Neural mechanisms of perceptual learning in the human brain

描述（由申请人提供）：该项目的长期目标是表征人类视觉系统中感知学习的神经相关。感知学习可以定义为通过训练对感知辨别能力的具体提高。人类在一生中都有能力学习新的和复杂的技能，而感知学习实验范式为研究这些过程提供了模型系统。此外，涉及感知学习的训练程序已被用于治疗学习障碍，如阅读障碍和弱视等发育障碍。因此，理解感知学习背后的神经机制对基础科学和公共卫生都有影响。这些研究将采用两个感知学习任务：运动方向识别任务和纹理方向识别任务。这些不同的任务涉及人类大脑中两种不同的视觉处理流。其中一个专门用于感知运动和空间位置，另一个专门用于感知视觉形式。人类受试者将在这些任务上接受训练，并对训练后行为表现的改善进行测量。为了研究这种行为表现增强的神经相关性，将使用功能性磁共振成像（fMRI）来测量知觉学习发生前后特定大脑区域的活动。fMRI实验将包括测量由视觉刺激引起的反应的振幅和估计在一些皮质区域的神经元群的选择性。[在感知学习之后，这些区域之间功能连接的变化也将被测量。选择性将在空间域和特征域（对刺激方向或运动方向的选择性）中定义。乙酰胆碱是一种神经递质，在大脑的注意力网络中起着重要作用。延长内源性乙酰胆碱（胆碱酯酶抑制剂）突触作用的药物是阿尔茨海默病最常见的治疗方法。虽然这些药物在生化水平上的作用已经被很好地表征，但它们的认知作用和这些作用的神经相关性却知之甚少。在知觉学习训练过程中，将给予胆碱酯酶抑制剂多奈哌齐（商品名：Aricept），以阐明乙酰胆碱在学习神经可塑性中的作用，并更好地了解这些药物改善阿尔茨海默病患者认知功能的机制。

DESCRIPTION (provided by applicant): The long-term objective of this project is to characterize neural correlates of perceptual learning in the human visual system. Perceptual learning can be defined as a specific improvement in the performance of a perceptual discrimination through training. Humans are capable of learning new and intricate skills throughout the lifespan, and perceptual learning experimental paradigms provide model systems for studying these processes. In addition, training procedures involving perceptual learning have been used to treat learning disorders like dyslexia and developmental disorders such as amblyopia. Therefore, understanding the neural mechanisms underlying perceptual learning has consequences for basic science as well as public health implications. Two perceptual learning tasks will be employed in these studies: a motion direction discrimination task and a texture orientation discrimination task. These tasks differentially involve two different visual processing streams in the human brain. One of these specialized for perception of motion and spatial location, and the other is specialized for perception of visual form. Human subjects will be trained on these tasks, and the improvements in behavioral performance resulting from this training will be measured. To study neural correlates of this enhancement in behavioral performance, functional magnetic resonance imaging (fMRI) will be used to measure the activity in defined brain areas before and after perceptual learning occurs. The fMRI experiments will include measurements of the amplitude of responses evoked by visual stimuli and estimates of selectivity of populations of neurons in a number of cortical areas. [Changes in functional connectivity among these areas following perceptual learning will also be measured.] Selectivity will be defined in the spatial domain and in the featural domain (selectivity for stimulus orientation or direction of motion). Acetylcholine is a neurotransmitter that plays an important role in attention networks in the brain. Drugs that prolong the synaptic actions of endogenous acetylcholine (cholinesterase inhibitors) are the most common treatment of Alzheimer's disease. Although the actions of these drugs at the biochemical level are well characterized, their cognitive effects and neural correlates of these effects are poorly understood. The cholinesterase inhibitor donepezil (trade name: Aricept) will be administered during the perceptual learning training procedures to shed light on the role of acetylcholine on learning neural plasticity and to better understand the mechanisms by which these drugs improve cognitive function in patients with Alzheimer's disease. PUBLIC HEALTH RELEVANCE: We will use magnetic resonance imaging (MRI) to measure brain activity in healthy human subjects before and after they undergo a training procedure that improves their ability to make visual discriminations. A variety of MRI measurements will be made to characterize the changes that take place in the brains of subjects as a result of this learning. In addition, the subjects will be administered donepezil, an Alzheimer's medication known to enhance cognition, and the effects of this drug on the perceptual and brain correlates of learning will be determined.