- Email: [email protected]
Toward a cognitive neuroscience of sleep
Sleep Medicine Reviews, Vol. 5, No. 6, pp 417–421, 2001
SLEEP MEDICINE
doi:10.1053/smrv.2001.0221, available online at http://www.idealibrary.com on
reviews
GUEST EDITORIAL
Toward a cognitive neuroscience of sleep R. Stickgold Department of Psychiatry, Massachusetts Mental Health Center, Harvard Medical School, Boston, USA
Of all the basic biological drives, including hunger, thirst, sexual arousal and sleepiness, the drive to sleep is the only one whose basic biological function was not clear two thousand years ago. Yet, as we enter the 21st century, researchers are still arguing over the functions of both sleep and dreams. There appear to be two reasons for this continued uncertainty. First, the sleep research community has been slow to accept that sleep serves many basically unrelated systems, including, for example, endocrine, immunologic, and thermoregulatory, as well as cognitive, functions [1–3]. But the second reason is the complexity of the relationships between sleep and cognition. While it is obvious to anyone who has skipped a night of sleep that cognitive functioning deteriorates with sleep deprivation, characterizing the precise deficits has been remarkably difficult. Largely this is a consequence of our basic ignorance of cognitive functioning in general. So it has only been with the development of the cognitive neurosciences that sleep researchers have been given the tools they need to even define this exciting and important question. The articles in this issue of Sleep Medicine Reviews provide a superb review of much of the work currently being done in this field. There are several ways to study the links between sleep and cognition. We can ask how cognition is altered during sleep or as a consequence of sleep. We can ask how cognition is altered by changes in
Correspondence should be addressed to: Robert Stickgold, Department of Psychiatry, Massachusetts Mental Health Center, Harvard Medical School, 74 Fenwood Road, Boston, MA 02115, USA. E-mail: [email protected] 1087–0792/01/060421+05 $35.00/0
the quality or quantity of sleep. We can even ask how sleep is altered by cognitive activities. And in all of these questions, “how” can refer to the nature of the changes, the brain mechanisms underlying the changes, or the evolutionary pressures that led to the changes. This is a tall order, and most work to date has focused on the first of these, the description of the changes themselves. Three of the articles in this issue attempt to dissect the actual cognitive dysfunctions caused by disturbed sleep, both in children [4] and in adults [5, 6]. Given that the cognitive impairment resulting from sleep deprivation plays such a major role in both highway fatalities and industrial accidents [7], it is not surprising that so much research has gone into understanding this very real public health problem. The extent of the problem is impressive. Blunden et al., for example, cite studies [8, 9] indicating that the community prevalence rate for excessive daytime sleepiness in children is in the range of 36–42%. The consequences are equally impressive. Blunden et al. [4] report in this issue that sleep related obstructive breathing disorders in children are associated with significant attentional and memory deficits, as well as a more general impairment in school performance and an increase in problematic behaviors. In a second article, Fulda and Schulz [6] report on cognitive performance in adults with various sleep disorders. Overall, they found poorer performance on tests of attention, memory, vigilance, motor functions, and driving skills in these patient populations. But what their extensive metaanalysis makes clear is that these findings are inconsistent, rarely being seen in even half of the 2001 Harcourt Publishers Ltd
418
Basic Research Paradigms Altered cognition during sleep Cognitive studies during sleep inertia Dream studies Altered cognition following sleep Learning and memory consolidation Affect regulation Recovery of attentional resources Unpacking sleep and circadian effects Altered cognition with disrupted sleep Sleep disorders Selective sleep stage deprivation Sleep curtailment Sleep deprivation
studies analysed (driving dysfunction being the notable exception, with 93% of studies finding significant impairment). All of this points to the continued elusiveness of the cognitive impairments associated with sleep disorders. In reality, we do not even know how to think about the problem yet. Are we seeing, for example, a breakdown in fundamental cognitive functions due to a generalized absence of rest or to the failure of active sleep-dependent restorative processes? In fact, it is not even clear that this is a system failure as opposed to, for example, a mechanism evolved to ensure sleep despite one’s desire to stay awake. In any case, the mechanisms involved remain unclear. Is this a failure primarily at a systems level, where, perhaps, specific brain regions are affected, or at a cellular level, where all cortical neurons are more or less equally affected? Another unanswered question is whether these deficits result from changes in the performance of specific brain/cognitive systems (e.g. frontal/executive) or from changes occurring at the cellular level, throughout the cortex (e.g. decreased noradrenergic neuromodulation/decreased arousal). Clearly, there remains a need to clarify the very nature of these sleep dependent changes in cognition, and in a third article, Jones and Harrison [5] address this problem. They specifically ask whether the cognitive deficits seen with sleep deprivation can be explained solely in terms of a loss of frontal lobe functions. On one level, they conclude that frontal lobe dysfunction can explain some, but not all, of the deficits observed, and they assign some of the deficits to “general sleepiness”. But on another
R. STICKGOLD Basic Research Questions What is the nature of these changes? What brain mechanisms underlie these changes? What functions are served by these processes?
