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.

  • Review Article
  • Published:

The role of phase synchronization in memory processes

Nature Reviews Neuroscience volume 12, pages 105–118 (2011)Cite this article

Subjects

Key Points

  • The term 'phase' denotes the angle corresponding to the momentary deflection of an oscillation. Phase synchronization of neural oscillations refers to the correlation of phase values between two brain regions.

  • Electroencephalography and local field potential oscillations reflect fluctuations in neuronal membrane potential and are thus related to changes in neural excitability and to spike timing. Therefore, phase synchronization between two brain regions reflects correlations of neural excitability and spike timing.

  • Correlated changes in neural excitability and spike timing are the basis for two major functions of phase synchronization: neural communication and spike timing-dependent plasticity. It is still an open question, however, how these functions interact with each other.

  • Increased phase synchronization has been observed during various memory processes, including working memory maintenance and long-term memory encoding and retrieval. Neural plasticity is probably most relevant for long-term memory formation, whereas neural communication is likely to play a part during both working and long-term memory processes.

  • Recent studies suggest that working and long-term memory operations, which have long been considered separately, are supported by overlapping brain regions, particularly the hippocampus. Phase synchronization could constitute a common neural signature of both working memory maintenance and long-term memory formation.

  • Computer models propose that cross-frequency coupling of the amplitude (and possibly even phases) of gamma oscillations to phases of theta oscillations supports the representation of multiple items in working memory. Indeed, modulations of cross-frequency phase–phase and phase–amplitude coupling have been observed depending on working memory operations.

  • Further data indicate that cross-frequency phase–amplitude and phase–phase coupling may also support long-term memory encoding of sequences and cued recall of spatial positions. Cross-frequency phase–phase and phase–amplitude coupling may constitute mechanisms that support the exchange of object representations between working and long-term memory.

  • Taken together, both empirical and theoretical evidence suggests that phase synchronization and complementary phase-based mechanisms provide a common 'neural protocol' for various memory-related operations.

Abstract

In recent years, studies ranging from single-unit recordings in animals to electroencephalography and magnetoencephalography studies in humans have demonstrated the pivotal role of phase synchronization in memory processes. Phase synchronization — here referring to the synchronization of oscillatory phases between different brain regions — supports both working memory and long-term memory and acts by facilitating neural communication and by promoting neural plasticity. There is evidence that processes underlying working and long-term memory might interact in the medial temporal lobe. We propose that this is accomplished by neural operations involving phase–phase and phase–amplitude synchronization. A deeper understanding of how phase synchronization supports the flexibility of and interaction between memory systems may yield new insights into the functions of phase synchronization in general.

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: Putative functions of phase synchronization.
Figure 2: Patterns of phase synchronization during working and long-term memory.
Figure 3: Cross-frequency phase–phase and phase–amplitude coupling.
Figure 4: An integrative view of memory-related synchronization mechanisms.

Similar content being viewed by others

References

  1. Buzsáki, G. Rhythms of the Brain (Oxford University Press, New York, 2006).

    Google Scholar 

  2. Steriade, M. Impact of network activities on neuronal properties in corticothalamic systems. J. Neurophysiol. 86, 1–39 (2001).

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  4. Lakatos, P. et al. An oscillatory hierarchy controlling neuronal excitability and stimulus processing in the auditory cortex. J. Neurophysiol. 94, 1904–1911 (2005).

    PubMed  Google Scholar 

  5. Elbert, T. & Rockstroh, B. Threshold regulation — a key to the understanding of the combined dynamics of EEG and event-related potentials. J. Psychophysiol. 4, 317–333 (1987).

    Google Scholar 

  6. Fröhlich, F. & McCormick, D. A. Endogenous electric fields may guide neocortical network activity. Neuron 67, 129–143 (2010).

    PubMed  PubMed Central  Google Scholar 

  7. Roelfsema, P. R., Engel, A. K., König, P. & Singer, W. Visuomotor integration is associated with zero time-lag synchronization among cortical areas. Nature 385, 157–161 (1997).

    CAS  PubMed  Google Scholar 

  8. Rodriguez, E. et al. Perception's shadow, long-distance synchronization of human brain activity. Nature 397, 430–433 (1999).

    CAS  PubMed  Google Scholar 

  9. Engel, A. K., Fries, P. & Singer, W. Dynamic predictions, oscillations and synchrony in top-down processing. Nature Rev. Neurosci. 2, 704–716 (2001).

    CAS  Google Scholar 

  10. Fries, P., Reynolds, J. H., Rorie, A. E. & Desimone, R. Modulation of oscillatory neuronal synchronization by selective visual attention. Science 291, 1560–1563 (2001).

