Arousal Instability Research Articles

Effect of valproate on the sleep microstructure of juvenile myoclonic epilepsy patients – a cross-sectional CAP based study

ObjectiveStudies looking at the effect of anti-epileptic medications on sleep microstructure of patients with epilepsy are almost non-existent. The aim of this study was to compare sleep microstructural characteristics of drug-naïve juvenile myoclonic epilepsy (JME) patients with those on valproate (VPA) monotherapy. MethodsThree age- (p = 0.287) and gender- (p = 0.766) matched groups (N = 20 in each group): (1) drug-naïve JME (mean age: 21.2 ± 4.06 years; M : F = 9:11); (2) JME on VPA (mean age: 21.85 ± 4.28 years; M : F = 11:9); (3) healthy controls (mean age: 23.2 ± 3.82 years; M : F = 9:11) underwent overnight polysomnography. Scoring and analysis of arousals American Sleep Disorders Association (ASDA, 2002), cyclic alternating pattern (CAP) (Terzano et al., 2002) parameters were performed. Comparison of arousal and CAP parameters was performed using one-way ANOVA, followed by pairwise comparisons using Fisher's LSD test (p ≤ 0.05). ResultsRapid eye movement (REM) arousal indices were higher in JME patients (Group 1 [p = 0.002] and Group 2 [p < 0.001]), whereas the overall and NREM arousal indices were comparable between the three groups. CAP rate was higher in JME patients as compared to controls (p < 0.001). Duration of phase A and its subtypes (p < 0.001) was reduced in drug-naïve patients as compared to VPA group and controls. Finally, percentage of phase A1 (p = 0.003) was decreased and A3 (p = 0.045) was increased in drug-naïve patients as compared to VPA group and controls. ConclusionsWe found significant alterations in REM arousal indices and several CAP parameters in JME patients. However, many of these alterations were not seen in the valproate group. This might indicate that anti-epileptic medications such as valproate may beneficially modulate arousal instability in JME patients, and hence promote sleep quality and continuity.

Withstanding the obstructive sleep apnea syndrome at the expense of arousal instability, altered cerebral autoregulation and neurocognitive decline.

The present review attempts to put together the available evidence and potential research paradigms at the interface of obstructive sleep apnea syndrome (OSAS), sleep micro- and macrostructure, cerebral vasoreactivity and cognitive neuroscience. Besides the significant health-related consequences of OSAS including hypertension, increased risk of cardio- and cerebrovascular events, notable neurocognitive lapses and excessive daytime somnolence are considered as potential burdens. The intermittent nocturnal hypoxia and hypercapnia which occur in OSAS are known to affect cerebral circulation and result in brain hypoperfusion. Arousal instability is then resulted from altered cyclic alternating patterns (CAPs) reflected in sleep EEG. In chronic state, some pathological loss of gray matter may be resulted from obstructive sleep apnea. This is proposed to be related to an upregulated proinflammatory state which may potentially result in apoptotic cell loss in the brain. On this basis, a pragmatic framework of the possible neural mechanisms which underpin obstructive sleep apnea-related neurocognitive decline has been discussed in this review. In addition, the impact of OSAS on cerebral autoregulation and sleep microstructure has been articulated.

A unifying computational framework for stability and flexibility of arousal.

Arousal and consciousness flexibly adjust to salient cues, but remain stable despite noise and disturbance. Diverse, highly interconnected neural networks govern the underlying transitions of behavioral state; these networks are robust but very complex. Frameworks from systems engineering provide powerful tools for understanding functional logic behind component complexity. From a general systems viewpoint, a minimum of three communicating control modules may enable flexibility and stability to coexist. Comparators would subtract current arousal from desired arousal, producing an error signal. Regulators would compute control signals from this error. Generators would convert control signals into arousal, which is fed back to comparators, to make the system noise-proof through self-correction. Can specific neurons correspond to these control elements? To explore this, here we consider the brain-wide orexin/hypocretin network, which is experimentally established to be vital for flexible and stable arousal. We discuss whether orexin neurons may act as comparators, and their target neurons as regulators and generators. Experiments are proposed for testing such predictions, based on computational simulations showing that comparators, regulators, and generators have distinct temporal signatures of activity. If some regulators integrate orexin-communicated errors, robust arousal control may be achieved via integral feedback (a basic engineering strategy for tracking a set-point despite noise). An integral feedback view also suggests functional roles for specific molecular aspects, such as differing life-spans of orexin peptides. The proposed framework offers a unifying logic for molecular, cellular, and network details of arousal systems, and provides insight into behavioral state transitions, complex behavior, and bases for disease.

