Instructor’s Manual
by David Vago
to accompany
The Mind’s Machine
Watson • Breedlove
Chapter 10: Biological Rhythms and Sleep
OVERVIEW OF THIS CHAPTER
Much of our experience of the universe comes in cycles: the endless parade of the
seasons, the waxing and waning of the moon, dawn breaking and night falling. Organisms
blend themselves into all these rhythms seamlessly, and viewed objectively, rhythmicity
is a remarkably pervasive feature of daily life across all living systems. Modern research
is revealing that diverse processes, ranging from gene transcription to human conception
rates, are subject to complex overlapping cyclical patterns. The first part of the chapter
provides an introduction to the functioning and neural bases of the biological timepieces
that track and predict rhythmic environmental events. The remainder of the chapter is
devoted to sleep, a phenomenon whose mechanisms remain among the most mysterious
of rhythmic behaviors. Disorders of sleep are the subject of much current research, and
they receive considerable coverage in the latter part of the chapter.
CHAPTER OUTLINE
PART I: BIOLOGICAL RHYTHMS
Many Animals Show Daily Rhythms in Activity
Circadian rhythms are generated by an endogenous clock
The Hypothalamus Houses a Circadian Clock
RESEARCHERS AT WORK: Transplants prove that the SCN produces a circadian
rhythm
In mammals, light information from the eyes reaches the SCN directly
Circadian rhythms have been genetically dissected in flies and mice
PART II: SLEEPING AND WAKING
Human Sleep Exhibits Different Stages
We do our most vivid dreaming during REM sleep
Different species provide clues about the evolution of sleep
Our Sleep Patterns Change across the Life Span
Mammals sleep more during infancy than in adulthood
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Most people sleep appreciably less as they age
Manipulating Sleep Reveals an Underlying Structure
Sleep deprivation impairs cognitive functioning but does not cause insanity
Sleep recovery may take time
BOX 14.1: Sleep Deprivation Can Be Fatal
What Are the Biological Functions of Sleep?
Sleep conserves energy
Sleep enforces niche adaptation
Sleep restores the body
Sleep may aid memory consolidation
Some humans sleep remarkable little, yet function normally
At Least Four Interacting Neural Systems Underlie Sleep
RESEARCHERS AT WORK: The forebrain generates slow-wave sleep
The reticular formation wakes up the forebrain
The pons triggers REM sleep
A hypothalamic sleep center was revealed by the study of narcolepsy
Sleep Disorders Can Be Serious, Even Life-Threatening
Some minor dysfunctions are associated with sleep
Insomniacs have trouble falling asleep or staying asleep
Although many drugs affect sleep, there is no perfect sleeping pill
KEY CONCEPTS
1. Types of biological rhythms: Life on Earth is rhythmic. Biological rhythms range in
length from minutes to seconds, can change over the course of a day, and in some cases
extend from months to years.
2. Mammals have evolved specific endogenous mechanisms (a biological clock) to
synchronize (entrain) their bodies and behavior to periodic external environmental cues
called zeitgebers, the primary one of which is daylight. In the absence of appropriate
environmental cues, the endogenous rhythm of the clock becomes apparent as a freerunning rhythm.
3. Phase shifting, entrainment, and jet-lag: Jet-lag is a common example of phase-shifting
that occurs in humans when flying between time-zones. Synchronizing stimuli (e.g., light)
can be described along with the function of melatonin secretion from the pineal gland, the
result of taking melatonin orally before bedtime, and the function of melanopsin, the
light-sensitive photopigment in retinal ganglion cells.
4. In mammals, the SCN clock receives entraining light stimulation directly from the eyes
via the retinohypothalamic pathway. A variety of other routes for light entrainment also
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exist; for example, in some animals light is detected directly by the pineal gland, and in
humans circadian rhythms may be phase-shifted by light applied to other body surfaces.