    CAS  PubMed  Google Scholar 

  11. Cavanagh, J. F., Cohen, M. X. & Allen, J. J. Prelude to and resolution of an error, EEG phase synchrony reveals cognitive control dynamics during action monitoring. J. Neurosci. 29, 98–105 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Eckhorn, R. et al. Coherent oscillations, a mechanism of feature linking in the visual cortex? Multiple electrode and correlation analyses in the cat. Biol. Cybern. 60, 121–130 (1988).

    CAS  PubMed  Google Scholar 

  13. Gray, C. M., König, P., Engel, A. K. & Singer, W. Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties. Nature 338, 334–337 (1989).

    CAS  PubMed  Google Scholar 

  14. Fries, P. A mechanism for cognitive dynamics, neuronal communication through neuronal coherence. Trends Cogn. Sci. 9, 474–480 (2005).

    PubMed  Google Scholar 

  15. König, P., Engel, A. K. & Singer, W. Integrator or coincidence detector? The role of the cortical neuron revisited. Trends Neurosci. 19, 130–137 (1996).

    PubMed  Google Scholar 

  16. Azouz, R. & Gray, C. M. Dynamic spike threshold reveals a mechanism for synaptic coincidence detection in cortical neurons in vivo. Proc. Natl Acad. Sci. USA 97, 8110–8115 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Daoudal, G. & Debanne, D. Long-term plasticity of intrinsic excitability: learning rules and mechanisms. Learn. Mem. 10, 456–465 (2003).

    PubMed  Google Scholar 

  18. Fries, P., Neuenschwader, S., Engel, A. K., Goebel, R. & Singer, W. Rapid feature selective neuronal synchronization through correlated latency shifting. Nature Neurosci. 4, 194–200 (2001).

    CAS  PubMed  Google Scholar 

  19. Jacobs, J., Kahana, M. J., Ekstrom, A. D. & Fried, I. Brain oscillations control timing of single-neuron activity in humans. J. Neurosci. 27, 3839–3844 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Womelsdorf, T. et al. Modulation of neuronal interactions through neuronal synchronization. Science 316, 1609–1612 (2007). A pivotal empirical study supporting the hypothesis that phase synchronization facilitates neuronal communication ('communication through coherence').

    CAS  PubMed  Google Scholar 

  21. Vinck, M. et al. Gamma-phase shifting in awake monkey visual cortex. J. Neurosci. 30, 1250–1257 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Llinas, R. R., Leznik, E. & Urbano, F. J. Temporal binding via cortical coincidence detection of specific and nonspecific thalamocortical inputs: a voltage-dependent dye-imaging study in mouse brain slices. Proc. Natl Acad. Sci. USA 99, 449–454 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Volgushev, M., Chistiakova, M. & Singer, W. Modification of discharge patterns of neocortical neurons by induced oscillations of the membrane potential. Neuroscience 83, 15–25 (1998).

    CAS  PubMed  Google Scholar 

  24. Miltner, W. H., Braun, C., Arnold, M., Witte, H. & Taub, E. Coherence of gamma-band EEG activity as a basis for associative learning. Nature 397, 434–436 (1999). One of the first studies describing the role of neural synchronization (in this case EEG coherence) in long-term memory processes.

    CAS  PubMed  Google Scholar 

  25. Weiss, S. & Rappelsberger, P. Long-range EEG synchronization during word encoding correlates with successful memory performance. Brain Res. Cogn. Brain Res. 9, 299–312 (2000).

    CAS  PubMed  Google Scholar 

  26. Fell, J. et al. Human memory formation is accompanied by rhinal-hippocampal coupling and decoupling. Nature Neurosci. 4, 1259–1264 (2001).

    CAS  PubMed  Google Scholar 

  27. Summerfield, C. & Mangels, J. A. Coherent theta-band EEG activity predicts item-context binding during encoding. Neuroimage 24, 692–703 (2005).

    PubMed  Google Scholar 

  28. Fell, J. et al. Rhinal-hippocampal connectivity determines memory formation during sleep. Brain 129, 108–114 (2006).

    PubMed  Google Scholar 

  29. Sato, N. & Yamaguchi, Y. Theta synchronization networks emerge during human object-place memory encoding. Neuroreport 18, 419–424 (2007).

    PubMed  Google Scholar 

  30. Fell, J., Ludowig, E., Rosburg, T., Axmacher, N. & Elger, C. E. Phase-locking within human mediotemporal lobe predicts memory formation. Neuroimage 43, 410–419 (2008). The first study to directly compare the predictive power of different medial temporal EEG measures for long-term memory formation — namely, phase synchronization, inter-trial phase locking and spectral power changes.

