Please write your name next to the reading you want to summarize

Readings Names email

Reading 1 Evelyn Chan evechan1322@gmail.com

Carskadon, M.A., Dement,

W.C. (2017). Normal human
sleep: an overview. In
Principles and Practices of
Sleep Medicine (Sixth
Edition). Kryger, M.E., Roth,
T., Dement, W.C. editors.

Reading 2 Amber Iny amber.triplets@gmail.com

Czeisler, C.A. & Buxton,

O.M. (2017). Human
Circadian Timing System
and Sleep-Wake Regulation.
In Principles and Practices
of Sleep Medicine (Sixth
Edition). Kryger, M.E., Roth,
T., Dement, W.C. editors.

Reading 3 Dariya Georgieva dariya9125@gmail.com

Kivelä, L., Papadopoulos, M.

R., & Antypa, N. (2018).
Chronotype and psychiatric
disorders. Current sleep
medicine reports, 4(2), 94-
103.

Reading 4 Rebeca Cruz rebeccacruz19@gmail.com

Anafi, R. C., Kayser, M. S.,

& Raizen, D. M. (2019).
Exploring phylogeny to find
the function of sleep. Nature
Reviews Neuroscience,
20(2), 109-116

Reading 5

Klinzing, J. G., Niethard, N.,

& Born, J. (2019).
Mechanisms of systems
memory consolidation
during sleep. Nature
neuroscience, 22(10), 1598-
1610

Reading 6 Cassidy Cartmill cassidycartmill@gmail.com

Lewis, P. A., & Bendor, D.
(2019). How targeted
memory reactivation
promotes the selective
strengthening of memories
in sleep. Current Biology,
29(18), R906-R912.

Reading 7

Walker, M. P. (2010). Sleep,

memory and emotion.
Progress in brain research,
185, 49-68.

Reading 8 Nesrine Mesli meslines1111@gmail.com

Buysse, D. & Harvey, A. G.

(2017). Insomnia: recent
developments and future
directions. In Principles and
Practices of Sleep Medicine
(Sixth Edition). Kryger, M.E.,
Roth, T., Dement, W.C.
editors

Reading 9 Bianca Coletta bcoletta99@gmail.com

Wamsley, E. J. (2013).
Dreaming, waking conscious
experience, and the resting
brain: report of subjective
experience as a tool in the
cognitive neurosciences.
Frontiers in psychology, 4.

Reading 10 Widaad Badourkhan widaad.bdk24@gmail.com

Tuominen, J., Stenberg, T.,

Revonsuo, A., & Valli, K.
(2019). Social contents in
dreams: an empirical test of
the social simulation theory.
Consciousness and
cognition, 69, 133-145.

Reading 11 Julia Lapena julialapena08@gmail.com

Malinowski, J. E., & Horton,

C. L. (2015). Metaphor and
hyperassociativity: the
imagination mechanisms
behind emotion assimilation
in sleep and dreaming.
Frontiers in Psychology, 6,
1132.

Midterm (Oct. 14th)

Reading 12 Lisa Pennel lisa.pennel@gmail.com

Hill, C. E., & Knox, S.

(2010). The use of dreams
in modern psychotherapy.
International review of
neurobiology, 92, 291-317.

Reading 13 Tala Masoud tjkm2002@gmail.com

Konkoly, K. R., Appel, K.,

Chabani, E., Mangiaruga,
A., Gott, J., Mallett, R., ... &
Paller, K. A. (2021). Real-
time dialogue between
experimenters and
dreamers during REM sleep.
Current Biology, 31(7),
1417-1427.

Reading 14 Passang Regyal paree207@gmail.com

Gieselmann, A., Ait Aoudia, M.,

Carr, M., Germain, A., Gorzka, R.,
Holzinger, B., ... &
Pietrowsky, R. (2019). Aetiology
and treatment of nightmare
disorder: State of the art and future
perspectives. Journal of sleep
research, 28(4), e12820.

Reading 15 Hannah Cami hannahccamilla@gmail.com

Carr, M., & Nielsen, T. (2017). A

novel Differential Susceptibility
framework for the study of
nightmares: Evidence for trait
sensory processing sensitivity.
Clinical psychology review, 58, 86-
96.

Reading 16

Boeve, B. F. (2010). REM sleep

behavior disorder. Annals of the
New York Academy of
Sciences, 1184(1), 15-54.

Reading 17 Cassandra Sorin cassiesorin17@gmail.com

 Nielsen, T., Svob, C., & Kuiken, D.
(2009). Dream-enacting behaviors
in a normal
population. Sleep, 32(12), 1629-
1636.

