Selective sleep deprivation after daily torpor in the Djungarian hamster

Sleep, daily torpor and hibernation are no longer considered homologous processes. Animals emerging from these states spend most of their time in sleep. After termination of the torpor-associated hypothermia, there is an initial high electroenecephalogram (EEG) slow-wave activity (SWA; 0.75-4.0 Hz) and a subsequent monotonic decline. Both of these features are similar to the effects elicited by prolonged waking. It was previously shown that when hamsters are not allowed to sleep immediately after emerging from torpor, an additional SWA increase above the level reached after sleep deprivation (SD) alone occurs during the delayed recovery. A similar manipulation in hibernating ground squirrels abolished the subsequent SWA increase, shedding doubt on the similarity of the regulatory aspects following torpor and hibernation. To further investigate the extent to which SWA is homeostatically regulated after torpor, Djungarian hamsters were subjected to 1.5 h partial non-rapid eye movement (NREM) sleep deprivation (NSD) that either immediately followed the emergence from torpor (T + NSD) or 4-h SD (SD + NSD). The NSD was attained by disturbing the animals when they exhibited NREM sleep with high amplitude slow-waves. To investigate whether regional aspects of sleep homeostasis are similar after torpor and SD, the EEG was recorded from a parietal and frontal derivation after 4-h SD. An increase in SWA in NREM sleep occurred after all conditions in both EEG derivations. There was no significant difference in SWA during the initial 1.5-h recovery when torpor, T + NSD and SD + NSD were compared. During recovery from torpor and SD, SWA was higher in the frontal than in the parietal derivation. Our results provide further evidence that torpor and SD have similar effects on sleep. The SWA increase did not disappear after the NSD; therefore, SWA is homeostatically regulated after daily torpor. The frontal predominance of slow waves encountered both after torpor and SD indicates that waking and torpor induce similar regional changes in EEG SWA.     

Sleep regulation in the Djungarian hamster: comparison of the dynamics leading to the slow-wave activity increase after sleep deprivation and daily torpor

STUDY OBJECTIVES: Emerging from daily torpor, Djungarian hamsters (Phodopus sungorus) show an initial increase in electroencephalographic slow-wave activity (power density between 0.75 and 4.0 Hz) during sleep that gradually declines. This feature is typical for sleep following prolonged waking and supports the hypothesis that sleep pressure increases during daily torpor. After hamsters were subjected to sleep deprivation or partial non-rapid eye movement sleep deprivation immediately following torpor, slow-wave activity remained high and decreased only when sleep was allowed. An analysis of the dynamics of the process underlying the build-up of sleep pressure during episodes of waking and torpor may provide insights into the regulation of normal sleep and wakefulness. We have analyzed in more detail the timecourse of the process that is common for waking and daily torpor and that could account for the subsequent increase in slow-wave activity. DESIGN: Continuous 24-hour recordings of electroencephalography, electromyography, cortical temperature, and electroencephalographic spectral analysis were performed. Torpor data of 28 hamsters and sleep-deprivation data of diverse durations collected previously in 15 hamsters were analyzed. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: Sleep deprivation. MEASUREMENTS AND RESULTS: Slow-wave activity invariably increased as a function of the duration of both prior waking and torpor. However, the time constant of the build-up of slow-wave activity was approximately 2.75 times slower during torpor compared to sleep deprivation. Brain temperature recorded during the torpor bouts was 10 degrees to 12 degrees C below euthermic brain temperature. Therefore, the temperature coefficient of the time constant for the slow-wave-activity increase is between 2.3 and 2.8, a range typical for biochemical processes. CONCLUSIONS: We conclude that the processes occurring during daily torpor in the Djungarian hamster are similar to those occurring during sleep deprivation, but the build-up of sleep pressure during torpor appears to be slowed down by the lower brain temperature.     

