Sleep Mar 19 2013x - Lakehead University

Psychology 2401
Foundations of Biopsychology
Alana Rawana
2013
RHYTHMIC ACTIVITY
 Environment is rhythmic
 Brains have evolved a variety of systems for rhythmic
control
•
Mammalian rhythmicity:
•
•
•
•
•
•
•
Thirst and hunger
States of arousal (alertness)
Hormonal secretion
Respiration
Heart rate
Electrical rhythms of the cortex
THE SLEEP WAKE CYCLE
ELECTROENCEPHALOGRAM
 EEG:
 Classic method of recording brain rhythms
 A measurement that enables us to take a generalized
look at the activity of the cerebral cortex
 Richard Caton (England, 1875)
•
•
Electrical recordings from the surface of dog and rabbit brains
Hans Berger (Austria, 1929)
•
•
First described the human EEG
Observed differences in EEG activity
What are EEG’s used for today?
ELECTROENCEPHALOGRAM
RECORDING BRAIN WAVES
 Method is non-invasive & painless
 Wire electrodes are taped to the scalp, along with a
conductive paste to lower the resistance
 Electrodes are placed on standard positions on the head
 Electrodes are connected to banks of amplifiers and
recording devices
 Small voltage fluctuations are measured between pairs of
electrodes
RECORDING BRAIN WAVES CONT’D
•
WHAT GENERATES THE OSCILLATIONS OF AN
EEG?
• An EEG measures voltages generated by dendritic
synaptic excitation of pyramidal cells of the cortex
• However, any single neuron does not contribute much
to the electrical signals recorded by the EEG
• Therefore, an EEG is a reflection of many thousands of
neurons firing simultaneously
EEG
CONSEQUENCES OF SUMMATION
•
The amplitude of EEG signal strongly depends, in
part, on how synchronous the activity of the
underlying neurons is.
•
•
Synchronous activity: when a group of cells are
simultaneously excited and the “mini” individual signals
summate to generate one large surface signal
Irregular activity: when a group of cells receives the
same amount of excitation but do not respond
simultaneously the summation does not amount to
much
Synchronous
activity
Magnetocephalography (MEG)
 Wherever electrical current flows a magnetic field is
generated
 Magnetic current detected by an array of 150 sensitive
magnetic detectors
 MEG vs EEG
 What are MEG’s used for today?
Magnetocephalography (MEG)
EEG RHYTHMS
•
EEG rhythms vary drastically depending on
particular states of behavior or pathology
• e.g. level of attentiveness, arousal, sleeping,
waking…coma, seizures
•
EEG rhythms are categorized according to their
frequency range…
TYPES OF RHYTHMS
•
•
•
•
Beta rhythms: fastest, greater than 14Hz, signal activated,
alert cortex
Alpha rhythms: 8-13Hz, signal awake but quiet and relaxed
states
Theta rhythms: 4-7Hz, signal some of the deep sleep states
Delta rhythms: very slow, very large in amplitude, less than
4Hz, hallmark of deep sleep
Normal EEG
 Alpha & beta waves
 Both sides of brain show similar patterns of electrical
activity
 No abnormal bursts of electrical activity & no slow
brain waves
 Proper response to photic stimulation
Abnormal EEG
Abnormal EEG (Cont’d…)
 Sudden bursts of electrical activity or sudden slowing
of brain waves
 Delta waves or too many theta waves in adults who are
awake.
 a "flat" or "straight-line" EEG
EEG Rhythms Cont’d…

