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: 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
• 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

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私人检查前额叶本地电路并分发 与州代表性相关的网络障碍与患者相关的功能障碍 精神病。项目1将与前额叶中神经元之间的突触介导的功能相互作用有关 网络与支持状态表示过程的计算。在AIM 1中，我们将量化功能 通过测量动作电位时机（“尖峰”）中的临时相关性来测量神经相互作用 神经元之间的突触相互作用。在AIM 2中，我们将通过药物破坏这些相互作用 阻断NMDA受体（NMDAR），该受体引起了一段时间的瞬时认知障碍。 猴子在DPX决策任务中犯了类似的行为错误模式， 精神分裂症。我们将记录前额叶皮层和解剖上连接的大脑区域的神经元活动 （后顶皮层和背纹状体）在认知障碍期间同时，而 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。我们将发现减少NMDAR突触传输如何改变功能相互作用 在额叶网络中的神经元之间，导致状态表示过程中的计算故障。 为了提供通往我们可以在人类中记录的神经信号的桥梁，我们将记录反映的中性信号 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），来自前额叶皮层和 仅连接的结构。我们将使用因果发现分析来确定可以 可以在人类中使用更有限的神经生理技术（针对项目3和4）。作为 项目4确定了特定的认知训练方案，以改善国家估计和状态稳定性 患有早期精神病的人，项目1将将这些范式反向猴子反译成猴子 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）。