Understanding visual working memory in Alzheimer's disease

描述(申请人提供)：最近的研究表明，与健康的老年人相比，阿尔茨海默病(AD)患者对简单视觉特征的视觉工作记忆(VWM)能力正常。相比之下，AD患者对复杂物体的视觉感觉能力降低，这是由于将复杂物体的视觉特征结合在一起的能力受损造成的。理解这种绑定障碍背后的认知和神经基础是至关重要的，因为VWM对于基本的视觉任务至关重要，例如导航新环境、注意风景的变化、在杂乱的空间中寻找物体和驾驶。几十年的研究表明，视觉工作记忆是一个复杂的过程，可以分为几个加工阶段。这包括编码的早期阶段，其创建先前观看的信息的心理表征，以及在不需要外部刺激的情况下存储表征的后期维护阶段。这些阶段中的每一个阶段都受到多种因素的调节，包括那些涉及感知、注意力和记忆的阶段。重要的是，注意缺陷是VWM约束性损害的候选来源，因为已知AD患者在某些条件下存在视觉注意缺陷，并且视觉注意参与编码和维持阶段。这项建议使用行为和脑电(EEG)方法来确定是否视觉注意的变化，而不是感知和记忆的变化，是导致AD患者在VWM中绑定特征的能力减弱的原因。具体目标针对调节VWM编码和维护阶段的不同因素。目标1将验证这样一种假设，即VWM结合中与AD相关的损害是由于信息编码到VWM过程中视觉注意力的减少所致。目标1下的一个行为和一个事件相关电位(ERP)实验将使用快速连续视觉呈现(RSVP)任务的变化来确定AD患者的绑定错误是由于导致信息丢失的知觉缺陷还是导致信息绑定不良的注意力缺陷造成的。目的2将检验这样一种假设，即VWM中与AD相关的结合损害是由于VWM中信息维持过程中视觉注意力的减少所致。Aim 2下的一项ERP实验将使用变化检测任务来确定AD患者对复杂对象的VWM能力降低是由于记忆衰退还是注意力绑定受损，而另一项行为实验将检查基于注意力的排练是否会减少AD患者的VWM绑定错误，并导致他们对复杂对象的VWM能力提高。这项研究的结果可能会为行为应用提供潜在的信息，以便根据AD患者视觉认知的变化来适应他们的生活环境。这一结果也可能为药理管理提供一个潜在的靶点。这类应用可通过延长AD患者的独立生活时间和改善患者的生活质量，帮助减轻家庭和一般医疗系统的经济负担。

DESCRIPTION (provided by applicant): Recent work has shown that patients with Alzheimer's disease (AD) have a normal visual working memory (VWM) capacity for simple visual features when compared to healthy older adults. In contrast, AD patients have reduced VWM capacity for complex objects, resulting from an impaired ability to bind the visual features of complex objects together. Understanding the cognitive and neural basis underlying this binding impairment is critical because VWM is vitally important for basic visual tasks, such as navigating new environments, noting changes in the landscape, finding objects in a cluttered space, and driving. Decades of previous research have indicated that VWM is a complex process that can be divided into several processing stages. These include an early stage of encoding that creates a mental representation of previously viewed information and a later stage of maintenance that stores the representation without requiring external stimulation. Multiple factors mediate each of these stages, including those involving perception, attention, and memory. Importantly, a deficit of attention stands out as a candidate source of VWM binding impairments because AD patients are known to have deficits of visual attention under certain conditions, and visual attention is involved in both encoding and maintenance stages. This proposal employs behavioral and electroencephalogram (EEG) methods to determine whether changes in visual attention, rather than perception and memory, underlie AD patients' diminished ability to bind features in VWM. The specific aims target the different factors that mediate VWM stages of encoding and maintenance. Aim 1 will test the hypothesis that AD-related impairments in VWM binding result from diminished visual attention during the encoding of information into VWM. One behavioral and one event-related potential (ERP) experiment under Aim 1 will use variations of the rapid serial visual presentation (RSVP) task to determine whether AD patients' binding errors result from perceptual deficits that lead to the loss of information or attentional deficits that lead to poor binding of information. Aim 2 will test the hypothesis that AD-related impairments in VWM binding result from diminished visual attention during the maintenance of information in VWM. One ERP experiment under Aim 2 will use a change detection task to determine whether AD patients' reduced VWM capacity for complex objects results from memory decay or impaired attentional binding, while one behavioral experiment will examine whether attention-based rehearsal will reduce VWM binding errors in AD patients and result in their improved VWM capacity for complex objects. The results of this research could potentially inform behavioral applications for accommodating the living environments for AD patients according to changes in their visual cognition. The results could also provide a potential target for pharmacological management. Such applications could help to ameliorate financial burdens on the family and the healthcare system in general by prolonging independent living and improving the quality of life of patients living with AD.