Chapter 19: Brain Rhythms and Sleep

The Electroencephalogram

• Electroencephalogram (EEG) - measurement of electrical activity from the surface of the scalp that shows generalized activity of the cerebral cortex

  • First discovered by Richard Canton to measure voltage of dog and rabbit brains

  • Hans Berger first described the human EEG in sleep-wake cycles

• EEG is noninvasive and painless; it uses electrodes to measure the voltage (low spatial resolution)

  • Wires from pairs of electrodes are fed to amplifiers, and each recording measure voltage differences between two points on the scalp

  • A typical EEG record is a set of many simultaneous squiggles, indicating voltage changes between pairs of electrodes

  • EEG measures thousands of underlying neurons, activated together (which creates a large enough signal to be measured)

    • Amplitude of the EEG signals are dependent on the number of active neurons and the synchronicity of the neurons firing

  • Tracks electrical potentials from the soma

  • EEG is measured in Hz (1/sec; cycles/sec)

• Magnetoencephalography (MEG) - used to measure neuron currents that produce a magnetic field

  • Better at localizing the sources of neural activity in the brain, particularly those deep below the surface

  • Used in experimental studies of the human brain and its cognitive functions and as an aid in the diagnosis of epilepsy and language disorders

• EEG rhythms vary and often correlate with particular states of behavior

  • Main EEG rhythms:

    • Delta rhythms - slow, less than 4 Hz, large in amplitude (deep sleep)

    • Theta rhythms - 4—7 Hz (sleep and wake states)

    • Alpha rhythms - 8—13 Hz, largest over the occipital cortex (quiet, waking states)

    • Mu rhythms - 8—13 Hz (largest over motor and somatosensory areas)

    • Beta rhythms - 15—30 Hz

    • Gamma rhythms - 30—80 Hz (activated or attentive cortex)

    • Spindles - brief 8—14 Hz waves (sleep)

    • Ripples - brief bouts of 80—200 Hz oscillations

  • Alertness and waking → high-frequency, low-amplitude rhythms

  • Nondreaming sleep states, certain drugged states, coma → low-frequency, high-amplitude rhythms

• Fourier Transformation - wave forms are combinations of sine waves

  • breaking EEG rhythms into its parts (sub-frequencies)

• A large set of neurons will produce synchronized oscillations by:

  • Taking cues from a central clock, or pacemaker (central conductor)

  • Sharing or distributing the timing function among themselves by mutually exciting or inhibiting one another (synchronization through activity)

• Neural oscillators consist of: a source of constant excitatory drive, feedback connections, and synaptic excitation and inhibition

  • The thalamus generates rhythmic activity because of the intrinsic properties of its neurons and because of its synaptic interconnections

    • During sleep, thalamic neurons enter a self-generated rhythmic state that prevents organized sensory info from being relayed to the cortex

  • In the awake cortex, synchronizing fast oscillations generated by different regions of cortex, may bind the various neural components into a single perceptual construction (speculation)

  • Oscillations may be the unavoidable consequence of so much feedback circuitry, unwanted but tolerated by necessity

• Seizure an extreme form of synchronous brain activity that results in very large EEG patterns and small motor patterns

  • Generalized seizure involves the entire cerebral cortex of both hemispheres, complete behavior disruption, loss of consciousness (tonic-clonic seizure)

  • Partial seizure involves a circumscribed area of cortex, abnormal sensation, aura (abnormal vision), or movement

  • Some seizures reflect an upset of the balance of synaptic excitation and inhibition in the brain

  • Other seizures may be due to excessively strong or dense excitatory interconnections

  • During a seizure, consciousness is lost, while all muscle groups may be driven by tonic (ongoing) activity or by clonic (rhythmic) patterns, or by both in sequence (tonic-clonic seizure)

  • Absence seizure involves less than 30 seconds of generalized 3 Hz EEG waves; body becomes still & the person is un responsive

• Epilepsy is a condition characterized by repeated seizures

  • A symptom of disease than a disease itself (tumors, trauma, genetics, infection, vascular disease, many cases unknown)

  • Some forms show a genetic predisposition

    • These genes code for a diverse array of proteins, including ion channels, transporters, receptors, and signaling molecules

Sleep

• Sleep is a readily reversible state of reduced responsiveness to, and interaction with, the environment

• Circadian Rhythms - most revolve around the sleep-wake cycle (24 hrs)

  • Vary throughout the day, but are synched

• Polysomnogram - a test of sleep cycles and stages through the use of continuous recordings of:

  • EEG, EMG (muscle activity), EOG (eye movement), ECG (heart rate), respiration rate, and other measures related to the sleep cycle

• Phases of Sleep:

