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articles
Early sleep triggers memory for
early visual discrimination skills
Steffen Gais, Werner Plihal, Ullrich Wagner and Jan Born Clinical Neuroendocrinology, Medical University of Lübeck, Ratzeburger Allee 160/Hs 23a, 23538, Lübeck, Germany Correspondence should be addressed to J.B. (born@kfg.mu-luebeck.de) Improvement after practicing visual texture discrimination does not occur until several hours after
practice has ended. We show that this improvement strongly depends on sleep. To specify the
process responsible for sleep-related improvement, we compared the effects of ‘early’ and ‘late’
sleep, dominated respectively by slow-wave and rapid eye movement (REM) sleep. Discrimination
skills significantly improved over early sleep, improved even more over a whole night’s sleep, but did
not improve after late sleep alone. These findings suggest that procedural memory formation is
prompted by slow-wave sleep-related processes. Late REM sleep may promote memory formation at
a second stage, only after periods of early sleep have occurred.
osci.nature
The consolidation of memories, a concept introduced a century retrieval testing, thus making it difficult to make straightforward ago1, is particularly supported by processes occurring during conclusions about the consolidation process22,23. To avoid these sleep. The earliest studies on this topic2,3 and later animal and problems, we dissociated functions of REM sleep and SWS for • http://neur
human studies4–6 provide considerable evidence that sleep helps visual procedural memory by splitting the night into two halves9.
to consolidate memories. Spatiotemporal patterns of neuronal In humans, the first half of sleep is normally dominated by peri- activity are replayed in the rat hippocampus during periods of ods of SWS, and there is little REM sleep. During late sleep, this slow-wave sleep (SWS) following learning. This replay has been pattern reverses. If REM sleep is essential for consolidation of linked to consolidation of declarative types of (spatial) memory discrimination skills, consolidation should be strengthened from occurring during this sleep stage7,8. Consistent with these find- a retention period encompassing predominantly REM sleep, ings, human memory for word pairs and spatial locations bene- rather than SWS, and vice versa. Accordingly, learning of texture fits significantly more from early sleep dominated by extended discrimination skills was compared after nocturnal retention SWS than from late sleep where REM sleep prevails9–11. Where- periods of either early or late sleep. In control conditions, sub- 2000 Nature America Inc.
as these observations pertain to a declarative type of memory jects remained awake throughout corresponding retention peri- that relies mainly on the integrity of the hippocampus and adja- ods. Improvement in texture discrimination was measured by cent temporal lobe structures, attention has only recently been comparing the minimum presentation time (stimulus to mask focused on non-declarative, procedural types of memory10–13.
onset asynchrony, SOA) necessary to discriminate orientation of Procedural knowledge refers to implicit (or pre-attentive) learn- a target feature, before and after the retention period.
ing of ‘habits’ or ‘how to’ memories by practicing sensory andmotor skills, respectively14. Unlike the declarative memory sys- tem, procedural memory does not necessarily involve hip- Sleep data confirmed that SWS dominated early sleep and REM pocampal functions but, depending on the type of task, relies on sleep dominated late sleep (Table 1). During initial learning
various neocortical and subcortical structures15,16.
before sleep, texture discrimination performance did not differ The performance improvement for a basic texture discrimi- between the early and late conditions (122 ± 6.7 ms versus nation task takes place in assemblies of neurons active at a very 120 ± 6.3 ms, p > 0.7). Subjects were retested after sleep, and early pre-attentive stage of visual processing17. Substantial their discrimination skills improved only after early sleep. Dur- improvement in perceptual performance of this task occurs eight ing late sleep and during both early and late wake intervals, dis- or more hours after it has ended, rather than during or immedi- crimination performance even decreased, that is, threshold SOA ately after practice; this finding indicates a slow, latent process of increased (Fig. 1a). This pattern was statistically confirmed by
learning18. Sleeping during the retention interval seems to be overall ANOVA with two within-group factors—threshold SOA particularly important for improvement19. Selective disruption before versus after the retention interval, and early versus late of REM sleep blocks overnight enhancement of the perceptual retention interval—and one between-group factor, sleep versus skill, whereas SWS disruption has no effect on enhancement12.
wake (F1,25 = 7.23, p < 0.02 for before/after × sleep/wake inter- These results led to the conclusion that the consolidation of tex- action; F1,25 = 9.74, p < 0.01 for main effect of before/after). Sep- ture discrimination, that is, enhancing the neural pathways arate analysis of the early and late conditions revealed this involved in this task and thereby improving task performance, is interaction to be significant for the early condition (F1,13 = 9.73, a process strongly dependent on REM sleep.
p < 0.01). Performance improvement, as measured by the However, the REM sleep deprivation protocol has been cri- decrease in threshold SOA, was significant after early sleep tiqued20,21 because it induces distinct emotional and cognitive (t7 = 2.33, p < 0.05), whereas wake controls showed an oppos- disturbances that interfere with task performance at the time of ing tendency toward increasing thresholds across the early reten- nature neuroscience • volume 3 no 12 • december 2000
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articles
tion interval (t6 = –2.22, p < 0.10). For Table 1. Sleep stages by experimental condition.