    PubMed  Google Scholar 

  31. Babiloni, C. et al. Hippocampal, amygdala, and neocortical synchronization of theta rhythms is related to an immediate recall during Rey auditory verbal learning test. Hum. Brain Mapp. 30, 2077–2089 (2009).

    PubMed  Google Scholar 

  32. Benchenane, K. et al. Coherent theta oscillations and reorganization of spike timing in the hippocampal-prefrontal network upon learning. Neuron 66, 921–936 (2010).

    CAS  PubMed  Google Scholar 

  33. Axmacher, N., Mormann, F., Fernández, G., Elger, C. E. & Fell, J. Memory formation by neuronal synchronization. Brain Res. Rev. 52, 170–182 (2006).

    PubMed  Google Scholar 

  34. Jutras, M. J. & Buffalo, E. A. Synchronous neural activity and memory formation. Curr. Opin. Neurobiol. 20, 150–155 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Markram, H., Lübke, J., Frotscher, M. & Sakmann, B. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275, 213–215 (1997).

    CAS  PubMed  Google Scholar 

  36. Abbott, L. F. & Nelson, S. B. Synaptic plasticity: taming the beast. Nature Neurosci. 3, 1178–1183 (2000).

    CAS  PubMed  Google Scholar 

  37. Caporale, N. & Dan, Y. Spike timing-dependent plasticity, a Hebbian learning rule. Annu. Rev. Neurosci. 31, 25–46 (2008).

    CAS  PubMed  Google Scholar 

  38. Buzsáki, G., Leung, L. W. & Vanderwolf, C. H. Cellular bases of hippocampal EEG in the behaving rat. Brain Res. 287, 139–171 (1983).

    PubMed  Google Scholar 

  39. Maurer, A. P. & McNaughton, B. L. Network and intrinsic cellular mechanisms underlying theta phase precession of hippocampal neurons. Trends Neurosci. 30, 325–333 (2007).

    CAS  PubMed  Google Scholar 

  40. Bragin, A. et al. Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat. J. Neurosci. 15, 47–60 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Sarnthein, J., Petsche, H., Rappelsberger, P., Shaw, G. L. & von Stein, A. Synchronization between prefrontal and posterior association cortex during human working memory. Proc. Natl Acad. Sci. USA 95, 7092–7096 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Fell, J. et al. Rhinal-hippocampal theta coherence during declarative memory formation, interaction with gamma synchronization? Eur. J. Neurosci. 17, 1082–1088 (2003).

    PubMed  Google Scholar 

  43. Sauseng, P. et al. Theta coupling in the human electroencephalogram during a working memory task. Neurosci. Lett. 354, 123–126 (2004).

    CAS  PubMed  Google Scholar 

  44. Serrien, D. J., Pogosyan, A. H. & Brown, P. Influence of working memory on patterns of motor related cortico-cortical coupling. Exp. Brain Res. 155, 204–210 (2004).

    PubMed  Google Scholar 

  45. Sauseng, P., Klimesch, W., Schabus, M. & Doppelmayr, M. Fronto-parietal EEG coherence in theta and upper alpha reflect central executive functions of working memory. Int. J. Psychophysiol. 57, 97–103 (2005).

    PubMed  Google Scholar 

  46. Kopp, F., Schröger, E. & Lipka, S. Synchronized brain activity during rehearsal and short-term memory disruption by irrelevant speech is affected by recall mode. Int. J. Psychophysiol. 61, 188–203 (2006).

    PubMed  Google Scholar 

  47. Payne, L. & Kounios, J. Coherent oscillatory networks supporting short-term memory retention. Brain Res. 1247, 126–132 (2009).

    CAS  PubMed  Google Scholar 

  48. Wittenberg, G. M. & Wang, S. S. Malleability of spike-timing-dependent plasticity at the CA3–CA1 synapse. J. Neurosci. 26, 6610–6617 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Spruston, N. & Cang, J. Timing isn't everything. Nature Neurosci. 13, 277–279 (2010).

    CAS  PubMed  Google Scholar 

  50. Mehta, M. R., Lee, A. K. & Wilson, M. A. Role of experience and oscillations in transforming a rate code into a temporal code. Nature 417, 741–746 (2002).

    CAS  PubMed  Google Scholar 

  51. Pavlides, C., Greenstein, Y. J., Grudman, M. & Winson, J. Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of theta-rhythm. Brain Res. 439, 383–387 (1988).

    CAS  PubMed  Google Scholar 

  52. Huerta, P. T. & Lisman, J. E. Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. Nature 364, 723–725 (1993).

    CAS  PubMed  Google Scholar 

  53. Hasselmo, M. E., Bodelón, C. & Wyble, B. P. A proposed function for hippocampal theta rhythm, separate phases of encoding and retrieval enhance reversal of prior learning. Neural Comput. 14, 793–817 (2002).

