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10.1146/annurev.psych.56.091103.070307

Annu. Rev. Psychol. 2006. 57:139–66

doi: 10.1146/annurev.psych.56.091103.070307
Copyright
c 2006 by Annual Reviews. All rights reserved
First published online as a Review in Advance on October 3, 2005

SLEEP, MEMORY, AND PLASTICITY

Matthew P. Walker1,2 and Robert Stickgold2
Sleep and Neuroimaging Laboratory1 and Center for Sleep and Cognition,2 Beth Israel
Deaconess Medical Center, Boston, Massachusetts 02215, and Department of Psychiatry,
Harvard Medical School, Boston, Massachusetts 02215;
email: [email protected], [email protected]
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Key Words declarative memory, procedural memory, reconsolidation, REM

sleep, learning
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■ Abstract Although the functions of sleep remain largely unknown, one of the
most exciting hypotheses is that sleep contributes importantly to processes of memory
and brain plasticity. Over the past decade, a large body of work, spanning most of the
neurosciences, has provided a substantive body of evidence supporting this role of sleep
in what is becoming known as sleep-dependent memory processing. We review these
findings, focusing specifically on the role of sleep in (a) memory encoding, (b) memory
consolidation, (c) brain plasticity, and (d ) memory reconsolidation; we finish with a
summary of the field and its potential future directions.

CONTENTS
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
DELINEATIONS AND DEFINITIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
Sleep States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
Memory Categories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Memory Stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
SLEEP AND MEMORY ENCODING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
Sleep and Memory Encoding—Human Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Sleep and Memory Encoding—Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
SLEEP AND MEMORY CONSOLIDATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
Human Studies—Declarative Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
Human Studies—Procedural Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
SLEEP AND BRAIN PLASTICITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
Modification of Posttraining Sleep and Brain Activation . . . . . . . . . . . . . . . . . . . . 155
Overnight Reorganization of Memory Representations . . . . . . . . . . . . . . . . . . . . . . 155
SLEEP AND MEMORY RECONSOLIDATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
Reconsolidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
Time Course of Reconsolidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Sleep and Reconsolidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160

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INTRODUCTION
An exciting renaissance is currently under way within the biological sciences, cen-
tered on the question of why we sleep, and focusing specifically on the dependence
of memory and plasticity on sleep. Although this resurgence is relatively recent
in the annals of sleep research, the topic itself has a surprisingly long history. In
the early nineteenth century, the British psychologist David Hartley proposed that
dreaming might alter the strength of associative memory links within the brain
(Hartley 1801). Yet it was not until 1924 that Jenkins and Dallenbach performed
the first systematic studies of sleep and memory to test Ebbinghaus’s theory of
memory decay (Jenkins & Dallenbach 1924). Their findings showed that memory
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retention was better following a night of sleep than after an equivalent amount
of time awake. However, they concluded that the memory benefit following sleep
was passive and resulted from a lack of sensory interference during sleep. They
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did not consider the possibility that the physiological state of sleep itself could
actively orchestrate these memory modifications.
It is only in the past half century, following the discovery of rapid eye move-
ment (REM) and non-REM (NREM) sleep (Aserinsky & Kleitman 1953), that
research began testing the hypothesis that sleep, or even specific stages of sleep,
actively participated in the process of memory development. This review explores
this relationship between what has become known as sleep-dependent memory
processing and its associated brain basis, sleep-dependent plasticity.

DELINEATIONS AND DEFINITIONS

We begin our discussion of interactions between sleep and memory by clarifying
the complexities that these terms encompass.

Sleep States
To begin, it is important to note that the brain does not reside in one single physi-
ological state across the 24-hour day, but instead cycles through periods of differ-
ing neural and metabolic activity, associated with distinct biological states, most
obviously divided into those of wake and sleep. Sleep itself has been broadly
divided into REM and NREM sleep, which alternate across the night in hu-
mans in a 90-minute cycle (Figure 1A). In primates and felines, NREM sleep
has been further divided into substages 1 through 4, corresponding to increasingly
deeper states of sleep (Rechtschaffen & Kales 1968) (Figure 1A). The deepest
NREM stages, stages 3 and 4, are collectively referred to as “slow wave sleep”
(SWS), based on a prevalence of low-frequency cortical oscillations in the elec-
troencephalogram (EEG). Dramatic changes in brain electrophysiology, neuro-
chemistry and functional anatomy accompany these sleep stages, making them
biologically distinct from the waking brain, and dissociable from one another
(Hobson & Pace-Schott 2002). Thus, sleep cannot be treated as a homogeneous
state, which either does or does not affect memory. Instead, each sleep stage
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SLEEP, MEMORY, AND PLASTICITY 141

possesses a set of physiological and neurochemical mechanisms that may con-

tribute uniquely to memory consolidation.

Memory Categories
In the same way that sleep cannot be considered homogeneous, the spectrum
of memory categories believed to exist in the human brain, and the processes
that create and sustain memory, appear equally diverse. Although often used as
a unitary term, “memory” is not a single entity. Human memory has been sub-
ject to several different classification schemes, the most popular based on the
distinction between declarative and nondeclarative memory (Schacter & Tulving
1994, Squire & Zola 1996) (Figure 1B). Declarative memory can be considered
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as the consciously accessible memories of fact-based information (i.e., knowing

“what”). Several subcategories of the declarative system exist, including episodic
memory (autobiographical memory for events of one’s past) and semantic mem-
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ory (memory for general knowledge, not tied to specific events) (Tulving 1985).
Current neural models of declarative memory formation emphasize the critical
importance of structures in the medial temporal lobe, especially the hippocampus
(Eichenbaum 2000), a structure that is thought to form a temporally ordered re-
trieval code for neocortically stored information, and to bind together disparate
perceptual elements of a single event. In contrast, nondeclarative memory is re-
garded as nonconscious, and includes procedural memory (i.e., knowing “how”),
such as the learning of actions, habits, and skills, as well as implicit learning, and
appears to be less dependent on medial temporal lobe structures.
Although these categories offer convenient and distinct separations, they rarely
operate in isolation in real life. For example, language learning requires a com-
bination of memory sources, ranging from nondeclarative memory for procedural
motor programs to articulate speech, to memory of grammatical rules and structure,
and through to aspects of declarative memory for the source of word selection. This
too must be kept in mind as we consider the role of sleep in learning and memory.

Memory Stages
Just as memory cannot be considered monolithic, there similarly does not appear to
be one sole event that creates or develops it. Instead, memory appears to develop in
several unique stages over time (Figure 1C). For example, memories can be initially
formed or “encoded” by engaging with an object or performing an action, leading to
the formation of a representation of the object or action within the brain. Following
encoding, the memory representation can undergo several subsequent stages of
development, the most commonly recognized of which is consolidation. The term
“memory consolidation” classically refers to a process whereby a memory, through
the simple passage of time, becomes increasingly resistant to interference from
competing or disrupting factors in the absence of further practice (McGaugh 2000).
That is to say, the memory becomes more stable. It should be noted, however,
that although most forms of memory appear to require subsequent consolidation
following encoding, not all tasks appear to be resistant to competitive interference
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almost immediately, and hence do not demonstrate this characteristic of time-

