Neural synchronization of human frontoparietal cortex

描述（由申请人提供）：神经活动在工作记忆（WM）表征的维持期间持续存在，并且被认为通过多个神经系统的协调，随着时间的推移和跨大脑区域整合感知和动作。然而，在理解WM协调大规模大脑网络的神经机制方面存在根本性的差距。这种知识的差距是一个关键问题，因为一系列的精神和神经症状源于原发性WM功能障碍。这项工作的长期目标是了解高级认知通过皮层感觉和运动功能的时间整合而出现的机制。该提案的目标是测试新模型，以了解神经元振荡的同步如何提供一种神经机制，用于构建支持认知的神经网络中不同节点之间的经常性相互作用。该项目的主要目的是使用颅内脑电图（iEEG）记录，从患有难治性癫痫的人类患者的前额叶和后顶叶皮质中测试神经振荡和同步在高级认知中的作用的recet理论的几个关键预测。这项研究的基本原理是，随着我们更好地理解大规模网络中节点相互作用以产生高层次认知的机制，我们将能够设计出理解精神疾病的基础，治疗和预防的策略。我们的目标将是测试，完善，并可能反驳，神经同步理论的原则，并将通过追求三个具体目标来实现：1）确定在WM维护期间神经振荡持续存在的频率; 2）测试WM维护是否增强了振荡的额顶叶耦合; 3）确定不同频段的神经振荡如何相互作用。基于执行记忆引导扫视任务的患者的额叶和顶叶皮质表面上的硬膜下电极记录的神经活动的强有力的初步数据证明了申请人手中的项目目标的可行性。在目标1下，伽马和阿尔法波段振荡是延迟周期（即，WM相关）以及空间选择性（即，双边化）。在目标2下，额叶和顶叶皮层的神经振荡在WM维持期间同步。在目标3下，在WM维持期间，低频振荡的相位调制高频振荡的功率。该方法是创新的，因为它利用了在额叶和顶叶皮层上具有硬膜下电极的极其罕见的患者群体，并且依赖于具有必要的灵敏度和时间分辨率的神经信号的iEEG记录来直接测试最近的神经同步理论。这项研究意义重大，因为它有望测试神经振荡如何在人脑中构建计算和通信的关键模型，从而提供一个全面的理论框架，临床研究人员可以在此框架内制定诊断和治疗精神和神经疾病的策略。 公共卫生相关性：这项拟议中的研究与公共卫生有关，因为我们对前额叶和顶叶皮层沟通和施加执行控制的机制的理解的进步对于阐明病理大脑中可能出错的机制是必要的。具体而言，拟议的研究与NIH的使命相关，因为它有望推进一个更强大的理论框架，临床研究人员可以在此框架内制定诊断和治疗精神和神经系统疾病的策略。

DESCRIPTION (provided by applicant): Neural activity persists during the maintenance of working memory (WM) representations and is thought to integrate perception and action over time and across brain areas through the coordination of multiple neural systems. Yet, there is a fundamental gap in understanding the neural mechanisms by which WM coordinates large-scale brain networks. This gap in knowledge is a critical problem because a host of psychiatric and neurologic symptoms stem from a primary WM dysfunction. The long-term goal of this work is to understand the mechanisms by which high-level cognition emerges through the temporal integration of sensory and motor functions across the cortex. The proposal's objective is to test new models of how the synchronization of neuronal oscillations may provide a neural mechanism for structuring recurrent interactions between different nodes in neural networks that support cognition. The central aim of the project is to test several critical predictions from recet theories of the role of neural oscillations and synchrony in high-level cognition using intracrania electroencephalography (iEEG) recordings from the prefrontal and posterior parietal cortices of human patients with pharmacologically intractable epilepsy. The rationale for the proposed research is that, as we better understand the mechanisms by which nodes in large-scale networks interact to give rise to high-level cognition, we will then be able to devise strategies fr understanding the basis, treatment, and prevention of mental disease. The objective will be to test, refine, and possibly refute, tenets of neural synchronization theories and will be accomplished by pursuing three specific aims: 1) Identify the frequencies at which neural oscillations persist during WM maintenance; 2) Test if WM maintenance enhances oscillatory frontal-parietal coupling; and 3) Determine how neural oscillations in different frequency bands interact. Strong preliminary data based on neural activity recorded from subdural electrodes on the surface of the frontal and parietal cortices of patients performing a memory guided saccade task demonstrate the feasibility of project aims in the applicant's hands. Under aim 1, gamma and alpha band oscillations were delay period (i.e., WM related) as well as spatially selective (i.e., contralateralized). Under aim 2, neural oscillations in frontal and parietal cortex synchronized during WM maintenance. Under aim 3, the phase of low frequency oscillations modulated the power of high frequency oscillations during WM maintenance. The approach is innovative because it capitalizes on an extremely rare population of patients with subdural electrodes over frontal and parietal cortex and relies on iEEG recording of neural signals that have the requisite sensitivity and temporal resolution to directly test recent theories of neural synchronization. The proposed research is significant because it is expected to test critical models of how neural oscillations structure computation and communication in the human brain thereby providing a thorough theoretical framework within which clinical researchers can develop strategies for the diagnosis and treatment of psychiatric and neurologic disorders. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because advancement in our understanding of the mechanisms by which the prefrontal and parietal cortex communicates and exerts executive control is necessary to illuminate the mechanisms that could go awry in the pathological brain. Specifically, the proposed research is relevant to NIH's mission because it is expected to advance a stronger theoretical framework within which clinical researchers can develop strategies for the diagnosis and treatment of psychiatric and neurologic disorders.