Sleep Medicine Reviews, Vol. 5, No. 6, pp 491–506, 2001
doi:10.1053/smrv.2001.0164, available online at http://www.idealibrary.com on
SLEEP
MEDICINE
reviews
PHYSIOLOGICAL REVIEW
Sleep states and memory processes in humans:
procedural versus declarative memory systems
C. Smith
Department of Psychology, Trent University, Peterborough, Ontario, Canada
KEYWORDS
humans, REM sleep,
NREM sleep, learning,
declarative memory,
procedural memory
Summary The present paper focuses on human studies attempting to relate sleep
states to memory processes. These studies typically present learning material to
participants and then examine their ability to recall this material after intervening posttraining sleep or sleep deprivation. Most experiments utilize either sleep recording or
sleep deprivation following task acquisition to reach their conclusions, although cueing
and position emission tomography (PET) scan studies have also been done. Results
strongly suggest that REM sleep is involved with the efficient memory processing of
cognitive procedural material but not declarative material. Although there are some
data to suggest that stage 3/4 or NREM sleep is necessary for declarative memory
consolidation, NREM may in fact simply be occurring at the same time as another
factor that is actually involved in the memory processing. Preliminary results suggest
that the length of the NREM–REM sleep cycle may be important for declarative
memory. Preliminary data also suggest that stage 2 sleep may be involved with the
memory for motor procedural but not cognitive procedural tasks. Sleep researchers
would do well to capitalize on the latest advancements in memory research by choosing
tasks that represent special memory systems and examining their relationships to
sleep states.  2001 Harcourt Publishers Ltd
INTRODUCTION
It has been over 75 years since Jenkins and Dallenbach [1] claimed that recall in humans improved
after an intervening night of sleep. Since this
pioneering report, a substantial number of studies
have been carried out to examine the possibility
that sleep is related to the cognitive processes of
learning and memory. Experiments have been done
using both animal and human subjects. The present
paper will focus on those studies using human
Correspondence should be addressed to: Dr Carlyle Smith,
Department of Psychology, Trent University, Peterborough,
Ontario, Canada, K9J 7B8. E-mail: csmith@trentu.ca
1087–0792/01/060491+16 $35.00/0
participants and paradigms that examine the effects
of sleep states on previously learned material.
One of the earliest reviews of this area [2]
examined the possible relationship between sleep
states and learning/memory in both animals and
humans. There was substantial evidence from animal
studies to support the idea that post-training REM
sleep was important for memory consolidation. The
human studies, however, provided mixed results.
The human studies cited as showing no relationship
between sleep and memory utilized simple memorization tasks. Those studies that reported a
positive sleep–memory effect utilized tasks requiring
more complex cognitive activity such as anagrams
or a test of story meaningfulness. Since then, research has shown that the types of memory tasks
used in these studies are very important.
 2001 Harcourt Publishers Ltd
492
THE EVOLUTION OF THE
UNDERSTANDING OF MEMORY
When the earlier sleep-learning studies were carried out, it was assumed that memory had three
phases. These included a very short registration
phase taking less than 1 s to occur followed by a
period (minutes to hours) after training, during
which learned material existed as relatively labile
short-term memory that was vulnerable to various
agents such as strong drugs or electroconvulsive
therapy (ECT). As the minutes turned to hours and
memory processing continued, the learned material
was considered less vulnerable to disruption. After
24 h (or even less), memory formation was considered complete and, thus, no longer vulnerable
to disruption. At this point a stable, permanent
long-term memory was considered to have been
formed. This process has been called consolidation
and most workers still use the concept of a
permanent “memory trace” existing in the brain
[3–5].
In many of the early sleep–memory animal studies,
it was assumed that the first few hours of sleep after
training were sufficient to observe the conversion of
learned material from short- to long-term memory
[2, 6, 7]. In humans, one night of sleep was considered sufficient. However, as time passed, reports
of vulnerability to such agents as drugs or ECT
went from hours to days to weeks, months and
years. For example, Squire et al. [8] reported that
a series of five ECT treatments in human adults
resulted in loss of memory for television shows
seen in the last 3 years, but not before. Thus,
although the phases leading to long-term memory
have remained more or less theoretically intact,
their timing and duration have been shown to be
quite variable.
Memory was traditionally thought to be a unitary
system. However, there are now considered to be
at least two kinds of memory in humans. Although
a variety of terms are used to describe each, one of
the most commonly utilized distinctions is between
declarative and procedural knowledge. Declarative
material has been described as “knowing that” and
refers to memories accessible to conscious recollection. “Knowing how” describes procedural
knowledge. These are memories of how to do some
skill or how to solve a problem. These two memory
systems are believed to have different functional
systems and even different neuroanatomical
C. SMITH
substrates. Memories can also be explicitly learned
or implicitly learned, meaning that they can be
consciously acquired or acquired without conscious
knowledge. Generally speaking, declarative material
is usually explicitly (consciously) learned and procedural material is usually implicitly (unconsciously)
learned [9, 10]. While this is a very rudimentary
coverage of the nature of the memory systems now
being studied, it will be sufficient for the purposes
of this review.
Since much of the knowledge about memory
systems has become available in the last 15 years or
so, earlier studies attempting to find a relationship
between sleep and learning/memory naturally assumed that memory was a single monolithic process.
More recent human studies have barely begun to
relate sleep states specifically to the multiple memory systems model.
APPROACHES TO THE STUDY OF
SLEEP AND MEMORY
There have been four main kinds of studies performed to study the relationship between sleep and
memory in humans. One approach has been to
train subjects on some task and then to record
the changes in sleep parameters (or some other
variables such as cerebral blood flow) on subsequent
nights. These values are compared to the participants’ own baseline sleep activity as well as to the
sleep activity of various non-learning and pseudolearning controls. The rationale for this method is
to observe changes in sleep or other physiological
activities correlated with learning progress.
