Neural Mechanisms of Reading Dysfunction in Schizophrenia

精神分裂症阅读障碍的神经机制

• 批准号: 10200005
• 负责人: DANIEL C. JAVITT
• 金额: $ 68.87万
• 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/10200005
• 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; multimodality; neurodegenerative phenotype; neuroimaging; 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，这与早期的障碍有关 听觉和视觉/动眼加工。这个项目评估阅读的结果和原因 使用多模式成像、眼球跟踪和计算建模相结合的Sz损伤。技术娴熟 阅读依赖于完整的听觉和视觉感觉整合，以及更高层次的认知。赤字 在早期的听觉加工中，Sz的指标是音调匹配和听觉可塑性受损以及 失配负波(MMN)的产生受损，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。视觉感觉加工的缺陷通过以下指标进行索引 对比度和运动敏感度，视觉事件相关电位(ERP)生成障碍，功能磁共振成像减少 皮质下和皮质早期视觉区域的激活。视觉动眼功能障碍反映在增加 Sz的重视率，以及阅读过程中注视相关电位(FRP)的产生受损。 在阅读过程中潜在的眼运动控制受损的过程可以用非线性建模 计算方法，如E-Z Reader，评估特定视觉、词汇变化的影响 以及跨人群和个人的离散眼球运动测量的眼动参数。这 项目由2个相互关联的组件组成。在SA1中，我们将评估阅读障碍的后果 从纽约州精神卫生办公室(NYS OMH)OnTrackNY计划招募的患者(n=120)。 OnTrackNY为首发精神分裂症(FESz)患者提供纵向服务，并广泛收集 临床和结果数据。我们将收集额外的阅读、认知和症状数据，并将评估 阅读障碍与结局的关系--使用两个横断面的中介/调节模型 而且是前瞻性的。60名FESZ受试者的亚样本将在1.5-2年的随访中重新研究。在SA2中，我们将 使用多模式成像方法研究潜在损伤的机制 结合了眼球跟踪、ERP/FRP和功能磁共振测量和计算建模。听觉和视觉 感觉功能将使用融合行为、事件相关电位和功能磁共振测量进行评估。眼球运动， FRP和fMRI将被收集到正常和未分割的文本，以便操纵旁凹负荷。 眼球运动障碍的模式将使用E-Z Reader或后续Eye-Reader跨组建模。 运动建模程序，以区分“自上而下”和“自下而上”贡献的效果。我们有 先前证明，临床高危(CHR)患者表现出视觉而不是听觉缺陷，类似于 Sz.在这里，我们将比较FESZ、CHR和健康对照(HC)人群的模式 (n=40/GRP)。该项目代表了对残疾人后果和原因的全面评估 在Sz的阅读，并将提供评估工具，以早期发现疾病前和 早期精神分裂症与靶点/“靶点参与”生物标记物的未来干预研究。