level, they point out that such concepts as frontal lobe function, executive function, attention and memory, remain inadequately defined and explained within the cognitive neuroscience community at large. The situation is not helped by the confusion within the sleep community over such concepts as general sleepiness. General sleepiness might, for example, be nothing more than the subjective experience of sleep deprivation-induced frontal lobe dysfunction. Still, looking at specific cognitive functions in intense detail, asking how sleep and sleep disruption affects these functions, is probably necessary if we are to finally sort out this complex problem. This is exactly the approach taken by researchers investigating the relationships between sleep, learning and memory, and the final two papers in this issue [10, 11] provide a valuable review of this field. Smith, in particular, reviews the human data on sleep-dependent memory consolidation and provides persuasive arguments against recent challenges [12, 13] to a role for REM in memory consolidation. Since the discovery of REM sleep, researchers have been studying the possible roles of sleep in learning and memory consolidation and integration. One of the great frustrations of this search has been that sometimes you see it and sometimes you don’t. In an attempt to explain the inconsistency of findings, Greenberg and Pearlman [14] proposed that “habitual reactions, which are closely linked with survival, are REM independent; but activities involving assimilation of unusual information require REM sleep for optimal consolidation” (p. 516). Later, Pearlman concluded that simpler tasks appeared
TOWARD A COGNITIVE NEUROSCIENCE OF SLEEP
419
unrelated to REM sleep, while the learning of more complex tasks was dependent on post-training REM sleep [15]. Both of these models built on the dichotomy between prepared and unprepared learning proposed earlier by Seligman [16]. He argued that tasks that could be carried out within an animal’s existing behavioral repertoire were learned rapidly, while tasks that required modification of this repertoire were learned more slowly. All of these descriptions are reminiscent of the processes of assimilation and accommodation through which, Piaget proposed, children learn about the world around them [17]. Assimilation, according to Piaget, is the process by which the brain/mind “incorporates all the given data of experience within its framework” (p. 6). This “framework” consists of a collection of models or “schemata” which the child develops to explain the external world. Insofar as the brain/mind views the world through these schemata, assimilation consists of pigeon-holing new information into existing schemata. In contrast, when these schemata prove inadequate for explaining novel information, they are modified to encompass the new information, a process that he called “accommodation”. What now seems plausible is that sleep plays a critical role in these processes. From this perspective, REM sleep would be necessary for the accommodation of existing schemata to explain novel data, but not for the simple assimilation of new data into pre-existing schemata. This would fit with Greenberg and Pearlman’s proposal that REM is important for learning unusual as opposed to habitual information [14], with Pearlman’s finding that REM is necessary for more complex tasks but not simpler one [15], and matches Seligman’s distinction between tasks that utilize an animal’s existing repertoire and those that require modifications of this repertoire [16]. Three of the reviews in this issue [5, 10, 11] provide evidence in support of this model. Ambrosini and Giuditta [10] review their rat studies supporting a two-step model of sleep-dependent memory consolidation. Citing the work of Kandel [18], they propose that “pre-existing brain circuits serving innate or previously acquired perceptual or motor programs dynamically compete with memories of novel experiences”. In their model, slowwave sleep (SWS) initiates the processing of “innate behavioral responses”, while REM serves to integrate new memories into “the multidimensional
