Pupillometry and Gaze-Tracking in Unrestrained Monkeys

描述(由申请人提供)：在人类疾病的非人类灵长类动物(NHP)模型中，瞳孔和动眼功能的测量对滥用药物对中枢神经系统(CNS)的调节和中枢神经系统的病理非常敏感。然而，传统上研究NHP的瞳孔和眼球运动功能的技术需要侵入性的程序，包括手术植入和/或将动物束缚在专门的椅子上。这些技术允许对视觉系统进行非常强大的分析，但限制了可以在NHP中利用眼睛跟踪的研究人员的数量。这项提议将把最先进的、基于计算机视频的眼睛跟踪设备与新的行为方法结合起来，开发一种在家中的NHP中进行瞳孔测量和凝视跟踪的方法。具体目标1是开发一种系统，该系统可以连接到非人类灵长类动物的笼子上，并允许在动物清醒和无拘无束时，基于计算机拍摄非人类灵长类动物的眼睛。要记录的测量包括估计瞳孔大小和猴子凝视的方向。具体目标2是开发一种测定瞳孔光反射的方法。通过测量吗啡对恒河猴和狒狒的影响，将验证对瞳孔光反射的确定。为了测试另外一种非人类灵长类物种的训练方法和设备，将在狒狒身上测量瞳孔测量法。具体目标3是开发一种系统，在恒河猴执行视觉顺畅追逐任务时测量凝视方向。平滑追踪任务的敏感性将通过测试安定对恒河猴眼球运动能力的影响来验证。具体目标4是开发一种基于对两种刺激的相对凝视时间的再认记忆测试，即恒河猴视觉配对比较测试。服用安定将测试范式对苯二氮卓类药物遗忘效应的敏感度。瞳孔扩张的测量将被包括在内，以解决由于认知负荷引起的扩张在这个范例中是否明显。家笼程序将使更多的研究人员能够利用眼球跟踪技术，降低这样做的技术难度。家庭笼式手术也将减少基于约束的方法所固有的对NHP受试者的压力。这里介绍的技术将对基于眼睛的测量的非传统用户最具吸引力，例如药理学家、神经毒物学家和行为心理学家。

DESCRIPTION (provided by applicant): Measures of pupillary and oculomotor function are exquisitely sensitive to modulation of the central nervous system (CNS) by drugs of abuse and CNS pathology in nonhuman primate (NHP) models of human diseases. However, techniques to study pupillary and oculomotor function in NHPs traditionally require invasive procedures including surgical implantation and/or restraint of the animals in specialized chairs. These techniques allow very powerful analyses of the visual system, but limit the number of researchers that can utilize eye-tracking in NHPs. This proposal will combine state-of-the-art, computerized video-based eye-tracking equipment with novel behavioral methods to develop a method for pupillometry and gaze-tracking in NHPs in their home cage. Specific Aim 1 is to develop a system that attaches to a nonhuman primate home cage and allows computer-based video recording of the nonhuman primate eye while the animal is awake and unrestrained. Measures to be recorded include estimates of pupil size and direction of the monkey's gaze. Specific Aim 2 is to develop a procedure for determination of pupillary light reflex. Determination of pupillary light reflex will be validated by measuring the effects of morphine in rhesus monkeys and baboons. Pupillometry will be measured in baboons to test the training methods and equipment in an additional nonhuman primate species. Specific Aim 3 is to develop a system to measure gaze direction while rhesus monkeys perform a visual smooth pursuit task. Sensitivity of the smooth pursuit task will be validated by testing the effects of diazepam on oculomotor performance of rhesus monkeys. Specific Aim 4 is to develop a test of recognition memory based on relative gaze times to two stimuli, the Visual Paired Comparisons test in rhesus monkeys. Administration of diazepam will test for the sensitivity of the paradigm to the amnesic effects of benzodiazepines. Measures of pupillary dilation will be included to address whether dilation due to cognitive load is evident in this paradigm. Home cage procedures will enable more researchers to eye-tracking techniques and reduce the technical difficulty of doing so. Home cage procedures will also reduce the stress to the NHP subjects inherent in restraint-based methods. The techniques presented here will be most attractive to non-traditional users of eye-based measures such as pharmacologists, neurotoxicologists and behavioral psychologists.