dependent consolidation (Goedert & Willingham 2002).
Recent findings have begun to extend the definition of consolidation. For ex-
ample, consolidation can be thought of as not only stabilizing memories, but also
as enhancing them—two processes that may be mechanistically distinct (Walker
2005). The stabilization phase of consolidation appears to occur largely during
wake cycles (Brashers-Krug et al. 1996, Muellbacher et al. 2002, Walker et al.
2003a). The enhancement stage appears to occur primarily, if not exclusively, dur-
ing sleep, either restoring previously lost memories (Fenn et al. 2003) or producing
additional learning (Fischer et al. 2002; Gais et al. 2000; Karni et al. 1994; Korman
et al. 2003; Stickgold et al. 2000a,b; Walker et al. 2002a,b), both without the need
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for further practice. From this perspective, the enhancement phase of memory
consolidation causes either the active restoration of a memory that had shown
behavioral deterioration, or the enhancement of a memory over its simple main-
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tenance. Thus, consolidation can be expanded to include more than one phase
of postencoding memory processing, with each phase occurring in specific brain
states such as wake or sleep, or even in specific stages of sleep (Brashers-Krug
et al. 1996; Karni et al. 1994; Muellbacher et al. 2002; Smith & MacNeill 1994;
Stickgold et al. 2000b; Walker 2005; Walker et al. 2002a, 2003a,b).
Following its initial stabilization, a memory can be retained for days to years,
during which time it can be recalled. But the act of memory recall itself is now be-
lieved to destabilize the memory representation, making it again labile and subject
to potential degradation. Reconsolidation therefore has been proposed to trans-
form the now destabilized memory into a restabilized form (Nader 2003). When a
destabilized memory is not reconsolidated, it can degrade relatively quickly.
Although this chapter focuses primarily on the effects of sleep on encoding, sta-
bilization, enhancement, and reconsolidation, it is important to note that additional
postencoding stages of memory processing should also be appreciated. These in-
clude the integration of recently acquired information with past experiences and
knowledge (a process of memory association), the anatomical reorganization of
memory representations (memory translocation), and even the active erasure of
memory representations, all of which appear to occur outside of awareness and
without additional training or exposure to the original stimuli (Stickgold & Walker
2005), and may also be considered stages of memory consolidation. It is interest-
ing to note that sleep has already been implicated in all of these steps (Crick &
Mitchison 1983, Stickgold 2002, Stickgold et al. 1999, Walker et al. 2003a).

SLEEP AND MEMORY ENCODING

Some of the first studies to investigate the relationship between sleep and human
memory examined the influence of sleep on posttraining consolidation (see sec-
tions below) rather than its influence on initial encoding. However, more recent
data have described the detrimental consequence of inadequate pretraining sleep
on successful memory encoding. The section below offers an overview of this
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SLEEP, MEMORY, AND PLASTICITY 143

evidence that spans a range of phylogeny and is supported across a variety of

descriptive levels, from molecules to behavior.

Sleep and Memory Encoding—Human Studies

One of the earliest studies to report the effects of sleep deprivation on declarative
memory encoding in humans was by Morris et al. (1960), who found that “temporal
memory” (memory for when events occur) was significantly disrupted by a night
of pretraining deprivation. These findings have been revisited in a more rigorous
study by Harrison & Horne (2000), again using the temporal memory paradigm.
The task comprised photographs of unknown faces, with the temporal memory
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component involving recency discrimination, together with a confidence judgment.

Significant impairments of temporal memory were evident in a group deprived of
sleep for 36 hours, which scored significantly lower than did controls; significant
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impairment was evident even in a subgroup that received caffeine to overcome

nonspecific effects of lower arousal. Furthermore, the sleep-deprived subjects dis-
played significantly worse insight into their memory-encoding performance.
Based on data from studies indicating that memory encoding (as measured by
the success of later recall) relies on the integrity of the prefrontal cortex (PFC)
(e.g., Brewer et al. 1998, Canli et al. 2000, Henson et al. 1999, Wagner et al. 1998),
and that baseline PFC reductions in cerebral metabolic rate are evident following
one night of deprivation, the authors hypothesized that sleep deprivation impaired
prefrontal function critical for effective memory encoding.
In similar studies, Drummond et al. (2000) directly examined this hypothesis
by using functional magnetic resonance imaging (fMRI) to investigate the effects
of 35-hour total sleep deprivation on encoding of a verbal memory task. As in
previous studies, total sleep deprivation resulted in significantly worse acquisition
of verbal learning. Surprisingly, however, subjects showed more PFC activation
during encoding when sleep deprived than when not sleep deprived. In contrast,
regions of the medial temporal lobe were significantly less activated during en-
coding when sleep deprived. Perhaps most interesting, the parietal lobes, which
were not activated during encoding following normal sleep, were significantly
activated after sleep deprivation. These findings confirm that sleep deprivation in-
duces a significant behavioral impairment in verbal memory encoding, and suggest
that these impairments are mediated by a dynamic set of bidirectional changes—
overcompensation by prefrontal regions combined with a failure of the medial
temporal lobe to engage normally, leading to compensatory activation in the pari-
etal lobes (Drummond & Brown 2001).
We recently investigated the impact of sleep deprivation on declarative memory
encoding of both emotional and nonemotional material (M.P. Walker, unpublished
results). Subjects were either sleep deprived for 36 hours or allowed to sleep
normally prior to an incidental memory encoding session composed of sets of
emotionally negative, positive, and neutral words. Following two subsequent nights
of sleep, subjects returned for an unexpected recognition task. Overall, subjects
in the sleep-deprived condition exhibited a 40% reduction in memory retention
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Figure 2 Sleep deprivation and encoding of emotional and nonemotional declarative mem-
ory. (A) Effects of 36 hours of total sleep deprivation on encoding of human declarative
memory when combined across all emotional and nonemotional categories. (B) Effects when
separated into emotional (positive and negative valence) and nonemotional (neutral valance)
categories.

relative to subjects who had slept normally prior to encoding (Figure 2A); these
results represent a striking impairment of declarative memory formation under
conditions of sleep deprivation. When these data were separated into the three
emotional categories (positive, negative, or neutral), the encoding deficit remained,
although the magnitude of effect differed across the emotion categories (Figure 2B).
Within the sleep control group, both positive and negative stimuli were associated
with superior retention levels relative the neutral condition, consonant with the
notion that emotion facilitates memory encoding (Phelps 2004). However, there
was severe disruption of encoding and hence later memory retention deficit for
neutral and especially positive emotional memory in the sleep-deprived group,
which exhibited a significant 59% retention deficit relative to the control condition
for positive emotional words. Most interesting, however, was the resistance of
negative emotional memory to sleep deprivation, showing a markedly smaller
(19%) and nonsignificant impairment.
These data indicate that sleep deprivation severely impairs the encoding of
declarative memories, resulting in significantly worse retention two days later.
Although the effects of sleep deprivation are directionally consistent across sub-
categories, the most profound impact is on the encoding of positive emotional
stimuli, and to a lesser degree, emotionally neutral stimuli, while the encoding of
negative stimuli appears more resistant to the effects of prior sleep deprivation.
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SLEEP, MEMORY, AND PLASTICITY 145

Sleep and Memory Encoding—Animal Studies

In animals, pretraining sleep deprivation has been demonstrated to impair the
encoding of numerous memory tasks (Smith 1985, Stern 1971). For example,
using the Morris water maze in a configuration that is hippocampally depen-
dent (nonvisible platform), Guan et al. (2004) demonstrated that 6 hours of total
sleep deprivation prior to training results in a severe disruption of encoding, as
assessed by retention 24 hours later. In contrast, learning of the nonspatial task
version (visible platform; hippocampally independent) was more resistant to prior
sleep deprivation, suggesting first that the impairments for spatial memory were
not a consequence of gross alternations in attention or stress, and second that
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sleep deprivation may selectively disrupt hippocampal-based encoding. Beaulieu