•
•
Obviously EEG recordings do not allow us to read a
persons thoughts, but they do allow us to tell if a
person is thinking
frequency:
amplitude rhythms are associated
with alertness, waking, and dreaming sleep states
frequency:
amplitude rhythms are associated
with non-dreaming sleep states and pathological
states of coma
Generation of Synchronous
Rhythms
 Activity of a large set of
neurons produce
synchronized oscillations in
one of two ways:
(1) They may take cues from
central clock (pacemaker)
(2) Share or distribute the
timing fcn among
themselves by mutually
exciting or inhibiting one
another
Synchronous Activity – Mammalian
Brain
 Rhythmic synchronous activity is usually
coordinated by a combination of the pacemaker &
collective methods
 Thalamus
 Can generate very rhythmic action potential
discharges
 How do thalamic neurons oscillate?
How do thalamic neurons
oscillate?
How do thalamic neurons
oscillate? (Cont’d…)
 Synaptic connections
between excitatory
and inhibitory
thalamic neurons
force each individual
neuron to conform to
the rhythm of the
group
 Coordinated rhythms
passed to cortex
Function of Brain Rhythms
•
Why are there so many rhythms?
•
Do they serve a purpose?
•
Obviously there are no satisfactory answers to either
of these questions… but there are a few decent
hypotheses
Functions of Brain Rhythms
Cont’d…
•
“Disconnection Hypothesis”:
• Sleep-related rhythms are the brain’s way of
disconnecting the cortex from sensory input
• AWAKE, sensory information is allowed to the
cortex via the thalamus
• ASLEEP, the thalamus goes on auto-pilot, the
neurons enter a self-regulated state that
prevents the relay of sensory input to the cortex
Functions of Brain Rhythms
Cont’d…
 Walter Freeman
 Neural rhythms coordinate activity between regions of
the NS
 Gamma rhythms
 Momentarily synchronizing fast oscillations generated
by different regions of cortex brain binds neural
components into a single perceptual construction
 Another plausible reason?
Seizures of Epilepsy
 Most extreme form of synchronous brain activity


Generalized seizure: involves the entire cortex of both
hemispheres
Partial seizure: involves a particular area of the cortex
Commonalities between the two?

