Sleep Phys learning goals

NREM sleep EEG parameters

includes stages 1-3, with decreasing frequency and increasing amplitude of brain waves.

REM sleep EEG patterns

REM sleep is marked by low-amplitude mixed-frequency EEG activity, resembling awake states.

EMG EEG patterns

EMG shows reduced muscle tone in REM sleep, while other stages show greater muscle activity.

heart rate and thermoregulation show ___

show a marked decrease in NREM sleep and fluctuate in REM sleep.

Sleep cycle steps

The sleep cycle alternates between NREM and REM stages in approximately 90-minute intervals. The cycle typically starts with NREM stages (light to deep sleep) and progresses into REM sleep, with the duration of REM increasing as the night progresses.

Sleep health

-adequate sleep duration,

-sleep quality, and

-sleep timing

how do we measure sleep health

Measurement tools include

-actigraphy,

-polysomnography, and

-self-reported questionnaires (e.g., Pittsburgh Sleep Quality Index).

What are the tools to measure excessive sleepiness/alertness

The Epworth Sleepiness Scale (ESS), with scores >10 indicating excessive daytime sleepiness.

The Maintenance of Wakefulness Test (MWT) is another tool to assess alertness, with a cutoff of <8 minutes to indicate sleepiness.

sleep homeostasis

is the drive to sleep that increases with wakefulness and dissipates during sleep.

circadian phase

The internal biological clock that dictates optimal sleep-wake times, influenced by the SCN.

How is sleep homeostasis measured

Sleep homeostasis is measured by monitoring sleep duration and sleep pressure through EEG and polysomnography.

how are circadian phases measured

 Circadian phase is typically measured using melatonin onset or core body temperature rhythms

how are circadian periods measured

Circadian period is measured using constant routine protocols and actigraphy.

The SCN is

located in the hypothalamus, coordinates circadian rhythms through the release of melatonin. It is the master pacemaker for regulating sleep and wake cycles in response to light.

How does light exposure affect the SCN and circadian rhythms

Light exposure, particularly blue light, influences the SCN and resets the biological clock. This has been shown through studies using light-dark cycles to manipulate circadian rhythms.

What is the physiology of circadian photo reception

 The retina detects light through melanopsin in specialized ganglion cells, sending signals to the SCN to synchronize circadian rhythms with the external environment.

What is the phase response curve

The phase response curve describes how light exposure at different times of day advances or delays circadian rhythms, with light exposure in the evening delaying and morning light advancing the clock.

Phase response curves to light vs. melatonin

 Light exposure has a direct impact on the SCN and circadian timing, while exogenous melatonin, when taken at specific times, can shift the phase of the circadian clock, though its effects are more delayed than light.

total sleep deprivation vs sleep restriction on cognitive performance

Total sleep deprivation impairs cognitive performance more significantly than sleep restriction, which leads to gradual impairment over multiple days.

cumulative sleep restriction impact

Cumulative sleep restriction progressively worsens cognitive performance and increases sleepiness, with both showing a threshold effect where performance is markedly reduced after several nights of restricted sleep.

What physiological processes modulate daily patterns of performance

sleep-wake homeostasis, circadian rhythms, and the influence of sleep disorders.

How is recovery of performance after sleep restriction

 Recovery is typically slow, with cognitive performance improving after extended recovery sleep but not fully returning to baseline in many cases.

How does circadian phase influence the sleep and wake function

 Circadian phase influences optimal alertness and performance, with performance peaking during the biological day and dipping during the night (especially during the circadian trough).

sleep differences between animals

Sleep varies greatly between species. For example, some animals have polyphasic sleep, while others, like humans, have a monophasic sleep cycle. Species like dolphins and birds may engage in unihemispheric sleep.

poly vs monophasic sleep

Poly means there is more than one period of sleeping in a long block of time over a 24 hr period while mono is one long block of time.

What are some physiological adaptations for sleep of animals under environmental pressures

Many species have developed unique sleep strategies based on their environment. For instance, migratory birds sleep with one hemisphere of the brain at a time, and animals in cold environments may have developed special postures for thermoregulation during sleep.

sleep vs hibernation vs torpor

Sleep is a regular physiological state, while hibernation and torpor are energy-conserving states with reduced metabolic activity. In torpor, animals can lower their body temperature significantly.

How does behavior change during sleep

 Sleep involves behavioral states such as reduced responsiveness to stimuli and the characteristic postures associated with sleep in various species.

what are common non-human model organisms used in sleep and circadian research

Common models include rats, fruit flies (Drosophila), and mice. These models help explore sleep regulation mechanisms and genetic factors influencing sleep.