network of associative brain circuits”. Put differently, SWS might support assimilation while REM sleep may be critical for accommodation. Similarly, Smith, in his review of sleep and memory in humans, suggests that REM dependency is seen in cases of “more complex declarative material” or when “less well developed strategies” are inadequate and subjects have to “develop new memory storage and/or retrieval strategies” [11], a perfect description of Piagetian accommodation. In this context, it is striking that Jones and Harrison find the most convincing evidence of a sleep deprivation effect on frontal functioning in a cognitive test [19] that is “both complex and dynamic, requiring planning skills, goal setting, monitoring and updating” [5]. Sleep deprivation resulted in large performance deficits, “largely due to [the subjects’] inability to keep up with events and develop contingency strategies” [5], another classic description of Piagetian accommodation. If REM and SWS process different types of information, they might well be stored differently, as well. Indeed, Seligman hypothesized that the mechanisms subserving the incorporation of new information into an organism’s pre-existing repertoire were distinctly different from those that modified the repertoire [16]. Since then, it has become clear that the brain contains multiple, anatomically distinct memory systems [20]. For example, medial temporal lobe structures, including the hippocampus, are critical for the storage and retrieval of episodic memories, while semantic memories, general knowledge, and both perceptual and motor skill learning depend on neocortical structures. Several lines of evidence now suggest that REM and NREM sleep process memories from different memory systems differentially. These include brain lesion [21] and brain imaging [22] studies, neural network modeling [23], and studies of cellular physiology [24–26] and neurochemistry [27]. Intriguingly, three limbic brain regions specifically activated during REM sleep, the anterior cingulate and medial orbitofrontal cortices and the central nucleus of the amygdala [22, 28], have been implicated in identifying and responding to ambiguous inputs [29] and mismatches between expectations and outcomes [30], precisely the types of events that would presumably require Piagetian accommodation [31]. How this all might fit together remains unclear. Ambrosini and Giuditta [10] suggest that SWSdependent consolidation (assimilation) may occur
R. STICKGOLD
420
exclusively in the hippocampus, while neocortical memories are integrated (accommodated) during REM, a concept that others have put forward as well [32]. Similarly, Smith argues that REM sleep consolidates procedural learning, which does not involve the hippocampus, but also includes learning that involves “high cognitive procedural content” [11] in this category. While a precise definition of what such learning encompasses is lacking, he suggests that studies of concepts in mathematics and physics would fit this category, as would learning to solve anagrams or to identify the meaning of a story. This feels like a description of neocortical memory systems integrating new information into non-episodic semantic memory networks, but further clarification is necessary. Taken together, all of these results suggest that SWS might support the assimilation of new information, primarily in the hippocampus, but also possibly in the neocortex [33–35], while REM sleep supports the accommodation of new memories within neocortical association networks. Who knows if such a model will turn out to be even close to the truth? But the real test of scientific research is its ability to promote new ways of thinking about old and recalcitrant problems, and the articles in this issue of Sleep Medicine Reviews will certainly stimulate such thinking in all of us.
REFERENCES 1. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet 1999; 354: 1435–1439. 2. Shaw PJ, Bergmann BM, Rechtschaffen A. Effects of paradoxical sleep deprivation on thermoregulation in the rat. Sleep 1998; 21: 7–17. 3. Rechtschaffen A. Current perspectives on the function of sleep. Perspect Biol Med 1998; 41: 359–90. 4. Blunden S, Lushington K, Kennedy D. Cognitive and behavioural performance in children with sleep related obstructive breathing disorders – a review. Sleep Med Rev 2001; 5: 447–461. 5. Jones K, Harrison Y. Frontal lobe function, sleep loss and fragmented sleep. Sleep Med Rev 2001; 5: 463–475. 6. Fulda S, Schulz H. Cognitive dysfunction in sleep disorders. Sleep Med Rev 2001; 5: 423–445. 7. Stein M. Less fun, less sleep, more work: An American portrait. National Sleep Foundation, 2001 8. Richards W, Ferdman RM. Prolonged morbidity due
9.
10.
11. 12.
13. 14.
