Multistable Dynamics of Connected Cortical Networks: Mechanisms and Modulation

描述（由申请人提供）：认知需要皮质网络之间电活动的精确协调。 这种功能连接的损害与精神分裂症和抑郁症等精神疾病的认知症状有关。 由单个神经元轴突形成的长程投射（LRP）可能提供了跨皮层网络出现宏观活动模式的机制。 然而，它仍然是未知的LRP，表现出相当大的传播延迟，可以支持跨网络的活动的时间精确的协调和同步。 长期目标是开发非侵入性脑刺激范例，恢复皮层区域之间受损的通信。 这里的目的是阐明因果关系的作用LRP在两个连接的皮层网络的动态与一种新的生物学-计算机混合系统的动机大规模的计算机模拟，并确定非侵入性的脑刺激范例，以调节相互连接的皮层网络的动态。 工作假设是：（1）LRP的传播延迟创建了由同步和非同步活动状态组成的多稳态景观，以及（2）两个网络的同时经颅交流电刺激（tACS）将诱导过渡到同步状态，该同步状态在刺激终止后由于网络多稳态而持续存在。 这项工作的基本原理是，了解非侵入性脑刺激如何调节互联网络的同步，将使合理设计新的脑刺激范例，增强大规模功能网络中的同步和信息流。 以下两个具体目标将被追求来测试工作假设：（1）确定长程投射（LRP）在互联皮层网络中出现宏观活动状态中的作用，以及（2）阐明通过LRP连接的两个网络的同时经颅交流电刺激（tACS）如何改变宏观活动状态。 我们的方法是创新的，因为它汇集了计算机模拟，切片电生理学，光遗传学和反馈控制，以建立一个平台，用于研究混合系统中的LRP，该系统具有生物相容性， 对LRP进行精确的实验控制。 这项工作的意义在于，了解LRP在塑造互联网络动态中的因果作用，将使tACS范式的发展直接针对以断开连接为特征的精神和神经疾病患者的连接皮层网络的相互作用动力学受损。

DESCRIPTION (provided by applicant): Cognition requires precise coordination of electric activity between cortical networks. Impairment of such functional connectivity has been associated with cognitive symptoms in psychiatric illnesses such as schizophrenia and depression. Long-range projections (LRPs) formed by axons of individual neurons likely provide the mechanism for the emergence of macroscopic activity patterns across cortical networks. Yet, it remains unknown how LRPs that exhibit substantial propagation delays can support temporally precise coordination and synchronization of activity across networks. The long-term goal is to develop non-invasive brain stimulation paradigms that reinstate impaired communication between cortical areas. The objective here is to elucidate the causal role of LRPs in the dynamics of two connected cortical networks with a novel biology-computer hybrid system motivated by large-scale computer simulations and to identify non-invasive brain stimulation paradigms to modulate the dynamics of interconnected cortical networks. The working hypothesis is that (1) the propagation delays of the LRPs create a multistable landscape composed of both synchronized and unsynchronized activity states and (2) that simultaneous transcranial alternating current stimulation (tACS) of both networks will induce transitions to synchronized states that persist after termination of stimulation due to network multistability. The rationale for this work is that understanding how non-invasive brain stimulation modulates synchronization of interconnected networks will enable the rational design of novel brain stimulation paradigms that enhance synchronization and information flow in large-scale functional networks. The following two specific aims will be pursued to test the working hypothesis: (1) to determine the role of long-range projections (LRPs) in the emergence of macroscopic activity states in interconnected cortical networks and (2) to elucidate how simultaneous transcranial alternating current stimulation (tACS) of two networks connected by LRPs alters macroscopic activity state. Our approach is innovative since it brings together computer simulations, slice electrophysiology, optogenetics, and feedback control to build a platform for the study of LRPs in a hybrid system that exhibits biological plausibility yet enables precise experimental control over the LRPs. The significance of this works is that understanding the causal role of LRPs in shaping the dynamics of interconnected networks will enable the development of tACS paradigms that directly target impaired interaction dynamics of connected cortical networks in patients with psychiatric and neurological illnesses characterized by disconnectivity.