Cued Reactivation of Motor Learning during Sleep Leads to Overnight Changes in Functional Brain Activity and Connectivity

James N Cousins, Wael El-Deredy, Laura M Parkes, Nora Hennies, Penelope A Lewis, James N Cousins, Wael El-Deredy, Laura M Parkes, Nora Hennies, Penelope A Lewis

Abstract

Sleep plays a role in memory consolidation. This is demonstrated by improved performance and neural plasticity underlying that improvement after sleep. Targeted memory reactivation (TMR) allows the manipulation of sleep-dependent consolidation through intentionally biasing the replay of specific memories in sleep, but the underlying neural basis of these altered memories remains unclear. We use functional magnetic resonance imaging (fMRI) to show a change in the neural representation of a motor memory after targeted reactivation in slow-wave sleep (SWS). Participants learned two serial reaction time task (SRTT) sequences associated with different auditory tones (high or low pitch). During subsequent SWS, one sequence was reactivated by replaying the associated tones. Participants were retested on both sequences the following day during fMRI. As predicted, they showed faster reaction times for the cued sequence after targeted memory reactivation. Furthermore, increased activity in bilateral caudate nucleus and hippocampus for the cued relative to uncued sequence was associated with time in SWS, while increased cerebellar and cortical motor activity was related to time in rapid eye movement (REM) sleep. Functional connectivity between the caudate nucleus and hippocampus was also increased after targeted memory reactivation. These findings suggest that the offline performance gains associated with memory reactivation are supported by altered functional activity in key cognitive and motor networks, and that this consolidation is differentially mediated by both REM sleep and SWS.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Schematic of experiment design.
Fig 1. Schematic of experiment design.
(a) Learning (L) of the SRTT task consisted of interleaved blocks of the cued and uncued sequence, and also random blocks. (b) The cued sequence is replayed during periods of SWS in groups of 12 sequences (CUE) and equivalent periods of silence (NO-CUE). (c) Retest (R) of the SRTT takes place the following morning in the MRI scanner, followed shortly afterwards by the explicit memory test outside of the scanner.
Fig 2. Performance improvement at retest.
Fig 2. Performance improvement at retest.
(a) Comparison of presleep sequence performance to early blocks of sequence retest showed a significant cueing effect. (b) Accuracy improvement was also significantly greater for the cued sequence at early blocks. (c) Performance improvement for both sequences was comparable at late sequence blocks and random blocks that followed. Error bars represent standard error of the mean (SEM) (S1 Data).
Fig 3. Changes in brain activity after…
Fig 3. Changes in brain activity after targeted-memory reactivation.
(a) The basic comparison between cued and uncued showed reduced activity in left caudate (−20, 24, −10) for the cued sequence. (b) SWS was associated with enhanced activation in bilateral caudate (16, 8, 20 and −12, 20, 12), and bilateral hippocampi (26, −34, 2 and −22, −34, 6) for the cued sequence relative to the uncued. (b) REM sleep was associated with cueing related activity enhancement in left cerebellum (−32, −54, −44 and 20 −72, −26), left superior parietal cortex (−28, −56, 68 and 22, −54, 38), left sensorimotor cortex (SMC) (−40, −32, 68), left dorsolateral prefrontal cortex (dlPFC) (−30, 34, 28) and right premotor cortex (PMC) (42, −2, 32 and 42, −2, 58). These findings were whole brain corrected (p < 0.05) and displayed as sagittal and coronal projections superimposed on a standard Montreal Neurological Institute (MNI) brain. Colour bar indicates t-values. Anatomical labelling based on peak z-score location.
Fig 4. Regions of increased functional connectivity…
Fig 4. Regions of increased functional connectivity after TMR.
A PPI analysis revealed enhanced connectivity for the cued sequence between left hippocampus (−22, −34, 6) and right putamen (36, −2, 4) and PMC (58, 4, 22). Contrasts displayed as sagittal and coronal projections superimposed on a standard MNI brain. Colour bar indicates t-values. Anatomical labelling based on peak z-score location.

References

    1. McClelland JL, McNaughton BL, O’Reilly RC. Why there are complementary learning systems in the hippocampus and neortex: Insights from the successes and failures of connectionist models of learning and memory. Psychol Rev. 1995;102(3): 419–57.
    1. Doyon J, Benali H. Reorganization and plasticity in the adult brain during learning of motor skills. Curr Opin Neurobiol. 2005;15: 161–7.
    1. Floyer-Lea A, Matthews PM. Distinguishable brain activation networks for short- and long-term motor skill learning. J Neurophysiol. 2005;94(1): 512–8.
