Effects of attention and acetylcholine on cortical stimulus representations

项目摘要/摘要 该项目长期目标是研究注意力和乙酰胆碱如何影响视觉 知觉和大脑对视觉环境的表现。乙酰胆碱是一种天然存在的 神经递质和乙酰胆碱的释放在持续注意期间升高。两者都有 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 人们对此知之甚少。这项拟议的工作将在健康的人类受试者中通过使用 功能磁共振成像(FMRI)测量大脑对视觉刺激的反应， 我们之前的研究表明，大脑中乙酰胆碱水平的增加会增强 大脑表示视觉环境的空间分辨率。拟议的研究将记录 确切地说，大脑的哪些区域介导了乙酰胆碱的这种效应，并将表征注意力的效应 关于大脑中空间分辨率的这些测量。空间分辨率提高的后果是 视觉感知也将被调查。这项工作可能对治疗黑色素瘤具有特殊的意义 黄斑变性，一种以中心视力丧失为特征的疾病。黄斑部疾病患者 退化必须完全依赖于周边视力，以及周边视力的低空间分辨率 严重损害他们阅读和识别人脸和其他视觉对象的能力。 我们还将研究乙酰胆碱和注意力对大脑可靠性的影响。 视觉环境的表示形式。我们的初步研究表明，增加乙酰胆碱水平 减少大脑对重复呈现的视觉刺激的反应的变异性。在其他工作中，我们 已经表明，增加乙酰胆碱显著促进知觉学习(视觉上的改善 跟踪特定任务实践的能力)。脑表征在增加后的稳定性增强 乙酰胆碱可能对知觉学习的改善负责。另外，我们发现， 乙酰胆碱可以促进注意力对知觉的有益影响。拟议的研究将直接 研究注意力、乙酰胆碱、大脑活动和视觉知觉之间的关系。 增强乙酰胆碱(胆碱酯酶抑制剂)作用的药物用于治疗认知障碍 阿尔茨海默氏症的缺陷。虽然这些药物的生化作用有很好的特征，但它们的 知觉和认知效应以及这些效应的神经关联还不太清楚。我们会 使用胆碱酯酶抑制剂多奈哌齐(商标名：Aricept)来操纵脑乙酰胆碱水平 为了阐明乙酰胆碱在注意力和知觉中的作用，并更好地理解 这些药物改善认知功能的机制。此外，更好地了解神经 关注的底物对于开发更有效的疾病治疗方法是重要的 注意力，包括注意力缺陷障碍、精神分裂症和阿尔茨海默氏症。

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.