So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

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

Human behavior shows large interindividual variation in temporal organization. Extreme "larks" wake up when extreme "owls" fall asleep. These chronotypes are attributed to differences in the circadian clock, and in animals, the genetic basis of similar phenotypic differences is well established. To better understand the genetic basis of temporal organization in humans, the authors developed a questionnaire to document individual sleep times, self-reported light exposure, and self-assessed chronotype, considering work and free days separately. This report summarizes the results of 500 questionnaires completed inapilotstudy.Individualsleeptimesshowlargedifferencesbetweenworkand freedays,exceptforextremeearlytypes.Duringtheworkweek,latechronotypes

/pdf/life-between-clocks-daily-temporal-patterns-of-human-2i1rqfyvgw.pdf

Life between clocks: daily temporal patterns of human chronotypes.

Humans may be subject to seasonal variations, as evidenced by the existence of seasonal affective disorder (SAD) and midwinter insomnia. However, some recent studies have shown that the seasonal variation in the phase of the circadian rhythm is relatively weak in healthy humans. In the present study, evidence is found that there is no seasonal variation in the phase of the endogenous circadian rhythm at all. Body temperature, cortisol excretion, and subjective alertness of six subjects recorded under constant routine conditions showed no systematic seasonal variation in circadian phases. This finding indicates that secondary zeitgebers blocked or counterbalanced the seasonal variation in the entrainment effect of the natural photoperiod. The human being may live in an environment in which the photoperiod has lost its status of primary zeitgeber.

Absence of seasonal variation in the phase of the endogenous circadian rhythm in humans

The role of endogenous circadian rhythmicity in autonomic cardiac reactivity to different stressors was investigated. A constant routine protocol was used with repeated exposure to a dual task and a cold pressor test. The 29 subjects were randomly divided into two groups in order to manipulate prior wakefulness. Group 1 started at 09:00 h immediately after a monitored sleep period, whereas group 2 started 12 h later. Measures of interbeat intervals (IBI), respiratory sinus arrythmia (RSA, a measure of parasympathetic activity), pre-ejection period (PEP, a measure of sympathetic activity), as well as core body temperature (CBT) were recorded continuously. Multilevel regression analyses (across-subjects) revealed significant (mainly 24 h) sinusoidal circadian variation in the response to both stressors for IBI and RSA, but not for PEP. Individual 24 + 12 h cosine fits demonstrated a relatively large interindividual variation of the phases of the IBI and RSA rhythms, as compared to that of the CBT rhythm. Sinusoidal by group interactions were found for IBI and PEP, but not for RSA. These findings were interpreted as an indication for endogenous circadian and exogenous parasympathetic (vagal) modulation of cardiac reactivity, while sympathetic reactivity is relatively unaffected by the endogenous circadian drive and mainly influenced by exogenous factors.

http://www.vu-ams.nl/fileadmin/user_upload/publications/Van_Eekelen_2004.pdf

Circadian variation in cardiac autonomic activity: reactivity measurements to different types of stressors.

In this study the effects of virtual reality exposure therapy (VRET) were investigated in patients with panic disorder and agoraphobia. The level of presence in VRET was compared between using either a head-mounted display (HMD) or a computer automatic virtual environment (CAVE). Results indicate that there was no relationship between the level of experienced presence and treatment outcome. Analyses indicate that VRET in general was more effective than no treatment. No differences in effectiveness were found between VRET using an HMD or CAVE.

Virtual Reality Exposure Treatment of Agoraphobia: a Comparison of Computer Automatic Virtual Environment and Head-Mounted Display

Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression.

The circadian activity rhythm was assessed over a one-week period using a wrist-worn activity monitor in 59 patients with a history of recurrent suicide attempts. In 40 of these patients a second recording was made 6 months later. Platelet serotonin (5-HT) and monoamine oxidase-B activity (MAO) were measured. Suicidal ideation, borderline personality disorder and impulsiveness were associated with the absence of a clear 24-hour periodicity in motor activity. Depressive mood and hopelessness were associated with a less regular bed-in time and a lower daytime activity. Platelet 5-HT as well as MAO correlated negatively with the amplitude of the circadian activity rhythm. Our results support the suggested link between suicidality, altered circadian activity and serotonergic function.

Gerard A. Kerkhof

Papers

Absence of seasonal variation in the phase of the endogenous circadian rhythm in humans

Circadian variation in cardiac autonomic activity: reactivity measurements to different types of stressors.

Virtual Reality Exposure Treatment of Agoraphobia: a Comparison of Computer Automatic Virtual Environment and Head-Mounted Display

Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression.

Suicidality, circadian activity rhythms and platelet serotonergic measures in patients with recurrent suicidal behaviour.