APPLICATION OF PSYCHOPHYSICAL MODELS TO VISUAL DISORDERS

描述(申请人提供)：这项研究的长期目标是将患者的视觉缺陷与潜在的细胞病理生理学联系起来。这项拟议的研究使用新的心理物理方法来监测细胞功能障碍，并建立定量模型来将青光眼视觉缺陷与神经节细胞损伤联系起来。这些目标将为开发新形式的视野奠定基础。具体目标是： 1)开发一种临床上有用的评估神经节细胞功能障碍的新方法。在过去的十年里，一种新的功能技术被开发出来，它是关于神经节细胞棘波产生的饱和，并已被应用于中心凹功能障碍的研究。这项拟议的研究将开发这种技术的一个版本，用于评估整个视野的功能障碍。临床版本将用于跟踪特定目标2的患者，并将在特定目标4中建模。 2)跟踪正在接受青光眼治疗的患者，使用足够精确的方法检测视觉功能的改善。我们已经证明，通过使用皮质机制汇总大量神经节细胞的反应的刺激，可以减少测试-重测的可变性。这些刺激物，连同在特定目标1中开发的方法，将用于监测青光眼缺陷的视觉功能。为此，我们将使用这些方法对接受青光眼治疗的患者进行跟踪，以评估神经节细胞功能障碍在确定缺陷深度方面的潜在作用。 3)通过对神经节细胞死亡和功能障碍的影响的定量模拟，评估青光眼缺陷的结构和功能数据。传统视野检查和我们的新测试的功能数据将与神经节细胞丢失的结构测量进行比较，以更准确地确定细胞功能障碍和细胞死亡在结构/功能比较中的潜在作用。 4)扩展我们的定量模型，从种群动力学和棘波序列分析的角度分析神经噪声的潜在影响。我们将使用对猕猴神经节细胞棘波序列的神经计量学分析和种群动态模拟来纳入生理上看似合理的神经噪音来源，区分神经节细胞敏感性降低和神经噪音增加之间的差异，并提供对细胞病理生理学不同方面的影响的更好理解。

DESCRIPTION (provided by applicant): The long-term objective of this research is to relate visual deficits in patients to the underlying cellular pathophysiology. The proposed research uses new psychophysical measures for monitoring cell dysfunction, and quantitative modeling to relate glaucomatous visual defects with ganglion cell damage. These aims will lay the foundation for development of new forms of perimetry. The Specific Aims are: 1) To develop a clinically useful version of a new method for evaluating ganglion cell dysfunction. Over the past decade a new functional technique has been developed in terms of saturation of ganglion cell spike generation, and has been applied to the study of foveal dysfunction. The proposed research will develop a version of this technique for evaluating dysfunction throughout the visual field. The clinical version will be used to follow patients in Specific Aim 2, and will be modeled in Specific Aim 4. 2) To follow patients being treated for glaucoma, using methods with sufficient precision to detect improvement in visual function. We have demonstrated that test-retest variability can be reduced by using stimuli for which cortical mechanisms summate responses of large numbers of ganglion cells. These stimuli, along with the method developed in Specific Aim 1, will be used to monitor visual function in glaucomatous defects. In this Aim we will use these methods to follow patients undergoing treatment for glaucoma, in order to evaluate the potential role of ganglion cell dysfunction in determining depth of defect. 3) To evaluate structural and functional data on glaucomatous defects using quantitative modeling of effects of ganglion cell death and dysfunction. Functional data for conventional perimetry and for our new tests will be compared with structural measures of ganglion cell loss, to more precisely define the potential roles of cell dysfunction and cell death in structure/function comparisons. 4) To extend our quantitative modeling by analyzing potential effects of neural noise in terms of population dynamics and spike train analysis. We will use both neurometric analysis of macaque ganglion cell spike trains and simulation of population dynamics to incorporate physiologically plausible sources of neural noise and distinguish between decreased sensitivity of ganglion cells vs. increased neural noise, and provide an improved understanding of the effects of different aspects of cellular pathophysiology.