Neural connectivity and dysconnectivity in schizophrenia: EEG and fMRI studies

描述（由申请人提供）： 古老的格言“空闲的头脑是魔鬼的游乐场”正在受到神经科学家的挑战，他们报告说，“空闲的头脑”不仅忙碌，而且可能还忙碌于重播之前的活动或将最近学到的材料巩固为长期记忆。大脑在默认模式网络（DMN）中空闲，其中缓慢变化的活动在大脑的大区域之间具有时间相关性。DMN表示受试者清醒和警觉但不参与目标导向任务的状态。它可以被认为是一盏探照灯，扫描内部和外部环境，或者是刺激独立的，自我参照的思想来源。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，抑制一切不必要的执行手头的任务。精神分裂症的特征性症状可能与空转大脑中的干扰有关，包括在任务需要时难以从空转切换到齿轮，以及听觉语言幻觉。 以静息态活动为出发点，我们拟利用EEG+fMRI数据研究（1）静息态活动与任务绩效之间的相互作用，（2）静息态活动时听觉和视觉皮层对探针的反应性，（3）自我启动行为对静息态活动的影响，旨在阐明精神分裂症的病理生理学。 为了解决这些问题，将在三个不同的实验中同时从70名精神分裂症患者和70名年龄和性别匹配的对照组中收集EEG + fMRI。第一个涉及执行图片-单词匹配任务，第二个涉及在休息扫描期间呈现音调和棋盘探测，第三个涉及谈话。 (1)我们的试验数据表明，EEG功率的波动反映了DMN的参与和脱离。我们预测，切换出DMN和从事TMN的失败将有助于病人的任务性能差的特点。(2)休息是听觉语言幻觉（AVH）的理想状态，因为它们经常发生在休息期间。我们的试验数据表明，在休息期间，DMN招募听觉皮层，特别是在产生幻觉的患者中，并且可能使听觉皮层相对难以接近外部声音。我们预测，在所有受试者的DMN活动的峰值期间，音调和棋盘格的处理将受到影响，其中音调处理在幻觉患者中受到更大的影响，因为他们将听觉皮层招募到DMN中。(3)在谈话过程中，听觉皮层与DMN分离，这可能使它对我们内部对话的声学体验和我们自己说话的声音反应更少。这可能是由于成功的行动的必然放电机制，这是功能失调的患者。我们预测在精神分裂症中这种模式会被打破。 每一个目标都致力于精神分裂症的病理生理学的异常静息状态活动的贡献。

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.