Biological factors that influence REM and NREM

These include neurotransmitters such as GABA, serotonin, and acetylcholine, as well as hormonal influences like melatonin and cortisol.

How does sleep change in the brain as it matures

As the brain matures, sleep becomes more organized, with a transition from polyphasic to monophasic sleep patterns, and the structure of sleep stages evolves.

Active vs quiet sleep (infants)

Active sleep in infants corresponds to REM sleep, while quiet sleep aligns with NREM sleep. These stages are considered immature forms of adult sleep.

What are the changes in sleep need that occur with child development

Sleep duration decreases with age, and the proportion of REM sleep decreases while NREM deep sleep increases. Napping becomes less frequent with age.

How does circadian timing and chronotypes(preference of wake and sleep times) change with age in children

Children tend to have earlier chronotypes, shifting to later bedtimes and wake times as they approach adolescence.

Chronotype

A person's natural tendency to sleep and wake at certain times, influenced by biological and environmental factors.

What happens if there is misalignment between sleep and biological timing in children

Misalignment between sleep and biological timing (e.g., early bedtimes) can result in sleep disturbances and daytime dysfunction.

What are common sleep problems in childhood

Common sleep problems in childhood include sleepwalking, night terrors, and insomnia. As children age, these issues often resolve or evolve into different types of sleep disturbances.

How does sleep change during the lifespan of an adult

As individuals age, sleep quality tends to decline. Older adults experience more fragmented sleep, reduced deep sleep (NREM), and increased sleep latency. Circadian rhythms also become less pronounced with age.

What are the differences in changes in sleep w/age vs age-related medical disorders

 Changes in sleep with age are primarily due to the natural aging process (e.g., reduced deep sleep and shorter sleep duration),

whereas sleep changes associated with age-related medical disorders (e.g., Alzheimer's, Parkinson's) are more pathological and can lead to severe disruptions in sleep architecture.

Insomnia related to adults

Sleep duration may decrease in older adults, but insomnia is more often a result of medical conditions, such as pain, depression, or neurological disorders, than the natural aging process.

How can medication affect sleep

Common medications in older adults, such as antidepressants, antihypertensives, and sleep aids, can contribute to both insomnia and daytime sedation, particularly in those who are sensitive to the sedative effects.

What are the consequences of sleep disruption for cognitive function in older adults

 Sleep disruption in older adults, especially insufficient sleep or fragmented sleep, is strongly linked to

-cognitive decline, including memory problems, difficulty concentrating, and an increased risk of dementia.

How do circadian rhythms change across the lifespan?

older adults often experience changes in circadian rhythm, including earlier sleep and wake times (advanced sleep phase), reduced amplitude of circadian rhythms, and a weaker response to external time cues.

energy conservation hypothesis

Sleep reduces metabolic activity and energy expenditure, particularly through a decrease in core body temperature.

restorative function hypothesis

Sleep helps repair and restore physiological systems, including the immune system.

memory consolidation hypothesis

Sleep plays a critical role in consolidating newly acquired information into long-term memory, with specific benefits for declarative and procedural memory.

synaptic plasticity hypothesis

Sleep enhances synaptic plasticity, promoting learning and memory.

immune regulation hypothesis

Sleep supports immune function by regulating cytokine production and enhancing immune responses.

Brain waste clearance hypothesis

The glymphatic system functions more efficiently during sleep, helping to clear metabolic waste products from the brain.

how does the basal forebrain promote wakefulness

with the neurotransmitter acetylcholine which leads to cortical arousal and attention

how does the locus coerulus promote wakefulness

With the neurotransmitter norepinephrine, which leads to vigilance, arousal, and attention

how does the raphe nuclei promote wakefulness

With the neurotransmitter seratonin which leads to mood, arousal, and NREM promotion

how does the VTA promote wakefulness

With the neurotransmitter dopamine which leads to motivation, reward, and alertness

how does the Tuberomammilary nucleus promote wakefulness

With the neurotransmitter histamine which leads to wakefulness, alertness, and prevents narcolepsy

How does the lateral hypothalamus promote wakefulness

With the nuerotransmitter oxrexin/hypocretin which stabilizes wake state; prevents narcolepsy

What are the brain regions promoting sleep

• Ventrolateral preoptic area (VLPO) and Median preoptic nucleus (MnPO), which release GABA and galanin to inhibit wake-promoting centers.
  

• VLPO is crucial for initiating and maintaining NREM sleep.