Epilepsy: a condition defined by repeated seizure
experiences
 ~ 1% of the American population has epilepsy
Seizures and Epilepsy (Cont’d…)
 The cause of seizures can
sometimes be identified
 Examples
 Different types of
seizures have different
underlying mechanisms
 Genetic predisposition
Convulsants & Anticonvulsants
GABA receptor antagonists are very potent convulsants:
 Block GABA receptors
 Seizure-promoting agents
 Common uses?
GABA receptor agonists are very potent anticonvulsants:
 Suppresses seizures by countering excitability in
various ways…
 E.g., prolong inhibitory influence of GABA
Behavioural Features of Seizures
 During more forms of generalized seizures:
 All cortical neurons are engaged
 Unconscious
 Muscles – tonic or clonic activity
 John Hughlings Jackson - Partial Seizures
Pathological Brain Activity:
Seizures & Epilepsy
Sleep
•
•
•
•
We spend about one-third of our lives sleeping
• One-quarter of this time is spent dreaming
Sleep is universal among higher vertebrates
Sleep is essential to our lives, like eating and breathing
Prolonged sleep deprivation can devastate proper
functioning and in some animals, lead to death
Sleep (Cont’d…)
•
DEFINITION OF SLEEP:
• Sleep is a readily reversible state of
reduced responsiveness to, and
interaction with, the environment
(anesthesia and coma do not count since
they are not readily reversible)
Rapid Eye Movement Sleep
 REM sleep
 When EEG looks more awake than asleep
 Your body (except eye and respiratory muscles) is
immobilized
 Dreaming sleep
 Non-REM sleep a.k.a., slow-wave sleep
 Period of rest
 Temperature and energy consumption lowered
 Heart rate, respiration, and kidney fcn all slow down
 Digestive processes speed up
 Brain rests
REM AND NON-REM SLEEP
William Dement (Stanford University):
REM SLEEP:
“An active, hallucinating brain in a paralyzed body”
NON-REM SLEEP:
“An idling brain in a movable body”
•
ultradian rhythms
How are sleep spindles generated?
Sleep Related Disorders
 Insomnia
 Affects at least 20% of population at some time
 Example case
 One of the most important causes of insomnia seems to
be sleeping medication
 Sleep Apnea
Sleep-Related Disorders (Cont’d…)
Why do we sleep?
 All birds, reptiles, and mammals appear to sleep
 Although only mammals and some birds have REM
phases
Cool Animal Sleep Facts
The Bottlenose Dolphin
• Have more reason not
to sleep
• Live in deep water and
must breathe air every
minute or so (no
napping)
• However, they still
manage to get as much
sleep as humans do
• How???
Bottlenose Dolphin
•
They sleep with one cerebral hemisphere at a time!
• About 2 hours asleep on one side, then 1 hour awake on both sides,
then 2 hours asleep on the other side…
• For a grand total of 12 hours a night
• Do not seem to have REM sleep
Indus River Dolphin
Sleep Theories
 Theories of restoration vs. theories of adaptation
 We sleep to rest and recover
 We sleep to keep us out of trouble
 Does sleep renew us the same way eating and drinking
do?
Functions of Dreaming and REM
Sleep
Dreams are difficult to study
• Modern studies tend to look at REM sleep rather
than dreams…REM sleep can be measured
objectively
• Remember, REM sleep and dreaming are not
synonymous
•
• Dreams can occur during non-REM sleep and many
peculiar things occur during REM sleep that have
nothing to do with dreaming
Dreaming and REM sleep (cont’d…)
•
•
Do we need to dream? Who knows.
But, we do need REM sleep
• If people are deprived of REM sleep for a few days
they will experience REM rebound
• Sleepers will attempt to enter REM more rapidly
and will spend more time in REM proportional to
the duration of their deprivation
• Studies have found that REM deprivation does not
cause any psychological harm during the daytime
Dream Theories
Sigmund Freud
• Dreams are disguised wish-fulfillment, an unconscious way
for us to express our sexual and aggressive fantasies, which
are forbidden to us when we are awake
• Hobson & McCarley (Harvard University)
• More biologically based theories
• “activation-synthesis hypothesis”
• Dreams are seen as associations and memories of the cortex
that are elicited by the random discharges of the pons
during REM sleep
•
Activation Synthesis Hypothesis
The pontine nucleus, via the thalamus, activate different
areas of the cortex, elicit images/emotions, and the cortex
attempts to synthesize the disparate images into a coherent
whole
• This process can account for the often bizarre and
nonsensical nature of many dreams; since they are
triggered by the semi-random activity of the pons
• Evidence
•
No definitive evidence but some intriguing hints
indicating the role of REM sleep and memory
consolidation
What many suggest:
• REM sleep deprivation in humans and rats can impair
their ability to learn new tasks
• Karni and colleagues found that people’s performance on a
visual task improved with REM sleep
•
