Neural Mechanisms of Reading Dysfunction in Schizophrenia

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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.