15.
16. 17. 18.
19.
20. 21.
22.
23.
24. 25.
26.
27.
to delays in the diagnosis and treatment of obstructive sleep apnea in children. Clin Pediatr 2000; 39: 103–108. Guilleminault C, Pelayo R, Leger D, Clerk A, Bocian RCZ. Recognition of sleep disordered breathing in children. Pediatrics 1996; 98: 871–882. Ambrosini MV, Giuditta A. Learning and sleep: the sequential hypothesis. Sleep Med Rev 2001; 5: 477– 490. Smith C. Sleep and cognition. Sleep Med Rev 2001; 5: 491–506. Vertes RP, Eastman KE. The case against memory consolidation in REM sleep. Behav Brain Sci 2000; 23: 867–876. Siegel JM. The REM sleep–memory consolidation hypothesis. Science 2001; 294: 1058–1063. Greenberg R, Pearlman CA. Cutting the REM nerve: an approach to the adaptive function of REM sleep. Perspect Biol Med 1974; 17: 513–521. Pearlman C. REM Sleep and information processing: Evidence from animal studies. Neurosci Biobehav Rev 1979; 3: 57–68. Seligman MEP. On the generality of the laws of learning. Psychol Rev 1970; 77: 406–418. Piaget J. The origins of intelligence in children. New York: International Universities Press, Inc, 1952. Kandel ER, Pittenger C. The past, the future and the biology of memory storage. Philos Trans R Soc Lond B Biol Sci 1999; 354: 2027–2052. Harrison Y, Horne JA. One night of sleep loss impairs innovative thinking and flexible decision making. Organization Behav Hum Decision Processes 1999; 78: 128–145. Schacter DL, Tulving E. Memory systems 1994. Cambridge, MA: MIT Press, 1994. McClelland JL, McNaughton BL, O’Reilly RC. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychol Rev 1995; 102: 419–457. Hobson JA, Stickgold R, Pace-Schott EF. The neuropsychology of REM sleep dreaming. Neuroreport 1998; 9: R1–R14. Hinton GE, Dayan P, Frey BJ, Neal RM. The “Wake– sleep” algorithm for unsupervised neural networks. Science 1995; 268: 1158–1161. Buzsa´ki G. The hippocampo-neocortical dialogue. Cerebr Cortex 1996; 6: 81–92. Wilson MA, McNaughton BL. Reactivation of hippocampal ensemble memories during sleep. Science 1994; 265: 676–679. Louie K, Wilson MA. Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep. Neuron 2001; 29: 145–156. Hasselmo ME. Neuromodulation: acetylcholine and
TOWARD A COGNITIVE NEUROSCIENCE OF SLEEP
421
memory consolidation. Trends Cogn Sci 1999; 3: 351–359. 28. Morrison AR, Sanford LD, Ross RJ. Initiation of rapid eye movement sleep: Beyond the brainstem. In: BN Mallick, S Inoue (eds.) Rapid Eye Movement Sleep. New York: Marcel Dekker, 1999: 51–68. 29. Kapp BS, Whalen PJ, Supple WF, Pascoe JP. Amygdaloid contributions to conditioned arousal and sensory information processing. In: JP Aggleton (ed.) The amygdala: Neurobiological aspects of emotion, memory, and mental dysfunction. New York: Wiley-Liss, 1992: 229–254. 30. Cohen JD, Botvinick M, Carter CS. Anterior cingulate and prefrontal cortex: who’s in control? Nat Neurosci 2000; 3: 421–423.
31. Fosse R. Personal communications. 32. Stickgold R. Sleep: off-line memory reprocessing. Trends Cogn Sci 1998; 2: 484–492. 33. Stickgold R, Whidbee D, Schirmer B, Patel V, Hobson JA. Visual discrimination task improvement: A multistep process occurring during sleep. J Cogn Neurosci 2000; 12: 246–254. 34. Stickgold R, Malia A, Maguire D, Roddenberry D, O’Connor M. Replaying the game: Hypnagogic images in normals and amnesiacs. Science 2000; 290: 350–353. 35. Stickgold R, Hobson JA, Fosse R, Fosse M. Sleep, learning and dreams: off-line memory reprocessing. Science 2001; 294: 1052–1057.