• Interesting to note that non-REM sleep deprivation actually enhanced
their performances
•
Karni hypothesized that this kind of visual memory
requires a period of time to strengthen, specifically via
REM sleep
Sleep Learning?
Neural Mechanisms of Sleep
•
•
•
Until the 1940s sleep was thought to be a passive
process…without sensory input, the brain will
fall asleep
However, experiments blocking sensory
afferents in animals did not eradicate their
sleep/wake cycles
We now know that sleeping is an active process
that includes the participation of a variety of
brain regions
Neural Mechanisms of Sleep
(Cont’d…)
1.
2.
3.
4.
The diffuse modulatory NT systems are the most critical
to the control of sleeping and waking
During waking, the locus coeruleus (NE) and the raphe
nuclei (5-HT) fire and enhance awake states (some ACh
neurons also participate as well)
These diffuse modulatory systems control rhythmic
behaviors of the thalamus, which controls many EEG
rhythms of the cortex (remember slow wave
rhythms…block flow of sensory information via the
thalamus to cortex)
Descending branches of these systems are involved in
inhibition of motor neurons
Localization of Sleep Mechanisms
in the Brain
•
•
•
Lesions of the brainstem of human can cause sleep and
coma suggesting the brain stem must play a role in
keeping us awake
Moruzzi (1940s) attempted to sort out the brain stem’s
control of waking and arousal
• Lesions in the midline structures of the brain stem
caused a state similar to non-REM sleep
• Lesions in the lateral tegmentum did not (this area
interrupts ascending sensory inputs)
• Stimulation of the lateral tegmentum transformed the
cortex from slow EEGs to awake EEGs (a more alert and
aroused state)
Called this area ASCENDING RETICULAR ACTIVATING
SYSTEM (ARAS)
Falling Asleep and the Non-REM
State
 Decrease in the firing rates of most brain stem
modulatory neurons
 Sleep spindles disappear
 Synchronization of activity due to neural
interconnections
Mechanisms of REM Sleep
•
•
•
•
•
•
Neurons of the motor cortex continue to fire rapidly and
attempt to command the muscles of the body but only
succeed with the eye, ear, and respiratory muscles
V1 is equally active in REM and non-REM
Extrastriate areas and limbic areas more active during
REM
Frontal lobe activity less active in REM sleep
The firing rates of the locus coeruleus and raphe nuclei
decrease to almost nothing
Sharp increase in firing rate of ACh neurons in the pons
PET Imaging
Why don’t we act out our dreams?
 Same core brain stem systems inhibit our spinal motor
neurons
 Adaptive
 REM sleep behaviour disorder
 Disruption of brain stem systems
 Lesions studies
Sleep-Promoting Factors
 John Pappenheimer (Harvard U.)
 Muramyl dipeptide facilitated no-REM sleep
 Found in spinal fluid of sleep-deprived goats
 Usually peptides are only produced by cell walls of
bacteria
 Maybe synthesized by bacteria in the intestines
 Interleukin-1
 Synthesized by brain
Sleep-Promoting Factors
(Cont’d…)
 Adenosine
 Acts as a neuromodulator at
synapses throughout brain
 Antagonists of adenosine
(e.g., caffeine and
theophylline)
 Administration of adenosine
or its agonists increase sleep
 Extracellular adenosine levels
are higher during waking
 Adenosine levels throughout
the day
How does adenosine promote
sleep?
 Inhibitory effect on modulatory systems for Ach, NE,
and 5-HT
 Neural activity in the awake brain increases adenosine
levels
 Brain will fall into the slow-wave synchronous activity
SIDE NOTE: How does caffeine
promote wakefulness?
 Four different adenosine
receptor subtypes have
been identified: A1, A2A,
A2B, A3
 Which one does caffeine
most potently block?
Another Sleep-Promoting Factor
 Melatonin
 Located just above tectum
 Derivative of tryptophan
 “Dracula of hormones”
Circadian Rhythms
Circadian rhythms: the daily cycles of daylight and
darkness that result from the spin of the earth
• The precise schedules vary from species to species
(some are active at night… some in the day)
• Many physiological and biochemical processes
fluctuate with the daily/monthly/yearly rhythms
•
• Body temperature, blood flow, urine production,
hormonal levels, hair growth, and metabolic rate
Zeitgebers
(from the German zeit=time and geber=giver):
environmental time cues
Light/dark, temperature, humidity…
In their presence, animals become entrained to the
day/night rhythm and maintain an activity of exactly 24
hours
In their absence, animals will settle into a rhythm of
activity/rest within 24 hours (more or less)…these
rhythms are free run
Free running period of mice (23 hours), hamsters (24
hours), and humans (24.5 - 25.5 hours)
Relationship Between Behaviour
and Physiology
 Problems occur when behaviour and physiology are
desynchronized
 When can this happen?
 Best cure?
Brain Clocks
•
Biological clocks consist of a few components:
Light-sensitive input pathway

