Does sleep promote motor learning? Implications for physical rehabilitation.

Each year, approximately 780,000 people in the United States experience a stroke, (1) with more than half experiencing a persistent loss of function. (2,3) Furthermore, stroke is a leading cause of disability in the United States) Stroke rehabilitation frequently includes learning new motor skills and re-learning old motor skills. As we do not completely understand how to best stimulate recovery of function through motor skill learning after stroke, research examining the mechanisms, procedures, or both that affect motor learning must be explored.

Mounting evidence demonstrates that sleep has an important role in motor learning and memory consolidation in young individuals who are healthy (defined as "neurologically intact" throughout this review) (see review articles (4-10)). Memory consolidation refers to either the stabilization or the enhancement of a motor skill, referred to as off-line learning, through the passage of time without additional practice. (11,12) Although some disagreement remains, (13-17) sleep has been shown to enhance motor performance on a task "off-line" when no further physical practice has taken place. (18-22) Participants who sleep between practice and retention testing demonstrate improvements in task performance compared with participants who stay awake. This has been shown in a variety of simple motor skill tasks. (18-22) Sleep between practice and retention testing has resulted in a 20% overnight improvement in motor skill performance of a finger-tapping task (19) and a 33% overnight improvement in performance of a finger-to-thumb opposition task. (22) A nap of 60 to 90 minutes has been demonstrated to be sufficient sleep to produce offline improvements in performance of motor tasks. (23,24)

The role of sleep in off-line motor skill memory consolidation for young people who are healthy also may depend on other factors, including which stage of memory formation is considered, the type of memory being consolidated, whether instruction is provided (ie, implicit versus explicit learning), and the task. The manner in which sleep-dependent off-line motor learning reconfigures neural circuits and the mechanisms underpinning the need for sleep to consolidate memories are questions currently under consideration. In this article, we will address each of the variables listed above that may affect sleep-dependent off-line learning.

Although sleep has been demonstrated to have an important role in off-line motor learning and memory consolidation in young people who are healthy, evidence suggests that sleep may not be critical for off-line motor learning in older people who are healthy. (25-27) Changes in sleep architecture experienced by older people, (28-31) which may limit the potential benefits of sleep, are one likely explanation for the lack of sleep-related off-line motor learning in this group. Emerging evidence suggests that individuals with brain damage, (32) particularly stroke, (27,33) benefit from sleep to enhance offline motor skill learning. Individuals with damage to the prefrontal cortex demonstrated a reduction of nearly 14% in overnight response time on the serial reaction time (SRT) task. (32) We recently found that people with stroke primarily in the middle cerebral artery distribution demonstrated a 12% overnight reduction in tracking error in an implicit version of a continuous tracking task and a 14% overnight reduction in error in an explicit version of the tracking task. (27) We have proposed that people with chronic stroke may be able to capitalize on sleep architecture changes that occur following stroke (34,35) to experience sleep-dependent skill enhancement. Based on our past and ongoing work, we believe that integration of sleep into clinical interventions may hasten recovery from stroke by allowing individuals to capitalize on sleep-dependent off-line motor learning.

Sleep Overview

Sleep is "defined behaviorally by four criteria: (1) reduced motor activity, (2) decreased response to stimulation, (3) stereotypic postures (in humans, for example, lying down with eyes closed), and (4) relatively easy reversibility (distinguishing it from coma, hibernation, and estivation)." (36(p937)) Sleep generally is classified into 2 different stages: non-rapid eye movement sleep (non-REM) and rapid eye movement (REM) sleep (Tab. 1). Non-REM sleep is divided into 4 characteristic substages corresponding to increasing depth of sleep, as shown using electroencephalograms (EEGs): stage 1 involves the transition from wakefulness to sleep and is characterized by sinusoidal alpha wave activity, stage 2 is characterized by sleep spindles and K complexes (clusters of low- and high-amplitude waves, respectively (36)), and stages 3 and 4 are grouped into slow-wave sleep (SWS) and are characterized by slow delta waves. (36) Rapid eye movement sleep, also known as paradoxical sleep because the EEG pattern is similar to the normal awake pattern, is characterized by REMs, ponto-geniculooccipital spikes, and muscle atonia. (36)

