Neural synchronization of human frontoparietal cortex

描述(申请人提供)：在维持工作记忆(WM)表征的过程中，神经活动持续存在，并被认为通过多个神经系统的协调，随时间和跨大脑区域整合感知和行动。然而，在理解WM协调大规模大脑网络的神经机制方面存在着根本性的差距。这种知识上的差距是一个严重的问题，因为许多精神和神经学症状源于原发的WM功能障碍。这项工作的长期目标是了解高级认知通过整个大脑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的模型，即神经元振荡的同步如何提供一种神经机制，用于在支持认知的神经网络中构建不同节点之间的经常性交互。该项目的中心目标是使用来自药物难治性癫痫患者的前额叶和后顶叶皮质的脑内脑电(IEEG)记录，测试Recet理论中关于神经振荡和同步性在高级认知中的作用的几个关键预测。这项研究的基本原理是，当我们更好地理解大规模网络中的节点相互作用以产生高级认知的机制时，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。其目的将是测试、提炼并可能驳斥神经同步理论的原理，并将通过追求三个具体目标来实现：1)确定WM维持期间神经振荡持续的频率；2)测试WM维持是否增强了振荡的额顶耦合；以及3)确定不同频段的神经振荡如何相互作用。基于执行记忆引导眼跳任务的患者额叶和顶叶皮质表面硬膜下电极记录的神经活动的强大初步数据表明，申请者手中的项目目标是可行的。在目标1下，伽马和阿尔法波段振荡是延迟周期(即与WM有关)以及空间选择性(即对侧)。在目标2下，WM维持期间额叶和顶叶皮质的神经振荡是同步的。在目标3下，在WM维护期间，低频振荡的相位调制了高频振荡的功率。这种方法是创新的，因为它利用了极少数额叶和顶叶皮质上有硬膜下电极的患者，并依赖于iEEG记录的神经信号，这些信号具有必要的灵敏度和时间分辨率，可以直接测试最近的神经同步理论。这项拟议的研究意义重大，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其中制定诊断和治疗精神和神经疾病的策略。 公共健康相关性：拟议的研究与公共健康相关，因为我们有必要进一步了解前额叶和顶叶皮质沟通和实施执行控制的机制，以阐明可能在病理性大脑中出错的机制。具体地说，这项拟议的研究与NIH的使命相关，因为它有望推进一个更强大的理论框架，在此框架下，临床研究人员可以制定诊断和治疗精神和神经疾病的策略。

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.