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

基本信息

批准号：
10597068
负责人：
MATTHEW V CHAFEE
金额：
$ 32.06万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
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/10597068
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 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 behavioral response cognitive training early psychosis improved indexing neural neurophysiology neurotransmission nonhuman primate pharmacologic psychosis risk response

项目摘要

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.

项目摘要：项目1 项目1的目的是使用非人类灵长类动物检查前额叶的本地本地电路并分布与状态相关的网络障碍代表与患者相关的功能障碍精神病。支持状态的计算网络代表AIM 1中的过程。通过测量动作电位时间（“尖峰”）中的时间相关性来测量神经相互作用 AIM 2中的神经元之间的突触相互作用阻止NMDA受体（NMDAR），该受体诱导了一段时间。在DPX决策任务期间，猴子犯了类似的行为错误模式精神分裂症。（后顶皮层和背纹状体）在此期间同时？猴子执行DPX和匪徒任务，使我们能够索引状态估计，状态学习和状态稳定过程。我们将发现如何减少NMDAR突触传输在额叶网络中的神经元之间，导致状态的计算失败代表过程。为了提供我们可以在人类中记录的神经信号的桥梁，我们将记录反映的神经信号微观的脑活动（单神经元动作电位），中尺度（A 皮质区域）和宏观（跨皮质区域的局部田间电势和脑电图），来自优先皮质和连接的结构同时使用因果发现分析来识别可以可以在人类中找到更有限的神经生理技术（对于项目3和4）项目4确定了特定的认知训练方案，以改善状态估计和稳定性患有早期精神病的人，项目1将对猴子进行反式翻译以识别训练引起的神经生理学吸引力网络参数的变化（微型，中和宏观）电路）。