Multiscale physiology and causal mechanisms of slow network fluctuations

摘要：项目（P）3的总体目标包含在中心目标3中： 使用人类中尺度和微观尺度测量对宏观尺度结果进行生理学解释， NHP。为此，P3将依赖NHP作为动物模型系统，以告知对人类的解释。 宏观神经成像（P1）和中尺度颅内记录研究（P2）以及生物物理建模 （P4）。NHP的工作将提供，1）同步头皮EEG/fMRI，行为认知和自主数据， 三种常见的任务和条件：联运注意，看电影和休息，2）刷和层状阵列 记录以定义微观细胞回路和生理过程，以及3）化学发生的靶点。 操纵目标1将连接P1的宏观尺度测量、慢脑的微观尺度生理学和中观尺度生理学 网络波动（SBNFs），通过定义跨分布式大脑区域的SBNFs，包括 内感受系统和一个经典的外感受系统，丘脑皮层听觉系统。提出 研究将包括在任务内和跨任务的多个站点的同步记录， 负面网络这将允许测试SBNF需要相反单位和LFP激活的假设 任务积极和任务消极网络中的水平，前岛叶皮层是与 SBNF网络从“不稳定”转换到更多任务参与的激活模式。目标2将定义流程 以及触发和调节SBNF动力学的结构。在这里，我们将首先增加 通过哌醋甲酯唤醒作为P1中人类研究的直接联系。我们还将用电刺激 迷走神经影响神经网络，包括胆碱能和多巴胺能系统， 内感受系统最后，在使用电微刺激进行初步范围探索研究后，我们将进行 前岛叶皮质（AIC）向前扣带回皮质投射的可逆性化学发生失活 (ACC)和基底核（NB），以检验这些通路在SBNF控制中的作用的假设 动力学P3将提供从神经生理学神经元记录到EEG和fMRI的关键信息 为P4中的详细细胞回路和网络建模以及P1和P2中的人体研究提供信息。

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.