    PubMed  Google Scholar 

  54. Baddeley, A. D. Working Memory (Oxford University Press, Oxford,1986).

    Google Scholar 

  55. Marr, D. A theory for cerebral neocortex. Proc. R. Soc. Lond. B Biol. Sci. 176, 161–234 (1970).

    CAS  PubMed  Google Scholar 

  56. Bliss, T. V. & Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 232, 331–356 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Muzzio, I. A., Kentros, C. & Kandel, E. What is remembered? Role of attention on the encoding and retrieval of hippocampal representations. J. Physiol. 587, 2837–2854 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Buzsáki, G. The hippocampo-neocortical dialogue. Cereb. Cortex 6, 81–92 (1996).

    PubMed  Google Scholar 

  59. Gazzaniga, M. S., Ivry, R. M. & Mangun, G. R. Cognitive Neuroscience: The Biology of the Mind 2nd edn, p311 (Norton & Company, New York, 2002).

    Google Scholar 

  60. Fuster, J. M. Memory in the Cerebral Cortex (MIT Press, Cambridge, Massachusetts, 1995).

    Google Scholar 

  61. Ruchkin, D. S., Grafman, J., Cameron, K. & Berndt, R. S. Working memory retention systems, a state of activated long-term memory. Behav. Brain Sci. 26, 709–728 (2003).

    PubMed  Google Scholar 

  62. D'Esposito, M. From cognitive to neural models of working memory. Philos. Trans. R. Soc. Lond. B Biol. Sci. 362, 761–772 (2007).

    PubMed  PubMed Central  Google Scholar 

  63. Harrison, S. A. & Tong, F. Decoding reveals the contents of visual working memory in early visual areas. Nature 458, 632–635 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Cohen, J. D. et al. Temporal dynamics of brain activation during a working memory task. Nature 386, 604–608 (1997).

    CAS  PubMed  Google Scholar 

  65. Lutzenberger, W., Ripper, B., Busse, L., Birbaumer, N. & Kaiser, J. Dynamics of gamma-band activity during an audiospatial working memory task in humans. J. Neurosci. 22, 5630–5638 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Babiloni, C. et al. Functional frontoparietal connectivity during short-term memory as revealed by high-resolution EEG coherence analysis. Behav. Neurosci. 118, 687–697 (2004).

    PubMed  Google Scholar 

  67. Tallon-Baudry, C., Bertrand, O. & Fischer, C. Oscillatory synchrony between human extrastriate areas during visual short-term memory maintenance. J. Neurosci. 21, RC177 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Axmacher, N., Schmitz, D. P., Wagner, T., Elger, C. E. & Fell, J. Interactions between medial temporal lobe, prefrontal cortex, and inferior temporal regions during visual working memory, a combined intracranial EEG and functional magnetic resonance imaging study. J. Neurosci. 28, 7304–7312 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Siegel, M., Warden, M. R. & Miller, E. K. Phase-dependent neuronal coding of objects in short-term memory. Proc. Natl Acad. Sci. USA 106, 21341–21346 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Axmacher, N. et al. Cross-frequency coupling supports multi-item working memory in the human hippocampus. Proc. Natl Acad. Sci. USA 107, 3228–3233 (2010). The first direct empirical evidence that multi-item working memory relies on cross-frequency coupling between the amplitude of high-frequency and the phase of low-frequency oscillations in the human hippocampus.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Engel, A. K. & Fries, P. Beta-band oscillations — signalling the status quo? Curr. Opin. Neurobiol. 20, 156–165 (2010).

    CAS  PubMed  Google Scholar 

  72. Huijbers, W., Pennartz, C. M. & Daselaar S. M. Dissociating the “retrieval success” regions of the brain: effects of retrieval delay. Neuropsychologia 48, 491–497 (2010).

    CAS  PubMed  Google Scholar 

  73. Gruber, T., Keil, A. & Müller, M. M. Modulation of induced gamma band responses and phase synchrony in a paired associate learning task in the human EEG. Neurosci. Lett. 316, 29–32 (2001).

    CAS  PubMed  Google Scholar 

  74. Eichenbaum, H. A cortical-hippocampal system for declarative memory. Nature Rev. Neurosci. 1, 41–50 (2000).

    CAS  Google Scholar 

  75. Fernández, G. & Tendolkar, I. The rhinal cortex, 'gatekeeper' of the declarative memory system. Trends Cogn. Sci. 10, 358–362 (2006).

    PubMed  Google Scholar 

  76. Jutras, M. J., Fries, P. & Buffalo, E. A. Gamma-band synchronization in the macaque hippocampus and memory formation. J. Neurosci. 29, 12521–12531 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Seidenbecher, T., Laxmi, T. R., Stork, O. & Pape, H. C. Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval. Science 301, 846–850 (2003). This study showed that amygdala–hippocampal coherence is increased in rodents after fear conditioning, suggesting that phase synchronization is also relevant for non-declarative long-term memory processes.