A second approach has been to deprive the
subject of total sleep or of some specific phase or
aspect of sleep following task acquisition in order
to induce possible memory impairments. Memory
for the task is then re-examined at some later
post-test time and related to the type of sleep
loss.
A third approach has been to have the subject
learn the task either just before bed or during the
night at some particular point. Then the subjects
are retested after only a partial night of sleep to
observe the efficacy of some particular sleep
phase.
A fourth, and much less utilized method, has
been to try to cue (usually auditory) subjects in the
night during various sleep stages. The cue is related
to the learning task and has sometimes resulted
SLEEP STATES AND MEMORY PROCESSES IN HUMANS
in memory enhancement. This is a method that
attempts positively to influence the course of the
memory formation during sleep, presumably while
it is occurring.
SLEEP AND MEMORY FOR
DECLARATIVE MATERIAL
Many of the earlier experiments [2] designed to
study memory utilized the recording or deprivation
approaches and their expectation was that the tasks
would be involved with REM sleep. Several did not
do polygraphic recording, but did compare learning
following sleep versus learning following awake conditions [11, 12]. Many of these studies utilized
learning tasks composed of declarative material.
Historically, one of the most popular tasks has been
the verbal learning task and virtually none of the
studies using this type of task observed REM sleep
parameter changes on the sleep nights following
training.
Changes in sleep parameters and
memory following acquisition of
declarative material: non-sleep
deprivation studies
Castaldo et al. [13] (Experiment 1) used both serially
presented trigrams and verbal paired associates (PA;
declarative memory tasks) but observed no postacquisition changes in any REM or NREM sleep
parameters.
Bertini and Torre [14] timed the recall of the
task to occur following experimentally induced REM
sleep rebound. They saw no facilitation of memory
for their PA task.
Yaroush et al. [15] compared the first and second
half of the night of sleep using a verbal paired
associates task. Some subjects learned the task at
bedtime, slept 4 h (composed of a high percentage
of stage 4 (NREM) and a low percentage of REM
sleep) and were then awakened and retested. They
showed superior memory to subjects awakened
after 4 h sleep, trained and allowed another 4 h
sleep (composed of a low percentage of NREM
and high percentage of REM sleep) before being
retested. There was also an “awake” group which
was not allowed to sleep and did not do as well as
the group getting large amounts of stage 4. The
authors concluded that while stage 4 facilitated
memory for the task, REM sleep did not.
493
Fowler et al. [16] did a very similar study. They
refined the paradigm by allowing the first half (sleep
during the first half of the night) subjects some
sleep prior to original learning. Again they found
that subjects trained on a PA task and allowed
some stage 4 were superior to the awake subjects.
However, the second half (sleep during the second
half of the night and high levels of REM) group was
also superior to the awake group on the PA task.
They also used a PA task involving nonsense shapes.
No group differences were found on this task.
These last-mentioned studies [15, 16] confounded
the time of day of learning and retesting with the
sleep–wake cycle.
Barrett and Ekstrand [17] controlled for time of
day using the Fowler et al. [16] design. They showed
that sleep composed predominantly of stage 4 was
better for PA memory than REM sleep, but that
when the prior sleep was composed of greater
amounts of REM sleep (although not exclusively
REM sleep), performance was also somewhat better
than in the awake group.
Benson and Feinberg [11] found that participants
that had a night of sleep after learning a PA task
showed superior memory to participants that stayed
awake for an equal amount of time. Since no sleep
recording was done, it is not possible to know
which state of sleep was most beneficial.
Grosvenor and Lack [12] also did a study using
PA tasks. While they did not sleep record, they
attempted to control for the amount of sleep between the first half and second half of the night.
They had two groups that stayed awake until half
the night was over and, after learning, either went
to sleep (ALS) or stayed awake (ALA). Another
two groups were allowed to sleep for the first half
of the night and then after learning, either slept
again for the second half of the night (SLS) or stayed
awake (SLA). All groups learned equally well. The
first recall test was 4 h later and the second 6 days
later. Subjects that stayed awake prior to learning
were superior at the 4 h recall to groups awakened
to learn the task. Post-sleep groups remembered
better than post-awake groups at the 4 h recall.
However, the retest 6 days later showed no benefit
of post-training sleep on the task. It was also concluded that there was no advantage of first half
sleep over second half sleep when prior condition
was controlled.
Much more recently, Plihal and Born [18] used
an early-night/late-night design to examine memory
C. SMITH
494
for both declarative and procedural material. They
found that subjects trained just before bed and
awakened 3 h later (after predominantly stage 4
sleep) were superior to a corresponding “awake”
group on the PA task, but not the procedural mirror
trace task. On the other hand, subjects trained in
the middle of the night, then allowed 3 h sleep
(predominantly of the REM type) were superior
on the procedural mirror trace task, but not the
declarative PA task compared to a corresponding
“awake” group when tested 3 h later.
Effect of total or selective sleep
deprivation on memory for declarative
material
A number of human studies have been done utilizing
the second major paradigm to study sleep states
and memory processes. As with the recording studies, REM sleep deprivation studies using verbal PA
tasks reported no learning deficits as a result of
selective REM sleep deprivation (REMD) following
task acquisition (Castaldo et al. [13], Chernik [19],
Ekstrand [20]). In a study by Ekstrand et al. [21],
not only was the PA task not impaired by REMD,
but performance was unaffected by stage 4 sleep
deprivation as well.
Lewin and Glaubman found no negative effect of
overnight REMD on memory for serial verbal word
lists or word clusters [22].
In more recent work by Smith [23], subjects
were given a paired associate task and a complex
logic task at the same training session. Groups were
allowed normal sleep, were exposed to REMD,
had NREM sleep interrupted or were totally sleep
deprived (TSD). Retesting was done 1 week later.
