The Role of Sleep in Cognition and Emotion - Matthew Walker

30 Pages·2009·0.68 MB·English

THE YEAR IN COGNITIVE NEUROSCIENCE 2009
The Role of Sleep in Cognition and Emotion
Matthew P. Walker
SleepandNeuroimagingLaboratory,DepartmentofPsychology&HelenWills
NeuroscienceInstitute,UniversityofCalifornia,Berkeley,California
As critical as waking brain function is to cognition, an extensive literature now indi-
catesthatsleepsupportsequallyimportant,differentyetcomplementaryoperations.
Thisreviewwillconsiderrecentandemergingfindingsimplicatingsleepandspecific
sleep-stage physiologies in the modulation, regulation, and even preparation of cog-
nitiveandemotionalbrainprocesses.First,evidencefortheroleofsleepinmemory
processingwillbediscussed,principallyfocusingondeclarativememory.Second,ata
neurallevelseveralmechanisticmodelsofsleep-dependentplasticityunderlyingthese
effectswillbereviewed,withasynthesisofthesefeaturesofferedthatmayexplainthe
orderedstructureofsleep,andtheorderlyevolutionofmemorystages.Third,accumu-
latingevidencefortheroleofsleepinassociativememoryprocessingwillbediscussed,
suggestingthatthelong-termgoalofsleepmaynotbethestrengtheningofindividual
memoryitems,but,instead,theirabstractedassimilationintoaschemaofgeneralized
knowledge.Fourth,thenewlyemergingbenefitofsleepinregulatingemotionalbrain
reactivitywillbeconsidered.Finally,andbuildingonthislattertopic,anovelhypoth-
esis and framework of sleep-dependent affective brain processing will be proposed,
culminatingintestablepredictionsandtranslationalimplicationsformooddisorders.
Keywords: sleep;learning;memory;encoding;consolidation;association;integration;
plasticity;emotion;affect;non-rapideyemovement(NREM)sleep;rapideyemovement
(NREM)sleep;offline;slowwavesleep(SWS),slow-waveactivity(SWA),sleepspindles
“Ifsleepdoesnotserveanabsolutelyvitalfunction,thenitis the vast amount of time this state takes from
thebiggestmistaketheevolutionaryprocesshasevermade.” our lives, we still lack any consensus function
forsleep.Inpart,thisisperhapsbecausesleep,
AllanRechtschaffen
likeitscounterpartwakefulness,mayservenot
UniversityofChicagoSleepLaboratory
one but many functions, for brain and body
Smithsonian,November1978
alike.
Centrally,sleepisabrainphenomenon,and
Introduction over the past 20 years, an exciting revival has
taken place within the neurosciences, one that
A perplexing question continues to elude focuses on the question of why we sleep, and
scientific judgment: “Why do we sleep?” In specificallytargetingtheroleofsleepinanum-
accepting the utility of evolution, as candidly berofcognitiveandemotionalprocesses.This
stated by pioneering sleep researcher Allan review aims to provide a synthesis of these re-
Rechtschaffen, sleep is likely to support a fun- cent findings in humans, with the goal of ex-
damental need of the organism. Yet, despite tracting consistent themes across domains of
brain function that appear to be regulated by
sleep. Providing a mechanistic foundation on
which to consider these findings, the first sec-
Address for correspondence: Matthew P. Walker, Sleep and
Neuroimaging Laboratory, Department of Psychology & Helen tionofthischapterbrieflysummarizesthebrain
Wills Neuroscience Institute, University of California, Berkeley, substrates of sleep: its neurochemistry, neuro-
California94720-1650,USA.Voice:510-642-5292;fax:[phone].
[email protected] physiology, and functional anatomy. The next
TheYearinCognitiveNeuroscience2009:Ann.N.Y.Acad.Sci.1156:168–197(2009).
doi:10.1111/j.1749-6632.2009.04416.x (cid:2)C 2009NewYorkAcademyofSciences.