& Godbout (2000) subsequently demonstrated that even selective deprivation of
REM sleep for eight hours prior to training is sufficient to impair encoding on
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this task. Furthermore, in a more complex configuration of the task that requires
increased frontal cortex involvement (continual switching of the platform loca-
tion), prior REM sleep deprivation induced even greater retest deficits, which
suggests that both basic hippocampal spatial memory and more complex spatial
learning requiring additional frontal involvement are susceptible to a lack of prior
REM.
REM sleep deprivation also has detrimental effects on the encoding of other hip-
pocampally mediated tasks, including one-way and two-way avoidance learning,
taste aversion, and passive avoidance tasks (see McGrath & Cohen 1978, Smith
1985). Even short (five-hour) bouts of pretraining REM sleep deprivation signifi-
cantly impair encoding of two-way avoidance learning in rats, producing deficits
that cannot be overcome by additional practice during training (Gruart-Masso et al.
1995).
An interesting dissociation of sleep deprivation effects is seen using a fear-
conditioning task. The contextual versus cued memory paradigm in animals offers
the ability to distinguish memory processing mediated primarily by the hippocam-
pus (context) from that mediated primarily by the amygdala (cue). Using this task,
Ruskin et al. (2004) demonstrated that pretraining sleep deprivation (predomi-
nantly REM) profoundly impaired contextual memory encoding (>50%) mea-
sured 24 hours later, whereas cued learning was largely unaffected. These data
suggest that pretraining sleep deprivation may affect memory encoding by neu-
roanatomically distinct systems, impairing hippocampal encoding processes while
having only minor effects on encoding mediated by the amygdala (McDermott
et al. 2003). These findings, which are strikingly similar to those described above
in humans, suggest that encoding of both neutral and positive memory events are
most severely impaired by sleep deprivation, while encoding of more negative
stimuli, presumably in concert with the amygdala, exhibit greater immunity.
Building on these behavioral findings, a number of animal studies have gone on
to explore the potential cellular and molecular underpinnings of sleep deprivation–
induced encoding deficits; many of these studies have focused on the hippocampus.
At the cellular level, REM sleep deprivation (ranging from of 24 to 72 hours) not
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only reduces the basic excitability of hippocampal neurons, but also significantly
impairs the formation of long-term potentiation [LTP; a foundational mechanism
of memory formation (Kandel 2001)] within those neurons (Davis et al. 2003,
McDermott et al. 2003). Furthermore, the LTP that does develop decays within
90 minutes, a finding that suggests that even in the event of successful LTP induc-
tion, hippocampal neurons are still unable to maintain these plastic changes after
REM deprivation (Davis et al. 2003).
At the molecular level, nerve growth factor is significantly reduced in the
hippocampus following six hours of REM sleep deprivation, and brain-derived
neurotrophic factor is significantly decreased in the brain stem and cerebellum
(Sei et al. 2000). This anatomically differentiated pattern of molecular disruption
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suggests a selective elimination of hippocampal nerve growth factor secretion,

normally a key event in the regulation of neuronal plasticity (Kandel 2001). Fi-
nally, Guan et al. (2004) have explored the impact of prior sleep deprivation on
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levels of extracellular signal–regulated kinase (ERK)—a protein intimately linked

to LTP formation and learning (Kelleher et al. 2004). When rats were trained on
the hippocampally dependent Morris water maze following three or six hours of
total sleep deprivation, behavioral encoding impairments were accompanied by
significantly reduced levels of hippocampal ERK in the six-hour group (Figure
3), and to a lesser extent, in the three-hour group. Interestingly, when rats were
allowed a short (two-hour) period of recovery sleep after the sleep deprivation,
subsequent memory encoding and hippocampal ERK returned to normal levels
(Figure 3).

SLEEP AND MEMORY CONSOLIDATION

In addition to the impact of prior sleep deprivation on memory encoding, a plethora
of work also demonstrates the impact of sleep deprivation after learning on later
memory consolidation. Through the use of a variety of behavioral paradigms, evi-
dence of sleep-dependent memory consolidation has now been found in numerous
species, including human and nonhuman primates, cats, rats, mice, and zebra finch.

Human Studies—Declarative Memory

Much of the early work investigating sleep and memory in humans focused on
declarative learning tasks. These studies offered mixed conclusions, some in fa-
vor of sleep-dependent memory processing, and others against it. For example, De
Koninck et al. (1989) demonstrated significant increases in posttraining REM sleep
after intensive foreign language learning, with the degree of successful learning
correlating with the extent of REM sleep increase. Such findings suggest that REM
sleep plays an active role in memory consolidation, and that posttraining increases
reflect a homeostatic response to the increased demands for such consolidation.
However, Meienberg (1977) found no evidence of altered posttraining sleep archi-
tecture following learning of a verbal memory task. Similar inconsistencies have
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SLEEP, MEMORY, AND PLASTICITY 147

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Figure 3 Phospho-extracellular signal-regulated kinase 2 (pERK2) in the rat hip-

pocampus. pERK2 levels were significantly reduced after six hours total sleep depri-
vation (6 hr TSD), but returned to above control levels after two hours recovery (2 hr
R) sleep following six hours sleep deprivation. Asterisk indicates significant difference
between the control and sleep-deprived rats.

been reported both for the degree to which encoding of declarative memories alters
subsequent sleep-stage properties and for the degree of learning impairment that
follows selective sleep deprivation (e.g., Chernik 1972; Empson & Clarke 1970;
Lewin & Glaubman 1975; Meienberg 1977; Plihal & Born 1997; Zimmerman
et al. 1970, 1978). Recently, several studies by Born and his colleagues have
shown actual improvement on a word-pair associates task after SWS-rich early
night sleep (Gais & Born 2004), as well as modification of this posttraining sleep
(Gais et al. 2002). These findings are striking in the face of earlier studies that
showed no effect. However, the discrepancy may reflect the nature of the word
pairs used. Whereas older studies used unrelated word pairs, such as dog–leaf,
Born used related word pairs, such as dog–bone (Gais & Born 2004). The nature
of the learning task thus shifts from forming and retaining completely novel as-
sociations (dog–leaf) to the strengthening or tagging of well-formed associations
(dog–bone) for subsequent recall.
Thus, as with memory encoding, the role of sleep in declarative memory con-
solidation, rather than being absolute, might depend on more subtle aspects of
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the information being learned. Indeed, several studies suggest that factors such as
task difficulty (Empson & Clarke 1970, Tilley & Empson 1978) and emotional
salience (Wagner et al. 2001) can strongly influence the degree of sleep depen-
dency. Furthermore, a thorough examination of different declarative memory cat-
egories, including episodic and semantic forms, has not been completed (Cipolli
& Salzarulo 1980), and such an investigation may further clarify the apparent con-
tradictions regarding the roles of both SWS and REM sleep in declarative memory
consolidation (Smith 2001).
Such studies have only begun to test sleep-related memory processes. Indeed,
all of these studies have used tasks of recall and recognition as outcome measures,
thereby focusing exclusively on processes of memory enhancement and resistance
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to normal decay, and no study has looked at such processes as memory stabiliza-
tion, association, translocation, and reconsolidation, discussed above. More recent
studies, however, have demonstrated that the strengths of associative memories
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are altered in a state-dependent manner. Two reports have shown that REM sleep
provides a brain state in which access to weak associations is selectively facilitated
(Stickgold et al. 1999), and flexible, creative processing of new information is en-
hanced (Walker et al. 2002b). It has also been demonstrated that, following initial
practice on a numeric-sequence problem-solving task, a night of sleep can trigger
insight into a hidden rule that can enhance performance strategy the following
morning (Wagner et al. 2004).
Taken as a whole, these studies suggest a rich and multifaceted role for sleep in
the processing of human declarative memories. Although contradictory evidence
is found for a role in the processing of simple, emotion-free declarative memories,
such as the learning of unrelated word pairs, a substantial body of evidence indi-
cates that both SWS and REM sleep contribute to the consolidation of complex,
emotionally salient declarative memories, embedded in networks of previously
existing associative memories. In light of this evidence, pronouncements of a lack
of relationship between REM sleep and “memory” (e.g., Siegel 2001, Vertes &
Eastman 2000) appear to be unfortunate overgeneralizations that disregard evi-
dence that specific sleep stages play distinct roles in different stages of memory
processing in separate memory systems.