Reading 18

Reading 19

Reading 1- Normal Human Sleep, An Overview

Two States: Rapid Eye Movement (REM) and non-REM (NREM) sleep
● They alternate cyclically during sleep episodes

NREM sleep (quiet sleep)

● relatively inactive yet actively regulating brain in a movable body
● Synchronous cortical EEG
● Sleep spindles K-complexes
● High voltage slow waves
● Low muscles tonus
● Minimal psychological activity
● Minimal or fragmented brain activity
● Conventionally divided into four stages

○ Stage one lowest arousal threshold, and stage four highest arousal threshold

REM sleep (active sleep)

● Activated brain in a paralyzed body
● Desynchronized EEG
● Muscles limp (atonic)
● Episodic bursts of active eye movements
● Cats have ponto-geniculo-occipital (PGO) wave
● Dreams!

Nightly Adult Sleep Cycle

● Begins in NREM, goes through stage 2,3, and 4 (updated version just N2 and
N3)
● Then first REM sleep after 80-100 min
● Then alternate NREM and REM every 90 min- ish
● NREM stage 3 and 4 (or N3) concentrate, clear early NREM
● REM sleep episodes longer across night
Age Changes and Sleep
● Newborns: REM before NREM and shorter sleep cycle (50 minutes)

○
More REM sleep in the first two years, then a shift as NREM slow
wave (stage 3 and 4) sleep emerges
● Slow-wave sleep decrease by 40% in preteen years and continue to decrease as
you age
● REM sleep time same across the board from past newborns (toddlers) to old age

Sleep Definition
● Sleep is a reversible behavioral state of perceptual disengagement from and
unresponsiveness to the environment

Sleep Onset
● Onset usually through NREM sleep
● Electromyogram (EMG)

○May show gradual reduction of muscle tonus as you approach sleep,

but overall, not that great of a measure
● Electrooculogram (EOG)
○ Shows slow, asynchronous eye movements, disappears several
minutes after EGG changes described bleow
○
Slow eye movements- coincides- person perceived sleep onset,
patients report they are still awake
● Electroencephalogram (EEG)
○ Changes from clear rhythmic alpha activity (awake waves) to low-
voltage mixed frequency pattern (stage one)
○ Occurs seconds to min after start slow eye movements
● Issues:
○ Onset stage 1 EEG not a clear indication of sleep across researchers

○ Some use K-complex or sleep spindles from stage two to

acknowledge sleep onset
○
Falling asleep is not a unitary event - wavering wake/sleep till sleep
usually takes over
● General consensus: EEG change to stage one, accompanied by slow eye
movements signals the onset of sleep
○ Can reliably detect within several seconds

Behavioral Concomitants of Sleep Onset

● Simple behavioral task

○ Volunteers asked to tap two switches alternately at steady pace

○ Simple behavior continues after onset of slow eye movements, persist

several seconds after EEG change stage 1 pattern
 ○ Then behavior stops only starting again after EEG becomes wake
pattern again
● Visual Response
○ Bright light in front of subject's eyes, asked to respond when light flash
seen, press microswitch taped to hand
○ EEG stage 1 or stage 2 pattern, response absent more than 85% of
time
○ Volunteers say after they did not see the flash when brain in these
stages= example of perceptual disengagment from environment
● Auditory Response
○ Series of tones played on earphone, subject instructed to respond
each time a tone is heard
○ Reaction time longer in proximity with stage one sleep, response
absent in further sleep stages
○ To return to responding, brain needs waking EEG pattern
● Olfactory response
○ Response here depends on sleep state/what the smeel is

○ Response graded scents (eg. Peppermint (neg) and pyridine (neg) )

maintained in stage one sleep
○ In later stages
■ Peppermint not consciously smelled in stage 2/4 or in
dreams
■ Pyridine never smelled in stage 4, occasionally in stage 2
or dreams
○ In conclusion, olfactory in humans, not great indication of sleep stages
● Response to meaningful stimuli
○ People have lower arousal threshold to their own names

○ Mothers more likely to hear their own babies cries compared to other
babies
○ Appropriate response to sleep improved when nonmeaningful stimulus
made meaningful by linking absence of response to punishment
■ Sirens, flashing lights, threat of electric shock
○ So, sensory processing does continue after onset of sleep
● Hypnic Myoclonic
○ general or localized muscle contraction very often associated with
rather vivid visual imagery
○ Occur more commonly with stress or unusal sleep schedules

○ Precise nature not understood

 ■ Marked dissociation of REM sleep: (hypnagogic
hallucination) imagery part of REM happens when there is
no normal REM sleep function that inhibits motor
movements
■ So response by person to image, result in movement or
jerk
○ Increased frequency events= irregular sleep schedules= increased
probability REM sleep happening at the wake-sleep transition
■ Though this is NOT NORMAL for adults!!!