Hypocretin (orexin) regulation of sleep-to-wake transitions.

The hypocretin (Hcrt), also known as orexin, peptides are essential for arousal stability. Here we discuss background information about the interaction of Hcrt with other neuromodulators, including norepinephrine and acetylcholine probed with optogenetics. We conclude that Hcrt neurons integrate metabolic, circadian and limbic inputs and convey this information to a network of neuromodulators, each of which has a different role on the dynamic of sleep-to-wake transitions. This model may prove useful to predict the effects of orexin receptor antagonists in sleep disorders and other conditions.

Subjective sleep quality in epilepsy patients with sleep-related seizures

Sleep quality is expected to be poor in epilepsy patients with sleep-related seizures as a consequence of the disruptive effect of seizures themselves on sleep patterns, a potentially heightened pre sleep emotional arousal due to patient’s worries about having seizures during sleep and associated sleep comorbidities. This study is aimed at investigating subjective sleep quality and features in adult patients with seizures occurring exclusively or predominantly during sleep. Patients affected with Nocturnal Frontal Lobe Epilepsy were not included. Fifty-seven subjects ( 18–72 years of age; 27 males), 27 (47.3%) diagnosed with sleep related undetermined epilepsy and 30 (52.7%) with focal epilepsy based on clinical, awake/sleep EEG and brain MRI findings, were investigated. Most of the patients (94%) had <1 seizure per month, with the seizures being in most cases generalized convulsive seizures during sleep. All the patients were given Pittsburgh questionnaire (PQ), Morningness – Eveningness Questionnaire (MEC), STAI 1 and 2, Beck Depression inventory (BDI). Patients reporting snoring and/or witnessed apneas during sleep underwent a nocturnal polysomnographic screening for obstructive sleep apnea (OSA). At the time of the questionnaire compiling the patients had had at least 1 seizure during the previous month (seizures recency) in 19% of the cases and they all were on antiepileptic drugs at bed time, with valproate, levetiracetam and carbamazepine, alone (89.5%) or in combination (10.5%) being the most frequently used drugs. Fifty-seven healthy subjects matched for age and sex served as controls. Univariate analyses were preliminary performed in comparing categorical (chi square test) and continuous variables ( T -test) between patients and controls and patients with PSQI >5 and those with PSQI <5. Neither PSQI total score (5.2 ± 3.6 in patients and 5.3 ± 3.4 in controls) nor its components differ significantly between patients and controls. PSQI >5 patients (39%) and PSQI <5 patients (61%) do not differ significantly for age (47.1 ± 15.0 vs. 43.9 ± 15.0 years), sex (41% vs. 50% males), STAI 1 ( 46.2 ± 13.2 vs. 37.9 ± 9.6) and STAI2 scores (44.2 ± 10.5 vs. 39 ± 10.7), BDI (12.8 ± 8.0 vs. 9.1 ± 9.0), MEQ chronotype, OSA prevalence (15.8% vs. 7.1%). As for illness-related parameters, PSQI >5 patients proved to have a significantly longer illness duration than PSQI <5 patients (17.5 ± 18.2 years vs 8.2 ± 0.3 years; p = 0.035) and a higher rate of seizures recency (54.5% vs. 15.4%; p = 0.04). Our data indicate that subjective sleep quality in adult patients with seizures occurring exclusively or predominantly during sleep is not poorer than in healthy controls. Patients’ sleep quality is influenced by some illness related parameters, with poor sleep quality being associated with longer disease duration and seizure recency. The relatively low frequency of seizures along with a blunting effect of antiepileptic treatment on arousal instability during sleep may explain the finding of a substantially good sleep quality in our patients series. However also epilepsy patients’ life style and their good compliance to sleep hygiene rules may account for a preserved sleep quality. The Authors wish to thank the technogists Valter Rustioni, Daniele Marchese, Laura Spelta, Federica Camasso for their technical support.

