Neuronal firing in the medial temporal lobe reflects human working memory workload, performance and capacity

The involvement of the medial temporal lobe (MTL) in working memory is controversially discussed. Critically, it is unclear whether and how the MTL supports performance of working memory. We recorded single neuron firing in 13 epilepsy patients while they performed a visual working memory task. The number of colored squares in the stimulus set determined the workload of the trial. We used the subjects’ memory capacity (Cowan’s K) to split them into a low and high capacity group. We found MTL neurons that showed persistent firing during the maintenance period. Firing was higher in the hippocampus for trials with correct compared to incorrect performance. Population firing predicted workload particularly during the maintenance period. Prediction accuracy of single trial activity was strongest for neurons in the entorhinal cortex of low capacity subjects. We provide evidence that low capacity subjects recruit their MTL to cope with an overload of working memory task demands. 1 Significance Humans are highly limited in processing multiple objects over a short period of time. The capacity to retain multiple objects in working memory is typically associated with frontal and parietal lobe functioning, even though medial temporal lobe (MTL) neural architecture seems capable to process such information. However, there are conflicting findings from patient, electrophysiological and neuroimaging studies. Here we show for the first time that correct performance, workload and individual performance differences are reflected in separate mechanisms of neural activity within the MTL during maintenance of visual information in working memory. The data suggest that low capacity subjects use the MTL to process the overload of information.