Basic Science of Representative Normal Human EEG Normal Human EEG Potentials Seyed M Mirsattari, MD, PhD, FRCPC Departments of Clinical Neurological Sciences, Medical Biophysics, Diagnostic

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  • Basic Science of

    Representative Normal

    Human EEG PotentialsSeyed M Mirsattari, MD, PhD, FRCPCDepartments of Clinical Neurological

    Sciences, Medical Biophysics, Diagnostic Imaging, Psychology

    University of Western OntarioLondon, Ontario

    EEG Course, CNSF, Vancouver, BCThursday June 16, 2011

  • ObjectivesTo understand the basic science of common human

    EEG potentials

    Representative normal EEG waveforms in wakefulness

    and sleep

    Wakefulness (alpha, theta)

    NREM sleep (sleep spindles, K complex, theta,


    REM sleep

  • Disclosure statement

    Dr. Mirsattari has nothing to disclose

  • EEG scalp recording: normal, awakeEEG scalp recording: normal, awake

  • Alpha rhythm

    posterior dominant rhythm


    lies in the posterior head regions

    frequency= 8 - 13 Hz

    attenuated with eye opening

  • Alpha rhythmmore than one site generates it within both cortical and subcortical regions

    Electrode locations

    Perez-Borja C et al., Electroencephal Clin Neurophysiol 1962;14:171-182

  • Theta rhythms4-7 Hz frequencies of varying amplitude and morphologiesabout 35% of normal young adults show intermittent 6-7 Hz of R) may occur in the elderly population

    Incidence= ~ 35%not an abnormal finding

  • Normal F-C theta in an awake 18 YO

  • Delta rhythmsFrequency:

  • Intermittent L mid-T during transition to drowsiness in a normal 84 YO

  • NREM sleepLow neuronal activityMetabolic rate and brain temp. are at their lowest.Sympathetic outflow decreases and HR and BP dropParasympathetic activity increases and then dominates

    Constricted pupilsIntact muscle tone and reflexesFour characteristic stages

  • NREM sleepStage 1 sleep:

    defined by the presence of vertex waves

    Stage 2 sleep:

    defined by the presence of sleep spindles

    and K complexes

    has the same features as stage 1 with

    progressive slowing of background


  • Stage 1 NREM sleepTransition from wakefulness to the onset of


    Lasts several minutes.

    Low-voltage EEG activity

    10 - 30 uV

    16 - 25 Hz

    Then, sinusoidal alpha

  • Normal sleepVertex waves (V waves)

    typically 200 msec

    diphasic sharp transients (maximal negativity

    at Cz)

    bilateral, synchronous, symmetric

    may be induced by auditory stimuli

    can be apiculate (esp. in children)

    never consistently lateralizes

    may be seen in stage 1 to 3 sleep

  • Normal sleep

    Sleep spindles

    transient, sinusoidal 12-14 Hz

    waxing and waning in amplitude

    seen in the central regions

    slower frequencies (10-12 Hz) in the F regions

  • Normal sleepK-complex

    a high-amplitude diphasic wave with an

    initial sharp transient followed by a high

    amplitude slow wave

    often associated with a sleep spindle in

    the F-C regions

    may be evoked by a sudden auditory


    persistent asymmetry of >50% is abnormal

    on the side of reduction

  • Stage 2 sleep with prominent POSTs, F-C sleep spindles and a T4 small sharp spike

  • Normal sleepSlow wave sleep:

    non-REM deep sleep

    1-2 Hz waves occupying variable amounts of the background

    Stage 3: occupying 20-50% of the recording with voltages of >75 V

    stage 4: occupying >50% of the recording

  • Slow wave sleep, intermittent POSTs and sleep spindles

  • EEG waves of NREM sleepEEG waves of NREM sleep

  • REM sleepRapid eye movements

    Loss of muscle tone

    Sawtooth waves in the EEG

    Alternates with non-REM deep sleep in cycles

    4-6X during a normal night's sleep

    non-REM sleep predominates the first part

    of the night

    REM sleep occurs in the last third of the


  • REM sleep with lateral rectus potentials in the anterior-lateral headregions induced by rapid eye movements

  • Sleep architecture and neurophysiologicalcharacteristics of sleep stages

    Diekelmann S, BornNature J. Neuroscience Review. 2010;11:114-126.

  • NREM sleep Generated by neurons in the preoptic

    region of the hypothalamus and adjacent

    basal forebrain

    Lesions in these regions cause


    Stimulation of these regions rapidly

    produces sleep onset

  • NREM sleep Hypothalamus role in NREM sleep

    modulates thalamic and cortical activity

    controls brainstem arousal systems

    Encephalitis lethargica (von-Economo C. J Nerv

    Ment Dis 1930;71: 249-59)

    Damage to the posterior hypothalamus results in

    excessive sleepiness

    Damage to the anterior hypothalamus results in


  • NREM sleepTwo populations of GABAergic neurons:

    the ventrolateral preoptic region

    active during spontaneous sleep

    the median preoptic region

    active during spontaneous sleep

    active during waking in sleep-deprived

    states, suggesting that this cell population

    mediates sleep debt.