Parasomnias: an updated review.

Parasomnias are abnormal behaviors emanating from or associated with sleep. Sleepwalking and related disorders result from an incomplete dissociation of wakefulness from nonrapid eye movement (NREM) sleep. Conditions that provoke repeated cortical arousals, or promote sleep inertia lead to NREM parasomnias by impairing normal arousal mechanisms. Changes in the cyclic alternating pattern, a biomarker of arousal instability in NREM sleep, are noted in sleepwalking disorders. Sleep-related eating disorder (SRED) is characterized by a disruption of the nocturnal fast with episodes of feeding after an arousal from sleep. SRED is often associated with the use of sedative-hypnotic medications; in particular, the widely prescribed benzodiazepine receptor agonists. Recently, compelling evidence suggests that nocturnal eating may in some cases be a nonmotor manifestation of Restless Legs Syndrome (RLS). rapid eye movement (REM) Sleep Behavior Disorder (RBD) is characterized by a loss of REM paralysis leading to potentially injurious dream enactment. The loss of atonia in RBD often predates the development of Parkinson's disease and other disorders of synuclein pathology. Parasomnia behaviors are related to an activation (in NREM parasomnias) or a disinhibition (in RBD) of central pattern generators (CPGs). Initial management should focus on decreasing the potential for sleep-related injury followed by treating comorbid sleep disorders. Clonazepam and melatonin appear to be effective therapies in RBD, whereas paroxetine has been reported effective in some cases of sleep terrors. At this point, pharmacotherapy for other parasomnias is less certain, and further investigations are necessary.

Cyclic alternating pattern analysis in REM sleep behavior disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is a type of REM parasomnia characterized by complex motor activity during REM sleep. In this study, cyclic alternating pattern (CAP) in patients with idiopathic RBD was analyzed to evaluate the expression of arousal instability of NREM sleep. A total of 31 idiopathic RBD patients and age- and gender-matched 21 control subjects were consecutively recruited. Conventional sleep polysomnographic recording parameters and CAP parameters were compared between RBD and the control group. The number of CAP cycles (120.13 ± 113.56, p = 0.007), CAP sequences (20.9 ± 18.15, p < 0.001), CAP index (25.14 ± 24.44, p = 0.017), and CAP rate (24.07 ± 13.22, p = 0.016) were all significantly higher in RBD patients compared to the control group. The increase in CAP sequences was observed in phase A2 and A3 subtypes while phase A1 subtype was significantly lower in RBD patients. A significant positive correlation was observed between disease duration with total CAP time (r = 0.289, p = 0.042) and A3 index (r = 0.32, p = 0.024). There was a negative correlation between the age and A1 index (r = -0.4491, p = 0.0001). To our knowledge this is the first polysomnographic clinical study which evaluated CAP parameters in RBD. Increased CAP rate found may be considered as a sign showing that NREM sleep may also be affected in RBD patients. Therefore, CAP analysis may be important to enlighten the pathogenesis of parasomnias.

Clonidine Has a Paradoxical Effect on Cyclic Arousal and Sleep Bruxism during NREM Sleep

Clonidine disrupts the NREM/REM sleep cycle and reduces the incidence of rhythmic masticatory muscle activity (RMMA) characteristic of sleep bruxism (SB). RMMA/SB is associated with brief and transient sleep arousals. This study investigates the effect of clonidine on the cyclic alternating pattern (CAP) in order to explore the role of cyclic arousal fluctuation in RMMA/SB. Polysomnographic recordings from a pharmacological study. University sleep research laboratory. Sixteen SB subjects received a single dose of clonidine or placebo at bedtime in a crossover design. Sleep variables and RMMA/SB index were evaluated. CAP was scored to assess arousal instability between sleep-maintaining processes (phase A1) and stronger arousal processes (phases A2 and A3). Paired t-tests, ANOVAs, and cross-correlations were performed. Under clonidine, CAP time, and particularly the number of A3 phases, increased (P≤0.01). RMMA/SB onset was time correlated with phases A2 and A3 for both placebo and clonidine nights (P≤0.004). However, under clonidine, this positive correlation began up to 40 min before the RMMA/SB episode. CAP phase A3 frequency increased under clonidine, but paradoxically, RMMA/SB decreased. RMMA/SB was associated with and facilitated in CAP phase A2 and A3 rhythms. However, SB generation could be influenced by other factors besides sleep arousal pressure. NREM/REM ultradian cyclic arousal fluctuations may be required for RMMA/SB onset.