Human Studies—Procedural Memory

The reliance of procedural, nondeclarative memory on sleep is now a robust and
persistent finding. These data span a wide variety of functional domains, including
both perceptual (visual and auditory) and motor skills.

MOTOR LEARNING Motor skills have been broadly classified into two forms—
motor adaptation (e.g., learning to use a computer mouse) and motor sequence
learning (e.g., learning a piano scale) (Doyon et al. 2003). Beginning with motor
sequence learning, a night of sleep can trigger significant improvements in speed
and accuracy on a sequential finger-tapping task, while equivalent periods of wake
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SLEEP, MEMORY, AND PLASTICITY 149

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Figure 4 Sleep-dependent motor skill learning. (A) Wake first: After morning training
(10 AM, unfilled bar), subjects showed no significant change in performance when tested
after 12 hours of wake time (10 PM, unfilled bar). However, when tested again following a
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night of sleep (10 AM, filled bar), performance had improved significantly. (B) Sleep first:
After evening training (10 PM, unfilled bar), subjects displayed significant performance im-
provements just 12 hours after training following a night of sleep (10 AM, filled bar), yet
expressed no further significant change in performance following an additional 12 hours of
wake time (10 PM, filled bar). (C) The amount of overnight improvement on the motor skill
task correlated with the percentage of stage 2 non-rapid eye movement (NREM) sleep in the
last (fourth) quarter of the night (stage 2 NREM4 ). Asterisks indicate significant improvement
relative to training, and error bars indicate standard error of the mean.

provide no significant benefit (Walker et al. 2002a). These sleep-dependent benefits

appear to be specific to both the motor sequence learned and hand used to perform
the task (Fischer et al. 2002, Korman et al. 2003). Furthermore, overnight learning
gains correlate with the amount of stage 2 NREM sleep, particularly late in the night
(Figure 4A–C) (Walker et al. 2002a). This sleep window corresponds to a time when
sleep spindles—a defining electrophysiological characteristic of stage 2 NREM—
reach peak density (De Gennaro et al. 2000). Spindles have been proposed to trigger
intracellular mechanisms required for synaptic plasticity (Sejnowski & Destexhe
2000), and they increase following training on a motor task (Fogel et al. 2001).
Thus, sleep spindles produced in late-night sleep may trigger key cellular events
that in turn initiate mechanisms for neural plasticity.
At the behavioral level, the motor sequence task described above has been
dissected to determine where in the motor program this sleep-dependent improve-
ment occurs (Kuriyama et al. 2004). More specifically, differences in transition
speeds between each of the separate key-press movements, before and after sleep,
were analyzed. For example, in the sequence 4-1-3-2-4, there are four unique key-
press transitions: (a) from 4 to 1, (b) from 1 to 3, (c) from 3 to 2, and (d ) from
2 to 4. When individual subjects’ transition-speed profiles were analyzed before
sleep, the speed of individual key-press transitions within the sequence were not
equal (Figure 5A, unfilled circles), with some transitions seemingly easy (fast) and
others problematic (slow), as if the entire sequence was being parsed into smaller
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Figure 5 Single-subject examples of changes in transition speeds. Within a five-element

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motor sequence (e.g., 4-1-3-2-4), there are four unique key press transitions: (a) from 4 to
1, (b) from 1 to 3, (c) from 3 to 2, and (d) from 2 to 4. (A) The transition profile at the
end of training before sleep (unfilled circles) demonstrated considerable variability, with
certain transitions being particularly slow (most difficult; “problem points”), whereas other
transitions appear to be relatively rapid (easy). Following a night of sleep (filled circles), there
was a specific reduction (improvement) in the time required for the slowest problem point
transition. (B) Similarly, at the end of training before a waking interval, transition profiles
were uneven (unfilled circles), with some particularly slow transitions (problem points) and
other relatively fast transitions (easy). However, in contrast to postsleep changes, no change
in transition profile was observed following eight hours of wake (filled circles).

subsequences during initial learning [a phenomena termed “chunking” (Sakai et al.

2003)]. Surprisingly, after a night of sleep, the problematic slow transitions (“prob-
lem points”) were preferentially improved, whereas transitions that had already
been effectively mastered prior to sleep did not change (Figure 5A, filled circles).
Most remarkable, however, in subjects who were trained and retested after an eight
hour waking interval across the day, no such improvement was seen in the profile
of key-press transitions at any location within the sequence (Figure 5B).
These findings suggest that the sleep-dependent consolidation process involves
the unification of smaller motor memory units into one single memory element
by selectively improving problem regions of the sequence. This overnight process
would therefore offer a greater degree of performance automation, effectively
optimizing speed across the motor program, and would explain the sleep-dependent
improvements in speed and accuracy previously reported. But more importantly,
it again suggests that the role of sleep is more subtle and complex than to simply
increase the strength of existing memory representations.
Using a different sequential finger-tapping task (finger-to-thumb movements
rather than keyboard typing), Fisher et al. (2002) have shown that sleep during
the first day or night following training is critical for the delayed performance im-
provements. In their case, however, they described a correlation between overnight
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SLEEP, MEMORY, AND PLASTICITY 151

improvement and amounts of REM sleep rather than stage 2 NREM. This discrep-
ancy remains to be resolved, but it is possible that the more novel finger-to-thumb
task requires REM sleep, whereas the keyboard typing version, a simple variant of
a well-learned skill (i.e., typing), is consolidated during stage 2 NREM. A simi-
larly subtle distinction has been reported by Robertson et al. (2004), who recently
demonstrated sleep-dependent enhancement of performance on a perceptual-motor
sequence task when there was explicit awareness of the presence of a repeating se-
quence, but not when awareness was only gained implicitly. In this study, delayed
overnight learning with explicit awareness correlated with amounts of NREM
sleep.
Moving from motor sequence learning to motor adaptation learning, Smith &
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MacNeill (1994) have shown that selective sleep deprivation impairs retention of
a visuomotor adaptation task. All subjects were trained and tested on the task and
were retested one week later. However, some subjects were either completely or
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selectively deprived of different sleep stages across the first night following mem-
ory acquisition. At later retest, subjects deprived of stage 2 NREM sleep showed
the most pronounced deficits in motor performance, which again suggests that
stage 2 NREM is a crucial determinant of successful motor memory enhancement.
Huber et al. (2004) have similarly demonstrated that following initial memory
acquisition of a motor reaching-adaptation task, delayed learning was observed
exclusively across a night of sleep, and not across equivalent periods of wake.
Furthermore, through the use of high-density EEG, they were able to show that
daytime motor skill practice was accompanied by a discrete increase in the sub-
sequent amount of NREM slow-wave EEG activity over the parietal cortex at the
start of the night, and that this increase in slow-wave activity was proportional
to the amount of delayed learning that developed overnight; subjects showing the
greatest increase in slow-wave activity in the parietal cortex that night produced
the largest motor skill enhancement the next day.
Taken together, these reports build a convincing argument in support of sleep-
dependent learning across several forms of motor skill memory. All these studies
indicate that a night of sleep triggers delayed learning, without the need for further
training. In addition, overnight motor skill improvements consistently display a
strong relationship to NREM sleep, and, in some cases, to specific NREM sleep-
stage windows at specific times in the night.

