Neural connectivity and dysconnectivity in schizophrenia: EEG and fMRI studies

精神分裂症的神经连接和连接失调：脑电图和功能磁共振成像研究

• 批准号: 8698377
• 负责人: Judith M Ford
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698377
• 关键词: Acoustics; Address; Affect; Age; Algorithms; Area; Attention; Auditory; Auditory Hallucination; Auditory area; Biological; Biological Neural Networks; Brain; Brain imaging; Brain region; Budgets; Characteristics; Cognitive; Cognitive deficits; Data; Devices; Drops; Electroencephalography; Emotional; Environment; Esthesia; Failure; Functional Magnetic Resonance Imaging; Functional disorder; Gender; Goals; Hallucinations; Healthcare; Label; Learning; Literature; Medical; Metabolic; Methodology; Methods; Mind; Morbidity - disease rate; Outcome; Outcome Measure; Patients; Pattern; Performance; Periodicity; Phase; Population; Process; Psychiatric therapeutic procedure; Psychotic Disorders; Recruitment Activity; Reporting; Research Personnel; Rest; SWI1; Scanning; Schizophrenia; Seeds; Sensory; Series; Signal Transduction; Sorting - Cell Movement; Source; Speech; Stimulus; Symptoms; Task Performances; Testing; Time; Verbal Auditory Hallucinations; Veterans; Visual Cortex; Voice; Work; awake; base; blood oxygen level dependent; experience; long term memory; memory process; mortality; novel; relating to nervous system; research study; response; sound; therapy development; tool

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.

描述（由申请人提供）： 古老的格言“闲置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，“闲置的头脑”不仅很忙，而且可能忙着重播以前的活动或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，其中缓慢变化的活动在大脑的大区域之间在时间上相关。 DMN 表示受试者清醒且警觉，但不参与目标导向任务的状态。它可以被认为是探照灯，扫描内部和外部环境，或者作为独立于刺激、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。它可以被认为是聚光灯，抑制执行手头任务所不需要的一切。精神分裂症的典型症状可能与闲置大脑的紊乱有关，包括在任务需要时难以从闲置状态切换到工作状态以及幻听。 以静息状态活动作为我们的概念起点，我们建议使用脑电图+功能磁共振成像数据来研究（1）静息状态活动与任务表现之间的相互作用，（2）静息状态活动期间听觉和视觉皮层对探针的反应， （3）自发行为对静息状态活动的影响，所有这些都是为了阐明精神分裂症的病理生理学。 为了解决这个问题，我们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者的脑电图 + 功能磁共振成像。第一个涉及执行图词匹配任务，第二个涉及在静息扫描期间呈现音调和棋盘探针，第三个涉及说话。 (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，未能退出 DMN 并参与 TMN 将导致患者任务表现不佳。 (2) 休息是幻听（AVH）的理想状态，因为它们经常在休息时发生。我们的试验数据表明，在休息期间，DMN 会募集听觉皮层，尤其是出现幻觉的患者，并且可能使听觉皮层相对难以接触到外部声音。我们预测，在所有受试者的 DMN 活动高峰期间，音调和棋盘的处理都会受到损害，其中幻觉患者的音调处理受到的影响更大，因为他们将听觉皮层招募到 DMN 中。 (3) 在说话过程中，听觉皮层与 DMN 脱离，这可能会使其对我们内部对话的声学体验和我们自己讲话的声音反应不那么敏感。这可能是由于伴随放电机制的成功作用，而该机制在患者中功能失调。我们预测精神分裂症的这种模式会被打破。 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影响。