Clock

Output pathway
Input pathways entrain the clock to keep it in rhythm with the
environment
• The clock will continue to function if the input pathway is
removed
• Output pathway control brain/body functions according to the
timing of the clock
•
Suprachiasmatic
nuclei (SCN)
SCN (Cont’d…)
•
Since behavior is synchronized with light/dark
cycles, there must be a photosensitive mechanism
involved
Retinal ganglion cells

via retinohypothalamic tract

Synapse directly on SCN neurons
The SCN Cont’d…
This retinal input is necessary and sufficient to
entrain waking/sleeping cycles with light/dark
cycles
• SCN neurons have very large receptive fields and
respond to luminance changes (not motion or
orientation)
• Surprisingly, the retinal cells that aid in
synchronizing the SCN are not rods or cones
•
• Eyeless mice cannot reset their clocks, but mice with
intact retinas lacking rods and cones can
SCN Mechanisms
•
•
•
SCN cells communicate with the rest of the brain
using action potentials
Rates of firing vary with circadian rhythm
However, action potentials are not necessary for SCN
neurons to maintain their rhythm
• Tetrodotoxin (TTX) blocks action potentials but does not affect the
rhythmicity of their metabolism and biochemical functions
•
SCN action potentials are like the hands of a clock;
removing them does not stop the clock from working,
but it does make telling time difficult
Seasonal Affective Disorder (SAD)
Seasonal Affective Disorder (SAD)
 A clinical condition characterized by regular onset
and remission of depressive episodes that follow a
seasonal pattern
Etiology Models
 Melatonin Hypothesis and
Circadian Models
 Monoamine Hypothesis
 The Dual Vulnerability
Hypothesis
Melatonin Hypothesis and
Circadian Models
 Phase delay
 Circadian
Rhythms
Monoamine Hypothesis
 Serotonin
 Controls appetite & sleep
 Precursor of melatonin
 Dopamine
The Dual-Vulnerability Hypothesis
 DVH
 2 vulnerability dimensions in SAD
 Seasonal vs. nonseasonal depression
Seasonality Study
Seasonality Study
 Changes in mood, eating patterns, energy levels,
socialization, sleep patterns and weight, which occur in
response to the changing seasons, are referred to as
seasonality (Kasper, Wehr, Bartko, Gaist & Rosenthal, 1989) .
 Individuals with seasonal mood changes often report the
atypical vegetative-somatic depressive symptoms such as
increased carbohydrate craving and food intake during
the winter (Rosenthal, Genhart, Sack, Skwere & Wehr, 1987).
 Seasonal affective disorder (SAD)
Study Findings
 Higher levels of seasonality was linked to more
severe depression symptoms, stress,
dysfunctional eating behaviours, and over-
eating.
 Seasonality predicted both disordering eating
behaviours and overeating, particularly in the
presence of stress. Study demonstrates
support for a diathesis-stress model
Jet Lag Disorder
Jet Lag Disorder
 Circadian misalignment, the inevitable
consequence of crossing time zones too rapidly for
the circadian system to keep pace
Possible Treatments:
 Prescribed Sleep Scheduling
 Circadian Phase Shifting
 Timed Melatonin Administration
 Promoting Sleep with Hypnotic Medication
 Promoting Alertness with Stimulant Medication
Prescribed Sleep Scheduling
 Conclusion: One study supports staying on a home-
based sleep schedule when time at destination is
planned to be brief (i.e., two days or less) in order to
limit jet lag symptoms. There are some data from jet
lag studies to support altering the scheduled timing of
sleep prior to eastward travel to help with entrainment,
though the impact of this on jet lag symptoms is not
entirely clear
Timed Light Exposure
 Conclusion: In a jet lag simulation study, appropriately
timed bright light exposure prior to travel was able to
shift circadian rhythms in the desired direction but
would require high motivation and strict compliance
with the prescribed light-dark schedule if prescribed
clinically. One trial with artificial light exposure upon
arrival produced equivocal results.
Timed Melatonin Administration
 The evidence is overall quite supportive that melatonin,
administered at the appropriate time, can reduce the
symptoms of jet lag and improve sleep following travel
across multiple time zones. Immediate-release
formulations in doses of 0.5 to 5 mg appear effective
Promoting Sleep With Hypnotic
Medication
 Although the number of studies is limited, the use of
hypnotic agents for jet lag-induced insomnia is a
rational treatment and consistent with the standard
recommendations for the treatment of short-term
insomnia. However, the effects of hypnotics on daytime
symptoms of jet lag have not been well-studied and are
unknown. In addition, any benefits to using hypnotics
must be weighed against the risk for side effects.
Because alcohol intake is often high during
international travel, the risk of interaction with
hypnotics should be emphasized with patients.
Promoting Alertness with
Stimulant Medications
 Conclusion: The use of caffeine to counteract jet lag
induced sleepiness seems rational, but the evidence is
very limited (2 studies). The alerting effects of these
agents must be weighed against their propensity to
disrupt sleep. One study suggested that a slow-release
caffeine formulation may enhance the rapidity of
circadian entrainment following eastward travel.
Therapeutic Sleep Deprivation
Major Depressive Disorder
 Associated with high degree of subjective distress and
psychosocial disability
 Lifetime prevalence rate of about 20% (Kessler et al., 2003)
 High relapse or recurrence rates
(50–90%), especially if there has been
prior depressive episodes (Piet & Hougaard,2011)
 Development of effective interventions is high priority
Therapeutic Sleep Deprivation
 I.e., Wake therapy, induced-wakefulness therapy =
chronobiological therapy
 Nonpharmacological therapy
 Counterintuitive
 Modes of SD
 Total sleep deprivation (TSD)

