1 / 116

Sleep Physiology-basic mechanisms of sleep & arousal

Sleep Physiology-basic mechanisms of sleep & arousal. In 1940’s Moruzzi & Magoun found that electrically + certain areas in the brain and brainstem produced cortical activation arousal states appear to be determined by an interaction among the brainstem, hypothalamus, thalamus & basal forebrain

arleen
Download Presentation

Sleep Physiology-basic mechanisms of sleep & arousal

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Sleep Physiology-basic mechanisms of sleep & arousal • In 1940’s Moruzzi & Magoun found that electrically + certain areas in the brain and brainstem produced cortical activation • arousal states appear to be determined by an interaction among the brainstem, hypothalamus, thalamus & basal forebrain • Dampening of arousal systems with concomitant active inhibition by thalamo-cortical systems produces sleep

  2. Basic mechanisms of sleep (cont) • Areas maintaining wakefulness include • oral pontine reticular formation • midbrain central tegmentum • posterior hypothalamus • Sleep promoting areas are located: • midline brainstem • dorsolateral medullary reticular formation • anterior hypothalamic preoptic region

  3. Interaction between sleep & wakefulness areas • Magnocellular nucleus basalis of Meynert located in the forebrain • intermingling of both sleep & arousal systems • sleep modulating center • both sleep and waking active sites • projections to neocortex and midbrain reticular formation • acetylcholine projections

  4. Sleep • Sleep is a behavioral state that differs from wakefulness by a readily reversible loss of reactivity to event’s in one’s environment. • Sleep is divided into stages based on: • electroencephalography (EEG) • electro-occulogram (EOG) • electromyogram (EMG)

  5. Sleep Stages • Non Rem (NREM) or slow wave sleep • I (light) theta, delta (low amplitude) horizontal eye • II (light) theta, delta, sleep spindles, K complexes • III (deep) high amplitude delta (20-50%) • IV (deep) high amplitude delta (>50%) • Rapid eye movement (REM) • EEG resembles awake state or NREM stage I • dramatic decrease in EMG activity

  6. Jet Lag

  7. Sleep • Electrical stimulation of nucleus tractus solitarius (NTS) produces slow wave sleep • Lesions in NTS produces cortical desynchronization (waking pattern of EEG) • NTS appears to inhibit more rostrally situated neurons in the ascending reticular activating system • Direct connections between NTS & major areas of the limbic system exist (ant. thalamus, hypothalamus, amygdala)

  8. Effect of pentobarbital on sleep

  9. Sleep (cont.) • Lesions in serotonin rich raphe nucleus produces insomnia • Parachlorophenylalanine (PCPA) a trytophan hydroxylase inhibitor also produces insomnia by blocking production of serotonin • SWS can be restored in PCPA induced insomnia by administration of 5 Hydroxytrytophan (5HTP)

  10. Sleep (cont) • Serotonin appears to modulate sleep through its effect on other hyponogenic factors in the anterior hypothalamus and suprachiasmatic nucleus • Serotonin is a melatonin precursor • Melatonin is synthesized and released by the pineal gland through sympathetic activation from the retino-hypothalamic tract

  11. Sleep (cont.) • Melatonin enhances sleep • prolonged bright light stimulation suppresses melatonin and sleep while subsequent melatonin injections can restore normal sleep patterns • Preoptic nucleus of ant. Hypothalamus appears to inhibit waking areas in the rostral midbrain and mesopontine reticular core

  12. Sleep (cont) • Prostaglandin D2 which is highly concentrated in the preoptic nucleus and induces both SWS and REM sleep • Prostaglandin inhibition by indomethacin can decrease diurnal sleep • The anterior hypothalamus may also promote sleep by inhibiting the waking area in the posterior hypothalamus • Factors such as triazolam, 5HTP, muramyl peptides, PGD2 have hypnogenic effects by acting on the anterior hypothalamus

  13. Slow wave sleep (SWS) • Sleep spindles and delta waves are physiologic events involving GABAergic neurons via inhibition promote brain deafferentation • Sedatives (barbituates) and hypnotics (benzodiazepines) stimulate GABA receptors and facilitate sleep • Sleep spindles are rhythmic cortical waveforms generated by oscillatory activity in nucleus reticularis of the thalamus

  14. Slow wave sleep (SWS) • Slow waves (delta) are generated in neocortical circuits arising in all cortical layers • An increase in GABAergic anterior hypothalamic preoptic and basal forebrain neurons is associated with SWS • Afferent input to anterior hypothalamus, serotonin, muramyl peptides, interleukins, PG’s that produce temp increase resulting in heat loss may induce SWS

  15. REM sleep • Cortical EEG is highly desynchronized (similar to waking) • Associated with pontine geniculate occipital spikes (PGO) • PGO spikes are associated with many phasic events such as rapid eye movements, changes in respiration, heart rate, muscle twitches, and dreaming