Memory Near Sleep Onset

● Transition wake to sleep produces memory impairment
● Sleep closes gate between short-term and long term memory storage
● Experiment: pre-sleep word pairs presented to volunteers over a loudspeakers of
1-minutes intervals
○ Subject awakened either 30 sec or 10 min after onset of sleep (EEG
stage one), then asked to recall words presented before sleep onset
○ 30-sec condition, associated consistent level of recall from whole 10
min before sleep onset
■ Long term and short term accessible
○ 10 min condition, recall good for only 10 to 4 min before sleep onset,
then fell off from that point until sleep onset
■ Only long term accessible
● Possible conclusion one: sleep inactivates transfer of storage from short to long
erm memory
● Possible conclusion two: encoding of info before sleep onset insufficient strength
to recall (anterograde amnesia)
● Pretty solid conclusion: if sleep persist around 10 min, memory lost a few min
before sleep
● Patients excessive sleepiness can expiree memory problems in day if sleep
becomes intrusive

Learning and Sleep

● Perceptual and motor learning in sleep – growing interest in this!
● Recent research- roles of REM and NREM sleep in this still under examination

Progression of Sleep Across the Night Pattern of Sleep in a Normal Young Adult
● Simplest case- young adult sleeping well, 8 hours per night
● First go through NREM sleep, REM sleep 80 min after

○ Then NREM and REM alternate between 90 minute cycle

● First Sleep Cycle
○ Stage One- 1-7 minutes at sleep onset
■ Low threshold arousal
■ Transitional stage
 ■ Severe disrupted sleep, increase amount/precent of stage
one
○ Stage 2- NREM
■ Sleep spindles or K complexes in EEG
■ Continues 10-25 minutes
■ More intense stimulus needed produce arousal
■ Same stimulus produce arousal stage one, make K-
complex, no awakening stage 2
○ Ascent lighter NREM sleep stages (brief 1-2 minute)

○ Followed by 5-10 min stage 2, interrupted by body movements

precede initial REM episode
○ First REM sleep short-lived (1-5 min)

○ REM episode arousal threshold variable

○ Theories to explain variable arousal threshold of REM sleep:

■ Person's selective attention to internal stimuli preclude
responses
■ Arousal stimulus incorporated into dream instead of waking
up
○SWS- synchronized sleep, synonym all NREM sleep in other species
distinct from
■ SWS (stages 3 and 4) in humans
● NREM-REM Cycle
○ NREM and REM sleep alternate through night in cyclic fashion

○ REM sleep longer across night

○ Stage 3 and 4 occupy less time second cycle, might disappear from
later cycles
○ average length first NREM-REM sleep cycle (70 –100 min)

○ the average length second and later cycles (90-120 min)

○ average period of the NREM-REM cycle ( 90 - 110 min) across night

Distribution of Sleep Stages across the Night

● Young adults SWS dominates NREM portion of sleep towards beginning 1/3

○ Homeostatic sleep system, highest at sleep onset diminshes across

night as sleep pressure lowers
● REM longest last 1/3 of night
○ Thought to be linked to circadian oscillator, gauged by swings in body
temperature

Length of Sleep
● Most young adults sleep 7.5 hours weekday and 8.5 weekends
 ● Volitional determinants (staying up late, waking by alarm, so on)
● Genetic determinants
● Length of prior wake
● Circadian rhythms: when one sleep determine how long one sleeps
● Sleep extended, REM sleep amount increases, as REM sleep depends on
persistence of sleep in peak circadian time to happen

Generalizations about Sleep in the Normal Young Adult

● Sleep is entered through NREM sleep.

● NREM sleep and REM sleep alternate with a period near 90 minutes.
● SWS predominates in the first third of the night and is linked to the initiation of sleep
and the length of time awake.
● REM sleep predominates in the last third of the night and is linked to the circadian
rhythm of body temperature.
● Wakefulness in sleep usually accounts for less than 5% of the night.
● Stage 1 sleep generally constitutes approximately 2% to 5% of sleep.
● Stage 2 sleep generally constitutes approximately 45% to 55% of sleep.
● Stage 3 sleep generally constitutes approximately 3% to 8% of sleep.
● Stage 4 sleep generally constitutes approximately 10% to 15% of sleep.
● NREM sleep, therefore, is usually 75% to 80% of sleep.
● REM sleep is usually 20% to 25% of sleep, occurring in four to six discrete episodes.

Factors Modifying Sleep Stage Distribution

● Age related difference sleep in newborn infant

● Wake to sleep through REM (active sleep)

● NREM-REM sleep present from birth but 50-60 min compared to 0- min in
adults
● Full EEG NREM emerge over 2-6 months of life

● Brain structure/function support high-voltage slow wave EEF activity, 3

and 4 stage more prominent
● SWS max in children, decline in age
● Impossible to wake young in SWS of night's first sleep cycle

● Children/mid-adolescence often "skip" first REM episode

○ Perhaps due to quantity/intensity of slow-wave activity early in

night
● Age 60 years, SWS might no longer be present in men, women may still
maintain SWS later
● absolute amount of REM sleep correlated with intellectual functioning,
declines with brain dysfunction in elderly
● Arousal during sleep increase with age
 ○ Extended wake episode increase (both where individual aware
and can report/ brief unremembered wake)
○ The last one probs related to other old-age associated sleep
disorders
● Sleep elderly- more individual diversity, can't ben generalized like young
adults