168
Walker:SleepinCognitionandEmotion 169
AWAKE
e REM
g
a
St NREM-1 S W S
ep NREM-2
e R E M
Sl NREM-3
NREM-4 stage-2 N R E M
12am 1am 2am 3am 4am 5am 6am 7am
Time
Figure 1. The human sleep cycle. Across the night, NREM and REM sleep cycle every
90 minutes in an ultradian manner, while the ratio of NREM to REM sleep shifts. During the
first half of the night, NREM stages 3 and 4 NREM (SWS) dominate, while stage 2 NREM
and REM sleep prevail in the latter half of the night. EEG patterns also differ significantly
between sleep stages, with electrical oscillations such as slow delta waves developing in
SWS, K-complexes and sleep spindles occurring during stage 2 NREM, and theta waves
seenduringREM.
section explores the role of sleep in memory thisorganizingprincipal(deepNREMearlyin
andbrainplasticityandalsoexaminescompet- the night, stage 2 NREM and REM late in
ing models of sleep-dependent learning. The thenight)remains unknown–anotherperplex-
thirdsectionaddressestheroleofsleepbeyond ingmysteryofsleep.
memoryconsolidation,inprocessesofassocia- As NREM sleep progresses, electroen-
tion, integration, and creativity. The final sec- cephalographic(EEG)activitybeginstoslowin
tion discusses the more recent and emerging frequency.Throughoutstage-2NREMthereis
role for sleep in emotional and affective brain the presence of phasic electrical events includ-
regulation. ing K-complexes (large electrical sharp waves
in the EEG) and sleep spindles (short syn-
chronized 10–16 Hz) EEG oscillations (Steri-
Sleep Neurobiology ade & Amzica 1998). The deepest stages of
NREM, stages 3 and 4, are often grouped
The sleep of mammalian species has been together under the term “slow wave sleep”
broadly classified into two distinct types: non- (SWS), reflecting the occurrence of low fre-
rapid eye movement (NREM) sleep and rapid quencywaves(1–4Hzand<1Hz),whichhave
eyemovement(REM)sleep,withNREMsleep themselves been termed “slow-wave activity”
beingfurtherdividedinprimatesandcatsinto (SWA), representing an expression of underly-
four substages (1–4) corresponding, in that or- ing mass cortical synchrony (Amzica & Steri-
der,toincreasingdepthofsleep(Rechtschaffen ade 1995). During REM sleep, however, EEG
& Kales 1968). In humans, NREM and REM waveforms once again change in their com-
sleep alternate or “cycle” across the night in position, associated with oscillatory activity in
an ultradian pattern every 90 min (Fig. 1). the theta band range (4–7 Hz), together with
Although this NREM−REM cycle length re- higher frequency synchronous activity in the
mains largely stable across the night, the ratio 30–80 Hz (“gamma”) range (Llinas & Ribary
of NREM to REM within each 90-min cycle 1993; Steriade et al. 1996). Periodic bursts of
changes,sothatearlyinthenightstages3and REM also take place, a defining characteristic
4 of NREM dominate, while stage 2 NREM of REM sleep, associated with the occurrence
andREMsleepprevailinthelatterhalfofthe of phasic endogenous waveforms expressed
night. Interestingly, the functional reasons for in, among other regions, the pons (P), lateral
170 AnnalsoftheNewYorkAcademyofSciences
geniculate nuclei of the thalamus (G), and the themodulation,regulation,andpreparationof
occipital cortex (O), and as such, have been numerousbrainfunctions.
termed“PGOwaves”(Callawayetal.1987).
As the brain passes through these sleep
stages, it also undergoes dramatic alterations Memory Processing
in neurochemistry. In NREM sleep subcorti- and Brain Plasticity
cal cholinergic systems in the brain stem and
forebrainbecomemarkedlylessactive(Hobson In considering the role of sleep in memory
et al. 1975; Lydic & Baghdoyan 1988), while processing, it is pertinent one appreciate that
firing rates of serotonergic raphe´ neurons and memories evolve (Walker & Stickgold 2006).
