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.

项目摘要 在脑损伤后恢复意识的过程中，监测向清醒的过渡是至关重要的， 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的行为变化有关的神经动力学。我们以前的工作 发现刺激前神经细胞核（aNGC）可以促进从昏迷样状态中唤醒， 状态我们建议通过aNGC招募多种唤醒途径，作为触发广泛的 激活导致清醒。值得注意的是，aNGC激活增加了额叶运动皮层的活动， 尽管高度麻醉，但通过调节aNGC至额叶运动皮质通路恢复了完全活动性 浓度暴露。我们还发现，从不同昏迷状态中出现的动物有一个共同的 皮层和运动唤醒的动态过程，可以从深度唤醒到高度唤醒一致地排序 程度.我们确定了五个皮质期，追踪低血糖昏迷和低血糖昏迷中恢复的运动行为。 一系列麻醉剂，无论是吸入或注射，以及传统的翻正反射测定。基于这些 研究结果，我们假设恢复清醒是一个共同的渐进过程，其中皮质模式包含 区分反射性和有目的性运动的意识度量。我们假设大脑皮层 将神经反应性与定义的行为联系起来的测量是一种适用的方法， 将对意识恢复的分析扩展到监测反射运动之外。 我们的提议加深了我们对皮质神经亚型，即神经元通路的贡献的理解。 潜在的aNGC诱导的额叶运动皮层活动的变化，以及区分 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 解释这些行为转变的大脑皮层模式由于无意识的病理状态是 非常异质，对普通复苏有一个清晰的理解有助于更好地理解 皮层活动和行为损伤造成的变异性。因此，我们将确定受损的神经元 神经回路影响已建立的皮层活动通路和动力学，这些通路和动力学是行为恢复的基础。拟议 因此，研究是有意义的，因为它们将建立机械对应，检查激活 神经通路及其动力学与习惯性和有意的行为有关，揭示了新的，医学上 相关生物标志物，其促进在麻醉苏醒期间对觉醒状态的稳健推断， 脑损伤后