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: 8710231
• 负责人: CHARLES J DUFFY
• 金额: $ 52.67万
• 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/8710231
• 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.

描述（由申请人提供）：单神经元神经生理学已经确定了猕猴背侧纹外皮层中光流分析的机制（Duffy 2004）。我们已经证明，视流感知缺陷与衰老和阿尔茨海默病 (AD) 中的导航障碍有关 (O'Brien 2001) (Mapstone 2010)。最近，我们通过记录人类视流事件相关电位（ERP）将这些研究联系起来，发现它们与衰老和 AD 中的知觉和导航损伤高度相关（Kavcic 2006）（Fernandez 2007）。我们现在已经记录了猴子的光流 ERP，创造了一个机会，将 ERP 与对视觉运动处理背后的细胞神经生理学的日益深入的理解联系起来。这些努力将阐明光流分析的皮质机制及其在衰老和 AD 中的衰退。我们假设视流 ERP 的组成部分与自下而上的背侧流视觉运动处理以及自上而下的注意力和任务相关机制的影响特别相关，这些机制被认为起源于后顶叶 (PPC) 和背外侧前额叶 (DLPFC)皮质。我们将在记忆引导扫视任务期间观察顺序光流刺激的猴子的研究中检验这一假设。这些研究将把皮层 MSTd 中单个神经元的记录与 STS（颞上沟）、PPC 和 DLPFC 中 LFP 的记录以及全颅阵列中 ERP 的记录结合起来。我们将采用三种并行方法来探讨将光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 反应的共变，以了解 ERP 组件的神经生理学基础。其次，我们将使用 ERP 组件中与年龄相关的变化来测试单个神经元和 LFP 反应的相关变化。第三，我们将利用药理学可逆失活来建立特定皮质区域、ERP 成分和潜在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行为变化的关系，将有助于检测和改善衰老和 AD 中的导航障碍。