noradrenergiclocuscoeruleusneuronsarealso Specifically, memories pass through discrete
reduced relative to waking levels (Aston-Jones stages in their “life span.” The conception of
& Bloom 1981; Shima et al. 1986). During amemorybeginswiththeprocessofencoding,
REM sleep both these aminergic populations resultinginastoredrepresentationofanexpe-
are strongly inhibited, while cholinergic sys- riencewithinthebrain(Paller&Wagner2002).
temsbecomeas/moreactivecomparedtowhat However,itisnowunderstoodthatavastnum-
theyareduringwake(Kametani&Kawamura berofpostencodingmemoryprocessescantake
1990;Marrosuetal.1995),resultinginabrain place (Stickgold & Walker 2005a). For mem-
state largely devoid of aminergic modulation ories to persist over the longer time course of
anddominatedbyacetylcholine. minutestoyears,anoffline,nonconsciousoper-
At a whole-brain systems level, neuroimag- ationofeventconsolidationappearstobenec-
ing techniques have revealed complex and essary, affording memories greater resistance
dramatically different patterns of functional todecay(aprocessofstabilization),orevenim-
anatomy associated with NREM and REM provedrecollection(aprocessofenhancement)
sleep (for review, see Nofzinger 2005). During (Robertsonetal.2004;Walker2005).Sleephas
NREM SWS, rostral brain-stem regions, tha- beenimplicatedinboththeencodingandcon-
lamicnuclei,basalganglia,hypothalamus,pre- solidationofmemory.
frontal cortex, cingulate corticies, and medial
regions of the temporal lobe all appear to un-
Sleep and Memory Encoding
dergoreducedactivity.However,duringREM
sleepsignificantelevationsinactivityhavebeen One of the earliest human studies to report
reported in the pontine tegmentum, thalamic the effects of sleep and sleep deprivation on
nuclei, occipital cortex, mediobasal prefrontal declarative memory encoding was by Morris
lobes, and associated limbic groups, including et al. (1960), indicating that “temporal mem-
theamygdala,hippocampus,andanteriorcin- ory” (memory involving when events occur)
gulate cortex. In contrast, the dorso−lateral was significantly disrupted by a night of pre-
prefrontalcortex,posteriorcingulate,andpari- training sleep loss. These findings have been
etalcortexappearleastactiveinREMsleep. revisited in a more rigorous study by Harri-
Although this summary only begins to de- son and Horne (2000), again using the tem-
scribetherangeofneuralprocessesthatareaf- poral memory paradigm. Significant impair-
fectedbythebrain’sdailytransitthroughsleep ments in retention were evident in a group of
states, it clearly demonstrates that sleep itself subjects deprived of sleep for 36 h, the sub-
cannotbetreatedasahomogeneousentity,one jects scoring significantly lower than controls,
whichmayormaynotaltercognitiveandemo- even in a subgroup that received caffeine to
tional processes. Instead, this constellation of overcome nonspecific effects of lower alert-
sleepstagesoffersarangeofdistinctneurobio- ness.Furthermore,thesleep-deprived subjects
logicalmechanismsthatcanpotentiallysupport displayed significantly worse insight into their
Walker:SleepinCognitionandEmotion 171
A B
* **
1.2 Sleep 1.6
n.s. Sleep Deprived
1.4
1.0
d')
y ( 1.2
enc 0.8 1.0
ci
Effi 0.6 0.8
g
n
di 0.6
o 0.4
c
En 0.4
0.2
0.2
0.0 0.0
ALL POSITIVE NEGATIVE NEUTRAL
STIMULUS TYPES STIMULUS TYPE
Figure 2. Sleep deprivation and encoding of emotional and nonemotional declarative memory. Effects
of38hoftotalsleepdeprivationonencodingofhumandeclarativememory(A)whencombinedacrossall
emotionalandnonemotionalcategories;(B)Whenseparatedbyemotional(positiveandnegativevalence)
and nonemotional (neutral valance) categories. †P < 0.08, ∗P < 0.05, ∗∗P < 0.01, error bars represent
SEM.
