Characterizing State Representation Impairments in People with Early Psychosis

项目总结：项目3 项目3的目的是确定支持状态的信息处理中的故障如何 神经回路中的表征与早期精神病的临床异质性有关。为此，我们将：(A) 招募年龄16-30岁的早期精神病患者(N=125)和人口学上相似的健康对照组(N=125) 年；(B)确定DPX和BANDIT任务的重测可靠性，作为对国家代表性的评估 过程；(C)使用DPX和DPX表征基线的行为表现和神经生理学 在同步EEG-fMRI期间完成班迪特任务；(D)在患者接受常规护理的同时对他们进行6个月的跟踪，以 描述他们的临床轨迹；(E)在六个月后重复行为和EEG-fMRI评估 (每组保留100例)。我们获得的数据将使我们能够检查 临床和实验措施，并调查如何改变临床和实验 这些措施涉及疾病危急阶段的6个月时间段。 项目3的总体目标是允许人类的神经宏观电路连接到行为和 猴子和小鼠的神经生理学实验(项目1和2)。这将使我们能够研究如何 在早期精神病中观察到的状态表征功能障碍--以及脑电和功能磁共振成像 活动时间、兴奋-抑制(E-I)平衡和噪声的神经生理学指标与临床相关 基线的异质性，以及6个月临床轨迹的异质性。在目标1中，我们计算重测 国家代表性措施的可靠性。在目标2中，我们描述和比较了行为特征， 状态表征过程中早期精神病和健康对照的脑电和功能磁共振成像。在目标3中，我们重新- 在同步EEG-fMRI中评估DPX和Bandit任务的性能，以表征 危重前6个月早期精神病患者的状态表征功能障碍 治疗。我们将确定计算参数的更改程度是从 与活动时间、E-I平衡和噪声相关的计算核心和神经生理学测量 (参见翻译神经生理学核心)，映射到生活质量的不同轨迹 因果发现分析。我们还将测试是否可以根据基线特征预测轨迹。 此外，我们的健康对照数据集将允许我们探索稳定性与变化的正常模式 在青少年和青壮年中观察6个月以上。

PROJECT SUMMARY: PROJECT 3 The purpose of PROJECT 3 is to determine how failures in information processing that supports state representation in neural circuits relate to clinical heterogeneity in early psychosis. To this end, we will: (a) Recruit people with early psychosis (N=125) and demographically similar healthy controls (N=125) aged 16-30 years; (b) Determine test-retest reliability of the DPX and Bandit tasks as assessments of state representation processes; (c) Characterize behavioral performance and neurophysiology at baseline using the DPX and Bandit tasks during simultaneous EEG-fMRI; (d) Follow patients for 6 months while they receive usual care, to delineate their clinical trajectories; (e) Repeat the behavioral and EEG-fMRI assessments after six months (N=100 retained per group). The data we acquire will allow us to examine the baseline relationships between clinical and experimental measures, and also to investigate how changes in clinical and experimental measures are related over a 6-month time period during a critical phase of illness. The overall goal of PROJECT 3 is to permit neural macro-circuit links in humans to the behavioral and neurophysiology experiments in monkeys and mice (PROJECTS 1 & 2). This will allow us to examine how state representation dysfunctions observed in early psychosis -- along with EEG and fMRI-derived neurophysiologic indices of activity timing, excitatory-inhibitory (E-I) balance, and noise -- relate to clinical heterogeneity at baseline, and to heterogeneity in 6-month clinical trajectories. In Aim 1, we compute the retest reliability of state representation measures. In Aim 2, we characterize and compare the features of behavior, EEG and fMRI in early psychosis and healthy controls during state representation processes. In Aim 3,we re- assess performance on the DPX and Bandit tasks during simultaneous EEG-FMRI, in order to characterize the course of state representation dysfunctions in early psychosis during the critical first 6 months of treatment. We will determine the extent to which changes in computational parameters derived from the COMPUTATIONAL CORE, and neurophysiologic measures related to activity timing, E-I balance, and noise (see TRANSLATIONAL NEUROPHYSIOLOGY CORE), map to distinct trajectories in quality of life using causal discovery analyses. We will also test whether trajectories can be predicted from baseline features. Additionally, our healthy control data set will permit us to explore normal patterns of stability vs. change as observed over 6 months in adolescents and young adults.