Transcript Lecture 14A

Videos
• Dog acting out a dream and runs into a wall:
http://youtu.be/grEypMDqvTE
• Narcolepsy: http://youtu.be/qVu-IcLoZtU
Sleep
Why do we sleep?
Why do we sleep?
• Sleep is a basic requirement for normal brain function:
• Lack of sleep 
– Mental fatigue: During Navy SEAL sleep deprivation training Stew Smith
reports: after about 3 days hallucinations started to set in. Smith recalls
mistaking an airplane for a flying horse, perceiving a bridge as a giant Pez
dispenser, and seeing a squat, muscular body builder where there was in fact a
fire hydrant.
– poor decision-making: In tests, those who have stayed awake for 24 hours
perform similarly to those with a blood alcohol content of 0.1% (=3 drinks) on
many mental and physical tasks.
– shortened attention span
– higher anxiety
– impaired memory
– impaired learning
– a grouchy mood
– a heightened risk of migraine and epileptic attacks
– can more than double the risk of death from cardiovascular disease.
– increased cancer growth and dampened the immune system's ability to control
cancers (demonstrated in mice).
– hinders the healing of wounds and burns (demonstrated in rats).
Total sleep loss
• Chronic and complete insomnia ultimately leads to death in
humans, rats, and flies alike.
• Rats totally sleep-deprived died within 11-32 days (faster than
food-deprived rats). All sleep deprived rats showed a
debilitated appearance, lesions on their tails and paws, and
weight loss in spite of increased food intake.
• In humans, Fatal familial insomnia: the average survival span
is 18 months
The disease has four stages:
1. The person has increasing insomnia, resulting in panic attacks,
paranoia, and phobias.
2. Hallucinations and panic attacks
3. Complete inability to sleep is followed by rapid loss of weight
4. Dementia, after which death follows.
• During sleep,
waste
products of
brain
metabolism
are removed
from the
interstitial
space among
brain cells
where they
accumulate.
• In waking, CSF flow is restricted to the brain surface—but
expands deep into the tissue during both slow-wave sleep
and anesthesia. The consequence is remarkable: The flow of
CSF through the interstitial space is increased 20-fold in slow
sleep compared to flow of CSF during waking.
Glymphatic System
• Until recently, the
prevailing view was
that the brain
recycles wastes on its
own - WRONG.
• beta-amyloid and
other wastes are not
recycled, but cleared
by the glymphatic
system.
• The flow of
glymphatic fluid
increases during sleep
because the space
between the cells
expands, which helps
to push fluid through
the brain tissue.
• The brain removes
unwanted proteins,
sweeping them out
for later degradation
by the liver.
Conclusions:
• Main function of sleep is maintenance.
• Metabolism is a dirty process.
• During sleep, waste products of brain metabolism
are removed from the interstitial space.
• During sleep there is also increased production of
oligodendrocytes  repair axons.
• Sleep is universal among vertebrates and has been found
in invertebrates
• The total number of hours of daily sleep varies from as
much as 20 hours in bats to as little as 3 to 4 hours in
giraffes and elephants
• Faster metabolism  longer sleep duration
• Smaller animals have faster metabolism  longer sleep
Sleep and memory
Researchers trained mice in a new skill - walking on top of a rotating rod
newly formed dendritic
spines (filled arrowheads)
sleeping mice formed significantly more new connections between neurons
• Sleep is good for memory consolidation (conversion of memory into
permanent memory).
• Memory improvement is most dramatic for procedural memory (riding
a bike, skating, playing the piano).
• Even a short nap can really improve memory.
Sleep and memory
• Important memories are consolidated.
• Unimportant memory traces are deleted:
• That includes most memories.
• Synapses encoding that memory are
disintegrated,
• synaptic spines are retracted.
• It is very important to forget!
• Sleep is important for both for
• memory consolidation and
• preparing the brain for new learning.
Sleep stages
Non-REM sleep = slow wave sleep = deep sleep
• Sleep is highly structured
• 1 complete cycle (Non-REM stage and REM stage) = 1.5hours
• The night sleep starts with you quickly falling down into very
short dream-filled REM-like state and then into deep sleep
Slow-wave (deep, non-REM) sleep
• During deep sleep Loud noise,
smells are unlikely to wake you up
• Many neurons are synchronized
(firing together in that training of
neuronal ensembles by
hippocampus) so we see high
amplitude EEG with low
frequency ~1Hz (Delta waves).
• Muscles are not paralyzed, so
sleep-walking, sleep-talking, and
bedwetting occur in this stage.
• If you wake up from slow wave
sleep you feel dreadful.
• When people are woken from
slow-wave sleep, they usually do
NOT report dreams.
• During slow-wave sleep CSF flow expands deep into the
brain tissue. The consequence is remarkable: The flow
of CSF through the interstitial space is increased 20-fold
in slow sleep compared to flow of CSF during waking.
REM (Rapid Eye Movement / Paradoxical sleep)
• EEG readings are irregular in frequency
and low in amplitude—similar to those
observed in awake individuals.