While all of the groups forgot a substantial amount
of their PA task, there were no differences among
the groups when retested 1 week later.
In further studies by Smith [24] subjects were
required to learn a word recognition task, a visual
non-verbal figure task as well as several procedural
tasks. Various groups were exposed to REMD (last
two REM periods of the night), NREM interruption,
TSD or normal rest. Groups did not differ on their
post-training retest of the recognition and visual
figure tasks 1 week later. Thus, there was no
differential effect of TSD or REMD on memory for
the declarative material.
The results of these recording and deprivation
studies provide very little support for a connection
between REM sleep and simple declarative memory.
SLEEP AND MEMORY FOR
PROCEDURAL MATERIAL
Many studies used training tasks that were either
of the procedural type or at least had what appeared
to be a procedural component. The tasks required
participants to engage in cognitive activity that was
more complex than simple recall or recognition
of previously memorized material. These studies
demonstrated a relationship between REM sleep
and memory.
Changes in recorded sleep parameters
following acquisition of procedural tasks
or tasks with a procedural component
Lewin and Gombosh [25] observed an increase in
REM sleep time in individuals exposed to tasks
designed to induce curiosity, ego-involvement, emotionality, and divergent thinking prior to sleep onset.
It is difficult to decide which of these tasks contributed the most toward the REM increases, since
all were presented at the same time.
Paul and Dittrichova [26] showed an increase in
REM sleep over baseline in infants which learned a
head turning response. No REM sleep increase
was observed in infants that failed to learn the
response.
Several experiments were done examining subjects’ adaptation to a set of lenses that distorted
the visual field. Two earlier studies concluded that
there was no REM sleep involvement [27, 28]. The
Allen et al. study [28], although it did provide a
formal set of learning situations, only utilized three
subjects. Further, the sampling method to estimate
REM sleep density was not extensive enough to
detect any changes in this measure. In the Zimmerman et al. [27] study, sleep variables were carefully
examined, but results did not include any formal
measures of adaptation to the prisms. A more
recent and thorough study examining both sleep
parameters [29] and dream content [30] found that
subjects did show an increase in %REM sleep and
decrease in REM density following adaptation to
the inverted lenses as measured by a variety of
formal learning tests. The dreams of these subjects
revealed a gradient of adaptation. Significant increases in content with motor and visual problems,
SLEEP STATES AND MEMORY PROCESSES IN HUMANS
misfortune and dreamer confusion were observed
in those subjects who had adapted the most completely. Those subjects that had not adapted so
well, did not exhibit this type of mental content.
Vershoor and Holdstock [31] presented a number
of visual and auditory tasks to both learning and
non-learning groups of undergraduate students. The
visual and auditory learning groups exhibited REM
sleep increases. Both the learning and non-learning
visual groups also increased in REM burst percentage, while the two auditory groups (learning
and non-learning) decreased their REM burst percentage. The authors concluded that excessive
stimulation accounted for the increases or decreases in REM bursts while the REM sleep increases
reflected learning.
Mandai et al. [32] found an increase in REM sleep
duration and number of REM episodes in subjects
who underwent 90 min training in translation of
Morse code. They also reported a high correlation
between retention, number of REMs and REM
density.
A study by Smith and Lapp [33] assessed the
effects of exams on sleep parameters. It was observed that 3–5 days after writing Christmas exams,
senior undergraduate psychology students showed
more eye movements and higher REM densities
than they had shown in their own baselines the
summer before and the summer after (when, by
contrast, very little learning was occurring). They
also exhibited higher values on these two measures
compared to same age non-learning controls [33].
A study examining sleep parameter changes in
individuals learning a second language in a total
French immersion environment (DeKoninck et al.
[34]) has reported a positive correlation between
learning progress over the 6-week course and
%REM sleep. Three subjects who did not improve
their grades throughout the course did not show
any %REM sleep increases. In an examination of the
dream mentation [35] of these subjects, it was
revealed that the students making the most progress
in the course were the first to have French incorporated into their dreams and they communicated more often in French in their dreams.
Scrima [36] presented narcoleptic patients with
both an anagram and trigram task followed by a
period of NREM sleep, REM sleep or no sleep.
Subjects performed best on memory for the more
complex anagram task after REM sleep and NREM
sleep resulted in better performance than no sleep.
495
Performance on the simpler trigram task was not
affected by either REM or NREM sleep.
Buchegger et al. [37, 38] studied the effects of
learning novel complex motor activity (trampolining) in novices over a period of 13 weeks and
observed marked increases in REM sleep but not
NREM sleep in successful participants. Control
groups exerted an equal amount of energy but did
not have to learn any novel motor movements
(soccer, gymnastic dancing). The REM and NREM
sleep of these latter groups was unchanged throughout the sessions. It was concluded that the important variable was the acquisition of the ability
to correctly move the body in space, a task requiring
complex and novel conceptualization.
Fanjuad et al. [39] asked medical students to learn
a variety of tasks including verbal and non-verbal
material, a topographical map and a Chinese puzzle.
Overall they observed a slight increase in REM sleep
compared to the subjects own baselines. This was
due to a larger amount of REM sleep in the second
REM period. On retest, only performance on the
topographical map task was improved, suggesting
that this task was largely responsible for the observed REM sleep changes.
Stickgold et al. [40] trained subjects on a visual
search task. They found that improvement on the
search task correlated highly with both the amount
of NREM sleep in the first quadrant and REM sleep
in the fourth quadrant of an 8 h night of sleep. The
combined correlations for the two states of sleep
accounted for 80% of the intersubject variance.
