The maintenance of items in working memory (WM) relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in WM by activating their phonological loop. We recorded local field potentials from the hippocampus, reconstructed beamforming sources of scalp EEG, and – additionally in four participants – recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the [4 8] Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.

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Significance 15Humans are highly limited in processing multiple objects over a short period of time. 16The capacity to retain multiple objects in working memory is typically associated with 17 frontal and parietal lobe functioning, even though medial temporal lobe (MTL) neural 18 architecture seems capable to process such information. However, there are 19 conflicting findings from patient, electrophysiological and neuroimaging studies. Here 20 we show for the first time that correct performance, workload and individual 21 performance differences are reflected in separate mechanisms of neural activity 22 within the MTL during maintenance of visual information in working memory. The 23 data suggest that low capacity subjects use the MTL to process the overload of 24 information. 25 Abstract 26The involvement of the medial temporal lobe (MTL) in working memory is 27 controversially discussed. Critically, it is unclear whether and how the MTL supports 28 performance of working memory. We recorded single neuron firing in 13 epilepsy 29 patients while they performed a visual working memory task. The number of colored 30

Background: The maintenance of items in working memory (WM) relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information between sensory areas and hippocampus during encoding and maintenance of WM items. Methods: Participants (N=15) performed a WM task where a string of letters was presented all at once, thus separating the encoding period from the maintenance period. Participants mentally replayed the letters during maintenance. We recorded sEEG from the hippocampus, scalp EEG and, additionally in 3 participants, temporo-parietal ECoG. Results: When analyzing the information flow to and from auditory cortex by Granger causality, the flow was from ECoG over auditory cortex to hippocampus with a peak in the 12-24 Hz beta range while letters were presented, and this flow was subsequently reversed during maintenance, while letters were maintained in memory. The same pattern appeared to and from hippocampus with ECoG over temporo-parietal cortex. For scalp EEG, the pattern appeared on temporal sites, albeit in the 4-12 Hz theta-alpha range. While the pattern was significantly structured for correct trials, it was unstructured for incorrect trials. Conclusions: The functional interaction between hippocampus and cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.