5. Experimental work—including lesion studies, genetic manipulations, and transplant
studies in which host animals adopted the donors’ rhythms—have established
conclusively that an endogenous clock is located in the suprachiasmatic nucleus of the
hypothalamus. Mutations of the gene tau demonstrates the mechanism for endogenous
rhythms originating in the SCN. Transplant experiments demonstrate rhythms following
the donor SCN.
6. Experimental evidence indicates that there is more than one endogenous clock. SCN
lesions do not abolish infradian or ultradian rhythms in mammals, and in mice the
Clock/Clock mutation abolishes free-running circadian rhythms but not free-running
ultradian rhythms. In species ranging from flies to mammals, rhythmicity is conferred on
individual cells through the actions of a molecular clock. This oscillator appears to be
entrained to light through the transcription of a complex of genes, including Tau,
Cryptochrome (Cry) and Period (Per).
7. EEG records and behavioral observations indicate that the sleep of many species,
including humans, exhibits a pattern of distinct stages and two distinct categories: slowwave sleep (SWS) and rapid-eye-movement (REM) sleep.
8. Human SWS stages may be distinguished on the basis of particular EEG
characteristics: Stage 1 SWS contains primarily regular oscillating alpha rhythms (8–12
Hz) and vertex spikes; stage 2 SWS contains discrete bursts of sleep spindles (12–14 Hz)
and K complexes; early stage 3 SWS is marked by the appearance of very slow, large
amplitude delta waves (0.5–4 Hz); and in late stage 3 SWS delta waves are present at
least 50% of the time. The progression through the stages is marked by decreasing
frequency and increasing amplitude in the EEG.
9. REM sleep is characterized by a return to fast, desynchronized EEG activity
resembling the awake state, complete loss of muscle tone, and rapid eye movements.
10. Human sleep exhibits an alternating cycle of REM and SWS every 90 to 110 minutes.
Sleep cycle length is shorter in smaller animals. Some species of mammals do not display
REM sleep at all, and some, notably the dolphin, engage in SWS in only one cerebral
hemisphere at a time.
11. Vivid dreaming involving imagery has been shown to occur during REM sleep;
dreaming during non-REM has been shown to involve vague thoughts. Nightmares have
been associated with REM, whereas night terrors have been associated with stage 3 SWS
and marked autonomic activation.
12. Only birds display both REM and SWS. The evolution of REM and SWS can be
discussed from the context of species-specific sleep behavior.
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13. Sleep patterns change dramatically over the life span. In humans, infants spend most
of their sleep time in REM sleep, which may contribute to neural development. The
proportion of sleep time spent in REM decreases with age. Sleep in the elderly is
characterized by less total sleep time, frequent awakenings and complaints of insomnia,
and a loss of stage 3 SWS.
14. Sleep deprivation impairs cognitive abilities, particularly for tasks that require
sustained attention. Sleep debts incurred by deprivation are partially recovered in sleep
subsequent to the deprivation. Long-term sleep deprivation can have very serious
consequences on health, particularly compromising immune function. A rare heritable
disorder associated with degeneration of the thalamus (fatal familial insomnia) causes
some people to become unable to sleep; this condition is lethal. A defect in the gene for
the prion protein is responsible for this degenerative disease.
15. Many different functions have been proposed for sleep, including bodily restoration,
energy conservation, niche adaptation, and memory consolidation. None of these
hypotheses, by themselves, appears to account entirely for the need to sleep or the
dramatic health consequences of sleep deprivation.
16. Little or no new learning occurs during sleep, but evidence suggests that memory for
new material is improved if learning is followed by sleep. Some data suggest that REM
sleep may be more beneficial for perceptual learning, whereas SWS may be more
beneficial for motor skill learning and consolidation of declarative types of memory.
Some researchers remain skeptical that any specific stage of sleep is beneficial for
memory consolidation.
17. Transecting the brain at different levels has provided a mechanism for mediating
SWS in the forebrain and reliance on input from the brainstem.
18. Many neural mechanisms are implicated in the generation and maintenance of sleep—
particularly mechanisms vested in the hypothalamus and brainstem, including the basal
forebrain, hypothalamus, locus coeruleus, and reticular formation. The basal forebrain
appears to be important for the production of SWS.