SLEEP MEDICINE
doi:10.1053/smrv.2001.0221, available online at http://www.idealibrary.com on
reviews
GUEST EDITORIAL
Toward a cognitive neuroscience of sleep R. Stickgold Department of Psychiatry, Massachusetts Mental Health Center, Harvard Medical School, Boston, USA
Of all the basic biological drives, including hunger, thirst, sexual arousal and sleepiness, the drive to sleep is the only one whose basic biological function was not clear two thousand years ago. Yet, as we enter the 21st century, researchers are still arguing over the functions of both sleep and dreams. There appear to be two reasons for this continued uncertainty. First, the sleep research community has been slow to accept that sleep serves many basically unrelated systems, including, for example, endocrine, immunologic, and thermoregulatory, as well as cognitive, functions [1–3]. But the second reason is the complexity of the relationships between sleep and cognition. While it is obvious to anyone who has skipped a night of sleep that cognitive functioning deteriorates with sleep deprivation, characterizing the precise deficits has been remarkably difficult. Largely this is a consequence of our basic ignorance of cognitive functioning in general. So it has only been with the development of the cognitive neurosciences that sleep researchers have been given the tools they need to even define this exciting and important question. The articles in this issue of Sleep Medicine Reviews provide a superb review of much of the work currently being done in this field. There are several ways to study the links between sleep and cognition. We can ask how cognition is altered during sleep or as a consequence of sleep. We can ask how cognition is altered by changes in
Correspondence should be addressed to: Robert Stickgold, Department of Psychiatry, Massachusetts Mental Health Center, Harvard Medical School, 74 Fenwood Road, Boston, MA 02115, USA. E-mail: [email protected] 1087–0792/01/060421+05 $35.00/0
the quality or quantity of sleep. We can even ask how sleep is altered by cognitive activities. And in all of these questions, “how” can refer to the nature of the changes, the brain mechanisms underlying the changes, or the evolutionary pressures that led to the changes. This is a tall order, and most work to date has focused on the first of these, the description of the changes themselves. Three of the articles in this issue attempt to dissect the actual cognitive dysfunctions caused by disturbed sleep, both in children [4] and in adults [5, 6]. Given that the cognitive impairment resulting from sleep deprivation plays such a major role in both highway fatalities and industrial accidents [7], it is not surprising that so much research has gone into understanding this very real public health problem. The extent of the problem is impressive. Blunden et al., for example, cite studies [8, 9] indicating that the community prevalence rate for excessive daytime sleepiness in children is in the range of 36–42%. The consequences are equally impressive. Blunden et al. [4] report in this issue that sleep related obstructive breathing disorders in children are associated with significant attentional and memory deficits, as well as a more general impairment in school performance and an increase in problematic behaviors. In a second article, Fulda and Schulz [6] report on cognitive performance in adults with various sleep disorders. Overall, they found poorer performance on tests of attention, memory, vigilance, motor functions, and driving skills in these patient populations. But what their extensive metaanalysis makes clear is that these findings are inconsistent, rarely being seen in even half of the 2001 Harcourt Publishers Ltd
418
Basic Research Paradigms Altered cognition during sleep Cognitive studies during sleep inertia Dream studies Altered cognition following sleep Learning and memory consolidation Affect regulation Recovery of attentional resources Unpacking sleep and circadian effects Altered cognition with disrupted sleep Sleep disorders Selective sleep stage deprivation Sleep curtailment Sleep deprivation
studies analysed (driving dysfunction being the notable exception, with 93% of studies finding significant impairment). All of this points to the continued elusiveness of the cognitive impairments associated with sleep disorders. In reality, we do not even know how to think about the problem yet. Are we seeing, for example, a breakdown in fundamental cognitive functions due to a generalized absence of rest or to the failure of active sleep-dependent restorative processes? In fact, it is not even clear that this is a system failure as opposed to, for example, a mechanism evolved to ensure sleep despite one’s desire to stay awake. In any case, the mechanisms involved remain unclear. Is this a failure primarily at a systems level, where, perhaps, specific brain regions are affected, or at a cellular level, where all cortical neurons are more or less equally affected? Another unanswered question is whether these deficits result from changes in the performance of specific brain/cognitive systems (e.g. frontal/executive) or from changes occurring at the cellular level, throughout the cortex (e.g. decreased noradrenergic neuromodulation/decreased arousal). Clearly, there remains a need to clarify the very nature of these sleep dependent changes in cognition, and in a third article, Jones and Harrison [5] address this problem. They specifically ask whether the cognitive deficits seen with sleep deprivation can be explained solely in terms of a loss of frontal lobe functions. On one level, they conclude that frontal lobe dysfunction can explain some, but not all, of the deficits observed, and they assign some of the deficits to “general sleepiness”. But on another
R. STICKGOLD Basic Research Questions What is the nature of these changes? What brain mechanisms underlie these changes? What functions are served by these processes?