memory-encoding performance, resulting in for emotional material. We have investigated
lowerpredictiveabilityofperformance. the impact of sleep deprivation on the encod-
Pioneering work by Drummond and col- ing of emotionally negative, positive, and neu-
leagues examined the neural basis of sim- tralwords(Walker,unpublishedresults).When
ilar memory impairments using functional combined across all stimulus types, subjects in
MRI (fMRI), investigating the effects of 35 h the sleep-deprived condition exhibited a strik-
of total sleep deprivation on verbal learning ing 40% reduction in the ability to form new
(Drummond et al. 2000). In those who were human memories under conditions of sleep
sleepdeprived,regionsofthemedialtemporal deprivation (Fig. 2A). However, when these
lobeweresignificantlylessactiveduringlearn- data were separated into the three affective
ing, relative to a control group that had slept, categories (negative, positive, or neutral), the
while the prefrontal cortex actually expressed magnitude of encoding impairment differed
greater activation. Most interesting, the pari- (Fig. 2B). In those that had slept, both posi-
etallobes,whichwerenotactivatedinthecon- tive and negative stimuli were associated with
trol group during learning, were significantly superior retention levels relative to the neutral
active in the deprivation group. Such findings condition,consistentwiththenotionthatemo-
suggest that inadequate sleep prior to learn- tionfacilitatesmemoryencoding(Phelps2004).
ing(atleastfollowingonenight)producesbidi- However, there was severe disruption of en-
rectionalchangesinepisodicencodingactivity, coding and hence later retention for neutral
involving the inability of the medial temporal and especially positive emotional memory in
lobetoengagenormallyduringlearning,com- thesleep-deprivedgroup.Incontrast,arelative
binedwithpotentialcompensationattemptsby resistance of negative emotional memory was
prefrontalregions,whichinturnmayfacilitate observedinthedeprivationgroup.Thesedata
recruitment of parietal lobe function (Drum- suggest that,whiletheeffectsofsleepdepriva-
mond&Brown2001). tionaredirectionallyconsistentacrossmemory
The impact of sleep deprivation on mem- subcategories, the most profound impact is on
ory formation may be especially pronounced theencodingofpositiveemotionalstimuli,and
172 AnnalsoftheNewYorkAcademyofSciences
to a lesser degree, emotionally neutral stimuli. gyrus(IFG)displayedasignificantpositive,po-
In contrast, the encoding of negative memory tentiallycompensatory,relationshipwithmem-
appears to be more resistant to the effects of ory performance in those who were sleep de-
priorsleeploss,atleastfollowingonenight. prived(Figs.3B&C).
Intriguingly, these data may offer novel in- Taken together, this collection of findings
sightsintoaffectivemooddisordersthatexpress indicate the critical need for sleep-before-
co-occurring sleep abnormalities (Benca et al. learning in the preparation of key neural
1992; Buysse 2004). Indeed, if one compares structuresforefficientnext-daylearning.With-
the profiles of memory encoding in Fig. 2B, out adequate sleep, hippocampal function
it is clear that those who slept encoded and becomesmarkedlydisrupted,resultinginade-
retained a balanced mix of both positive and creased ability for recording new experiences,
negativememories.Incontrast,thosewhodid the extent of which appears to be further gov-
not sleep displayed a skewed relative distribu- erned by alterations in prefrontal encoding
tion of encoding, resulting in an overriding dynamics.
dominance of negative memories, combined
with a retention deficit of positive and neutral
Sleep and Memory Consolidation
memories. This selective alteration in mem-
ory encoding may provide an experimental Usingavarietyofbehavioralparadigms,ev-
explanationforthehigherincidenceofdepres- idencefortheroleofsleepinmemoryconsoli-
sioninpopulationsthatsuffer sleep disruption dation has now been reported across a diverse
(Shafferyetal.2003;Buysse2004),which,due range of phylogeny. Perhaps the earliest refer-
to these specific deficits, may impose a neg- encetothebeneficialimpactofsleeponmem-
ative remembering bias, despite the fact that ory is by the Roman rhetorician Quintilian,
thesesubjectsexperiencedequallypositive-and whostated:
negative-reinforcingeventhistories.