Paradoxical insomnia: The role of CAP and arousals in sleep misperception

Objective The relationship between CAP parameters and subjective time perception during sleep in primary insomnia was investigated. Patients and methods Data collected from all-night PSG recordings of 20 patients with a diagnosis of paradoxical insomnia (misperceptors) were compared with those of 20 normal gender- and age-matched subjects (controls). Besides sleep staging, scoring measures included CAP parameters and EEG arousals. Results Patients and controls presented non-significant differences in the amounts of objective sleep time (464 min vs. 447 min) and objective sleep latency (9 min vs. 8 min). Compared to controls, misperceptors reported a significantly shorter time of perceived sleep (285 min vs. 461 min) and a significantly longer duration of perceived sleep latency (51 min vs. 22 min). In spite of the 11 objective awakenings, misperceptors reported only 4 subjective awakenings, while controls described 2 of the 5 objective awakenings. Arousal index (31.7/h vs. 18.6/h) and total CAP rate (58.1% vs. 35.5%) were significantly higher in misperceptors. In the sleep period between objective and subjective sleep onset, CAP rate was 64.4% in misperceptors and 45.1% in controls ( p < 0.002). Insomniacs showed significantly higher amounts of CAP rate in stage 1 (62.7% vs. 37.5%) and in stage 2 (53.3% vs. 33.1%), but not in slow wave sleep. CAP phase A2 subtypes were significantly increased in misperceptors (31% vs. 24%). Conclusions The study points out the topical role of enhanced activation and arousal instability not only in the first part of the night (mismatch between objective and subjective sleep onset) but also in the misperception of consecutive objective awakenings which are subjectively grouped together as a single prolonged event.

Physiological arousal: a role for hypothalamic systems.

The lateral hypothalamus (LH) has long been known as a homeostasis center of the brain that modulates feeding behavior, arousal and reward. The hypocretins (Hcrts, also called orexins) and melanin-concentrating hormone (MCH) are neuropeptides produced in two intermingled populations of a few thousand neurons in the LH. The Hcrts have a prominent role in regulating the stability of arousal, since Hcrt system deficiency leads to narcolepsy. MCH is an important modulator of energy balance, as MCH system deficiency in mice leads to leanness and increased metabolism. Recently, MCH has been proposed to modulate rapid eye movement sleep in rodents. In this review, we propose a working model of the cross-talk between Hcrt and MCH circuits that may provide an arousal balance system to regulate complex goal-oriented behaviors.

Addiction and arousal: The hypocretin connection

The hypocretins, also known as orexins, are two neuropeptides now commonly described as critical components to maintain and regulate the stability of arousal. Several lines of evidence have raised the hypothesis that hypocretin-producing neurons are part of the circuitries that mediate the hypothalamic response to acute stress. Intracerebral administration of hypocretin leads to a dose-related reinstatement of drug and food seeking behaviors. Furthermore, stress-induced reinstatement can be blocked with hypocretin receptor 1 antagonism. These results, together with recent data showing that hypocretin is critically involved in cocaine sensitization through the recruitment of NMDA receptors in the ventral tegmental area, strongly suggest that activation of hypocretin neurons play a critical role in the development of the addiction process. The activity of hypocretin neurons may affect addictive behavior by contributing to brain sensitization or by modulating the brain reward system. Hypocretinergic cells, in coordination with brain stress systems may lead to a vulnerable state that facilitates the resumption of drug seeking behavior. Hence, the hypocretinergic system is a new drug target that may be used to prevent relapse of drug seeking.

