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与n -甲基D-有关