Multistable Dynamics of Connected Cortical Networks: Mechanisms and Modulation

连接皮质网络的多稳态动力学：机制和调制

• 批准号: 8803947
• 负责人: Flavio Frohlich
• 金额: $ 21.96万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-25 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8803947
• 关键词: Area; Autistic Disorder; Axon; Biological; Biology; Brain; Cognition; Communication; Computer Simulation; Data; Development; Electrophysiology (science); Exhibits; Feedback; Fostering; Goals; Health; Human; Hybrid Computers; Hybrids; Impairment; Individual; Injection of therapeutic agent; Life; Mental Depression; Mental disorders; Mission; Modeling; Neurobehavioral Manifestations; Neurologic; Neurons; North Carolina; Outcome Study; Patients; Pattern; Phase; Property; Public Health; Research; Role; Schizophrenia; Shapes; Slice; System; Testing; Time; Universities; Work; base; design; electric field; improved; innovation; novel; novel strategies; optogenetics; public health relevance; relating to nervous system

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.

描述（由申请人提供）：认知需要皮层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。 由单个神经元的轴突形成的远程投射（LRP）可能为跨皮质网络出现宏观活动模式提供了机制。 然而，尚不清楚表现出大量传播延迟的 LRP 如何支持跨网络活动的时间精确协调和同步。 长期目标是开发非侵入性脑刺激范例，以恢复皮质区域之间受损的沟通。 这里的目标是通过大规模计算机模拟驱动的新型生物计算机混合系统来阐明 LRP 在两个连接的皮层网络动力学中的因果作用，并确定非侵入性脑刺激范例来调节互连皮层的动力学网络。 工作假设是：(1) LRP 的传播延迟创建了一个由同步和不同步活动状态组成的多稳态景观，(2) 两个网络的同步经颅交流电刺激 (tACS) 将诱导向持续同步状态的转变由于网络多稳定性而终止刺激后。 这项工作的基本原理是，了解非侵入性脑刺激如何调节互连网络的同步将能够合理设计新颖的脑刺激范例，从而增强大规模功能网络中的同步和信息流。 将追求以下两个具体目标来检验工作假设：（1）确定远程预测（LRP）在互连皮质网络中宏观活动状态出现中的作用，以及（2）阐明同时经颅交替由 LRP 连接的两个网络的电流刺激（tACS）会改变宏观活动状态。 我们的方法是创新的，因为它将计算机模拟、切片电生理学、光遗传学和反馈控制结合在一起，构建了一个在混合系统中研究 LRP 的平台，该平台表现出生物学合理性，但能够实现 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有助于开发 tACS 范式，该范式直接针对以断开连接为特征的精神和神经疾病患者中互联皮层网络受损的相互作用动态。