• When people are woken from REM
sleep, they usually report vivid dreams.
• Eyes move rapidly under closed lids,
breathing becomes irregular and heart
rate increases.
• Motor neurons are completely inhibited
(so that you don’t enact your dreams;
common experience: nightmare want
to run  but cannot move muscles).
• Horses and many other animals can
sleep while standing, but must
necessarily lie down for REM sleep
because of inhibition of tonic muscles).
• People even lose some of the ability to
regulate their body temperature during
REM
How do marine mammals sleep?
• unlike terrestrial mammals, dolphins, whales, and seals
cannot go into a sleep.
• The consequences of falling into a sleep for marine
mammalian species can be suffocation and drowning.
• Thus, dolphins, whales, and seals engage in
unihemispheric sleep, which allows one brain hemisphere
to remain fully functional, while the other goes to sleep.
• The hemisphere that is asleep, alternates so that both
hemispheres can be fully rested.
• Just like terrestrial mammals, seals that sleep on land have
both hemispheres of their brain shut down at the same
time.
Do animals have dreams?
• Dog acting out a dream and runs into a wall:
http://youtu.be/grEypMDqvTE
• Animals also dream in REM sleep. By
destroying neurons in the brain stem that
inhibit movement during sleep, researchers
found that sleeping cats rose up and attacked
or were startled by invisible objects—
ostensibly images from their dreams.
Do animals have
dreams?
• The absence of REM
sleep in the echidna
suggests that this
stage of the sleep
cycle evolved some
140 million years
ago, when
marsupials and
placentals diverged
from the monotreme
line. (Monotremes
were the first
mammals to develop
from reptiles.)
No REM
REM
Rats Dream About
the Places They
Want to Explore
•
•
•
•
•
As an animal explores an area it creates a mental map of the space. When the animal is in
one location, a few neurons in the hippocampus called ‘place cells’ will fire. If the animal
moves to a new spot, other place cells fire instead. Each time the animal returns to that
spot, the same place cells will fire. Thus, as the animal moves, a place-specific pattern of
firing emerges which can be used to reconstruct the animal's position.
After exploring a space, the hippocampus may replay the new place-specific pattern of
activity during sleep to consolidate the memory of the space.
Experiments: rats were allowed to run up to the junction in a T-shaped track. The animals
could see into each of the arms, but not enter them. Food was then placed in one of the
inaccessible arms. Researchers recorded the firing of place cells when animals were on the
track and during a rest period afterwards.
Then the rats were allowed onto the inaccessible arms, and again their brain activity was
recorded.
In the rest period after the rats first viewed the inaccessible arms:
–
the place cell pattern that would later form the mental map of a journey to and from the food-containing
arm was activated.
– the place cell pattern that would become the mental map of the other inaccessible arm was NOT
activated.
•
Therefore, the perception of reward influences which place cell pattern is simulated in the
mind during rest. An implication of these findings is that the brain preferentially simulates
future experiences that are deemed to be functionally significant, such as those associated
with reward.
Sleep stages and memory
• Deep sleep is important for consolidation of memories "as they
happened." Hippocampus is driving reactivation of neuronal
ensembles as they formed during the sensory experience.
• In REM sleep  there is no input from hippocampus to neocortex
 neuronal ensembles are activated in neocortex spontaneously
– Suppose you have visited three birthday parties and saw a candle on a
Ben’s cake and on John’s cake and on Jake’s cake.
– During REM birthday video is played back and common elements are
selected. Neurons that encode cakes with candles are hyper-activated
 generalization: all BD are associated with cakes and candles.
– REM sleep is important for generalization: Paris is capital of France, and
London and Madrid are other capitals
– During REM sleep norepinephrine release is suppressed and emotional
memories can be recalled without being emotional.
– In this regard REM sleep plays a role of a good therapy session - one
analyses the self.
Slow-wave sleep compared with presleep wakefulness
Lower (note the nose)
Middle
Top (note the ears)
light purple indicates greatest reduction of rCBF
• Frontal lobe (including both lateral and medial &
ventral PFC) shows clear reduction of regional Cerebral
Blood Flow (rCBF), while the posterior cortex does not.
• Recall that memory is consolidated in the posterior
cortex; hippocampus is driving activation of neuronal
ensembles in the posterior cortex, not in the PFC.
REM sleep compared with slow wave sleep
red indicates greatest increase of rCBF
• In REM sleep  No input from hippocampus to neocortex.
• Note that the lateral PFC is also inactive. The PFC puppeteer is asleep and
hippocampus is asleep. But you have dreams… who is activating those
neuronal ensembles that produce the content of the dreams?
• They activate spontaneously generating all kinds of vivid mental scenes.
• REM sleep is important for generalization: Suppose you have neuronal
ensembles of birthdays activated. Neurons that encode cakes are hyperactivated  generalization: all BD are associated with cakes.
• Note ventromedial PFC activation – emotional bran is at work, probably
assessing the scenarios painted by the vivid dreams. Is this scenario good
for my survival? for the advance along the social ladder?
