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

与精神病相关的幻觉和认知障碍可能由N-甲基-D-天冬氨酸支持 天冬氨酸(NMDA)受体功能低下。在由开发的研究领域标准(RDoC)内 国家精神卫生研究所，精神病疾病的特征，也可以在 健康受试者给予NMDA受体拮抗剂，属于认知系统范畴。在 这一领域、听觉感知和处理速度与拟议的工作最相关。研究 重点阐述了这种认知系统在精神病和精神病易感性方面的异常功能 受试者群体可能会增加对这些症状的理解。 脑电(EEG)在阐明NMDA受体之间的潜在联系方面具有巨大的潜力 功能减退和疾病症状。已知伽马(30-80赫兹)振荡是由快速- 刺激性中间神经元和锥体神经元微电路和NMDA受体在快速反应中起重要作用 中间神经元活性激增。使用频谱分解来分析脑电，特定频率的振荡， 包括伽马波段，都可以在毫秒的基础上被分离和提取。听觉稳态 反应(ASSR)经常被用来研究精神分裂症患者受损的脑电伽马振荡。这些任务使用 以固定频率(例如，每25毫秒或40赫兹)进行短持续时间的重复听觉刺激 相同频率的ASSR。具体地说，40赫兹的ASSR通常在诱发反应中被降低 功率，并在试验中显示出更多的振荡相位变异性或降低的相位同步 精神分裂症。这些缺陷也在一级亲属和处于临床高点的个人中观察到。 精神病的风险(CHR)。最近，从ASSR派生的两个额外指标已经证明 对精神病病理生理学的敏感性。这些措施是：(1)地震前的自然伽马能带功率。 刺激基线周期，它在精神分裂症中异常升高；(2)40赫兹ASSR振荡 相角，这在精神分裂症患者中明显延迟。 在之前对9个实验室进行的一系列研究中，我们从以下地点收集了40赫兹的ASSR 慢性病(即5年病程)精神病患者、早期疾病(即病程5年)精神病患者 患者、慢性阻塞性肺疾病受试者和广泛年龄范围的健康对照。我们建议将这些 现有的超过1000名男性和女性(12-61岁)的脑电数据，跨越诊断和 健康谱。该项目将通过使用ASSR相位延迟和自发来扩展先前的工作 (基线)比较精神病疾病阶段的伽马功率。它们之间的任何关联 伽马测量和幻觉症状分级，神经心理测试处理速度， 年龄或性别将会确定。40赫兹ASSR的纵向影响将在CHR中进行评估。

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.