Distributed dynamics & cognition in a large-scale primate cortical circuit model

项目摘要 这项资助更新的目标是发展灵长类动物大脑皮层的理论和大规模电路建模 有许多相互关联的领域，用于分布式工作记忆和灵活的决策过程， 多巴胺调节这项研究计划旨在应对理解认知的挑战 超越局部回路，进入复杂的全球大脑。由于最近的一项研究， 可用的介观定向和加权数据的猕猴皮层区域间的连接。我们有 已经发表了几篇关于开发大规模多区域动态皮层回路的论文 猕猴模型，包括具有层状皮质结构的种群率模型和 尖峰网络模型我们的计算工作将与五个实验合作进行。 研究猕猴的实验室（厄尔米勒（麻省理工学院），约翰邓肯（牛津大学，英国），斯特凡埃弗林 （加拿大安大略西部大学）、亨利肯尼迪（法国里昂ISERM）和卡尔齐勒斯（于利希 University，德国））。具体目标1将是建立一个大规模的皮层电路模型， 猕猴的分布式工作记忆。假设：分布式自我维持活动 工作记忆的模式依赖于中观区域间联系的组合 在大脑的层次结构中，电路特性的性质和梯度。具体目标2将是 研究高层次的持续活动的高维动力学 时间变化假设：NMDA/AMPA受体比率在自上而下投射时高于 自下而上，短期塑性有一个宏观梯度。两者结合起来， 复杂的时空记忆神经群体活动，更好地描述了在一个 高维状态空间具体目标3将是扩展模型，以模拟决策- 基于规则的灵活感觉运动行为。假设：同一模型被赋予 不同的表示（空间位置，诸如颜色和运动方向的对象特征，规则编码， 在不同的皮层区域中，可以用来模拟基于规则的灵活决策任务， 工作记忆任务具体目标4将是研究神经调节和NMDA缺陷， 这个大规模的灵长类皮层模型。假设：多巴胺调制显示了一个宏观的 梯度沿着皮层层次，和NMDA受体的损伤优先影响自上而下 而不是在全球大脑中自下而上的信号传递。总的来说，拟议的研究将摆脱 对全球大脑中复杂动力学和认知功能的基本见解。它还将产生一个 开创性和强大的计算平台，用于大规模大脑系统的基础研究， 灵长类动物，以及精神疾病如精神分裂症的跨水平回路机制研究。

Project Summary The goal of this grant renewal is to develop theory and large-scale circuit modeling of the primate cortex with many interconnected areas, for distributed working memory and flexible decision processes as well as its dopamine modulation. This research program is designed to meet the challenge of understanding cognition beyond local circuits towards the complex global brain. The proposed work is now feasible thanks to recently available mesoscopic directed- and weighted data for inter-areal connections of macaque cortex. We have already published several papers on the development of a large-scale, multi-regional dynamical cortical circuit model of macaque monkey, including a population rate model endowed with a laminar cortical structure and a spiking network model. Our computational work will be undertaken in collaborations with five experimental labs working on macaque monkeys (Earl Miller (MIT), John Duncan (Oxford University, UK), Stefan Everling (Western University, Ontario, Canada), Henry Kennedy (ISERM, Lyon, France) and Karl Zilles (Jülich University, Germany)). Specific Aim 1 will be to build a large-scale cortical circuit model of macaque monkey for distributed working memory. Hypothesis: distributed self-sustained activity patterns underlying working memory depend on a combination of the mesoscopic inter-areal connection properties and gradients of circuit properties across a brain’s hierarchy. Specific Aim 2 will be to investigate high-dimensional dynamics of persistent activity underlying a high degree of temporal variations. Hypothesis: NMDA/AMPA receptor ratio is higher at top-down projections than bottom-up ones, and there is a macroscopic gradient of short-term plasticity. The two combined contribute to complex spatiotemporal mnemonic neural population activity that is better described by trajectories in a high-dimensional state space. Specific Aim 3 will be to expand the model to simulate decision- making and rule-based flexible sensorimotor behavior. Hypothesis: the same model endowed with different representations (spatial location, object features such as color and motion direction, rule encoding, respectively) in different cortical areas can be used to simulate rule-based flexible decision tasks as well as working memory tasks. Specific Aim 4 will be to study of neuromodulation and NMDA deficits of this large-scale primate cortical model. Hypothesis: dopamine modulation displays a macroscopic gradient along the cortical hierarchy, and impairment of NMDA receptors preferentially affects top-down rather than bottom-up signaling in the global brain. Taken together, the proposed research will shed fundamental insights into complex dynamics and cognitive functions in the global brain. It will also yield a pioneering and powerful computational platform for basic research on large-scale brain systems of the primates, as well as cross-level circuit mechanistic studies of psychiatric disorders like Schizophrenia.