  • Rapid Eye Movement (REM) sleep - characterized by an fast, low EEG rhythms (paradoxical sleep), the body (except the eyes and respiratory muscles) being immobilized, and conjuring vivid, detailed illusions (dreams)

    • The oxygen consumption of the brain is higher in REM sleep than when the brain is awake and concentrating on difficult mathematical problems

    • Atonia - the paralysis that occurs during REM sleep caused by an almost total loss of skeletal muscle tone

    • Physiological control systems are dominated by sympathetic activity during REM sleep

      • The body’s temperature control system quits

      • Heart and respiration rates increase but become irregular

      • The clitoris and penis become engorged with blood and erect

    • Non-REM sleep - characterized by large, slow EEG rhythms and no complex dreams

      • Increases activity of the parasympathetic ANS

• The Sleep Cycle:

  • Begins with a period of non-REM sleep

    • 75% of total sleep time is spent in non-REM and 25% in REM, with periodic cycles between these stages throughout the night

  • Non-REM sleep is divided into four stages:

    • Stage 1: first entering stage 1 non-REM sleep; falling asleep and light sleep (theta rhythms)

    • Stage 2: occasional 8-14 Hz oscillation of the EEG (sleep spindle), via a thalamic pacemaker; high-amp sharp wave (K complex); no eye movements

    • Stage 3: EEG records large-amp, slow delta rhythms; few eye and body movements (slow wave sleep)

      • Stage 4: deep sleep, EEG records are large, with 2 Hz rhythms or less (slow wave sleep)

        • Sleep then ascends to stage 3, then into REM, with fast EEG beta and gamma rhythms and sharp and frequent eye movements (not deep sleep)

    • Ultradian Rhythms - we slide through the stages of non-REM, REM, non-REM, repeating the cycle about every 90 mins

  • During the night, the duration of non-REM sleep reduces, and REM periods increase

    • Each REM period is followed by at least 30 mins of non-REM sleep before the next REM period can begin

  • Sleep requirements do not decrease between preadolescence and early teen years, but changes in circadian timing mechanisms make it progressively harder for teens to fall asleep early in the evening

• Theories of Restoration and Adaptation

  • Restoration: we sleep to rest and recover and to prepare to be awake again

    • Prolonged sleep deprivation can lead to serious physical and behavioral problems

      • Yoked design - what happens to one subject happens to the other, except the independent variable

      • Glymphatic system - release of buildup from the brain to the lymph nodes via CSF that happens when we sleep

    • It is possible that brain regions such as the cerebral cortex can achieve some form of essential “rest” only during non-REM sleep

  • Adaptation: we sleep to keep us out of trouble, to hide from predators when we are most vulnerable or from other harmful features of the environment, or to conserve energy

  • Memory Consolidation: we sleep to consolidate our memories from the day

    • Experiment: place cells in rodents fired in response to stimuli throughout a maze in similar patterns while the rodent slept

    • Experiment: Individuals that learned a task, slept normally, and redid the task were better than those that were deprived of REM sleep

      • Slow wave sleep had no effect on how people performed the tasks

• Modern explanations of dreaming lean heavily on studies of REM sleep rather than dreaming because the phenomena of REM can be objectively observed

  • Even then, dreams and REM are not synchronous

  • The activation-synthesis hypothesis states that dreams are associations and memories of the cerebral cortex that are elicited by the random discharges of the pons during REM sleep (PGO waves)

    • Does not explain how random activity can trigger the complex and fluid stories of dreams, nor how it can evoke dreams that recur

• Sleep disorders include insomnia and sleep apnea

• REM behavior disorders include the lack of atonia during REM sleep, atonia during wake (cataplexy), and atonia during stage 1 or when waking up

• Sleep is an active process that requires the participation of a variety of brain regions

  • The neurons most critical to the control of sleeping and waking are part of the diffuse modulatory NT systems

  • The brain stem modulatory neurons using NE and 5-HT fire during waking and enhance the awake state (REM-off cells); some neurons using ACh enhance critical REM events (REM-on cells), and other cholinergic neurons are active during waking

  • The diffuse modulatory systems control the rhythmic behaviors of the thalamus, which in turn controls many EEG rhythms of the cerebral cortex; slow, sleep-related rhythms of the thalamus apparently block the flow of sensory info up to the cortex

  • Sleep also involves activity in descending branches of the diffuse modulatory systems, such as the inhibition of motor neurons during dreaming

• Lesions in the brain stem of humans can cause sleep and coma, suggesting that the brain stem has neurons whose activity is essential to keeping us awake

• Several sets of neurons increase their firing rates in anticipation of awakening and during various forms of arousal

  • Locus coeruleus cells w/ NE

  • Raphe nuclei cells w/ 5-HT

  • Brain stem and basal forebrain cells w/ ACh

  • Midbrain neurons w/ histamine

  • Hypothalamic neurons w/ hypocretin (orexin)

