Multiscale physiology and causal mechanisms of slow network fluctuations

慢网络波动的多尺度生理学和因果机制

• 批准号: 10639546
• 负责人: CHARLES E SCHROEDER
• 金额: $ 73.77万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-15 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10639546
• 关键词: Animal Model; Anterior; Archives; Area; Arousal; Attention; Auditory system; Automobile Driving; Back; Basal Nucleus of Meynert; Behavioral; Biological Models; Brain; Cells; Cognitive; Coupling; Data; Data Set; Electric Stimulation; Electroencephalography; Electrophysiology (science); Functional Magnetic Resonance Imaging; Genetic; Goals; Human; Implant; Link; Measures; Medial geniculate body; Methods; Microscopic; Modeling; Neurobiology; Neurons; Pathway interactions; Pattern; Pharmaceutical Preparations; Physiological; Physiological Processes; Physiology; Prefrontal Cortex; Process; Pupil; Reaction Time; Rest; Ritalin; Role; Saccades; Scalp structure; Site; Structure; System; Testing; Thalamic structure; Update; Vagus nerve structure; Work; auditory pathway; behavior measurement; biophysical model; cholinergic; cingulate cortex; designer receptors exclusively activated by designer drugs; electrical microstimulation; functional magnetic resonance imaging/electroencephalography; genetic manipulation; interest; movie; network models; neural network; neuroimaging; neurophysiology; novel; parabrachial nucleus; pharmacologic; vagus nerve stimulation

ABSTRACT: The overarching goal of Project (P) 3 is subsumed under Center Aim 3: Advance the physiological interpretation of macroscale findings using meso- and microscale measures in humans and NHPs. To do so, P3 will rely on NHPs as an animal model system to inform the interpretation of human macroscale neuroimaging (P1) and mesoscale intracranial recording studies (P2) and the biophysical modeling (P4). NHP work will provide, 1) simultaneous scalp EEG/fMRI, behavioral-cognitive and autonomic data under three common tasks and conditions: intermodal attention, movie watching and rest, 2) brush and laminar array recordings to define the microscopic cell circuits and physiological processes, and 3) targets for chemogenetic manipulation. Aim 1 will link the macroscale measures of P1 meso- and microscale physiology of slow brain network fluctuations (SBNFs), by defining SBNFs across distributed brain areas, including both the interoceptive system and a classic exteroceptive system, the thalamocortical auditory system. Proposed studies will include simultaneous recordings from multiple sites within and across task positive and task negative networks. This will allow testing the hypothesis that SBNFs entail opposing unit and LFP activation levels in task positive and task negative networks, with the anterior insular cortex a key site associated with SBNF network switching from ‘restive’ to more task engaged activation patterns. Aim 2 will define processes and structures triggering and modulating SBNF dynamics. Here, we will first pharmacologically increase arousal via Methylphenidate as a direct link to human studies in P1. We will also electrically stimulate the Vagus Nerve which impacts on neural networks including cholinergic and dopaminergic system and the interoceptive system. Finally, after initial range-finding studies using electrical µ-stimulation, we will conduct reversible chemogenetic inactivation of anterior insular cortex (AIC) projections to the anterior cingulate cortex (ACC) and nucleus basalis (NB) to test hypotheses on the roles of these pathways in control of SBNF dynamics. P3 will provide crucial information from neurophysiological neuronal recordings to EEG and fMRI informing the detailed cell-circuit and network modeling in P4 and the human studies in P1 and P2.

摘要：项目（P）3的总体目标在中心目标下包含 使用人类和微观措施的宏观结果的生理解释 NHP。为此，P3将依靠NHP作为动物模型系统来告知人类的解释 宏观神经影像学（P1）和颅内记录研究（P2）和生物物理模型 （P4）。 NHP工作将提供1）简单的头皮脑电图/fMRI，行为认知和自主数据下 三个常见的任务和条件：联想的关注，电影观看和休息，2）刷和层流阵列 定义微观细胞电路和物理过程的记录，以及3）化学发生的目标 操纵。 AIM 1将链接慢性脑P1中和微观生理学的宏观测量 网络波动（SBNF），通过定义分布式大脑区域的SBNF，包括 感受性系统和经典的扩展​​系统，即丘脑皮层听觉系统。建议的 研究将包括来自任务正面和跨任务中多个站点的简单录音 负网络。这将允许测试SBNF需要相反单元和LFP激活的假设 任务正面和任务负面网络的水平，前岛皮层与关键站点相关联 SBNF网络从“静止”转换为更多的任务激活模式。 AIM 2将定义流程 以及触发和调节SBNF动力学的结构。在这里，我们将在药理学上首先增加 唤醒通过哌醋甲酯作为与P1人类研究的直接联系。我们还将电刺激 迷走神经会影响神经网络，包括胆碱能和多巴胺能系统以及 感受性系统。最后，在使用电µ刺激的初始范围调查研究之后，我们将进行 前岛状皮层（AIC）向前扣带回皮层的可逆化学发生灭活（AIC） （ACC）和Bassalis核（NB）测试这些途径在控制SBNF中的作用的假设 动力学。 P3将提供从神经生理学神经元记录到脑电图和fMRI的重要信息 在P4和P2中的P4和人类研究中告知详细的细胞电路和网络建模。