Integrating Neurophysiological Views of the Aging Visual System

整合衰老视觉系统的神经生理学观点

• 批准号: 8353155
• 负责人: CHARLES J DUFFY
• 金额: $ 63.2万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8353155
• 关键词: Affect; Aging; Alzheimer' s Disease; Animal Model; Area; Attention; Automobile Driving; Behavior; Behavioral; Cephalic; Clinical; Detection; Dorsal; EP300 gene; Elderly; Event-Related Potentials; Foundations; Goals; Human; Impairment; Injection of therapeutic agent; Lateral; Lidocaine; Link; Macaca; Memory; Monkeys; Motion; Muscimol; Neurons; Parietal; Parietal Lobe; Perception; Prefrontal Cortex; Process; Research; Role; Saccades; Sensory; Shapes; Signal Transduction; Site; Space Perception; Speed; Stimulus; Stream; Structure of superior temporal sulcus; System; Testing; Variant; Visual; Visual Motion; Visual system structure; age effect; age related; extrastriate; extrastriate visual cortex; neuromechanism; neurophysiology; optic flow; response; therapy development; visual stimulus; young adult

DESCRIPTION (provided by applicant): Single neuron neurophysiology has identified mechanisms of optic flow analysis in macaque dorsal extrastriate cortex (Duffy 2004). We have shown that optic flow perceptual deficits are associated with navigational impairments in aging and Alzheimer's disease (AD) (O'Brien 2001) (Mapstone 2010). Recently, we linked these lines of research by recording human optic flow event related potentials (ERPs), finding that they are highly correlated with perceptual and navigational impairments in aging and AD (Kavcic 2006) (Fernandez 2007). We have now recorded optic flow ERPs in monkeys, creating an opportunity to relate ERPs to the growing understanding of the cellular neurophysiology underlying visual motion processing. These efforts will elucidate the cortical mechanisms of optic flow analysis and its decline in aging and AD. We hypothesize that components of optic flow ERPs are specifically linked to the effects of bottom-up dorsal stream visual motion processing, and top-down attention and task related mechanisms thought to originate in posterior parietal (PPC) and dorso-lateral prefrontal (DLPFC) cortices. We will test this hypothesis in studies of monkeys viewing sequential optic flow stimuli during a memory guided saccade task. These studies will integrate the recording of single neurons in cortical area MSTd with the recording of LFPs in STS (superior temporal sulcus), PPC, and DLPFC, and with the recording of ERPs in a full cranial array. We will take three parallel approaches to probing the cortico-cortical interactions that link optic flow analysis to behavioral task demands and ERPs. First, we will analyze the co-variation in the responses of single neurons, LFPs, and ERPs to understanding the neurophysiological foundations of ERP components. Second, we will use age-related variation in ERP components to test for correlated variation in single neuron and LFP responses. Third, we will use pharmacological reversible inactivation to establish relations between specific cortical areas, ERP components, and the underlying neurophysiological response mechanisms. Understanding the neural mechanisms of visual motion processing, and its relationship to age-related changes in behavior, will promote the detection and amelioration of navigational impairments in aging and AD. PUBLIC HEALTH RELEVANCE: Neurons in monkey dorsal extrastriate cortex process the visual motion in optic flow to support navigation. Navigational impairments in aging and Alzheimer's disease (AD) are associated with deficits in optic flow perception and changes in both sensory and attentional components of optic flow cortical evoked responses. We will now combine the recording of single neuron responses, local field potentials, and event related potentials in monkeys engaged in an optic flow related behavioral task. Our goal is to elucidate the origin and function of sensory and attentional responses to optic flow. These studies will identify the neural mechanisms underlying the debilitating navigational impairments that limit functional independence in aging and AD.

描述（由申请人提供）：单个神经元神经生理学已经鉴定出猕猴背外层皮质中的光流分析的机制（Duffy 2004）。我们已经表明，视流感知缺陷与老龄化和阿尔茨海默氏病的导航障碍有关（AD）（O'Brien 2001）（Mapstone 2010）。最近，我们通过记录人类光流事件相关电位（ERP）将这些研究线联系起来，发现它们与衰老和AD的感知和导航障碍高度相关（Kavcic 2006）（Fernandez 2007）。现在，我们记录了猴子中的视流ERP，创造了一个机会，将ERP与对视觉运动处理基础的细胞神经生理学的不断了解相关联。这些努力将阐明光流分析的皮质机制及其在衰老和AD的下降。我们假设光流ERP的组成部分与自下而上的背面视觉运动处理的影响以及被认为起源于后顶叶（PPC）和Dorso-Liendal-Liendal Pretfrental（DLPFC）皮尔特（DLPFC）皮质的自上而下的注意力和任务相关机制有关。我们将在记忆引导的扫视任务期间对猴子查看顺序光流刺激的研究中检验这一假设。这些研究将使皮质区域MSTD中的单个神经元与STS（上颞沟），PPC和DLPFC中的LFP和LFP的记录以及在完整颅阵列中记录ERP的记录。我们将采用三种平行的方法来探测将光学流分析与行为任务需求和ERP联系起来的皮质皮质相互作用。首先，我们将分析单个神经元，LFP和ERP的响应中的共同变化，以了解ERP成分的神经生理基础。其次，我们将使用与年龄相关的ERP组件变化来测试单个神经元和LFP响应中相关变化。第三，我们将使用药理学可逆的失活来建立特定皮质区域，ERP成分与潜在的神经生理反应机制之间的关系。了解视觉运动处理的神经机制及其与年龄相关的行为变化的关系，将促进衰老和AD中导航障碍的检测和改善。 公共卫生相关性：猴子背部皮层的神经元过程的视觉运动中的视觉运动以支持导航。衰老和阿尔茨海默氏病（AD）的导航障碍与视觉感知的缺陷以及视流皮质诱发反应的感觉和注意力成分的变化有关。现在，我们将结合从事相关行为任务的猴子中单个神经元反应，局部场电位和事件相关电位的记录。我们的目标是阐明感觉和注意力流的注意力和注意力的起源和功能。这些研究将确定限制衰老和AD功能独立性的导航障碍的神经机制。