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Neurobiology of Sleep

Neurobiology of Sleep. Subimal Datta Sleep Research Laboratory Department of Psychiatry Boston University School of Medicine, Boston, MA. 25 th Birthday. Happy Birthday!. 9 Years of Sleep 2.5 Years of Dreaming. Sleep Medicine.

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Neurobiology of Sleep

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  1. Neurobiology of Sleep Subimal Datta Sleep Research Laboratory Department of Psychiatry Boston University School of Medicine, Boston, MA

  2. 25th Birthday Happy Birthday! 9 Years of Sleep 2.5 Years of Dreaming

  3. Sleep Medicine • Sleep ranks among the 3 most important considerations in maintaining good health • Accompanied by good nutrition and stress management • 62% of US population experiences sleep problems • 80% of US adults have NEVER discussed sleep problems with their physician • Societal bias equates sleepiness with laziness

  4. Objectives of this Lecture • To describe methods for the objective identification of different stages of sleep • To describe the patterns of sleep, and factors influencing those patterns • To describe circadian and homeostatic aspects of sleep • To describe neuronal substrates of sleep

  5. Definition and QualitativeDescription of Sleep • Sleep is a reversible behavioral state of perceptual disengagement from, and unresponsiveness to, the environment. • Species-specific postural recumbence • Behavioral quiescence • Elevated arousal threshold • Rapid arousal after moderate stimulation • Perceptual disengagement from environment • Dreams • Other behaviors: sleep walking, sleep talking, tooth grinding, and some physical activities may also bee seen during sleep.

  6. Sleep is a special activity of the brain.

  7. Non-rapid Eye Movement (NREM) Sleep -Stage 1 -Stage 2 -Stage 3 -Stage 4 Rapid Eye Movement (REM) Sleep -Phasic -Tonic Stages of Sleep

  8. Standard Physiological Variables Electroencephalogram (EEG) Electrooculogram (EOG) Electromyogram (EMG) Additional Variables Respiratory Movements Blood Oxygen Saturation Heart Rate Leg Movements Polysomnography (PSG)

  9. Electroencephalogram(EEG) • Reflects local potentials at the level of cerebral cortex, specifically a summary of local synaptic potentials on cortical pyramidal neurons. • Type, location and mutual synchronization of these potentials is reflected in different shape, amplitude and frequency of recorded brain waves.

  10. Electrode Placement C3 A1 A2

  11. EEG FREQUENCY AMPLITUDE Beta > 13 Hz < 5 mV Alpha 8-13 Hz 5-15 mV Theta 4-7 Hz 10-50 mV Delta < 4 Hz > 50 mV

  12. EEG EEG Sharpwave EEG Typical EEG signs for the identification of different stages of sleep K Complex EEG EEG EEG

  13. Electromyogram (EMG) Awake NREM Sleep REM Sleep • Three electrodes are placed beneath the chin, overlying Mentalis/submentalis muscles. • Sometime, the Anterior tibialis EMG is important to evaluate patients with PLM disorder.

  14. Electrooculogram (EOG) +cornea retina EOG is measured based on corneo-retinal potential. As eyeballs move, the electrical potential field changes with reference to electrodes.

  15. Wakefulness and Transition toNon-REM Sleep

  16. Non-REM Sleep: Stage 1

  17. NREM Sleep: Stages 2-4 Stage 2 Stage 3 Stage 4

  18. Outline of Standard Criteria for Scoring NREM sleep Stages • Stage 1 EEG:Relatively low voltage, mixed frequency; may be theta (3-7 cps) activity with greater amplitude; Vertex sharp waves; Synchronous high-voltage theta bursts in children EMG:Tonic activity, may be slight decrease from waking EOG:Slow eye movements

  19. Stage 2 EEG:Sleep spindles (waxing and waning at 12-14 cps, ≥ 0.5 sec); K complex (negative sharp wave followed immediately by slower positive components; maximal in vertex; spontaneous or in response to sound) EMG:Tonic activity, low level EOG:Occasionally slow eye movements near sleep onset