19. Classification of sleep disorders can be described as disorders of insomnia, disorders
of excessive drowsiness, disorders of sleep-waking schedule, and dysfunctions associated
with sleep or partial arousal. Insomnia is a prevalent sleep disorder involving difficulty in
falling asleep or difficulty in staying asleep. In narcolepsy, sufferers experience periodic
attacks of sleepiness during the day, and they may even experience cataplexy. It appears
that defects in the orexin signaling system are responsible for symptoms of narcolepsy.
Milder forms of sleep disorders include somnambulism (sleep walking) and sleep
enuresis (bed-wetting), both of which are treatable. Other forms of sleep disorders are
related to unreliable respiration during sleep, such as sleep apnea or sudden infant death
syndrome.
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20. Humans have searched for soporifics for millennia, but as yet no perfect sleeping pill
exists. Modern sleep drugs, notably benzodiazepines such as triazolam (Halcion) or nonbenzodiazepines like Ambien and Lunesta, interact with GABA receptors to promote
sleep. Such drugs have significant undesirable effects, including suppression of REM
sleep, “sleep drunkenness” during the day, and REM rebound effects at termination of
treatment.
SAMPLE LECTURE OUTLINE
(Bulleted items are grouped into suggested slides for lecture presentation. Textbook
figures are available on the Instructor’s Resource Library disc.)
Biological Rhythms
•
Biological rhythms are regular fluctuations in a living process
o Circadian rhythms have a rhythm of about 24 hours
o Ultradian rhythms such as bouts of activity, feeding, and hormone release
repeat more than once a day
o Infradian rhythms such as body weight and reproductive cycles repeat less
than once a day
Many Animals Show Daily Rhythms in Activity
•
•
•
Diurnal—active during the light
Nocturnal—active during the dark
Circadian rhythms are generated by an endogenous (internal) clock
•
A free-running animal is maintaining its own cycle with no external cues, such as
light (Figure 10.2a)
The period, or time between successive cycles, may not be exactly 24 hours
•
•
•
•
A phase shift is the shift in activity in response to a synchronizing stimulus, such
as light or food
Entrainment is the process of shifting the rhythm
The cue that an animal uses to synchronize with the environment is called a
zeitgeber or “time-giver” (Figure 10.2b)
The Hypothalamus Houses an Endogenous Circadian Clock
•
•
The biological clock is located in the suprachiasmatic nucleus (SCN)—above the
optic chiasm in the hypothalamus
Studies in SCN-lesioned animals showed disrupted circadian rhythms (Figure
10.3)
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•
Isolated SCN cells maintain electrical activity synchronized to the previous light
cycle
•
•
Transplant studies proved that the SCN produces a circadian rhythm
Hamsters with SCN lesions received a SCN tissue transplant from hamsters with a
very short period, ~20 hours
Circadian rhythms were restored but matched the shorter period of the donor
(Figure 10.5)
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•
•
•
•
•
•
•
•
Circadian rhythms entrain to light-dark cycles using different pathways, some
outside of the eye
The pineal gland in amphibians and birds is sensitive to light
Melatonin is secreted to inform the brain about light
In mammals, light information goes from the eye to the SCN via the
retinohypothalamic pathway (Figure 10.6)
Some retinal ganglion cells project to the SCN
Most contain melanopsin, a special photopigment, that makes them sensitive to
light
Molecular studies in Drosophila using mutations of the period gene helped to
understand the circadian clock in mammals
SCN cells in mammals make two proteins:
o Clock
o Cycle
•
•
Clock and Cycle proteins bind together to form a dimer
The Clock/Cycle dimer promotes transcription of two genes:
o Period (per)
o Cryptochrome (cry)
•
•
Per and Cry proteins bind to each other and also to Tau
The Per/Cry/Tau protein complex enters the nucleus and inhibits the transcription
of per and cry
No new proteins are made until the first set degrades (Figure 10.7)
The cycle repeats ~every 24 hours
•
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•
Gene mutations show how important the clock is to behavior in constant
conditions:
o In tau mutations the period is shorter than normal
o Double Clock mutants—severely arrhythmic (Figure 10.8)
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•
