Rethinking the neuroanatomical organization of cognition: Recognition memory in visual cortex

项目摘要 到2035年，65岁以上的美国居民人数将超过35岁以下的人数， 占美国人口的20%。与此同时，到2050年，世界人口预计将增加17%， 1.6 10亿65岁或以上的人。记忆力的渐进性缺陷是衰老的一个常见事实，除了 是阿尔茨海默病的主要症状然而，治疗记忆障碍，如在衰老中看到的， 和老年痴呆症是有限的。一个障碍是，我们仍然没有彻底了解如何 大脑系统在功能上被组织成在健康的大脑中产生记忆。基于案例研究，如 病人H.M.，传统的认知理论是用计算过程来解释记忆和知觉的 由可分离的大脑区域（或不同的大脑网络）组成。相反，代表性层次（R-H） 一个假设是，一个大脑区域可以参与任何认知任务，如果它包含最佳的表征， 解决任务。这个建议的具体目标是测试我的总体假设， 根据表征，区域有助于认知任务--无论是知觉任务还是记忆任务 它们包含。R-H理论假设认知的组织（即，记忆和知觉）， 大脑是更好地理解方面的一个层次连续的代表，而不是解剖 模块（或限定的“网络”）用于不同的认知过程，如“情景记忆”。中央 这个建议的假设是陈述性记忆可能是在感觉皮层中计算的，而不涉及大脑皮层。 内侧颞叶（MTL）。目标1将决定是否识别记忆可以支持 规范存储器区域之外的结构（即，MTL），在已知介导感知的大脑区域 (e.g.,视觉皮层）。在这项功能磁共振成像研究中，我将测试参与者的（长期的，陈述性的）识别记忆， 他们研究过的刺激。我假设，如果要记住的项目是抽象的视觉对象， 视觉特征的连接，如果任务需要识别熟悉的与新的连接， 特征，那么支持记忆的大脑区域将落在MTL之外，在视觉皮层部位，如外侧 枕叶皮质目标2将测试老化（与早期MTL劣化相关）是否导致更大的 高水平的联想刺激比低水平的视觉刺激的识别记忆的赤字。我会 使用目标1中的视觉刺激，沿着类似的词对刺激。我们假设MTL 网络老化恶化。我的工作假设，来自R-H理论，是老年人会 相对于年轻的成年人，单词对的表现比视觉刺激差，因为单词对（但不是视觉刺激） 刺激）需要高水平的表示，这是MTL依赖的。该提案具有翻译和 理论意义这些结果将决定R-H理论是否能更好地解释 人类大脑如何产生认知这两个目标可能为改进诊断和治疗奠定基础 老年痴呆症和老年痴呆症的记忆障碍，可能减轻病人的痛苦和家庭负担。

PROJECT SUMMARY By 2035, the number of US residents over 65 years will surpass the number under the age of 35 years, totaling 20% of the US population. Meanwhile, by 2050 the world population is projected to increase by 17%, to include 1.6 billion people aged 65 or older. Progressive deficits in memory are a common fact of aging, in addition to being a primary symptom of Alzheimer's disease. Yet, treatments for memory disorders such as seen in aging and Alzheimer's are limited. One obstacle is that we still have not attained a thorough understanding of how brain systems are functionally organized to produce memory in the healthy brain. Based on case studies like patient H.M., traditional accounts of cognition explain memory and perception in terms of processes computed by separable brain regions (or distinct brain networks). In contrast, the Representational-Hierarchical (R-H) account posits that a brain region can be engaged in any cognitive task, if it contains optimal representations for solving the task. The specific objective of this proposal is to test my overarching hypothesis that brain regions contribute to a cognitive task – be it perceptual or mnemonic – according to the representations they contain. The R-H Theory postulates that the organization of cognition (i.e., memory and perception) in the brain is better understood in terms of a hierarchical continuum of representations, as opposed to anatomical modules (or circumscribed "networks") for distinct cognitive processes like "episodic memory". The central hypothesis of this proposal is that declarative memory may be computed in sensory cortex without involving the medial temporal lobe (MTL). Aim 1 will determine whether recognition memory can be supported by structures outside of canonical memory regions (i.e., MTL), in brain areas known to mediate perception (e.g., visual cortex). In this fMRI study, I will test participants' (long-term, declarative) recognition memory for stimuli they have studied. I hypothesize that if to-be-remembered items are abstract visual objects comprising conjunctions of visual features, and if the task requires recognition of familiar versus novel conjunctions of features, then the brain regions supporting memory will fall outside of MTL, in visual cortical sites such as lateral occipital cortex. Aim 2 will test whether aging (associated with incipient MTL deterioration) leads to greater deficits in recognition memory for high-level associative stimuli than for low-level visual stimuli. I will use the visual stimuli from Aim 1, along with analogously constructed word-pair stimuli. We assume that MTL networks deteriorate in aging. My working hypothesis, derived from the R-H Theory, is that older adults will perform worse for word pairs than visual stimuli, relative to younger adults, because word-pairs (but not visual stimuli) require high-level representations, which are MTL-dependent. This proposal has translational and theoretical significance. The results will determine whether the R-H Theory provides a better explanation of how human brains give rise to cognition. Both aims may lay the groundwork for improved diagnosis and treatment of memory disorders in aging and Alzheimer's, potentially alleviating patient suffering and familial burdens.