REM sleep during the first 6 h was not related to
task improvement. Interestingly, the study provides
some evidence for memory processing during a
specific time period during the night. There is
substantial evidence for REM “windows” in animal
studies, where REM sleep episodes at certain times
after the end of training are the important times
for memory consolidation to occur. REM at times
outside of these windows is not apparently necessary for consolidation (see Smith [24, 41, 42] for
reviews). The study by Stickgold et al. [40] is one
of the two to suggest the existence of human REM
windows within a single night of sleep. The study
by Smith and Lapp [33], reviewed earlier, also
suggested the existence of a REM window at the
end of the night of sleep. This change in REM sleep
manifested in an increased number of REMs in the
fifth REM period as well an increased REM density
in the fourth REM period 3–5 days following college
examinations.
496
Effect of total or selective sleep
deprivation on memory for tasks with a
procedural component
In a study by Smith [23] utilizing both a PA and a
complex logic (procedural) task, groups experienced REMD, NREM awakening, TSD or were
allowed normal sleep. Memory for the logic task
was severely impaired in the REMD and TSD groups,
strongly implicating REM sleep as important for
the memory of procedural material. In a second
experiment [23], subjects learned the complex logic
task. Following this, one group experienced REMD
for the first two REM periods of the night and then
was allowed to sleep normally. A second group
experienced REMD during the last two REM periods
of the night after having slept normally for the first
half of the night. Compared to a third, non-REMD
group, both of the REMD groups were equally
impaired on memory for the logic task when retested 1 week later. Thus REM during the first or last
part of the night was equally valuable for memory
efficiency. In yet another study [23], evaluating only
the effect of TSD, it was observed that TSD was
capable of inducing this same level of memory loss.
Surprisingly, TSD was able to induce memory loss
not only if experienced on the night of task acquisition, but also if experienced 2 nights (48–72 h)
later. On the other hand, TSD one night after task
acquisition or 3 nights after task acquisition (24–48 h
or 72–96 h later) had no effect on memory for the
logic task. These results demonstrate the vulnerability of some kinds of memory long after (2
days) the end of training.
Empson and Clarke [43] showed that REMD after
serial word list acquisition did not produce any
memory deficits while these same subjects exhibited
memory loss for more difficult material including
meaningless sentences and anomalous prose passages. NREM-deprived controls got significantly less
stage 4 than did REMD subjects, but were still
superior on these latter tasks.
In a study by Tilley and Empson [44], subjects
were tested for retention of a story by means
of free recall following either REMD or stage 4
deprivation. REMD subjects showed poorer retention for this material. In another report [45],
they examined two sets of PA and two stories.
While the PA tasks were unaffected, the most
impaired group on story recall was the group with
no REM sleep at all. Interestingly, a few subjects
C. SMITH
were inadvertently allowed a small amount of REM
sleep. These subjects had much better story recall
than those getting no REM sleep, suggesting that
even partial REM sleep within a REM period may
be important for memory consolidation.
Karni et al. [46] had subjects learn a visual detection task. Participants showed improvement on
this task after a normal night of sleep. REM sleep
deprivation prevented improvement in the task,
while NREM awakenings did not prevent this improvement from taking place.
A variety of tasks [24] were presented to college
students including word recognition, word fragment
completion, visual memory, Corsi block tapping and
Tower of Hanoi. Following acquisition of these
tasks, the REMD group was deprived of the last
two REM periods of the night. Control groups
included a NREMD group, a TSD group, a normally
rested sleep-recorded group and a normally rested
home control group. Retest took place 1 week
later. It was observed that the REMD and TSD
groups were not impaired on the declarative word
recognition or visual memorization task, but were
impaired on the procedural word fragment completion, Corsi block tapping and Tower of Hanoi
tasks compared to the other three experimental
groups [24].
A few results do not apparently fit cleanly into
either the declarative/procedural category [43, 44,
47]. For example, consistent with the theory, Empson and Clarke [43] reported no deficits in memory for a serial word list following REM sleep
deprivation. However, these same experimenters
also presented meaningless sentences and anomalous prose, material that would have to be
considered declarative. Post-training REM sleep
deprivation for these two tasks resulted in memory
deficits. Likewise, Tilley and Empson [44, 47], consistent with the declarative/procedural dichotomy
and REM sleep, showed that PA tasks were not
vulnerable to REM sleep deprivation. On the other
hand, they reported in the same studies that remembering the essence of stories was impaired
by REM sleep loss. Thus, while simple declarative
material (word lists, paired associates) was “immune” to REM sleep deprivation, memory for the
more complex declarative material (anomalous
prose, meaningless sentences, stories) was impaired
by REM sleep deprivation in three studies [43, 44,
47].
One explanation might simply be the level of
SLEEP STATES AND MEMORY PROCESSES IN HUMANS
difficulty of the declarative material. Perhaps the PA
tasks were too easily memorized and thus not
vulnerable to sleep loss while the more complex
material was not. This seems somewhat unlikely,
since several studies presented PA tasks which were
difficult enough that they were never completely
learned [23, 24], yet, subsequent REM sleep deprivation and total sleep deprivation had no effect
on memory for these tasks.
A more likely possibility is that of familiarity of
storage and/or response strategies. College students comprised the great majority of subjects in
these studies and their familiarity with the words
presented and their ability to give the simple response is based on many years of similar school
activity. It would be reasonable to assume that these
students have long since developed a strategy to
memorize and to retrieve this type of material.
On the other hand, perhaps they had less welldeveloped strategies to deal with the anomalous
prose, meaningless sentences and stories. The idea
that cognitive storage and/or retrieval strategies
are helpful for remembering complex unfamiliar
declarative material is well established. An obvious
example is “chunking” or the memorizing of long
strings of numbers by storing them in groups or
chunks of three to four numbers.
It seems reasonable that many real-life learning
situations have both a declarative and a procedural
component. For example, the words to a new
language might be considered declarative material,
but the use of these words would be procedural.
