Testing a Novel Theoretical Framework for the Human Medial Temporal Lobes in Perception and Memory During Spatial Navigation

 描述(由申请人提供)：本项目的目标是测试一种新的理论框架，该框架将人类内侧颞叶的记忆和导航功能联系起来。虽然在大鼠和人类身上进行的大量研究表明，内侧颞叶对导航和记忆的重要性，但这两种功能仍然缺乏联系。我们的理论框架认为，人类内侧颞叶的损伤会导致高分辨率感知和记忆中细节绑定的缺陷。因此，该模型的一个预测是，内侧颞叶受损的患者在导航过程中将显示出编码高分辨率空间细节的缺陷。这将具体表现在导航过程中空间精确度的损害，而不是患者是否使用远端地标(向心)或自我定向(以自我为中心)提示进行导航。这与其他导航模型形成鲜明对比，其他模型认为MTL损伤将损害同心导航，但不会损害自我中心导航。我们将测试我们的模型，让患者在一个大舞台上导航，寻找一个隐藏的平台，并将他们的表现与一组年龄和智商匹配的健康对照组进行比较。我们模型的第二个预测是，内侧颞叶损伤将损害导航过程中时空细节的绑定。我们将通过比较患者在试验中必须记住多个空间位置时的表现来测试我们模型的这一预测。我们预计，与对照组相比，患者的表现会随着他们必须记住的位置数量的增加而恶化。这与其他导航和记忆模型的预测形成鲜明对比，其他模型表明，无论患者必须记住多少位置，都会损害局部中心记忆。因此，我们的模型提供了新颖但可测试的预测，即这笔R03种子赠款将有助于我们的发展。使用虚拟现实和针对内侧颞叶的高分辨率磁共振成像(MRI)等创新工具也将进一步加深我们对中风等神经疾病如何影响大脑功能和认知的理解。

 DESCRIPTION (provided by applicant): The goal of this project is to test a novel theoretical framework that relates memory and navigation functions of the human medial temporal lobes. While numerous studies in rats and humans suggest the importance of the medial temporal lobes to navigation and memory, these two functions remains poorly linked. Our theoretical framework argues that damage to the human medial temporal lobes results in deficits in both high-resolution perception and binding of details in memory. Thus, one prediction of this model is that patients with medial temporal lobe damage will show deficits in encoding high-resolution spatial details during navigation. This will manifest specifically in impairments in spatial precison during navigation rather than whether patients use distal landmarks (allocentric) or self-orientation (egocentric) cues to navigate. This contrasts with other models of navigation that suggest that MTL damage will impair allocentric but not egocentric navigation. We will test our model by having patients navigate a large arena, searching for a hidden platform, and compare their performance with a group of age and IQ matched healthy controls. A second prediction of our model is that medial temporal lobe damage will impair binding of spatiotemporal details during navigation. We will test this prediction of our model by comparing patient performance when they must remember multiple spatial locations over trials. We expect patient performance to worsen as a function of the number of locations they must remember compared to controls. This contrasts with the predictions of other models of navigation and memory, which suggest impairments in allocentric memory regardless of the number of locations the patient must remember. Our model thus provides novel yet testable predictions that this R03 seed grant will be instrumental in helping us to develop. Use of innovative tools such as virtual reality and high-resolution magnetic resonance imaging (MRI) targeting the medial temporal lobes will also further our understanding of how neural disease such as stroke impacts both brain function and cognition more generally.