Neural substrates of awakening probed with optogenetic control of hypocretin neurons

The neural underpinnings of sleep involve interactions between sleep-promoting areas such as the anterior hypothalamus, and arousal systems located in the posterior hypothalamus, the basal forebrain and the brainstem. Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has been linked to narcolepsy. However, it is unknown whether electrical activity arising from Hcrt neurons is sufficient to drive awakening from sleep states or is simply correlated with it. Here we directly probed the impact of Hcrt neuron activity on sleep state transitions with in vivo neural photostimulation, genetically targeting channelrhodopsin-2 to Hcrt cells and using an optical fibre to deliver light deep in the brain, directly into the lateral hypothalamus, of freely moving mice. We found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep. Notably, photostimulation using 5-30 Hz light pulse trains reduced latency to wakefulness, whereas 1 Hz trains did not. This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology.

A Review of Neuroimaging in Obstructive Sleep Apnea

The authors reviewed neuroimaging studies of obstructive sleep apnea (OSA) to summarize findings, evaluate their contribution to a current understanding of the neurophysiology of the disorder, and propose directions for future research. Manuscripts were identified using the National Institutes of Health PubMed literature search system. Search terms included obstructive sleep apnea, sleep apnea, imaging, neuroimaging, magnetic resonance imaging, MRI, functional magnetic resonance imaging, fMRI, magnetic resonance spectroscopy, and MRS. Inclusion criteria required that research articles (1) were written in English, (2) examined an adult population, and (3) focused on imaging of the brain. Support for structural abnormalities is mixed, but converging evidence suggests the hippocampus may be atrophic in patients with OSA. Neurochemical evidence is supportive of white-matter impairment in OSA, particularly in the frontal lobes. Functional studies utilizing respiratory challenges report widespread neural differences in motor, sensory, and autonomic brain regions. Functional neuroimaging cognitive challenges have reported either a lack of brain activation in dorsolateral prefrontal cortex or increased neural response in frontal lobe, cingulate, thalamus, cerebellum, and juncture of parietal and temporal lobes, depending on the cognitive task employed. The current literature examining neuroimaging-derived neural correlates in patients with OSA has made many important preliminary contributions. Future studies would be strengthened by consideration of potential moderating participant characteristics, such as sex, age, education, OSA severity, and comorbid conditions. Additional investigation employing neuroimaging techniques is needed to advance our understanding of the neurophysiology of OSA.

Addiction and Arousal: Alternative Roles of Hypothalamic Peptides: Figure 1.

The importance of the lateral hypothalamus in the regulation of reward and motivation has long been recognized. However, the neuronal network involved in such a hypothalamic regulation of reward remains essentially unknown. Recently, hypocretin-containing neurons, a group of hypothalamic neurons known to be associated with the stability of arousal, have emerged as important structures in the control of brain reward function. This review summarizes a Mini-Symposium presented at the 2006 Annual Meeting of the Society for Neuroscience.

Relationship of Epileptic Discharges to Arousal Instability and Periodic Leg Movements in a Case of Nocturnal Frontal Lobe Epilepsy: A Stereo-EEG Study

We describe the case of a patient with nocturnal frontal lobe epilepsy, presenting with periodic leg movements during sleep and complaining of excessive daytime sleepiness. With the support of intracerebral electroencephalogram recordings and the corroboration of the postoperative outcome, periodic leg movements during sleep and excessive daytime sleepiness appeared to be associated to enhanced arousal instability induced by by recurrent epileptic discharges not detectable on scalp electroencephalogram.

The Corticotropin-Releasing Factor-Hypocretin Connection: Implications in Stress Response and Addiction

The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. Recent data have raised the hypothesis that hypocretin neurons are also part of the circuitries that mediate the hypothalamic stress response. In particular, we have recently demonstrated that corticotrophin-releasing factor (CRF)-immunoreactive terminals make direct synaptic contacts with hypocretin-expressing neurons and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. Furthermore, CRF excites hypocretinergic cells ex vivo through CRF-R1 receptors. Activation of hypocretinergic neurons in response to acute stress is severely impaired in CRF-R1 knockout mice. Moreover, the stress response is impaired in hypocretin-deficient mice. We propose that upon stressor stimuli, CRF stimulates the release of hypocretins, and this circuit contributes to activation and maintenance of arousal associated with the stress response and addiction.