    1. Doyon J, Bellec P, Amsel R, Penhune V, Monchi O, Carrier J, et al. Contributions of the basal ganglia and functionally related brain structures to motor learning. Behav Brain Res. 2009;199(1): 61–75. 10.1016/j.bbr.2008.11.012
    1. Penhune VB, Doyon J. Cerebellum and M1 interaction during early learning of timed motor sequences. Neuroimage. 2005;26(3): 801–12.
    1. Fischer S, Nitschke MF, Melchert UH, Erdmann C, Born J. Motor memory consolidation in sleep shapes more effective neuronal representations. J Neurosci. 2005;25(49): 11248–55.
    1. Walker MP, Stickgold R, Alsop D, Gaab N, Schlaug G. Sleep-dependent motor memory plasticity in the human brain. Neuroscience. 2005;133(4): 911–7.
    1. Debas K, Carrier J, Orban P, Barakat M, Lungu O, Vandewalle G, et al. Brain plasticity related to the consolidation of motor sequence learning and motor adaptation. Proc Natl Acad Sci. 2010;107(41): 17839–44. 10.1073/pnas.1013176107
    1. Debas K, Carrier J, Barakat M, Marrelec G, Bellec P, Tahar AH, et al. Off-line consolidation of motor sequence learning results in greater integration within a cortico-striatal functional network. Neuroimage. 2014;99: 50–8. 10.1016/j.neuroimage.2014.05.022
    1. Albouy G, Sterpenich V, Balteau E, Vandewalle G, Desseilles M, Dang-Vu T, et al. Both the hippocampus and striatum are involved in consolidation of motor sequence memory. Neuron. 2008;58(2): 261–72. 10.1016/j.neuron.2008.02.008
    1. Albouy G, Sterpenich V, Vandewalle G, Darsaud A, Gais S, Rauchs G, et al. Interaction between hippocampal and striatal systems predicts subsequent consolidation of motor sequence memory. PLoS ONE. 2013;8(3): e59490 10.1371/journal.pone.0059490
    1. Genzel L, Dresler M, Cornu M, Jäger E, Konrad B, Adamczyk M, et al. Medial prefrontal-hippocampal connectivity and motor memory consolidation in depression and schizophrenia. Biol Psychiatry. 2015;77(2): 177–86. 10.1016/j.biopsych.2014.06.004
    1. Albouy G, Fogel S, King BR, Laventure S, Benali H, Karni A, et al. Maintaining vs. enhancing motor sequence memories: Respective roles of striatal and hippocampal systems. Neuroimage. 2015;108: 423–34. 10.1016/j.neuroimage.2014.12.049
    1. Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010;11(2): 114–26. 10.1038/nrn2762
    1. Genzel L, Kroes MCW, Dresler M, Battaglia FP. Light sleep versus slow wave sleep in memory consolidation: a question of global versus local processes? Trends Neurosci. 2014;37(1): 10–9. 10.1016/j.tins.2013.10.002
    1. Genzel L, Robertson EM. To Replay, Perchance to Consolidate. PLoS Biol. 2015;13(10): e1002285 10.1371/journal.pbio.1002285
    1. Lewis PA, Durrant SJ. Overlapping memory replay during sleep builds cognitive schemata. Trends Cogn Sci. 2011;15(8): 343–51. 10.1016/j.tics.2011.06.004
    1. Wilson MA, McNaughton BL. Reactivation of hippocampal ensemble memories during sleep. Science. 1995;265(5172): 676–679.
    1. Bendor D, Wilson MA. Biasing the content of hippocampal replay during sleep. Nat Neurosci. 2012;15(10): 1439–44. 10.1038/nn.3203
    1. Pennartz CMA, Lee E, Verheul J, Lipa P, Barnes CA, McNaughton BL. The ventral striatum in off-line processing: ensemble reactivation during sleep and modulation by hippocampal ripples. J Neurosci. 2004;24(29): 6446–56.
    1. Ramanathan DS, Gulati T, Ganguly K. Sleep-dependent reactivation of ensembles in motor cortex promotes skill consolidation. PLoS Biol. 2015;13(9): e1002263 10.1371/journal.pbio.1002263
    1. Girardeau G, Benchenane K, Wiener SI, Buzsáki G, Zugaro MB. Selective suppression of hippocampal ripples impairs spatial memory. Nat Neurosci. 2009;12(10): 1222–3. 10.1038/nn.2384
    1. Yang G, Lai CSW, Cichon J, Ma L, Li W, Gan W- B. Sleep promotes branch-specific formation of dendritic spines after learning. Science. 2014;344: 1173–8. 10.1126/science.1249098
    1. Peigneux P, Laureys S, Fuchs S, Destrebecqz A, Collette F, Delbeuck X, et al. Learned material content and acquisition level modulate cerebral reactivation during posttraining rapid-eye-movements sleep. Neuroimage. 2003;20(1): 125–34.
