the neurobiology of sleep and sleep disorders
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The Neurobiology of Sleep and Sleep Disorders. Tamara Blutstein, Ph.D. Department of Neuroscience Tufts University School of Medicine May 1, 2013. What is Sleep?. - PowerPoint PPT PresentationTRANSCRIPT
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The Neurobiology of Sleep and Sleep Disorders
Tamara Blutstein, Ph.D.Department of Neuroscience
Tufts University School of MedicineMay 1, 2013
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What is Sleep?
“a natural periodic state of rest for the mind and body, in which the eyes usually close and
consciousness is completely or partially lost so that there is a decrease in bodily movement and
responsiveness to external stimuli”
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The Function of Sleep
• Important to overall health and well being– Severe cognitive and physical consequences of sleep deprivation – Strong rebound of sleep following sleep loss – Evolutionarily conserved
• There are a number of sleep disorders– Insomnia, sleep apnea, restless leg syndrome, narcolepsy
• Sleep disruptions are associated with a number of neurological disorders– Parkinson’s disease, Alzheimer’s disease, depression
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Two Process Model of Sleep• Balance between sleep and wake determined by 2 factors
– Circadian • 24hr cyclic rhythm generated by the SCN that entrains the sleep-wake cycle to the daily
light-dark cycle– Homeostatic
• Determined by sleep need• Homeostatic drive to sleep increases with time awake and peaks just before the beginning
of the sleep period
Lu and Zee 2010
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Sleep Stages
Wake- desynchronized EEG and high EMG activity
NREM sleep- high amplitude, slow-wave EEG (delta frequency 0.5-4Hz) and low EMG activity relative to wakefulness
REM sleep- regular theta activity (4-8Hz) on EEG, coupled with low EMG activity relative to that of NREM sleep
WAKE
NREM
REM
EEG
EEG
EEG
EMG
EMG
EMG
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Human SleepWAKE
NREM SleepDivided into 4 stages
Stage 12-5% of TST
Transition from wake to sleepStage 2
45-55% of TSTIncreased slow waves, presence of sleep
spindles and K complexesStage 3 and 4 10-20% of TST
Slow-wave sleep (SWS), greatest early in sleep period
REM Sleep20-25% TST
Episodes longer as sleep progresses
Stiller and Postolache 2005
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Neurobiology of Sleep:Wake-Promoting Systems
Espana and Scammell 2011
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Neurobiology of Sleep:NREM
Espana and Scammell 2011
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Regulation fo Wake and Sleep:Flip-Flop Switch
Lu and Zee 2010
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Neurobiology of Sleep:REM
Espana and Scammell 2011
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Neurotransmitters Involved in Sleep/Wake
Espana and Scammell 2011
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International Classification of Sleep Disorders
• Insomnias• Sleep-related breathing disorders• Hypersomnias of central origin• Circadian rhythm sleep disorders• Parasomnias• Sleep-related movement disorders • Isolated symptoms (apparently normal variants
and unresolved issues)• Other sleep disorders
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Insomnias
• Most common• Difficulty initiating and maintaining sleep,
early morning awakening, non-restorative sleep
• Occurs 3-4 times per week and persisting for more than a month
• Sleep difficulty occurs despite adequate opportunity and circumstances for sleep and associated with daytime dysfunction
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Primary Insomnias
• Adjustment insomnia• Psychophysiological insomnia• Paradoxical insomnia• Idiopathic insomnia• Inadequate sleep hygiene• Behavioral insomnia of childhood
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Secondary Insomnias
• Insomnia due to a drug or substance• Insomnia due to a medical condition• Insomnia not due to a substance or known
physiological condition• Physiologic Insomnia, unspecified
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Causes of Insomnia
• Hyperactivity of HPA axis• Imbalance of flip-flop switch regulating
transition from sleep to wake
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Treatment for Insomnias:Cognitive-Behavioral
Buysse 2013
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Treatment for Insomnias:Pharmacology
Buysse 2013
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Treatment for Insomnias:Pharmacology
Buysse 2013
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Sleep-Related Breathing Disorders
• Characteristic feature: disordered ventilation during sleep
• Primary central sleep apnea• Primary sleep apnea of infancy• Sleep-related hypoventilation/hypoxemic
syndromes• Obstructive sleep apnea
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Obstructive Sleep Apnea
CPAP
Ioachimescu and Collop 2012
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Hypersomnia of Central Origin
• Primary complaint is daytime sleepiness and the cause is not disturbed nocturnal sleep or misaligned circadian rhythms
• Daytime sleepiness: inability to stay alert and awake during the major waking episodes of the day, resulting in unintended lapses into sleep
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• Recurrent hypersomnia• Idiopathic hypersomina with or without
long sleep time• Hypersomnia due to a medical condition• Narcolepsy-cataplexy syndrome
Hypersomnia of Central Origin
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Narcolepsy-Cataplexy Syndrome
• Onset in adolescents and young adults • Narcolepsy with cataplexy, without, and
secondary narcolepsy • Irresistible desire to fall asleep in
inappropriate circumstances• Triggered by emotional factors such as
laughter, rage or anger
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• Video
Narcolepsy-Cataplexy Syndrome
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Narcolepsy-Cataplexy Syndrome
Burgess and Scammell 2012
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Circadian Rhythm Sleep Disorders
• Delayed sleep phase• Advanced Sleep
Phase• Jet lag• Shift work
Drake 2010
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Circadian Rhythm Sleep Disorders
• Changes in the period length of the circadian clock
• Impaired response to light• Altered function of clock genes or products• Behavior therapy, Light therapy and
Chronotherapy
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Parasomnias
Tinuper et al 2012
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• NREM parasomnias, impaired arousal mechanisms and the persistence of sleep drive result in a failure of the brain to fully transition into wake
• REM parasomnias-failure of mechanisms that induce muscle atonia
• Most treatments are similar to those used for insomnia
• Safety measures
Parasomnias
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Sleep-Related Movement Disorders
• Characterized by relatively simple, stereotyped movements that disturb sleep
• Bruxism • Rhythmic movement disorder• Nocturnal leg cramps• Restless leg syndrome
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Isolated Symptoms, Apparently Normal Variants and Unresolved Issues
• Long sleepers• Short sleepers• Snoring• Sleep talkers• Sleep related sexual disorders
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Espana and Scammell 2011
Drug Effects on Sleep
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Consequences of Sleep Loss
Wulff et al 2010
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Consequences of Sleep Loss
Wulff et al 2010
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Consequences of Sleep Loss
Wulff et al 2010
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Neurological Disorders and Sleep
Wulff et al 2010
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Sleep in Psychiatric Disease
Wulff et al 2010
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Sleep in Psychiatric Disease
Wulff et al 2010
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Sleep in Psychiatric Disease
Wulff et al 2010
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Sleep in Neurodegenerative Disease
Wulff et al 2010
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• Therapeutic target• Mechanistic overlap• Identification of risk
factors and vulnerability
Neurological Disorders and Sleep