Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Evidence for grid cells in a human memory network

Nature volume 463, pages 657–661 (2010)Cite this article

Subjects

Abstract

Grid cells in the entorhinal cortex of freely moving rats provide a strikingly periodic representation of self-location1 which is indicative of very specific computational mechanisms2,3,4. However, the existence of grid cells in humans and their distribution throughout the brain are unknown. Here we show that the preferred firing directions of directionally modulated grid cells in rat entorhinal cortex are aligned with the grids, and that the spatial organization of grid-cell firing is more strongly apparent at faster than slower running speeds. Because the grids are also aligned with each other1,5, we predicted a macroscopic signal visible to functional magnetic resonance imaging (fMRI) in humans. We then looked for this signal as participants explored a virtual reality environment, mimicking the rats’ foraging task: fMRI activation and adaptation showing a speed-modulated six-fold rotational symmetry in running direction. The signal was found in a network of entorhinal/subicular, posterior and medial parietal, lateral temporal and medial prefrontal areas. The effect was strongest in right entorhinal cortex, and the coherence of the directional signal across entorhinal cortex correlated with spatial memory performance. Our study illustrates the potential power of combining single-unit electrophysiology with fMRI in systems neuroscience. Our results provide evidence for grid-cell-like representations in humans, and implicate a specific type of neural representation in a network of regions which supports spatial cognition and also autobiographical memory.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The mean firing directions of directional grid cells are aligned with the grid.
Figure 2: fMRI: virtual reality arena and experimental logic.
Figure 3: Modulation of entorhinal cortical activity by running direction with six-fold rotational symmetry, and correlation with spatial memory.
Figure 4: fMRI adaptation to running direction and to runs at 60° from it.

Similar content being viewed by others

References

  1. Hafting, T., Fyhn, M., Molden, S., Moser, M. B. & Moser, E. I. Microstructure of a spatial map in the entorhinal cortex. Nature 436, 801–806 (2005)

    Article  ADS  CAS  Google Scholar 

  2. McNaughton, B. L., Battaglia, F. P., Jensen, O., Moser, E. I. & Moser, M. B. Path integration and the neural basis of the ‘cognitive map’. Nature Rev. Neurosci. 7, 663–678 (2006)

    Article  CAS  Google Scholar 

  3. Burgess, N., Barry, C. & O’Keefe, J. An oscillatory interference model of grid cell firing. Hippocampus 17, 801–812 (2007)

    Article  Google Scholar 

  4. Hasselmo, M. E. A model of episodic memory: mental time travel along encoded trajectories using grid cells. Neurobiol. Learn. Mem. 92, 559–573 (2009)

    Article  Google Scholar 

  5. Barry, C., Hayman, R., Burgess, N. & Jeffery, K. J. Experience-dependent rescaling of entorhinal grids. Nature Neurosci. 10, 682–684 (2007)

    Article  CAS  Google Scholar 

  6. Sargolini, F. et al. Conjunctive representation of position, direction, and velocity in entorhinal cortex. Science 312, 758–762 (2006)

    Article  ADS  CAS  Google Scholar 

  7. Boccara, C. N. et al. Grid cells in presubiculum and parasubiculum. FENS Abstr 4, 128.21 (2008)

    Google Scholar 

  8. Whitlock, J. R., Sutherland, R. J., Witter, M. P., Moser, M. B. & Moser, E. I. Navigating from hippocampus to parietal cortex. Proc. Natl Acad. Sci. USA 105, 14755–14762 (2008)

    Article  ADS  CAS  Google Scholar 

  9. Logothetis, N. K. What we can do and what we cannot do with fMRI. Nature 453, 869–878 (2008)

    Article  ADS  CAS  Google Scholar 

  10. Jeewajee, A., Barry, C., O’Keefe, J. & Burgess, N. Grid cells and theta as oscillatory interference: electrophysiological data from freely moving rats. Hippocampus 18, 1175–1185 (2008)