Most students do not spend many hours per year
memorizing meaningless sentences or anomalous
prose. They would probably have greater trouble
memorizing and/or retrieving this material than
simple words and this suggests the possibility that
they would have to develop new memory storage
and/or retrieval strategies. While it could be argued
that students would likely have had a more welldeveloped strategy for learning stories, in the studies mentioned [44, 47], the demand characteristics
of the response were changed (subjects were asked
for the essence of the stories rather than verbatim
story recall ), possibly requiring new retrieval strategies.
Thus subjects might have had to develop new
strategies to handle the storage and/or retrieval of
this less familiar material. REM sleep could be involved in the formation of these new cognitive
procedural storage/retrieval strategies. While it is
497
not possible to decide this question based on the
available data, the idea is quite testable and further,
carefully designed studies can shed more light on
this problem.
The overview of the above recording and deprivation studies indicates that those studies using
training tasks which were clearly of a declarative
nature did not require REM sleep following acquisition for increased memory efficiency. On the
other hand, those tasks that were clearly procedural
or had a procedural component appeared to require
REM sleep for maximum learning efficiency.
INFLUENCING MEMORY
PROCESSING DURING SLEEP BY
CUEING
It has been reported in animal studies by Hennevin
and Hars [48, 49] that when an ear shock was used
as the conditioned stimulus (CS) in a two-way
shuttle shock avoidance task, enhanced memory for
the task was induced by presenting sub-awakening
threshold CS pulses to the rats during post-training
REM sleep. These rats showed superior performance to control animals. It was concluded that
the CS pulses acted as a “reminder” to the brain
to process further the recently learned CS–UCS
(unconditioned stimulus of foot shock) relationship.
In humans [50], individuals learned to decipher
Morse signals. During subsequent REM sleep one
group was randomly presented with auditory
“clicks”, such that most occurred when there were
no actual rapid eye movements occurring. A second
group received clicks that coincided with the actual
rapid eye movements of their REM sleep episodes.
Compared to a non-stimulated (“non-clicked”)
group, enhanced memory for the group receiving
REM-coincident clicks was reported.
Smith and Weeden [51] had subjects learn a
complex logic task either in the presence or absence
of a clicking sound. There were four groups: 1)
clicks during learning followed by REM-coincident
clicks during subsequent REM sleep (clicks delivered
to the ear at the maximum deflection of the horizontal eye movement); 2) no clicks during learning
followed by REM-coincident clicks during subsequent REM sleep; 3) clicks during learning followed by clicks delivered during tonic REM sleep
(quiet REM sleep with no REMs); 4) no clicks during
learning and no clicks during the night. The group
498
C. SMITH
getting clicks during training and then clicks coincident with the REMs of REM sleep were 23%
better than all of the other groups.
These studies indicate that REM sleep is related
not only to procedural task memory but add to the
possibility that the phasic component of REM sleep
is an important component of memory processing.
to sleep and memory studies and provides fertile
ground for further research.
FUNCTIONAL IMAGING STUDIES
There are many animal and human studies that have
examined the role of the medial temporal region,
especially the hippocampus in memory processing.
Although the functions of the many structures which
provide input and output to this structure are not
yet completely understood, it is becoming increasingly clear that the hippocampus is essential
for normal declarative memory [9, 55–61]. From
the analysis of the human sleep studies done to this
point, it does not seem that REM sleep is involved
with this type of learning. The data supporting the
idea that NREM sleep is involved with declarative
memory is mixed and more data will be required
before this idea is confirmed. That the hippocampus
is not involved with sleep states (especially REM)
and memory is apparently at odds with recent data
from animal studies [62–64]. However, understanding the role of the hippocampus and sleep in
humans must await further research.
While REM sleep appears to be involved with a
variety of procedural tasks, the number of human
studies attempting to pinpoint structures related to
procedural memory are not nearly as numerous as
for declarative memory. One group [61] demonstrated in normal humans using PET scans, that
the visual association cortex was involved in a
visual priming task, while the hippocampus was not.
Another group [65, 66], examining patients with
Parkinson’s disease, have evidence to suggest that
the neostriatum and prefrontal cortex are involved
with cognitive procedural, but not declarative memory. Maquet et al. [52] showed that a number of
structures, including the extrastriate, left premotor,
superior parietal, left primary sensorimotor, supplementary motor, precuneus, anterior cingulate
and cerebellum were involved in acquisition of a
procedural SRT task.
Thus, while the brain structures involved with
procedural memory appear to vary with type of
task being presented, none of the tasks appear to
involve the hippocampus. Memory researchers are
now in the process of trying to integrate brain
structures with different types of memory systems.
To date, only one imaging study has been published
which directly examined the effects of learning a
task and the sleep patterns of the learner. Maquet
et al. [52] presented two groups of subjects with a
serial reaction time (SRT) task. One group had PET
scans taken during the task acquisition, the second
group had PET scans taken while they were in quiet
waking, NREM and REM sleep. A third group was
not trained but was scanned as was the second
group in various stages of sleep. Those brain areas
which were significantly more active during REM
sleep of trained subjects compared to the nontrained subjects, and involved in the execution of
the task during waking included the extrastriate
cortex (bilaterally), the left premotor cortex (all
subjects were right handed) and the mesencephalon.
The results strongly suggest that further processing
of the task was occurring during REM sleep. There
was no such comparable activity in quiet waking,
stage 2 or stage 4 sleep.
IS THE NREM–REM CYCLE
IMPORTANT?
There are few studies that have adequately controlled for or reported lengthening or shortening
of the NREM–REM sleep cycle length. Two recent
reports suggest that it may be an important factor.