  16. REM sleep (cont.) • PGO spikes originate from REM-ON cells in medial pontine reticular formation & adjacent reticular tegmental nucleus • In animals REM sleep has been eliminated by placing lesions ventral to locus ceruleus • REM sleep can be induced by cholinergic stimulation of the pons • REM-OFF cells are represented by noradrenergic cells of locus ceruleus which become silent during REM

  17. REM sleep (cont.) • Many antidepressants are REM suppressors; which increase activity of norepinephrine and/or serotonin • Progressive decrease in muscle tone associated with hyperpolarization of motor neurons • Rheobase 30% greater in REM sleep

  18. REM behavior disorder • Normally REM sleep is associated with a progressive decrease in muscle tone associated with hyperpolarization of motor neurons • In this disorder there is persistant muscular tone during REM • Characterized by bursts of excessive limb & body movements • Cause in humans unknown • In cats lesions of the pons that destroy area just ventral to the locus ceruleus

  19. Other changes in sleep • Reduction in body and brain temperature at onset of sleep associated with vasodilation • general decrease in metabolism • reduced thermosensitivity of hypothalamic preoptic nucleus • Suprachiasmatic nucleus serves as an endogenous clock influencing both sleep and body temperature in a closely coupled fashion.

  20. Other changes in sleep (cont) • Brain metabolism decreases 20-35% in SWS • Cerebral blood flow decreases during SWS • Adenosine appears to be a somnogenic neurotransmitter (caffeine blocks hypothalamic adenosine receptors) • Sleep onset is associated with inhibition of TSH, cortisol, & stimulation of GH & Prolactin

  21. Potential Sleep Promoting Factors • Many also have immune functions • Muramyl peptides • Lipopolysaccharides • Prostaglandin D2 • Interleukin I • Interferon alpha2 • Tumor necrosis factor • Delta sleep-inducing peptide • Vasoactive intestinal peptide • Serotonin/melatonin • Prolactin

  22. Function of Sleep • Restores normal levels of brain activity and normal balance among different parts of CNS (restore natural balance) • Physiologic effects on the rest of the body • decreased SNS, increased Para effects in slow wave sleep • enhanced immune function • common factors

  23. Link between sleep & weight loss • Sleep deprivation • can raise cortisol • Cortisol  insulin which promotes fat storage • Can contribute to insulin resistance • Linked to obesity, CV disease, type II diabetes • High fat, high sugar diet can lead to insulin resistance •  slow wave sleep (stage III and IV non REM) • Linked with  levels of growth hormone • Has an important role in fat loss and muscle growth • Individuals who sleep longer (>9 hr) less likely to be obese than individuals who sleep shorter (<6 hr) (I.J.Obesity&Metabolic Disorders 24; 1683, 2000.)

  24. Epilepsy (seizures) • Uncontrolled excessive activity of either part or all of the CNS “electrical storm” • Predisposition greater than incidence • Disrupts normal brain function • Epileptogenic circuitry • lowered threshold and/or facilitation

  25. Epilepsy • Causes • Trauma • Oxygen Deprivation • Tumors • Infections • Toxic States • (In1/2 of all cases the cause is unknown). • Incidence • .5-1% of population (2nd most common neurological disease)

  26. Epilepsy • Precipitating causes of a seizure • strong emotional stimuli • alkalosis (hyperventilation) • drugs • fever • loud noises or flashing lights • Termination of a seizure • neuronal fatigue • active inhibition (inhibitory NT)?

  27. Types of Seizures • Grand Mal (Tonic-Clonic) • Petite Mal (Absence) • Psychomotor (Focal) • Jacksonian • Myoclonic • Atonic • Status Epilepticus

  28. Grand Mal • Aura • altered sensation prior to seizure, e.g. tingling • Tonic phase • rigid stiffening of body, loss of consciousness • Tonic-clonic phase • strong muscle contractions & convulsions, over within minutes • Post-ictal phase • return to consciousness; may be associated with confusion, stupor, slurred speech, weakness

  29. Epilepsy • Treatment • Drugs • phenobarbital • dilantin • tegratol • depekene (Valproic Acid) • Surgery • excision of epileptic foci • Vagal stimulator • Chiropractic adjustments

  30. Evoked Potentials (EP) • Sensory EP is a change in EEG resulting from stimulation of a sensory pathway • Sensory EP is extracted from EEG using computer averaging techniques • EEG is recorded during repetitive natural stimulation (eg. tap on skin or flash of light) • Computers samples the EEG before & after stimulation & sample data are averaged.

