IPHY 4580: Sleep Physiology Exam #1

Sleep

- reversible behavioral state of perceptual disengagement from, and unresponsiveness to the environment

- complex combination of physiological and behavioral processes

Observational studies

Do not tell us about the underlying physiology/processes in the brain that regulate, or are impacted by sleep

Circadian process

-Tells the brain what time of day it is

- signal dissipates at some point and allows the manifestation of sleep to occur

Homeostatic process

- Tells the brain how long we've been awake

- increases exponentially with the duration of prior wakefulness

Sleep pressure

- the homeostatic drive to sleep

- increases the longer we are awake

-dissipates through the course of sleep and starts again when we wake up

Sleep inertia

- state characterized by cognitive impairment, grogginess, and disorientation that is experienced upon rising from sleep

- has an impact on performance

- can be used as an indicator for adequate sleep

What determines compensation for sleep debt?

Combination of duration and intensity of sleep

Sleep homeostasis

- increased urge to sleep when sleep is insufficient/absent

- reduced urge to sleep in response to prior, adequate sleep

Determinants of sleep intensity

- duration of wakefulness (longer awake = more sleepy)

- arousal thresholds for sound and tactile stimuli are higher during slow wave sleep

sleep parameters and duration of wakefulness

Relationship is not linear

EEG sleep intensity

- Indicator of sleep pressure and sleep depth in low frequency

- greatest at the start of sleep and dissipates as sleep pressure decreases

Delta wave activity

- Indicator of slow wave activity

- unlikely to wake up during this stage

- highest in stage 3 and 4 NREM sleep

- increases proportionally with prior wakefulness

- decreases over the course of sleep

- independent of the circadian phase at which sleep is initiated

Naps and EEG activity

SWA is less powerful

NREM sleep

- synchronous, w/ characteristic waveforms like sleep spindles, K complexes, and high-voltage slow waves

- minimal or fragmentary mental activity

- relatively inactive, yet actively regulating brain in a moveable body

REM sleep

- EEG activation, muscle atonia, and episodic bursts of rapid eye movements

- tonic vs phasic distinction

REM phasic sleep

In humans: rapid eye movements, muscle twitches, cardiorespiratory irregularities

Sleep onset

- in normal human adults: entered through NREM sleep

Sleep onset parameters

K complex or sleep spindles on and EEG

Components of sleep health

- sleep duration: 7 or more hours for adults aged 18-60

- sleep timing

- sleep regularity

- sleep quality

Health consequences associated with inadequate sleep

If you sleep < 6-7 hours a night: weight gain and obesity, diabetes, heart disease and stroke, depression, impaired performance, risk of accidents, cancer, impaired immune function, increased pain

Social jet lag

- Our body's biological clock and our actual sleep schedules don't match up

- average mid-sleep time increases during the weekend when we are not working

- greatest difference in our 20s, decreases as we age

COVID and sleep habits

In college students

- time in bed devoted to sleep increased by ~30 minutes during weekdays and by ~24 minutes on weekends

- sleep regularity improved by ~12 minutes

- sleep timing became later by ~50 minutes during weekdays and by ~25 minutes on weekends

Phylogeny

The study of relationships among different groups of organisms and their evolutionary development

Evolution

The change in the characteristics of a species over several generations...relies on the process of natural selection

Sleep in mammals

- cyclical alteration between NREM and REM sleep

- Total sleep time (TST): varies from < 3h to > 20h — not a lot of consistency between members of the same phylogenetic order

- REM varies from 0-8h per 24h day

Cortex size and sleep

Does not correlate with sleep amount

Dolphin and beluga whale sleep

these mammals can sleep with one hemisphere awake and the other asleep, little to no REM sleep

Walrus sleep

- unihemispheric SWS in water and bilateral SWS on land

- spontaneous wakefulness— 3 days without evidence of sleep rebound

Mammalian sleep duration

- correlation with body mass, basal metabolic rate (BMR), brain size, trophic level, and food availability