    Article  CAS  Google Scholar 

  11. Doeller, C. F., King, J. A. & Burgess, N. Parallel striatal and hippocampal systems for landmarks and boundaries in spatial memory. Proc. Natl Acad. Sci. USA 105, 5915–5920 (2008)

    Article  ADS  CAS  Google Scholar 

  12. Fernandez, G., Brewer, J. B., Zhao, Z., Glover, G. H. & Gabrieli, J. D. Level of sustained entorhinal activity at study correlates with subsequent cued-recall performance: a functional magnetic resonance imaging study with high acquisition rate. Hippocampus 9, 35–44 (1999)

    Article  CAS  Google Scholar 

  13. Olsen, R. K. et al. Performance-related sustained and anticipatory activity in human medial temporal lobe during delayed match-to-sample. J. Neurosci. 29, 11880–11890 (2009)

    Article  CAS  Google Scholar 

  14. Epstein, R., Graham, K. S. & Downing, P. E. Viewpoint-specific scene representations in human parahippocampal cortex. Neuron 37, 865–876 (2003)

    Article  CAS  Google Scholar 

  15. Grill-Spector, K., Henson, R. & Martin, A. Repetition and the brain: neural models of stimulus-specific effects. Trends Cogn. Sci. 10, 14–23 (2006)

    Article  Google Scholar 

  16. Park, S., Intraub, H., Yi, D. J., Widders, D. & Chun, M. M. Beyond the edges of a view: boundary extension in human scene-selective visual cortex. Neuron 54, 335–342 (2007)

    Article  CAS  Google Scholar 

  17. Bakker, A., Kirwan, C. B., Miller, M. & Stark, C. E. Pattern separation in the human hippocampal CA3 and dentate gyrus. Science 319, 1640–1642 (2008)

    Article  ADS  CAS  Google Scholar 

  18. Ekstrom, A. D. et al. Cellular networks underlying human spatial navigation. Nature 425, 184–188 (2003)

    Article  ADS  CAS  Google Scholar 

  19. Taube, J. S. Head direction cells and the neuropsychological basis for a sense of direction. Prog. Neurobiol. 55, 225–256 (1998)

    Article  CAS  Google Scholar 

  20. Chen, L. L., Lin, L. H., Green, E. J., Barnes, C. A. & McNaughton, B. L. Head-direction cells in the rat posterior cortex. I. Anatomical distribution and behavioral modulation. Exp. Brain Res. 101, 8–23 (1994)

    Article  CAS  Google Scholar 

  21. Byrne, P., Becker, S. & Burgess, N. Remembering the past and imagining the future: a neural model of spatial memory and imagery. Psychol. Rev. 114, 340–375 (2007)

    Article  Google Scholar 

  22. Wolbers, T., Wiener, J. M., Mallot, H. A. & Buchel, C. Differential recruitment of the hippocampus, medial prefrontal cortex, and the human motion complex during path integration in humans. J. Neurosci. 27, 9408–9416 (2007)

    Article  CAS  Google Scholar 

  23. Maguire, E. A. Neuroimaging studies of autobiographical event memory. Phil. Trans. R. Soc. Lond. B 356, 1441–1451 (2001)

    Article  CAS  Google Scholar 

  24. Schacter, D. L., Addis, D. R. & Buckner, R. L. Remembering the past to imagine the future: the prospective brain. Nature Rev. Neurosci. 8, 657–661 (2007)

    Article  CAS  Google Scholar 

  25. O’Keefe, J. & Nadel, L. The Hippocampus as a Cognitive Map (Oxford Univ. Press, 1978)

    Google Scholar 

  26. Howard, M. W., Fotedar, M. S., Datey, A. V. & Hasselmo, M. E. The temporal context model in spatial navigation and relational learning: toward a common explanation of medial temporal lobe function across domains. Psychol. Rev. 112, 75–116 (2005)

    Article  Google Scholar 

  27. Pastalkova, E., Itskov, V., Amarasingham, A. & Buzsaki, G. Internally generated cell assembly sequences in the rat hippocampus. Science 321, 1322–1327 (2008)