level, they point out that such concepts as frontal lobe function, executive function, attention and memory, remain inadequately defined and explained within the cognitive neuroscience community at large. The situation is not helped by the confusion within the sleep community over such concepts as general sleepiness. General sleepiness might, for example, be nothing more than the subjective experience of sleep deprivation-induced frontal lobe dysfunction. Still, looking at specific cognitive functions in intense detail, asking how sleep and sleep disruption affects these functions, is probably necessary if we are to finally sort out this complex problem. This is exactly the approach taken by researchers investigating the relationships between sleep, learning and memory, and the final two papers in this issue [10, 11] provide a valuable review of this field. Smith, in particular, reviews the human data on sleep-dependent memory consolidation and provides persuasive arguments against recent challenges [12, 13] to a role for REM in memory consolidation. Since the discovery of REM sleep, researchers have been studying the possible roles of sleep in learning and memory consolidation and integration. One of the great frustrations of this search has been that sometimes you see it and sometimes you don’t. In an attempt to explain the inconsistency of findings, Greenberg and Pearlman [14] proposed that “habitual reactions, which are closely linked with survival, are REM independent; but activities involving assimilation of unusual information require REM sleep for optimal consolidation” (p. 516). Later, Pearlman concluded that simpler tasks appeared
TOWARD A COGNITIVE NEUROSCIENCE OF SLEEP
419
unrelated to REM sleep, while the learning of more complex tasks was dependent on post-training REM sleep [15]. Both of these models built on the dichotomy between prepared and unprepared learning proposed earlier by Seligman [16]. He argued that tasks that could be carried out within an animal’s existing behavioral repertoire were learned rapidly, while tasks that required modification of this repertoire were learned more slowly. All of these descriptions are reminiscent of the processes of assimilation and accommodation through which, Piaget proposed, children learn about the world around them [17]. Assimilation, according to Piaget, is the process by which the brain/mind “incorporates all the given data of experience within its framework” (p. 6). This “framework” consists of a collection of models or “schemata” which the child develops to explain the external world. Insofar as the brain/mind views the world through these schemata, assimilation consists of pigeon-holing new information into existing schemata. In contrast, when these schemata prove inadequate for explaining novel information, they are modified to encompass the new information, a process that he called “accommodation”. What now seems plausible is that sleep plays a critical role in these processes. From this perspective, REM sleep would be necessary for the accommodation of existing schemata to explain novel data, but not for the simple assimilation of new data into pre-existing schemata. This would fit with Greenberg and Pearlman’s proposal that REM is important for learning unusual as opposed to habitual information [14], with Pearlman’s finding that REM is necessary for more complex tasks but not simpler one [15], and matches Seligman’s distinction between tasks that utilize an animal’s existing repertoire and those that require modifications of this repertoire [16]. Three of the reviews in this issue [5, 10, 11] provide evidence in support of this model. Ambrosini and Giuditta [10] review their rat studies supporting a two-step model of sleep-dependent memory consolidation. Citing the work of Kandel [18], they propose that “pre-existing brain circuits serving innate or previously acquired perceptual or motor programs dynamically compete with memories of novel experiences”. In their model, slowwave sleep (SWS) initiates the processing of “innate behavioral responses”, while REM serves to integrate new memories into “the multidimensional
