Neuronal Correlates of Memory in the Human Temporal Lobe

描述（由申请人提供）：我们的总体目标是更好地了解健康和疾病中人类记忆的神经元基础。尽管有大量的研究，但在人类单个神经元水平上，关于陈述性记忆的大脑机制的数据非常缺乏。这些数据可以弥合动物基础神经元研究和人类功能性磁共振成像（fMRI）研究之间的差距。从植入人内侧颞叶（MIL）区域的深度电极直接记录是可能的，因为我们的受试者是癫痫患者，他们需要放置电极来识别癫痫发作病灶，以便以后切除。到目前为止，我们的NIH资助的研究已经阐明了编码和检索过程中单个神经元对复杂视觉刺激的反应的关键特征。现在，我们的主要目标是表征人类陈述性记忆过程的所有三个主要方面：（1）联想表征，（2）事件的时间顺序组织，（3）相关记忆中共同特征的提取。我们建议使用更接近人类情景记忆的任务，包括刺激序列和刺激关联以及沉浸式虚拟现实导航任务。这项研究的中心假设是内侧颞叶的神经元使用两种编码来进行陈述性记忆：（1）基于神经元放电频率的速率编码，它是稀疏的，受到抑制的强化，对复杂刺激具有高度特异性，但非常抽象。正是这种代码构成了共同特征的联想表示和抽象的基础。以及（2）时间代码，基于由振荡模式和神经元放电的相位锁定驱动的尖峰的定时。正是这种代码构成了事件的时间顺序组织的基础。我们仍然是能够在单个神经元水平和局部场电位水平上解决这些关于人类记忆的基本问题的主要小组。我们的研究为理解和管理阿尔茨海默氏症，颞叶癫痫和其他神经系统疾病的记忆障碍铺平了道路。

DESCRIPTION (provided by applicant): Our overall goal is to provide a better understanding of the neuronal basis of human memory in health and disease. Despite considerable research, there is a critical dearth of data at the single neuron level in humans on brain mechanisms underlying declarative memory. Such data can bridge the gap between basic neuronal research in animals, and human functional magnetic resonance imaging (fMRI) research. Direct recording from depth electrodes implanted in human medial temporal lobe (MIL) areas is possible because our subjects are epilepsy patients who require electrode placement to identify the seizure focus for later resection. Our NIH-funded studies to date have elucidated key characteristics of single neuron responses to complex visual stimuli during encoding and retrieval. Now our primary objective is to characterize single neuronal responses and local field potentials (LFPs) during all three major aspects of human declarative memory processes: (1) associative representations, (2) temporal sequential organization of events, and (3) abstraction of common features among related memories. We propose to use tasks that more closely approximate human episodic memory, including sequences of stimuli and stimulus associations and an immersive virtual reality navigational task. The central hypothesis of this study is that neurons in the medial temporal lobe use two codes for declarative memory: (1) a rate code, based on neuronal firing rate, which is sparse, accentuated by inhibition, highly specific to complex stimuli, yet strikingly abstract. It is this code that underlies associative representations and abstraction of common features. And (2) a temporal code, based on timing of spikes that is driven by oscillatory patterns and phase locking of neuronal firing. It is this code that underlies temporal sequential organization of events. We remain the main group in a position to address these fundamental questions about human memory at both the single neuron level and the level of local field potentials. Our studies pave the way to understanding and managing memory impairment in Alzheimer's, temporal lobe epilepsy and other neurological diseases.