Prior Sleep History

● Prior sleep history: sleep loss one plus nights shows sleep pattern favor SWS in
recovery, in place of REM sleep
○ Recovery sleep prolonged and deeper

○ Higher arousal threshold

● If person deprived of REM or SWS specifically, preference will be a rebound of
that deprived stage
● Irregular sleep schedule: premature REM sleep (SOREMPs)
● Labatory sleep evaluation: delayed onset of REM sleep, skipping first REM
episode or disrupted.
○ REM sleep in lab less than normal REM sleep

Circadian Rhythms
● REM: circadian distribution peaks morning hours, coincident trough of core body
temperature rhythm
●If sleep onset delayed until park REM of circadian rhythm (early morning)
REM sleep may predominate and can occur at onset of sleep!
● Studies of person sleeping environment free of time cues- timing of sleep
onset/length of sleep occur as function of circadian phase
● Secondary peak of sleep onset, afternoon napping
● Offset sleep occurs rising limb of circadian body temperature curve
Temperature
● Extreme temperature sleeping environment disrupt sleep
● REM sleep more sensitive to temperature-related disruption than is NREM
● Mammals minimal ability thermoregulate during REM

●
Affects response to temperature extreme, conditions less a problem early
in the night, but more so later, when in REM sleep
● Sweating/shivering regular in NREM, limited in REM sleep

Drug Ingestion

● Benzodiazepines suppress SWS

● Tricyclic antidepressants, monoamine oxidase inhibitors, and certain selective
serotonin reuptake inhibitors tend to suppress REM sleep
● leading to a pattern of REM sleep without motor inhibition or an
 ● Fluoxetine is associated with rapid eye movements across all sleep stages (“Prozac
eyes”).
● Withdrawal from drugs that selectively suppress a stage of sleep tends to be
associated with a rebound of that sleep stage.
● acute withdrawal from a benzodiazepine compound is likely to produce an
increase of SWS;
● acute withdrawal from a tricyclic antidepressant or monoamine oxidase
inhibitor is likely to produce an increase of REM sleep•
● Acute pre-sleep alcohol intake can produce an increase in SWS and REM sleep
suppression early in the night,
● followed by REM sleep rebound in the latter portion of the night as the
alcohol is metabolized
● Low doses of alcohol have minimal effects on sleep stages, but they can
increase sleepiness late at night
● Acute effects of marijuana (tetrahydrocannabinol [THC]) include minimal sleep
disruption, characterized by a slight reduction of REM sleep.
● Chronic ingestion of THC produces a long-term suppression of SWS.

Narcolepsy

● abnormally short delay to REM sleep, marked by SOREMPs

● Consistent, but NREM sleep can also occur
● dissociation of components of REM sleep into the waking state results in hypnagogic
hallucinations, sleep paralysis, and cataplexy (sudden loss of muscle tone while
person is awake)
● Short REM sleep latency
● Infancy

● Sleep reversal or jet lag

● Chronic restriction or disruption of sleep

● Depression

Sleep Apnea
● Associated suppression of SWS or REM secondary to sleep-related breathing
problems

Sleep Fragmentation
● Sleep fragmentation and increased frequency arousal in association number of sleep
disorder/other medical disorders
● Also often involve increase in absolute amount/proportion of stage one sleep

Reading 2
Czeisler, C.A. & Buxton, O.M. (2017). Human Circadian Timing System and Sleep-Wake
Regulation. In Principles and Practices of Sleep Medicine (Sixth Edition). Kryger, M.E., Roth,
T., Dement, W.C. editors. **Available as an ebook through McGill Library catalog.

● Circadian oscillations/ biological clocks are found in all species from prokaryotes to
humans

● Defining characteristics- endogenous rhythmicity that persists independent of

periodic changes in the external environment, a near-24-hour period and the
capacity for environmental input to modify or reset the timing or phase.

· The Mammalian Circadian Pacemaker-

o The suprachiasmatic nucleus (SCN) in the anterior hypothalamus is the central

neural pacemaker of the circadian timing system

o Multiple distributed circadian oscillators drive daily rhythms in peripheral systems

and pacemakers like the SCN convey internal synchrony to these distributed
oscillators

· Influence of Sleep and Circadian Rhythms on Human Physiology

● When endogenous circadian rhythms are entrained or synchronized to the 24 hour

day, the temporal profile of each of these parameters is affected by a combo of
factors- timing of sleep wake state, the circadian pacemaker, posture, mood,
exercise and environmental lighting

§ To take apart and see the effects of the circadian system, the constant routine
protocol has been used- participants undergo continued enforced wakefulness
during the day and night in a constant posture at a constant level of minimal
physical activity and in constant, relatively dim, ambient illumination