Early sleep
Late sleep
t
interval in both the sleep and wakegroups, we found a significant main p < 0.02). Separate analysis of sleep nificant before/after × early/late inter- Time (in minutes, and in percent of total sleep time; mean ± s.e.m.) spent in each sleep stage during early and action (F1,13 = 8.20, p < 0.02) for late sleep. Right column, results for pairwise statistical analysis by t-test. *p < 0.001.
sleeping subjects and a significantmain effect of before/after(F1,12 = 10.39, p < 0.01) for the wake control group, thus con- mance on the well-learned task at 2200 hours, 0300 hours and firming a selective improvement in discrimination skills after the 0800 hours was compared to performance on a task with a new early retention sleep, and a decrease in performance especially target location, which differed at each test. The subjects’ perfor- mance was comparable for all three times of testing, for familiar In a supplementary study, we examined the improvement in stimuli (82 ± 14 ms, 79 ± 10 ms and 86 ± 17 ms respectively) and texture discrimination after a 12-hour retention interval, which for novel stimuli (122 ± 26 ms, 120 ± 23 ms and 134 ± 23 ms), either was at night and contained an 8-hour period of sleep, or excluding essential effects of circadian rhythm on discrimination was during the day and did not contain a period of sleep. As skills (p > 0.50 for all comparisons). Performance on familiar expected from previous studies18, the threshold SOA in this stimuli was better than performance on novel stimuli (p < 0.001 experiment decreased from 130 ± 14.3 ms before sleep to 105 ± 12.1 ms after sleep (t5 = 6.07, p < 0.001) in those subjects osci.nature
tested over a night retention interval. However, subjects’ perfor- DISCUSSION
mance did not improve during the day retention interval of equal Data from the main study showed that texture discrimination skills length (141 ± 10.9 ms before versus 143 ± 13.4 ms after, during the night improved only if the retention interval contained t5 = –0.337, p > 0.7). In addition, the improvement in discrimi- SWS-dominated early sleep; during late sleep alone, threshold SOA • http://neur
nation skill during the full period of nocturnal sleep was com- even increased. Texture discrimination skills also deteriorated when pared with that observed in the main experiment during a period subjects were kept awake during the retention phase (main effect of early sleep alone. Whereas task performance before sleep was across wake conditions). This pattern cannot be explained by cir- comparable for both of these conditions (130 ± 14.3 ms versus cadian rhythms because discrimination skills improved when sub- 122 ± 6.7 ms, p > 0.5), the improvement during the entire night jects slept during the early retention interval but did not improve was about three times greater than the improvement during early when they were kept awake during this time. In addition, circadi- sleep alone (t12 = –3.23, p < 0.01; Fig. 1b).
an rhythms did not influence performance on a well-learned or A second supplementary study focused on the possible influ- novel discrimination task. Because the wake control group was ences of circadian rhythm on discrimination performance, and deprived of sleep, their fatigue at retrieval testing may have 2000 Nature America Inc.
tested subjects on a well-learned task. As expected, discrimina- impaired texture discrimination performance. However, if the tion task training led to an asymptotic reduction in threshold improvement in texture discrimination was only due to sleep before SOA (first session, 115 ± 7 ms; tenth session, 85 ± 6 ms). Perfor- retrieval testing, improvement should also have occurred after late Fig. 1. Improvements in visual discrimination skill. (a) Difference in threshold SOA between learning and retrieval testing, after retention intervals
during the early or late half of the night (mean ± s.e.m.). Subjects either slept for three hours during the retention interval, or were kept awake
throughout the time interval. Asterisk, p < 0.05, for difference between conditions. Threshold SOA decreased only across the early sleep retention
condition. †, p < 0.05, for a comparison with learning performance before the retention interval. (b) Difference in threshold SOA between learning
and retrieval testing after the early sleep retention interval (white bar), the 12-hour retention intervals of a whole night’s sleep (black bar), and the
awake daytime period (gray bar). Larger improvement in visual discrimination was observed after a whole night’s sleep, than after a period of early
sleep alone. **p < 0.01 for dif-
ference between conditions.
††p < 0.01 for a comparison
with learning performance
before the retention interval.
(c) Individual performance
curves for two subjects tested
on the early sleep condition
(circles) and late sleep condi-
tion (triangles). Filled symbols,
performance at initial learning
before sleep; open symbols,
performance at retrieval test-
ing after sleep. Horizontal line,
80% correct responses.