Adults fall asleep by entering non-REM sleep first, followed by REM sleep; these phases then alternate cyclically every 90 to 110 minutes through 4 to 6 cycles a night. (36, 37) The ratio of non-REM to REM sleep changes as the night progresses, with SWS being prevalent in the first haft of the night and stage 2 non-REM and REM sleep dominating in the latter half of the nights

Young adults spend the largest amount of sleep in stage 2 non-REM sleep, followed by REM sleep and SWS, with the least amount of time spent in stage 1 non-REM sleep (Tab. 1). Although a range of values is expected (as demonstrated by the 25th-75th percentile of sleep period time in Table 1 for a 20-year-old and a 60-year-old), aging individuals experience a reduction in total sleep time compared with young adults as well as decreased time spent in REM sleep and SWS, (28,29) whereas the amount of time spent in stage 2 non-REM sleep remains fairly stable (Tab. 1). (28) The decline in REM sleep begins around 50 years of age, (28) whereas the reduction in SWS starts in adolescence and progresses with age. (36) Older adults also experience a reduction in the number of sleep spindles, (30,31) which are bursts of brain activity of 12 to 14 Hz (38,39) occurring predominantly during stage 2 non-REM sleep. Based on the pattern of changes in sleep architecture with aging, we hypothesize that the normal evolution of sleep architecture associated with aging limits the ability of older adults who are healthy to benefit from sleep-dependent off-line motor learning.

Alterations in sleep patterns are a common experience for many people after stroke. Three to four months after the occurrence of stroke, nearly 60% of individuals experience insomnia. (40) Sleep-wake disorders, such as insomnia, excessive daytime sleepiness or fatigue, or hypersomnia, are experienced by 20% to 40% of individuals following stroke and are attributable to a number of factors, including depression, sleep apnea, complications of the stroke, and medications. (41) Following acute stroke, alterations in sleep architecture occur. These changes include a reduction in total sleep time and sleep efficiency as well as an increase in waking after the initiation of sleep. (35,42,43) Reductions in REM sleep (44) and stage 2 to 4 non-REM sleep (42) also have been reported following acute stroke. Although the sleep parameters of people with chronic stroke are poorly characterized, evidence suggests sleep patterns may not normalize with a progression from acute to chronic stroke; 53% of people with chronic stroke (5-24 months poststroke; average age=49 years, range=18-75 years; Tab. 1) showed different sleep EEG characteristics, including more time in stage 2 non-REM sleep while spending about the same amount of time in REM sleep, (34) compared with published norms for a 49-year-old who was healthy. (28) Furthermore, the number of sleep spindles increases from acute to chronic stroke. (35) We propose that these changes in sleep characteristics actually enable people with chronic stroke to benefit from sleep and produce off-line motor skill learning.

Mechanisms Influencing Sleep-Dependent Off-line Motor Learning: Evidence From Young Adults Who Are Healthy

Although sleep has been shown to promote off-line motor skill learning in young people who are healthy, (18-22) it appears that various factors may influence or interact with this beneficial effect of sleep. Each of these variables is discussed in more detail.

Stages of Memory Formation

The role of sleep in motor learning likely depends on which stage of memory processing is being considered. Motor memory develops over time in at least 4 distinct stages (Tab. 2). (45) The first stage is encoding or acquisition, when the memory is initially formed into a representation in the brain. This stage is followed by consolidation, when the memory is taken from a labile form and made more permanent. Walker and colleagues (21,46) further divided Consolidation into 2 different categories: stabilization and enhancement (Tab. 2). Stabilization refers to the maintenance of motor skill performance across time without further practice and is not dependent on sleep, whereas enhancement refers to an improvement in performance of a skill off-line and is thought to be dependent on the activity of sleep. The third step in motor memory processing is storage, when the memory is maintained in the brain over time. The final step is recall, when the motor memory is able to be brought out of storage for further use.

Sleep may differentially affect each stage of motor memory processing, although consolidation appears to be the most frequently studied stage and may be the stage most affected by sleep. The permissive environment created during sleep allows the memory trace initially encoded during practice to be consolidated into a more-permanent form. This consolidated memory trace is thought to be fairly stable across time until recalled from memory during subsequent task practice. Following recollection, the motor memory is capable of being modified and is believed to undergo another period of consolidation (called "reconsolidation") for that memory to again be placed into more-permanent storage. Reconsolidation also may be a sleep-dependent process, but more research is needed on this topic. (10,47,48)

