Mechanisms and Functions of Cortical Activity to Restore Behavior

皮层活动恢复行为的机制和功能

• 批准号: 10737217
• 负责人: Diany Paola Calderon
• 金额: $ 61.13万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737217
• 关键词: Affect; Anesthesia procedures; Anesthetics; Animals; Anterior; Area; Arousal; Auditory; Automobile Driving; Awareness; Behavior; Behavioral; Biological Assay; Biological Markers; Brain; Brain Injuries; Brain Stem; COVID-19 survivors; Cell Nucleus; Coma; Conscious; Consciousness Disorders; Cues; Decerebration procedure; Deglutition; Diabetic Coma; Doppler Ultrasound; Exhibits; Face; Goals; Head; Hour; Image; Individual; Inhalation; Injury; Knowledge; Learning; Link; Lip structure; Maps; Measurement; Measures; Mediating; Medical; Methods; Modeling; Monitor; Motor; Motor Activity; Motor Cortex; Movement; Mus; Neural Pathways; Neurons; Pathologic; Pathway interactions; Patients; Pattern; Persons; Population; Population Dynamics; Preparation; Process; Prognosis; Prosencephalon; Public Health; Quality of life; Recovery; Reflex action; Reporting; Rodent; Signal Transduction; Silicon; Stimulus; System; Techniques; Time; Touch sensation; Ultrasonography; Unconscious State; Wakefulness; Water; Work; auditory stimulus; basal forebrain; behavioral response; deep learning; density; experimental study; extracellular; frontal lobe; goal oriented behavior; imaging system; improved; innovation; kinematics; motor behavior; neural; neural circuit; neuromechanism; novel; optogenetics; recruit; response; restoration; sensory stimulus; sound; temporal measurement; tongue root

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.

项目概要 监测脑损伤后恢复意识过程中向清醒状态的转变至关重要， 麻醉，以及那些意识改变的 COVID-19 幸存者。然而，我们有一个不精确的 了解与受试者醒来时行为变化相关的神经动力学。我们之前的工作 发现刺激巨细胞前核（aNGC）可促进从昏迷样状态中苏醒 状态。我们建议通过 aNGC 招募多种唤醒途径作为触发广泛的唤醒途径 激活导致觉醒。值得注意的是，aNGC 激活增加了额叶运动皮层活动， 尽管处于高度麻醉状态，但仍通过调节 aNGC 至额叶运动皮层通路恢复了完全活动能力 浓度暴露。我们还表明，从不同的昏迷状态中苏醒的动物有一个共同点 皮质和运动唤醒的动态过程，可以从深到高唤醒一致排序 水平。我们确定了五个皮质周期，用于追踪低血糖昏迷和 一系列麻醉剂，无论是吸入还是注射，以及传统的翻正反射测定。基于这些 研究结果表明，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 区分反射性运动和有目的运动的意识度量。我们假设皮质 将神经反应性与定义行为联系起来的测量是一种适用的方法，可以 将意识恢复的分析扩展到监测反射运动之外。 我们的建议加深了我们对皮质神经亚型、神经元通路的贡献的理解 aNGC 引起的额叶运动皮层活动的潜在变化，以及区分的时间动态 在我们的啮齿动物低唤醒模型中，自发行为的启动是反射性的。此外，我们将建立 解开这些行为转变的皮质模式。由于无意识的病理状态是 差异很大，对普通恢复有清晰的了解有助于更好地理解 皮质活动和行为损伤造成的变异性。因此，我们将确定神经受损的程度 回路影响已建立的皮层活动路径和行为恢复背后的动态。拟议的 因此，研究意义重大，因为它们将建立机械对应关系，检查激活 神经通路及其动态与习惯性和有意行为相关，揭示了新颖的、医学上的 相关生物标志物促进对麻醉苏醒期间的唤醒状态进行强有力的推断 脑损伤后。