- higher BMR = less NREM sleep

- inverse relationship between gestation period and REM sleep time

Torpor

- Form of dormancy used by mammals and birds that can be used daily

- entered and exited through sleep

- can recur in a circadian rhythm or last for weeks/months

- can be aroused, but slow response when stimulated

Hibernation

- adaptation to cold or food scarcity

- entered and terminates in the form of NREM sleep

- body temp can reduce to below 10 C to as low as -3 C

- greatly reduced energy consumption

- difficult to arouse — takes minutes to fully wake up

Common feature of torpor and hibernation

Decreases in metabolism and body/brain temperature

Sleep vs daily torpor

- torpor does not meet the same functional needs that sleep does

- torpor has less powerful slow wave activity

Sleep vs. hibernation

- animals arouse regularly from hibernation despite the high energetic costs of arousals

- animals arouse from hibernation and go to sleep

- SWA is high at the initiation of post-hibernation sleep and subsequently decreases

Sleep in birds

- don't lose muscle tone when asleep

- episodes of NREM and REM sleep (in short episodes)

- NREM sleep: 2.5 minutes

- REM sleep: 9 seconds

- waterfowl can sleep while swimming

- birds can sleep while flying

Migrating birds

During migration season: duration of time awake increases

Sleep in lower vertebrates and invertebrates

- they not meet the electrophysiologic criteria for the definition of sleep

- however, demonstrate the characteristics of sleep

Basic definition of sleep

- minimal movement

- typical sleep posture

- reduced responsiveness/increased threshold to external stimuli

- quickly reversible

Characteristics of sleep in flies

- sex differences

- age related changes

- caffeine/histamine agonists increase wakefulness

- immune challenge alters sleep

- sleep rebound after sleep deprivation

- sleep deprivation induces inflammation; impairs learning

Sleep in newborns

- active sleep: declines from ~50% at birth to ~20-25% at 12 months

- quiet sleep: trace alternant disappears by 6 weeks; sleep spindles appear at 4 weeks; NREM stages differentiate by 6-9 weeks; K complexes appear at 6 months; SWS at 3-6 months

- intermediate sleep: declines across first year

- sleep cycle: ~50 minutes at birth

Active sleep (newborns)

- uneven respiration

- muscle atonia, but facial muscle activity

- continuous EEG activity

- REM

Quiet sleep (newborns)

- even respiration

- inactive

- discontinuous EEG (trace alternant)

- no eye movements

Napping and development

Frequency of napping at least one day or more a week decreases with age into adolescence

SWA and development

- increases through early development

- a ~90 minute cycle appears around 2-5 years old

- SWS and SWA decline by 40% between tanner stages 1-5

tanner scale for onset and progression of puberty

- scale of physical development in children, adolescents, and adults

- defines physical measurements of development

- based on external primary and secondary sex characteristics (size of breasts, genitals; testicular volume; development of pubic hair)

- stage 1: prepubertal

- stage 5: mature

Causes of developmental change in SWA

- cortical synaptic density increases during the first year —> provides appropriate substrate for synchronized EEG activity

- cortical synapses proliferate and then are pruned across development —> reduces EEG amplitude and SWA

Sleep across the lifespan

- "normal is a moving target and spans an age(development)-dependent range

- biologically regulatory processes change predictably

- phase delay, then phase advance

- shorter sleep with age

Sleep across lifespan (graphic)

- around ages 35-75: sleep patterns remain relatively the same, then change

- decrease SWS, increase in interruptions during the night that disturb sleep

Colorado Longitudinal Twin Study

- sleep problems declined over time

- early sleep problems don't seem to have appreciable implications for later executive functioning

- however, those whose sleep problems decrease more across time show better general executive control in late adolescence

Socio-cultural behaviors that impact sleep

- infant co-sleeping

- children spending "quality time w/ parents

- adolescents and school start times

- college students and life-style choices

Newborn/infant sleep patterns

- More active in sleep

- 50% REM

- several periods of sleep

- need naps

Toddler sleep patterns

Sleep begins to resemble adult patterns

Sleep patterns in children

Experience more deep sleep

Adolescent sleep patterns

- shift to later sleep-wake cycle

- experience daytime sleepiness

Adult sleep patterns

need regular sleep schedule to obtain sufficient, quality sleep

Older adult sleep pattern

- more likely to have medical problems

- sleep disorders

- sleep less efficiently

Changes in sleep with age

- reduced total sleep time (TST)

- reduced sleep efficiency

- reduced SWS (stage 3 and 4)

- increased wakefulness after sleep onset (WASO)

- all lead to reduced homeostatic sleep drive

Odds ratio (OR)

