Effects of attention and acetylcholine on cortical stimulus representations

项目总结/摘要 这个项目的长期目标是描述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征。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 乙酰胆碱和注意力增强视觉感知的各个方面，但潜在的大脑机制是 不太了解。拟议的工作将解决这些问题，在健康的人类受试者， 功能性磁共振成像（fMRI）来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增加会增强大脑的功能。 大脑对视觉环境表征的空间分辨率。拟议的研究将记录 究竟是哪些大脑区域介导了乙酰胆碱的这种作用，也将表征注意力的作用。 对大脑空间分辨率的测量。增强空间分辨率的后果 还将研究视觉感知。这项工作可能对治疗 黄斑变性，一种以中心视力丧失为特征的疾病。患有黄斑的患者 退化必须完全依赖于周边视觉，并且周边视觉的低空间分辨率 严重损害了他们阅读和识别人脸和其他视觉物体的能力。 我们还将研究乙酰胆碱和注意力对大脑的可靠性的影响。 视觉环境的表现。我们的初步研究表明乙酰胆碱水平的增加 减少了大脑对视觉刺激重复呈现的反应的变化。在其他工作中，我们 已经表明，增加乙酰胆碱显着提高知觉学习（改善视觉 （1）具体任务的执行能力）。大脑表征的稳定性增强， 乙酰胆碱可能是感知学习能力提高的原因。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。该研究将直接 研究注意力、乙酰胆碱、大脑活动和视觉感知之间的关系。 增强乙酰胆碱作用的药物（胆碱酯酶抑制剂）用于治疗认知障碍。 老年痴呆症的缺陷。尽管这些药物的生化作用已得到很好的表征， 知觉和认知效应以及这些效应的神经相关性还不太清楚。我们将 使用胆碱酯酶抑制剂多奈哌齐（商品名：安理申）， 为了阐明乙酰胆碱在注意力和感知中的作用，并更好地了解 这些药物改善认知功能的机制。此外，更好地了解神经 注意力的底物对于开发更有效的疾病治疗是重要的， 注意力障碍，包括注意力缺陷障碍、精神分裂症和阿尔茨海默病。

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.