    CAS  PubMed  Google Scholar 

  78. Narayanan, R. T. et al. Dissociated theta phase synchronization in amygdalo-hippocampal circuits during various stages of fear memory. Eur. J. Neurosci. 25, 1823–1831 (2007).

    PubMed  Google Scholar 

  79. Reymann, K. G. & Frey, J. U. The late maintenance of hippocampal LTP: requirements, phases, 'synaptic tagging', 'late-associativity' and implications. Neuropharmacology 52, 24–40 (2007).

    CAS  PubMed  Google Scholar 

  80. Jones, M. W. & Wilson, M. A. Theta rhythms coordinate hippocampal-prefrontal interactions in a spatial memory task. PLoS Biol. 3, e402 (2005).

    PubMed  PubMed Central  Google Scholar 

  81. Montgomery, S. M. & Buzsáki, G. Gamma oscillations dynamically couple hippocampal CA3 and CA1 regions during memory task performance. Proc. Natl Acad. Sci. USA 104, 14495–14500 (2007). In this study, intrahippocampal phase synchronization between areas CA1 and CA3 was shown to increase during retrieval of information in a delayed spatial alternation task.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Paré, D. Role of the basolateral amygdala in memory consolidation. Prog. Neurobiol. 70, 409–420 (2003).

    PubMed  Google Scholar 

  83. Cave, C. B. & Squire, L. R. Intact verbal and nonverbal short-term memory following damage to the human hippocampus. Hippocampus 2, 151–163 (1992).

    CAS  PubMed  Google Scholar 

  84. Gaffan, D. & Murray, E. A. Monkeys (Macaca fascicularis) with rhinal cortex ablations succeed in object discrimination learning despite 24-hr intertrial intervals and fail at matching to sample despite double sample presentations. Behav. Neurosci. 106, 30–38 (1992).

    CAS  PubMed  Google Scholar 

  85. Young B. J., Otto T., Fox G. D. & Eichenbaum H. Memory representation within the parahippocampal region. J. Neurosci. 17, 5183–5195 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Axmacher, N. et al. Sustained neural activity patterns during working memory in the human medial temporal lobe. J. Neurosci. 27, 7807–7816 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Nichols, E. A., Kao, Y. C., Verfaellie, M. & Gabrieli, J. D. Hippocampus, working memory and long-term memory for faces: evidence from fMRI and global amnesia for involvement of the medial temporal lobes. Hippocampus 16, 604–616 (2006).

    PubMed  PubMed Central  Google Scholar 

  88. Schon, K., Hasselmo, M. E., Lopresti, M. L., Tricarico, M. D. & Stern, C. E. Persistence of parahippocampal representation in the absence of stimulus input enhances long-term encoding, a functional magnetic resonance imaging study of subsequent memory after a delayed match-to-sample task. J. Neurosci. 24, 11088–11097 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Ranganath, C. & D'Esposito, M. Medial temporal lobe activity associated with active maintenance of novel information. Neuron 31, 865–873 (2001).

    CAS  PubMed  Google Scholar 

  90. Stern, C. E., Sherman, S. J., Kirchhoff, B. A. & Hasselmo, M. E. Medial temporal and prefrontal contributions to working memory tasks with novel and familiar stimuli. Hippocampus 11, 337–346 (2001).

    CAS  PubMed  Google Scholar 

  91. Olson, I. R., Moore, K. S., Stark, M. & Chatterjee, A. Visual working memory is impaired when the medial temporal lobe is damaged. J. Cogn. Neurosci. 18, 1087–1097 (2006).

    PubMed  Google Scholar 

  92. Cohen, N. J. & Eichenbaum, H. Memory, Amnesia, and the Hippocampal System (The MIT Press, Cambridge, Massachusetts,1993).

    Google Scholar 

  93. Henke, K. A model for memory systems based on processing modes rather than consciousness. Nature Rev. Neurosci. 11, 523–532 (2010).

    CAS  Google Scholar 

  94. Piekema, C., Kessels, R. P., Mars, R. B., Petersson, K. M. & Fernandez, G. The right hippocampus participates in short-term memory maintenance of object-location associations. Neuroimage 33, 374–382 (2006).

    PubMed  Google Scholar 

  95. Aggleton, J. P., Shaw, C. & Gaffan, E. A. The performance of postencephalitic amnesic subjects on two behavioural tests of memory, concurrent discrimination learning and delayed matching-to-sample. Cortex 28, 359–372 (1992).