Context- but not familiarity-dependent forms of object recognition are impaired following excitotoxic hippocampal lesions in rats

Dual-process models of recognition memory in animals propose that recognition memory is supported by two independent processes that reflect the operation of distinct brain structures: a familiarity process that operates independently of the hippocampus and a context-dependent (episodic) memory process that is dependent on the hippocampus. A novel variant of an object recognition procedure was used to examine this proposal. Healthy rats showed a preference for exploring a novel object rather than a familiar object: a familiarity-dependent recognition effect. They also showed a preference for exploring a familiar object that was presented in a different spatiotemporal context rather than a familiar object that was presented either in a different spatial or temporal context: a context-dependent form of recognition that is sensitive to "what" object has been presented "where" and "when." Rats with excitotoxic hippocampal lesions showed the familiarity-dependent but not the context-dependent form of recognition. The results provide support for dual-process theories of recognition memory.     

The perirhinal-entorhinal cortex, but not the hippocampus, is critical for expression of individual recognition in the context of the Coolidge effect

The Coolidge effect is a phenomenon in which males show renewed sexual interest in a novel female following copulation to satiety with another female. In golden hamsters, this phenomenon depends on the ability to recognize conspecifics using chemosensory cues processed through the main olfactory system. Here we tested whether olfactory targets in the hippocampal system support this natural form of recognition memory. Male hamsters received ibotenic acid lesions of the perirhinal-entorhinal cortex (PR-ENT) or hippocampus (H) and were allowed to copulate to satiety with a female conspecific, then were presented with two anesthetized females, the familiar mate and an unfamiliar female that copulated with another male. Sham-operated and H-lesioned subjects preferentially investigated the novel female, indicating intact recognition of individual identity. By contrast, PR-ENT-lesioned males failed to discriminate familiar and novel females, and this deficit could not be attributed to abnormal copulatory behavior during mating. All subjects were able to detect and discriminate between female odors when presented in isolation during a habituation-discrimination test, indicating that behavioral deficits shown by PR-ENT males were not due to anosmia or a general investigatory deficit. Thus, the perirhinal-entorhinal cortex, but not the hippocampus, is critical for the recognition of familiar conspecifics in this naturalistic situation. This study reveals an essential role for the perirhinal-entorhinal cortex, but not the hippocampus, in a natural form of recognition memory within the social behavior of hamsters. The findings show a strikingly similar pattern to the effects of selective damage to the same brain regions on performance in standard recognition memory tasks by rats and monkeys. Therefore, the present data extend our understanding of the differential role of structures of the hippocampal memory system, showing continuity across species and between formal laboratory tests and the function of memory in natural social behavior.     

Consolidation of strictly episodic memories mainly requires rapid eye movement sleep

STUDY OBJECTIVES: The aim of this study is to examine the effects of sleep deprivation during the first or second half of the night on episodic memory consolidation. Episodic memory is defined as memory for events located in time and space. It is also characterized by autonoetic consciousness, which gives a subject the conscious sensation of traveling back in time to relive the original event and forward into the future. DESIGN: Consolidation of episodic information was tested after 4-hour retention intervals, which followed learning and occurred during either the early or late half night, respectively dominated by slow wave sleep (SWS) or rapid eye movement (REM) sleep, or corresponding periods of wakefulness. SETTING: Data collection occurred in the sleep laboratory. PARTICIPANTS: Forty-three young healthy subjects: 9 men and 34 women, age ranging from 18 to 26 years (mean 20.18 +/- 1.94 years) were included in this study. INTERVENTIONS: Waking after a 4-hour retention interval filled with early or late sleep, or 4-hour sleep deprivation, during early or late period of night. MEASUREMENTS AND RESULTS: The cognitive task, named the What-Where-When test, was specially designed to assess factual, spatial, and temporal components of episodic memory. This task was associated with the Remember/Know paradigm to assess autonoetic consciousness. We measured performance on immediate free recall, delayed free recall (after a 4-hour interval of wakefulness or sleep), and delayed recognition. We also calculated a forgetting rate for each feature (factual, spatial, and temporal) and, for the recognition task, scores of autonoetic consciousness (R responses). REM-sleep deprivation was associated with significantly lower recall of spatial information compared to SWS deprivation (P < .01) or late sleep (P < .05) conditions. REM-sleep deprivation was also associated with a higher forgetting rate of temporal information as compared to the early sleep condition (P< .01). Finally, REM-sleep deprivation led subjects to give significantly fewer R responses, indicative of true memories, as compared to SWS deprivation (P < .05). CONCLUSIONS: These results suggest that consolidation of truly episodic memories mainly involves REM sleep.     