    Article  ADS  CAS  Google Scholar 

  28. Gaffan, D. Scene-specific memory for objects: a model of episodic memory impairment in monkeys with fornix transection. J. Cogn. Neurosci. 6, 305–320 (1994)

    Article  CAS  Google Scholar 

  29. Knierim, J. J. Neural representations of location outside the hippocampus. Learn. Mem. 13, 405–415 (2006)

    Article  Google Scholar 

  30. Eichenbaum, H., Yonelinas, A. P. & Ranganath, C. The medial temporal lobe and recognition memory. Annu. Rev. Neurosci. 30, 123–152 (2007)

    Article  CAS  Google Scholar 

  31. Recce, M. & O’Keefe, J. The tetrode: a new technique for multiunit extracellular recording. Soc. Neurosci. Abstr. 15, 1250 (1989)

    Google Scholar 

  32. Weiskopf, N., Hutton, C., Josephs, O. & Deichmann, R. Optimal EPI parameters for reduction of susceptibility-induced BOLD sensitivity losses: a whole-brain analysis at 3 T and 1.5 T. Neuroimage 33, 493–504 (2006)

    Article  Google Scholar 

  33. Hutton, C. et al. Image distortion correction in fMRI: A quantitative evaluation. Neuroimage 16, 217–240 (2002)

    Article  Google Scholar 

  34. Andersson, J. L., Hutton, C., Ashburner, J., Turner, R. & Friston, K. Modeling geometric deformations in EPI time series. Neuroimage 13, 903–919 (2001)

    Article  CAS  Google Scholar 

  35. Ashburner, J. & Friston, K. J. Unified segmentation. Neuroimage 26, 839–851 (2005)

    Article  Google Scholar 

  36. Büchel, C., Holmes, A. P., Rees, G. & Friston, K. J. Characterizing stimulus-response functions using nonlinear regressors in parametric fMRI experiments. Neuroimage 8, 140–148 (1998)

    Article  Google Scholar 

  37. Fischl, B. et al. Predicting the location of entorhinal cortex from MRI. Neuroimage 47, 8–17 (2009)

    Article  Google Scholar 

  38. Insausti, R., Tunon, T., Sobreviela, T., Insausti, A. M. & Gonzalo, L. M. The human entorhinal cortex: a cytoarchitectonic analysis. J. Comp. Neurol. 355, 171–198 (1995)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge K. Jeffery and J. O’Keefe for providing help and facilities for single-unit recording; the Wellcome Trust Centre for Neuroimaging at UCL for providing help and scanning facilities; J. Krupic and R. Hayman for help with single-unit data collection; A. Jeewajee for help with analyses; J. King for help with virtual reality programming; and useful discussions with P. Dayan, K. Friston, U. Frith, C. Hall, A. Jeewajee, J. O’Keefe and M. Witter. This work was funded by the UK Medical Research Council and the European Union (SpaceBrain grant).

Author Contributions C.F.D., C.B. and N.B. jointly conceived and designed the experiments. C.F.D. performed the fMRI experiment and data analyses; C.B. performed the single-unit experiment and data analyses; N.B. gave direction on analyses; all authors discussed the analyses and results and contributed to writing the paper.

Author information

Authors and Affiliations

  1. UCL Institute of Cognitive Neuroscience, London WC1N 3AR, UK

    Christian F. Doeller, Caswell Barry & Neil Burgess

  2. UCL Institute of Neurology, London WC1N 3BG, UK

    Christian F. Doeller & Neil Burgess

  3. UCL Department of Cell and Developmental Biology, London WC1E 6BT, UK

    Caswell Barry

  4. UCL Institute of Behavioural Neuroscience, University College London, London WC1H 0AP, UK

    Caswell Barry

Authors
  1. Christian F. Doeller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caswell Barry
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neil Burgess
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Christian F. Doeller or Neil Burgess.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-18 with Legends. (PDF 8238 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Doeller, C., Barry, C. & Burgess, N. Evidence for grid cells in a human memory network. Nature 463, 657–661 (2010). https://doi.org/10.1038/nature08704

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature08704

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing