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

项目摘要 这次拨款更新的目标是发展灵长类皮质的理论和大规模电路模型。 具有许多相互关联的区域，用于分布式工作内存和灵活的决策过程以及其 多巴胺的调制。这个研究项目是为了迎接理解认知的挑战而设计的 超越局部回路，通向复杂的全球大脑。由于最近的工作，拟议的工作现在是可行的 猕猴皮质区域间连接的可用介观定向和加权数据。我们有 已经发表了几篇关于发展大规模、多区域动态大脑皮层环路的论文 猕猴模型，包括具有层状皮质结构的种群速率模型和 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(英国牛津大学)、斯特凡·埃弗林 (加拿大安大略省西部大学)、亨利·肯尼迪(法国里昂伊瑟姆)和卡尔·齐尔斯(Jülich 德国大学))。具体目标1将是建立一个大规模的大脑皮层电路模型 用于分布式工作记忆的猕猴。假设：分布式自我维持活动 工作记忆的基本模式取决于中观区域间连接的组合 整个大脑层次结构的电路特性的特性和梯度。具体目标2将是 研究持续活动的高维动力学，其背后的高度 时间上的变化。假设：在自上而下的预测中，NMDA/AMPA受体比率高于 自下而上，并且存在短期塑性的宏观梯度。这两个因素加在一起形成了 复杂的时空助记神经群体活动，更好地描述在一个 高维状态空间。具体目标3将是扩展模型以模拟决策- 制定和基于规则的灵活的感觉运动行为。假设：相同的模型被赋予了 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， 分别)可用于模拟基于规则的灵活决策任务以及 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质模型。假设：多巴胺的调制表现为宏观的 沿皮质层级的梯度，NMDA受体的损害优先影响自上而下 而不是在全球大脑中发出自下而上的信号。总而言之，拟议中的研究将不再是 对全球大脑中复杂的动力学和认知功能的基本见解。它还将产生一个 用于大规模脑系统基础研究的开创性和强大的计算平台 灵长类动物，以及精神分裂症等精神障碍的跨级电路机制研究。

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.