Spike Timing Defects and State Representation Impairments in Nonhuman Primates

非人类灵长类动物的尖峰计时缺陷和状态表征损伤

• 批准号: 10377364
• 负责人: MATTHEW V CHAFEE
• 金额: $ 35.54万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10377364
• 关键词: Action Potentials; Anatomy; Area; Back; Behavior Control; Behavioral; Belief; Biology; Brain; Cells; Clinical; Cognition; Cognitive deficits; Corpus striatum structure; DNA Sequence Alteration; Data; Decision Making; Defect; Dorsal; Electrodes; Electroencephalography; Equilibrium; Exhibits; Failure; Functional disorder; Genetic; Human; Impaired cognition; Impairment; Individual; Learning; Link; Measures; Mediating; Monkeys; N-Methyl-D-Aspartate Receptors; Neural Network Simulation; Neuronal Plasticity; Neurons; Noise; Parietal; Parietal Lobe; Patients; Pattern; Perception; Perceptual Disorders; Persons; Pharmacology; Play; Prefrontal Cortex; Process; Production; Psychoses; Regimen; Role; Schizophrenia; Series; Signal Transduction; Silicones; Structure; Symptoms; Synapses; Synaptic Receptors; Synaptic Transmission; Techniques; Testing; Thinking; Time; Training; Translating; base; behavioral response; cognitive training; early psychosis; improved; indexing; neurophysiology; neurotransmission; nonhuman primate; psychosis risk; relating to nervous system

PROJECT SUMMARY: PROJECT 1 The purpose of PROJECT 1 is to use nonhuman primates to examine prefrontal local circuit and distributed network impairments associated with state representation dysfunctions of relevance to individuals with psychosis. PROJECT 1 will relate synaptically mediated functional interactions between neurons in prefrontal networks to computations that support state representation processes. In Aim 1, we will quantify functional neural interactions by measuring temporal correlations in the timing of action potentials (‘spikes’) imposed by synaptic interactions between the neurons. In Aim 2, we will disrupt those interactions by pharmacologically blocking NMDA receptors (NMDAR), which induces a period of transient cognitive impairment during which monkeys commit similar patterns of behavioral errors during the DPX decision-making task as do people with schizophrenia. We will record neural activity in prefrontal cortex and anatomically connected brain areas (posterior parietal cortex and the dorsal striatum) concurrently during the period of cognitive impairment, while monkeys perform the DPX and Bandit tasks, which allow us to index state estimation, state learning, and state stability processes. We will discover how reducing NMDAR synaptic transmission alters functional interactions between neurons in prefrontal networks, leading to computational failures in state representation processes. To provide a bridge to neural signals that we can record in humans, we will record neural signals that reflect brain activity at the microscale (single neuron action potentials), mesoscale (local field potentials within a cortical area) and macroscale (local field potentials and EEG across cortical areas) from prefrontal cortex and connected structures simultaneously. We will use causal discovery analysis to identify the parameters that can be found with more limited neurophysiological techniques available in humans (for PROJECTS 3 and 4). As PROJECT 4 identifies specific cognitive training regimens that improve state estimation and state stability in individuals with early psychosis, PROJECT 1 will back-translate these paradigms to monkeys to identify training-induced changes in attractor network parameters at the neurophysiological (micro-, meso- and macro- circuit) levels.

项目概要：项目1 项目1的目的是使用非人灵长类动物来检查前额局部回路和分布的 与个体相关的状态表征功能障碍相关的网络损伤， 精神病项目1将涉及前额叶皮层神经元之间的突触介导的功能相互作用。 网络到支持状态表示过程的计算。在目标1中，我们将量化功能 神经相互作用，通过测量动作电位（“尖峰”）的时间相关性， 神经元之间的突触相互作用。在目标2中，我们将通过药理学方法破坏这些相互作用 阻断NMDA受体（NMDAR），这会诱导一段时间的短暂认知障碍， 猴子在DPX决策任务中犯下的行为错误模式与人类相似。 精神分裂症我们将记录前额叶皮层和解剖学上相连的大脑区域的神经活动 （后顶叶皮层和背侧纹状体）同时在认知障碍期间，而 猴子执行DPX和Bandit任务，这使我们能够索引状态估计，状态学习和状态 稳定过程。我们将发现减少NMDAR突触传递如何改变功能性相互作用 前额叶网络中的神经元之间，导致状态表示过程中的计算失败。 为了提供一个桥梁，我们可以记录在人类的神经信号，我们将记录神经信号， 微尺度（单神经元动作电位）、中尺度（局部场电位）的脑活动 皮层区域）和宏观尺度（局部场电位和跨皮层区域的EEG）， 同时连接结构。我们将使用因果发现分析来确定可以 在人类可用的更有限的神经生理学技术中发现（对于项目3和4）。作为 项目4确定了特定的认知训练方案，可以改善状态估计和状态稳定性， 对于患有早期精神病的个体，项目1将把这些范式反向翻译到猴子身上， 训练引起的神经生理学（微观，中观和宏观）吸引子网络参数的变化 电路）水平。