  • Median preoptic sleep active neurons control the transitions from wake to NREM

    sleep mediate sleepiness

    active in waking in the sleep-deprived animal and increase activity prior to sleep onset

    Cells in the ventrolateral preoptic neurons are important in maintaining sleep continuity and in the homeostatic control of REM sleep.

    They are inactive during waking They maintain elevated levels of activity

    throughout NREM sleep

    NREM sleep

    Gvilia I et al. J Neurosci 2006;26:9426-33; Szymusiak R et al. Ann N Y Acad Sci 2008;1129:275-86

  • NREM sleep One subgroup of median and ventrolateral

    preoptic neurons maintains their NREM sleep

    activity in REM sleep

    The remaining sleep active neurons are maximally

    active in NREM and have greatly reduced activity in

    REM sleep.

    Gvilia I et al. J Neurosci 2006;26:9426-33; Szymusiak R et al. Ann N Y Acad Sci 2008;1129:275-86

  • Physiology of sleep spindles generated from the activity of rhythmically firing neurons.

    nucleus reticularis thalami (NRT) & thalamocortical neurons (TC)

    nucleus reticularis: GABAergic neurons Firing rate = 7-14 Hz low threshold Ca2+ spikes Ca2+ enters through voltage sensitive channels

    open when the cell is relatively hyperpolarizedAfter the Ca2+ spikes, membrane currents return the cell to the hyperpolarized state, restarting the process.Steriade M. Sleep, epilepsy and thalamic reticular inhibitory neurons.Trends Neurosci 2005;28:317-24.

  • Physiology of sleep spindlesThalamocortical neuron (TC)

    RTN - induced IPSPs

    Rebound depolarization

    Hyperpolarization activates low threshold

    Ca2+ potential (LTCP) in the TC neurons.

    Depolarization of TC neurons produces

    action potentials and cortical EPSPs and


    EEG records sleep spindles

  • ThalamoThalamo--corticocortico--thalamicthalamic looploop

    Pyramidal cell

    Inhibitory interneuron

    Thalamocortical relay neuron

    Cerebral Cortex

    Nucleus ReticularisThalami (NRT)

    ThalamoreticularNeuron (TC) Thalamus

    Low threshold Ca2+ potential (LTCP) in TC neurons

    Crunelli V, et al. Cell Calcium 2006;40(2):175-190.

  • Calcium Channels Display Selective permeability to calcium (voltage-gated)

    Type Gated by Protein Gene Location Function

    L-type High voltage Cav1.1Cav1.2Cav1.3Cav1.4


    Neurons, Skeletal Muscle, ventricular

    myocytes, bone

    Cav1.1: Malignant hyperthermia, hypokalemic periodic paralysis. Cav1.2: congenital stationary night blindnessCav1.3: upregulated in aging brain

    P/Q-type High voltage Cav2.1 CACNA1A Neurons Famlial Hemiplegic Migraine, Episodic Ataxia associated with primary

    generalized epilepsy.

    N-type High voltage Cav2.2 CACNA1B Neurons unknown

    R-Type Intermediate voltage

    Cav2.3 CACNA1E Neurons unknown

    T-type Low-voltage Cav3.1Cav3.2Cav3.3


    Neurons, Cardiac Myocytes

    Are enhanced in several animal models of epilepsy,

    no monogenetic defects reported yet in humans.

  • T-type calcium Channels

    Talavera K, Nilius B. Cell Calcium 2006;40:97-114.

  • Current view of T-type Ca2+channel neurophysiology

    Crunelli V, et al. Cell Calcium 2006;40(2):175-190.

  • Sleep theta waves and HTBs

    Thalamocortical relay neuron

    Crunelli V, et al. Cell Calcium 2006;40(2):175-190.

  • Sleep K-complex and the role of ITwindow in slow (< 1Hz) oscillation

    Crunelli V, et al. Cell Calcium 2006;40(2):175-190.

  • Physiology of sleep spindles

    Thalamocortical relay neuron

    Crunelli V, et al. Cell Calcium 2006;40(2):175-190.

  • Physiology of delta waves and the slow (

  • Physiology of delta waves

    Similar to sleep spindles

    Higher levels of membrane hyperpolarization

    Slower membrane oscillations

  • NREM sleepThe histamine-containing neurons of the posterior hypothalamus are important in maintaining the waking state.

    They are tonically active in waking, greatly reduce discharge in NREM sleep and become nearly silent in REM sleep.

    This discharge profile is shared by noradrenergic neurons of the locus coeruleus, serotonergicneurons of the raphe nuclei, and hypocretin-containing neurons of the hypothalamus, all of which have been shown to increase waking when activated.

  • Nuclei in the pon