Types of Memory

The role of sleep in memory consolidation is thought to depend on the type of memory being considered. Typically, a memory is divided into 1 of 2 classifications: declarative memory, if the memory can be recalled consciously, such as memories of facts and events, and nondeclarative memory, if the memory cannot be recalled consciously, such as a memory of skill performance (ie, riding a bicycle). (49,50) Procedural memory is a subset of nondeclarative memory and is assessed through the testing of motor skills. (49) Declarative and procedural memories differ not only in the ability to consciously recall the memory but also in the brain areas involved supporting these memories. Declarative learning and memory depend on the integrity of the medial temporal lobe, (51,52) whereas procedural learning and memory are supported by more-distributed neural circuits, including the sensorimotor cortex, the cerebellum, and the basal ganglia. (53-55) Due to the distributed brain areas supporting procedural memory, it is much less likely that brain damage, such as stroke, would completely abolish procedural learning.

There is some agreement among researchers concerning which stage of sleep is important for the consolidation of a certain memory types; however, several discrepancies persist. Two different theories explain the role of the various sleep stages on the consolidation of different memory traces. These are the dual-process theory and the sequential hypothesis, with recent studies (56,57) showing increased support for the latter. According to the dual-process theory, a single sleep stage (ie, REM sleep or SWS) acts on and, therefore, is necessary to form distinct memory traces (ie, procedural versus declarative), depending on which memory system that trace is from. (6) According to the sequential hypothesis, memories are consolidated through the ordered sequence of non-REM sleep followed by REM sleep, so that both stages of sleep are necessary for consolidation. (58) In reality, these 2 theories are not mutually exclusive in that both non-REM and REM sleep stages are important for memory consolidation, but some memory traces may require more SWS (ie, declarative memory), whereas other memory traces may require more stage 2 non-REM or REM sleep (ie, procedural memory). (6)

Although some conflict remains, current consensus indicates that SWS is important for declarative memory consolidation. For example, declarative memory of word list recall (59,60) was facilitated by periods of early nocturnal sleep, which corresponds to SWS. Other research demonstrates that REM sleep is important for consolidating declarative memories, such as for the learning of a foreign language. (61) The discrepancy of which stage of sleep is important for the consolidation of declarative memory may result from differences in the type of memory being formed. Episodic memory (memory of events) and semantic memory (memory of facts), both types of declarative memory, appear to require different stages of sleep for consolidation; semantic memory may require REM sleep to consolidate, whereas episodic memory may require anywhere from one to all stages of sleep. (6) Wagner et al (62) suggested that REM sleep is important for the consolidation of declarative memory that has an emotional content, but emotionally neutral declarative memory does not seemingly benefit significantly from sleep.

Procedural memory likely requires stage 2 non-REM sleep, (59,60,63,64) REM sleep, (59,60,65) or both for consolidation. Overnight improvement in the performance of a finger-tapping task was found to correlate with the amount of stage 2 non-REM sleep, (19) whereas overnight improvement in a similar sequential finger-to-thumb opposition task correlated with the amount of REM sleep. (22) Another factor to consider is the cognitive requirement of the skill being learned, with less cognitively taxing procedural skills benefiting from stage 2 non-REM sleep and more cognitively involved procedural tasks benefiting from REM sleep for consolidation. (66) Another interesting caveat in the determination of which stage of sleep is important for procedural memory consolidation is the initial skill level of the learner; REM sleep is important when the motor skill to be learned is entirely novel, whereas stage 2 non-REM sleep is beneficial for learning if some degree of ability is already present and the motor skill is being refined. (67)

Another explanation for discrepancies regarding which sleep cycle is important for consolidation of particular types of memories centers on the need for an ordered sleep cycle (sequential hypothesis (58)). Stickgold et al (56) and Gais et al (57) demonstrated that performance of a visual discrimination task was enhanced following the ordered sequence of SWS followed by REM sleep. These behavioral data provide support for the sequential hypothesis of ordered non-REM sleep followed by REM sleep to stimulate memory consolidation.

In summary, memories are likely consolidated through the repeated pattern of non-REM sleep followed by REM sleep, with SWS being more important for declarative memory consolidation and stage 2 non-REM sleep, REM sleep, or both being more important for procedural memory consolidation. However, many other variables such as the emotional content of the memory, the cognitive load of the task, and the initial skill level of the learner appear to affect which stage of sleep is critical for declarative and procedural memory consolidation. Future studies should seek to clarify the role of the various sleep stages in procedural and declarative memory consolidation.