What are the neurochemicals involved in NREM

NREM sleep: Dominated by GABA and galanin, which inhibit arousal systems to promote deep sleep.

what are the neurochemicals involved in REM sleep

• REM sleep: Characterized by increased acetylcholine activity and decreased norepinephrine, serotonin, and histamine activity, promoting muscle atonia and vivid dreaming

What mutations are associated with Advanced sleep wake phase disorder

 Associated with mutations in PER3, PER1, and CK1δ/ε genes.

What mutations are associated with Delayed sleep wake phase disorder

Linked to PER3, PER1, and CK1δ/ε mutations.

What mutations are associated with narcolepsy type 1

Linked to mutations in the HLA-DQB1*0602 gene.

what mutation is associated with short sleep

Mutations in DEC2/P385R gene result in a natural short sleep phenotype.

Core clock gene transcription-translational positive feedback

Positive feedback: Clock and Bmal1 proteins form a heterodimer that activates transcription of the Per and Cry genes.

Core clock gene transcription-translational negative feedback

• Negative feedback: PER and CRY proteins dimerize and inhibit Clock/ Bmal1 transcription, leading to their degradation, resetting the cycle.

what is the influence of PER3 polymorphism on sleep and circadian physiology

The PER3 polymorphism (5-repeat vs. 4-repeat) affects the individual's sleep-wake cycle, with individuals with PER3 5/5 genotypes showing increased cognitive deficits and EEG slowing during biological night after sleep deprivation. However, the polymorphism does not significantly impact melatonin or cortisol rhythms during constant routine.

what is the impact of molecular clocks on cellular function and drug targets

Molecular clocks impact cellular processes like gene expression, cell cycle regulation, and metabolism. They influence drug efficacy by modulating circadian rhythms and optimizing drug delivery or action. For instance, certain chemotherapy drugs are more effective when administered during specific circadian phases.

how does caffeine influence cellular clock period and circadian phase

Caffeine lengthens the circadian period in human cells, affecting the timing of the circadian rhythm. It acts via the Adenosine A1 receptor, which alters the feedback loop between the Clock and Bmal1 genes, thereby affecting the phase and period of the circadian rhythm.

Compare and contrast classes of drugs promoting sleep and their mechanisms:

• GABA-A receptor agonists (e.g., zolpidem, eszopiclone) enhance GABAergic inhibition, promoting sleep.
  

• Melatonin receptor agonists (e.g., ramelteon) mimic melatonin, helping to synchronize circadian rhythms.
  

• Orexin antagonists (e.g., suvorexant) inhibit wake-promoting orexin signaling, promoting sleep.

What is the underlying brain mechanism occuring with wakefulness-promoting drugs

Amphetamines, modafinil, and caffeine increase norepinephrine, dopamine, and serotonin signaling, which activate wakefulness-promoting centers in the brain, reducing sleep pressure and enhancing alertness.

acute effects of common drugs on sleep

Drugs like benzodiazepines can promote quick sleep onset but may disrupt sleep architecture, reducing REM and SWS.

chronic effects of common drugs on sleep

Long-term use of sleep medications can lead to tolerance, dependence, and disrupted natural sleep patterns, especially in benzodiazepines

How does sleep change with depression

Depression is often linked to reduced SWS and increased REM sleep.

How do antidepressants affect sleep

Antidepressants may improve sleep continuity, but some classes (e.g., SSRIs) can suppress REM sleep.

Chronopharmacology

Chronopharmacology refers to the timing of drug administration to align with the body’s circadian rhythms, optimizing drug efficacy and minimizing side effects.

How does sleep alter sensory and motor physiology

Sensory processing is diminished during sleep, especially in NREM. However, the brain remains sensitive to certain stimuli, such as auditory signals, which can evoke K-complexes or arousals, especially in emotionally meaningful contexts.

How does sleep stage, time of night, sleep deprivation and age affect arousal thresholds

Arousal thresholds are lower during light sleep (stage 1), higher during deep sleep (SWS), and influenced by sleep deprivation and age. Older adults tend to have lower arousal thresholds. Sleep deprivation causes higher arousal threshold as well.

What physiological parameters become responsive to environmental stimuli during sleep

Heart rate, blood pressure, and brain activity (EEG) respond to external stimuli like sound, temperature, and touch during sleep

What are the auditory properties of an effective fire alram and how drugs influence arousal thresholds

Effective fire alarms should be high-pitched and between 70-75 dB at the pillow level to ensure awakening. Drugs like sedatives increase arousal thresholds, while stimulants lower them.