§ The temporal profile of many physiologic variables are altered and the
components of these rhythms that are driven by endogenous circadian
pacemaker can be separated from those that reflect changes in the sleep-wake
state, posture, or periodic external environment

§ Body temp declines during sleep

§ Sleep and changes in posture, light intensity, and activity level generate a drop in
body temperature relative to wake- this sleep induced drop in temperature
combines with the circadian driven decline in body temp during biological night

§ Urine volume exhibits a robust oscillation under constant routine conditions that is
also influenced by sleep wake state

§ Rhythmicity in some variables is independent of sleep wake state-

§ The temporal pattern of melatonin is relatively unchanged whether a

participant is asleep or awake all night but does show age dependent
 and sleep deprivation related amplitude changes, posture also
influences melatonin concentrations somewhat

§ Overall profile of cortisol is relatively unchanged if you stay awake one

night but will elevate if you stay awake the following afternoon and
evening

§ Hormones that are sensitive to sleep wake state-

§ Thyroid stimulating hormone- sleep inhibits TSH release during peak of the
endogenous circadian TSH rhythm, which would otherwise occur in the
middle of the night- this suppression is associated with slow wave sleep
and relative delta power in the EEG

§ Growth hormone, prolactin, and para thyroid hormone levels show

increase during sleep

§ Growth hormone levels blunted by sleep deprivation are increased during

wakefulness the following day so that average 24 hour levels are similar

§ Leptin levels exhibit circadian rhythmicity in interaction with energy intake

and expenditure and sleep duration

● Ghrelin levels exhibit a day night variation related to energy intake

related to the presence of sleep and to sleep duration

● Ultradian variations in renin release from the kidney are closely linked
to timing of the REM-NREM cycle: increased delta power in EEG is
associated with increased levels of renin and decreased SWS is associated
with a decrease

● Even in the absence of sleep, prolactin and parathyroid hormone also

have an endogenous circadian component that is lowest a few hours after
habitual wake-up time, and GH responses to exogenous growth
hormone–releasing hormone exhibit a circadian rhythm

● Effects of Light On Human Circadian Rhythms-

· The light dark cycle is the primary environmental signal that synchronizes circadian
systems in a wide array of species, including humans

· Direct retinal input travels thru the retinohypothalamic tract- a monosynaptic pathway
by which information about the environmental light dark cycle reaches the SCN

· The 3 cone system and rods- the visual photoreceptors are not required for transmitting
light signals to the circadian system- a distinct set of ganglion cells in the inner retinal
layer that project to the SCN are intrinsically photosensitive- melanopsin is the active
photopigment

· Daytime and nighttime retinal exposure to monochromatic blue (460nm) light improves
reaction time, reduces attentional failures and improves EEG correlates of alertness
· Photic suppression of melatonin secretion-

§ Neural pathway from SCN to the pineal gland allows for regulation of the pineal
output of melatonin by the SCN including inhibition of melatonin release by
retinal light exposure through a retinohypothalamic pathway

§ Preservation of this process in otherwise totally blind people suffering from

damage to the outer retina lead to the discovery of the distinct visual system
that mediates photic entrainment

§ The loss of conscious light perception does not necessarily indicate the loss of
photic input to the circadian timing system, although that is the case in most
blind individuals without light perception.

§ In natural-light-only conditions, the internal circadian clock is synchronized to solar

time with melatonin onset near sunset and melatonin offset before wake time
and after sunrise, at a significantly earlier circadian phase

§ Evening reading from an electronic tablet that emits short-wavelength– enriched

visible light delays endogenous circadian melatonin phase and the timing of REM
sleep and increases evening alertness, sleep latency, and morning sleepiness
compared with reading a printed book

§ So, nocturnal artificial light can interfere with sleep and lead to chronic sleep
deficiency- bc it affects melatonin levels

· Human Phase-Response Curves to Light

§ The phase-response curve is used to characterize the synchronizing effects of light

on a circadian pacemaker

§ In humans, measurement of the phase of endogenous circadian rhythms on a

constant routine has been used to estimate both the initial circadian phase of
the pacemaker before a stimulus and the final circadian phase after a stimulus,
with the difference representing the phase shift

§ All circadian systems exhibit a characteristic photic PRC, in which the largest light-
induced phase shifts are generated in the biologic night.

§ Phase delays are generated in response to light stimuli late in the biologic day and
early in the biologic night, and phase advances are generated from stimuli in the
late biologic night and early biologic day

§ Appropriate light intensities can shift the phase of the human pacemaker in
morning and late afternoon or evening as well as at night. This has important
clinical implications, such as use of phototherapy to reset circadian phase in
delayed or advanced sleep phase disorder.

