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.

Boosting slow oscillations during sleep potentiates memory

Abstract

There is compelling evidence that sleep contributes to the long-term consolidation of new memories1. This function of sleep has been linked to slow (<1 Hz) potential oscillations, which predominantly arise from the prefrontal neocortex and characterize slow wave sleep2,3,4. However, oscillations in brain potentials are commonly considered to be mere epiphenomena that reflect synchronized activity arising from neuronal networks, which links the membrane and synaptic processes of these neurons in time5. Whether brain potentials and their extracellular equivalent have any physiological meaning per se is unclear, but can easily be investigated by inducing the extracellular oscillating potential fields of interest6,7,8. Here we show that inducing slow oscillation-like potential fields by transcranial application of oscillating potentials (0.75 Hz) during early nocturnal non-rapid-eye-movement sleep, that is, a period of emerging slow wave sleep, enhances the retention of hippocampus-dependent declarative memories in healthy humans. The slowly oscillating potential stimulation induced an immediate increase in slow wave sleep, endogenous cortical slow oscillations and slow spindle activity in the frontal cortex. Brain stimulation with oscillations at 5 Hz—another frequency band that normally predominates during rapid-eye-movement sleep—decreased slow oscillations and left declarative memory unchanged. Our findings indicate that endogenous slow potential oscillations have a causal role in the sleep-associated consolidation of memory, and that this role is enhanced by field effects in cortical extracellular space.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Slow oscillatory stimulation enhances declarative memory performance.
Figure 2: Synchronization of slow oscillatory EEG activity.
Figure 3: EEG activity during the 1-min intervals between periods of slow oscillation stimulation and between corresponding periods of sham stimulation.

Similar content being viewed by others

References

  1. Stickgold, R. Sleep-dependent memory consolidation. Nature 437, 1272–1278 (2005)

    Article  ADS  CAS  Google Scholar 

  2. Sejnowski, T. J. & Destexhe, A. Why do we sleep?. Brain Res. 886, 208–223 (2000)

    Article  CAS  Google Scholar 

  3. Steriade, M. & Timofeev, I. Neuronal plasticity in thalamocortical networks during sleep and waking oscillations. Neuron 37, 563–576 (2003)

    Article  CAS  Google Scholar 

  4. Huber, R., Ghilardi, M. F., Massimini, M. & Tononi, G. Local sleep and learning. Nature 430, 78–81 (2004)

    Article  ADS  CAS  Google Scholar 

  5. Buzsáki, G. & Draguhn, A. Neuronal oscillations in cortical networks. Science 304, 1926–1929 (2004)

    Article  ADS  Google Scholar 

  6. Jefferys, J. G. & Haas, H. L. Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission. Nature 300, 448–450 (1982)

    Article  ADS  CAS  Google Scholar 

  7. Hutcheon, B. & Yarom, Y. Resonance, oscillation and the intrinsic frequency preferences of neurons. Trends Neurosci. 23, 216–222 (2000)

    Article  CAS  Google Scholar 

  8. Marshall, L., Mölle, M., Hallschmid, M. & Born, J. Transcranial direct current stimulation during sleep improves declarative memory. J. Neurosci. 24, 9985–9992 (2004)

    Article  CAS  Google Scholar 

  9. Steriade, M. The corticothalamic system in sleep. Front. Biosci. 8, d878–d899 (2003)

    Article  CAS  Google Scholar 

  10. Buzsáki, G. Memory consolidation during sleep: a neurophysiological perspective. J. Sleep Res. 7, (Suppl. 1)17–23 (1998)

    Article  Google Scholar 

  11. Mölle, M., Marshall, L., Gais, S. & Born, J. Learning increases human electroencephalographic coherence during subsequent slow sleep oscillations. Proc. Natl Acad. Sci. USA 101, 13963–13968 (2004)

    Article  ADS  Google Scholar 

  12. Mölle, M., Yeshenko, O., Marshall, L., Sara, S. J. & Born, J. Hippocampal sharp wave-ripples linked to slow oscillations in rat slow-wave sleep. J. Neurophysiol. 96, 62–70 (2006)

    Article  Google Scholar 

  13. Wolansky, T., Clement, E. A., Peters, S. R., Palczak, M. A. & Dickson, C. T. Hippocampal slow oscillation: a novel EEG state and its coordination with ongoing neocortical activity. J. Neurosci. 26, 6213–6229 (2006)

    Article  CAS  Google Scholar 

  14. Mölle, M., Marshall, L., Gais, S. & Born, J. Grouping of spindle activity during slow oscillations in human non-rapid eye movement sleep. J. Neurosci. 22, 10941–10947 (2002)

