Understanding Executive Function and Dysfunction in Schizophrenia through Cortical Oscillatory Dynamics

认知表现被认为对精神分裂症患者的日常社会心理功能至关重要，而执行功能（EF）被认为是最关键的缺陷之一。由于概念和方法上的问题，对EF缺陷的本质及其在明显精神病理学中的作用的理解仍然是有限的。健康个体和精神分裂症患者的血流动力学和电磁成像结果表明，脑区域和活动模式参与EF，但神经元网络通信转化为EF的机制尚不清楚。理解机制似乎对理解精神分裂症的功能失调EF至关重要。拟议的项目旨在通过绘制健康个体和精神分裂症患者的振荡动力学神经元网络通信来识别和模拟支持EF的机制。磁电和脑电图活动将在选择激活EF的任务中进行监测，并结合先进的方法来绘制振荡动力学。假设包括(1)振荡动力学是跨越前额叶和后脑区的（局部）功能特异性神经元回路之间（整体）和（局部）内部通信的关键；(2)定义区域之间的神经元同步反映了一种被认为是协调过程基础的主动采样机制；(3)任务相关动力学随基线状态而变化，从而可以预测任务相关的大脑功能和行为表现模式。(4)精神分裂症患者正在进行的和任务相关的振荡动力学之间的关系被破坏，导致主动采样能力不足和EF不足。任务选择是基于EF的分类和已发表的区分EF相关方面的建议，基于将MEG和EEG测量与EF的工作记忆维持和干扰控制方面联系起来的证据，以及我们的工作证据，支持振荡动力学假设作为各自功能的表现。我们希望这项工作能够支持EF的性质和组织的概念建模，阐明振荡活动在正常和异常认知中的作用，并提高对与认知功能障碍相关的精神分裂症中神经元网络通信中断的理解。这将反过来支持对精神分裂症精神病理学发展潜在基础的关键振荡动力学的建模。这些发现将具有诊断和治疗的双重应用。

Cognitive performance is viewed as essential to daily psychosocial function in schizophrenia, with executive function (EF) considered one of the most critical areas of deficit. Understanding the nature of EF deficits and their role in manifest psychopathology is still considered as limited, handicapped by problems of concept and method. Hemodynamic and electromagnetic imaging results in healthy individuals and schizophrenia patients have suggested brain regions and activity patterns as involved in EF, but the mechanism of translation of neuronal network communication into EF remains unclear. Understanding mechanisms seem critical to understanding dysfunctional EF in schizophrenia. The proposed project seeks to identify and model mechanisms supporting EF by mapping neuronal network communication via oscillatory dynamics in healthy individuals and schizophrenia patients. Magneto- and electroencephalographic activity will be monitored in tasks selected to activate EF, and advanced methods are combined for mapping oscillatory dynamics. Hypotheses include (1) oscillatory dynamics are key in communication between (global) and within (local) function-specific neuronal circuits spanning prefrontal and posterior regions subserving EF, (2) neuronal synchrony between defined regions reflects an active sampling mechanism thought to be fundamental in coordinated processes, (3) task-related dynamics vary with baseline state such that patterns of task-related brain function and behavioral performance can be predicted, (4) the relationship between ongoing and task-related oscillatory dynamics is disrupted in schizophrenia, contributing to deficient active sampling capacity and deficient EF. Task selection is based on EF taxonomies and published recommendations for distinguishing relevant facets of EF, on evidence connecting MEG and EEG measures to the working memory maintenance and interference control facets of EF on which we focus here, and on evidence from our work supporting the hypothesis of oscillatory dynamics as a manifestation of the respective functions. We expect this work to support conceptual modeling of the nature and organization of EF, to clarify the role of oscillatory activity in both normal and abnormal cognition, and to improve understanding of disruption in neuronal network communication in schizophrenia associated with dysfunctional cognition. This will in turn support modeling of the critical oscillatory dynamics potentially fundamental to the development of schizophrenia psychopathology. Such findings would have both diagnostic and therapeutic applications.