How is motor physiology changed during REM

REM sleep is characterized by muscle atonia due to GABAergic inhibition of motor neurons, which prevents acting out dreams

what are the consequences of muscle atonia failure in older adults with dementia

Failure of muscle atonia (e.g., REM Behavior Disorder) can lead to injuries like falls and trauma due to motor activity during sleep.

distinguish motor disorders during sleep

Motor disorders during sleep refer to conditions such as

-REM Behavior Disorder, which involves acting out dreams during REM,

-sleepwalking, and

-PLMS, which is involuntary leg jerks often during NREM

Compare the influence of sleep-wakefulness versus circadian influence on daily hormone patterns:

Sleep-wakefulness impacts hormones like growth hormone and prolactin, which show stronger sleep-driven rhythms.

Circadian rhythms control hormones like cortisol and melatonin, which peak and fall at specific times, independent of sleep

Effects of acute total sleep deprivation versus chronic sleep loss on endocrine physiology:

Acute sleep deprivation increases cortisol and decreases growth hormone secretion, while chronic sleep loss can lead to dysregulation of insulin, leptin, and ghrelin.

Influence of circadian misalignment on hormone release patterns

Circadian misalignment (e.g., from jet lag or shift work) causes disrupted hormone release, particularly melatonin and cortisol, which can have detrimental health effects.

impact of biological timing of food intake on metabolism

Eating during the biological night disrupts metabolism, leading to impaired glucose regulation, increased insulin resistance, and potential weight gain.

How does Core body temperature change during sleep

Core body temperature (CBT) follows a circadian rhythm, typically lowest at night and highest in the early evening. Humans typically fall asleep during the declining phase of CBT and wake during its rising phase

How does distal skin temperature change during sleep

it increases before sleep begins

How does distal proximal temperature change during sleep

The distal-proximal temperature gradient narrowing as sleep begins. A rapid rise in DPG is associated with shorter sleep onset latency (SOL).

Brain areas involved in thermoregulation and how these brain regions interact with wakefulness-sleep regions:

Preoptic nuclei (POA) in the anterior hypothalamus regulate thermoregulation. Warm-sensitive neurons in the POA promote sleep and vasodilation, while cold-sensitive neurons are active during wakefulness and promote thermogenesis. These regions work in conjunction with the sleep-promoting VLPO and wake-promoting regions like the locus coeruleus.

Where are temperature sensitive neurons in the brain and what are their firing patterns

Warm-sensitive neurons (30%) in the POA increase firing with increased temperature, promoting sleep. Cold-sensitive neurons (<10%) increase firing when temperature decreases, contributing to thermogenesis and being more active during wakefulness.

How does skin temperature information feedback to the brain

Skin temperature is detected via TRP (transient receptor potential) channels in the skin, which send input to the POA. This feedback helps modulate the body's thermoregulatory responses, such as vasodilation or vasoconstriction, based on temperature signals.

What is the altered relationship between body temp rhythms and sleep timing in insomnia

In sleep-onset insomnia (SOI), there is a delayed decline in CBT before sleep onset.

Conversely, in sleep maintenance insomnia and early morning awakening (EMA), CBT declines earlier than normal. This misalignment between body temperature rhythms and sleep timing may contribute to insomnia symptoms.

How can skin temperature be manipulated to impact arousal

Mild warming of the skin (e.g., wearing socks, taking a hot bath) can help facilitate the decline of CBT and improve sleep onset. This has been shown to increase SWS and sleep efficiency, particularly in individuals with insomnia.

IL-1B influence on sleep

 IL-1β promotes NREM sleep and inhibits wake-active neurons in the preoptic area, contributing to sleep.

IL-6 influence on sleep

IL-6 is elevated during infections, promotes sleep, and has a circadian rhythm.

TNF-a influence on sleep

TNF-α also promotes NREM sleep and is elevated in conditions like insomnia.

How does the circadian system influence immune function

Circadian clocks exist in immune tissues, and PER2 and Rev-Erbα rhythms regulate cytokine production. Herpesvirus infections are more severe during the sleep phase, showing circadian modulation of immune responses.

How do cytokines influence neurobiology of sleep and wakefulness

Imflammatory

IL-1β increases NREM sleep by inhibiting wake-promoting neurons.

TNF-α increases NREM sleep in mice, while

IL-6 is elevated during insomnia and affects both immune function and sleep patterns.

Anti-inflammatory
- IL-1ra (IL-1ra blocks IL-1 effects on sleep)
- IL-10 (reduce NREM)

how does sleep loss impact the immune system

Sleep deprivation reduces the effectiveness of the immune system, including impairing antibody production. It has been shown to lower immune response to vaccinations, such as for hepatitis B and influenza.

How can immune challenges influence sleep

Immune challenges like infection can alter sleep patterns, typically increasing NREM sleep and causing sleep fragmentation. Severe infections can disrupt REM sleep and lead to immune-related sleep changes.