨细胞前核(ANGC)可促进从昏迷状态中唤醒 州政府。我们建议通过aNGC招募多个觉醒途径，作为触发广泛的 激活会导致觉醒。值得注意的是，激活aNGC增加了额叶运动皮质的活动，并 在高麻醉状态下，通过调节神经生长因子-额叶运动皮质通路恢复完全活动能力 集中暴露。我们还表明，从不同的昏迷状态中出现的动物有一个共同的 皮层和运动觉醒的动态过程可以从深到高进行一致的排序 级别。我们确定了跟踪低血糖昏迷患者恢复运动行为的五个大脑皮层周期 一系列麻醉药，无论是吸入的还是注射的，以及常规的翻正反射分析。基于这些 发现，我们假设恢复清醒是一个常见的渐进过程，其中皮质模式包含 区分反身性动作和有目的动作的意识尺度。我们假设大脑皮层 将神经反应与定义的行为联系起来的测量是一种适用的方法，它可以 将对意识恢复的分析扩展到监视反射性运动之外。 我们的建议加深了我们对皮质神经亚型、神经通路的贡献的理解 潜在的aNGC诱导的额叶运动皮质活动的变化，以及区分 在我们的啮齿动物低觉醒模型中，对自发行为的反射。此外，我们还将建立 打开这些行为转换的大脑皮层模式。因为无意识的病理状态是 异质性很大，对普通复苏有一个清晰的了解有助于更好地理解 损伤对皮质活动和行为造成的可变性。因此，我们将确定神经损伤程度 回路影响已建立的皮层活动通路和作为行为恢复基础的动力学。建议数 因此，研究具有重要意义，因为它们将建立机械性的对应关系，检查 神经通路及其动力学与揭示医学新奇行为的习惯性和有意行为有关 相关的生物标记物，促进清醒状态的强大推断在麻醉和 在脑损伤后。

Project Summary Monitoring the transition to wakefulness is critical during restoration to consciousness after brain injury, anesthesia, and in those COVID-19 survivors that have altered consciousness. However, we have an imprecise understanding of neural dynamics linked to behavioral changes as subjects awaken. Our previous work discovered that stimulating the anterior nucleus gigantocellularis (aNGC) promotes arousal from a coma-like state. We proposed recruiting multiple arousal pathways through aNGC as an avenue to triggering widespread activation resulting in wakefulness. Notably, aNGC activation increased frontal-motor cortical activity and restored full mobility through modulation of an aNGC-to-frontal-motor-cortex pathway despite high anesthetic concentration exposure. We also showed that animals emerging from diverse coma-like states share a common dynamic process of cortical and motor arousal that can be consistently sequenced from deep to high arousal levels. We identified five cortical periods that tracked restored motor behavior in a hypoglycemic coma and a range of anesthetics, whether inhaled or injected, alongside conventional righting reflex assays. Based on these findings, we postulate that restoring waking is a common progressive process in which cortical patterns contain metrics of consciousness that distinguish reflexive from purposeful movements. We hypothesize that cortical measurements that link neural responsiveness to defined behaviors are an applicable method that can extend the analysis of the recovery of consciousness beyond monitoring reflexive movements. Our proposal deepens our understanding of the contribution of cortical neural subtypes, the neuronal pathways underlying aNGC-induced changes in frontal-motor cortical activity, and the temporal dynamics that distinguish reflexive from the initiation of voluntary behaviors in our rodent-low arousal models. In addition, we will establish the cortical patterns that unpack these behavioral transitions. Since pathological states of unconsciousness are vastly heterogeneous, having a clear understanding of ordinary recovery serves to better appreciate the variability imposed by the injury to cortical activity and behavior. Thus, we will identify how damaged neural circuits affect established cortical activity pathways and dynamics that underlie behavior recovery. The proposed studies are thus significant because they will establish the mechanistic correspondence, examining activation of neural pathways and their dynamics linked to habitual and intentional behaviors that reveal novel, medically relevant biomarkers that promote a robust inference of arousal states during emergence from anesthesia and after brain injury.