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

Nature Neuroscience volume 20, pages 590601 (2017) | Download Citation

  • An Erratum to this article was published on 26 July 2017

This article has been updated

Abstract

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.

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Change history

  • 04 May 2017

    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 horizontal 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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Acknowledgements

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 information

Affiliations

  1. Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Jan Kamiński
    • , Shannon Sullivan
    • , Adam N Mamelak
    •  & Ueli Rutishauser
  2. Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Jeffrey M Chung
    •  & Ueli Rutishauser
  3. Department of Neurosurgery, Huntington Memorial Hospital, Pasadena, California, USA.

    • Ian B Ross
  4. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Ueli Rutishauser
  5. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.

    • Jan Kamiński
    •  & Ueli Rutishauser

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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ueli Rutishauser.

Integrated supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–6 and Supplementary Table 1

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    Supplementary Methods Checklist

Videos

  1. 1.

    Dynamic version of attractor dynamics in state space during working memory encoding and maintenance.

    Illustration of the mean trajectories in neuronal state space formed by the three demixed principal components (dPCs) associated with picture identity during encoding (thin line) and maintenance (thick line). The transition from thin to thick lines indicates the onset of the maintenance period. Points of time are indicated in the upper left corner. Colors mark different images (only 4 of the total 5 are shown for clarity). Compare to Fig. 8a.

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DOI

https://doi.org/10.1038/nn.4509

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