    CAS  PubMed  Google Scholar 

  96. Hannula, D. E., Tranel, D. & Cohen, N. J. The long and the short of it, relational memory impairments in amnesia, even at short lags. J. Neurosci. 262, 8352–8359 (2006).

    Google Scholar 

  97. Olson, I. R., Page, K., Moore, K. S., Chatterjee, A. & Verfaellie, M. Working memory for conjunctions relies on the medial temporal lobe. J. Neurosci. 26, 4596–4601 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Shrager, Y., Levy, D. A., Hopkins, R. O. & Squire, L. R. Working memory and the organization of brain systems. J. Neurosci. 28, 4818–4822 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Ranganath, C., Cohen, M. X. & Brozinsky, C. J. Working memory maintenance contributes to long-term memory formation, neural and behavioral evidence. J. Cogn. Neurosci. 17, 994–1010 (2005).

    PubMed  Google Scholar 

  100. Sauseng, P. et al. Brain oscillatory substrates of visual short-term memory capacity. Curr. Biol. 19, 1846–1852 (2009). This elegant study separated the neural mechanisms underlying maintenance of relevant and suppression of irrelevant items during working memory, and shows that the former relies on cross-frequency phase–phase and phase–amplitude coupling of theta and gamma oscillations.

    CAS  PubMed  Google Scholar 

  101. Demiralp, T. et al. Gamma amplitudes are coupled to theta phase in human EEG during visual perception. Int. J. Psychophysiol. 64, 24–30 (2007).

    PubMed  Google Scholar 

  102. Mormann, F. et al. Phase/amplitude reset and theta-gamma interaction in the human medial temporal lobe during a continuous word recognition memory task. Hippocampus 15, 890–900 (2005).

    PubMed  Google Scholar 

  103. Canolty, R. T. et al. High gamma power is phase-locked to theta oscillations in human neocortex. Science 313, 1626–1628 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Lisman, J. E. & Idiart, M. A. Storage of 7 ± 2 short-term memories in oscillatory subcycles. Science 267, 1512–1515 (1995).

    CAS  PubMed  Google Scholar 

  105. Jensen, O. & Lisman, J. E. Hippocampal sequence-encoding driven by a cortical multi-item working memory buffer. Trends Neurosci. 28, 67–72 (2005). A groundbreaking theoretical work suggesting that cross-frequency coupling underlies both the representation of multiple items in a working memory buffer and the encoding of these items into long-term memory.

    CAS  PubMed  Google Scholar 

  106. Jensen, O. & Colgin, L. L. Cross-frequency coupling between neuronal oscillations. Trends Cogn. Sci. 11, 267–269 (2007).

    PubMed  Google Scholar 

  107. Tort, A. B. et al. Dynamic cross-frequency couplings of local field potential oscillations in rat striatum and hippocampus during performance of a T-maze task. Proc. Natl. Acad. Sci. USA 105, 20517–20522 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Tort, A. B., Komorowski, R. W., Manns, J. R., Kopell, N. J. & Eichenbaum, H. Theta-gamma coupling increases during the learning of item-context associations. Proc. Natl Acad. Sci. USA 106, 20942–20947 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. O'Keefe, J. & Recce, M. L. Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3, 317–330 (1993).

    CAS  PubMed  Google Scholar 

  110. Senior, T. J., Huxter, J. R., Allen, K., O'Neill, J. & Csicsvari, J. Gamma oscillatory firing reveals distinct populations of pyramidal cells in the CA1 region of the hippocampus. J. Neurosci. 28, 2274–2286 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Jensen, O. & Lisman, J. E. Hippocampal CA3 region predicts memory sequences: accounting for the phase precession of place cells. Learn. Mem. 3, 279–287 (1996).

    CAS  PubMed  Google Scholar 

  112. Lisman, J. & Buzsáki, G. A neural coding scheme formed by the combined function of gamma and theta oscillations. Schizophr. Bull. 34, 974–980 (2008).

    PubMed  PubMed Central  Google Scholar 

  113. Harris, K. D., Csicsvari, J., Hirase, H., Dragoi, G. & Buzsaki, G. Organization of cell assemblies in the hippocampus. Nature 424, 552–556 (2003).

    CAS  PubMed  Google Scholar 

  114. Hasselmo, M. E. & Eichenbaum, H. Hippocampal mechanisms for the context-dependent retrieval of episodes. Neural Netw. 18, 1172–1190 (2005).

    PubMed  PubMed Central  Google Scholar 

  115. Lisman, J. E., Talamini, L. M. & Raffone, A. Recall of memory sequences by interaction of the dentate and CA3, a revised model of the phase precession. Neural Netw. 18, 1191–1201 (2005).

    PubMed  Google Scholar 

  116. Tass, P. et al. Detection of n:m phase locking from noisy data: application to magnetoencephalography. Phys. Rev. Lett. 81, 3291–3294 (1998).

