fMRI of Eye Movement Phenotype in Schizophrenia

描述（由申请人提供）：精神分裂症的病因病理生理学尚不完全清楚。有证据支持精神分裂症的遗传易感性和平稳追踪眼球运动（SPEM）异常之间的关联，并且已经表明SPEM可以作为分子遗传学研究中的表型。然而，报告的SPEM异常的神经基础还没有很好地理解，甚至更少有人知道遗传效应是如何转化为异常的神经回路控制SPEM。SPEM异常的生物学机制及其与精神分裂症表型的关系的知识可能会提供关键的见解这种疾病的病因。拟议研究的目标是联合收割机功能磁共振成像（fMRI）和SPEM措施，研究1）精神分裂症相关SPEM损伤的潜在神经机制; 2）家庭中与追求相关的成像变化聚集的程度。我们已经建立了行为模型的视网膜运动和视网膜外运动信号的相对贡献，以顺利追求维持健康受试者和精神分裂症患者的亲属。结果表明，在健康受试者的性能主要取决于预测，或视网膜外运动输入，而精神分裂症患者的亲属表现出赤字的追求反应的这一组成部分。这种缺陷可能会导致增加对即时视网膜运动感觉输入的依赖，以保持平稳的追求。我们假设，这种模式的行为异常有一个神经生理学的基础，将在功能磁共振成像信号中检测到的视网膜外运动处理通路的激活减少伴随着一个补偿性的增加，在负责视网膜运动处理的区域激活。我们进一步假设，这种模式的神经活动将存在于受影响的先证者的临床上未受影响的兄弟姐妹，支持遗传影响的神经回路控制预测顺利追求缺陷精神分裂症。

DESCRIPTION (provided by applicant): The etiopathophysiology of schizophrenia is incompletely understood. Evidence supports an association between genetic liability for schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, and it has been suggested that SPEM can serve as a phenotype in molecular genetic studies. However, the neural basis of reported abnormalities in SPEM is not well understood, and even less is known about how genetic effects are translated into aberrant neural circuit controlling SPEM. Knowledge of the biological mechanisms underlying SPEM abnormalities and their relationship to the schizophrenia phenotype may provide critical insights into the etiology of this disease. The goal of the proposed research is to combine functional magnetic resonance imaging (fMRI) and SPEM measures to study 1) the underlying neural mechanism of schizophrenia-related SPEM impairments; and 2) the degree to which pursuit-related imaging changes aggregate in families. We have behaviorally modeled the relative contributions of retinal motion and extraretinal motion signals to smooth pursuit maintenance in healthy subjects and in relatives of schizophrenia patients. The results indicate that performance in healthy subjects depends primarily on the predictive, or extraretinal motion input, while relatives of schizophrenia patients show deficits in this component of the pursuit response. This deficit may lead to an increased reliance on the immediate, retinal motion sensory input to maintain smooth pursuit. We hypothesize that this pattern of behavioral abnormality has a neurophysiological basis that will be detectable in fMRI imaging signal as reduced activation in the extraretinal motion processing pathway accompanied by a compensatory increase in activation in regions responsible for retinal motion processing. We further hypothesize that this pattern of neural activity will be present in the clinically unaffected siblings of affected probands, supporting a genetic influence on the neural circuit controlling predictive smooth pursuit deficit in schizophrenia.