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Published April 2017 | Supplemental Material
Journal Article Open

Persistently active neurons in human medial frontal and medial temporal lobe support working memory


Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance.

Additional Information

© 2017 Macmillan Publishers Limited. Received 01 December 2016. Accepted 18 January 2017. Published online 20 February 2017. We thank J. Minxa, R. Adolphs and J. Dubois for discussion and the staff and physicians of the Epilepsy Monitoring Unit at Cedars-Sinai Medical Center and the Huntington Memorial Hospital for invaluable assistance. This work was supported by the National Science Foundation (1554105 to U.R.), the National Institute of Mental Health (R01MH110831 to U.R.), the McKnight Endowment Fund for Neuroscience (to U.R.), a NARSAD Young Investigator grant from the Brain & Behavior Research Foundation (23502 to U.R.) and the Pfeiffer Foundation (to U.R.). Author Contributions: J.K. and U.R. designed the experiments. J.K. and U.R. performed experiments. J.K., S.S. and U.R. performed analysis. A.N.M. and I.B.R. performed surgery. J.M.C. provided patient care. J.K. and U.R. wrote the paper. All of the authors discussed the results at all stages of the project. Data availability: The data that support the findings of this study are available on reasonable request from the corresponding author. The data are not publicly available because they contain information that could compromise research participant privacy/consent. Code availability: Analysis was performed in Matlab using the publicly available software packages Osort, ndt and EEGLAB together with custom-developed analysis routines. The authors declare no competing financial interests.


In the version of this article initially published, the pink and gray symbols were switched in the key to Figure 7d and the plot of the outlier data points was mis-scaled relative to the axes. In Figure 6b, the x axis was numbered 0 through 1 instead of −1 through 0. The errors have been corrected in the HTML and PDF versions of the article.

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August 19, 2023
October 20, 2023