· Photic Resetting of the Pineal Melatonin Rhythm

§ Circadian rhythms are expressed in many physiologic and neurobehavioural

variables, so the phase of the pacemaker can be estimated by using any of these
variables as a marker
 § In humans, body temp rhythm is the preferred marker as it can accurately
represent the underlying pacemakers characteristics under certain conditions

§ Melatonin can be even more precise, as it is less influenced by sleep and posture

§ The endogenous circadian melatonin rhythm can be reset to any desired phase
within 2 to 3 days by light exposure

§ Photic stimuli designed to suppress the amplitude of the endogenous circadian

temp cycle also suppress the melatonin rhythm amplitude

§ Practical advantages to using melatonin as circadian marker- melatonin in human

saliva correlates well with that in plasma and it allows the evaluation of
circadian phase non-invasively

· Human Dose- Response Curve to Circadian Phase-Resetting Effects of Light

§ In addition to wavelength and circadian phase, the degree of light induced phase
shift also depends on light stimulus intensity and consecutive days of exposure

§ More light intensity and more exposure= more shift

· NONPHOTIC CIRCADIAN PHASE RESETTING AND REENTRAINMENT

o Such as social cues, exercise, food, environmental cues other than light

o Appropriately timed exposure to exercise results in phase advances

· INVESTIGATING CIRCADIAN AND SLEEP WAKE DEPENDENT MODULATION

● THE KLEITMAN PROTOCOL- Separation from 24-hour environmental and

behavioural cues

§ Nathaniel Kleitman- first investigator to study human circadian rhythms in

absence of periodic 24 hour cues in the external environment

§ Core body temp records from participant in Mammoth Cave, Kentucky who
underwent a 28 hour imposed sleep wake schedule were compared to lab
data collected from the same participant living on a 24 hour routine

§ 24 hr schedule- 7 cycles of body temp rhythm over 1 week

§ 28 hour schedule- 7 cycles of body temp but only 6 sleep wake cycles

§ Separated the influence of timing of the sleep wake schedule from

that of the circadian pacemaker

§ This is called forced desynchrony protocol

§ Separating circadian modulation and sleep wake modulation-

§ Constant routine protocol doesn’t permit complete unconfounded

separation of circadian and homeostatic influences on
neurobehavioural and physiologic variables

§ However, in the Kleitman forced desynchrony protocol, sleep and

wake are distributed more evenly in the entire circadian cycle-
therefore possible to average data over the successive circadian
cycles or successive sleep wake episodes to separate these
components

§ Neurobehavioural Functions: interaction of sleep homeostat and

circadian rhythm to keep up neurobehavioural functions:

· In the first half of the day following wake time, there is little
homeostatic sleep drive because it was discharged by the prior
sleep episode, so both alertness and cognitive performance are
high

· In the latter half of the waking episode, when homeostatic sleep

drive would otherwise cause alertness and cognitive
performance to decline, the circadian drive rises and opposes
that decline, thereby sustaining a high, stable level of alertness
throughout the normal waking day.

· Performance in the 3 hours before the onset of melatonin

secretion (i.e., the wake maintenance zone) is significantly
improved compared with performance during a 3-hour block
earlier in the biologic day, despite a longer time awake. This
effect is greater after extended wakefulness (i.e., on day 2 of a
circadian rhythm), when homeostatic sleep pressure is high

· Neurobehavioral performance, as measured by reaction time,

can be preserved during this circadian wake maintenance zone
even under conditions of chronic sleep restriction

· Sleep and Wake:

o Under entrained conditions, a consolidated bout of sleep is

maintained with minimal wake during the scheduled sleep
episode by initiating the sleep episode at the end of the
wake maintenance zone (3 hours before onset of melatonin
secretion)

o During entrained conditions, homeostatic drive for sleep is

greatest after an extended bout of wake at sleep onset and
facilitates sleep in the first half of the night; in the latter half
of the sleep episode, as homeostatic drive declines, the
circadian drive for sleep becomes greater, thus maintaining
elevated sleep drive thru the end of the sleep episode- the 2
drives interact to maintain sleep throughout the night
 o The magnitude of the circadian rhythms of sleepiness and
performance increases with increasing homeostatic sleep
drive. Thus, when increasing homeostatic sleep pressure
combines with an adverse circadian phase, the drive for
sleep is so great that slow eye movements and lapses of
attention often intrude involuntarily during wake

· Internal sleep structure:

o REM sleep propensity varies with circadian phase

o Spontaneous desynchrony, free-running participants who

chose to go to bed near the peak of the REM sleep
propensity rhythm usually exhibited sleep-onset REM sleep
episodes

o With the forced-desynchrony protocol, significant and

substantial circadian and sleep-dependent variations in
NREM sleep propensity were also observed, whereas the
robust sleep-dependent decline in slow wave activity was
associated with only a small but statistically significant
variation of slow wave activity as a function of circadian
phase

o EEG- low freq sleep spindle activity in NREM sleep parallels

the endogenous circadian melatonin rhythm

o Timing and internal structure of sleep are profoundly

dependent on an interaction between robust circadian and
homeostatic regulatory factors, with circadian factors
predominant in the regulation of REM sleep and with sleep
dependent factors predominant in the regulation of slow
wave sleep

