In summary, although actigraphy is not as accurate as PSG for determining some sleep measurements, studies are in general agreement that actigraphy, with its ability to record continuously for long time periods, is more reliable than sleep logs which rely on the patients' recall of how many times they woke up or how long they slept during the night and is more reliable than observations which only capture short time periods Actigraphy can provide information obtainable in no other practical way It can also have a role in the medical care of patients with sleep disorders However, it should not be held to the same expectations as polysomnography Actigraphy is one-dimensional, whereas polysomnography comprises at least 3 distinct types of data (EEG, EOG, EMG), which jointly determine whether a person is asleep or awake It is therefore doubtful whether actigraphic data will ever be informationally equivalent to the PSG, although progress on hardware and data processing software is continuously being made Although the 1995 practice parameters paper determined that actigraphy was not appropriate for the diagnosis of sleep disorders, more recent studies suggest that for some disorders, actigraphy may be more practical than PSG While actigraphy is still not appropriate for the diagnosis of sleep disordered breathing or of periodic limb movements in sleep, it is highly appropriate for examining the sleep variability (ie, night-to-night variability) in patients with insomnia Actigraphy is also appropriate for the assessment of and stability of treatment effects of anything from hypnotic drugs to light treatment to CPAP, particularly if assessments are done before and after the start of treatment A recent independent review of the actigraphy literature by Sadeh and Acebo reached many of these same conclusions Some of the research studies failed to find relationships between sleep measures and health-related symptoms The interpretation of these data is also not clear-cut Is it that the actigraph is not reliable enough to the access the relationship between sleep changes and quality of life measures, or, is it that, in fact, there is no relationship between sleep in that population and quality of life measures? Other studies of sleep disordered breathing, where actigraphy was not used and was not an outcome measure also failed to find any relationship with quality of life Is it then the actigraph that is not reliable or that the associations just do not exist? The one area where actigraphy can be used for clinical diagnosis is in the evaluation of circadian rhythm disorders Actigraphy has been shown to be very good for identifying rhythms Results of actigraphic recordings correlate well with measurements of melatonin and of core body temperature rhythms Activity records also show sleep disturbance when sleep is attempted at an unfavorable phase of the circadian cycle Actigraphy therefore would be particularly good for aiding in the diagnosis of delayed or advanced sleep phase syndrome, non-24-hour-sleep syndrome and in the evaluation of sleep disturbances in shift workers It must be remembered, however, that overt rest-activity rhythms are susceptible to various masking effects, so they may not always show the underlying rhythm of the endogenous circadian pacemaker In conclusion, the latest set of research articles suggest that in the clinical setting, actigraphy is reliable for evaluating sleep patterns in patients with insomnia, for studying the effect of treatments designed to improve sleep, in the diagnosis of circadian rhythm disorders (including shift work), and in evaluating sleep in individuals who are less likely to tolerate PSG, such as infants and demented elderly While actigraphy has been used in research studies for many years, up to now, methodological issues had not been systematically addressed in clinical research and practice Those issues have now been addressed and actigraphy may now be reaching the maturity needed for application in the clinical arena

The role of actigraphy in the study of sleep and circadian rhythms.

Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of "sleep and memory" research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems.

https://www.zora.uzh.ch/id/eprint/77770/1/physiol_rev_93.pdf

About sleep's role in memory

1.0 BACKGROUND ACTIGRAPHY HAS BEEN USED TO STUDY SLEEP/WAKE PATTERNS FOR OVER 20 YEARS. The advantage of actigraphy over traditional polysomnography (PSG) is that actigraphy can conveniently record continuously for 24-hours a day for days, weeks or even longer. In 1995, Sadeh et al.,1 under the auspices of the American Sleep Disorders Association (now called the American Academy of Sleep Medicine, AASM), reviewed the current knowledge about the role of actigraphy in the evaluation of sleep disorders. They concluded that actigraphy does provide useful information and that it may be a “cost-effective method for assessing specific sleep disorders...[but that] methodological issues have not been systematically addressed in clinical research and practice.” Based on that task force’s report, the AASM Standards of Practice Committee concluded that actigraphy was not indicated for routine diagnosis or for assessment of severity or management of sleep disorders, but might be a useful adjunct for diagnosing insomnia, circadian rhythm disorders or excessive sleepiness.2 Since that time, actigraph technology has improved, and many more studies have been conducted. Several review papers have concluded that wrist actigraphy can usefully approximate sleep versus wake state during 24 hours and have noted that actigraphy has been used for monitoring insomnia, circadian sleep/wake disturbances, and periodic limb movement disorder.3,4 This paper begins where the 1995 paper left off. Under the auspices of the AASM, a new task force was established to review the current state of the art of this technology.

