Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference^1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta–gamma phase–amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory^1,2, with frontal control managing maintenance of working memory content in storage-related areas^3,4,5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.

在工作记忆中保留信息是一个要求很高的过程，它依赖于认知控制来保护特定于备忘录的持久活动免受干扰^1,2。然而，认知控制如何调节工作记忆存储尚不清楚。在这里，我们表明额叶控制和海马持续活动的相互作用是通过 theta-gamma 相位-幅度耦合（TG-PAC）来协调的。我们记录了人类内侧颞叶和额叶中的单个神经元，而患者在其工作记忆中保留了多个项目。在海马体中，TG-PAC 指示工作记忆负荷和质量。我们鉴定出在 θ 相和伽马振幅的非线性相互作用期间选择性尖峰的细胞。当认知控制需求较高时，这些 PAC 神经元的尖峰时间与额叶 θ 活动相协调。通过引入与海马中持续活跃的神经元的噪声相关性，PAC 神经元塑造了群体代码的几何形状。这导致了与行为改善相关的工作记忆内容的更高保真度表示。我们的结果支持工作记忆的多组件架构^1,2，其中前端控制管理存储相关区域中工作记忆内容的维护^3,4,5。在此框架内，海马 TG-PAC 整合了整个大脑区域的认知控制和工作记忆存储，从而提出了一种对感觉驱动过程进行自上而下控制的潜在机制。