Type of Instruction

Another factor to consider when examining the role of sleep in off-line procedural motor learning and memory consolidation is the type of instruction a person receives prior to practicing a skill. Explicit learning occurs when the individual is aware of the regularities of the skill being learned. Explicit instruction can be provided prior to task practice (ie, when a therapist informs a patient of the steps required to stand up from a chair), or a patient can gain explicit awareness during physical task practice (ie, when the patient becomes consciously aware of the steps needed to stand up from a chair through practice without instruction). Implicit learning occurs without the awareness of the task regularities (ie, the patient "figures out" how to stand up from a chair without being consciously aware of each of the steps involved).

When the influence of sleep is not considered, explicit instruction either may aid (68-70) or may inhibit (71-73) procedural learning in people who are healthy, depending on the nature of the instruction (74,75) and the task. (71,76) The type of instruction delivered to young people who are healthy appears to influence whether off-line motor learning is related to sleep or simply the passage of time. In a study by Robertson et al, (77) young participants who were healthy and who practiced a sequential motor task implicitly (ie, had no awareness of the sequence being practiced) demonstrated performance improvements both following sleep and after a similar length of time being awake. In contrast, if participants were provided explicit instruction regarding the practiced sequence, off-line motor skill enhancement occurred only following a period of sleep. These findings indicate that for young people who are healthy, implicit motor memory consolidation occurs off-line simply with the passage of time (whether or not this time includes sleep), whereas explicit motor memory consolidation occurs off-line only during sleep. (77) Concurrent evidence supports the hypothesis that explicit memories and awareness are preferentially enhanced off-line during sleep. (78-80)

It is possible that the implicit and explicit memory systems interact or compete with one another during learning and memory consolidation. In a study by Wagner et al, (81) participants who slept between practicing a sequence and undergoing retention testing demonstrated an improved ability to detect a hidden rule compared with participants who did not sleep during the intervening interval. However, sleep resulted in a significant decrease in reaction time only in those participants who did not discover the hidden rule. These findings suggest that explicit memory is enhanced at the expense of implicit memory for this particular task, (82) which would support the theory that different memory systems interact during formation. (83)

It is possible that off-line implicit motor skill learning appears to be time-dependent because sleep enhances only certain aspects of an implicit motor task (ie, motor, spatial, or temporal parameters), which may be masked when overall off-line skill learning is considered. Evidence, however, does support this contention. Off-line enhancement of the spatial regularities of an implicit motor task were shown to be dependent on sleep following practice, whereas learning of the motor pattern was enhanced off-line through the passage of time without sleep. (84) These findings demonstrate that particular components of an implicit motor memory may be enhanced off-line through different mechanisms; some components may require sleep for off-line enhancement, whereas other components simply rely on the passage of time. (85)

In summary, mounting evidence demonstrates that explicit learning and memory are enhanced off-line by sleep. Discrepancies persist regarding whether sleep or the passage of time produces off-line consolidation of an implicit motor task. However, the lack of apparent sleep-dependent off-line learning of implicit motor tasks may be due to the fact that only certain components of an implicit motor skill are enhanced by sleep, and the enhancement of certain components may be masked by a lack of overall task improvement.

Type of Task

The beneficial effect of sleep on motor learning and memory consolidation also may be reliant on the type of procedural task being considered. Two important classifications for motor tasks are discrete and continuous skills. Discrete skills are movements with an obvious beginning and end, such as throwing a ball or reaching for a cup, whereas continuous skills, such as walking or knitting, do not have an obvious start or finish. (86) Although the distinction between discrete and continuous tasks is useful to classify research tasks, these classifications frequently are less defined in the clinic, where more-complicated, "real-life" tasks are utilized. Studies to date examining the influence of sleep in off-line motor performance enhancement in young people who are healthy have used only discrete tasks during practice, including a finger-to-thumb opposition task, (19-22,78,87) a sequential finger-tapping task, (77,86,88,89) and the SRT task. (70,71,90-92) Recent evidence demonstrates that although sleep enhances performance of a number of simple discrete tasks, sleep may not benefit all kinds of discrete tasks; a probabilistic version of the SRT task was not enhanced off-line by a night of sleep. (93)