  20. Stage 3 EEG:≥ 20≤50% high amplitude (> 75 V), slow frequency (≤ 2 cps); maximal in the frontal EMG: Tonic activity, low level EOG:None, picks up EEG • Stage 4 EEG:>50% high amplitude, slow frequency EMG: Tonic activity, low level EOG:None, picks up EEG

  21. Orthodox of NREM Sleep DEEPER SLEEP SLEEP STAGE 4 3 2 1 AWAKE GREATER SYNCHRONY

  22. Rapid Eye Movement (REM) Sleep Human Rat

  23. Signs of REM Sleep • EOG: Rapid eye movements (REMs) • EEG: High frequency low amplitude EEG; Sawtooth waves; theta activity; PGO/P-waves • EMG: Antigravity or postural muscles are paralyzed • Muscle jerks • Penile/clitoral tumesence

  24. Signs of REM Sleep • Thermoregulation is absent (poikilothermia) • Irregular breathing, including brief hypopneas and apneas • Unstable cardiac system (variable heart rate and blood pressure). Indeed some speculate that the phasic excitation of the cardiac system during REM may trigger heart attacks • Dream

  25. The Progression of Sleep Stages Across a Single Night Wake S1 S2 Sleep-Wake Stages S3 S4 REM Mov. 6 4 7 3 5 2 24 1 Time in Hour

  26. Generalizations About Sleep in the Normal Young Adult Human • Sleep is entered through NREM. • NREM sleep and REM sleep alternate with a period near 90 min. • Slow wave sleep predominates in the first third of the night and is linked to the initiation of sleep. • REM sleep predominates in the last third of the night and is linked to the circadian rhythm of body temperature.

  27. - Continuation • Wakefulness within sleep usually accounts for less than 5 percent of the night. • Stage 1 sleep generally comprises about 2 to 5 percent of sleep. • Stage 2 sleep generally comprises about 45 to 55 percent of sleep. • Stage 3 sleep generally comprises about 3 to 8 percent of sleep.

  28. - Continuation • Stage 4 sleep generally comprises about 10 to 15 percent of sleep. • NREM sleep, is therefore, is usually 75 to 80 percent of total sleep. • REM sleep is usually 20 to 25 percent of total sleep, occurring in four to six discrete episodes.

  29. How do these wake and sleep stages play out over the night and day? • Circadian Rhythm (24 hours) • Sleep Homeostasis

  30. Circadian Rhythm of Sleep 3 4 2 1 Days

  31. Clock in the Brain • Overwhelming evidence indicates that the suprachiasmatic nucleus (SCN), a paired structure located in the anterior hypo-thalamus contains a circadian pacemaker. • Circadian rhythms are abolished with complete lesions of the SCN. • SCN transplants into the third ventricle and hypothalamus restores rhythmicity in previously arrhythmic animals.

  32. CIRCADIAN BODY RHYTHMS SCN

  33. MELATONIN NIGHT

  34. Sleep Homeostasis • Sleepiness increases in proportion to prior awake time • There is a “pressure” to keep awake and sleep time balanced • There is a need for recovery sleep after sleep deprivation

  35. Age-related Changes in Sleep Pattern

  36. Age-related Changes in Total Amount of Daily Sleep 40 25 20 18.9 15 3.8

  37. Sleep in Elderly Earlier sleep onset Early morning awakenings • Daytime sleepiness • Loss of delta sleep • Reduced REMs and dream recall

  38. Brain Areas ● Hypothalamus ●Basal Forebrain ●Brainstem:Pons CEREBRAL CORTEX Neurotransmitters ● Ach ●Glutamate ● GABA ●Histamine ● NE ●5-HT ● Peptides ●NO THALAMUS PONS SPINAL CORD

  39. Mechanisms of SWS Generation EEG Cortex Hpc Cerebellum Thalamus Midbrain scp R AC Sol POA TMN Pons OX Medulla

  40. Brainstem Network for REM Sleep Sign Generation

  41. Thank You!

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