Neural Mechanisms of Reading Dysfunction in Schizophrenia

精神分裂症阅读障碍的神经机制

• 批准号: 10399585
• 负责人: DANIEL C. JAVITT
• 金额: $ 68.05万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10399585
• 关键词: Alcohol consumption; Assessment tool; Auditory; Auditory system; Behavioral; Biological Markers; Clinical; Clinical Management; Cognition; Computer Models; Contrast Sensitivity; Data; Development; Disease; Early Diagnosis; Education; Employment; Evaluation; Event-Related Potentials; Eye Movements; Family; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Generations; Human Resources; Impaired cognition; Impairment; Individual; Intervention; Intervention Studies; Investigation; Language; Literacy Programs; Measures; Mediating; Mediation; Mental Health; Methods; Modeling; Multimodal Imaging; Nerve Degeneration; New York; Occupational; Onset of illness; Outcome; Outcome Study; Patient Recruitments; Patients; Pattern; Pharmaceutical Preparations; Population; Population Control; Prevalence; Process; Quality of life; Reader; Reading; Role; Saccades; Schizophrenia; School-Age Population; Schools; Sensory; Services; Societies; Stimulus; Symptoms; Testing; Text; Training Programs; Visual; Work; auditory processing; base; eighth grade; eleventh grade; first episode schizophrenia; follow-up; functional outcomes; gaze; high risk; high school; imaging approach; improved; indexing; information processing; lexical; literacy; method development; motion sensitivity; multimodal neuroimaging; multimodality; neurodegenerative phenotype; neuromechanism; oculomotor; phonology; programs; prospective; reading ability; reading difficulties; recruit; remediation; sample fixation; screening program; sensory integration; service utilization; side effect; skills; social; social cognition; social determinants; success; visual information; visual tracking

Schizophrenia (Sz) is associated with deficits in reading ability that interrelate with disturbances in early auditory and visual/oculomotor processing. This project evaluates consequences and causes of reading impairment in Sz using combined multimodal imaging, eye tracking and computational modeling. Skilled reading depends upon intact auditory and visual sensory integration, as well as higher-order cognition. Deficits in early auditory processing in Sz are indexed by impaired tone matching and auditory plasticity, as well as by impaired generation of mismatch negativity (MMN) and reflect dysfunction within subcortical and cortical components of the early auditory system. Deficits in visual sensory processing are indexed by reduced contrast and motion sensitivity, impaired generation of visual event-related potentials (ERP), reduced fMRI activation of subcortical and cortical early visual regions. Visual oculomotor deficits are reflected by increased rates of refixation in Sz, as well as impaired generation of the fixation-related potential (FRP) during reading. Processes underlying impaired oculomotor control during reading may be modeled using non-linear computational approaches, such as E-Z Reader, which evaluate effects of alterations in specific visual, lexical and oculomotor parameters on discrete eye movement measures across populations and individuals. This project consists of 2 interrelated components. In SA1, we will evaluate consequences of reading impairment in patients (n=120) recruited from the New York State Office of Mental Health (NYS OMH) OnTrackNY program. OnTrackNY provides longitudinal services to first-episode schizophrenia (FESz) patients and collects extensive clinical and outcome data. We will collect additional reading, cognition and symptom data and will evaluate the relationship of reading dysfunction to outcome using mediation/moderation modeling both cross-sectionally and prospectively. A subsample of 60 FESz subjects will be restudied at 1.5-2 yr follow-up. In SA2, we will investigate mechanisms underlying the impairments using a multi-modal imaging approach incorporating combined eye-tracking, ERP/FRP, and fMRI measures and computational modeling. Auditory and visual sensory function will be assessed using convergent behavioral, ERP and fMRI measures. Eye-movements, FRP and fMRI will be collected to both normal and unsegmented text in order to manipulate parafoveal load. Patterns of eye movement disturbance will be modeled across groups using E-Z Reader or successor eye- movement modeling programs to differentiate effects of “top down” vs. “bottom up” contributions. We have previously demonstrated that clinical high risk (CHR) individuals show visual but not auditory deficits similar to those of Sz. Here, we will compare patterns between FESz, CHR and healthy control (HC) populations (n=40/grp). This project represents a comprehensive evaluation of consequences and causes of impaired reading in Sz, and will provide assessment tools for early detection of reading deficits within premorbid and early-stage schizophrenia and targets/“target engagement” biomarkers for future interventional research.

精神分裂症 (Sz) 与阅读能力缺陷有关，而阅读能力缺陷又与早期的障碍相关。 该项目评估阅读的后果和原因。 使用组合多模态成像、眼动追踪和计算建模来损伤 Sz。 阅读取决于完整的听觉和视觉感觉统合，以及高阶认知缺陷。 Sz 的早期听觉处理过程中，音调匹配和听觉可塑性受损，以及 错配负性（MMN）的产生受损并反映皮质下和皮质内的功能障碍 早期听觉系统的组成部分的缺陷通过减少来表示。 对比和运动敏感性、视觉事件相关电位 (ERP) 生成受损、功能磁共振成像 (fMRI) 降低 皮层下和皮层早期视觉区域的激活表现为视觉动眼神经缺陷的增加。 Sz 的再注视率，以及阅读过程中注视相关电位 (FRP) 的产生受损。 阅读过程中动眼神经控制受损的过程可以使用非线性模型 计算方法，例如 E-Z Reader，评估特定视觉、词汇变化的影响 以及动眼参数对人群和个体离散眼动测量的影响。 项目由 2 个相互关联的部分组成，在 SA1 中，我们将评估阅读障碍的后果。 患者 (n=120) 是从纽约州心理健康办公室 (NYS OMH) OnTrackNY 项目招募的。 OnTrackNY 为首发精神分裂症 (FESz) 患者提供纵向服务并收集广泛的信息 我们将收集额外的阅读、认知和症状数据，并评估 使用横断面的中介/调节模型来研究阅读功能障碍与结果的关系 前瞻性地，我们将在 1.5-2 年的随访中重新研究 60 名 FESz 受试者的子样本。 使用多模态成像方法研究损伤背后的机制 结合了眼动追踪、ERP/FRP 和功能磁共振成像测量以及听觉和视觉模型。 将使用聚合行为、ERP 和功能磁共振成像测量来评估感觉功能。 FRP 和 fMRI 将被收集为正常文本和未分段文本，以便控制中心凹负荷。 将使用 E-Z Reader 或后续的眼动障碍模型对各组进行建模。 我们有运动建模程序来区分“自上而下”与“自下而上”贡献的效果。 先前证明，临床高风险（CHR）个体表现出类似于以下情况的视觉缺陷，但没有听觉缺陷 在这里，我们将比较 FESz、CHR 和健康对照 (HC) 人群之间的模式。 (n=40/grp) 该项目是对受损后果和原因的综合评估。 Sz 阅读，并将提供评估工具，以便及早发现病前和患病期间的阅读缺陷 早期精神分裂症和未来介入研究的目标/“目标参与”生物标志物。