Due to the variations in task requirements, continuous and discrete tasks utilize different mechanisms of motor control. Because discrete tasks often are performed rapidly and without time for feedback, these types of skills likely rely on a motor program, whereas continuous tasks, which are performed for a longer period of time, likely depend on feedback to make corrective movements as necessary online. (86) Furthermore, continuous tasks often are more complex than discrete tasks. A review by Wuff and Shea (94) concluded that the factors influencing learning of simple motor skills do not automatically apply to complex motor skill learning due to the additional degrees of freedom. Therefore, although evidence strongly supports sleep-dependent off-line learning of discrete tasks, it remains to be determined whether the beneficial influence of sleep on off-line skill enhancement will generalize to a continuous task in young people who are healthy. One study demonstrated that more-complex motor tasks produced greater sleep-dependent off-line motor learning. (95) Perhaps "real-life" complex motor tasks, such as those conducted during rehabilitation following brain injury, may benefit even more from sleep to produce off-line motor skill enhancement. This supposition remains to be determined by future research.

Neuroimaging and Sleep-Dependent Off-line Learning

Neuroimaging techniques have determined that the same areas of the brain activated during acquisition of a motor skill are reactivated during REM sleep. (96,97) Reactivation during sleep may lead to changes in functional couplings of neural circuits and the modification of synaptic connections that were established during acquisition of the motor skill, both of which may lead to sleep-dependent off-line learning. (97,98) However, none of these studies examined whether reactivation occurred during non-REM sleep, leaving it unclear whether the pattern of REM sleep followed by non-REM sleep works to shift brain activity. Functional magnetic resonance imaging has been used to elucidate changes in the representation of motor memory following sleep in young people who are healthy, with certain areas of the brain demonstrating increased activity following sleep and other areas demonstrating reduced activity. (87,99) These studies provide insight into the widespread changes in brain activity associated with off-line sleep-dependent motor memory consolidation in young adults who are healthy.

Neural Mechanisms of Sleep-Dependent Memory Consolidation

Sleep is thought to provide a permissive environment that promotes various cellular and molecular mechanisms that enable the consolidation of memories. The various mechanisms include activity of neuroendocrine molecules, gene transcription, and protein synthesis. (47,100,101) An increase in acetylcholine and a decrease in serotonin during REM sleep in rodents have been shown to facilitate protein synthesis and long-term potentiation (LTP) in the hippocampus. (102)

Furthermore, the unique electrophysiological events of both REM sleep (ie, ponto-geniculo-occipital spikes) and non-REM sleep (ie, sleep spindles) are thought to play a role in long-term synaptic potentiation. (5,101) In particular, sleep spindles, which are characteristic of stage-2 non-REM sleep, have been demonstrated to play an important role in sleep-dependent memory improvement. (23,66,103) Sleep spindles are hypothesized to depolarize the postsynaptic membrane, resulting in a large influx of calcium ions that leads to a cascade of cellular events; these events result in gene expression and protein synthesis necessary for LTP of the postsynaptic membrane. (46,101)

The "replaying" of a memory during sleep is thought to result in a functional coupling of the synapses, leading to LTP of the neural circuit responsible for that memory trace. Ribeiro and Nicolelis (104) proposed that reactivation of the neural circuits associated with a memory trace occurs during SWS, whereas the expression of genes necessary for remodeling of the circuit, and thus memory storage, occurs during REM sleep. The "synaptic homeostasis hypothesis" (105) proposes a very different role for SWS. This hypothesis suggests that the purpose of SWS is to downscale the synaptic connections formed during awake learning, making neural connections more efficient.

Studies using in vivo recordings of neural activity frequently are conducted in animals because of obvious limitations in the ability to conduct these studies in humans. Furthermore, many animal studies examining the role of sleep or sleep deprivation in learning utilize "hippocampus-dependent" learning paradigms in rats; these learning paradigms may be very different from procedural learning in humans, which is not thought to rely on the integrity of the hippocampus. Therefore, although the animal studies provide very important insight into the cellular and molecular underpinnings of sleep-dependent memory consolidation, there currently is a void between the physiological findings from the animal studies and the behavioral findings in humans. (106)