- measure of association between an exposure and an outcome

- represents the odds than an outcome will occur given a particular exposure compared to the odds of the outcome occurring in the absence of that exposure

OR = 1

exposure does not affect odds of outcome

OR > 1

exposure is associated with higher odds of outcome

OR < 1

exposure is associated with lower odds of outcome

Consequences of disturbed sleep in adults

- difficulty sustaining attention

- slowed response time

- difficulty with memory

- decreased performance

Factors affecting ability to sleep in older adults

- medical illness

- medications/polypharmacy

- circadian rhythm disturbances

- primary sleep disorders

Medical conditions co-morbid with insomnia

- pain (one of the strongest inducers of arousal)

- neurological disorders (restless leg syndrome, dementia/AD, Parkinson's)

- organ-system failures (angina, CHF, asthma, COPD, gastric reflux, incontinence, benign prostatic hyperplasia

Psychiatric conditions co-morbid with insomnia

- mood disorders (MDD, bipolar)

- anxiety disorders (GAD, panic disorder, PTSD)

- adjustment disorders

- psychotic disorders

- substance abuse

Drugs that contribute to insomnia

- hypnotics

- anti-hypertensives

- anti-histamines

- tranquilizers

- anti-depressants

Sedating drugs, if taken during the day can induce napping, and might interfere w/ night time sleep

Ascending reticular activating system (ARAS)

- neurons reside in the brain stem and project to the thalamic nuclei

- in thalamus, neurons synapse on diffuse projection pathways to the cerebrum

Arousal

- global process that is facilitated by several discrete neuronal groups localized within and adjacent to the pontine and midbrain reticular formation and its extension into the hypothalamus

- concurrent changes in systems: autonomic, motor, endocrine, sensory

Properties of arousal-promoting systems

-neurons have long, projecting axons w/ extensive terminal fields —> impinge upon multiple regions of the brain stem and forebrain

- evidence: increased discharge during arousal or wake status compared with sleep

- redundancy: allows other systems to compensate for a defect in a particular system, or changes in receptor sensitivity

- activated and deactivated w/in seconds of a change in behavioral state

Major nuclei involved in the control of wakefulness

- lateral hypothalamus (LH)

- basal forebrain (BF)

- tuberomammillary nucleus (TMN)

- raphe nucleus (dorsal and median)

- locus coeruleus (LC)

- PPT

- LDT

Major nuclei involved in the control of sleep

- MnPO/VLPO

- PeF

- TMN

- Raphe

- LC

- PPC

- LDT

- vPAG

sleep promoting neurotransmitters

adenosine, pro-inflammatory cytokines, prostaglandin D2, GHRH

adenosine

- basal forebrain, VLPO

- byproduct of ATP catabolism

- inhibits Ach in basal forebrain

- activates VLPO

- increases during wakefulness

Pro-inflammatory cytokines

- IL-1 and TNF-alpha generally induce NREM sleep and suppress REM sleep

- IL-1 (-) wake-active neurons in the pre-optic area

prostaglandin D2

- promotes NREM sleep

- circulates in CSF

- (+) DP1 receptors to release adenosine --> A2a receptors in BF and VLPO --> (-) TMN

GHRH

- GH surge associated w/ first stage 3/4 SWS episodes

- (+) GABAergic hypothalamic neurons

- Activates c-Fos expression in GABAergic neurons in MnPO and VLPO

serotonin

- inverse relationship between it and REM sleep

GABAergic neurons in vlPAG

- active during NREM

- INHIBIT entry into REM (REM-OFF)

GABAergic neurons in SLD

- (-) vlPAG neurons --> REM-ON

Noradrenaline and 5-HT in DR

- (+) REM-OFF and (-) REM-ON

- silent during REM

cholinergic neurons

- (-) REM-OFF and (+) REM-ON

orexin

(+) REM-OFF

VLPO

(-) REM-OFF

glutamate

- SLD: (+) inhibitory interneurons in the medulla and spinal cord --> (-) motorneurons --> REM atonia

- PB/PC: (+) forebrain and produce characteristic REM EEG

stage 1 sleep

- persists for 1-7 minutes at the onset of sleep

- easy to arouse

- transitional stage throughout the night

stage 2 sleep

- signaled by sleep spindles or K-complexes

- more intense stimulus is required to cause arousal

- EEG voltage begins to appear