Stress and Arousal: The Corticotrophin-Releasing Factor/Hypocretin Circuitry

The hypocretins (also know as orexins) are two neuropeptides now commonly described as critical components for maintaining and regulating the stability of arousal. Several lines of evidence have raised the hypothesis that hypocretin-producing neurons are part of the circuitries that mediate the hypothalamic response to acute stress. New data indicate that the corticotrophin-releasing factor (CRF) peptidergic system directly innervates hypocretin-expressing neurons. CRF depolarizes hypocretin neurons, and this effect is blocked by a CRF-R1 antagonist. Furthermore, activation of hypocretinergic neurons by stress is impaired in CRF-R1 knockout mice. These data suggest that CRF-R1 receptor mediates the stress-induced activation of the hypocretinergic system. A significant amount of evidence also indicates that hypocretin cells connect reciprocally to the CRF system. We propose that upon stressor stimuli, CRF activates the hypocretin system, which relays these signals to brain stem nuclei involved in the modulation of arousal as well as to the extended amygdala, a structure involved in the negative motivational state that drives addiction.

Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response.

The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. We tested whether the hypocretinergic system is a critical component of the stress response activated by the corticotropin-releasing factor (CRF). Our results show that CRF-immunoreactive terminals make direct contact with hypocretin-expressing neurons in the lateral hypothalamus and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. We also demonstrate that application of CRF to hypothalamic slices containing identified hypocretin neurons depolarizes membrane potential and increases firing rate in a subpopulation of hypocretinergic cells. CRF-induced depolarization was tetrodotoxin insensitive and was blocked by the peptidergic CRF-R1 antagonist astressin. Moreover, activation of hypocretinergic neurons in response to acute stress was severely impaired in CRF-R1 knock-out mice. Together, our data provide evidence of a direct neuroanatomical and physiological input from CRF peptidergic system onto hypocretin neurons. We propose that, after stressor stimuli, CRF stimulates the release of hypocretins and that this circuit contributes to activation and maintenance of arousal associated with the stress response.

Vaginal Laser Doppler Flowmetry Pre- and Posthysterectomy

The objective of this study was to demonstrate the applicability of laser doppler flowmetry to pre- and posthysterectomy vaginal blood flow assessment. We used laser Doppler flowmetry to measure pre-and postoperational vaginal blood flow in 8 premenopausal women undergoing benign hysterectomies; we also measured serum E2, FSH, FT and administered a brief sexual function questionnaire. We analyzed data using two tailed t-test for paired samples. We found no significant differences at the P < .05 level of significance for vaginal blood flow. Accompanying values of estradiol, FSH, and free testosterone remained unchanged as well. A brief sexual function assessment revealed improvement or stability of libido, arousal, orgasm, and partner relatedness. Laser doppler flowmetry is an objective, reproducible measure of vaginal blood flow and may be used to investigate posthysterectomy sexual function.

The Cyclic Alternating Pattern Decreases as a Consequence of Total Sleep Deprivation and Correlates with EEG Arousals

The aim of this study was to assess the sensitivity of the cyclic alternating pattern (CAP) parameters to the increased need for recuperation that follows one night of sleep deprivation. Nine normal male subjects were recorded for 3 nights [adaptation, baseline (BSL) and recovery (REC)]. BSL and REC nights were separated by a 40-hour sleep deprivation. Recovery after sleep deprivation was characterized by a decrease in stage 1, stage 2 and sleep latency, and an increase in slow wave sleep (SWS) and the sleep efficiency index, while rapid eye movement (REM) and non-REM (NREM) time did not differ as compared to BSL sleep. CAP parameters were significantly affected by sleep deprivation, and the main results were the following: (1) the CAP rate (time spent in CAP phases/NREM time) significantly decreased from 38.85 to 31.47%, and (2) within phase A subtypes, there was a significant decrease in A3 subtypes (from 38.11 to 19.57). Furthermore, the number of arousals scored according to American Sleep Disorders Association rules strongly correlated with A3 subtypes during both the BSL (r = 0.79) and REC nights (r = 0.95). These results indicate that recuperative processes after sleep deprivation are also associated with a lesser arousal instability as defined by the reduction of the CAP rate, which is strongly correlated with EEG arousals.