Sleep enhances memory consolidation in children

Sleep is an active state that plays an important role in the consolidation of memory. It has been found to enhance explicit memories in both adults and children. However, in contrast to adults, children do not always show a sleep‐related improvement in implicit learning. The majority of research on sleep‐dependent memory consolidation focuses on adults; hence, the current study examined sleep‐related effects on two tasks in children. Thirty‐three typically developing children aged 6–12 years took part in the study. Actigraphy was used to monitor sleep. Sleep‐dependent memory consolidation was assessed using a novel non‐word learning task and the Tower of Hanoi cognitive puzzle, which involves discovering an underlying rule to aid completion. Children were trained on the two tasks and retested following approximately equal retention intervals of both wake and sleep. After sleep, children showed significant improvements in performance of 14% on the non‐word learning task and 25% on the Tower of Hanoi task, but no significant change in score following the wake retention interval. Improved performance on the Tower of Hanoi may have been due to children consolidating explicit aspects of the task, for example rule‐learning or memory of previous sequences; thus, we propose that sleep is necessary for consolidation of explicit memory in children. Sleep quality and duration were not related to children's task performance. If such experimental sleep‐related learning enhancement is generalizable to everyday life, then it is clear that sleep plays a vital role in children's educational attainment.     

Sleep‐dependent consolidation of face recognition and its relationship to REM sleep duration,REM density and Stage 2 sleep spindles

Face recognition is a highly specialized capability that has implicit and explicit memory components. Studies show that learning tasks with facial components are dependent on rapid eye movement and non‐rapid eye movement sleep features, including rapid eye movement sleep density and fast sleep spindles. This study aimed to investigate the relationship between sleep‐dependent consolidation of memory for faces and partial rapid eye movement sleep deprivation, rapid eye movement density, and fast and slow non‐rapid eye movement sleep spindles. Fourteen healthy participants spent 1 night each in the laboratory. Prior to bed they completed a virtual reality task in which they interacted with computer‐generated characters. Half of the participants (REMD group) underwent a partial rapid eye movement sleep deprivation protocol and half (CTL group) had a normal amount of rapid eye movement sleep. Upon awakening, they completed a face recognition task that contained a mixture of previously encountered faces from the task and new faces. Rapid eye movement density and fast and slow sleep spindles were detected using in‐house software. The REMD group performed worse than the CTL group on the face recognition task; however, rapid eye movement duration and rapid eye movement density were not related to task performance. Fast and slow sleep spindles showed differential relationships to task performance, with fast spindles being positively and slow spindles negatively correlated with face recognition. The results support the notion that rapid eye movement and non‐rapid eye movement sleep characteristics play complementary roles in face memory consolidation. This study also raises the possibility that fast and slow spindles contribute in opposite ways to sleep‐dependent memory consolidation.     