VISUAL PERCEPTUAL LEARNING Learning of a visual texture discrimination task,

which does not benefit from 4–12 hours of wake following training (Stickgold et al.
2000b), improves significantly following a night of sleep (Karni et al. 1994) and
appears to require both SWS and REM sleep. Selective disruption of REM sleep
resulted in a loss of overnight improvement (Karni et al. 1994). Similarly, selective
deprivation of either early sleep (normally dominated by SWS) or late-night sleep
(normally dominated by REM and stage 2 NREM) impair overnight consolidation,
a finding that suggests that consolidation is initiated by SWS-related processes,
but that subsequent REM sleep then promotes additional enhancement (Gais et al.
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Figure 6 Sleep-dependent visual skill learning. Subjects were trained (during which time,
baseline performance was measured) and then retested at a later time; improvement [ms
(milliseconds)] in performance is illustrated across time. Each subject was retested only
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once, and each point represents a separate group of subjects. (A) Wake versus sleep: Subjects
who were trained and then retested on the same day, after either 3, 6, 9, or 12 hours of
subsequent wake (unfilled squares) showed no significant improvement as a consequence of
the passage of waking time across at any of the four time points. In contrast, subjects who
were trained and then retested 8, 12, 15, or 23 hours after one night of sleep (filled squares)
showed a significant improvement occurring as a consequence of sleep. In total, n = 57,
with n = 7 to 9 for individual points. (B) Sleep and sleep deprivation. Subjects (n = 89)
who were trained and retested 1–7 days later (filled bars) continued to improve after the
first night, without additional practice. Subjects (n = 11) sleep deprived the first night after
training showed no improvement (crosshatched bar), even after two nights of recovery sleep.
(C) Overnight improvement was correlated with the percent of slow-wave sleep (SWS) in
the first quarter of the night (SWS1 ) and rapid eye movement (REM) sleep in the last quarter
of the night (REM4 ). ∗ p < 0.05; error bars indicate standard error of the mean.

2000). Overnight improvement is specifically sleep dependent, not time dependent

(Figure 6A) (Stickgold et al. 2000b), and correlates positively with the amount of
both early-night SWS and late-night REM sleep. Indeed, the product of these two
sleep parameters explains more than 80% of intersubject variance (Figure 6C). In
addition, these delayed performance benefits are absolutely dependent on the first
night of sleep following acquisition (Figure 6B) (Stickgold et al. 2000a).

AUDITORY LEARNING Evidence of sleep-dependent auditory skill learning has

also been reported. Using a pitch memory task, Gaab et al. (2004) have shown that
delayed performance improvements develop only across a night of sleep and not
across similar wake periods. Atienza and colleagues have also described evidence
of both time- and sleep-dependent auditory memory consolidations, including
sleep-dependent changes in brain-evoked response potentials (ERPs) (Atienza et al.
2002, 2004). Although posttraining sleep deprivation did not prevent continued
behavioral improvements, ERP changes normally associated with the automatic
shift of attention to relevant stimuli failed to develop following a posttraining night
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SLEEP, MEMORY, AND PLASTICITY 153

of sleep deprivation. These findings make clear the danger of presuming that a lack
of behavioral improvement is equivalent to an absence of beneficial plastic changes
within the brain, and they highlight the importance of using combined behavioral
and physiological analyses. Finally, Fenn et al. (2003) have shown periods of wake
following training on a synthetic speech-recognition task result in a degradation
of task performance that a subsequent night of sleep can restore, which suggests
a process of sleep-dependent consolidation capable of reestablishing previously
learned complex auditory skill memory.
It therefore appears that, as with motor skills, learning of perceptual skills, both
visual and auditory, depends on sleep for the development of delayed learning, and
several different sleep stages may be involved in producing this form of overnight
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consolidation.

PROCEDURAL MEMORY AND DAYTIME NAPS Although the majority of sleep-depe-

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ndent studies have investigated learning across a night of sleep, several reports
have begun to examine the benefits of daytime naps on perceptual and motor skill
tasks. Based on evidence that motor learning continues to develop overnight, the
influence of daytime naps on the sequential finger-tapping task has been explored
(Walker & Stickgold 2005). Two groups of subjects were trained on the task in the
morning. One group subsequently obtained a 60- to 90-minute midday nap while
the other group remained awake. When retested later that same day, those subjects
who napped displayed a significant 16% learning enhancement, whereas those
who did not nap showed no significant improvement (Figure 7). This nap-mediated
improvement is, however, at the expense of subsequent overnight learning. Thus,
although the control subjects showed 24% improvement overnight, the nap subjects
showed only an additional 7%, for a total of 23%—essentially identical to that seen
in the control group.
As with motor skill learning, daytime naps also appear to benefit visual skill
learning, although the characteristics of these effects are subtly different. Mednick
and colleagues have shown that if a visual skill task is repeatedly administered
across the day, performance deteriorates rather than remaining stable or improving
(Mednick et al. 2002). This may reflect a selective fatigue of brain regions recruited
during task performance, a characteristic not observed in the motor system. How-
ever, if a 30- to 60-minute daytime nap is introduced among these repeated tests,
the performance deterioration is ameliorated. If a longer nap period is introduced,
ranging from 60 to 90 minutes and containing both SWS and REM sleep, perfor-
mance not only returns to baseline, but also is enhanced (Mednick et al. 2003).
Furthermore, these benefits did not prevent additional significant improvements
across the following night of sleep, in contrast to findings for motor skill task
performance.
Together these studies build a cohesive argument that daytime naps confer a
robust learning benefit to both visual and motor skills and, in the case of visual skill
learning, are capable of restoring performance deterioration caused by repeated
practice across the day.
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Figure 7 Daytime naps and motor skill learning. Subjects practiced the motor skill task in
the morning, and either obtained a 60- to 90-minute midday nap or remained awake across
the first day. When retested later that same day, subjects who experienced a 60- to 90-minute
nap (filled bar, Across Day) displayed significant performance speed improvements of 16%,
whereas subjects who did not nap showed no significant enhancements (unfilled bar, Across
Day). When retested a second time after a full night of sleep, subjects in the nap group showed
only an additional 7% increase in speed overnight (filled bar, Overnight), whereas subjects
in the control group expressed a significant 24% overnight improvement following sleep
(unfilled bar, Overnight). Therefore, 24 hours later, the groups averaged nearly the same total
amount of delayed learning (filled and unfilled bars, Total). Asterisks indicate significant
improvement and error bars indicate standard error of the mean.