Sleep is synchronized to external events, including light and dark
Stimuli like lights, food, jobs, and alarm clocks entrain us to be awake or to sleep
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•
In the absence of cues, humans have a free-running period of approximately 25
hours (Figure 10.9)
Human Sleep Exhibits Different Stages
•
•
Electrical brain potentials can be used to classify levels of arousal and states of
sleep
Electroencephalography (EEG) records electrical activity in the brain
•
Two distinct classes of sleep:
o Slow-wave sleep (SWS) can be divided into four stages and is characterized
by slow-wave EEG activity
o Rapid-eye-movement sleep (REM) is characterized by small amplitude, fastEEG waves, no postural tension, and rapid eye movements
•
The pattern of activity in an awake person contains many frequencies:
o Dominated by waves of fast frequency and low amplitude (15–20 Hz)
o Known as beta activity or desynchronized EEG
Alpha rhythm occurs in relaxation, a regular oscillation of 8–12 Hz
•
•
Four stages of slow-wave sleep: (Figure 10.10)
o Stage 1 sleep
 Shows events of irregular frequency and smaller amplitude, as well as
vertex spikes, or sharp waves
 Heart rate slows, muscle tension reduces, eyes move about
 Lasts several minutes
o Stage 2 sleep
 Defined by waves of 12–14 Hz that occur in bursts, called sleep spindles
 K-complexes appear—sharp negative EEG potentials
o Early Stage 3 sleep
 Continued sleep spindles as in stage 2
 Defined by the appearance of large-amplitude, very slow waves called
delta waves
 Delta waves occur about once per second
o Late Stage 3 sleep
 Delta waves are present about half the time
•
REM sleep follows SWS
o Active EEG with small-amplitude, high-frequency waves, like an awake
person
o Muscles are relaxed—called paradoxical sleep
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•
In a typical night of young adult sleep: (Figure 10.11)
o Sleep time ranges from 7–8 hours
o 45–50% is stage 2 sleep, 20% is REM sleep
o Cycles last 90–110 minutes, but cycles early in the night have more stage 3
SWS, and later cycles have more REM sleep
•
At puberty, most people shift their circadian rhythm of sleep so that they get up
later in the day (Figure 10.12)
However, most high schools require adolescents to arrive even earlier
Later starts improved attendance and enrollment, and reduced depression and inclass sleeping
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•
Vivid dreams occur during REM sleep, characterized by:
o Visual imagery
o Sense that the dreamer is “there”
Nightmares are frightening dreams that awaken the sleeper from REM sleep
Night terrors are sudden arousals from stage 3 SWS, marked by fear and
autonomic activity
•
REM sleep evolved in some vertebrates:
o Nearly all mammals display both REM and SWS
o Birds also display both REM and SWS sleep
•
Dolphins do not show REM sleep, perhaps because relaxed muscles are
incompatible with the need to come to the surface to breathe (Figure 10.14)
In dolphins and birds, only one brain hemisphere enters SWS at a time—the other
remains awake
•
Our Sleep Patterns Change across the Life Span
•
•
Mammals sleep more during infancy than in adulthood (Figure 10.15)
Infant sleep is characterized by:
o Shorter sleep cycles
o More REM sleep—50%, which may provide essential stimulation to the
developing nervous system
•
As people age, total time asleep declines, and times awakened increase (Figure
10.16)
The biggest loss is time spent in stage 3: (Figure 10.17)
o At age 60, only half as much time is spent as at age 20
o By age 90, stage 3 has disappeared
•
Manipulating Sleep Reveals an Underlying Structure
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•
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Effects of sleep deprivation—the partial or total prevention of sleep: (Figure
10.18)
o Increased irritability
o Difficulty in concentrating
o Episodes of disorientation
Effects can vary with age and other factors
•
Sleep recovery is the process of sleeping more than normally, after a period of
deprivation (Figure 10.19)
o Night 1—stage 3 sleep is increased, but stage 2 is decreased
o Night 2—most recovery of REM sleep, which is more intense than normal
with more rapid eye movements
•
Sleep deprivation can be fatal
o Total sleep deprivation compromises the immune system and leads to death
o The disease fatal familial insomnia is inherited—in midlife, people stop
sleeping and die 7–24 months after onset of the insomnia (Box 10.1)
What Are the Biological Functions of Sleep?