Sleep-Dependent Off-line Learning in Older Adults Who Are Healthy

The majority of studies to date examining sleep-dependent off-line performance enhancement have been conducted using young people who are healthy. Furthermore, the variables affecting the beneficial role of sleep (ie, the type of instruction provided) have largely been examined with young participants who are healthy. In recent years, emerging work demonstrates that older people who are healthy do not benefit from sleep to enhance motor learning. Older adults failed to demonstrate sleep-dependent off-line enhancement of both explicit and implicit versions of a procedural sequence learning task, (25) a declarative memory word-pair association task, (26) or explicit and implicit versions of a continuous tracking task. (27,33) We examined whether specific components of movement on a continuous tracking task (ie, spatial component, temporal component, or both) were differentially enhanced by sleep but perhaps masked by an overall lack of off-line performance enhancement. However, this does not appear to be the case; in our work, older people who were healthy failed to demonstrate off-line sleep-dependent improvements of either spatial tracking accuracy (Fig. 1A) or time lag of tracking (a measure of temporal accuracy; Fig. 1B) of a continuous tracking task. (107) Therefore, older adults who are healthy fail to benefit from sleep to promote off-line memory enhancement, regardless of the type of memory examined (procedural or declarative), the type of instruction provided (implicit or explicit), or the type of task utilized (discrete SRT task or continuous tracking task).

We propose that the changes in sleep architecture often demonstrated by older individuals limit the potential benefits of sleep. With normal aging, people typically experience a reduction in the total time spent in a sleep state as well as a reduction in the time spent in REM sleep and SWS, (28,29) whereas time spent in stage 2 non-REM sleep appears to remain consistent (Tab. 1). (28) Older individuals also frequently experience a reduction in the number of sleep spindles. (30,31) Evidence suggests that stage 2 non-REM sleep, (19) REM sleep, (22) or both are associated with consolidation of simple motor tasks off-line for young people who are healthy. In particular, sleep spindles, which are a characteristic component of stage 2 non-REM sleep, are thought to be an important mechanism of sleep-dependent off-line memory improvement. (23,66,103) We hypothesize that older adults fail to demonstrate sleep-dependent off-line motor learning because they experience a reduction in both the time spent in REM sleep and the number of sleep spindles.

[FIGURE 1 OMITTED]

If the hypothesis that older adults who are healthy do not demonstrate sleep-dependent off-line motor learning due to changes in their sleep characteristics is correct, it would follow that altering the sleep characteristics of older adults may enable these individuals to benefit from sleep to enhance off-line motor learning; indeed, this has been demonstrated to be true. Increased time spent in REM sleep, greater REM density, and decreased REM latency through the use of sleep-aid medication were correlated with enhanced performance of older adults on a word-recall task. (108) If REM sleep is important for promoting off-line motor learning, as suggested by the findings of Fischer and colleagues' study of young people who were healthy, (22) the findings of the study by Schredl et al (108) suggest that older individuals may benefit from sleep to enhance off-line learning if underlying changes in sleep architecture are addressed. No apparent attempts were made by Schredl et al to relate other sleep stages or characteristics such as stage 2 non-REM sleep or sleep spindle activity with performance improvement; therefore, potential benefits of modifying these sleep parameters in older adults via medication or other means remain to be determined.

Sleep-Dependent Off-line Learning After Stroke

There is little doubt that individuals following stroke are able to learn new motor skills. (109-113) People were able to learn an implicit motor skill following a lesion in the middle cerebral artery distribution affecting the sensorimotor cortex (69) and the basal ganglia, (70) but providing them with explicit instruction disrupted implicit learning. However, the role of sleep in off-line motor learning or the sleep characteristics of study participants had never been directly considered until recently. (27,33,107)

Emerging evidence has demonstrated that people with brain injury benefit from sleep to enhance off-line motor learning. In a recent study by Gomez Beldarrain et al, (32) individuals with damage to the prefrontal cortex due to stroke, tumor, or trauma demonstrated sleep-dependent off-line learning of a finger sequencing task. Our research suggests that people with chronic stroke benefit from sleep to enhance motor skill learning of both implicit and explicit versions of a continuous tracking task. (27,33) We also have demonstrated that sleep promotes off-line motor learning through both improved spatial tracking accuracy (Fig. 2A) and anticipation of upcoming movements (a measure of temporal tracking error; Fig. 2B) in people with chronic stroke. (107) Therefore, the few studies to date examining the importance of sleep in promoting off-line motor skill learning suggest that individuals with damage to the brain benefit from sleep to enhance off-line learning of both discrete motor tasks (32) and continuous motor tasks, (27,33) regardless of type of instruction provided (ie, sleep enhanced both implicit and explicit versions of a continuous tracking task), (27,33) and learning of both the spatial and temporal components of a tracking task. (107)