SLEEP AND BRAIN PLASTICITY

Memory formation depends on brain plasticity—lasting structural and/or func-
tional neural changes in response to stimuli (such as experiences). If sleep is
to be considered a critical mediator of memory consolidation, then evidence of
sleep-dependent plasticity would greatly strengthen this claim. In this section, we
consider a mounting wealth of data describing sleep-dependent brain plasticity;
our focus is on neuroimaging studies in humans (see Walker & Stickgold 2004 for
a detailed discussion of cellular and molecular data).
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SLEEP, MEMORY, AND PLASTICITY 155

Modification of Posttraining Sleep and Brain Activation

Several studies have investigated whether daytime training is capable of modify-
ing functional brain activation during subsequent sleep. Based on animal studies,
neuroimaging experiments have explored whether the signature pattern of brain ac-
tivity elicited while practicing a memory task actually reemerges, i.e., is “replayed,”
during subsequent sleep. Using brain imaging, Maquet and colleagues have shown
that patterns of brain activity expressed during training on a serial reaction time mo-
tor task reappear during subsequent REM sleep, whereas no such change in REM
sleep brain activity occurs in subjects who received no daytime training (Maquet
et al. 2000). Furthermore, the extent of learning during daytime practice exhibits
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a positive relationship to the amount of reactivation during REM sleep (Peigneux

et al. 2003). As with previously described animal studies (Datta 2000), these find-
ings suggest that it is not simply experiencing the task that modifies subsequent
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sleep physiology, but the process of learning itself. Similar findings have been re-
ported using a virtual maze task. Daytime task learning is initially associated with
hippocampal activity. Then, during posttraining sleep, there was a reemergence of
hippocampal activation, this time specifically during SWS. The most compelling
finding, however, is that the amount of SWS reactivation in the hippocampus is
proportional to the amount of next-day task improvement, which suggests that
this reactivation leads to off-line memory improvement (Peigneux et al. 2004).
Such sleep-dependent replay may potentially modify synaptic connections estab-
lished within specific brain networks during practice, strengthening some synaptic
circuits while potentially weakening others in the endeavor of refining the memory.

Overnight Reorganization of Memory Representations

A second approach, which more directly examines sleep-dependent plasticity,
compares patterns of brain activation before and after a night of sleep. In con-
trast to approaches that measure changes in functional activity during sleep,
this technique aims to determine whether improved performance results from
an overnight, sleep-dependent restructuring of the neural representation of the
memory. Using the sleep-dependent motor skill task, differences between pat-
terns of brain activation before and after sleep have recently been investigated
using fMRI (Walker et al. 2005a). Following a night of sleep, and relative to an
equivalent intervening period awake, increased activation was identified in motor
control structures of the right primary motor cortex (Figure 8A) and left cerebel-
lum (Figure 8B)—changes that allow more precise motor output (Ohyama et al.
2003) and faster mapping of intention to key-press (Ungerleider et al. 2002).
There were also regions of increased activation in the medial prefrontal lobe
and hippocampus (Figure 8C,D), structures recently identified as supporting im-
proved sequencing of motor movements (Koechlin et al. 2000, 2002; Poldrack &
Rodriguez 2003; Schendan et al. 2003). In contrast, decreased activity postsleep
was identified bilaterally in the parietal cortices (Figure 8E), possibly ref-
lecting a reduced need for conscious spatial monitoring (Muller et al. 2002,
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156 WALKER
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Seitz et al. 1990, Toni et al. 1998) as a result of improved task automation
(Kuriyama et al. 2004), together with regions of signal decrease throughout the
limbic system (Figure 8F–H), which suggests a decreased emotional task burden.
In total, these results suggest that sleep-dependent motor learning is associated with
a large-scale plastic reorganization of memory throughout several brain regions,
allowing skilled motor movements to be executed more quickly, more accurately,
and more automatically following sleep. These findings hold important implica-
tions for understanding the brain basis of perfecting real-life skills and may signify
a potential role for sleep in clinical rehabilitation following brain damage.
fMRI has also been used to investigate whether overnight reorganization simi-
larly occurs in sensory-perceptual systems using the sleep-dependent visual texture
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discrimination task described earlier (Walker et al. 2005b). Subjects were trained
with or without intervening sleep. Relative to the condition without sleep, retest
following sleep was associated with significantly greater activation in an area of
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primary visual cortex corresponding to the visual target location. However, there
were also several other regions of increased postsleep activity, throughout both the
ventral object recognition (inferior parietal and occipital-temporal junction) and
dorsal object location (superior parietal lobe) pathways (Ungerleider & Haxby
1994), together with corresponding decreases in the right temporal pole, a region
involved in emotional visual processing. Thus, a night of sleep appears to reor-
ganize the representation not only of procedural motor but also of visual skill
memories, with greater activation throughout the visual processing streams offer-
ing improved identification of both the stimulus form and its location in space,
and with signal decreases in the temporal pole reflecting a reduced emotional task
burden resulting from the overnight learning benefits.
Maquet et al. (2003) have investigated the detrimental effects of sleep depri-
vation on underlying brain activity using a visuomotor adaptation task—the only
such study to date. Subjects were trained on the task, tested, and retested three
days later, with half the subjects deprived of sleep the first night. At retest, subjects
performed both the previously learned motor task and a new, related task. Controls,
who slept all three nights, showed both enhanced behavioral performance at retest
and a selective increase in activation in the superior temporal sulcus (a region in-
volved in the evaluation of complex motion patterns) relative to subjects deprived
of sleep the first night. In contrast, no such enhancement of either performance or
brain activity was observed in these subjects, indicating that sleep deprivation had
interfered with a latent process of plasticity and consolidation. This study indi-
cates that sleep deprivation disrupts not only consolidation, but also the underlying
neural mechanisms that support it.

SLEEP AND MEMORY RECONSOLIDATION

Reconsolidation
Recent studies (Nader 2003) suggest that upon recall of previously consolidated in-
formation, the memory returns to an unstable state, once more requiring
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SLEEP, MEMORY, AND PLASTICITY 157

consolidation, or “reconsolidation.” But we know much less about memory recon-

solidation than we do about memory consolidation. Although originally reported
in the 1960s (Misanin et al. 1968, Schneider & Sherman 1968), the details of mem-
ory reconsolidation have only recently come under intensive investigation (Nader
2003), and most of these more recent studies have focused on the degree to which
the process of reconsolidation is the same as or different from the initial processes
of encoding and stabilization (Alberini 2005). But additional questions have not
been as widely addressed. Conceptually, a consolidated memory can undergo at
least four processes: (a) reactivation, which leads to (b) destabilization, which in
turn leads to either (c) degradation or (d ) reconsolidation. Yet the temporal evolu-
tion of these individual steps, the mechanisms and brain states that produce them,
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and even their biological functions, remain unclear.

