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）与阅读能力的缺陷有关，这些缺陷与早期精神分裂症的障碍有关。 听觉和视觉/视觉处理。这个项目评估阅读的后果和原因 使用组合的多模态成像、眼动跟踪和计算建模来评估Sz的损伤。技术 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Sz的早期听觉处理中，通过受损的音调匹配和听觉可塑性以及 不匹配负波（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。视觉感觉处理的缺陷通过减少 对比度和运动敏感度，视觉事件相关电位（ERP）生成受损，功能性磁共振成像降低 皮层下和皮层早期视觉区的激活。视力缺陷反映在增加 Sz的再固定率，以及阅读过程中固定相关电位（FRP）的产生受损。 阅读期间受损的眼神经控制的潜在过程可以使用非线性模型来建模， 计算方法，如E-Z阅读器，评估特定视觉，词汇 和眼动参数对人群和个体的离散眼动测量的影响。这 项目由两个相互关联的部分组成。在SA 1中，我们将评估阅读障碍的后果， 从纽约州精神卫生办公室（NYSOMH）OnTrackNY项目招募的患者（n=120）。 OnTrackNY为首发精神分裂症（FESz）患者提供纵向服务， 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 阅读功能障碍与结果的关系，使用中介/适度模型， 和前瞻性。将在1.5-2年随访时重新研究60例FESz受试者的子样本。在SA 2中，我们将 使用多模态成像方法研究损伤的潜在机制， 结合眼动追踪、ERP/FRP和fMRI测量和计算建模。听觉和视觉 将使用会聚行为、ERP和fMRI测量来评估感觉功能。眼球运动， 将收集正常和未分割文本的FRP和fMRI，以操纵椎旁负荷。 将使用E-Z阅读器或后续眼动仪对各组的眼动障碍模式进行建模。 运动建模程序，以区分“自上而下”与“自下而上”贡献的效果。我们有 先前证明，临床高风险（CHD）个体表现出类似于 那些Sz。在这里，我们将比较FESz，ESTA和健康对照（HC）人群之间的模式 （n=40/组）。该项目代表了对损害的后果和原因的全面评估， Sz的阅读，并将提供评估工具，用于早期发现患病前和患病后的阅读缺陷。 早期精神分裂症和未来干预研究的目标/“目标参与”生物标志物。