Precision and binding as two dimensions of medial temporal lobe amnesia

项目摘要 对人类内侧颞叶的损害会导致显著的且往往是长期的缺陷 言语记忆迟缓，称为内侧颞叶健忘症。而医学的模型 诸如陈述性记忆理论之类的颞叶功能假设了一个受限的角色 对于内侧颞叶的记忆功能，认知方面的共识越来越多 神经科学表明，这种缺陷还包括表征方面的损害。 对其他认知领域很重要，如知觉、注意力、工作记忆、 语言和空间导航。在这里，我们提出了一个新的模型来更好地解释 伴随着内侧颞叶病变的认知缺陷的范围。我们的模特 假设人类内侧颞叶功能最好描述为 同时涉及代表性精确度和约束性，预测赤字将增加 任务需求沿着这两个关键维度增加。AIM 1测试中的实验 我们的模型特别关注在以下上下文中测试表征精度 记忆和导航，让我们能够比较这些实验的结果 与陈述性记忆理论预测的结果相反。实验将包括测试 双侧内侧颞叶患者，包括以病变为主的患者 仅限于海马体，健康参与者的高分辨率fMRI研究 更好地确定海马区对精确度和 有约束力的。目标2将确定我们的模型的预测能力，结合 基于功能磁共振成像的网络建模，以解释伴随单侧内侧的缺陷 在治疗过程中因手术切除而导致的颞叶损伤 药物难治性癫痫。这项建议的预期结果是： 1)更完整地说明内侧颞叶病变的后果， 尤其是对海马体，对认知的影响 单独的神经心理测量2)更完整的效果预测模型 单侧颞叶切除对术后认知结果的影响 允许更大的灵活性来确定哪些患者应该接受 神经刺激(RNS)与切除3)建模是否为内侧外以及如何内侧 颞叶皮质网络可以弥补切除后功能的丧失4) 潜在地，新疗法的灵感涉及认知干预或 以遗忘样症状患者的完整皮质组织为靶点的神经刺激。

Project Abstract Lesions to the human medial temporal result in striking and often long-lasting deficits in delayed verbal memory, termed medial temporal lobe amnesia. While models of medial temporal lobe function, such as declarative memory theory, hypothesize a restricted role for the medial temporal lobe in memory function, a growing consensus in cognitive neuroscience suggests that such deficits also include impairments in representations important to other areas of cognition, such as perception, attention, working memory, language, and spatial navigation. Here, we propose a novel model to better account for the range of cognitive deficits that accompany medial temporal lobe lesions. Our model hypothesizes that human medial temporal lobe function can best be described as involving both representational precision and binding, predicting increasing deficits as task-demands increase along these two critical dimensions. Experiments in Aim 1 test our model with a particular focus on testing representational precision in the context of memory and navigation to allow us to compare the outcomes from these experiments against those predicted by declarative memory theory. Experiments will include testing with bilateral medial temporal lobe patients, including those with lesions primarily restricted to the hippocampus, and high-resolution fMRI studies in healthy participants to better determine the mechanistic basis of hippocampal contributions to precision and binding. Aim 2 will determine the predictive capacity of our model, in conjunction with fMRI-based network modeling, to explain deficits accompanying unilateral medial temporal lesions that occur as a result of surgical resections during treatment of pharmacologically intractable epilepsy. The anticipated outcomes from the proposal are: 1) a more complete account of the consequences of medial temporal lobe lesions, particularly to the hippocampus, on cognition than can be provided by neuropsychological measures alone 2) a more complete predictive model of the effects of unilateral temporal lobe resection on cognitive outcomes post-resection, possibly allowing greater flexibility in determining which patients should undergo responsive neurostimulation (RNS) vs. resection 3) modeling whether and how extra-medial temporal lobe cortical networks can compensate for lost function following resection 4) potentially, inspiration for novel therapies involving cognitive interventions or neurostimulation targeting intact cortical tissue in patients with amnestic-like symptoms.