    CAS  Google Scholar 

  117. Schack, B., Klimesch, W. & Sauseng, P. Phase synchronization between theta and upper alpha oscillations in a working memory task. Int. J. Psychophysiol. 57, 105–114 (2005).

    CAS  PubMed  Google Scholar 

  118. Palva, J. M., Palva, S. & Kaila, K. Phase synchrony among neuronal oscillations in the human cortex. J. Neurosci. 25, 3962–3972 (2005). One of the first studies highlighting the relevance of m:n phase–phase coupling for working memory processes.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. James, W. The Principles of Psychology (Holt, Rinehard & Winston, New York,1890).

    Google Scholar 

  120. Craik, F. I. M. & Lockhart, R. S. Levels of processing: a framework for memory research. J. Verb. Learn. Verb. Behav. 11, 671–684 (1972).

    Google Scholar 

  121. Axmacher, N., Elger, C. E. & Fell, J. Working memory-related hippocampal deactivation interferes with long-term memory formation. J. Neurosci. 29, 1052–1060 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Hebb, D. O. in Brain Mechanisms and Learning (ed. Delafresnaye, J. F.) 37–51 (Oxford University Press, London, 1961).

    Google Scholar 

  123. Hulme, C., Maughan, S., Brown & G. D. A. Memory for familiar and unfamiliar words, evidence for a long-term memory contribution to short-term memory span. J. Mem. Language 30, 685–701 (1991).

    Google Scholar 

  124. Jensen, O. & Lisman, J. E. Theta/gamma networks with slow NMDA channels learn sequences and encode episodic memory: role of NMDA channels in recall. Learn. Mem. 3, 264–278 (1996).

    CAS  PubMed  Google Scholar 

  125. Schack, B. & Weiss, S. Quantification of phase synchronization phenomena and their importance for verbal memory processes. Biol. Cybern. 92, 275–287 (2005). One of the first studies to show simultaneous effects of theta and gamma phase synchronization and m:n phase–phase coupling between these frequencies during memory formation.

    PubMed  Google Scholar 

  126. Colgin, L. L. et al. Frequency of gamma oscillations routes flow of information in the hippocampus. Nature 462, 353–357 (2009).

    CAS  PubMed  Google Scholar 

  127. Palva, J. M., Monto, S., Kulashekhar, S. & Palva, S. Neuronal synchrony reveals working memory networks and predicts individual memory capacity. Proc. Natl Acad. Sci. USA 107, 7580–7585 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Gelbard-Sagiv, H., Mukamel, R., Harel, M., Malach, R. & Fried, I. Internally generated reactivation of single neurons in human hippocampus during free recall. Science 322, 96–101 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Lisman, J. E. & Grace, A. A. The hippocampal–VTA loop, controlling the entry of information into long-term memory. Neuron 46, 703–713 (2005).

    CAS  PubMed  Google Scholar 

  130. Wittmann, B. C. et al. Reward-related fMRI activation of dopaminergic midbrain is associated with enhanced hippocampus-dependent long-term memory formation. Neuron 45, 459–467 (2005).

    CAS  PubMed  Google Scholar 

  131. Mecklinger, A. The control of long-term memory, brain systems and cognitive processes. Neurosci. Biobehav. Rev. 34, 1055–1065 (2010).

    PubMed  Google Scholar 

  132. Nunez, P. L. Neocortical Dynamics and Human EEG Rhythms (Oxford University Press, New York, 1995).

    Google Scholar 

  133. Pfurtscheller, G. & Aranibar, A. Event-related cortical desynchronization detected by power measurements of scalp EEG. Electroencephalogr. Clin. Neurophysiol. 42, 817–826 (1977).

    CAS  PubMed  Google Scholar 

  134. Heinzle, J., König, P. & Salazar, R. F. Modulation of synchrony without changes in firing rates. Cogn. Neurodyn. 1, 225–235 (2007).

    PubMed  PubMed Central  Google Scholar 

  135. Gregoriou, G. G., Gotts, S. J., Zhou, H. & Desimone, R. High-frequency, long-range coupling between prefrontal and visual cortex during attention. Science 324, 1207–1210 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Frien, A., Eckhorn, R., Bauer, R., Woelbern, T. & Kehr, H. Stimulus-specific fast oscillations at zero phase between visual areas V1 and V2 of awake monkey. Neuroreport 5, 2273–2277 (1994).

    CAS  PubMed  Google Scholar 

  137. König, P. & Schillen, T. B. Stimulus-dependent assembly formation of oscillatory responses: I. synchronization. Neural Comput. 3, 155–166 (1991).