•
Four functions of sleep:
o Energy conservation
o Niche adaptation
o Body restoration
o Memory consolidation
•
One role of sleep is to conserve energy
o Muscular tension, heart rate, blood pressure, temperature, and rate of
respiration are reduced
•
•
Sleep helps animals avoid predators—animals sleep during the part of the day
when they are most vulnerable (Figure 10.20)
The ecological niche for each species is the unique assortment of opportunities
and challenges in its environment
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•
•
Sleep restores the body by replenishing metabolic requirements, such as proteins
Most growth hormone is only released during SWS
Proper sleep is essential for immune function
•
Sleep may aid memory consolidation
o Sleep during the interval between learning and recall may reduce interfering
stimuli
o Memory typically decays and sleep may slow this down
o Or sleep, especially REM, may actively contribute through processes that
consolidate the learned material
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•
•
A challenge to sleep theories is the existence of a few people who hardly sleep at
all yet are normal and healthy (Figure 10.21)
Whatever the function of sleep, these people fill it with a brief nap
At Least Four Interacting Neural Systems Underlie Sleep
•
Sleep is an active state mediated by:
o A forebrain system—displays SWS
o A brainstem system—activates the forebrain
o A pontine system—triggers REM sleep
o A hypothalamic system—affects the other three
•
Transection experiments showed that different sleep systems originate in different
parts of the brain
o The isolated brain is made by an incision between the medulla and the spinal
cord (Figure 10.22a)
 Animals showed signs of sleep and wakefulness, proving that the networks
reside in the brain
o An isolated forebrain is made by an incision in the midbrain (Figure 10.22b)
 The electrical activity in the forebrain showed constant SWS, but not
REM—thus, the forebrain alone can generate SWS
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•
•
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The constant SWS activity in the forebrain is generated by the basal forebrain, a
ventral region
Neurons in this region become active at sleep onset and release GABA
o GABA activates receptors in the nearby tuberomammillary nucleus
o GABA receptors are also stimulated by general anesthetics to produce slow
waves resembling SWS
The reticular formation is able to activate the cortex (Figure 10.23)
o Electrical stimulation of this area will wake up sleeping animals
o Lesions of this area promote sleep
The forebrain and reticular formation seem to guide the brain between SWS and
wakefulness
•
•
•
An area of the pons, near the locus coeruleus, is responsible for REM sleep
Some neurons in this region are only active during REM sleep
They inhibit motoneurons to keep them from firing, disabling the motor system
during REM sleep (Figure 10.24)
•
•
The study of narcolepsy revealed the hypothalamic sleep center
Narcolepsy sufferers:
o Have frequent sleep attacks and excessive daytime sleepiness
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o Do not go through SWS before REM sleep
o May show cataplexy—a sudden loss of muscle tone, leading to collapse
•
Narcoleptic dogs have a mutant gene for a hypocretin receptor
o Hypocretin normally prevents the transition from wakefulness directly into
REM sleep
o Interfering with hypocretin signaling leads to narcolepsy (Figure 10.25)
•
Hypocretin neurons in the hypothalamus project to other brain centers: the basal
forebrain, the reticular formation, and the locus coeruleus (Figure 10.26)
Axons also go to the tuberomammillary nucleus, whose inhibition induces SWS
The hypothalamus seems to contain a hypocretin-based sleep center that controls
wakefulness, SWS sleep, or REM sleep
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•
•
•
Sleep paralysis is the brief inability to move just before falling asleep, or just after
waking up
It may be caused by the pontine center continuing to signal for muscle relaxation,