The Role of Actigraphy in the Study of Sleep and Circadian Rhythms AMERICAN ACADEMY OF SLEEP MEDICINE REVIEW PAPER

Stress precipitates depression and alters its natural history Major depression and the stress response share similar phenomena, mediators and circuitries Thus, many of the features of major depression potentially reflect dysregulations of the stress response The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction) Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes Patients with atypical depression present with a syndrome that seems the antithesis of melancholia They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction

https://www.neurotransmitter.net/Gold.pdf

Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states

Heterochromatin has been defined as deeply staining chromosomal material that remains condensed in interphase, whereas euchromatin undergoes de-condensation. Heterochromatin is found near centromeres and telomeres, but interstitial sites of heterochromatin (knobs) are common in plant genomes and were first described in maize. These regions are repetitive and late-replicating. In Drosophila, heterochromatin influences gene expression, a heterochromatin phenomenon called position effect variegation. Similarities between position effect variegation in Drosophila and gene silencing in maize mediated by "controlling elements" (that is, transposable elements) led in part to the proposal that heterochromatin is composed of transposable elements, and that such elements scattered throughout the genome might regulate development. Using microarray analysis, we show that heterochromatin in Arabidopsis is determined by transposable elements and related tandem repeats, under the control of the chromatin remodelling ATPase DDM1 (Decrease in DNA Methylation 1). Small interfering RNAs (siRNAs) correspond to these sequences, suggesting a role in guiding DDM1. We also show that transposable elements can regulate genes epigenetically, but only when inserted within or very close to them. This probably accounts for the regulation by DDM1 and the DNA methyltransferase MET1 of the euchromatic, imprinted gene FWA, as its promoter is provided by transposable-element-derived tandem repeats that are associated with siRNAs.

Role of transposable elements in heterochromatin and epigenetic control

The circadian rhythms of sleep-wakefulness, rectal temperature, and plasma melatonin were measured in 10 healthy male subjects for five consecutive seasons. To minimize direct effects of seasonally changing environmental factors, the subjects stayed in a living facility for 4 days in each season, where ambient temperature, humidity, and social contacts were controlled, while the light intensity of the living room was substantially influenced by natural daylight. Seasonal variations were found in the timing of sleep, the mean body temperature, the phases of circadian temperature and melatonin rhythms, and the phase relation between sleep and the rectal temperature rhythm. The subjects went to bed earliest in summer, intermediate in spring and autumn, and latest in winter. A similar but more pronounced seasonality was observed in the wake-up time, which was earlier in summer than in winter. The acrophases of the rectal temperature and plasma melatonin rhythms, which were calculated by fitting a cosine curve, were located in an earlier time of day in summer than in winter. The phase-angle difference of the rectal temperature rhythm to sleep varied seasonally and was more positive in summer than in winter. These findings indicate that not only the external (to the local time) but also the internal (between circadian rhythms) phase relations of the human circadian rhythms depend on season.

Seasonal variation in the human circadian rhythm: dissociation between sleep and temperature rhythm.

Midday exposure to bright light changes the circadian organization of plasma melatonin rhythm in humans

Sleep EEG of eight healthy males and eight females aged 54–72 years were recorded at their homes. The electroencephalograms were visually scored and analyzed by spectral analysis using the FFT method. There were no significant differences in sleep parameters except for a higher percentage of stage 3 + 4 in females. The spectral power of the delta band EEG was classified into two frequencies: 0.5–2 Hz and 2–4 Hz. The total amount of the delta band spectral power through the night was significantly larger in females. Periodic fluctuation of delta band power was observed in females along with non-rapid eye movement–rapid eye movement cycles.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1440-1819.1999.00508.x

Gender difference of slow wave sleep in middle aged and elderly subjects

Several articles have appeared over the last years devoted to mental side effects during zonisamide (ZNS) treatment. In this study, we were particularly interested in psychotic episodes. Seventy-four epileptic patients with a history of ZNS treatment were surveyed retrospectively over the period spanning 1 March 1984 to 30 June 1994. They were divided into two groups according to the presence or absence of psychotic episodes during ZNS treatment. We analysed various factors pertaining to psychotic episodes during ZNS treatment. Of the 74 patients 14 had psychotic episodes. We found that the incidence of psychotic episodes during ZNS treatment was several times higher than the previously reported prevalence of epileptic psychosis, and that the risk of psychotic episodes was higher in young patients. In 13 patients, psychotic episodes occurred within a few years of commencement of ZNS. In children, obsessive-compulsive symptoms appeared to be related to psychotic episodes. It is important to terminate ZNS as soon as possible if psychotic episodes develop and never restart, even if seizures become worse. It cannot definitely be proved that ZNS causes psychotic episodes, as information on mental side effects during ZNS monotherapy is scant, but it does appear likely that ZNS contributes to psychotic episodes during polytherapy.

Psychotic episodes during Zonisamide treatment

Vitamin B12 (methylcobalamin) was administered orally (3 mg/day) to 9 healthy subjects for 4 weeks. Nocturnal melatonin levels after exposure to bright light (ca. 2500 lx) were determined, as well as the levels of plasma melatonin over 24 h. The timing of sleep was also recorded. Vitamin B12 was given blind to the subjects and crossed over with placebo. We found that the 24-h melatonin rhythm was significantly phase-advanced (1.1 h) in the vitamin B12 trial as compared with that in the placebo trial. In addition, the 24-h mean of plasma melatonin level was much lower in the vitamin B12 trial than with the placebo. Furthermore, the nocturnal melatonin levels during bright light exposure were significantly lower in the vitamin B12 trial than with the placebo. On the other hand, vitamin B12 did not affect the timing of sleep. These findings raise the possibility that vitamin B12 phase-advances the human circadian rhythm by increasing the light sensitivity of the circadian clock.

Masako Kohsaka

Papers

Seasonal variation in the human circadian rhythm: dissociation between sleep and temperature rhythm.

Midday exposure to bright light changes the circadian organization of plasma melatonin rhythm in humans

Gender difference of slow wave sleep in middle aged and elderly subjects

Psychotic episodes during Zonisamide treatment

Effects of vitamin B12 on plasma melatonin rhythm in humans: increased light sensitivity phase-advances the circadian clock?