[it]isacuriousfact,ofwhichthereasonisnotobvious,that
Theimpactofsleepdeprivationontheneu-
theintervalofasinglenightwillgreatlyincreasethestrength
raldynamicsassociatedwithdeclarativemem-
ofthememory....Whateverthecause,thingswhichcould
oryencodinghasrecentlybeenexaminedusing notberecalledonthespotareeasilycoordinatedthenextday,
event-relatedfMRI(Yooetal.2007a).Inaddi- andtimeitself,whichisgenerallyaccountedoneofthecauses
tion to performance impairments under con- of forgetfulness, actually serves to strengthen the memory.
(Hammond2004).
dition of sleep deprivation, and relative to a
controlgroupthatslept,ahighlysignificantand In the early eighteenth and twentieth cen-
selective deficit was identified in bilateral re- turies respectively, David Hartley (Hartley
gionsofthehippocampus—astructureknown 1801) and Jenkins and Dallenback (Jenkins &
to be critical for learning new episodic infor- Dallenbach1924)indicatedthatthestrengthof
mation (Eichenbaum 2004) (Fig. 3A). While a memory may be better preserved by periods
these findings indicated that, at a group level, ofsleepthanitisbyequivalentperiodsoftime
sleepdeprivationmarkedlyimpairshippocam- awake.Followingthediscoveryofdiscretesleep
pal memory function, when examined within stages (Aserinsky & Kleitman 1953), research
each group separately, the success of encod- investigatingtheinfluenceofsleeponmemory
ing, from low to high, was further associated has become gradually more complex at both
with activity in different regions of the pre- a behavioral and mechanistic level. A robust
frontal lobe. In those that slept prior to learn- andconsistentliteraturehasdemonstratedthe
ing, the right dorsal/middle lateral prefrontal needforsleepafterlearninginthesubsequent
cortex showed a strong positive relationship consolidation and enhancement of procedural
with the proficiency of memory encoding. In memories;theevidenceforwhichhasrecently
contrast, a region in the right inferior frontal been reviewed elsewhere (Walker & Stickgold
Walker:SleepinCognitionandEmotion 173
Figure3. Neuralbasisofsleep-deprivation-inducedencodingdeficits.(A)Regionsofde-
creasedencodingactivationinthesleepdeprivationgrouprelativetothesleepcontrolgroup
in bilateral posterior hippocampus, together with a histogram of parameter estimates (effect
size) of averaged hippocampal activity in each group. Effects are significant atP< 0.001;
>5 contiguous voxels. (B) correlation analysis with memory performance showing regions
ofsignificantassociationbetweenencoding-relatedactivationandmemoryperformance(d’)
acrosssubjectsinthesleepcontrolgroup(peak–rightMiddle/dorso-lateralprefrontalcortex),
and(C)inthesleepdeprivationgroup(peak–rightInferiorfrontalgyrus).ModifiedfromYoo
etal.2007a.
2006).Earlyworkfocusingontheroleforsleep effect of sleep on the consolidation of declar-
in declarative memory processing was some- ative memory—our focus here (Smith 2001;
what less consistent, but more recent findings Ellenbogen et al. 2006b; Walker & Stickgold
have now begun to reveal a robust beneficial 2006;Marshall&Born2007).
174 AnnalsoftheNewYorkAcademyofSciences
Several reports by Born and his colleagues *
showed offline improvement on a word-pair
association task following sleep, an improve- 100
ment attributed to early night sleep, rich in
**
SWS(Plihal&Born1997,1999;Gais&Born
80
2004). More recently, the same group demon-
strated that, in addition to classically defined
slowdeltawaves(0.5–4Hz),theveryslowcorti- all
c 60
caloscillation(<1Hz)appearstobeimportant e
R
for the consolidation of declarative memories. nt
e
Following subject learning of a word-pair list, c
er 40
atechniquecalled“directcurrentstimulation” P
was used to induce slow oscillation-like field
potentialsintheprefrontalcortex(inthiscase, 20
at 0.75 Hz) during early night SWS (Marshall
etal.2006).Directcurrentstimulationnotonly
increased the amount of slow oscillations dur- 0
Wake Sleep Wake-I Sleep-I
ing the simulation period (and for some time
(no interference) (interference)
after), but also enhanced next-day word-pair
Condition
retention, suggesting a critical role for SWS
neurophysiologyintheofflineconsolidationof Figure 4. Impact of sleep on the consolidation
andstabilizationofdeclarativememory.Percentcor-
episodicfacts.