    PubMed  Google Scholar 

  138. Traub, R. D., Whittington, M. A., Stanford, I. M. & Jefferys, J.G. A mechanism for generation of long-range synchronous fast oscillations in the cortex. Nature 383, 621–624 (1996).

    CAS  PubMed  Google Scholar 

  139. Bibbig, A., Traub, R. D. & Whittington, M. A. Long-range synchronization of gamma and beta oscillations and the plasticity of excitatory and inhibitory synapses, a network model. J. Neurophysiol. 88, 1634–1654 (2002).

    PubMed  Google Scholar 

  140. Vicente, R., Gollo, L. L., Mirasso, C. R., Fischer, I. & Pipa, G. Dynamical relaying can yield zero time lag neuronal synchrony despite long conduction delays. Proc. Natl Acad. Sci. USA 105, 17157–17162 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Skaggs, W. E., McNaughton, B. L., Wilson, M. A. & Barnes, C. A. Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6, 149–172 (1996).

    CAS  PubMed  Google Scholar 

  142. Lachaux, J. P., Rodriguez, E., Martinerie, J. & Varela, F. J. Measuring phase synchrony in brain signals. Hum. Brain Mapp. 8, 194–208 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work is supported by grants from the German Research Foundation (SFB TR3, project A9 and DFG project FE366/5-1). We thank J. Jitsev, P. Klaver, N. Maier, L. Melloni, P. Sauseng and B. Staresina for valuable comments on an earlier draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, Bonn, D-53105, Germany

    Juergen Fell & Nikolai Axmacher

Authors
  1. Juergen Fell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikolai Axmacher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juergen Fell.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Juergen Fell and Nikolai Axmacher's homepage

Glossary

Local field potential

A neural voltage fluctuation recorded from the extracellular space, which mainly originates from postsynaptic potentials.

Neural oscillation

A periodic and continuous (wave-like) variation of a neural signal.

Oscillatory phase

The angle that corresponds to the momentary deflection of an oscillation (referring to the cosine function; for example, 0° at the peak and 180° at the trough of an oscillation).

Gamma frequency range

The frequency range between 30–100Hz.

Inactivation time constant

A variable controlling the temporal characteristics of the spontaneous inactivation of an ion channel, as described by an exponential decay function.

Coincidence-sensitive neurons

Neurons that predominantly discharge action potentials if simultaneously activated by multiple presynaptic neurons, defining a narrow time window for activation.

Hebbian learning

A cellular mechanism of learning, proposed by Donald Hebb, according to which the connection between a presynaptic and a postsynaptic cell is strengthened if the presynaptic cell is successful in activating a postsynaptic cell.

Spike timing-dependent plasticity

A special kind of neural plasticity that depends on time delays between the action potentials of the presynaptic and the postsynaptic neuron.

Spike–field coherence

The preferential firing of action potentials predominantly during a specific phase range of field potential oscillations.

Theta frequency range

The frequency range between 3–8Hz.

Spike doublets

Two action potentials that are separated by a brief temporal interval.

Material-specific buffer for short-term storage

A specialized short-term maintenance system for verbal (phonological loop) or spatial (visuo-spatial sketchpad) information.

Beta frequency range

The frequency range between 12–30Hz.

Spectral coherence

A traditional measure of synchronization between two brain regions, which comprises both the synchronization of phases and the co-variation of power (squared amplitude) of neural oscillations.

Declarative memory

Memory of consciously accessible content — for example, memory of experiences with their specific temporal and spatial contexts (episodic memory), and memory of facts (semantic memory).

Delta frequency range

The frequency range between 1–3Hz.

Aversive conditioning

A type of unconscious (non-declarative) learning that occurs when a stimulus (for example, a specific tone) is repeatedly accompanied by an unpleasant sensation such as an electric shock. After learning, presentation of the stimulus alone induces the physiological response associated with the unpleasant sensation.

Delayed matching-to-sample task

A typical working memory paradigm in which information about a single test item has to be maintained for several seconds. Afterwards, subjects have to indicate whether a probe item matches the test item.

Place cell

A hippocampal neuron that specifically responds to stimuli in certain spatial locations. Its firing rate increases when an animal or subject approaches the respective location.

Alpha frequency range

The frequency range between 8–12Hz.

Microelectrode recording

An electrophysiological recording with a microelectrode (which has a diameter of several μm) that enable researchers to measure individual action potentials in animals or humans.

Macroelectrode recording

An electrophysiological recording using macroelectrodes (contact size in the mm range), which allow electroencephalography recordings from within the animal or human brain.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fell, J., Axmacher, N. The role of phase synchronization in memory processes. Nat Rev Neurosci 12, 105–118 (2011). https://doi.org/10.1038/nrn2979

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2979

This article is cited by

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