Investigating Computation and Communication in Multi-Scale Brain Networks

描述（由申请人提供）： 该提案旨在阐明多尺度脑网络中的跨水平耦合（CLC）-即表征大脑组织的不同空间和时间水平之间的相互作用，特别关注单个神经元中的尖峰与它们嵌入其中的大规模动态功能网络的分布式活动之间的联系。这个项目将阐明多尺度耦合的本质，并研究控制这些相互作用的因果机制。这项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临床干预新设备的设计提供一种新的途径。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，结合新颖的建模和分析方法。这种方法最近被用于证明多个脑区域之间的振荡相位耦合协调单个神经元以及解剖学上分散的功能细胞组装体的尖峰（Canolty等人，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，为多尺度脑网络中的功能相互作用提供了一个引人注目的例子。该提案建立在这些结果的基础上，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，并研究通过使用电刺激的因果干预对CLC进行外部控制的潜力。第一个具体的目标，针对CLC的特性，研究如何在不同的行为任务，不同的神经元群体之间，在长时间的学习，并在压力下操作性条件反射的多尺度脑网络中的CLC的变化。第二个目标，CLC的靶向控制，研究了使用电刺激直接映射网络连接的可行性，并通过夹带不同模式的振荡网络耦合来因果地影响神经元的活动和行为。总之，这两个目标提供了一个充满活力的新的研究议程的重点，针对令人兴奋的，但知之甚少的现象CLC的方式，可能会立即证明有效的临床应用的发展是有用的。 公共卫生相关性： 对多尺度脑网络中跨水平耦合（CLC）的机制和功能的更深入了解-以及可以控制它的方法-将促进基于刺激的临床设备和康复治疗的发展，以帮助创伤性脑损伤或中风后的恢复。因此，该项目旨在为神经科学中有关多尺度脑网络动态的基本问题提供答案，同时提高大量神经系统患者的生活质量。

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.