Sleep enhances inhibitory behavioral control in discrimination learning in rats

Sleep supports the consolidation of memory, and it has been proposed that this enhancing effect of sleep pertains in particular to memories which are encoded under control of prefrontal–hippocampal circuitry into an episodic memory system. Furthermore, repeated reactivation and transformation of such memories during sleep are thought to promote the de-contextualization of these memories. Here, we aimed to establish a behavioral model for the study of such sleep-dependent system consolidation in rats, using a go/nogo conditional discrimination learning task known to essentially depend on prefrontal–hippocampal function. Different groups of rats were trained to criterion on this task and, then, subjected to 80-min retention intervals filled with spontaneous morning sleep, sleep deprivation, or spontaneous evening wakefulness. In a subsequent test phase, the speed of relearning of the discrimination task was examined as indicator of memory, whereby rats were either tested in the same context as during training or in a different context. Sleep promoted relearning of the conditional discrimination task, and this effect was similar for testing memory in the same or different context (p < 0.001). Independent of sleep and wakefulness during the retention interval, animals showed faster relearning when tested in the same context as during learning, compared with testing in a different context (p < 0.001). The benefitting effect of sleep on discrimination learning was primarily due to an enhancing effect on response suppression during the nogo stimulus. We infer from these results that sleep enhances memory for inhibitory behavioral control in a generalized context-independent manner and thereby might eventually also contribute to the abstraction of schema-like representations.     

Excitotoxic lesions of the pre- and parasubiculum disrupt object recognition and spatial memory processes

Rats with bilateral ibotenic acid lesions centered on the pre- and parasubiculum and control rats were tested in a series of spatial memory and object recognition memory tasks. Lesioned rats were severely impaired relative to controls in both the reference and working memory versions of the water maze task and displayed a delay-dependent deficit in a delayed nonmatch to place procedure conducted in the T-maze. Lesioned rats also displayed reduced exploration in a novel environment, and performance was altered in an object recognition procedure as compared with the control group. These findings indicate that the pre- and parasubiculum plays an important role in the processing of both object recognition and spatial memory.     

Experimental sleep fragmentation impairs spatial reference but not working memory in Fischer/Brown Norway rats

Sleep fragmentation is a common symptom in sleep disorders and other medical complaints resulting in excessive daytime sleepiness. The present study seeks to explore the effects of sleep fragmentation on learning and memory in a spatial reference memory task and a spatial working memory (WM) task. Fischer/Brown Norway rats lived in custom treadmills designed to induce locomotor activity every 2 min throughout a 24-h period. Separate rats were either on a treadmill schedule that allowed for consolidated sleep or experienced no locomotor activation. Rats were tested in one of two water maze-based tests of learning and memory immediately following 24 h of sleep interruption. Rats tested in a spatial reference memory task (eight massed acquisition trials) with a 24-h follow-up probe trial to assess memory retention showed no differences in acquisition performance but were impaired on the 24 h retention of the platform location. In contrast, the performance of rats tested in a spatial WM task (delayed matching to position task) was not impaired. Therefore, sleep fragmentation prior to testing impairs the ability to retain spatial reference memories but does not impair spatial reference memory acquisition or spatial WM in Fischer-Norway rats.     

Role of the pineal gland in hibernators: a concept proposed to clarify why hibernators have to leave torpor and sleep

The contention that torpor during hibernation might not be a kind of sleep but a kind of sleep deprivation may be correct, as it can be conceptually explained. Sleep is part of life and cannot be part of the torpor state, which has no reactions. The state of torpor has a time limit and, if this is not observed, death follows by freezing. The evolutional differences particularly in pineal gland physiology may explain the differences between the blueprints governing vital reflexes in humans and hibernators.     

A time for learning and a time for sleep: the effect of sleep deprivation on contextual fear conditioning at different times of the day

Study Objectives:

Sleep deprivation negatively affects memory consolidation, especially in the case of hippocampus-dependent memories. Studies in rodents have shown that 5 hours of sleep deprivation immediately following footshock exposure selectively impairs the formation of a contextual fear memory. In these studies, both acquisition and subsequent sleep deprivation were performed in the animals'' main resting phase. However, in everyday life, subjects most often learn during their active phase.

Design:

Here we examined the effects of sleep deprivation on memory consolidation for contextual fear in rats when the task was performed at different times of the day, particularly, at the beginning of the resting phase or right before the onset of the active phase.

