Control of working memory by phase-amplitude coupling of human hippocampal neurons.

Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. 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 memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3-5. 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.

Dataset of human-single neuron activity during a Sternberg working memory task.

We present a dataset of 1809 single neurons recorded from the human medial temporal lobe (amygdala and hippocampus) and medial frontal lobe (anterior cingulate cortex, pre-supplementary motor area, ventral medial prefrontal cortex) across 41 sessions from 21 patients that underwent seizure monitoring with depth electrodes. Subjects performed a screening task (907 neurons) to identify images for which highly selective cells were present. Subjects then performed a working memory task (902 neurons), in which they were sequentially presented with 1-3 images for which highly selective cells were present and, following a maintenance period, were asked if the probe was identical to one of the maintained images. This Neurodata Without Borders formatted dataset includes spike times, extracellular spike waveforms, stimuli presented, behavior, electrode locations, and subject demographics. As validation, we replicate previous findings on the selectivity of concept cells and their persistent activity during working memory maintenance. This large dataset of rare human single-neuron recordings and behavior enables the investigation of the neural mechanisms of working memory in humans.