The Neurobiology of Sleep and Sleep Disorders Tamara Blutstein, Ph.D. Department of Neuroscience Tufts University School of Medicine May 1, 2013
Dec 23, 2015
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?
“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”
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
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
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
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
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
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
Primary Insomnias
• Adjustment insomnia• Psychophysiological insomnia• Paradoxical insomnia• Idiopathic insomnia• Inadequate sleep hygiene• Behavioral insomnia of childhood
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
Causes of Insomnia
• Hyperactivity of HPA axis• Imbalance of flip-flop switch regulating
transition from sleep to wake
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
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
• Recurrent hypersomnia• Idiopathic hypersomina with or without
long sleep time• Hypersomnia due to a medical condition• Narcolepsy-cataplexy syndrome
Hypersomnia of Central Origin
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
Circadian Rhythm Sleep Disorders
• Delayed sleep phase• Advanced Sleep
Phase• Jet lag• Shift work
Drake 2010
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
• 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
Sleep-Related Movement Disorders
• Characterized by relatively simple, stereotyped movements that disturb sleep
• Bruxism • Rhythmic movement disorder• Nocturnal leg cramps• Restless leg syndrome
Isolated Symptoms, Apparently Normal Variants and Unresolved Issues
• Long sleepers• Short sleepers• Snoring• Sleep talkers• Sleep related sexual disorders
• Therapeutic target• Mechanistic overlap• Identification of risk
factors and vulnerability
Neurological Disorders and Sleep