• norepinephrine release is suppressed  SNS is not activated as much 
even emotional memories do not produce panic attack.
Mechanism of
dreaming could be
somewhat similar
to that of
hallucinations
•
•
•
placebo
LSD
During REM, most likely it is multiple areas of the cortex that are activated synchronously
that creates the weird nature of dreams.
Similarly: “… under LSD, compared to placebo, disparate regions in the brain communicate
with each other when they don’t normally do so. In particular, the visual cortex increases its
communication with other areas of the brain, which helps explain the vivid and complex
hallucinations experienced under LSD, and the emotional flavour they can take.”
“On the other hand, the neuronal networks that normally fire together when the brain is at
rest, sometimes called the ‘default mode network’, we saw reduced blood flow — something
we’ve also seen with psilocybin — and that neurons that normally fire together lost
synchronization. That correlated with our volunteers reporting a disintegration of their sense
of self, or ego. This known effect is called ‘ego dissolution': the sense that you are less a
singular entity, and more melded with people and things around you. We showed that this
could be experienced independently of the hallucinatory effects — the two don’t necessarily
go together.”
Post-sleep wakefulness when
compared with REM sleep as baseline
red indicates greatest increase of rCBF
• Note dramatic increase in lateral PFC activation. The
PFC puppeteer is back to work controlling the puppets
(neuronal ensembles in the posterior cortex).
• In wakefulness your mental world is much more
controlled by your PFC (top-down recall, mental
synthesis, analysis) than during sleep.
What causes one to fall into sleep?
• Circulating hormones?
• Brain nuclei?
• Accumulation of Adenosine?
• Melatonin - a hormone
that anticipates the
daily onset of darkness
• Photosensitive cells in
the retina detect light
and indirectly send
signal the into the
pineal gland that
produces melatonin.
If one girl falls asleep, can the other
girl stay awake?
•
•
•
•
•
In these sisters: One brain can be
asleep while the other brain may be
awake  brain nuclei
•
The Hensel girls are the rarest form of
conjoined twins, the result of a single
fertilised egg which failed to separate
properly in the womb.
They have two spines (which join at the
pelvis), two hearts, two oesophagi, two
stomachs, three kidneys, two gall
bladders, four lungs (two of which are
joined), one liver, one ribcage, a shared
circulatory system and partially shared
nervous systems.
From the waist down, all organs,
including the intestine, bladder and
reproductive organs, are shared.
While they were born with three arms,
one was removed surgically.
Although Brittany - the left twin - can't
feel anything on the right side of the
body and Abigail - the right twin - can't
feel anything on her left, instinctively
their limbs move as if co-ordinated by
one person, even when typing e-mails on
the computer.
It is rare for twins conjoined the way that
Abby and Brittany are to survive into
adulthood, but despite this they are in
good health, without heart defects or
organ failure.
Adenosine / Caffeine
• Local control of alertness level
• As neurons fire, they use ATP and produce adenosine.
• With a continued wakeful state, over time adenosine
from ATP accumulates in synapses.
• Adenosine activates adenosine receptors that increase
drowsiness.
• The caffeine molecule is competitive inhibitor of
adenosine.
• As a result, caffeine temporarily prevents or relieves
drowsiness, and thus maintains or restores alertness.
Central control of
alertness level:
Reticular formation
• Reticular formation
in the brainstem is
important for setting
alertness level
• The reticular formation has projections to the thalamus and
cerebral cortex that allow it to exert control over which sensory
signals reach the cerebrum and come to our conscious attention.
• It plays a central role in states of consciousness like alertness and
sleep (it is a pacemaker for slow sleep Delta waves).
• Injury to the reticular formation can result in irreversible coma.
Neuropeptide Orexin is the ultimate flip flop
switch between sleep and wakefulness
• Orexin is the neurotransmitter
released in hypothalamus by a small
nucleus that consist of 10,000.
• Orexin strongly excites various brain
nuclei important in wakefulness.
• Orexin-producing cells integrate
metabolic, circadian and sleep debt
influences to determine whether an
individual should be asleep or awake.
• Central administration of orexin
strongly promotes wakefulness,
increases body temperature and
locomotion, and elicits a strong
increase in energy expenditure.
• Insomniacs taking an orexin
blocker, suvorexant, fell asleep
faster and slept an hour longer.
“Orexin flip flop
switch”
System that
promotes sleep
•
System that
promotes wake •
Narcolepsy: http://youtu.be/qVu-IcLoZtU
The most common form of narcolepsy, in which
the sufferer briefly loses muscle tone
(cataplexy), is caused by a lack of orexin in the
brain due to destruction of the cells that
produce it.
• Narcolepsy results in excessive daytime
sleepiness and cataplexy, whereby a person
falls into REM sleep, with all their skeletal
muscles paralyzed in response to strong,
usually positive, emotions.
• One woman in England has been declared dead
three times and once woke up in morgue.
What causes one to fall into sleep?
•
•
•
•
Circulating hormones? – Yes. E.g. melatonin
Brain nuclei? – Yes. E.g. