Persistent neuronal firing in the medial temporal lobe supports performance and workload of visual working memory in humans.

The involvement of the medial temporal lobe (MTL) in working memory is controversially discussed. Recent findings suggest that persistent neural firing in the hippocampus during maintenance in verbal working memory is associated with workload. Here, we recorded single neuron firing in 13 epilepsy patients (7 male) while they performed a visual working memory task. The number of colored squares in the stimulus set determined the workload of the trial. Performance was almost perfect for low workload (1 and 2 squares) and dropped at high workload (4 and 6 squares), suggesting that high workload exceeded working memory capacity. We identified maintenance neurons in MTL neurons that showed persistent firing during the maintenance period. More maintenance neurons were found in the hippocampus for trials with correct compared to incorrect performance. Maintenance neurons increased and decreased firing in the hippocampus and increased firing in the entorhinal cortex for high compared to low workload. Population firing predicted workload particularly during the maintenance period. Prediction accuracy of workload based on single-trial activity during maintenance was strongest for neurons in the entorhinal cortex and hippocampus. The data suggest that persistent neural firing in the MTL reflects a domain-general process of maintenance supporting performance and workload of multiple items in working memory below and beyond working memory capacity. Persistent neural firing during maintenance in the entorhinal cortex may be associated with its preference to process visual-spatial arrays.