Predictive Functions and Neural Mechanisms of Spontaneous Cortical Activity

自发皮质活动的预测功能和神经机制

基本信息

  • 批准号:
    10572486
  • 负责人:
  • 金额:
    $ 19.41万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-05-01 至 2027-04-30
  • 项目状态:
    未结题

项目摘要

The mammalian cortex is spontaneously active even in the absence of external stimuli. Initially dismissed as neural noise, pioneering work established that the internal brain states produced by spontaneous activity are highly structured and responsible for the dramatic variability in both neural and perceptual responses to the same sensory stimulus. The discovery that varying spontaneous cortical states (SCS) drive different responses to identical stimuli suggested that altered perceptions of the environment across psychiatry could derive from aberrant SCS. On this basis, ongoing resting state fMRI studies continue to search for reproducible links between SCS and psychiatric diagnoses, including schizophrenia, depression, and PTSD, among others. Yet our fundamental understanding of the cognitive processes and circuit mechanisms underlying SCS remains limited. One leading theory, drawn from human fMRI recordings during visual detection tasks, suggests that SCS represent predictions about the environment. In this model, predictive spontaneous cortical states influence perceptual decision making on the basis of prior beliefs. However, several critical gaps remain in this theory. At present, there is no causal evidence, either through closed-loop behavior or direct neural modulation, linking SCS to perceptual decisions. Moreover, the circuit mechanisms of SCS, including the role of interneurons in producing SCS and specific cortical areas in driving spontaneous cortex-wide states, are completely unknown. My proposal aims to address these knowledge gaps by investigating SCS in a mouse model. Having trained mice in a two-alternative forced choice visual detection task, I have applied optical imaging of the dorsal cortex to find that specific spontaneous states predict behavioral response. Leveraging my preliminary data, I will investigate how specific interneuron types contribute to SCS (Aim 1), test the causal influence of predictive SCS over perceptual decisions through a closed-loop behavior (Aim 2), and apply optogenetic modulation of neural activity to test the role of a specific cortical area, the retrosplenial cortex, in driving predictive SCS (Aim 3). The proposed studies will offer novel insights into the neurocognitive mechanisms underlying spontaneous activity, including in human resting state fMRI. In the process, I will supplement my background in human resting state neuroimaging with critical training in rodent behavior, psychophysics methods, and optogenetics. My proposal will be guided by a world-class advisory committee consisting of my primary mentor Dr. Karl Deisseroth, an expert in optogenetics and animal behavior, Dr. Michael Stryker, a mouse visual system expert, Dr. Brian Wandell, an expert in perceptual decision making, Dr. Robert Malenka, a rodent nervous system expert, and Dr. Nolan Williams, an expert in human neuromodulation. I will further take full advantage of the vibrant training environment at Stanford by engaging in targeted coursework and high-quality professional development. By the end of the fellowship, I will be positioned to launch a career as an independent investigator studying how the neurocognitive processes embedded in spontaneous activity contribute to psychiatric illness.
哺乳动物的大脑皮层即使在没有外界刺激的情况下也是自发活动的。最初被驳回, 神经噪声,开创性的工作建立了自发活动产生的内部大脑状态, 高度结构化,并负责神经和感知反应的戏剧性变化, 感官刺激发现不同的自发皮层状态(SCS)驱动不同的反应, 相同的刺激表明,精神病学对环境的感知改变可能来自于 异常脊髓束在此基础上,正在进行的静息状态功能磁共振成像研究继续寻找可重复的联系, SCS和精神病诊断,包括精神分裂症、抑郁症和创伤后应激障碍等。然而我们的 对SCS的认知过程和电路机制的基本理解仍然有限。 一个领先的理论,从人类在视觉检测任务中的功能磁共振成像记录中得出, 代表了对环境的预测。在这个模型中,预测性自发皮层状态影响 基于先前信念的感性决策。然而,这一理论中仍然存在几个关键的空白。在 目前,没有因果关系的证据,无论是通过闭环行为或直接的神经调制,连接 SCS到知觉决策。此外,SCS的电路机制,包括中间神经元在 在驱动自发的全皮层状态中产生SCS和特定的皮层区域是完全未知的。 我的建议旨在通过在小鼠模型中研究SCS来解决这些知识缺口。已经培训 在小鼠的二选一强迫选择视觉检测任务中,我应用了背侧皮层的光学成像 发现特定的自发状态可以预测行为反应。利用我的初步数据,我会 研究特定的中间神经元类型如何促进SCS(目标1),测试预测SCS的因果影响 通过闭环行为(Aim 2)进行感知决策,并将神经元的光遗传学调制应用于 活动,以测试特定皮质区域(压后皮质)在驱动预测性SCS中的作用(目标3)。 这些研究将为自发性神经认知机制提供新的见解。 活动,包括在人类静息状态的功能磁共振成像。在这个过程中,我将补充我在人类休息方面的背景知识 在啮齿动物行为,心理物理学方法和光遗传学方面进行严格的培训。我 我的建议将由一个世界级的咨询委员会指导,该委员会由我的主要导师卡尔·戴瑟罗斯博士组成, 光遗传学和动物行为学专家迈克尔斯特赖克博士,小鼠视觉系统专家布莱恩博士 温德尔博士,一位知觉决策专家,罗伯特·马伦卡博士,一位啮齿动物神经系统专家,和罗伯特·马伦卡博士。 诺兰威廉姆斯,人类神经调节专家。我将进一步充分利用充满活力的培训 在斯坦福大学的环境,通过从事有针对性的课程和高质量的专业发展。由 结束的奖学金,我将被定位为启动职业生涯作为一个独立的调查研究如何 自发活动中的神经认知过程会导致精神疾病。

项目成果

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Anish Mitra其他文献

Anish Mitra的其他文献

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{{ truncateString('Anish Mitra', 18)}}的其他基金

An fMRI investigation of propagated intrinsic activity in early development and autism
早期发育和自闭症中传播的内在活动的功能磁共振成像研究
  • 批准号:
    9247037
  • 财政年份:
    2014
  • 资助金额:
    $ 19.41万
  • 项目类别:
An fMRI investigation of propagated intrinsic activity in early development and autism
早期发育和自闭症中传播的内在活动的功能磁共振成像研究
  • 批准号:
    8833464
  • 财政年份:
    2014
  • 资助金额:
    $ 19.41万
  • 项目类别:
An fMRI investigation of propagated intrinsic activity in early development and autism
早期发育和自闭症中传播的内在活动的功能磁共振成像研究
  • 批准号:
    8926704
  • 财政年份:
    2014
  • 资助金额:
    $ 19.41万
  • 项目类别:

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