Mazzoni et al. [53] presented word pairs to elderly
subjects, and after an intervening night of sleep,
tested their cued recall. The level of recall was
positively correlated with the average duration of
the NREM–REM sleep cycles. This same laboratory
[54], in a more detailed study, again using word
pairs as their memory task, demonstrated that it
was disturbed sleep cycle activity rather than just
loss of either NREM or REM sleep that contributed
to declarative memory loss. While more data are
required, these studies point to a manipulation that
has not been systematically explored with respect
HOW DO THE RESULTS FROM
HUMAN SLEEP STUDIES RELATE
TO BRAIN STRUCTURES?
SLEEP STATES AND MEMORY PROCESSES IN HUMANS
When these relationships are more clearly understood, we may be able to understand how they
interact with sleep state mechanisms.
BRAIN PATHOLOGY INDUCED
SLEEP LOSS AND MEMORY
A number of authors [67–69] have examined
patients with bilateral pontine lesions who were
completely paralyzed (“locked-in” syndrome) and
were almost completely lacking in REM sleep. It
might be expected that such individuals would show
memory impairments. However, the assessment of
memory was not very sophisticated in these studies.
The authors noted that these individuals demonstrated memory for events and people (declarative material) [67–69]. In a few cases, patients
with bilateral pontine damage who were conscious,
mobile and verbally communicative have been observed [69–72]. For example, Lavie et al. [71] reported recording from a male with a pontine lesion.
He showed virtually no REM sleep (approximately
2%), but was otherwise normal. He recovered from
his wound and lived a fairly normal life, becoming
a lawyer. Perret et al. [72] studied the sleep of a
male adult with extensive nigro-striatal damage. He
showed no sign of REM or stage 4 sleep. He
was presented with an array of tasks and it was
concluded that there was no memory loss despite
this abnormal situation. A close examination of the
tasks used in these studies indicates that they were
all of a declarative nature. While these reports do
indicate that the individuals have coped well with
their problems and appear to lead normal lives,
they do not necessarily demonstrate memory normality. It is more likely that the rate of learning
REM sensitive material is slower than for normal
individuals, although still able to occur at this somewhat slower, less efficient rate. This is certainly the
case in REM sleep deprivation studies [23, 24, 43–46,
73]. Material not sensitive to REM sleep would be
unaffected. These reports simply do not address
such a possibility.
MEMORY IN PATIENTS TAKING
REM-SUPPRESSING DRUGS
It is widely known that virtually all major antidepressant drugs, including the monoamine oxidase
499
inhibitors (MAOIs) [74], the tricyclic antidepressants (TCAs) [75] and the selective serotonin
reuptake inhibitors (SSRIs) [76] profoundly reduce
the amount of REM sleep. The REM-suppressing
effect of these drugs may be the reason for their
success [77, 78]. It might be expected that individuals
taking such drugs would be at a disadvantage in
terms of their efficiency in learning cognitive procedural material and there have been reports of
some of these drugs inducing memory loss. The
most potent substance is the drug amitriptyline [79,
80], although the memory loss observed after this
drug is apparently due to its strong anticholinergic
effects rather than to its REM sleep suppressing
properties. Another drug reported to induce memory loss is trazodone, a TCA that reportedly has a
sedating effect. However, the many antidepressant
REM-suppressing drugs without either of these
properties have not been associated with memory
loss [79–81]. While there have been many reports
that cognitive function is not impaired as a result
of REM-suppressing drugs, the tests were mostly
of the declarative type – (MAOIs) [82–84], (TCAs)
[81, 85–88] and SSRIs [80, 81, 86, 89]. Furthermore,
the design of the studies was invariably to assess
individuals at various times after drug administration. There were no tests which re-examined patients on material learned several days
previously (after intervening sleep). Thus, it is not
surprising that authors found their patients to be
living relatively normal lives. These individuals would
behave quite normally in terms of remembering
names, places and facts required of any declarative
task. Further, they would also be able to learn
cognitive procedural material. They simply would
not be expected to learn this kind of material as
efficiently as would an individual getting a normal
amount of REM sleep each night. The difference
would only become obvious over the long term of
days and weeks.
THE CASE FOR REM SLEEP AND
MEMORY FOR PROCEDURAL BUT
NOT DECLARATIVE MATERIAL
The examination of studies using declarative and/
or procedural tasks suggests that REM sleep is not
involved with consolidation of declarative material.
Six of the seven non-deprivation studies [12–16,
18] indicated no specific REM sleep effect. The
500
seventh study [16] reported that the group receiving
the last half of the night of sleep (high in REM and
low in NREM or stage 4) performed better than
subjects who had stayed awake. On the other hand,
14 of 16 non-deprivation studies that utilized tasks
of a procedural nature or tasks that had a procedural
component [25, 26, 29–40] all reported increases
in some component of REM sleep. Some of the
studies reported increases in the number of minutes
of REM sleep or %REM sleep, while others observed
increases in number of actual REMs and REM densities. The two studies that did not report REM sleep
changes were both studies in which the subjects
were exposed to visual distortion using special
prisms [27, 28]. As mentioned above, both had
some methodological problems, although a third,
more recent study did report REM sleep changes
as a result of this manipulation [29]. Two of the
non-deprivation recording studies examined dream
content as well [30, 35] and the dream content
reflected learning progress.
For the REMD studies, all seven experiments
using declarative material reported lack of effect on
memory [13, 19–21, 23, 24]. By contrast, seven
REMD studies reported impairment of memory for
procedural material [23] (two experiments), [24,
43–46].
The brain imaging study [52] also supports the
idea of REM sleep being involved with procedural
memory.
Results of the two cueing studies [50, 51] indicated not only that REM sleep is important for
procedural memory, but that the actual phasic component of REM sleep is an important indicator and
possible mechanism for memory processing.