even when awake
Sleep Disorders Can Be Serious, Even Life-Threatening
•
Sleep disorders in children:
o Night terrors and sleep enuresis (bed-wetting) are associated with SWS
o Somnambulism (sleepwalking) occurs during stage 3 SWS, and may persist
into adulthood
•
REM behavior disorder (RBD) is characterized by organized behavior, from an
asleep person
o It usually begins after age 50 and may be followed by beginning symptoms of
Parkinson’s disease
o This suggests damage in the brain motor systems
•
Sleep-onset insomnia is a difficulty in falling asleep, and can be caused by
situational factors, such as shift work or jet lag
Sleep-maintenance insomnia is a difficulty in staying asleep and may be caused by
drugs or neurological factors
•
•
•
In sleep apnea, breathing may stop or slow down when muscles in the chest and
diaphragm relax too much or respiratory neurons in the brain stem don’t signal
properly
o Sleep apnea may be accompanied by snoring
Sleep state misperception occurs when people report insomnia even when they
were asleep
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•
•
•
•
Sudden infant death syndrome (SIDS) is sleep apnea resulting from immature
respiratory pacemaker systems or arousal mechanisms
Putting babies to sleep on their backs can prevent suffocation due to apnea (Photo,
p. 297)
Most sleeping pills bind to GABA receptors throughout the brain
Continued use of sleeping pills:
o Makes them ineffective
o Produces marked changes in sleep patterns that persist even when not taking
the drug
o Can lead to drowsiness and memory gaps
REFERENCES FOR LECTURE DEVELOPMENT
Books and Articles
Carskadon, M. A. (Ed.). (1993). Encyclopedia of sleep and dreaming. New York:
Macmillan.
Cooper, R. (Ed.). (1994). Sleep. New York: Chapman and Hall.
Dunlap, J. C., Loros, J. L., and DeCoursey, P. J. (2003). Chronobiology: Biological
timekeeping. Sunderland, MA: Sinauer Associates.
International Congress on Chronobiology. (1998). Biological clocks: Mechanisms and
applications: Proceedings of the international congress on chronobiology, Paris,
September 7–11, 1997. New York: Elsevier.
Kryger, M. K., Roth, T., and Dement, W. C. (1999). Principles and practice of sleep
medicine. New York: Saunders.
Lange, T., Dimitrov, S., and Born, J. (2010) Effects of sleep and circadian rhythm on the
human immune system. Annals of the NY Academy of Sciences, 1193 (1): 48–59.
Pressman, M. R., and Orr, W. C. (Eds.). (1997). Understanding sleep: The evaluation and
treatment of sleep disorders. Washington, DC: American Psychological Association.
Schwartz, W. J. (Ed.). (1997). Sleep science: Integrating basic research and clinical
practice. Basel, Switzerland: Karger.
Takahashi, J. S. (1995). Molecular neurobiology and genetics of circadian rhythms in
mammals. Annual Review of Neuroscience, 18: 531–554.
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Tononi, G. and C. Cirelli (2006). Sleep function and synaptic homeostasis. Sleep
Medicine Review, 10 (1): 49–62.
Online Resources
Center for Sleep Research (UCLA Semel Institute, Psychiatry and Biobehavioral
Sciences)
Contains a wide variety of information on sleep and rhythms research, links to other sites,
and teaching resources.
http://www.semel.ucla.edu/sleepresearch
National Sleep Foundation
Contains a wide variety of information related to sleep, sleep disorders, current research,
polls, and other resources.
http://www.sleepfoundation.org/
Night Terror Resource Center
Contains resources specifically for night terrors.
http://nightterrors.org/
Sleep-Wake Disorders: Behavioral and Circadian Rhythm Issues in Excessive Daytime
Sleepiness (video on The Doctor’s Channel)
Michael Thorpy, MD, director of the Sleep-Wake Disorders Center at Montefiore
Medical Center in New York City, provides recent epidemiological information related to
excessive daytime sleepiness and sleep disorders on a physicians’ Internet television
service.
http://www.thedoctorschannel.com/view/sleep-wake-disorders
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