title: Phase of Spontaneous Slow Oscillations during Sleep Influences Memory-Related Processing of Auditory Cues.
abstract: Slow oscillations during slow-wave sleep (SWS) may facilitate memory consolidation by regulating interactions between hippocampal and cortical networks. Slow oscillations appear as high-amplitude, synchronized EEG activity, corresponding to upstates of neuronal depolarization and downstates of hyperpolarization. Memory reactivations occur spontaneously during SWS, and can also be induced by presenting learning-related cues associated with a prior learning episode during sleep. This technique, targeted memory reactivation (TMR), selectively enhances memory consolidation. Given that memory reactivation is thought to occur preferentially during the slow-oscillation upstate, we hypothesized that TMR stimulation effects would depend on the phase of the slow oscillation. Participants learned arbitrary spatial locations for objects that were each paired with a characteristic sound (eg, cat-meow). Then, during SWS periods of an afternoon nap, one-half of the sounds were presented at low intensity. When object location memory was subsequently tested, recall accuracy was significantly better for those objects cued during sleep. We report here for the first time that this memory benefit was predicted by slow-wave phase at the time of stimulation. For cued objects, location memories were categorized according to amount of forgetting from pre- to post-nap. Conditions of high versus low forgetting corresponded to stimulation timing at different slow-oscillation phases, suggesting that learning-related stimuli were more likely to be processed and trigger memory reactivation when they occurred at the optimal phase of a slow oscillation. These findings provide insight into mechanisms of memory reactivation during sleep, supporting the idea that reactivation is most likely during cortical upstates.
  
  
  CONCLUSIONS
  Slow-wave sleep (SWS) is characterized by synchronized neural activity alternating between active upstates and quiet downstates. The slow-oscillation upstates are thought to provide a window of opportunity for memory consolidation, particularly conducive to cortical plasticity. Recent evidence shows that sensory cues associated with previous learning can be delivered subtly during SWS to selectively enhance memory consolidation. Our results demonstrate that this behavioral benefit is predicted by slow-oscillation phase at stimulus presentation time. Cues associated with high versus low forgetting based on analysis of subsequent recall performance were delivered at opposite slow-oscillation phases. These results provide evidence of an optimal slow-oscillation phase for memory consolidation during sleep, supporting the idea that memory processing occurs preferentially during cortical upstates.
authors.affiliation: Northwestern University, Evanston, Illinois 60208-2710 lbatterink@northwestern.edu.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Batterink
authors.affiliation: Northwestern University, Evanston, Illinois 60208-2710.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Creery
authors.affiliation: Northwestern University, Evanston, Illinois 60208-2710.
authors.forename: Ken A
authors.identifier: http://orcid.org/0000-0003-4415-4143
authors.initials: KA
authors.lastname: Paller
mesh_terms: D000161:Acoustic Stimulation; D001307:Auditory Perception / Q000502:physiology*; D001364:Awareness; D001683:Biological Clocks / Q000502:physiology*; D001931:Brain Mapping; D003463:Cues; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D005260:Female; D005583:Fourier Analysis; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D055815:Young Adult
keywords: memory consolidation; memory reactivation; phase; slow oscillation; slow-wave sleep
references.citation: Cereb Cortex. 2015 Nov;25(11):4169-79
references.pmid: 24962994
references.citation: Front Neurol. 2012 Apr 05;3:40
references.pmid: 22493589
references.citation: Trends Neurosci. 2010 May;33(5):220-9
references.pmid: 20207025
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2065-9
references.pmid: 12576550
references.citation: J Cogn Neurosci. 2014 Jan;26(1):143-53
references.pmid: 23984946
references.citation: Neuron. 2000 Dec;28(3):991-9
references.pmid: 11163282
references.citation: Nat Rev Neurosci. 2005 Feb;6(2):119-30
references.pmid: 15685217
references.citation: Prog Brain Res. 2011;193:93-110
references.pmid: 21854958
references.citation: Nat Neurosci. 2012 Oct;15(10):1439-44
references.pmid: 22941111
references.citation: Science. 2000 Oct 27;290(5492):812-6
references.pmid: 11052946
references.citation: Science. 2007 Mar 9;315(5817):1426-9
references.pmid: 17347444
references.citation: J Neurosci. 2008 Dec 31;28(53):14467-80
references.pmid: 19118181
references.citation: Neuron. 2002 Dec 19;36(6):1183-94
references.pmid: 12495631
references.citation: Nat Neurosci. 2007 Jan;10(1):100-7
references.pmid: 17173043
references.citation: Science. 2015 May 29;348(6238):1013-5
references.pmid: 26023137
references.citation: J Neurosci. 2009 Jun 17;29(24):7869-76
references.pmid: 19535598
references.citation: J Neurosci Methods. 2004 Mar 15;134(1):9-21
references.pmid: 15102499
references.citation: Psychol Res. 2012 Mar;76(2):192-203
references.pmid: 21541757
references.citation: Nat Neurosci. 2012 Aug;15(8):1114-6
references.pmid: 22751035
references.citation: Nature. 2006 Nov 30;444(7119):610-3
references.pmid: 17086200
references.citation: PLoS One. 2014;9(7):e101567
references.pmid: 24999803
references.citation: Curr Opin Neurobiol. 2000 Apr;10(2):180-6
references.pmid: 10753801
references.citation: Sleep. 2015 May;38(5):755-63
references.pmid: 25515103
references.citation: Trends Cogn Sci. 2013 Mar;17(3):142-9
references.pmid: 23433937
references.citation: Neuroscience. 1997 Nov;81(1):213-22
references.pmid: 9300413
references.citation: Philos Trans R Soc Lond B Biol Sci. 1971 Jul 1;262(841):23-81
references.pmid: 4399412
references.citation: Nat Rev Neurosci. 2010 Feb;11(2):114-26
references.pmid: 20046194
references.citation: Neuron. 1998 Nov;21(5):1123-8
references.pmid: 9856467
references.citation: Science. 2009 Nov 20;326(5956):1079
references.pmid: 19965421
references.citation: Science. 1994 Jul 29;265(5172):676-9
references.pmid: 8036517
references.citation: J Sleep Res. 2013 Feb;22(1):22-31
references.pmid: 22913273
references.citation: J Neurosci. 2002 Dec 15;22(24):10941-7
references.pmid: 12486189
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7041-5
references.pmid: 8041742
references.citation: Psychol Rev. 1995 Jul;102(3):419-57
references.pmid: 7624455
references.citation: J Neurosci Methods. 2016 Feb 1;259:101-14
references.pmid: 26617321