While much remains to be done, there is clearly
a strong relationship between procedural memory
and REM sleep. It is probably premature to decide
which component of REM sleep is most clearly
involved with memory processing. In fact, the facet
of REM sleep that changes following learning may
depend on a number of factors, of which the most
obvious is type of task. By contrast, there would
appear to be no relationship between memory of
simple declarative material and REM sleep.
THE CASE FOR NREM SLEEP AND
MEMORY
Several recording (non-deprivation) studies have
suggested a relationship between NREM sleep or
C. SMITH
stage 3/4 and memory for declarative tasks [16–18,
53]. On the other hand, six studies [13, 19–21, 23,
24] found no effect of NREM deprivation on memory for declarative tasks.
For procedural tasks, Scrima [36] reported that
NREM sleep was better than staying awake for
memory of difficult trigrams. Stickgold et al. [40]
have shown that the amount of NREM in the first
quarter of the night is highly correlated with the
efficient learning of a visual detection task. However,
Karni et al. [46] have reported, using the same visual
detection task, that NREM deprivation did not
impair memory. These results seem contradictory.
If amount of NREM sleep is highly correlated with
the ability to do this task, it seems logical that
NREM deprivation would induce memory deficits
but it does not appear to do so.
This paradoxical situation can be seen in other
studies as well. If NREM sleep is important for
memory processing, it might be expected that subjects exposed to TSD (where both REM and NREM
sleep are deprived) would exhibit even worse performance than selectively REM deprived subjects.
That is, one might expect that the NREM sleep
deprivation would provide a component of the
deficit. In two studies that examined both declarative and procedural material, this was not the
case. In one study [23], individuals learned a complex
logic task. For the logic task, the groups exposed
to TSD and to REMD showed inferior memory to
the NREM awakened and normal sleep groups and
the last two groups did not differ. Thus, not only
was the NREM awakened group not different from
normal controls, the TSD group, exposed to both
REM and NREM sleep deprivation, did not exhibit
a worse performance than participants exposed to
REMD alone. In another study [24], subjects were
asked to learn a variety of declarative and procedural
tasks. Groups included normally rested controls,
REMD (last two REM periods of the night), NREM
awakening and TSD. Again, testing occurred 1 week
later. The three procedural tasks were poorly remembered by the REMD and TSD subjects compared to the other three groups. Yet they were
not different from each other, even though TSD
included deprivation of NREM as well as REM
sleep. As previously noted, the PA and word recognition tasks were not impaired by TSD (which
includes NREM deprivation) or by the NREM
awakenings compared to the normally rested
controls.
SLEEP STATES AND MEMORY PROCESSES IN HUMANS
Stickgold et al. [40] have proposed a two-stage
process based on the visual search task which
requires NREM sleep in the first quadrant and
REM sleep in the last quadrant of the night for
learning efficiency to be maximized. It seems likely
that some factor that accompanies NREM sleep
but which is not disturbed by NREM deprivation,
such as levels of glucocorticoids, is at work Plihal
et al. [90].
The NREM data do not indicate clear differences
according to a declarative–procedural dichotomy
as is found with REM studies. One important variable
seems to be the retest time. Retesting done shortly
(24 h or less) after training in non-deprivation studies [16–18, 53] provides data suggesting a positive
relationship between NREM sleep and memory
while studies with retest several days to 1 week
later do not [12, 23, 24]. Thus a role for NREM
sleep in memory processing is possible, but much
more research needs to be done before that role
is understood.
Interestingly, there is evidence for stage 2 being
involved in the consolidation of a motor procedural
task. Smith and MacNeill [91] have shown that
memory for a pursuit rotor task 1 week after
initial acquisition can be impaired by either stage
2 deprivation or interruption. In very recent work
[73], it has been found that while a motor task
requiring a complex cognitive adjustment (mirror
trace task) is sensitive to REMD, direct tracing
(simple motor procedural) task is sensitive to
stage 2 sleep interruption and not to REMD.
Although more work must be done, it appears
that there is a different mode of processing for
cognitive motor procedural than for simple motor
procedural tasks that may involve different sleep
stages.
501
types of memory). Many of the concepts now being
used by memory theorists have not been examined
using sleep parameters as variables. As an example,
Tulving and Schacter [92] have argued for some
years that priming requires a separate memory
system, yet only one study has ever examined this
type of task in connection with sleep deprivation
[24].
As the nature of new memory systems becomes
clear, their interaction with sleep mechanisms
can be more precisely studied. Experiments on
memory systems using sleep as a variable will
undoubtedly add to the understanding of these
systems. There are already preliminary data (as
mentioned above) that procedural motor memory
may not be a unitary system but can be dissociated
depending on the amount of cognitive involvement
[91].
Future sleep–memory research in humans should
focus on learning tasks that are considered by
memory theorists to utilize functionally distinct
systems. Then, using the combined techniques of
sleep recording or sleep deprivation following task
acquisition, it will be possible to decide if the sleep
state is necessary for memory or simply correlated
with memory processing. As well as sleep recording
and sleep deprivation, the use of other techniques,
such as the PET scan, will provide new insights into
the nature of the sleep–memory relationship. The
study of sleep states in conjunction with memory
processes will allow us to understand further some
of the functions of sleep. On the other hand, the
comprehension of memory systems will not be
complete until its relationship to the states of sleep
is understood.
Practice Points
FUTURE DIRECTIONS
In this paper the assumption has been made that
all of the learning tasks utilized in the sleep–memory
studies were either declarative (and likely explicit)
or procedural (and probably implicit) in nature. In
future, as we learn more about memory systems,
these assumptions will undoubtedly turn out to be
too general. In particular, the term procedural may
not be broad enough to include all the types of
learning that are not declarative (many authors
prefer the term “non-declarative” to describe these
1. Adult patients attempting to do a lot of learning should be warned that the rate at which
they learn procedural material will be reduced
if they are not sleeping well or if their sleep
onset times are frequently changed (e.g. shiftwork).