    • Axons project widely in the brain and excite the cell types above

    • Hypocretin

      • promotes wakefulness

      • inhibits REM sleep

      • facilitates neurons that enhance certain kinds of motor behavior

      • involved in the regulation of neuroendocrine and autonomic systems

    • The loss of hypocretin neurons in the lateral hypothalamus leads to the sleep disorder narcolepsy

      • Can result in excessive daytime sleepiness, cataplexy (sudden muscular paralysis), sleep paralysis, hypnagogic hallucinations

      • Antagonist to the VLPA sleep-promoting region on the arousal systems to keep the systems activated

• Falling asleep involves a progression of changes over several minutes, culminating in the non-REM state

  • EEG sleep spindles → slow delta rhythms

    • Synchronization is due to neural interconnections within the thalamus and between the thalamus and cortex

• During REM, there is increased extrastriate activity, which is internally generated, limbic activation (for the emotional component of dreams), and low frontal lobe activity

• The firing rate of the locus coeruleus and raphe nuclei decreases to almost nothing before the onset of REM; there is a sharp increase in firing rates of cholinergic neurons in the pons (which may induce sleep) before the onset of REM

• The same core brain systems that control the sleep processes of the forebrain also inhibit our spinal motor neurons, preventing the descending motor activity from expressing itself as actual movement

  • REM sleep behavior disorder is the condition in which people, usually elderly men act out their dreams

• Extracellular levels of natural brain adenosine are higher during waking than while sleeping, and increase during prolonged waking periods and sleep deprivation; they decrease during sleep

  • Adenosine has an inhibitory effect on the diffuse modulatory systems for ACh, NE, and 5-HT that tend to promote wakefulness

  • Nitric oxide (NO) is a sleep-promoting factor that triggers the release of adenosine

  • Interleukin-1, a cytokine (immune signaling chemical), promotes non-REM sleep and stimulates the immune system (induces fatigue and sleepiness)

  • Melatonin, a hormone secreted by the pineal body, is released at night and helps initiate and maintain sleep; sends info to the SCN

Circadian Rhythms

• Circadian rhythms the daily cycles of daylight and darkness that result from the spin of the Earth

  • Most physiological and biochemical processes in the body also rise and fall with daily rhythms

    • ex: body temp., blood flow, urine production, hormone levels, hair growth, and metabolic rate

  • Circadian rhythms are biological in the brain and are adjusted by external stimuli

  • Zeitgebers - environmental time cues (light/dark, temp, and humidity variations); keeps organisms in phase

    • In the absence of zeitgebers, mammals rhythms free-run in a period more or less than 24 hours

  • Desynchronization, like jet lag, occurs when we force our bodies into a new sleep-wake cycle

• A biological clock that produces circadian rhythms consists of several components:

  • Light sensor → Clock → Output pathway

    • One or more input pathways are sensitive to light and dark and entrain the click and keep its rhythm coordinated with the circadian rhythms of the environment

    • The clock itself continues to run and keep its basic rhythm even when the input pathway is removed

    • Output pathways from the clock allow it to control certain brain and body functions according to the timing of the clock

  • Suprachiasmatic nucleus (SCN) - pair of neuron clusters in the hypothalamus that serve as a biological clock

    • Located on either side of the midline, bordering the third ventricle

    • Removal of both nuclei abolishes the circadian rhythmicity of physical activity, sleeping and waking, and feeding and drinking

    • Lesions in the SCN do not abolish sleeping

  • Axons from ganglion cells in the retina, via the retinohypothalamic tract, synapse directly on the dendrites of SCN neurons

    • This input from the retina is necessary and sufficient to entrain sleeping and waking cycles to night and day

    • SCN neurons respond to the luminance of light stimuli rather than their orientation or motion

      • Light-sensitive ganglion cells, with the photopigment melanopsin, are slowly excited by light, and their axons send a signal directly to the SCN that can reset the circadian clock that resides there

  • SCN cells communicate their rhythmic message to the rest of the brain through efferent axons, using APs, and rates of SCN cell firing vary with a circadian rhythm

    • APs are not necessary for SCN neurons to maintain their rhythm

    • In Drosophila and mice, the molecular clock system involves a variety of clock genes

      • Using protein synthesis (more protein builds up during the day, inhibits promoter factors, and inhibiting protein synthesis [negative feedback])

    • Light info from the retina resets the clocks in the SCN neurons each day, but the SCN neurons also communicate with each other

  • All cells’ clocks scattered throughout the body’s organs are under the control of the SCN

    • The SCN has a strong circadian influence on the:

      • ANS

      • body temp.

      • adrenal gland hormones (cortisol)

      • neural circuits that control feeding, movement, and metabolism