Measurements and Results:

Results show that sleep deprivation immediately following training affects consolidation of contextual fear, independent of time of training. However, in the resting phase memory consolidation was impaired by 6 hours of posttraining sleep deprivation, whereas, in the active phase, the impairment was only seen after 12 hours of sleep deprivation. Since rats sleep at least twice as much during the resting phase compared with the active phase, these data suggest that the effect of sleep deprivation depends on the amount of sleep that was lost. Also, control experiments show that effects of sleep deprivation were not related to the amount of stimulation the animals received and were therefore not likely an indirect effect of the sleep-deprivation method.

Conclusion:

These results support the notion that sleep immediately following acquisition, independent of time of day, promotes memory consolidation and that sleep deprivation may disrupt this process depending on the amount of sleep that is lost.

Citation:

Hagewoud R; Whitcomb SN; Heeringa AN; Havekes R; Koolhaas JM; Meerlo P. A time for learning and a time for sleep: the effect of sleep deprivation on contextual fear conditioning at different times of the day. SLEEP 2010;33(10):1315-1322.     

Sleep Deprivation Specifically Impairs Short-term Olfactory Memory in Drosophila

Study Objectives:

Sleep is crucial to memory consolidation in humans and other animals; however, the effect of insufficient sleep on subsequent learning and memory remains largely elusive.

Design:

Learning and memory after 1-day sleep deprivation (slpD) was evaluated using Pavlovian olfactory conditioning in Drosophila, and locomotor activity was measured using the Drosophila Activity Monitoring System in a 12:12 light-dark cycle.

Results:

We found that slpD specifically impaired 1-h memory in wild type Canton-S flies, and this effect could persist for at least 2 h. However, alternative stresses (heat stress, oxidative stress, starvation, and rotation stress) did not result in a similar effect and left the flies’ memory intact. Mechanistic studies demonstrated that flies with either silenced transmission of the mushroom body (MB) during slpD or down-regulated cAMP levels in the MB demonstrated no slpD-induced 1-h memory impairment.

Conclusion:

We found that slpD specifically impaired 1-h memory in Drosophila, and either silencing of MB transmission during slpD or down-regulation of the cAMP level in the MB protected the flies from slpD-induced impairment.

Citation:

Li X; Yu F; Guo A. Sleep deprivation specifically impairs short-term olfactory memory in drosophila. SLEEP 2009;32(11):1417-1424.     

Sleep stabilizes visuomotor adaptation memory: a functional magnetic resonance imaging study

The beneficial effect of sleep on motor memory consolidation is well known for motor sequence memory, but remains unsettled for visuomotor adaptation in humans. The aim of this study was to characterize more clearly the influence of sleep on consolidation of visuomotor adaptation using a between‐subjects functional magnetic resonance imaging (fMRI) design contrasting sleep to total sleep deprivation. Our behavioural results, based on seven different parameters, show that sleep stabilizes performance whereas sleep deprivation deteriorates it. During training, while a set of cerebellar, striatal and cortical areas is activated in proportion to performance improvement, the recruitment of the hippocampus and frontal cortex protects motor memory against the detrimental effects of sleep deprivation. During retest after sleep loss a cerebello–cortical network, usually involved in the earliest stage of learning, was recruited to perform the task. In contrast, no changes in cerebral activity were observed after sleep, suggesting that it may only support the stabilization of the visuomotor adaptation memory trace.     

