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Memory retrieval modulates spatial tuning of single neurons in the human entorhinal cortex

Nature Neuroscience volume 22, pages 2078–2086 (2019)Cite this article

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Abstract

The medial temporal lobe is critical for both spatial navigation and memory. Although single neurons in the medial temporal lobe activate to represent locations in the environment during navigation, how this spatial tuning relates to memory for events involving those locations remains unclear. We examined memory-related changes in spatial tuning by recording single-neuron activity from neurosurgical patients performing a virtual-reality object–location memory task. We identified ‘memory-trace cells’ with activity that was spatially tuned to the retrieved location of the specific object that participants were cued to remember. Memory-trace cells in the entorhinal cortex, in particular, encoded discriminable representations of different memories through a memory-specific rate code. These findings indicate that single neurons in the human entorhinal cortex change their spatial tuning to target relevant memories for retrieval.

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Fig. 1: Task overview.
Fig. 2: Examples of place and memory-trace cells.
Fig. 3: Place cell activity.
Fig. 4: Trace-fields shift according to memory for cued object locations.
Fig. 5: Memory-trace cells track subjective memory during retrieval.
Fig. 6: Memory-trace cell activity is correlated between the hold period and response period.
Fig. 7: Entorhinal cortex memory-trace cell activity predicts cued memory across hold and response periods.

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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 could compromise research participant privacy and consent.

Code availability

Task was coded using the publicly available programming library PandaEPL64. Analysis was performed in Matlab and spike sorting in Python using the publicly available software package Combinato52. Analysis code is available on reasonable request from the corresponding author.

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Acknowledgements

We are grateful to the patients for participating in our study. This work was supported by NIH grants R01-MH104606 (to J.J.) and S10-OD018211 (to C.S.), NSF grants BCS-1724243 and BCS-1848465 (to J.J.), and NSF Graduate Research Fellowship DGE 16-44869 (to S.E.Q.). We thank Andrew Watrous (University of Texas, Austin), Melina Tsitsiklis (Columbia University), Ida Momennejad (Columbia University), Mariam Aly (Columbia University), Nicole Long (University of Virginia), and Niko Kriegeskorte (Columbia University) for helpful comments and suggestions.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Columbia University, New York, NY, USA

    Salman E. Qasim, Jonathan Miller & Joshua Jacobs

  2. Department of Neurological Surgery, Emory University, Atlanta, GA, USA

    Cory S. Inman, Robert E. Gross & Jon T. Willie

  3. Department of Neurological Surgery, University of Texas Southwestern, Dallas, TX, USA

    Bradley Lega & Jui-Jui Lin

  4. Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA

    Ashwini Sharan & Chengyuan Wu

  5. Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA

    Michael R. Sperling

  6. Jefferson Comprehensive Epilepsy Center, Jefferson University Hospitals, Philadelphia, PA, USA

    Michael R. Sperling

  7. Department of Neurological Surgery, Baylor College of Medicine, Houston, TX, USA

    Sameer A. Sheth

  8. Department of Neurological Surgery, Columbia University, New York, NY, USA

    Guy M. McKhann

  9. Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA

    Elliot H. Smith

  10. Department of Neurology, Columbia University, New York, NY, USA

    Catherine Schevon

  11. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

    Joel M. Stein

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  1. Salman E. Qasim
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Contributions

J.J. conceived the experiment; R.E.G., J.T.W., B.L., A.S., C.W., S.A.S., and G.M.M. performed surgical procedures; S.E.Q., J.M., M.R.S., C.S., E.H.S., J.-J.L., and C.S.I. performed data collection and recording; J.M.S. processed neuroimaging data; S.E.Q. analyzed the data; and S.E.Q. and J.J. wrote the manuscript.

Corresponding author

Correspondence to Joshua Jacobs.

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Peer review information Nature Neuroscience thanks Stefan Leutgeb and other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figures 1–14 and Supplementary Tables 1 and 2.

Reporting Summary

Supplementary Video 1

This video depicts the task instructions that participants are given at the beginning of a session, followed by two encoding trials and one retrieval trial for an object.

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Qasim, S.E., Miller, J., Inman, C.S. et al. Memory retrieval modulates spatial tuning of single neurons in the human entorhinal cortex. Nat Neurosci 22, 2078–2086 (2019). https://doi.org/10.1038/s41593-019-0523-z

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