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是由N-甲基D- 天冬氨酸（NMDA）受体功能减退。在研究领域标准（RDoC）中， 国家精神卫生研究所，精神病的特点，这也可以暂时产生， 给予NMDA受体拮抗剂的健康正常受试者属于认知系统领域。内 这个领域、听觉感知和处理速度与所提出的工作最相关。研究 专注于精神病和精神病脆弱性中这种认知系统的异常功能 受试者群体可以增加对这些症状的理解。 脑电图（EEG）具有很大的潜力，以阐明潜在的联系， 功能减退和疾病症状。伽马（30- 80 Hz）振荡已知是由快速- 棘波中间神经元和锥体神经元微回路，和NMDA受体在快速- 刺激中间神经元活动使用频谱分解分析EEG，频率特异性振荡， 包括伽马波段在内的信号可以在毫秒的基础上被隔离和提取。听觉稳态 ASSR常用于研究精神分裂症患者受损的EEG伽马振荡。这些任务使用 以固定频率的重复听觉刺激的短持续时间序列（例如，每隔25 ms或40 Hz） 用同样的频率做ASSR特别是，40-Hz ASSR通常在诱发反应中降低 功率和表现出更多的振荡相位变异性，或减少相位同步，在试验中， 精神分裂症这些缺陷也在一级亲属和临床高血压患者中观察到。 精神病风险（Risk）最近，来自ASSR的两个额外的措施已经证明， 对精神病病理生理学的敏感性这些措施是：（1）自发伽马波段功率在前， 刺激基线期，这是异常升高的精神分裂症，和（2）40-Hz ASSR振荡 相位角，这在精神分裂症中明显延迟。 在9个实验室先前进行的一系列研究中，我们收集了40 Hz ASSR， 慢性病（即病程> 5年）精神病患者，早期疾病（即病程<= 5年）精神病 患者、受试者和广泛年龄范围的健康对照。我们建议将这些 来自1000多名男性和女性（12-61岁）的现有EEG数据，跨诊断和 健康谱该项目将通过使用ASSR相位延迟和自发 （基线）伽马功率比较精神病疾病的阶段。这两者之间的任何联系 伽马测量和幻觉症状评级，神经心理学处理速度测试， 年龄或性别将被确定。将在CHR中评估对40 Hz ASSR的纵向影响。

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.