Time Course of Reconsolidation

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Determining the time course over which destabilization develops is difficult since
neither cellular-molecular nor behavioral correlates have been identified. But its
duration has been studied extensively because, by definition, the destabilized state
ends when reconsolidation is completed. For example, when reconsolidation of
learning on a radial maze task was blocked with propanalol either 5 minutes,
2 hours, or 5 hours after reexposure to the maze (and, presumably, reactivation of
the memory), error rates, measured 24 hours after reactivation, increased sixfold,
threefold, or not at all, respectively (Przybyslawski et al. 1999), which suggests a
half-life for the destabilized state of about 2 hours. Inhibition of reconsolidation
for conditioned taste aversion showed a similar half-life for the destabilized state,
on the order of 1 hour, with reconsolidation again apparently complete by 6 hours
(Gruest et al. 2004). Similarly, protein synthesis inhibitors injected 6 hours after
reexposure had no effect on destabilized fear-conditioned memories (Nader et al.
2000). Thus, reconsolidation would appear to be complete (and hence, destabi-
lization ended) 6 hours after reexposure, at which time the memory trace is again
resistant to interference.
Once destabilized, and in the absence of subsequent reconsolidation, degrada-
tion of a memory has generally been considered a passive process, perhaps based on
molecular turnover. Alternatively, it may be that the memory is not degraded at all,
but its recall blocked. The nature of this degradation currently remains unclear, and
degradation is defined behaviorally as diminished performance of the learned task.
Little data is available on the time course over which degradation occurs. Fol-
lowing reactivation and blockade of reconsolidation, previously learned behaviors
are still intact 2 hours (Suzuki et al. 2004) and 4 hours (Debiec et al. 2002, Duvarci
& Nader 2004, Nader et al. 2000) later, with no sign that degradation has begun.
This makes sense because reconsolidation appears to take at least this long and it
would be counterproductive for memories to begin to degrade before reconsolida-
tion normally has completed. At the other end of the process, any degradation of
the memory appears to be complete 24 hours after reactivation (Boccia et al. 2004,
Debiec & Ledoux 2004, Duvarci & Nader 2004; see also Myers & Davis 2002).
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Hints of the complex mechanisms governing reconsolidation as well as its pos-

sible function come from studies showing that inhibitors of cholinergic (Boccia
et al. 2004) and noradrenergic (Przybyslawski et al. 1999) neuromodulation can
also block reconsolidation. In addition, N-methyl-D-aspartate antagonists report-
edly can block the destabilization normally associated with reactivation (Nader
et al. 2004). Thus, the reconsolidation process appears to be controlled by a num-
ber of neuromodulators and plasticity-related neurotransmitters. But perhaps the
most direct evidence of a functional role for modulation of reconsolidation comes
from human studies of sleep-dependent memory processing.

Sleep and Reconsolidation

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As was described above for memory consolidation, it generally has been assumed
that reconsolidation processes progress over a fixed time, independent of brain
state. Yet as more and more phases of consolidation are found to be influenced
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by, and in some cases dependent on, sleep, it is important to ask what role sleep
might play in reconsolidation and its associated processes. Although few data
pertain directly to this question, we offer the hypothesis that both degradation
and reconsolidation processes can, and in some circumstances must, occur dur-
ing sleep. Indeed, most rodent studies of reconsolidation have been carried out
during the light (sleep) phase of the circadian cycle, and it is likely that ani-
mals in these studies slept between reactivation and subsequent measurements of
reconsolidation.
Evidence suggesting a role for sleep comes again from the human motor se-
quence task discussed above (Walker et al. 2003a). When retested 24 hours after
training (on day 2), subjects showed overnight sleep-dependent enhancements
of both speed and accuracy (Figure 9A, none). However, if subjects trained on
a second, competing sequence 10 minutes after the first sequence on day 1, in-
terference effects on sleep-dependent consolidation were observed the next day
(Figure 9A, 10 ); the normal delayed overnight improvement in accuracy was com-
pletely blocked (Walker et al. 2002a). When the time between learning the two
sequences was increased from 10 minutes to either 6 hours or 24 hours, no sig-
nificant interference was observed (Figure 9A, 6 hr and 24 hr). Thus, stabilization
of the memory occurred over a period between 10 minutes and 6 hours, affording
the original memory immunity from the interfering effects of a second competing
memory, immunity that was still present 24 hours later, following sleep.
In contrast, when the original memory was reactivated at 24 hours (through
90 seconds of rehearsal), just prior to interference training on day 2, a 57% de-
crease in accuracy was seen across the subsequent night of sleep (Figure 9B, 48 hr),
returning subjects’ accuracy to slightly below the level seen at the end of the origi-
nal training session. Thus, reactivation led to destabilization of the sleep-enhanced
memory. Presumably, under normal conditions, in the absence of competing in-
terference training, the memory would become restabilized over the next 6 hours,
becoming once again resistant to interference, although such reconsolidation was
not explicitly measured.
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SLEEP, MEMORY, AND PLASTICITY 159

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Figure 9 Reconsolidation of sleep-dependent learning. (A) Consolidation: Overnight im-

provement in accuracy was blocked by interference training (a second competing motor
sequence, filled bars) at 10 , but not at 6 hours posttraining relative to controls without inter-
ference (none, unfilled bar). (B) Reconsolidation: Interference training 10 after reactivation
(retest time 24 hours, gray bar) did not cause an immediate deterioration in the overnight
improvement, but 24 hours after reactivation and interference training, the initial overnight
improvement was abolished (retest time 48 hours, gray bar). Asterisks indicate significant
improvement; error bars indicate standard error of the mean; values are calculated as the
percentage difference in accuracy between successive test-retest intervals.
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These results lead to two conclusions. First, reconsolidation can be blocked by

ecologically relevant stimuli, such as a competing learning experience, and without
resorting to extreme electrical or chemical interventions (Walker et al. 2003a) pre-
viously used to prevent reconsolidation. Second, the deterioration in performance
might be limited to a reversal of earlier sleep-dependent consolidation.

SUMMARY
Over the past 25 years, the field of sleep and memory has grown exponentially,
with the number of publications per year doubling between the years 2000 and
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2004. These reports, ranging from cellular and molecular studies in animals to
behavioral studies in humans, have provided a wealth of converging evidence
that sleep-dependent mechanisms of neural plasticity lead to the consolidation of
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learning and memory across a range of animal species.

At the molecular level, inadequate pretraining sleep appears to compromise
hippocampally dependent modulation of molecules critically involved in memory
formation, resulting in impaired memory encoding. Significant numbers of genes
also appear to be up-regulated specifically in brain tissue during posttraining sleep,
and at least one immediate early gene related to synaptic plasticity, zif-286, is up-
regulated during REM sleep expressly in response to environmental or direct elec-
trical stimulation of the hippocampus (for a review, see Walker & Stickgold 2004).
At the electrophysiological level, studies in rats have shown that retention of
learning of a shuttle-box avoidance task increases subsequent P-wave density, and
is strongly correlated with this increase, while in humans, spindle density increases
following training on a declarative memory task and, again, this increase correlates
with subsequent improvement on the task. In rats, patterns of neuronal activation
expressed during waking exploration reappear during subsequent sleep; in humans,
patterns of regional brain activation seen during daytime task training are repeated
during subsequent REM sleep.
At the behavioral level, animal studies have found robust increases in REM
sleep following task training, and decrements in performance after REM depriva-
tion, even when retesting is delayed until one week after the period of deprivation.
In contrast, several animal studies have failed to find evidence of either increased
REM sleep or deterioration following deprivation. Most likely this reflects a com-
bination of methodological problems and conditions under which consolidation
is, in fact, not sleep dependent. Similarly, human studies have provided examples
where increases in REM sleep are seen following training, where REM or stage
2 NREM deprivation diminishes subsequent performance, and where overnight
improvement correlates with REM, SWS, or stage 2 NREM sleep. Furthermore,
these overnight learning benefits are associated with a system-level reorganization
of memory throughout the brain.
It is now clear that sleep mediates learning and memory processing, but the way
in which it does so remains largely unknown. The future of the field is truly exciting,
 23 Nov 2005 15:3 AR ANRV264-PS57-06.tex XMLPublishSM (2004/02/24) P1: OKZ

SLEEP, MEMORY, AND PLASTICITY 161

and the challenge to neuroscience will be to uncover the mechanisms of brain

plasticity that underlie sleep-dependent memory processing and to expand our
understanding of sleep’s role beyond encoding, consolidation, and reconsolidation,
into the constellation of additional processes that are critical for efficient memory
development. Work across the neurosciences will be necessary to answer these
questions, but with the current rate of growth of research in the field, the next
decade should provide important advances in our understanding of this critical
function of sleep. By way of this multidisciplinary approach, and with a measured
appreciation of the fundamental role that sleep plays in consolidating and reforming
memories, we can look forward to new advances in understanding memory and
treating its disorder.
Annu. Rev. Psychol. 2006.57:139-166. Downloaded from www.annualreviews.org

ACKNOWLEDGMENTS
This work was supported by grants from the National Institutes of Health (MH48,
by University of Sussex on 04/29/12. For personal use only.

