Defining the Electrophysiological Dynamics of the Default Mode Network

描述（由申请人提供）：人类默认网络（DN）内的异常活动模式，是一组功能连接的大脑区域，在内省思维期间参与，在感觉运动处理期间被抑制，与认知和行为障碍相关的神经精神疾病，如精神分裂症，抑郁症，自闭症谱系障碍或ADHD。例如，功能性磁共振成像（fMRI）研究表明，DN活动的异常模式可能在一定程度上与精神分裂症的思维障碍特征有关。功能性磁共振成像显示，在各种神经精神疾病状态下，DN功能障碍可能不是共同病理生理过程的结果。尽管有这种假设，但对DN的电生理动力学知之甚少，而这些信息对于在系统水平上理解异常功能的机制至关重要。本提案中概述的实验的总体目标是使用两种技术来定义DN的电生理动力学：1，皮质电图（ECoG），利用硬脑膜下ECoG电极植入的标准护理，在难治性癫痫患者的术前评估中；2，高频头皮脑电图（EEG）。具体目标1将使用ECoG来确定在诱发事件相关的内省、“自我参照”任务和语言任务引起的DN抑制期间DN内神经反应的快速和动态时间。在具体目标2中，我们将使用ECoG来表征DN与语言或任务正网络之间的相互作用，以阐明DN干扰任务表现的神经元机制。然而，ECoG的使用仅限于需要开颅手术暴露的人群。因此，在具体目标3中，我们将利用脑电图方法中的新方法，并使用ECoG作为金标准，检查脑电图将脑电活动定位到DN深部皮质区域的能力。基于他在功能成像方面的背景，我们设计了一个培训计划，并组建了一个由神经外科医生、神经学家和电生理学家组成的杰出团队，为候选人提供将电生理学纳入他的研究活动所必需的知识。未来多模式方法的应用，在精神病学人群中采用功能成像和电生理学来追求DN功能，为描述DN功能障碍的范围和对心理健康生物学基础的贡献提供了一种非常敏感的手段。

DESCRIPTION (provided by applicant): Abnormal patterns of activity within the human default network (DN), which is a constellation of functionally connected brain regions that is engaged during introspective thought and suppressed during sensorimotor processing, has been linked to the cognitive and behavioral impairments associated with host of neuropsychiatric disorders such as schizophrenia, depression, autism spectrum disorder or ADHD. For instance, functional magnetic resonance imaging (fMRI) studies have revealed that aberrant patterns of DN activity may in part orchestrate disordered-thinking characteristic to schizophrenia. DN dysfunction, as illuminated with fMRI, across various neuropsychiatric disease states is likely not a consequence of a shared pathophysiologic process. Despite this assumption, remarkably little is known about the electrophysiological dynamics of the DN, information that is crucial to a mechanistic understanding of abnormal function at a systems level. The overall goal of the experiments outlined in this proposal is to define the electrophysiological dynamics of the DN using two techniques: 1, electrocortiography (ECoG), capitalizing on the standard-of-care implantation of subdural ECoG electrodes in the presurgical evaluation of individuals with intractable epilepsy and 2, high frequency scalp-based electroencephalography (EEG). Specific Aim 1 will use ECoG to determine the rapid and dynamic timing of neural responses within the DN during an evoked event-related introspective, 'self-referential' task and during DN suppression engendered by a linguistic task. In Specific Aim 2, we will use ECoG to characterize the interactions between the DN and a language or task positive network to elucidate the neuronal mechanisms underlying DN interference on task performance. However, use of ECoG is limited to populations requiring craniotomies for surgical exposure. Therefore, in Specific Aim 3 we will capitalize on new approaches in EEG methodology and examine the ability of EEG to localize electrical activity to the deep cortical regions of the DN, using ECoG as the gold standard. Building upon his background in functional imaging, a training program has been designed and a distinguished team of neurosurgeons, neurologists and electrophysiologists has been assembled to provide the candidate with the knowledge necessary to incorporate electrophysiology into his research activities. The future application of a multimodal approach, employing both functional imaging and electrophysiology to the pursuits of DN function in psychiatric populations provides an exquisitely sensitive means of profiling the range and contributions of DN dysfunction to the biological basis of mental health.