rect recall for B words from the original A-B pair
Rather than simply testing memory recall,
after a 12-h retention interval of either wake or
Ellenbogenandcolleagueshavesincerevealed sleepfollowingnointerferenceorinterferencelearn-
the extent of sleep’s ability to protect declar- ing (list A-C). †P< 0.10, ∗P< 0.05, ∗∗P< 0.001;
ative memories using experimentally induced error bars indicate SEM. Modified from Ellenbogen
2006a.
learning disruption (Ellenbogen et al. 2006a).
Takingadvantageofaclassicinterferencetech-
nique called the A-B–A-C paradigm, subjects cantly more resistant to interference, whereas,
first learned unrelated word-paired associates, across a waking day, memories were far more
designatedaslistA-B(e.g.,leaf-wheel,etc.).Af- susceptible to this antagonistic learning chal-
ter sleep at night, or wakefulness during the lenge. Yet it was only by using an interfering
day,halfofthesubjectsineachgrouplearneda challenge, that of the A-C list, that the true
new,interferinglistcontaininganewassociate benefitofsleep’sprotectionofmemorywasre-
pairedwiththefirstword,designatedaslistA-C vealed,abenefitthatwouldnotnecessarilyhave
(e.g., leaf-nail, etc.), before being tested on the beenevidentinastandardstudy−testmemory
original A-B list (e.g., leaf-wheel, etc.). In the paradigm.
groups that did not experience the interfering One mechanism proposed as underlying
challenge—that is, those who were simply be- theseeffectsonhippocampal-dependentlearn-
ing trained and then tested on list A-B—sleep ingtasks(seenextsection,also)isthereactiva-
providedamodestbenefittomemoryrecollec- tionofmemoryrepresentationsatnight.Acon-
tion(Fig.4A).However,whentestingthegroups siderable number of reports have investigated
thatwereexposedtointerferinglistlearning(list the firing patterns of large networks of indi-
A-C) prior to recalling the original list (list A- vidual neurons across the wake−sleep cycle in
B),alargeandsignificantprotectivebenefitwas animals. The signature firing patterns of these
seen in those that slept (Fig. 4B). Thus, mem- hippocampal and cortical networks, expressed
ories tested after a night of sleep were signifi- duringwakingperformanceofspatialtasksand
Walker:SleepinCognitionandEmotion 175
novelexperiences,appeartobe“replayed”dur- ualdeclarativememories,andmayindicatean
ingsubsequentSWS(andinsomestudies,also active reprocessing of hippocampal-bound in-
REM) (Wilson & McNaughton 1994; Skaggs formationduringSWS.
& McNaughton 1996; Dave et al. 1998; Dave
& Margoliash 2000; Poe et al. 2000; Louie &
Models of Sleep-Dependent
Wilson2001;Ribeiroetal.2004;Jones&Wil-
Memory Processing
son 2005; Ji & Wilson 2007). Homologous ev-
idence has been reported in the human brain Elucidating the neural mechanisms that
using a virtual maze task in combination with control and promote sleep-dependent human
positronemissiontomography(PET)scanning memoryconsolidationremainsanactivetopic
(Peigneux et al. 2004). Daytime learning was ofresearch,anddebate(Miller2007).Itisper-
initially associated with hippocampal activity. haps unlikely that multiple different memory
Then, during posttraining sleep, there was a systems,involvingdiversecorticaland/orsub-
reemergenceofhippocampalactivation,specif- corticalnetworks,requirethesameunderlying
icallyduringSWS.Mostcompelling,however, neuralmechanismsfortheirmodulation.Even
wasthattheamountofSWSreactivationinthe iftheydo,itisnotclearthatthisprocesswould
hippocampus was proportional to the amount rely on just one type of sleep-stage physiology
of next-day task improvement, suggesting that (Giudittaetal.1995).Atpresent,twointriguing
thisreactivationisassociatedwithofflinemem- models of sleep-dependent plasticity, relevant
oryimprovement. to declarative memory, have been offered to
Building on the framework that memories, account for the overnight facilitation of recall,
particularly those involving the hippocampus, whichbuildondifferentaspectsofneuralactiv-
are reactivated at night during sleep, Rasch ity during sleep: (1) hippocampal−neocortical
et al. have taken advantage of the classical dialogue,(2)synaptichomeostasishypothesis.
