Precision and binding as two dimensions of medial temporal lobe amnesia

内侧颞叶遗忘症二维的精确性和结合力

• 批准号: 10178134
• 负责人: ARNE D EKSTROM
• 金额: $ 53.9万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10178134
• 关键词: Affect; Amnesia; Area; Attention; Bilateral; Binding; Biological Assay; Brain; Brain Hypoxia-Ischemia; Breathing; Code; Cognition; Cognitive; Cognitive deficits; Complex; Consensus; Data; Delayed Memory; Dimensions; Encephalitis; Excision; Financial compensation; Functional Magnetic Resonance Imaging; Grant; Hippocampus (Brain); Human; Impaired cognition; Impairment; Intervention; Intractable Epilepsy; Language; Lesion; Measures; Medial; Memory; Modeling; Network-based; Neuropsychological Tests; Neuropsychology; Operative Surgical Procedures; Outcome; Partial Epilepsies; Participant; Patients; Pattern; Perception; Pharmacological Treatment; Pharmacology; Play; Population; Primary Lesion; Process; Recovery of Function; Resolution; Rest; Role; Short-Term Memory; Stroke; Symptoms; Temporal Lobe; Testing; Tissues; aged; base; cognitive function; cognitive neuroscience; cognitive recovery; experience; experimental study; flexibility; gray matter; improved; insight; long term memory; neocortical; nervous system disorder; network models; neuromechanism; novel; novel marker; novel strategies; novel therapeutics; predictive modeling; predictive tools; recruit; relating to nervous system; spatial memory; stroke patient; theories; two-dimensional; way finding

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.

项目摘要 人类内侧颞叶损伤会导致显着且往往是长期的功能缺陷 言语记忆延迟，称为内侧颞叶遗忘症。虽然内侧模型 颞叶功能，例如陈述性记忆理论，假设其作用有限 对于内侧颞叶的记忆功能，认知界日益达成共识 神经科学表明，这种缺陷还包括表征障碍 对其他认知领域很重要，例如感知、注意力、工作记忆、 语言和空间导航。在这里，我们提出了一种新颖的模型来更好地解释 伴随内侧颞叶病变的一系列认知缺陷。我们的模型 假设人类内侧颞叶功能可以最好地描述为 涉及表征精度和结合力，预测赤字不断增加 任务需求沿着这两个关键维度增加。目标 1 测试中的实验 我们的模型特别关注在以下情况下测试表征精度 记忆和导航使我们能够比较这些实验的结果 与陈述性记忆理论的预测相反。实验将包括测试 双侧内侧颞叶患者，包括主要病变的患者 仅限于海马体，并且对健康参与者进行高分辨率功能磁共振成像研究 更好地确定海马对精度和作用的贡献的机制基础 绑定。目标 2 将确定我们模型的预测能力，并结合 基于功能磁共振成像的网络模型，解释单侧内侧的缺陷 治疗期间因手术切除而发生的颞部病变 药物难治性癫痫。该提案的预期成果是： 1）更完整地说明内侧颞叶病变的后果， 特别是对于海马体，其认知能力比 单独的神经心理学测量 2) 更完整的影响预测模型 单侧颞叶切除术对切除后认知结果的影响，可能 允许更大的灵活性来确定哪些患者应该接受反应性治疗 神经刺激 (RNS) 与切除术 3) 建模是否以及如何外侧 颞叶皮质网络可以补偿切除后丧失的功能 4) 潜在地，涉及认知干预或新疗法的灵感 针对具有遗忘样症状的患者的完整皮质组织进行神经刺激。