08:00 of day 1 until 22:00 of day 2 (38 hours)
 Partial sleep deprivation (PSD)


Early: First half of night from 22:00 until 02:00
Late: Second half of night from 02:00 until 22:00
Supporting Evidence
 Pflug and Töille (1971): TSD can induce temporary
remissions in depressed (unipolar) patients
 Responses within hours – shorter time lag than other
drugs and psychotherapies (Wirz-Justice et al., 2005)
 PSD in second half of night shows similar effects (Schilgen
and Töille, 1980)
 More than two thirds of unmedicated patients
responded to SD with a 20-60% improvement in mood
compared to baseline values (Rudolf & Töille, 1978; Giedke & Schwärzler,
2002)
 Meta-analysis of 61 studies by Wu and Bunney (1990):
Marked antidepressive effect in 59% of patients
Limitations
 80% sink back into depression following one night of sleep
(Wu & Bunney, 1990)
 50% relapse into depressed mood after a nap (Wiegand et al., 1987)
 Early morning naps worse than naps later in day
 Microsleep – may prevent response or induce relapse
(Hemmeter, Hemmeter-Spernal & Krieg, 2010)
 Approximately 1/3 of patients do not benefit from SD
 Increased tiredness
 May intensify depressive symptomatology
 Agitation and restlessness associated with exhaustion
 Occurs in 2-7% of therapeutic SDs (Giedke, Geilenkirchen, & Hauser,
1992)
Stabilizing The
Antidepressant Effect
 Recommendations of
the Committee on
Chronotherapeutics in
Affective Disorders of
the International
Society for Affective
Disorders
 + mood stabilizer (Goodwin
& Jamison, 2007)
 Repeated = (two-[total
sleep deprivation] or
three-times [partial
sleep deprivation] per
week)
Supporting Evidence: Predictors of
SD
 Diurnal variation of mood
 Typical sleep disturbance
 Increased tiredness
 Frequent nocturnal awakenings
 Early morning awakening
 Un- or less-disturbed function of the hypothalamic-
pituitary-adrenal axis and increased metabolic activity of
the ventral anterior cingulate
(Hemmeter, Hemmeter-Spernal & Krieg, 2010)
 More “activation”
 Less tired, more behavioural activation (Clark, Dupont, Golshan, & Gillin,
1997)
Limitations: Side Effects of SD
 Vegetative symptoms i.e., increased appetite (Pflug, 1976)
 Fatigue (Pflug, 1976)
 Headaches (Bhanji & Roy, 1975)
 In epilepsy: high risk of
inducing seizures
(Nakken, Solaas, Kjeldsen, Friis, Pellock, & Corey, 2005)
 Nonspecific stress (Suh et al., 2007)
Summary
Sleep deprivation works as an antidepressant tx if paired
with daily light therapy, administration of SSRIs,
lithium (bipolar), or a short phase advance of sleep
 Combinations of these interventions show great
promise in the treatment of depression.
State of Research on Underlying
Mechanisms
 Controversy: No conclusive explanation for rapid relief of
depression and immediate relapse into depression after
sleep
 Unlikely that psychological mechanisms can provide
complete explanation – due to rapidity of changing mood
 Neuroimaging:
 Results indicated increased activity in ventral anterior
cingulate cortex & medial prefrontal cortex in SD responders
compared to nonresponders (Wu et al., 1992)

Anterior cingulate is innervated by serotonin and dopamine systems
(Wu, Buchsbaum, & Bunney, 2001).

Mobilization: Decreased metabolism of serotonin and dopamine
after SD as serotonin and dopamine are both enhanced after SD
(Gardner, Fornal , & Jacobs, 1997)
`