Multiscale physiology and causal mechanisms of slow network fluctuations

摘要：项目(P)3的总体目标被归入中心目标3：推进 使用人类和人类的中、微观尺度测量对宏观尺度结果的生理学解释 国家卫生保健计划。要做到这一点，P3将依靠NHPS作为动物模型系统来告知对人类的解释 大尺度神经成像(P1)和中尺度颅内记录研究(P2)和生物物理模拟 (P4)。NHP的工作将提供，1)同步的头皮EEG/fMRI，行为-认知和自主神经数据 三种常见的任务和条件：多模式注意、看电影和休息，2)刷子和层状排列 用于定义微观细胞回路和生理过程的记录，以及3)化学发生的靶点 操纵。目标1将P1的宏观测量与慢脑的中、微观生理联系起来 网络波动(SBNF)，通过定义分布在不同脑区的SBNF，包括 内感系统和经典的外感系统，丘脑皮质听觉系统。建议 研究将包括在任务积极和任务之间的多个站点的同时录音 负面网络。这将允许检验SBNFS需要相反的单位和LFP激活的假设 任务积极网络和任务消极网络的水平，与前岛叶皮质相关的关键部位 SBNF网络从“不稳定”的激活模式切换到更多任务参与的激活模式。目标2将定义流程 以及触发和调制SBNF动力学的结构。在这里，我们将首先从药理上增加 在P1中，通过哌醋甲酯的唤醒与人类研究有直接联系。我们还将电刺激 迷走神经对胆碱能和多巴胺能系统等神经网络的影响 联觉系统。最后，在使用电刺激进行初步测距研究后，我们将进行 前岛叶皮质(AIC)向前扣带皮质投射的可逆性化学发生失活 (ACC)和基底核(NB)，以检验关于这些通路在SBNF控制中的作用的假说 动力学。P3将提供从神经生理神经元记录到EEG和fMRI的关键信息 告知P4中详细的单元电路和网络建模，以及P1和P2中的人体研究。

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.