Effect of sleep deprivation on emotional working memory

The emotional dysregulation and impaired working memory found after sleep loss can have severe implications for our daily functioning. Considering the intertwined relationship between emotion and cognition in stimuli processing, there could be further implications of sleep deprivation in high‐complex emotional situations. Although studied separately, this interaction between emotion and cognitive processes has been neglected in sleep research. The aim of the present study was to investigate the effect of 1 night of sleep deprivation on emotional working memory. Sixty‐one healthy participants (mean age: 23.4 years) were either sleep deprived for 1 night (n = 30) or had a normal night’s sleep (n = 31). They performed an N‐back task with two levels of working memory load (1‐back and 3‐back) using positive, neutral and negative picture scenes. Sleep deprivation, compared with full night sleep, impaired emotional working memory accuracy, but not reaction times. The sleep‐deprived participants, but not the controls, responded faster to positive than to negative and neutral pictures. The effect of sleep deprivation was similar for both high and low working memory loads. The results showed that although detrimental in terms of accuracy, sleep deprivation did not impair working memory speed. In fact, our findings indicate that positive stimuli may facilitate working memory processing speed after sleep deprivation.     

Effects of early and late nocturnal sleep on priming and spatial memory.

A wordstem priming task (nondeclarative memory), and a mental spatial rotation task (declarative memory) were presented to subjects of an experimental "sleep" group (n = 11) and of a "wake" control group (n = 10). Repetition priming effects and recall of spatial memory were tested after 3-hr retention intervals, which followed learning and were placed either in the early or in the late half of the night. Sleep group subjects slept during the retention intervals while subjects of the wake group stayed awake. As expected, early retention sleep was dominated by slow wave sleep (SWS), whereas rapid eye movement (REM) sleep prevailed during late retention sleep. After early retention sleep, recall of spatial memory was superior to that after late retention sleep (p < 0.01), and also to that after retention intervals of wakefulness (p < 0.05). In contrast, priming was more effective after late than early retention sleep (p < 0.05). It appears that early sleep dominated by SWS facilitates consolidation of declarative memory whereas late sleep dominated by REM sleep facilitates consolidation of nondeclarative memory.     

Donepezil Improves Episodic Memory in Young Individuals Vulnerable to the Effects of Sleep Deprivation

Study Objectives:

We investigated if donepezil, a long-acting orally administered cholinesterase inhibitor, would reduce episodic memory deficits associated with 24 h of sleep deprivation.

Design:

Double-blind, placebo-controlled, crossover study involving 7 laboratory visits over 2 months. Participants underwent 4 functional MRI scans; 2 sessions (donepezil or placebo) followed a normal night''s sleep, and 2 sessions followed a night of sleep deprivation.

Setting:

The study took place in a research laboratory.

Participants:

26 young, healthy volunteers with no history of any sleep, psychiatric, or neurologic disorders.

Interventions:

5 mg of donepezil was taken once daily for approximately 17 days.

Measurements and Results:

Subjects were scanned while performing a semantic judgment task and tested for word recognition outside the scanner 45 minutes later. Sleep deprivation increased the frequency of non-responses at encoding and impaired delayed recognition. No benefit of donepezil was evident when participants were well rested. When sleep deprived, individuals who showed greater performance decline improved with donepezil, whereas more resistant individuals did not benefit. Accompanying these behavioral effects, there was corresponding modulation of task-related activation in functionally relevant brain regions. Brain regions identified in relation to donepezil-induced alteration in non-response rates could be distinguished from regions relating to improved recognition memory. This suggests that donepezil can improve delayed recognition in sleep-deprived persons by improving attention as well as enhancing memory encoding.

Conclusions:

Donepezil reduced decline in recognition performance in individuals vulnerable to the effects of sleep deprivation. Additionally, our findings demonstrate the utility of combined fMRI–behavior evaluation in psychopharmacological studies.

Citation:

Chuah LYM; Chong DL; Chen AK; Rekshan WR; Tan JC; Zheng H; Chee MWL. Donepezil improves episodic memory in young individuals vulnerable to the effects of sleep deprivation. SLEEP 2009;32(8):999-1010.     