● POTENTIAL FEEDBACK PATHWAYS:

§ The neurobehavioral variables influenced by the circadian pacemaker and the

sleep homeostat can influence the sleep-wake state

§ Studies demonstrating that melatonin receptors can be found on cells within

the human SCN draw attention to a potential feedback pathway from the
pineal gland to the SCN through circulating melatonin. Several physiologic
studies suggest that exogenous melatonin has a phase-resetting effect on
the human circadian pacemaker

§ Examination of the temporal profile of endogenous melatonin secretion

during the forced-desynchrony protocol shows a daily circadian increase in
melatonin levels coincident with a decrease in wake. This melatonin rise
might open a gate that allows sleep to occur.
-INTRINSIC PERIOD OF THE HUMAN CIRCADIAN PACEMAKER:

o 24.15 HOURS

o Significantly shorter in women than men

-AGING AND CIRCADIAN SLEEP WAKE REGULATION:

o Prevalence of disrupted sleep in older people

o On average, the circadian clock is set to an earlier hour, and the amplitude of
some endogenous circadian rhythms is lower in older people than it is in young
adults

o However, intrinsic circadian period does not shorten with age in healthy humans

o Older people usually awaken at an earlier circadian phase, they are typically
exposed to light earlier, this earlier light exposure, which will reset the circadian
pacemaker to an earlier hour, likely accounts for the earlier average entrained
circadian phase observed in older people

o Older participants are much less vulnerable to the adverse effect of sleep loss and
misalignment of circadian phase on neurobehavioural performance

-INFLUENCE OF SOCIAL AND WORK RELATED FACTORS:

o Self-selection of sleep and wake times in humans is an important factor in sleep

wake regulatory system

o Although circadian and homeostatic drives for sleep influence the choice of sleep
and wake times through a feedback pathway, social factors (e.g., child care,
school and work responsibilities, entertainment, social interaction) and
environmental factors (e.g., noise, artificial light, alarm clocks) often override
those biologic determinants

o Rotating shift work- when people choose to work in direct opposition to the
modulation of circadian and homeostatic regulatory systems, resulting in
internal temporal dissociation, fragmented sleep, and impaired wake.

o Sleep inertia- decrements in neurobehavioural performance and alertness that

immediately follow the sleep to wake transition- has been shown to persist for 2
hours after a long sleep episode and is most profound within the first few
minutes after awakening

-SUMMARY:

o The circadian pacemaker interacts with sleep-wake regulatory processes to

influence many physiologic variables: hormone levels, autonomic nervous
system activity, neurobehavioral performance, and the propensity for and
timing and internal structure of sleep.

o Environmental, social, behavioral, and genetic factors, pharmacologic agents, and

age influence most elements of this system
 o Under ordinary circumstances, when people sleep at night in darkness and are
awake in daylight, it is difficult to distinguish the relative contributions of the
sleep homeostat and that of the circadian pacemaker to a given recurrent daily
characteristic, symptom, or disorder of sleep or wakefulness

● It is currently possible, although difficult, to experimentally dissociate these

factors for research purposes (e.g., using the forced-desynchrony protocol in
humans or suprachiasmatic lesions in animals). Clinically feasible techniques,
such as measurement of dim-light salivary melatonin onset, can provide useful
information about circadian phase

Reading 3 - CHRONOTYPE AND PSYCHIATRIC DISORDERS

Intro:
● Circadian preference can influence physical and mental health, in terms of well-
being, but also sickness and disease
● 3 circadian types: the morning, the intermediate and the evening type
● Around 40% of adults belong in one of the two extreme circadian types
● review is to provide an overview of psychiatric disorders and their associations with
the morningness-eveningness dimension.

Chronotype and Mood disorders

Chronotype and Depression in Young Populations
● Evening types were more likely to report both internalizing problems—including
depression and somatic complaints—and suicidality
● also associated with depression independent of insomnia
● more likely to report a past diagnosis of a depressive disorder, and an earlier onset of
depressive symptoms

