Yaron Dagan

Daytime sleep condenses the time course of motor memory consolidation

Two behavioral phenomena characterize human motor memory consolidation: diminishing susceptibility to interference by a subsequent experience and the emergence of delayed, offline gains in performance. A recent model proposes that the sleep-independent reduction in interference is followed by the sleep-dependent expression of offline gains. Here, using the finger-opposition sequence–learning task, we show that an interference experienced at 2 h, but not 8 h, following the initial training prevented the expression of delayed gains at 24 h post-training. However, a 90-min nap, immediately post-training, markedly reduced the susceptibility to interference, with robust delayed gains expressed overnight, despite interference at 2 h post-training. With no interference, a nap resulted in much earlier expression of delayed gains, within 8 h post-training. These results suggest that the evolution of robustness to interference and the evolution of delayed gains can coincide immediately post-training and that both effects reflect sleep-sensitive processes.

Circadian rhythm sleep disorders following mild traumatic brain injury

Objective: To describe the physiologic and behavioral characteristics of circadian rhythm sleep disorders (CRSDs) following minor traumatic brain injury (mTBI) in patients complaining of insomnia. Methods: Forty two patients with insomnia complaints following mTBI were screened. Those suspected of having CRSD underwent actigraphy, saliva melatonin and oral temperature measurement, and polysomnography. All patients also filled out a self-reported questionnaire to determine their circadian preference. Results: Fifteen of the 42 patients (36%) with complaints of insomnia following mTBI were diagnosed with CRSD. Eight patients displayed a delayed sleep phase syndrome (DSPS), whereas seven displayed an irregular sleep–wake pattern (ISWP). Whereas all patients with DSPS exhibited a 24-hour periodicity of oral temperature rhythm, three of seven patients with ISWP lacked such a daily rhythm. In addition, ISWP patients exhibited smaller amplitude of oral temperature rhythm vs the DSPS group. Subjective Morningness–Eveningness Questionnaire scores were in accordance with the clinical diagnosis of DSPS or ISWP based on actigraphy. Conclusions: Minor traumatic brain injury might contribute to the emergence of circadian rhythm sleep disorders. Two types of these disorders were observed: delayed sleep phase syndrome and irregular sleep–wake pattern. The types differed in the subjective questionnaire scores and had distinct profiles of melatonin and temperature circadian rhythms.

Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study.

Sleep deprivation is extremely common in the intensive care unit (ICU), and this lack of sleep is associated with low melatonin secretion. The objective of the current study was to explore the effect of exogenous melatonin administration on sleep quality in patients hospitalized in the pulmonary intensive care unit (ICU). We performed a double-blind, placebo-controlled study in the pulmonary ICU of a tertiary care hospital. Eight adult patients hospitalized in the pulmonary ICU with respiratory failure caused by exacerbation of chronic obstructive pulmonary disease (COPD) or with pneumonia were studied. Patients received either 3 mg of controlled-release melatonin or a placebo at 22:00, and sleep quality was evaluated by wrist actigraphy. Treatment with controlled-release melatonin dramatically improved both the duration and quality of sleep in this group of patients. Our results suggest that melatonin administration to patients in intensive care units may be indicated as a treatment for sleep induction and resynchronization of the “biologic clock.” This treatment may also help in the prevention of the “ICU syndrome” and accelerate the healing process. (Chronobiology International, 17(1), 71–76, 2000)

The effects of coffee consumption on sleep and melatonin secretion

BACKGROUND In this study we examined the effects of caffeine on sleep quality and melatonin secretion. Melatonin is the principal hormone responsible for synchronization of sleep. Melatonin secretion is controlled by neurotransmitters that can be affected by caffeine. METHODS In the first part of the study, six volunteers drank either decaffeinated or regular coffee in a double-blind fashion on one day, and the alternate beverage 7 days later. Sleep parameters were assessed by actigraphy. In the second part of the study, the subjects again drank either decaffeinated or regular coffee, and they then collected urine every 3h for quantitation of 6-sulphoxymelatonin (6-SMT), the main metabolite of melatonin in the urine. RESULTS We found that drinking regular caffeinated coffee, compared to decaffeinated coffee, caused a decrease in the total amount of sleep and quality of sleep, and an increase in the length of time of sleep induction. Caffeinated coffee caused a decrease in 6-SMT excretion throughout the following night. CONCLUSIONS The results of our study confirm the widely held belief that coffee consumption interferes with sleep quantity and quality. In addition, we found that the consumption of caffeine decreases 6-SMT excretion. Individuals who suffer from sleep abnormalities should avoid caffeinated coffee during the evening hours.

Evaluating the Role of Melatonin in the Long-Term Treatment of Delayed Sleep Phase Syndrome (DSPS)

Delayed sleep phase syndrome (DSPS) involves a mismatch between the usual daily schedule required by the individuals environment and his or her circadian sleep-wake pattern. Patients suffering from DSPS are treated with chronotherapy, light therapy, or melatonin administration. While chronotherapy and light therapy are demanding and difficult treatments that usually lead to compliance problems, melatonin administration is a relatively simple and easy treatment option. Previous studies carried out on relatively small samples of DSPS patients have shown that melatonin has a sleep-promoting and entraining action when taken in the evening. The present study, which accompanied routine treatment in our sleep clinic, examined the efficiency of melatonin treatment in a relatively large population of DSPS subjects by means of subjective reports. The 61 subjects, 37 males and 24 females, were diagnosed with DSPS by means of clinical assessment and actigraphy at our sleep clinic. Their mean pretreatment falling asleep and waking times were 03:09 (SD = 86.22 minutes) and 11:31 (SD = 98.58 minutes), respectively. They were treated with a 6-week course of 5 mg of oral melatonin taken daily at 22:00. A survey questionnaire was sent to the home of each subject 12-18 months after the end of the treatment; the survey investigated the efficiency of the melatonin treatment and its possible side effects. Of the patients, 96.7% reported that the melatonin treatment was helpful, with almost no side effects. Of these, 91.5% reported a relapse to their pretreatment sleeping patterns within 1 year of the end of treatment. Only 28.8% reported that the relapse occurred within 1 week. The pretreatment falling asleep and waking times of patients in whom the changes were retained for a relatively long period of time were significantly earlier than those of patients whose relapse was immediate (t = 2.18, p < .05; t = 2.39, p < .05, respectively), with no difference in sleep duration. The implications of these findings, as well as further research possibilities, are discussed.