Sleep deprivation impairs binding of information with its context

Binding information to its context in long-term memory is critical for many tasks, including memory tasks and decision making. Failure to associate information to its context could be an important aspect of sleep deprivation effects on cognition, but little is known about binding problems from being sleep-deprived at the time of encoding. We studied how sleep deprivation affects binding using a well-established paradigm testing the ability to remember auditorily presented words (items) and their speakers (source context). In a laboratory study, 68 healthy young adults were randomly assigned to total sleep deprivation or a well-rested control condition. Participants completed an affective item and source memory task twice: once after 7-hour awake during baseline and again 24 hours later, after nearly 31 hours awake in the total sleep deprivation condition or 7 hours awake in the control condition. Participants listened to negative, positive, and neutral words presented by a male or female speaker and were immediately tested for recognition of the words and their respective speakers. Recognition of items declined during sleep deprivation, but even when items were recognized accurately, recognition of their associated sources also declined. Negative items were less bound with their sources than positive or neutral items, but sleep deprivation did not significantly affect this pattern. Our findings indicate that learning while sleep-deprived disrupts the binding of information to its context independent of item valence. Such binding failures may contribute to sleep deprivation effects on tasks requiring the ability to bind new information together in memory.     

Dorsal subcoeruleus nucleus (SubCD) involvement in context-associated fear memory consolidation

The neurobiological mechanisms of emotional memory processing can be investigated using classical fear conditioning as a model system, and evidence from multiple lines of research suggests that sleep influences consolidation of emotional memory. In rodents, some of this evidence comes from a common finding that sleep deprivation from 0 to 6 h after fear conditioning training impairs processing of conditioned fear memory. Here, we show that during a 6-h session of sleep–wake (S–W) recording, immediately after a session of context-associated fear conditioning training, rats spent more time in wakefulness (W) and less time in slow-wave sleep (SWS) and rapid eye movement (REM) sleep. This context-associated fear conditioning training-induced reduction in SWS lasts for 2 h, and the REM sleep reduction lasts throughout the entire 6-h post-training S–W recording period. Interestingly, these reductions in SWS and REM sleep during this 6-h period did not impair memory consolidation for context-associated fear conditioning. The results of this study show, for the first time, that lesions within the dorsal part of the subcoeruleus nucleus (SubCD), which were unintentionally caused by the implantation of bipolar recording electrodes, impair consolidation of context-associated fear conditioning memory. Together, the results of these experiments suggest that emotional memory processing associated with fear conditioning can be completed successfully within less than a normal amount of sleep, but it requires a structurally and functionally intact SubCD, an area in the brain stem where phasic pontine wave (P-wave) generating cells are located.     

Random number generation during sleep deprivation: effects of caffeine on response maintenance and stereotypy

Neurophysiological and functional imaging studies have demonstrated that frontal regions of the brain are particularly responsive to homeostatic sleep pressure. Previous neuropsychological studies indicate that sleep deprivation causes impairments in prefrontal cortical function. Random number generation (RNG) is thought to provide a sensitive index of executive functions that rely on the prefrontal cortex. The present study tested the hypothesis that sleep deprivation would impair RNG and that caffeine would mitigate this impairment. Healthy young men (n = 21) participated in two 40-h sleep deprivations 1 week apart. During each sleep deprivation period subjects received either caffeine or placebo according to a randomized, double-blind cross-over design, and they completed an oral RNG task at 3-h intervals. Comparison of test sessions at analogous times of day revealed that sleep deprivation was associated with significant drops in the number of responses, a threefold increase in the percentage of rule violations, 59% greater response redundancy and a 20% increase in stereotypy of adjacent response pairs. Sleep deprivation did not consistently alter counting tendency. Caffeine ameliorated the decrease in the number of responses but did not mitigate other deficits in RNG that arose during sleep deprivation. These findings are consistent with prior reports of diminished vigilance and increased perseveration during extended wakefulness. They support the conclusion that caffeine preserves simple aspects of cognitive performance during sleep deprivation, whereas caffeine may not prevent detrimental effects of sleep deprivation on some complex cognitive functions.