network of associative brain circuits”. Put differently, SWS might support assimilation while REM sleep may be critical for accommodation. Similarly, Smith, in his review of sleep and memory in humans, suggests that REM dependency is seen in cases of “more complex declarative material” or when “less well developed strategies” are inadequate and subjects have to “develop new memory storage and/or retrieval strategies” [11], a perfect description of Piagetian accommodation. In this context, it is striking that Jones and Harrison find the most convincing evidence of a sleep deprivation effect on frontal functioning in a cognitive test [19] that is “both complex and dynamic, requiring planning skills, goal setting, monitoring and updating” [5]. Sleep deprivation resulted in large performance deficits, “largely due to [the subjects’] inability to keep up with events and develop contingency strategies” [5], another classic description of Piagetian accommodation. If REM and SWS process different types of information, they might well be stored differently, as well. Indeed, Seligman hypothesized that the mechanisms subserving the incorporation of new information into an organism’s pre-existing repertoire were distinctly different from those that modified the repertoire [16]. Since then, it has become clear that the brain contains multiple, anatomically distinct memory systems [20]. For example, medial temporal lobe structures, including the hippocampus, are critical for the storage and retrieval of episodic memories, while semantic memories, general knowledge, and both perceptual and motor skill learning depend on neocortical structures. Several lines of evidence now suggest that REM and NREM sleep process memories from different memory systems differentially. These include brain lesion [21] and brain imaging [22] studies, neural network modeling [23], and studies of cellular physiology [24–26] and neurochemistry [27]. Intriguingly, three limbic brain regions specifically activated during REM sleep, the anterior cingulate and medial orbitofrontal cortices and the central nucleus of the amygdala [22, 28], have been implicated in identifying and responding to ambiguous inputs [29] and mismatches between expectations and outcomes [30], precisely the types of events that would presumably require Piagetian accommodation [31]. How this all might fit together remains unclear. Ambrosini and Giuditta [10] suggest that SWSdependent consolidation (assimilation) may occur
R. STICKGOLD
420
exclusively in the hippocampus, while neocortical memories are integrated (accommodated) during REM, a concept that others have put forward as well [32]. Similarly, Smith argues that REM sleep consolidates procedural learning, which does not involve the hippocampus, but also includes learning that involves “high cognitive procedural content” [11] in this category. While a precise definition of what such learning encompasses is lacking, he suggests that studies of concepts in mathematics and physics would fit this category, as would learning to solve anagrams or to identify the meaning of a story. This feels like a description of neocortical memory systems integrating new information into non-episodic semantic memory networks, but further clarification is necessary. Taken together, all of these results suggest that SWS might support the assimilation of new information, primarily in the hippocampus, but also possibly in the neocortex [33–35], while REM sleep supports the accommodation of new memories within neocortical association networks. Who knows if such a model will turn out to be even close to the truth? But the real test of scientific research is its ability to promote new ways of thinking about old and recalcitrant problems, and the articles in this issue of Sleep Medicine Reviews will certainly stimulate such thinking in all of us.
REFERENCES 1. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet 1999; 354: 1435–1439. 2. Shaw PJ, Bergmann BM, Rechtschaffen A. Effects of paradoxical sleep deprivation on thermoregulation in the rat. Sleep 1998; 21: 7–17. 3. Rechtschaffen A. Current perspectives on the function of sleep. Perspect Biol Med 1998; 41: 359–90. 4. Blunden S, Lushington K, Kennedy D. Cognitive and behavioural performance in children with sleep related obstructive breathing disorders – a review. Sleep Med Rev 2001; 5: 447–461. 5. Jones K, Harrison Y. Frontal lobe function, sleep loss and fragmented sleep. Sleep Med Rev 2001; 5: 463–475. 6. Fulda S, Schulz H. Cognitive dysfunction in sleep disorders. Sleep Med Rev 2001; 5: 423–445. 7. Stein M. Less fun, less sleep, more work: An American portrait. National Sleep Foundation, 2001 8. Richards W, Ferdman RM. Prolonged morbidity due
9.
10.
11. 12.
13. 14.
15.
16. 17. 18.
19.
20. 21.
22.
23.
24. 25.
