Cortico-Hippocampal Circuit Dynamics in Humans

项目摘要：快速学习的能力是人类认知的定义特征之一。 尽管它很重要，但控制人类快速学习的回路机制尚不清楚。一直以来 提出先验知识或“心理图式”通过前额叶-海马区促进快速学习 网络互动促进新联想记忆的习得。然而，经验证据是有限的。 支持这种学习模式的证据。此外，FAST背后的电路动力学比较 人类和非人类灵长类动物之间还没有进行过学习。该提案在系统之间架起桥梁 跨灵长类物种的神经科学，解决了三个基本知识差距：1)电路动力学 在支持联想和分类学习的前额叶皮质和海马体之间，2) 过夜睡眠对记忆保持的影响，3)神经活动和回路的共性和差异 人类与非人类灵长类动物在学习过程中的动态变化。为了建立跨物种的比较， 我们将在人类身上进行一系列与非人类灵长类项目密切相关的实验，以阐明 基于快速图式和基于范畴的大脑皮质-海马区相互作用的电路机制 学习。癫痫患者的术前评估提供了一个独特而有力的机会 直接研究这些大脑网络。特别是，我们将使用大规模的高密度颅内电极来 记录患者在进行联合和治疗时前额叶皮质和海马区的神经信号 分类学习。我们还将利用记录人类单个神经元的独特能力 海马区和前额内侧区域，直接比较不同物种的神经活动。我们的研究将 极大地促进了学习和记忆的神经生物学，对学习和记忆的损伤形成了 各种神经系统疾病，如阿尔茨海默病、自闭症、重度抑郁症和癫痫。 了解快速学习的神经机制将为开发电路提供关键的框架 对记忆障碍者的特殊干预。

PROJECT SUMMARY: The ability to learning rapidly is one of the defining features of human cognition. Despite its importance, the circuit mechanism that governs rapid learning in humans is unknown. It has been proposed that prior-knowledge or a “mental schema” facilitates rapid learning via prefrontal-hippocampal network interactions to improve acquisition of novel associative memory. There is, however, limited empirical evidence supporting this model of learning. Moreover, comparisons of circuit dynamics underlying rapid learning have not been conducted between humans and nonhuman primates. The proposal bridges systems neuroscience across primate species and addresses three fundamental knowledge gaps: 1) Circuit dynamics between the prefrontal cortex and hippocampus that support associative and categorical learning, 2) The influence sleep overnight on memory retention, 3) Commonalities and differences in neural activity and circuit dynamics between human and nonhuman primates during learning. To establish cross-species comparisons, we will conducts a set of experiments in humans tightly linked to the nonhuman primate projects to elucidate the circuit mechanisms of cortical-hippocampal interactions during rapid schema-based and categorical learning. The pre-surgical evaluation of patients with epilepsy provides a unique and potent opportunity to study these brain networks directly. Specially, we will use large-scale high-density intracranial electrodes to record neural signals from prefrontal cortex and hippocampus while patients perform associative and categorical learning. We will also leverage the unique ability to record single neurons in the human hippocampus and medial prefrontal regions to directly compare neural activity across species. Our studies will greatly advance the neurobiology of learning and memory, for which impairments form core clinical features of diverse neurological disorders such as Alzheimer's disease, autism, major depression, and epilepsy. Understanding the neural mechanisms of rapid learning will provide critical framework to develop circuit specific intervention in people with disordered memory.