psychologyeffectofcue-dependentrecall,and
Hippocampal−NeocorticalDialogue
translated it into a sleep-dependent consolida-
tion paradigm (Rasch et al. 2007). It is well There is considerable agreement that struc-
known that memory can be strongly modu- tures within the medial temporal lobe (MTL),
lated by smell (Cann & Ross 1989); most of us most notably the hippocampal complex, are
have associated the smell of a certain perfume crucial for the formation and retrieval of new
orcolognewithaparticularperson,andwhen declarativememories.Thesestructuresarebe-
weencounterthatsameperfumeagain,itoften lieved to guide the reinstatement of recently
resultsinthepowerfulcuedrecallofmemories formed memories by binding together pat-
ofthatparticularperson.Inthisstudy,however, terns of cortical activation that were present
followinglearningofaspatialmemorytaskthat atthetimeofinitiallearning.Aclassicalmodel
waspairedwiththesmellofrose,theodorwas of declarative memory consolidation suggests
not re-presented at retrieval, but instead dur- that information initially requires MTL bind-
ing subsequent SWS that night—a time when ing, but over time, and by way of slow of-
consolidation was presumed to be occurring. fline processes, it is eventually integrated into
Relativetoacontrolconditionwheretheodor neocortical circuits (Fig. 5). Neocortical struc-
was not presented again during SWS, the re- turesthusbecometheeventualstoragesitefor
perfusion of the rose scent at night resulted in consolidatedepisodicmemoriesthroughcross-
significantlyimprovedrecallthefollowingday. cortical connections, and, as a consequence,
Moreover, the re-presentation of the odor re- the MTL is not necessary for these memo-
sultedingreater(re)activationofthehippocam- ries’ retrieval. Therefore, the classical model
pus during SWS. These findings support the of memory consolidation holds that neocorti-
role of SWS in the consolidation of individ- calstructuresbecomeincreasingimportantfor
176 AnnalsoftheNewYorkAcademyofSciences
Figure 5. Modelofsleep-dependenthippocampal-neocorticalmemoryconsolidation.At
encodingthehippocampusrapidlyintegratesinformationwithindistributedcorticalmodules.
Successive sleep-dependent reactivation of this hippocampal–cortical network leads to pro-
gressivestrengtheningofcortico-corticalconnections,whichovertime,allowthesememories
tobecomeindependentofthehippocampusandgraduallyintegratedwithpreexistingcortical
memories.ModifiedfromFrankland&Bontempi2005.
the retention and retrieval of successfully con- sites,therebyreinforcingthem(Fig.5).Eventu-
solidated episodic memories, while the corre- ally,thisstrengtheningwouldallowtheoriginal
spondingcontributionofthehippocampuspro- information to be activated in the cortex, in-
gressively decreases (Squire 1992; McClelland dependentofthehippocampus.Buzsaki(1996)
etal.1995;Squire&Zola1996;Squire2004). hassinceadvancedontheseideas,proposinga
It should be noted, however, that controversy modelofconsolidationthatinvolvestwostages
remainsabouttheroleoftheseMTLstructures or states of hippocampal activity, the first in-
intheretrievalofdeclarativememoriesafterthe volving a mode of “recording” during wake,
passageoftime.Thishasledtotheemergence whichshiftstoasecondstage,involving“play-
ofalternateconsolidationmodels,mostnotably back” mode during NREM SWS, specifically
Nadel and Moscovitch’s “multiple trace the- during bursts of neural activity called “sharp-
ory” (Nadel & Moscovitch 1997; Moscovitch waves.”
