Multimodal approaches towards a better understanding of feelings of familiarity

熟悉是一种基本的记忆过程，它提醒我们以前经历过一些事情。研究人员使用了三种常用的方法来测量熟悉度。这项研究报告说，与年轻人相比，健康老年人的熟悉度不足很小，有时甚至很大。遗忘型轻度认知障碍（aMCI）在熟悉性研究中特别令人感兴趣，因为最早的病理发生在嗅周皮层（即，Braak和Braak的“transentorhinal”皮质）和内嗅皮质，这两个区域显示aMCI中的细胞损失和皮质变薄。大多数神经影像学研究发现，嗅周激活与熟悉性相关，对局灶性病变患者的研究发现，熟悉性缺陷损害了嗅周皮层。因此，与健康的老年人相比，假设aMCI中的熟悉度受损是合乎逻辑的，但证据是均匀混合的：当条件支持高水平的回忆时，aMCI中的熟悉度是多余的，但当条件支持低水平的回忆时，aMCI中的熟悉度受损，与健康的同龄人相比。我认为，在aMCI中，回忆的贡献更大，这掩盖了熟悉度的不足，并且可能在健康的老龄化中，我们需要利用新的方法来测量无回忆背景下的熟悉度。我建议在健康的年轻人和老年人的熟悉性研究中监督HQP，患有嗅周皮质病变的成年人，以及患有aMCI导致的神经退行性嗅周皮质的老年人。前五个实验将从行为的角度研究熟悉度。实验1，2和5将集中在熟悉的编码操作，通过改变刺激的频率是偶然编码之前的频率评级。实验3、4和5将侧重于检索操作熟悉性，使用响应截止日期程序和无识别识别程序。在最强大的编码和检索操作的熟悉度的生物标志物，然后将在实验6，7和8中进一步检查，使用事件相关电位，瞳孔放大，和皮肤电导反应。我预测，与健康的年轻人相比，健康的老年人，特别是由于aMCI或病变而导致嗅周皮层受损的人，将表现出熟悉缺陷和早期旧/新事件相关的潜在影响，瞳孔扩张和皮肤电导潜伏期受损。这项建议注意到呼吁挑战的基本概念，回忆和熟悉是随机独立的，并提供了一个多模态的方法，将重塑该领域的熟悉感的理解。了解被保留和受损的熟悉感将使我们更好地理解人类记忆经验的范围。

Familiarity is a fundamental memory process that alerts us that we have experienced something before. Researchers have used one of three prevailing methods used to measure familiarity. This research has reported small and sometimes significant familiarity deficits in healthy older adults, compared to younger adults. Amnestic mild cognitive impairment (aMCI) is of particular interest in the study of familiarity because the earliest pathology occurs in the perirhinal cortex (i.e., Braak & Braak's ‘transentorhinal' cortex) and entorhinal cortex, two regions that show cell loss and cortical thinning in aMCI. Most neuroimaging research finds perirhinal activation associated with familiarity, and research with patients with focal lesions finds familiarity deficits damage to the perirhinal cortex. It would thus be logical to hypothesize that familiarity is impaired in aMCI, compared to healthy older adults, but the evidence is evenly mixed: when conditions support high levels of recollection, familiarity is spared in aMCI, but when conditions support low levels of recollection, familiarity is impaired in aMCI, compared to their healthy counterparts. I suggest that higher contributions of recollection overshadow familiarity deficits in aMCI, and potentially in healthy aging, and that we need to utilize new methods to measure familiarity in recollection-free contexts.******I propose to supervise HQP in the study of familiarity in healthy younger and older adults, adults with lesioned perirhinal cortex, and older adults with neurodegenerated perirhinal cortex due to aMCI. The first five Experiments will examine familiarity from a behavioural perspective. Experiments 1, 2, and 5 will focus on encoding manipulations of familiarity, by varying the frequency with which stimuli are incidentally encoded prior to frequency ratings. Experiments 3, 4, and 5 will focus on retrieval manipulations familiarity, using a response deadline procedure, and a recognition-without-identification procedure. Biomarkers of familiarity in the most robust encoding and retrieval manipulations will then be further examined in Experiments 6, 7, and 8, using event-related potentials, pupil dilation, and skin conductance responses. I predict that compared to healthy young adults, healthy older adults and especially people with damaged perirhinal cortex due to aMCI or lesions will demonstrate familiarity deficits and compromised early old/new event-related potential effects, pupil dilation, and skin conductance latency.******This proposal heeds calls to challenge the fundamental notion that recollection and familiarity are stochastically independent, and provides a multimodal approach that will reshape the field's understanding of feelings of familiarity. Understanding both spared and impaired feelings of familiarity will provide us with a better understanding of the range of human mnemonic experience.