Because the studies that demonstrate sleep-dependent off-line motor learning in people with chronic stroke were not conducted in a sleep laboratory, we can only hypothesize what mechanisms enabled these individuals to benefit from sleep. One hypothesis is that individuals with stroke are able to capitalize on changes in sleep architecture that occur following chronic stroke to promote off-line motor learning (Tab. 1). However, little is known regarding sleep architecture in people with chronic stroke. One study (34) demonstrated that more than half of the participants with chronic stroke experienced alterations in sleep architecture compared with normative data. (28) Individuals with chronic stroke spent about the same amount of time in REM sleep but more time in stage 2 non-REM sleep (34) compared with published norms. (28) Furthermore, the number of sleep spindles increases from acute to chronic stroke. (35) We propose that the alterations in sleep architecture demonstrated by people with chronic stroke (the ability to maintain adequate amounts of REM sleep, increase stage 2 non-REM sleep, (34) and increase sleep spindle activity (35)) enables them to demonstrate sleep-dependent skill enhancement. Much work utilizing sleep laboratories is needed to evaluate EEG data and better understand the potential alterations in sleep architecture demonstrated by individuals with chronic stroke to support our suppositions.

Another potential explanation for why people with chronic stroke demonstrate sleep-dependent offline motor skill learning is that study participants performed the tracking task using their less-affected upper extremity. (27,33,107) Using the less-affected upper extremity would correspond primarily with neuronal activity in the nonlesioned hemisphere of the brain. Studies using transcranial magnetic stimulation demonstrated that transcollosal inhibition present in a healthy brain is reduced following stroke, (114,115) which can result in hyperexcitability of the nonlesioned hemisphere. (116,117) This, we hypothesize, may create a permissive environment for sleep-dependent off-line memory consolidation in the stroke-damaged brain. Future work is needed to confirm this contention. Regardless of the mechanism, it appears that people after a stroke benefit from sleep-dependent off-line motor learning to further enhance skill acquisition. This offers a promising and novel opportunity that may be exploited by rehabilitation specialists to speed or enhance recovery of function after stroke.

[FIGURE 2 OMITTED]

Studies demonstrating sleep-dependent off-line motor learning in individuals with chronic stroke who used their less-affected upper extremity to perform the task raise the following question: Would sleep-dependent off-line motor learning be observed if the more-affected upper extremity is used for practice? At this point, it is unclear whether altered hemispheric excitability affects the patterns of sleep or its effect on motor learning. Because motor practice increases hemispheric excitability, (118,119) it may be that the effects of motor practice would prepare the lesioned hemisphere to benefit from sleep. Alternately, because studies using transcranial magnetic stimulation have demonstrated that stroke increases the threshold for motor excitability in the lesioned hemisphere, (120-125) it is possible that the benefits of sleep would be negated by the high motor threshold. These 2 competing theories should be addressed in future studies.

Clinical Applications

Because stroke is a leading cause of long-term adult disability in the United States and Canada, it is imperative that any factor that could potentially improve recovery and enhance function for this group of people should be explored. In addition, because of the large number of people with stroke who have sleep alterations, understanding the role of sleep in off-line motor learning and memory consolidation in the damaged brain has tremendous implications for rehabilitation.

Evidence to date suggests that people with chronic stroke demonstrate sleep-dependent off-line motor learning of both implicit and explicit versions of a continuous sequencing task. (27,33) Furthermore, sleep enhances both spatial and temporal movement components of a continuous tracking task after stroke. (107) This effect is unique to stroke; age- and sex-matched controls who were healthy did not experience sleep- or time-dependent off-line motor learning on either version of the tracking task and did not show off-line learning of the spatial or temporal movement components of the task. (27,33,107)

To exploit these findings for the benefit of individuals with stroke, sleep should be encouraged between therapy sessions to promote off-line learning of the skill practiced during therapy. Therapy may need to be conducted later in the day or in the evening prior to sleeping, or a nap following a therapy session may need to be encouraged. Furthermore, adequate sleep following stroke may need to be ensured by providing a quiet environment to sleep while in the hospital, reducing sleep disturbances and addressing potential sleep-limiting conditions that frequently occur following stroke, such as sleep apnea, depression, and medication side effects.