Circadian rhythm sleep disorders: toward a more precise definition and diagnosis.

The present article presents a survey of the characteristics of our case series of 322 patients suffering from circadian rhythm sleep disorders (CRSDs), a case-control study comparing a group of 50 CRSD patients and 56 age- and gender-matched normal subjects, and a proposal for new guidelines for improving the diagnosis of CRSD. The major findings were that 83.5% of our CRSD patients who seek medical help are of the delayed sleep phase syndrome (DSPS) type; 89.6% report that the onset of CRSD occurred in early childhood or adolescence; CRSD exhibits no gender differences: a familial trait exists in 44% of patients; and learning disorders (19.3%) and personality disorders (22.4%) in the DSPS-type patients are of high prevalence. The findings of this study point to the importance of clinician awareness of the clinical picture of patients presenting with CRSD so that early diagnosis and effective treatment can be achieved to prevent harmful consequences.

Autonomic changes during wake–sleep transition: A heart rate variability based approach

Autonomic function during sleep and wakefulness has been extensively investigated, however information concerning autonomic changes during the wake to sleep transition is scarce. The objective of the present study was to non-invasively characterize autonomic function and additional physiologic changes during sleep onset in normal and abnormal sleep. The estimation of autonomic function was based on time-frequency analysis of the RR interval series, using the power components in the very-low-frequency range (0.005-0.04 Hz), low-frequency (0.04-0.15 Hz), and high-frequency range (0.15-0.5 Hz). The ratio of low to high frequency power represented the sympathovagal balance. Thirty-four subjects who underwent whole night polysomnography were divided into 3 groups according to their complaints and study results: normal subjects, apneic patients (OSAS), and subjects with various sleep disorders (VSD). The results indicated a significant increase in RR interval during sleep onset, although its variability decreased; respiratory rate did not change, yet respiration became more stable; EMG amplitude and its variability decreased with sleep onset. Very-low-frequency power started to decrease significantly 2 min before sleep onset in all groups; low-frequency power decreased and high-frequency power did not change significantly in all groups, accordingly their ratio decreased and reflected a shift towards parasympathetic predominance. Although autonomic function displayed similar behavior in all subjects, OSAS and VSD patients presented a higher sympathovagal balance reflecting enhanced sympathetic predominance in those groups compared to normal subjects, both before and after sleep onset. All parameters reached a nadir at a defined time point during the process of falling asleep. We conclude that the wake-sleep transition period represents a transitional process between two physiologically different states; this transition starts with a decrease in the very slow oscillations in heart rate that anticipates a step-change resetting of autonomic function, followed by a decrease in sympathovagal balance towards the end of the process.

Melatonin Treatment in Adolescents With Delayed Sleep Phase Syndrome

This retrospective study describes the effects of long-term treatment with melatonin in 33 adolescents (age range, 10-18 years) with delayed sleep phase syndrome (DSPS). Patients were treated with oral melatonin, 3 to 5 mg/day for an average period of 6 months. During the treatment, sleep onset was advanced and sleep duration was longer. Treatment was also associated with a decrease in the proportion of patients reporting school difficulties. No adverse effects of melatonin were noted. This study indicates that long-term treatment with melatonin can be beneficial for adolescents with DSPS in terms of sleep-wake schedule and school performance.

Sleep quality in children with attention deficit hyperactivity disorder: an actigraphic study.

Abstract  The aim of the present study was to compare the sleep of 12 children with attention deficit hyperactivity disorder (ADHD) with that of 12 normal controls. The children were examined in their natural environment, using continuous actigraphic monitoring over several consecutive nights, as well as undergoing subjective parental reports. It was hypothesized that children diagnosed with ADHD would suffer from reduced sleep quality than children without ADHD. This hypothesis was supported by the actigraphic measures, but not supported by the subjective parental reports. It was also found that the sleep quality of the two groups differed over the course of the night, which suggests a difference in sleep architecture. Various possible explanations for these findings, their implications regarding the relationship between sleep and ADHD, and the resulting treatment ramifications are discussed, and suggestions for further research are provided.

Diastolic blood pressure is the first to rise in association with early subclinical obstructive sleep apnea: lessons from periodic examination screening

BACKGROUND Obstructive sleep apnea syndrome (OSAS) is associated with long-term cardiovascular morbidity. Little is known about these relations at early stages. We conducted a case-control study in which we analyzed the clinical characteristics of young adults who underwent a periodic health examination and were screened for, and eventually found to experience, OSAS. METHODS We identified 121 subjects newly diagnosed in a sleep study as having OSAS, and 229 matched control subjects in which screening for OSAS was negative. All had a medical interview, physical examination, and routine laboratory tests. RESULTS Subjects who had OSAS had a higher, body mass index (3-kg/m(2) difference) and a higher diastolic blood pressure (4-mm Hg difference) value, without elevation in systolic blood pressure. There was no metabolic difference (lipids profile and fasting glucose levels) between groups. CONCLUSIONS Diastolic blood pressure is higher early in the course of OSAS. Long term follow-up may determine effects of prevention and early intervention in OSAS and associated hypertension.