Threshold SOA is the point
where performance curves
cross the horizontal line.
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Fig. 2. Experimental protocol. Schedule (a) for the ‘early’ and ‘late’ sleep condition and (b) for the ‘early’ and ‘late’ wake control condition. Blank
fields, times when subjects were awake; gray fields, intervals of sleep; black fields, time of texture discrimination task.
sleep. Moreover, initial task performance was very similar before Comparable amounts of time were spent in REM sleep during early and late retention intervals, which argues against any con- the REM sleep deprivation condition of that study (19 ± 6 min) siderable influence of fatigue or circadian variation.
and the early sleep condition of our study (24.3 ± 4.1 min). The osci.nature
The finding that performance improved only after early sleep amounts of time spent in SWS during the SWS deprivation com- suggests that processes related to this period of sleep facilitate con- ponent of the previous study (30 ± 12 min) and during the late solidation of these procedural skills. The predominance of SWS sleep condition of our study (31.6 ± 4.1 min) were also compa- and associated cortical changes in excitability24 and transmitter rable. However, the REM sleep deprivation protocol of the pre- • http://neur
turnover25 may be an essential prerequisite for this facilitation.
vious study differed from our approach, in that this stage was Besides SWS dominance, early sleep is also characterized by var- disrupted after the REM sleep process was initiated. REM sleep ious neurohormonal changes, such as an inhibition of pituitary- deprivation leads to substantial fragmentation of sleep architec- adrenal release, which may be involved in memory consolidation.
ture. Resulting from the frequent arousals during REM sleep, Although studies in rodents indicate memory enhancement for emotional as well as attentive disturbances can be observed6,22,23.
emotionally aversive tasks after administration of glucocorticoids These disturbances particularly affect retrieval testing perfor- (particularly into the basolateral amygdala26), human studies with mance after sleep20,21. Considering our finding of improved tex- systemic administration of glucocorticoids during early noctur- ture discrimination after early sleep, it is difficult to determine nal sleep consistently show an impairment of declarative memo- why SWS deprivation did not disturb consolidation12. Howev- 2000 Nature America Inc.
ry function during this period27,28.
er, in the previous experiments, despite repetitive arousals, sub- The present findings contrast with results from a previous jects spent an average of 30 minutes in SWS, in which the experiment, in which selective deprivation of REM sleep pre- consolidation process may have been initiated29.
vented an improvement in texture discrimination skill across A supplementary experiment addressed two further issues.
nocturnal sleep, and deprivation of SWS sleep had no effect12.
First, it indicated that sleep is necessary after practice to stimulate Fig. 3. Task Displays. Example of a stimulus (a) and a mask (b). All line positions varied slightly from trial to trial and the ‘T’ or ‘L’ in the center of the
screen was rotated randomly. The target texture (three diagonal lines), upper left quadrant of the stimulus display (a).
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any consistent improvement in visual discrimination. When sub- synaptic long-term potentiation and activity-dependent synap- jects were tested during the daytime wake phase, some subjects togenesis known to depend on modulatory influences from cer- improved, whereas others deteriorated in performance. The fail- tain neurotransmitters and neurohormonal inputs35–39.
ure of wake retention intervals to stimulate significant improve- Experimental variation of transmitter and neurohormonal lev- ment in discrimination skills confirms previous data18,19. Second, els during selected sleep periods is a possible approach to deter- when improvement after a full night of sleep was compared with mining the synaptic mechanisms involved in the different steps of improvement observed in the main experiment following early sleep alone, a striking interdependence of early and late sleep wasrevealed. The improvement across the entire sleep period was about three times greater than the improvement after early sleep Subjects were healthy non-smokers (19–35 years old), with normal or alone (Fig. 1a). This difference was not only attributable to the
corrected to normal vision. They slept seven to nine hours per night, and longer retention interval across the full night, because a reten- had no major disruptions of the sleep–wake cycle during the six weeks tion interval of equal length without sleep had no effect on task before experimentation. They were not allowed to ingest caffeine or alco-hol, or sleep during the day before experimental nights. Before the exper- performance. Rather, the better performance after a full night of iment, subjects were accustomed to sleeping under laboratory conditions.
sleep suggests a two-step consolidation process.