    1. Laureys S, Peigneux P, Phillips C, Fuchs S, Degueldre C, Aerts J, et al. Experience-dependant changes in cerebral functional connectivity during human rapid eye movement sleep. Neuroscience. 2001;105(1): 521–5.
    1. Peigneux P, Laureys S, Fuchs S, Collette F, Perrin F, Reggers J, et al. Are spatial memories strengthened in the human hippocampus during slow wave sleep? Neuron. 2004;44(3): 535–45.
    1. Rasch B, Büchel C, Gais S, Born J. Odor cues during slow-wave sleep prompt declarative memory consolidation. Science. 2007;315(5817): 1426–9.
    1. Cousins JN, El-Deredy W, Parkes LM, Hennies N, Lewis PA. Cued memory reactivation during slow-wave sleep promotes explicit knowledge of a motor sequence. J Neurosci. 2014;34(48): 15870–6. 10.1523/JNEUROSCI.1011-14.2014
    1. Oudiette D, Paller KA. Upgrading the sleeping brain with targeted memory reactivation. Trends Cogn Sci. 2013;17(3): 142–9. 10.1016/j.tics.2013.01.006
    1. Antony JW, Gobel EW, O’Hare JK, Reber PJ, Paller KA. Cued memory reactivation during sleep influences skill learning. Nat Neurosci. 2012;15(8): 1114–6. 10.1038/nn.3152
    1. Schönauer M, Geisler T, Gais S. Strengthening procedural memories by reactivation in sleep. J Cognitive Neurosci. 2014;26(1): 143–53.
    1. Sterpenich V, Schmidt C, Albouy G, Matarazzo L, Vanhaudenhuyse A, Boveroux P, et al. Memory reactivation during rapid eye movement sleep promotes its generalization and integration in cortical stores. Sleep. 2014;37: 1061–75. 10.5665/sleep.3762
    1. van Dongen E V, Takashima A, Barth M, Zapp J, Schad LR, Paller KA, et al. Memory stabilization with targeted reactivation during human slow-wave sleep. Proc Natl Acad Sci U S A. 2012;109(26): 10575–80. 10.1073/pnas.1201072109
    1. Cordi MJ, Diekelmann S, Born J, Rasch B. No effect of odor-induced memory reactivation during REM sleep on declarative memory stability. Front Syst Neurosci. 2014;8(September): 1–7.
    1. Albouy G, King BR, Maquet P, Doyon J. Hippocampus and striatum: Dynamics and interaction during acquisition and sleep-related motor sequence memory consolidation. Hippocampus. 2013;23(11): 985–1004 10.1002/hipo.22183
    1. Rasch B, Born J. In search of a role of REM sleep in memory formation. Neurobiol Learn Mem. 2015;122: 1–3. 10.1016/j.nlm.2015.04.012
    1. Fischer S, Hallschmid M, Elsner AL, Born J. Sleep forms memory for finger skills. Proc Natl Acad Sci U S A. 2002;99(18): 11987–91.
    1. Plihal W, Born J. Effects of early and late nocturnal sleep on declarative and procedural memory. J Cogn Neurosci. 1997;9(4): 534–47. 10.1162/jocn.1997.9.4.534
    1. Rasch B, Gais S, Born J. Impaired off-line consolidation of motor memories after combined blockade of cholinergic receptors during REM sleep-rich sleep. Neuropsychopharmacology. 2009;34(7): 1843–53. 10.1038/npp.2009.6
    1. Rasch B, Pommer J, Diekelmann S, Born J. Pharmacological REM sleep suppression paradoxically improves rather than impairs skill memory. Nat Neurosci. 2009;12(4): 396–7. 10.1038/nn.2206
    1. Vertes RP, Eastman KE. The case against memory consolidation in REM sleep. Behav Brain Sci. 2000;23(6): 867–76.
    1. Louie K, Wilson MA. Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep. Neuron. 2001;29(1): 145–56.
    1. Giuditta A, Ambrosini M V, Montagnese P, Mandile P, Cotugno M, Grassi Zucconi G, et al. The sequential hypothesis of the function of sleep. Behav Brain Res. 1995;69(1–2): 157–66.
    1. Nissen MJ, Bullemer P. Attentional requirements of learning: Evidence from performance measures. Cognitive Psychol. 1987;19(1): 1–32.