26.
27.
to delays in the diagnosis and treatment of obstructive sleep apnea in children. Clin Pediatr 2000; 39: 103–108. Guilleminault C, Pelayo R, Leger D, Clerk A, Bocian RCZ. Recognition of sleep disordered breathing in children. Pediatrics 1996; 98: 871–882. Ambrosini MV, Giuditta A. Learning and sleep: the sequential hypothesis. Sleep Med Rev 2001; 5: 477– 490. Smith C. Sleep and cognition. Sleep Med Rev 2001; 5: 491–506. Vertes RP, Eastman KE. The case against memory consolidation in REM sleep. Behav Brain Sci 2000; 23: 867–876. Siegel JM. The REM sleep–memory consolidation hypothesis. Science 2001; 294: 1058–1063. Greenberg R, Pearlman CA. Cutting the REM nerve: an approach to the adaptive function of REM sleep. Perspect Biol Med 1974; 17: 513–521. Pearlman C. REM Sleep and information processing: Evidence from animal studies. Neurosci Biobehav Rev 1979; 3: 57–68. Seligman MEP. On the generality of the laws of learning. Psychol Rev 1970; 77: 406–418. Piaget J. The origins of intelligence in children. New York: International Universities Press, Inc, 1952. Kandel ER, Pittenger C. The past, the future and the biology of memory storage. Philos Trans R Soc Lond B Biol Sci 1999; 354: 2027–2052. Harrison Y, Horne JA. One night of sleep loss impairs innovative thinking and flexible decision making. Organization Behav Hum Decision Processes 1999; 78: 128–145. Schacter DL, Tulving E. Memory systems 1994. Cambridge, MA: MIT Press, 1994. McClelland JL, McNaughton BL, O’Reilly RC. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychol Rev 1995; 102: 419–457. Hobson JA, Stickgold R, Pace-Schott EF. The neuropsychology of REM sleep dreaming. Neuroreport 1998; 9: R1–R14. Hinton GE, Dayan P, Frey BJ, Neal RM. The “Wake– sleep” algorithm for unsupervised neural networks. Science 1995; 268: 1158–1161. Buzsa´ki G. The hippocampo-neocortical dialogue. Cerebr Cortex 1996; 6: 81–92. Wilson MA, McNaughton BL. Reactivation of hippocampal ensemble memories during sleep. Science 1994; 265: 676–679. Louie K, Wilson MA. Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep. Neuron 2001; 29: 145–156. Hasselmo ME. Neuromodulation: acetylcholine and
TOWARD A COGNITIVE NEUROSCIENCE OF SLEEP
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memory consolidation. Trends Cogn Sci 1999; 3: 351–359. 28. Morrison AR, Sanford LD, Ross RJ. Initiation of rapid eye movement sleep: Beyond the brainstem. In: BN Mallick, S Inoue (eds.) Rapid Eye Movement Sleep. New York: Marcel Dekker, 1999: 51–68. 29. Kapp BS, Whalen PJ, Supple WF, Pascoe JP. Amygdaloid contributions to conditioned arousal and sensory information processing. In: JP Aggleton (ed.) The amygdala: Neurobiological aspects of emotion, memory, and mental dysfunction. New York: Wiley-Liss, 1992: 229–254. 30. Cohen JD, Botvinick M, Carter CS. Anterior cingulate and prefrontal cortex: who’s in control? Nat Neurosci 2000; 3: 421–423.
31. Fosse R. Personal communications. 32. Stickgold R. Sleep: off-line memory reprocessing. Trends Cogn Sci 1998; 2: 484–492. 33. Stickgold R, Whidbee D, Schirmer B, Patel V, Hobson JA. Visual discrimination task improvement: A multistep process occurring during sleep. J Cogn Neurosci 2000; 12: 246–254. 34. Stickgold R, Malia A, Maguire D, Roddenberry D, O’Connor M. Replaying the game: Hypnagogic images in normals and amnesiacs. Science 2000; 290: 350–353. 35. Stickgold R, Hobson JA, Fosse R, Fosse M. Sleep, learning and dreams: off-line memory reprocessing. Science 2001; 294: 1052–1057.