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性。感知学习可以被定义为通过训练在感知辨别的性能上的特定改进。人类能够在整个生命周期中学习新的复杂技能，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，如阅读障碍和发育障碍，如弱视。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重要意义。在这些研究中将采用两个知觉学习任务：运动方向辨别任务和纹理方向辨别任务。这些任务不同地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。人类受试者将接受这些任务的训练，并将测量由这种训练产生的行为表现的改善。为了研究这种行为表现增强的神经相关性，功能性磁共振成像（fMRI）将用于测量感知学习发生前后定义的大脑区域的活动。功能磁共振成像实验将包括测量视觉刺激引起的反应幅度和估计一些皮层区域神经元群体的选择性。[还将测量感知学习后这些区域之间功能连接的变化。]选择性将在空间域和特征域中定义（刺激方向或运动方向的选择性）。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）的突触作用的药物是阿尔茨海默病最常见的治疗方法。虽然这些药物在生物化学水平上的作用已经得到了很好的表征，但它们的认知效应和这些效应的神经相关性却知之甚少。胆碱酯酶抑制剂多奈哌齐（商品名：安理申）将在知觉学习训练过程中给药，以阐明乙酰胆碱对学习神经可塑性的作用，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。 公共卫生相关性：我们将使用磁共振成像（MRI）来测量健康受试者在接受训练程序之前和之后的大脑活动，以提高他们的视觉辨别能力。将进行各种MRI测量，以表征由于这种学习而在受试者大脑中发生的变化。此外，受试者将被给予多奈哌齐，这是一种已知的增强认知的阿尔茨海默氏症药物，并且将确定这种药物对学习的感知和大脑相关性的影响。

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.