2. Children often do not sleep long enough or
suffer from poor sleep for various reasons.
Parents should be warned that progress in
school, sports and other activities such as
music may suffer as a result. Improving sleep
quality will improve learning ability.
C. SMITH
502
3. It may be necessary to give patients drugs
such as MAOIs, TCAs or SSRIs which are
known to suppress REM sleep. The patient
should be informed of this REM sleep suppressing effect and how it will likely impact
on them. They should realize that the rate at
which they can acquire complex cognitive
procedural material will be reduced.
4. Patients attempting to refine fine motor movements (sports, musical instruments, etc.)
should be made aware that stage 2 loss or
interruption can lead to slower progress. If
the patient suffers many awakenings in the
night or must get up at such times as to miss
the last hour or so of sleep, progress in
learning skills will be reduced and more training will be required.
5.
6.
7.
Research Agenda
1. The role of partial REM sleep deprivation
following acquisition of procedural material
should be examined more thoroughly. Are
there REM windows?
2. Memory for procedural tasks may be vulnerable to REM sleep loss several days after
the end of acquisition, not just the same day
as acquisition. Thus, real world tasks like
learning a second language would be remembered best when a good sleep night
follows the day of acquisition and also follows
2 days after the day of acquisition.
3. The degree to which school children learn
procedural material should be examined
more closely. Some topics, like mathematics
and physics would have high cognitive procedural content. Second language learning
also has an important procedural component. Timing of presentation of this material with respect to expected subsequent
sleep could result in increased learning efficiency. For example, offering math on Friday, when it is likely that many young children
will stay up beyond normal bedtimes, should
be avoided.
4. The study of the REM dreams of subjects
who have recently learned procedural material may lead to a better understanding of
8.
9.
10.
11.
12.
sleep–memory systems and possibly dream
formation mechanisms.
Cueing is a novel new method of examining
the sleep-memory relationship and many
questions remain, including: 1) how many
cues have to be presented? 2) Why is the
time of presentation at the REM deflection
so important? 3) Is one particular time of
the night important? This research paradigm
could provide interesting information about
the nature of the REM sleep–memory relationship.
Although it is expensive and time consuming,
PET scan technology, combined with sleep
recording could provide invaluable information about the neural mechanisms of
the sleep–memory relationship.
Manipulation of the NREM–REM cycle may
provide us with information about the relationship between sleep parameters and declarative memory and should be further
explored.
An adequate study, including a set of
procedural tasks with retesting at least
several days after acquisition has yet to be
done comparing patients on REM-suppressing medication with normal matched
controls.
Cognitive procedural tasks (not motor procedural) should be used to examine the
relationship between REM sleep and memory.
The nature of the phasic component of REM
sleep (REM sleep densities and number of
REMs) and its relationship to cognitive procedural memory is not clear and should be
systematically examined
Stage 2 sleep loss may well limit the rate at
which people learn and refine motor skills.
This possibility should be examined in real
life situations. This could be particularly important to pre-school and grade-school children, since they are particularly busy with
this type of learning.
Retesting of individuals should take place at
least several days after the end of acquisition
and/or sleep deprivation in order to see that
these effects are of such an enduring nature
that they can be generalized to practical
situations
SLEEP STATES AND MEMORY PROCESSES IN HUMANS
13. Virtually no systematic studies have examined the role of REM sleep displacement
such as occurs in individuals involved in shift
work. Attempts to train individuals on procedural tasks while they are exposed to
changing sleep times may be a very inefficient
method of teaching. If so, such groups as
nurses, interns, police and pilots should not
be asked to learn crucial cognitive procedural
material while doing shift work.
503
15.
16.
17.
18.
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APPENDIX 1.
GLOSSARY OF TERMS
Declarative memory: Memories accessible to
conscious recollection. Declarative memories are
usually explicit in nature.
Procedural memory: Memory for certain ways
of doing things, solving problems or how to make
certain motor movements. Procedural memories
are usually implicit in nature.
Cognitive procedural memory: Memory for certain ways of doing things or solving problems.
Mirror trace task: Requires the participant to
trace between the lines of a double lined figure
with a pencil by watching their hand in a mirror.
Participants cannot see their hand directly and must
try to draw a continuous line around the figure,
staying between the lines. Considered to be a
cognitive procedural task.
Motor procedural memory: Memory of how to
make specific motor movements.
Skill memory: Same as motor procedural.
Explicit learning: The individual is consciously
aware of learning the material required.
Implicit Learning: The individual is not consciously
aware that s/he is learning, but at a later time can
demonstrate that the information was acquired.
Paired associates (PA): A task in which a number
of word pairs are presented, one pair at a time
C. SMITH
during acquisition. The number of training trials can
vary, but the test involves presenting one of the
two words alone. The participant must respond by
giving the other member of the pair from memory.
Priming: A type of memory in which exposure
to a particular stimulus facilitates perception of that
stimulus or related stimuli. Tasks take the form of
simple figures or words which are initially presented.
On retest, fragments or parts of these figures or
words are presented and the participant is able to
recall the material despite its incompleteness.
Anagram: A series of letters that may form a
word. Subjects are asked to rearrange the letters
to form a new word.
Trigram: Three letter consonant groupings that
do not spell actual words. Lists of these trigrams
are presented to participants and after several presentations, the participant is asked to predict the
next trigram s/he would see in the list, based on
the one they are presently observing.
Verbal learning: Tasks requiring subjects to learn
lists of words, or pairs of words (PA) are all considered to be types of verbal learning.
Word fragment completion task: Special case of
priming. Words are presented at training. Then at
the retest only certain letters are presented with
spaces where the other letters should go. Participants are able to “guess” the correct words
(as opposed to other words) because they have
recently been exposed to them during training.