&Nadel1998),whichpositsthathippocampal Interestingly, these models make two pre-
involvement is always critical for the retrieval dictions about the impact of sleep on declar-
of episodic (but not semantic) memories, and ative memory. The first is that declarative
that these memories remain permanently de- memories from the day prior should be more
pendentonhippocampal−neocorticalconnec- resistant to interference the next day, due
tions (for discussion beyond the scope of this to the increased cortico−cortical connections
reviewseeFrankl&Bontempi2005). formedduringovernightconsolidation(Fig.5).
In addition to its role in binding distributed It is precisely this behavioral effect that was
cortical memory components, Marr and, also, reported in the study by Ellenbogen et al.
McClellandetal.suggestedthatthehippocam- (2006a) showing greater post-sleep resistance
pus plays a critical role in reactivating these to interference, using the A-B–A-C paradigm.
networks,specificallyduringsleep(Marr1970; A second and far less considered benefit of
McClelland et al. 1995). This process of re- this sleep-dependent dialogue is the encod-
activation, over multiple sleep cycles across a ing capacity of the hippocampus (Fig. 5). If
nightand/ormultipleoccurrencesofsleepover the strengthening of cortico−cortical connec-
many nights, would gradually strengthen the tions takes place during sleep, albeit itera-
initiallyweakconnectionsbetweenneocortical tively, then blocking sleep after hippocampal
Walker:SleepinCognitionandEmotion 177
Figure6. Enhancementofhippocampaldeclarativememorybydaytimenaps.(A)Correlationofrecog-
nition memory for recent and remote items related to individual slow-wave sleep durations. (B) Correlation
between recognition memory activity and longer slow-wave sleep duration in the left hippocampus (Hi).
ModifiedfromTakashimaetal.2006.
learningshouldnegatethisofflinetransfer,pre- increasing time following learning, there was
ventingthedevelopmentofindependencefrom progressively greater recall activity in medial
(or “refreshing” of) the hippocampus, and by prefrontal regions, and a continued dissipa-
doing so, decrease the capacity for new hip- tionofretrieval-relatedactivitywithinthehip-
pocampal learning the next day. This sec- pocampus. Advancing on these findings, Ma-
ond premise appears to accurately explain the quet and colleagues have since demonstrated
findingsdiscussedinthesectionaboveonmem- that one night of posttraining sleep depriva-
ory encoding (Yoo et al. 2007b), which de- tion,evenfollowingrecoverysleep,significantly
scribe a significant impairment of hippocam- impairs the normal modulation of hippocam-
palencodingactivitywhensleephasnottaken pal activity associated with episodic memory
place (through deprivation) being associated recollection (Gais et al. 2007). Furthermore,
with a decreased ability to form new episodic first-night sleep deprivation also prevented an
memories. increase in hippocampal connectivity with the
Tworecentreportshaveprovidedfurtherev- medial prefrontal cortex, a development that
idence in support of this sleep-dependent dia- was only observed in those that slept after
logueandneuraltransformationofdeclarative learning.
memory. In the first such report, Takashima While no one study has yet demonstrated
and colleagues examined the benefit of day- thattheneuralsignatureoflearningduringthe
timenapsonepisodicdeclarativememorycon- day is subsequently reactivated and driven by
solidation (Takashima et al. 2006). In addi- characteristics of SWS at night, and that the
tiontoalong-termevaluationofmemoryover extentofthesepropertiesareconsequentlypro-
3 months, there was also a short-term eval- portional to the degree of next-day recall and
uation of memory across the first day, which memoryreorganization,collectively,theyoffer
included an intervening nap period (90 min) anempiricalfoundationonwhichtoentertain
between training and testing of the original thispossibility.
studied (“remote”) stimuli. Interestingly, the
SynapticHomeostasisHypothesis
duration of NREM SWS during the inter-
vening nap correlated positively with later- InrecentyearsanorthogonaltheoryofSWS
recognition memory performance (Fig. 6A), and learning has emerged, one which postu-
yet negatively with retrieval-related activity in lates a role for sleep in regulating the synap-
the hippocampus (Fig. 6B). Furthermore, with tic connectivity of the brain—principally the