  31. Evoked Potentials (cont) • Sensory EP consist of multiple components related to various aspects of subcortical & cortical processing (scalp electrodes) • Clinically useful for assessing the function of sensory systems or evaluating demyelinating diseases (eg. M.S.) • Destruction of myelin causes conduction velocity to decrease which increase latencies

  32. Mental Illness • Affect core elements that define humanity • personality, goal directed behavior, language, creativity, abstract thinking, emotion, mood, social organization • Neural disruptions are probably complex, multiple, not readily observable • occur at biochemical or molecular level • range from mild to severe

  33. Mental Illness • Mild • obsessive-compulsive personality • antisocial personality • Severe • dementias • schizophrenia • bipolar disorder • major depression • anxiety disorders (e.g. panic attacks)

  34. Schizophrenia (shattered mind) • Characterized by a mixture of S/S of which no single one is necessarily present • significant deterioration in functioning • relatively chronic course • very incapacitating (60% morbidity) • onset early in life (late teens-early twenties) • Is a disease of neural connectivity caused by multiple factors that affect brain development • Multiple hits • Some combination of genetic and non genetic factors

  35. Schizophrenia - symptoms • Positive symptoms • distortions or exaggerations of normal cognitive or emotional functions • delusions • hallucinations • disorganized speech • bizarre behavior • mesolimbic • ventral tegmental area to many areas of limbic system

  36. Schizophrenia-symptoms • Negative symptoms • loss or decrease of normal functions • alogoria -poverty of speech or empty content • flat affect-decrease in ability to express emotion • anhedonia-inability to experience pleasure • avolition -inability to initiate or persist in goal directed behavior • attentional impairment • tend to impair the persons ability to function in daily life more so than positive symptoms • mesocortical • ventral tegmental area to neocortex

  37. Schizophrenia • Various symptoms suggest possible involvement of a variety of cortical and subcortical areas • Anatomical abnormalities include enlargement of ventricles and prominent sulci due to abnormal brain development • Mixture of genes and environment as causative factors

  38. Schizophrenia-causes • Genetics • Concordance in monozygotic twins- 40% • Concordance in dizygotic twins- 10% • Non genetic factors • poor nutrition • infections during pregnancy or childhood • toxins-damage neurons or affect NT systems • radiation-mutations

  39. Schizophrenia-Dopamine • Exaggerated Dopamine activity (working hypothesis but is oversimplified) • at key sites-limbic areas, language areas • dopamine receptor blockers (type 2) • increased dopamine receptors • L-dopa causing schizophrenic symptoms • increased levels of dopamine metabolites

  40. Disorders of Mood • Depression • Mania • Anxiety Disorders

  41. Terms • Mood • sustained emotional state • Affect is a sign- what can be observed • Normal affective responses • Euphoria, elation, pleasure, surprise, anger, anxiety, disappointment, sadness, grief, despair, depression

  42. Unipolar Depresssion • First described in Hippocratic writings in 5th century B.C. • Moods were thought to depend upon the balance of the four humors • blood, phlegm, yellow bile, black bile • An excess of black bile was thought to cause depression • melancholia means black bile

  43. Unipolar Depression • Most likely several disorders • Untreated, typically lasts 4-12 months • Characterized by pervasive unpleasant mood that is present most of the day • inability to experience pleasure (anhedonia) • generalized loss of interest

  44. Unipolar Depression • Additional symptoms (3 to make Dx) • disturbed sleep • diminished appetite (sometimes overeating) • loss of E • decreased sex drive • restlessness • retardation of thoughts/actions • difficultly in concentrating • indecisiveness • low self esteem • guilt/pessimistic thoughts • thoughts about dying & suicide

  45. Unipolar depression • Additionally symptoms may show a diurnal variation usually worse in mornings • schizophrenia & other neurological diseases need to be excluded • Incidence-5% of population (U.S.= 8 mil) • Average age 30 • Subtypes • (endogenous) melacholic • reactive

  46. Bipolar (Manic-Depressive) • Gives rise to Euphoria (Manic phase) • Similar to unipolar depression with mania • Mania • elevated expansive or irritable mood which lasts at least a week • overactivity (including speech) • social intrusiveness • increased energy & libido • decreased need for sleep • reckless involvements

  47. Depression (in general) • Strong genetic predisposition • concordance in monozygotic twins =50% (even when reared apart) • Incidence of suicide in biologic relatives of depressed adoptees 6-10 X higher than biologic relatives of normal adoptees • stress can play a role • average age of onset has declined over last 60 years

  48. Triad Brain Shrinkage Depression Chronic low Back pain

  49. Treatment of Depression • Electroconvulsive therapy (ECT)- 90% • Drugs-70% • MAO inhibitors • Tricyclic • Specific Serotonin uptake blockers • Lithium Salts • Alternatives-?% • St. John’s Wort • Chiropractic • Omega 3 Fatty Acids

  50. ECT • In use for over 50 years • full remission or marked improvement in about 90% of patients with well defined major depression • 6-8 trts at 2 day intervals over 2-4 wks. • Anesthesia with complete muscle relaxation • therapeutic change in aminergic receptor sensitivity

More Related