The experiments were approved by the Ethics Committee of the Med- Thus, although our data do not suggest that REM sleep is of primary importance for the learning of visual discrimination In the main experiment, each of 15 subjects participated in two exper- skills, REM sleep may add to consolidating memories once the imental nights, which were about one week apart. On these nights, sub- effects of early sleep have been manifested. A previous correla- jects learned a texture discrimination task with the retention interval tional study19 used the same discrimination task as our study, between learning and retrieval testing encompassing either the early or and showed that the improvement in texture discrimination skills late half of the night. Subjects were randomly assigned to either a sleep is correlated with the amount of time spent in SWS in the begin- group (n = 8), which had a 3-hour period of sleep during the retention ning of the night, and the time spent in REM sleep toward the interval, or a control group, which remained awake during the retention osci.nature
end of the night. The present data extends this finding, and pro- All sleep and wake periods could vary to a limited degree, to individually vides the first experimental evidence for a two-step process of adapt them to a subject’s normal sleep–wake rhythm (Fig. 2), but eight
memory formation during sleep, in which the second, REM hours between learning and retrieval testing were required, because oth- sleep-related step is only effective after memory processes have erwise, no improvement could be expected for the task18. Sleep time was • http://neur
been initiated in a first SWS-related step. Our experimental obser- measured from sleep onset. Subjects were woken during the first stage-two vations show that REM-rich late sleep alone is ineffective for sleep occurring after three hours of sleep. During the time the subjects memory consolidation, and that visual discrimination skills after were awake, they were not allowed to visually or physically strain them- an eight-hour sleep period (containing normal amounts of both selves. Most of the time, they played board games or listened to music.
SWS and REM sleep) are, on average, more than three times more Two supplementary experiments were done to control for effects of cir- cadian rhythm on retention and discrimination performance, respectively.
improved than after a period of early sleep alone. The view of a In the first experiment, 12-hour retention intervals between learning and two-step memory consolidation process would also integrate retrieval testing encompassed either nighttime (2100 hours–0900 hours; findings that arousals during REM sleep deteriorate consolida- n = 6) or daytime (0900 hours–2100 hours; n = 6). The nighttime inter- tion of texture discrimination skills after early sleep and SWS val included a complete 8-hour sleep interval beginning at 2300 hours.
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have initiated consolidation12. Once memory traces have gained In the second supplementary experiment, seven subjects were tested on some strength, neocortical stimulation during REM sleep could a well-learned task. They reported to the laboratory for 10 consecutive lead to a reactivation of previously encoded materials, sharpen- days, practicing the discrimination task with the target displayed in one ing the traces30,31. Whether the small amount of REM sleep dur- location. Afterward, subjects spent one experimental night in the labora- ing early sleep (as well as the small amount of SWS in late sleep) tory, being tested for discrimination performance at 2200 hours, have a particular function in this kind of sequential consolida- 0300 hours and 0800 hours. They slept two times for three hours duringthese nights (2300–0200 hours and 0400–0700 hours). At each test, per- tion process remains to be determined.
formance on the well-learned task was compared to performance on a Based on its local (retinotopic) nature, texture discrimination novel discrimination task, with the target displayed in a new location.
is considered to take place early during visual processing in the The visual discrimination task was designed as described17. It was car- primary visual cortex and closely associated areas17,32. The learn- ried out in a silent and dark environment. Stimuli were presented on a ing of texture discrimination occurs at a pre-attentive level, and Macintosh PowerPC computer with a 17-inch monitor (75 Hz). Subjects hence represents a fundamental type of procedural memory. In were asked to react by pressing keys on a keyboard. Each session con- this regard, the selective improvement in discrimination skills sisted of 1250 trials, each composed of three sequential displays. First, a after a period of early sleep diverges from previous studies in cross was displayed in the center of the screen. Subjects were told to leave which a greater enhancement of procedural memory was their eyes fixed at this point throughout the trial. After they pressed akey, there was a blank screen interval of 250–300 ms. Second, the target observed after periods of late rather than early retention display (Fig. 3a) was shown for 10 ms, followed by another blank screen
sleep10,11,13. One of those studies used a mirror-tracing task; the interval. Third, the mask was presented for 100 ms (Fig. 3b). Exposure
other used a word-stem priming task. Those tasks seem to be to the mask overrode the remains of the target display on the retina. Thus, more complex than the texture discrimination task. The influ- discrimination difficulty could be systematically increased by reducing ence of REM sleep may become increasingly important with more the stimulus to mask onset asynchrony (SOA).
complex tasks13,33,34, although the neurophysiological meaning of The target displays were 16° of visual angle in size and contained a field ‘task complexity’ in this context remains to be specified.
of 19 × 19 horizontal bars with a randomly rotated ‘T’ or ‘L’ shaped figure The neurophysiological mechanisms underlying sleep-asso- in the center. The target (three horizontally or vertically aligned diagonal ciated facilitation of procedural memories are unclear. Improve- bars) was located in the peripheral visual field at a distance of 3°–5° of ment in texture discrimination skills may be a result of visual angle from the center. After each trial, subjects had to report by keypress the letter in the center of the display and the target orientation, that use-dependent changes in cell connectivity within V1 and close- is, the alignment of the three diagonal lines. Discrimination of the cen- ly connected areas17,32. These changes might involve processes of nature neuroscience • volume 3 no 12 • december 2000
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