    Article  Google Scholar 

  15. Plihal, W. & Born, J. Effects of early and late nocturnal sleep on declarative and procedural memory. J. Cogn. Neurosci. 9, 534–547 (1997)

    Article  CAS  Google Scholar 

  16. Walker, M. P. & Stickgold, R. Sleep-dependent learning and memory consolidation. Neuron 44, 121–133 (2004)

    Article  CAS  Google Scholar 

  17. Walker, M. P., Brakefield, T., Hobson, J. A. & Stickgold, R. Dissociable stages of human memory consolidation and reconsolidation. Nature 425, 616–620 (2003)

    Article  ADS  CAS  Google Scholar 

  18. Gais, S. & Born, J. Declarative memory consolidation: mechanisms acting during human sleep. Learn. Mem. 11, 679–685 (2004)

    Article  Google Scholar 

  19. Peigneux, P. et al. Are spatial memories strengthened in the human hippocampus during slow wave sleep?. Neuron 44, 535–545 (2004)

    Article  CAS  Google Scholar 

  20. Wiltgen, B. J., Brown, R. A., Talton, L. E. & Silva, A. J. New circuits for old memories: the role of the neocortex in consolidation. Neuron 44, 101–108 (2004)

    Article  CAS  Google Scholar 

  21. Nitsche, M. A. & Paulus, W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 57, 1899–1901 (2001)

    Article  CAS  Google Scholar 

  22. Francis, J. T., Gluckman, B. J. & Schiff, S. J. Sensitivity of neurons to weak electric fields. J. Neurosci. 23, 7255–7261 (2003)

    Article  CAS  Google Scholar 

  23. Massimini, M. & Amzica, F. Extracellular calcium fluctuations and intracellular potentials in the cortex during the slow sleep oscillation. J. Neurophysiol. 85, 1346–1350 (2001)

    Article  CAS  Google Scholar 

  24. Shu, Y., Hasenstaub, A., Duque, A., Yu, Y. & McCormick, D. A. Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential. Nature 441, 761–765 (2006)

    Article  ADS  CAS  Google Scholar 

  25. Rosanova, M. & Ulrich, D. Pattern-specific associative long-term potentiation induced by a sleep spindle-related spike train. J. Neurosci. 25, 9398–9405 (2005)

    Article  CAS  Google Scholar 

  26. Werk, C. M., Harbour, V. L. & Chapman, C. A. Induction of long-term potentiation leads to increased reliability of evoked neocortical spindles in vivo.. Neuroscience 131, 793–800 (2005)

    Article  CAS  Google Scholar 

  27. Lutzenberger, W. & Elbert, T. Safety Assessment of NMR Clinical Equipment (ed. Schmidt, K. H.) 36–45 (Thieme, Stuttgart, 1987)

    Google Scholar 

  28. Rush, S. & Driscoll, D. A. Current distribution in the brain from surface electrodes. Anesth. Analg. 47, 717–723 (1968)

    Article  CAS  Google Scholar 

  29. Steriade, M., Contreras, D., Amzica, F. & Timofeev, I. Synchronization of fast (30–40 Hz) spontaneous oscillations in intrathalamic and thalamocortical networks. J. Neurosci. 16, 2788–2808 (1996)

    Article  CAS  Google Scholar 

  30. Doran, S. M. The dynamic topography of individual sleep spindles. Sleep Res. Online 5, 133–139 (2003)

    Google Scholar 

Download references

Acknowledgements

We thank H. Koller for help in designing the stimulation apparatus, H. Schuster, H. Siebner, B. Rasch and U. Wagner for discussions of our results, and A. Otterbein, S. Uyanik, P. Paul, R. Krebs and M. Rohwer for technical assistance. This work is supported by the Deutsche Forschungsgemeinschaft.

Author Contributions L.M. and H.H. conducted the experiments. L.M., M.M. and J.B. analysed the data and wrote the paper.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Lisa Marshall or Jan Born.

Ethics declarations

Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Notes 1

This file contains Supplementary Methods and Results, describing the methods in detail and corresponding supplementary results (including analyses of spindle counts and controls of unspecific cognitive and hormonal effects); Supplementary Figure 1 and Legend, Supplementary Table 1: Sleep during the nights of Stimulation and Sham stimulation and Supplementary references. (PDF 401 kb)

Supplementary Notes 2

This file contains the lists in English and German used in the word-paired associate learning task. (PDF 73 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marshall, L., Helgadóttir, H., Mölle, M. et al. Boosting slow oscillations during sleep potentiates memory. Nature 444, 610–613 (2006). https://doi.org/10.1038/nature05278

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05278

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

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