Effects of attention and acetylcholine on cortical stimulus representations

注意力和乙酰胆碱对皮质刺激表征的影响

• 批准号: 9197301
• 负责人: MICHAEL A SILVER
• 金额: $ 37万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9197301
• 关键词: Acetylcholine; Address; Affect; Alzheimer' s Disease; Anatomy; Animals; Area; Aricept; Attention; Attention Deficit Disorder; Behavioral; Biochemical; Brain; Cholinesterase Inhibitors; Cognitive; Cognitive deficits; Data; Dependence; Development; Disease; Drug effect disorder; Electrophysiology (science); Environment; Face; Functional Magnetic Resonance Imaging; Human; Imaging Techniques; Impairment; Individual; Lateral; Light; Location; Macular degeneration; Maps; Measurement; Measures; Mediating; Methods; Modeling; Names; Neurons; Neurotransmitters; Parietal; Patients; Perception; Perceptual learning; Performance; Peripheral; Pharmaceutical Preparations; Pharmacology; Physiological; Population; Procedures; Property; Reaction Time; Research; Resolution; Role; Schizophrenia; Signal Transduction; Silver; Stimulus; Synapses; Testing; Thalamic structure; Time; V1 neuron; Vision; Visual; Visual Cortex; Visual Fields; Visual Perception; Visual Psychophysics; Visual attention; Visuospatial; Work; base; cholinergic; cognitive function; donepezil; effective therapy; human subject; imaging modality; imaging study; improved; neural correlate; neurochemistry; receptive field; relating to nervous system; response; sensory cortex; sensory gating; sensory input; spatial integration; sustained attention; therapy development; visual stimulus

Project Summary/Abstract The long-term objective of this project is to characterize how attention and acetylcholine affect visual perception and the brain's representation of the visual environment. Acetylcholine is a naturally occurring neurotransmitter, and acetylcholine release is elevated during periods of sustained attention. Both acetylcholine and attention enhance aspects of visual perception, but the underlying brain mechanisms are poorly understood. The proposed work will address these questions in healthy human subjects by using functional magnetic resonance imaging (fMRI) to measure the brain's responses to visual stimuli, Our previous studies have shown that increasing levels of acetylcholine in the brain enhances the spatial resolution of the brain's representation of the visual environment. The proposed research will document exactly which brain areas mediate this effect of acetylcholine and will also characterize the effects of attention on these measures of spatial resolution in the brain. The consequences of enhanced spatial resolution for visual perception will also be investigated. This work may have particular significance for the treatment of macular degeneration, a disease characterized by loss of central vision. Patients suffering from macular degeneration must rely exclusively on peripheral vision, and the low spatial resolution of peripheral vision severely impairs their ability to read and to recognize faces and other visual objects. We will also examine the effects of acetylcholine and attention on the reliability of the brain's representations of the visual environment. Our preliminary studies show that increasing acetylcholine levels reduces the variability of the brain's response to repeated presentations of a visual stimulus. In other work, we have shown that increasing acetylcholine dramatically boosts perceptual learning (the improvement in visual ability following practice of particular tasks). The enhanced stability of brain representations following increases in acetylcholine may be responsible for the improvement in perceptual learning. In addition, we have found that acetylcholine can facilitate the beneficial effects of attention on perception. The proposed research will directly examine the relationships among attention, acetylcholine, brain activity, and visual perception. Drugs that enhance the effects of acetylcholine (cholinesterase inhibitors) are used to treat cognitive deficits in Alzheimer's disease. Although the biochemical actions of these drugs are well characterized, their perceptual and cognitive effects and the neural correlates of these effects are less well understood. We will use the cholinesterase inhibitor donepezil (trade name: Aricept) to manipulate brain acetylcholine levels in order to shed light on the role of acetylcholine in attention and perception and to better understand the mechanisms by which these drugs improve cognitive function. In addition, a better understanding of the neural substrates of attention is important for the development of more effective treatments of diseases that affect attention, including attention deficit disorder, schizophrenia, and Alzheimer's disease.

项目摘要/摘要 该项目的长期目标是表征注意力和乙酰胆碱如何影响视觉 感知和大脑对视觉环境的表示。乙酰胆碱是一种天然发生的 在持续关注期间，神经递质和乙酰胆碱释放升高。两个都 乙酰胆碱和注意力增强了视觉感知的各个方面，但潜在的大脑机制是 理解不佳。拟议的工作将通过使用健康的人类受试者解决这些问题 功能磁共振成像（fMRI），以测量大脑对视觉刺激的反应， 我们以前的研究表明，大脑中乙酰胆碱水平的升高会增强 大脑对视觉环境表示的空间分辨率。拟议的研究将记录 确切的脑区域介导了乙酰胆碱的这种作用，还将表征注意力的影响 在这些大脑空间分辨率的措施上。增强空间分辨率的后果 视觉感知也将进行研究。这项工作对于处理 黄斑变性，一种以中央视力丧失为特征的疾病。患有黄斑的患者 退化必须仅依靠外围视力，以及外周视觉的低空间分辨率 严重损害他们阅读和识别面部和其他视觉对象的能力。 我们还将检查乙酰胆碱和注意力对大脑可靠性的影响 视觉环境的表示。我们的初步研究表明，乙酰胆碱水平升高 降低了大脑对视觉刺激反复表现的反应的变化。在其他工作中，我们 已经表明，增加乙酰胆碱会大大提高感知学习（视觉的改善 练习特定任务的能力）。随后大脑表示的稳定性增强 在乙酰胆碱中，可能导致了感知学习的改善。此外，我们发现 乙酰胆碱可以促进注意力对感知的有益影响。拟议的研究将直接 检查注意力，乙酰胆碱，大脑活动和视觉感知之间的关系。 增强乙酰胆碱作用（胆碱酯酶抑制剂）的药物用于治疗认知 阿尔茨海默氏病的缺陷。尽管这些药物的生化作用表现得很好，但 感知和认知效应以及这些作用的神经相关性知之甚少。我们将 使用胆碱酯酶抑制剂多匹齐（商标名称：artept）操纵脑乙酰胆碱水平 为了阐明乙酰胆碱在注意力和感知中的作用，并更好地理解 这些药物改善认知功能的机制。此外，对神经的理解有更好的理解 关注的基材对于发展影响影响的疾病的更有效治疗很重要 注意，包括注意缺陷障碍，精神分裂症和阿尔茨海默氏病。