Chronotype and Depression in Adult and Clinical Populations

● Eveningness has been associated with an increased likelihood of reporting
depressive symptomatology, increased symptom severity, and being diagnosed with
a depressive disorder
● Contradictory finding, in a study involving psychiatric inpatients, morning types were
more likely to suffer from depression
● Among depressed individuals, evening types tend to exhibit worse symptom severity
and report increased psychological distress, higher suicidality and more impairment
in their daily lives (including work), and more symptoms of anxiety
● Evening preference is associated with increased comorbidity in clinical samples
● Eveningness → lower behavioral activation system (BAS) → leads to lower reward
responsiveness and lower positive affect → depressive symptoms
● Evening types also exhibit difficulties with affect regulation, consequently putting
them at risk for experiencing affective disturbances, such as depression
● impaired emotion regulation, especially higher self-blame and reduced positive
reappraisal
● increased rumination levels
● Sleep disturbances
Chronotype and Bipolar Disorder
● Bipolar patients are more likely to be evening types
● Eveningness was associated with elevated depressive symptoms and the use of
mood stabilizers among all patients
● Overall, eveningness appears to be more directly associated with symptoms of
depression rather than mania among bipolar patients
● Studies for and against

Chronotype and Seasonal Affective Disorder

● Evening-type adolescents have been found to report higher mood seasonality
● seasonal worsening of mood during winter months was accompanied with a shift
towards eveningness
● Positive results: light therapy for patients with both seasonal and non-seasonal
depression

Chronotype and Anxiety Disorders

Chronotype and Anxiety Disorders in Young Populations
● Eveningness has been associated with trait anxiety in female adolescents
● Increased anxiety and psychosomatic symptoms have also been observed among
evening-type undergraduate students
● evening-type students reported experiencing more anxiety in general, and more
obsessive-compulsive and phobic symptoms in particular
● Eveningness was also not associated with anxiety disorders (obsessive-compulsive
disorder, panic disorder, separation anxiety, social phobia) among adolescents after
sleep complaints were controlled for
● Studies for and against

Chronotype and Anxiety Disorders in Adults

● Evening types appear to be more vulnerable to anxiety
● increased physiological arousal, as indicated by increased heart rate and systolic
blood pressure and decreased heart rate variability, both during conditions of rest
and stress
● Evening-type firefighters and military veterans showing increased PTSD symptoms
● Studies for and against

Chronotype and Psychotic Disorders

● limited attention in comparison to other mental health conditions
● psychotic patients were more frequently morning-oriented
● Studies for and against

Chronotype and Addictive Disorders

Chronotype and Addictive Disorders in Young Populations
● evening chronotype is considered a major risk factor for substance use among young
people
● Adolescents and young adults with a tendency towards eveningness report higher
levels of both experimental and habitual cigarette smoking
 ● More alcohol, excessive alcohol consumption is also used by evening type
adolescents
● higher consumption of illegal drugs (cannabis, cocaine, ecstasy, and amphetamines)
● compulsive internet use among young adults
● exhibit increased engagement with computer games and social media, and
problematic mobile phone usage

Chronotype and Addictive Disorders in Adults

● Evening types are more likely to smoke cigarettes and to consume alcohol, also in
higher amounts
● More than twice as likely to be smokers
● Greater risk of developing alcohol dependence
● Use alcohol in the evenings for its sedative properties
● cannabis addiction, non-substance addiction (such as gambling), and poly-substance
use
● Neuroimaging studies : how circadian alterations could influence reward-related brain activity
→ Evening types also exhibited increased ventral striatum reactivity in response to receiving
the reward, alcohol consumption and more symptoms of alcohol dependence
● Personality type characterized by greater impulsivity, disinhibition, and sensation
seeking

Chronotype and Sleep Disorders

Chronotype and Sleep Disorders in Adolescents
● 13 yo → shift to eveningness bc of biological, social, and behavioral influences, such as
pubertal changes, lessened parental control, and recreational activities
● social schedules not adaptable → chronic sleep deprivation
● report more irregular sleep-wake cycles, poorer subjective sleep quality, and more
daytime sleepiness, more napping
● Delayed sleep phase syndrome (DSPS) → may result in chronic fatigue, low mood, and
academic difficulties (when individuals are unable to synchronize their internal schedules
with external (e.g., school) requirements)

Chronotype and Sleep Disorders in Adults

● Evening types report decreased subjective sleep quality, insufficient sleep, excessive
daytime sleepiness, and trouble initiating sleep, more severe insomnia symptoms
● more frequent nightmares and use more hypnotic medications
● heightened risk for the development of DSPS
● increases the risk for serious mental health problems
● Insomnia = more prevalent in morning types
● Hypersomniacs = more prevalent in evening types
● sleep apnea has been associated with both the morning and evening chronotypes
among overweight and obese individuals

Chronotype and Eating Behavior/Disorders

● Morning-type individuals → exhibit healthier/more regular eating habits and higher control
over their eating
 ● Neuroticism might predispose individuals to both eveningness and uncontrolled
eating
● Evening types → less physically active and report poorer perceived health
● Evening types → increased body mass index (BMI), but, not risk factor for obesity
● association btw bulimic behavior and evening preference in uni students
● less dietary restraint and more uncontrolled eating
● reductions in eating disorder symptoms were also associated with a shift towards
morningness
Conclusion
● increased risk of a number of adverse mental health outcomes for individuals who
exhibit a preference for evening hours