Time Cells in the Human Brain Support Working Memory Maintenance

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.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-01-14
DOI
https://doi.org/10.64898/2026.01.12.699074
Primary Topic
Memory and Neural Mechanisms
Type
article
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article

Time Cells in the Human Brain Support Working Memory Maintenance

Taufik A. Valiante, Jiannis Taxidis, Xiaoxuan Xiao, Ueli Rutishauser
bioRxiv (Cold Spring Harbor Laboratory)
Memory and Neural Mechanisms
article

Time Cells in the Human Brain Support Working Memory Maintenance

Taufik A. Valiante, Jiannis Taxidis, Xiaoxuan Xiao, Ueli Rutishauser
article en

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.

bioRxiv (Cold Spring Harbor Laboratory)
California Institute of Technology (US), Cedars-Sinai Medical Center (US), University Health Network (CA), University of Toronto (CA), Hospital for Sick Children (CA), Krembil Research Institute
Openalex Percentile: Top 88%
Memory and Neural Mechanisms
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Time Cells in the Human Brain Support Working Memory Maintenance — Taufik A. Valiante, Jiannis Taxidis, et al. · bioRxiv (Cold Spring Harbor Laboratory) (2026) | TGRS Research Map | TGRS