Secondary data analysis of existing data to explore the RDoC construct of agency across the psychosis spectrum using fMRI and EEG

使用 fMRI 和 EEG 对现有数据进行二次数据分析，探索整个精神病谱系的 RDoC 代理结构

• 批准号: 9884515
• 负责人: Judith M Ford
• 金额: $ 7.67万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-12 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9884515
• 关键词: Address; Age; Animals; Auditory; Auditory area; Awareness; Behavior; Biological Assay; Brain; Cerebellum; Cerebral cortex; Clinical; Cognitive; Conscious; Data; Data Analyses; Delusions; Diagnosis; Electroencephalography; Elements; Esthesia; Event-Related Potentials; Failure; Feedback; Female; First Degree Relative; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Hallucinations; Hearing; Human; Lead; Liquid substance; Magnetic Resonance Imaging; Mediating; Modeling; Morbidity - disease rate; Motor; Movement; Patients; Phenotype; Process; Psychotic Disorders; Research Domain Criteria; Rest; Role; Sampling; Schizophrenia; Seeds; Sensory; Severities; Side; Site; Source; Suggestion; Symptoms; System; Thalamic structure; Unconscious State; Work; Youth; associated symptom; base; bipolar patients; expectation; experience; high risk; male; mortality; psychotic symptoms; sound; transmission process; vocalization

Cardinal symptoms of psychotic illnesses, such as delusions and hallucinations, are associated with high morbidity and mortality, motivating efforts to understand their pathophysiology. These symptoms may be underpinned by misperceptions and misinterpretations of sensations that result from a basic inability to recognize that you are the agent of the self-generated experiences you are having. If mechanisms underlying agency are dysfunctional, sensations that should have been predicted, but were not, might take on inappropriate salience and lead to the construction of delusional cognitive schema to explain aberrant experience. Abnormal functioning of this agentive system may characterize psychosis and psychosis vulnerability. Very move we make is accompanied by a copy of the motor plan that generates an expectation of its sensory consequences, which is then compared to the actual sensation. Through this comparison process errors are detected and corrected. This is likely done by rapid cerebellar side loops, out of awareness. Vocalization is used to study this comparison process across the animal kingdom. In all cases, auditory responsiveness is suppressed during vocalizing compared to when the sound is coming from other sources. In humans, this is seen as suppression of the N1 component of the EEG-based event-related potential, emanating from auditory cortex. Consistent with suggestions of deficits in this mechanism in schizophrenia, we have shown that suppression of N1 during vocalizing is reduced in psychosis and psychosis vulnerability. When N1 is decomposed into its basic elements, specifically theta band power and inter-trial coherence (ITC), suppression of theta ITC is more sensitive to psychosis and delusions. We propose to use suppression of N1 and theta ITC during vocalization as assays of agency. In a large multi-site study, we used resting state magnetic resonance imaging (fMRI) data to calculate functional connectivity and found that psychosis is associated with hypo-connectivity between thalamus and cerebellum, especially in patients with delusions. We propose to extend this work using cerebellar seeds derived from agentive tasks (vocalizing and pressing a button to hear a tone), and relate cerebellar dysconnectivity to psychotic symptoms associated with dysfunctions of agency and EEG assays of agency. We propose to align existing resting state fMRI and EEG-based vocalization data from two sites, from males and females (12-62 years old), across diagnoses and the wellness spectrum: clinical high-risk youth, schizophrenia, schizoaffective, psychotic bipolar patients and their 1st degree relatives, and healthy controls.

精神病的主要症状，例如妄想和幻觉，与高 发病率和死亡率，激发人们努力了解其病理生理学。这些症状可能是 由于基本无能力而导致对感觉的误解和误解 认识到你是你所拥有的自我生成体验的代理人。如果潜在的机制 代理功能失调，本来应该预测但没有预测到的感觉可能会出现 不恰当的突出并导致构建妄想认知图式来解释异常 经验。该代理系统功能异常可能是精神病和精神病的特征 脆弱性。 我们所做的每一个举动都附有一份运动计划的副本，该计划产生了对其的期望 感官后果，然后与实际感觉进行比较。通过这个比较过程 错误被检测并纠正。这很可能是在无意识的情况下由快速的小脑侧循环完成的。 发声用于研究动物界的这种比较过程。在所有情况下，听觉 与声音来自其他来源时相比，发声期间的反应性受到抑制。在 人类，这被视为基于 EEG 的事件相关电位的 N1 分量的抑制， 从听觉皮层发出。与精神分裂症这一机制存在缺陷的建议一致，我们 研究表明，发声过程中 N1 的抑制会减少精神病和精神病脆弱性。 当 N1 分解为其基本元素，特别是 theta 频段功率和试验间相干性 (ITC) 时， 抑制 theta ITC 对精神病和妄想更加敏感。我们建议使用抑制 发声期间的 N1 和 theta ITC 作为代理分析。 在一项大型多中心研究中，我们使用静息态磁共振成像 (fMRI) 数据来计算 功能连接性，发现精神病与丘脑和丘脑之间的连接性低下有关 小脑，尤其是有妄想症的患者。我们建议使用小脑种子来扩展这项工作 源自主动任务（发声和按下按钮听到声音），并将小脑联系起来 与代理和脑电图检测功能障碍相关的精神病症状的脱节 机构。 我们建议将来自两个站点的现有静息状态 fMRI 和基于 EEG 的发声数据进行对齐， 男性和女性（12-62 岁），跨诊断和健康范围：临床高危青少年， 精神分裂症、分裂情感性、精神病双相情感障碍患者及其一级亲属，以及健康对照。