832; MH65,292; MH06,9935; and MH67,754) and the National Science Founda-
tion (BCS-0121953).

The Annual Review of Psychology is online at http://psych.annualreviews.org

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SLEEP, MEMORY, AND PLASTICITY C-1

Annu. Rev. Psychol. 2006.57:139-166. Downloaded from www.annualreviews.org
by University of Sussex on 04/29/12. For personal use only.

Figure 1 The sleep cycle, memory systems, and memory stages. (A) The human
sleep cycle. Across the night, rapid eye movement (REM) and non-REM (NREM)
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 slow wave
sleep (SWS) dominate, whereas stage 2 NREM and REM sleep prevail in the latter
half of the night. Electroencephalogram patterns also differ significantly between
sleep stages, with electrical oscillations such as K-complexes and sleep spindles
occurring during stage 2 NREM, slow (0.5–4 Hz) delta waves developing in SWS,
and theta waves seen during REM. (B) Memory systems. Human memory is most
commonly divided into declarative forms, including episodic and semantic memory,
and nondeclarative forms, including an array of different types including procedural
skill memory. (C) Developing stages of memory. Following initial encoding of a
memory, several ensuing stages are proposed, beginning with consolidation and
including integration of the memory representation and translocation of the repre-
sentation or erasure of the memory. Also, following later recall, the memory
representation is believed to become unstable once again, requiring periods of
reconsolidation.
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C-2 WALKER ■ STICKGOLD

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Figure 8 Sleep-dependent motor memory reorganization in the human brain. Subjects

were trained on a sleep-dependent motor skill task and then tested 12 hours later, either fol-
lowing a night of sleep or following intervening wake, during a functional magnetic reso-
nance imaging (fMRI) brain-scanning session. Scans after sleep and wake were compared
(subtracted), resulting in regions showing increased fMRI activity postsleep (in red/yellow;
A–D) or decreased signal activity (in blue; E–H) postsleep, relative to postwake. Activation
patterns are displayed on three-dimensional rendered brains (top panel of each graphic),
together with corresponding coronal sections (bottom panel of each graphic). Following
sleep, regions of increased activation were identified in the right primary motor cortex
(A), the left cerebellum (B), the right hippocampus (C ), and the right medial prefrontal cor-
tex (D). Regions of decreased activity postsleep were expressed bilaterally in the parietal
lobes (E), together with the left insula cortex (F), left temporal pole (G), and left fronto-
polar area (H ) , all regions of the extended limbic system. All data are displayed at a cor-
rected threshold of p
0.05.
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Annual Review of Psychology

Volume 57, 2006

CONTENTS
Frontispiece—Herbert C. Kelman xvi
PREFATORY
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Interests, Relationships, Identities: Three Central Issues for Individuals and

Groups in Negotiating Their Social Environment, Herbert C. Kelman 1
BRAIN MECHANISMS AND BEHAVIOR: EMOTION AND MOTIVATION
by University of Sussex on 04/29/12. For personal use only.

Emotion and Cognition: Insights from Studies of the Human Amygdala,

Elizabeth A. Phelps 27
STRESS AND NEUROENDOCRINOLOGY
Stressful Experience and Learning Across the Lifespan, Tracey J. Shors 55
REWARD AND ADDICTION
Behavioral Theories and the Neurophysiology of Reward, Wolfram Schultz 87
GENETICS OF BEHAVIOR
Genetics of Affective and Anxiety Disorders,
E.D. Leonardo and René Hen 117
SLEEP
Sleep, Memory, and Plasticity, Matthew P. Walker and Robert Stickgold 139
COMPARATIVE PSYCHOLOGY, ETHOLOGY, AND EVOLUTION
Neuroecology, David F. Sherry 167
EVOLUTIONARY PSYCHOLOGY
The Evolutionary Psychology of Facial Beauty, Gillian Rhodes 199
LANGUAGE AND COMMUNICATION
Explanation and Understanding, Frank C. Keil 227
ADOLESCENCE
Adolescent Development in Interpersonal and Societal Contexts,
Judith G. Smetana, Nicole Campione-Barr, and Aaron Metzger 255
INDIVIDUAL TREATMENT
Enduring Effects for Cognitive Therapy in the Treatment of Depression
and Anxiety, Steven D. Hollon, Michael O. Stewart, and Daniel Strunk 285
vii
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viii CONTENTS

FAMILY/MARITAL THERAPY
Current Status and Future Directions in Couple Therapy,
Douglas K. Snyder, Angela M. Castellani, and Mark A. Whisman 317
ATTITUDE CHANGE AND PERSUASION
Attitudes and Persuasion, William D. Crano and Radmila Prislin 345
BARGAINING, NEGOTIATION, CONFLICT, SOCIAL JUSTICE
Psychological Perspectives on Legitimacy and Legitimation, Tom R. Tyler 375
INDIVIDUAL DIFFERENCES AND ASSESSMENT
Annu. Rev. Psychol. 2006.57:139-166. Downloaded from www.annualreviews.org

Personality and the Prediction of Consequential Outcomes, Daniel J. Ozer

and Verónica Benet-Martı́nez 401
ENVIRONMENTAL PSYCHOLOGY
by University of Sussex on 04/29/12. For personal use only.

Child Development and the Physical Environment, Gary W. Evans 423

MARKETING AND CONSUMER BEHAVIOR
Consumer Psychology: Categorization, Inferences, Affect, and Persuasion,
Barbara Loken 453
STRUCTURES AND GOALS OF EDUCATIONAL SETTINGS
Classroom Goal Structure, Student Motivation, and Academic
Achievement, Judith L. Meece, Eric M. Anderman,
and Lynley H. Anderman 487
DATA ANALYSIS
Analysis of Longitudinal Data: The Integration of Theoretical Model,
Temporal Design, and Statistical Model, Linda M. Collins 505
TIMELY TOPICS
The Internet as Psychological Laboratory, Linda J. Skitka
and Edward G. Sargis 529
Family Violence, Patrick Tolan, Deborah Gorman-Smith, and David Henry 557
Understanding Affirmative Action, Faye J. Crosby, Aarti Iyer,
and Sirinda Sincharoen 585

INDEXES
Subject Index 613
Cumulative Index of Contributing Authors, Volumes 47–57 637
Cumulative Index of Chapter Titles, Volumes 47–57 642

ERRATA
An online log of corrections to Annual Review of Psychology chapters
may be found at http://psych.annualreviews.org/errata.shtml