Neural connectivity and dysconnectivity in schizophrenia: EEG and fMRI studies

描述(由申请人提供)： 一句古老的谚语“闲置的头脑是魔鬼的游乐场”正受到神经学家的挑战，他们报告说，不仅“闲置的头脑”很忙，而且它可能忙于重温以前的活动，或者将最近学到的材料巩固到长期记忆中。大脑在默认模式网络(DMN)中闲置，在该网络中，缓慢变化的活动在大脑的大片区域之间具有时间相关性。DMN表示受试者处于清醒和警觉的状态，但不参与目标导向的任务。它可以被认为是一盏探照灯，扫描着内部和外部环境，或者是一种独立于刺激、自我参照的思想的来源。必要时，大脑可以从DMN切换到任务模式网络(TMN)。TMN表示专注于执行任务的注意力状态。它可以被认为是一个聚光灯，抑制了执行手头任务所不必要的一切。精神分裂症的特征症状可能是与空闲的大脑相关的障碍，包括当任务需要时难以从空闲状态切换到工作状态，以及听觉语言幻觉。以静息状态活动为概念起点，我们建议利用EEG+fMRI数据来研究(1)静息状态活动与任务绩效之间的相互作用，(2)静息状态活动中听觉和视觉皮质对探测的反应，以及(3)自我启动行为对静息状态活动的影响，旨在阐明精神分裂症的病理生理学。为了解决每个问题，将在三个不同的实验中同时收集70名精神分裂症患者和70名年龄和性别匹配的对照组的EEG+fMRI。第一个任务是完成图片-单词匹配任务，第二个任务是在静止扫描期间呈现音调和棋盘探头，第三个任务是交谈。(1)我们的试验数据表明，脑电功率的波动反映了与DMN的接触和脱离。我们预测，未能切换出DMN并参与TMN将导致患者较差的任务表现特征。(2)休息是听觉言语幻觉(AVH)的理想状态，因为它们经常发生在休息时。我们的试验数据表明，在休息时，DMN招募听觉皮质，特别是在出现幻觉的患者中，可能会使听觉皮质相对难以受到外部声音的影响。我们预测，在DMN活动的高峰期，所有受试者对音调和棋盘的处理都将受到影响，其中幻觉患者的音调处理受到的影响更大，因为他们将听觉皮质重新招募到DMN。(3)在说话过程中，听觉皮质脱离了DMN，这可能使它对我们内部对话的声音体验和我们自己的语音反应都变得不那么灵敏。这可能是由于推论放电机制的成功作用，而这在患者中是功能失调的。我们预测这种模式在精神分裂症中会崩溃。每个目标都涉及异常静息状态活动对精神分裂症病理生理学的贡献。

DESCRIPTION (provided by applicant): The old adage, "An idle mind is the devil's playground" is being challenged by neuroscientists who are reporting that not only is the "idle mind" busy, but it may be busy replaying previous activity or consolidating recently learned material into long term memories. The brain idles in a default mode network (DMN) in which slowly changing activity is temporally correlated between large areas of the brain. The DMN denotes a state in which the subject is awake and alert, but not involved in a goal directed task. It can be thought of as a searchlight, scanning the internal and external environment, or as a source of stimulus-independent, self-referential thought. When necessary, the brain can switch out of the DMN and into the task mode network (TMN). The TMN denotes a state of attention focused on performing a task. It can be thought of as a spotlight, suppressing everything not necessary for performing the task at hand. Characteristic symptoms of schizophrenia may be associated disturbances in the idling brain, including difficulties switching out of idle and into gear when tasks demand it and auditory verbal hallucinations. Using resting state activity as our conceptual starting point, we propose to use EEG+fMRI data to study (1) the interaction between resting state activity and task performance, (2) the responsiveness of auditory and visual cortex to probes during resting state activity, and (3) the effect of self-initiated actions on resting state activity, all with the goal of elucidating the pathophysiology of schizophrenia. To address each, EEG + fMRI will be collected simultaneously from 70 patients with schizophrenia and 70 age- and gender-matched controls during three different experiments. The first involves performing a picture-word matching task, the second involves presentation of tone and checkerboard probes during a resting scan, and the third involves talking. (1) Our pilot data suggest that fluctuations in EEG power reflect engagement and disengagement from DMN. We predict that failures to switch out of the DMN and engage the TMN will contribute to poor task performance characteristic of patients. (2) Rest is an ideal state for auditory verbal hallucinations (AVH) as they often occur during rest. Our pilot data suggest that during rest, DMN recruits auditory cortex, especially in patients who hallucinate, and may make auditory cortex relatively inaccessible to external sounds. We predict that processing of tones and checkerboards will be compromised during the peak of DMN activity in all subjects, with tone processing being more affected in hallucinating patients, because of their recruitment of auditory cortex into the DMN. (3) During talking, auditory cortex is disengaged from the DMN, perhaps making it both less responsive to the acoustic experience of our internal dialog and to the sounds of our own speech. This may be due to the successful action of the corollary discharge mechanism, which is dysfunctional in patients. We predict a break down in this pattern in schizophrenia. Each aim addresses the contribution of abnormal resting state activity to the pathophysiology of schizophrenia.