    1. Durrant SJ, Cairney SA., Lewis PA. Overnight consolidation aids the transfer of statistical knowledge from the medial temporal lobe to the striatum. Cereb Cortex. 2013;23: 2467–78. 10.1093/cercor/bhs244
    1. Cairney SA, Durrant SJ, Hulleman J, Lewis PA. Targeted memory reactivation during slow wave sleep facilitates emotional memory consolidation. Sleep. 2014;37: 701–7. 10.5665/sleep.3572
    1. Diekelmann S, Biggel S, Rasch B, Born J. Offline consolidation of memory varies with time in slow wave sleep and can be accelerated by cuing memory reactivations. Neurobiol Learn Mem. 2012;98(2): 103–11. 10.1016/j.nlm.2012.07.002
    1. Walker MP, Brakefield T, Morgan A, Hobson JA, Stickgold R. Practice with sleep makes perfect: sleep-dependent motor skill learning. Neuron. 2002;35(1): 205–11.
    1. Fogel SM, Smith CT. Learning-dependent changes in sleep spindles and stage 2 sleep. J Sleep Res. 2006;15(3): 250–5.
    1. Fogel SM, Albouy G, Vien C, Popovicci R, King BR, Hoge R, et al. fMRI and sleep correlates of the age-related impairment in motor memory consolidation. Hum Brain Mapp. 2014;35: 3625–45. 10.1002/hbm.22426
    1. Cohen DA, Pascual-Leone A, Press DZ, Robertson EM. Off-line learning of motor skill memory: a double dissociation of goal and movement. Proc Natl Acad Sci U S A. 2005;102(50): 18237–41.
    1. Robertson EM, Pascual-Leone A, Press DZ. Awareness modifies the skill-learning benefits of sleep. Curr Biol. 2004;14(3): 208–12.
    1. Spencer RMC, Sunm M, Ivry RB. Sleep-dependent consolidation of contextual learning. Curr Biol. 2006;16(10): 1001–5.
    1. Albouy G, Fogel S, Pottiez H, Nguyen VA, Ray L, Lungu O, et al. Daytime sleep enhances consolidation of the spatial but not motoric representation of motor sequence memory. PLoS ONE. 2013;8(1): e52805 10.1371/journal.pone.0052805
    1. Karni A, Meyer G, Rey-Hipolito C, Jezzard P, Adams MM, Turner R, Ungerleider LG. The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex. Proc Natl Acad Sci U S A. 1995;95(3): 861–868.
    1. Ohyama T, Nores WL, Murphy M, Mauk MD. What the cerebellum computes. Trends Neurosci. 2003;26(4): 222–7.
    1. Kelly RM, Strick PL. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J Neurosci. 2003;23(23): 8432–44.
    1. Tunovic S, Press DZ, Robertson EM. A physiological signal that prevents motor skill improvements during consolidation. J Neurosci. 2014;34(15): 5302–10. 10.1523/JNEUROSCI.3497-13.2014
    1. Breton J, Robertson EM. Flipping the switch: mechanisms that regulate memory consolidation. Trends Cogn Sci. 2014;18(12): 629–34. 10.1016/j.tics.2014.08.005
    1. Paus T. Location and function of the human frontal eye- field : A selective review. Neuropsychologia. 1996;34(6): 475–83.
    1. Boecker H, Jankowski J, Ditter P, Scheef L. A role of the basal ganglia and midbrain nuclei for initiation of motor sequences. Neuroimage. 2008;39(3): 1356–69.
    1. Barakat M, Carrier J, Debas K, Lungu O, Fogel S, Vandewalle G, et al. Sleep spindles predict neural and behavioral changes in motor sequence consolidation. Hum Brain Mapp. 2013;34: 2918–28. 10.1002/hbm.22116
    1. Barakat M, Doyon J, Debas K, Vandewalle G, Morin A, Poirier G, et al. Fast and slow spindle involvement in the consolidation of a new motor sequence. Behav Brain Res. 2011;217(1): 117–21. 10.1016/j.bbr.2010.10.019
    1. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1972;9(1): 97–113.
    1. Hoddes E, Zarcone V, Smythe H, Phillips R, Dement WC. Quantification of sleepiness: A new approach. Psychophysiology. 1973;10(4): 431–436.
    1. Iber C, Ancoli-Israel S, Chesson A, and Quan SF. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications Westchester: American Academy of Sleep Medicine; 2007.
    1. Friston KJ, Holmes AP, Worsley KJ, Poline J- P, Frith CD, Frackowiak RSJ. Statistical parametric maps in functional imaging: A general linear approach. Hum Brain Mapp. 1995;2(4): 189–210.
    1. Slotnick SD, Moo LR, Segal JB, Hart J. Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes. Cogn Brain Res. 2003;17(1): 75–82.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe