Cortico-Hippocampal Circuit Dynamics in Humans

快速学习的能力是人类认知的定义特征之一。 尽管它的重要性，控制人类快速学习的电路机制是未知的。已经 提出先验知识或“心理图式”通过前额叶-海马促进快速学习， 网络互动，以提高新的联想记忆的收购。然而，有限的经验 支持这种学习模式的证据。此外，比较电路动态基础快速 人类和非人类灵长类之间还没有进行过学习。该提案将系统连接起来， 神经科学跨越灵长类物种，并解决了三个基本的知识差距：1）电路动力学 支持联想和分类学习的前额叶皮层和海马体之间的联系，2） 影响夜间睡眠对记忆保持，3）神经活动和回路的共同点和差异 人类和非人类灵长类动物在学习过程中的动力学。为了建立跨物种比较， 我们将在人类身上进行一系列与非人类灵长类项目紧密相关的实验， 在快速的基于图式的和分类的认知过程中皮层-海马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效的机会， 直接研究这些大脑网络特别地，我们将使用大规模高密度颅内电极， 记录患者进行联想和记忆时前额皮质和海马的神经信号， 分类学习我们还将利用记录人类单个神经元的独特能力， 海马体和内侧前额叶区，以直接比较不同物种的神经活动。我们的研究将 极大地推进了学习和记忆的神经生物学，其中损伤形成了学习和记忆的核心临床特征。 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。 理解快速学习的神经机制将为开发电路提供关键框架 对记忆力紊乱的人进行特定的干预。

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.