Secondary data analysis of auditory steady-state response to explore the RDoC cognitive system constructs across the psychosis spectrum

听觉稳态反应的二次数据分析，以探索整个精神病谱系的 RDoC 认知系统结构

• 批准号: 10333412
• 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: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10333412
• 关键词: Acoustic Stimulation; Address; Age; Attention; Auditory; Auditory Perception; Binding; Biological Assay; Biological Markers; Bipolar Disorder; Brain; Brain region; Bypass; Categories; Chronic; Chronically Ill; Clinical; Cognition; Cognitive; Cognitive deficits; Communication; Data; Data Analyses; Development; Diagnosis; Disease; Electroencephalography; Electrophysiology (science); Equilibrium; Event; Event-Related Potentials; Exhibits; Female; First Degree Relative; Frequencies; Functional disorder; Glutamates; Goals; Hallucinations; Human; Impaired cognition; Impairment; Individual; Interneurons; Interview; Ketamine; Laboratories; Link; MATRICS Consensus Cognitive Battery; Measures; Methods; Modeling; Motivation; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; National Institute of Mental Health; Neurons; Neuropsychology; Neurosciences; Parvalbumins; Pathologic; Patients; Perception; Phase; Play; Process; Psychoses; Pyramidal Cells; Reporting; Research; Research Domain Criteria; Rodent; Role; SCAP2 gene; Schizoaffective Disorders; Schizophrenia; Sensory; Series; Signal Transduction; Stimulus; Symptoms; System; Testing; Time; Training; Work; age related; antagonist; auditory processing; base; clinical high risk for psychosis; cognitive system; cognitive testing; falls; follow up assessment; follow-up; gamma-Aminobutyric Acid; glutamatergic signaling; high risk; hippocampal pyramidal neuron; insight; male; millisecond; neural circuit; normal aging; processing speed; psychosis risk; relating to nervous system; response; sex; sound; tool

Hallucinations and cognitive impairments associated with psychosis may be underpinned by N-methyl D- aspartate (NMDA) receptor hypofunction. Within the Research Domain Criteria (RDoC) developed by the National Institute of Mental Health, features of psychosis illness, which can also be transiently produced in healthy normal subjects given NMDA receptor antagonists, fall under the Cognitive System domain. Within this domain, auditory perception and processing speed are most relevant to the proposed work. Research focused on the abnormal functioning of this cognitive system in both psychosis and psychosis vulnerability subject groups may increase understanding of these symptoms. Electroencephalography (EEG) has great potential to elucidate the potential link between NMDA receptor hypofunction and symptoms of illness. Gamma (30-80Hz) oscillations are known to be generated by fast- spiking interneuron and pyramidal neuron microcircuits, and NMDA receptors play an important role in fast- spiking interneuron activity. Using spectral decomposition to analyze EEG, frequency-specific oscillations, including the gamma band, can be isolated and extracted on a millisecond basis. The auditory steady-state response (ASSR) is often used to study impaired EEG gamma oscillations in schizophrenia. These tasks use short-duration trains of repetitive auditory stimulation at a fixed frequency (e.g., every 25ms or 40-Hz) to evoke an ASSR at that same frequency. In particular, the 40-Hz ASSR is typically reduced in evoked response power and exhibits more oscillation phase variability, or reduced phase synchrony, across trials in schizophrenia. These deficits have also been observed in first-degree relatives and individuals at clinical-high risk (CHR) for psychosis. More recently, two additional measures derived from ASSR have demonstrated sensitivity to psychosis pathophysiology. These measures are (1) spontaneous gamma band power in the pre- stimulus baseline period, which is abnormally elevated in schizophrenia, and (2) the 40-Hz ASSR oscillation phase angle, which is significantly delayed in schizophrenia. In a series of previously conducted studies across 9 laboratories, we collected 40-Hz ASSRs from chronically ill (i.e. > 5 years duration) psychosis patients, early illness (i.e. <= 5 years duration) psychosis patients, CHR subjects, and a wide age range of healthy comparison controls. We propose to align these existing EEG data from over one thousand males and females (12-61 years old), across diagnoses and the wellness spectrum. This project will extend prior work by using ASSR phase delay and spontaneous (baseline) gamma power to compare stages of psychosis illness. Any association between these gamma measures and hallucination symptom ratings, neuropsychological speed of processing tests, age, or sex will be determined. Longitudinal effects on 40-Hz ASSR will be assessed in CHR.

与精神病相关的幻觉和认知障碍可能是由 N-甲基 D- 造成的 天冬氨酸 (NMDA) 受体功能减退。在由 RDoC 制定的研究领域标准 (RDoC) 内 国家心理健康研究所，精神病的特征，也可以在短期内产生 给予 NMDA 受体拮抗剂的健康正常受试者属于认知系统领域。之内 这个领域、听觉感知和处理速度与拟议的工作最相关。研究 重点关注该认知系统在精神病和精神病脆弱性中的异常功能 受试者群体可能会增加对这些症状的了解。 脑电图 (EEG) 具有阐明 NMDA 受体之间潜在联系的巨大潜力 功能减退和疾病症状。已知伽马（30-80Hz）振荡是由快速产生的 尖峰中间神经元和锥体神经元微电路和 NMDA 受体在快速 中间神经元活动激增。使用频谱分解来分析脑电图、特定频率振荡、 包括伽玛波段，可以在毫秒的基础上分离和提取。听觉稳态 反应（ASSR）通常用于研究精神分裂症患者脑电图伽玛振荡受损。这些任务使用 以固定频率（例如，每 25 毫秒或 40 赫兹）进行短时重复听觉刺激以唤起 同一频率的 ASSR。特别是，40 Hz ASSR 的诱发反应通常会降低 功率并表现出更多的振荡相位可变性，或减少的相位同步，在试验中 精神分裂症。这些缺陷也在临床高水平的一级亲属和个人中观察到。 精神病的风险（CHR）。最近，来自 ASSR 的另外两项措施已证明 对精神病病理生理学的敏感性。这些措施是（1）自发伽马带功率在预 刺激基线期，在精神分裂症中异常升高，以及 (2) 40 Hz ASSR 振荡 相位角，在精神分裂症中显着延迟。 在之前在 9 个实验室进行的一系列研究中，我们收集了来自以下机构的 40 Hz ASSR： 慢性病（即病程 > 5 年）精神病患者、早期患病（即病程 <= 5 年）精神病 患者、CHR 受试者以及各种年龄范围的健康对照。我们建议调整这些 来自超过 1000 名男性和女性（12-61 岁）的现有脑电图数据，涵盖诊断和 健康谱。该项目将通过使用 ASSR 相位延迟和自发性来扩展先前的工作 （基线）伽马功率用于比较精神病的阶段。这些之间的任何关联 伽玛测量和幻觉症状评级，处理测试的神经心理学速度， 年龄或性别将被确定。对 40 Hz ASSR 的纵向影响将在 CHR 中进行评估。