Analysis of human cortical networks during sustained visuospatial attention

描述(申请人提供)：这个项目的长期目标是：1)确定人脑皮质区域中有助于视觉空间注意的功能网络，以及2)确定操纵突触水平的乙酰胆碱对这些功能网络的生理影响。人类利用空间注意力来选择与他们当前行为目标最相关的视野部分。如果视觉刺激出现在有人看管的位置，观察者对刺激的感知比同样的刺激出现在无人看管的位置更准确。这种知觉的改善被认为是由于注意力信号通过顶叶皮质传递到早期的视觉皮质区域。然而，将这些注意信号传递到视觉皮质的神经通路在很大程度上是未知的。乙酰胆碱是一种神经递质，在大脑的注意力网络中发挥着重要作用。延长内源性乙酰胆碱(胆碱酯酶抑制剂)突触作用的药物可以改善受试者在注意力任务中的表现。然而，关于乙酰胆碱对注意信号的生理影响，我们知之甚少。许多以注意力网络受损为特征的大脑紊乱证明了注意力对行为的根本重要性。注意力异常是注意力缺陷障碍的中心症状。此外，许多与阿尔茨海默病相关的精神障碍都可以追溯到注意力不集中。我们将使用神经成像(功能磁共振成像，或fMRI)来测量受试者在执行要求注意力的任务时特定大脑区域的活动。在任务执行过程中，这些区域的活动变化将通过使用我们团队最近开发的连贯和部分连贯方法在确定的大脑区域进行比较，以表征注意路径和注意信号流向视觉皮质。此外，受试者将接受多奈哌齐(商标：Aricept)、一种胆碱酯酶抑制剂和阿尔茨海默氏症药物的治疗，以提高注意力。这种药物对潜在注意力的功能网络的影响将被测量。与公众健康的相关性我们将使用磁共振成像(MRI)来测量健康受试者在特定视觉位置保持注意力时的大脑活动。许多大脑区域的活动将被比较，以确定负责视觉注意力的大脑区域网络。此外，受试者将接受多奈哌齐的治疗，这是一种已知的改善注意力的阿尔茨海默氏症药物，我们将测量这种药物对大脑活动和持续注意力期间大脑区域之间通信的影响。

DESCRIPTION (provided by applicant): The long-term objectives of this project are 1) to identify functional networks of cortical areas in the human brain that subserve visual spatial attention, and 2) to determine the effects of manipulation of synaptic levels of acetylcholine on the physiology of these functional networks. Humans employ spatial attention to select portions of the visual field that are most relevant for their current behavioral goals. If a visual stimulus appears in an attended location, observers perceive the stimulus more accurately than if the same stimulus is presented to an unattended location. This improvement in perception is thought to be due to attention signals that are transmitted by parietal cortex to early visual cortical areas. However, the neural pathways that carry these attention signals to visual cortex are largely unknown. 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) improve performance on attention tasks in human subjects. However, very little is known regarding the physiological effects of acetylcholine on attention signals. The fundamental importance of attention for behavior is demonstrated by the many brain disorders characterized by compromised attention networks. Attention abnormalities are the central symptom in Attention Deficit Disorder. Additionally, many of the mental impairments that have been associated with Alzheimer's disease can be traced to a failure of attention. We will use neuroimaging (functional magnetic resonance imaging, or fMRI) to measure the activity in defined brain areas while subjects are performing attention-demanding tasks. Changes in activity in these areas during task performance will be compared across the identified brain areas, using coherency and partial coherency methods recently developed by our group, to characterize attention pathways and flow of attention signals to visual cortex. In addition, subjects will be administered donepezil (trade name: Aricept), a cholinesterase inhibitor and Alzheimer's medication that enhances attention. The effects of this drug on the functional networks underlying attention will be measured. PUBLIC HEALTH RELEVANCE We will use magnetic resonance imaging (MRI) to measure brain activity in healthy human subjects while they are maintaining attention at a defined visual location. The activity in many brain areas will be compared to identify the network of brain regions that is responsible for visual attention. In addition, the subjects will be administered donepezil, an Alzheimer's medication known to improve attention, and we will measure the effects of this drug on brain activity and the communication between brain areas during sustained attention.