General Anesthetics and Cerebral Cortical Sensory Integration

全身麻醉与大脑皮层感觉统合

基本信息

  • 批准号:
    8609575
  • 负责人:
  • 金额:
    $ 30.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1997
  • 资助国家:
    美国
  • 起止时间:
    1997-08-01 至 2016-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this project is to understand the mechanisms by which general anesthetics remove consciousness and allow its return during emergence. Our general hypothesis is that anesthetics remove consciousness by disrupting the functional integration across cortical neuronal networks. The proposed project builds upon our decade-long investigation into the systems neuroscience mechanisms of anesthesia. In our previous work, we focused on the effect of volatile anesthetics on the power and coherence of gamma oscillations, and on their preferential role in cortico-cortical feedback vs. feedforward signaling as a putative neuronal correlate of unconsciousness. Here we extend this work to test the hypothesis for the first time that loss and return of consciousness (righting reflex) in anesthetized rats correlates with reversible, nonlinear transitions in functional connectivity, complexity, and information capacity of the neuronal network. To this end, we will study the concentration-dependent effect of three representative anesthetic agents with substantially different pharmacological profiles: desflurane, propofol, and dexmedetomidine to find a common, agent-invariant neuronal correlate of unconsciousness. As an alternative means of modulating the state of consciousness without changing the anesthetic drug effects, subcortical stimulation of the ascending activating system in the brainstem and basal forebrain will also be performed. Parallel spike trains and local field potentials will be recorded from visual and adjacent association cortices using chronically implanted multielectrode arrays in unrestrained rats, and excitatory and inhibitory connectivity, complexity and information capacity in neuronal networks during both spontaneous ongoing activity and during visual stimulation will be derived. The effect of anesthetics on avalanche dynamics of negative local field potential events will be determined. Local and long-range feedforward and feedback connectivity will be delineated with respect to their cortical layer-specificity. We hypothesize that the diversity of cortical states, ocal and interregional cortical connectivity, and interaction complexity are maximal in the awake, attentive state, reduced by anesthesia when consciousness is lost, reversed by cortical activation, and that the principal target of anesthetic action is feedback connectivity both within and among cortical regions. The proposed work should advance our understanding of the neural mechanism of anesthesia, and more generally, the neurobiological basis of consciousness at an integrative level. The findings should facilitate the development of novel methods for electrophysiological monitoring of the state of consciousness under anesthesia, and the development of new anesthetic agents with specific hypnotic effects.
描述(申请人提供):本项目的总体目标是了解全身麻醉剂清除意识并使其在苏醒时恢复的机制。我们的一般假设是,麻醉剂通过扰乱皮层神经元网络的功能整合来消除意识。这个拟议的项目建立在我们对麻醉的系统神经科学机制长达十年的研究基础上。在我们之前的工作中,我们集中在挥发性麻醉药对伽马振荡的功率和一致性的影响,以及它们在皮质反馈与前馈信号中的优先作用,作为一种假定的神经元无意识关联。在这里,我们将这项工作扩展到首次检验这一假说,即麻醉大鼠的意识丧失和恢复(翻正反射)与神经网络功能连通性、复杂性和信息能力方面的可逆、非线性转变相关。为此,我们将研究三种具有显著不同药理学特征的代表性麻醉剂的浓度依赖效应:地氟烷、异丙酚和右美托咪啶,以寻找一种共同的、不变的无意识神经元关联。作为一种在不改变麻醉药物效果的情况下调节意识状态的替代方法,还将对脑干和基底前脑的上行激活系统进行皮质下刺激。在自由状态的大鼠中,使用长期植入的多电极阵列,从视觉和相邻的联想皮层记录平行的棘波序列和局部场电位,并得出神经元网络在自发持续活动和视觉刺激期间的兴奋性和抑制性连接性、复杂性和信息容量。麻醉剂对负局域场电位事件雪崩动力学的影响将被确定。局部和远程前馈和反馈的连通性将根据它们的皮质层特异性来描述。我们假设,在清醒的注意力状态下,皮层状态的多样性、局部和区域间的皮质连通性以及相互作用的复杂性是最大的,当意识丧失时被麻醉降低,而被皮质激活逆转,麻醉作用的主要目标是两者内的反馈连通性。 在大脑皮层区域之间。这项拟议的工作应该会促进我们对麻醉的神经机制的理解,更广泛地说,在一个综合的水平上理解意识的神经生物学基础。这一发现将有助于开发新的方法来监测麻醉下的意识状态,并开发具有特定催眠作用的新麻醉剂。

项目成果

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Anthony George Hudetz其他文献

Anthony George Hudetz的其他文献

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{{ truncateString('Anthony George Hudetz', 18)}}的其他基金

Neuroimaging of Anesthetic Modulation of Human Consciousness
人类意识麻醉调节的神经影像学
  • 批准号:
    8577913
  • 财政年份:
    2013
  • 资助金额:
    $ 30.6万
  • 项目类别:
Neuroimaging of Anesthetic Modulation of Human Consciousness
人类意识麻醉调节的神经影像学
  • 批准号:
    8698776
  • 财政年份:
    2013
  • 资助金额:
    $ 30.6万
  • 项目类别:
Neuroimaging of Anesthetic Modulation of Human Consciousness
人类意识麻醉调节的神经影像学
  • 批准号:
    10188553
  • 财政年份:
    2013
  • 资助金额:
    $ 30.6万
  • 项目类别:
Neuroimaging of Anesthetic Modulation of Human Consciousness
人类意识麻醉调节的神经影像学
  • 批准号:
    8825523
  • 财政年份:
    2013
  • 资助金额:
    $ 30.6万
  • 项目类别:
Neuroimaging of Anesthetic Modulation of Human Consciousness
人类意识麻醉调节的神经影像学
  • 批准号:
    9033919
  • 财政年份:
    2013
  • 资助金额:
    $ 30.6万
  • 项目类别:
Neuroimaging of Anesthetic Modulation of Human Consciousness
人类意识麻醉调节的神经影像学
  • 批准号:
    9920153
  • 财政年份:
    2013
  • 资助金额:
    $ 30.6万
  • 项目类别:
Neuroimaging of Anesthetic Modulation of Human Consciousness
人类意识麻醉调节的神经影像学
  • 批准号:
    9075170
  • 财政年份:
    2013
  • 资助金额:
    $ 30.6万
  • 项目类别:
General Anesthetics and Cerebral Cortical Sensory Integration
全身麻醉与大脑皮层感觉统合
  • 批准号:
    10206336
  • 财政年份:
    1997
  • 资助金额:
    $ 30.6万
  • 项目类别:
VOLATILE ANESTHETICS AND CEREBRAL BLOOD FLOW REGULATION
挥发性麻醉剂与脑血流调节
  • 批准号:
    6019346
  • 财政年份:
    1997
  • 资助金额:
    $ 30.6万
  • 项目类别:
Anesthetics & cerebral cortical sensory integration
麻醉剂
  • 批准号:
    6687447
  • 财政年份:
    1997
  • 资助金额:
    $ 30.6万
  • 项目类别:
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