The findings that sleep enhances offline learning of a continuous tracking task following chronic stroke (27,33) provide the first evidence that sleep affects off-line learning of a continuous task; until recently, only the role of sleep in discrete tasks had been considered. These findings have important clinical implications, considering many of the movements performed during daily life and activities being learned or re-learned following stroke include movements that are continuous in nature, such as walking.

Evidence that sleep enhances both the spatial and temporal components of a movement following chronic stroke (107) suggests that therapists should incorporate activities that practice both of these components with these individuals. For example, practicing placing a cup on a cupboard of differing heights would emphasize the spatial component of this arm reaching task, whereas practicing the task in various sequences (ie, taking the cup out of the dishwasher and placing it on the cupboard versus washing the cup, drying the cup, and then placing it on the cupboard) would allow patients to anticipate the upcoming cup placing to emphasize the temporal component of the task.

Although recent studies have demonstrated sleep-dependent off-line motor learning following damage to the brain, (32) including chronic stroke, (27,33,107) many questions remain unanswered. Future studies should assess whether these findings will generalize to a clinically relevant activity, such as walking or bed mobility. Research is needed to determine the neural mechanisms that allow individuals following stroke to benefit from sleep to promote offline motor learning. Additional evidence is needed to determine why older adults who are healthy fail to demonstrate sleep-dependent off-line motor learning and whether normalizing sleep parameters through mechanisms such as medications can induce sleep-dependent skill enhancement. Despite these unanswered questions, therapists should consider encouraging sleep following therapy sessions as well as promoting healthy sleep in their patients with chronic stroke to promote off-line motor learning of the skills practiced during rehabilitation.

Both authors provided concept/idea/research design, writing, data collection, data analysis, project management, fund procurement, subjects, and facilities/equipment. Dr Boyd provided institutional liaisons, clerical/secretarial support, and consultation (including review of manuscript before submission).

This work was supported by funds awarded to Dr Siengsukon from the Foundation for Physical Therapy and funds awarded to Dr Boyd from the North Growth Foundation, the Vancouver Coastal Health Research Institute and Foundation, and the Heart and Stroke Foundation of British Columbia.

This article was submitted October 1, 2008, and was accepted December 29, 2008.

DOI: 10.2522/ptj.20080310

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CF Siengsukon, PT, PhD, is Research Assistant Professor, Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, 3901 Rainbow Blvd, Mail Stop 2002, Kansas City, KS 66160 (USA). Address all correspondence to Dr Siengsukon at: csiengsukon@ kumc.edu.

LA Boyd, PT, PhD, is Assistant Professor and Canada Research Chair, University of British Columbia, Vancouver, British Columbia, Canada.

Table 1.
Summary of Sleep Stages

                                                 Characteristic
                            Characteristic        Waveform From
    Type of Sleep              Activity        Electroencephalograms

Rapid eye movement          Muscle atonia;      Low-voltage,
                              rapid eye           mixed-frequency
                              movements           pattern;
                                                  ponto-geniculo-
                                                  occipital spikes
Non-rapid eye movement

  Stage 1                     Slow rolling      Sinusoidal alpha
                              of eyes             wave activity
                                                  (10 Hz)

  Stage 2                                       Sleep spindles
                                                  (12-14 Hz) and K
                                                  complexes

  Slow-wave sleep                               High-amplitude slow
    (stages 3 and 4)                              delta waves
                                                  (0.5-2 Hz)

                                    Time Spent (a) (%)

                             Young      Older       People
    Type of Sleep           Adults     Adults     With Stroke

Rapid eye movement           17-23      13-20         17

Non-rapid eye movement
  Stage 1                     3-7        7-12         13

  Stage 2                    45-55      39-55         61

  Slow-wave sleep            19-25       5-16          5
  (stages 3 and 4)

(a) 25th-75th percentiles of sleep period times for 20-year-olds
(young adults) and 60-year-olds (older adults) were derived from
Danker-Hopfe et al. (28) Average total sleep times for participants
with chronic stroke (average age=49 years, range=18-75) were derived
from Vock et al. (34)

Table 2.
Stages of Memory Formation

Stage of Memory              Description
   Formation

Encoding             Memory representation formed

Consolidation        Memory becomes more permanent

  Stabilization      Maintenance of motor skill
                       performance off-line;
                       not dependent on sleep

  Enhancement        Improvement in performance
                       of a skill off-line;
                       sleep dependent

Storage              Maintenance of memory over time

Recall               Memory brought out of storage for use