Time Cells in the Human Brain Support Working Memory Maintenance

Abstract

Working memory (WM), the active retention of information over short periods, is a fundamental cognitive function, yet its underlying neural mechanisms remain unclear. In rodents, cue-selective "time cells" fire at specific timepoints after a WM memory cue, collectively forming sequences that encode cue-memory and elapsed time, providing a temporal code for maintaining information across time intervals. Whether similar dynamics support WM in the human brain is unknown. Here, we analyzed intracranial single-neuron recordings from medial frontal and medial temporal regions of patients performing a WM task. We found time cells with temporally tuned activation during WM maintenance, collectively forming robust sequences that tiled a delay period. Time-cell coordination in the hippocampus predicted successful WM maintenance, whereas in the pre-supplementary motor area it reflected memory load. Furthermore, we identified distributed cue-selective time cells that encoded both the identity of a memorandum and elapsed maintenance time, providing a temporally structured mnemonic code that complements persistent firing of concept cells. Together, these findings establish time-cell sequences as a conserved neural mechanism supporting human working memory.