Investigating Computation and Communication in Multi-Scale Brain Networks

描述（由申请人提供）：本提案旨在阐明多尺度脑网络中的跨水平耦合（CLC），即表征不同时空脑组织水平之间的相互作用，特别关注单个神经元的峰值与它们所嵌入的大规模动态功能网络的分布式活动之间的联系。该项目将澄清多尺度耦合的本质，并研究这些相互作用可以控制的因果机制。本研究的一个关键动机是，多尺度CLC可能为创伤性脑损伤或中风后的康复治疗和设计新的临床干预设备提供新的途径。重要的是，该项目采用了脑机接口（BMI）研究中使用的实时、慢性、多位点、高密度微电极阵列记录技术，并结合了新的建模和分析方法。这种方法最近被用于证明多个脑区之间的振荡相位耦合协调单个神经元的峰值以及解剖上分散的功能细胞组合（Canolty等，2010，PNAS）。这些结果表明，大规模网络活动的动态模式可能有助于调节神经元集合，为多尺度大脑网络中的功能相互作用提供了一个引人注目的例子。本研究以这些结果为基础，旨在进一步表征多尺度脑网络中相互作用的功能作用，它们对任务条件和各种其他实验操作的依赖性，并通过电刺激的因果干预来研究CLC的外部控制潜力。第一个具体目标是针对CLC的特征，研究CLC在多尺度脑网络中如何在不同行为任务、不同神经元群、长时间学习和操作性条件反射的压力下发生变化。第二个目标是针对中脑细胞的控制，研究使用电刺激直接映射网络连接的可行性，并通过引入不同模式的振荡网络耦合来因果影响神经元的活动和行为。总之，这两个目标为一个充满活力的新研究议程提供了焦点，以一种可能被证明对有效临床应用的发展立即有用的方式，针对CLC令人兴奋但知之甚少的现象。

DESCRIPTION (provided by applicant): This proposal seeks to elucidate cross-level coupling (CLC) in multi-scale brain networks - that is, characterizing interactions between different spatial and temporal levels of brain organization, with a particular focus on the connection between spiking in single neurons and the distributed activity of the large-scale, dynamic functional networks in which they are embedded. This project will clarify the nature of multi-scale coupling and investigate causal mechanisms by which these interactions can be controlled. A key motivation for this research is that multi-scale CLC may provide a novel route for rehabilitative therapies and the design of new devices for clinical intervention following traumatic brain injury or stroke. Importantly, this project employs the real-time, chronic, multi-site, high-density microelectrode array recording techniques used in brain-machine interface (BMI) research combined with novel modeling and analysis methods. This approach was recently used to demonstrate that oscillatory phase coupling between multiple brain areas coordinates the spiking of single neurons as well as anatomically-dispersed functional cell assemblies (Canolty, et al., 2010, PNAS). These results, showing that dynamic patterns of large-scale network activity may serve to regulate neuronal ensembles, provide a striking example of functional interactions in multi-scale brain networks. This proposal builds on these results with the aim of further characterizing the functional role of interactions in multi-scale brain networks, their dependence on task conditions and various other experimental manipulations, and investigates the potential for external control of CLC via causal intervention using electrical stimulation. The first specific aim, targeting characterization of CLC, investigates how CLC in multi-scale brain networks changes across different behavioral tasks, between distinct neuronal groups, over extended periods of learning, and under pressure from operant conditioning. The second aim, targeting control of CLC, investigates the feasibility of using electrical stimulation to directly map network connectivity and causally influence neuronal activity and behavior by entraining different patterns of oscillatory network coupling. Together, these two aims provide the focus for a vigorous new research agenda targeting the exciting but poorly understood phenomenon of CLC in ways that may prove immediately useful in the development of effective clinical applications. PUBLIC HEALTH RELEVANCE: A greater understanding of the mechanisms and functions of cross-level coupling (CLC) in multi-scale brain networks - together with methods by which it can be controlled - will facilitate the development of stimulation- based clinical devices and rehabilitative therapies to aid recovery following traumatic brain injury or stroke. This project is therefore positioned to provide answers to fundamental questions in neuroscience concerning the dynamics of multi-scale brain networks while simultaneously improving the quality of life for large numbers of neurological patients.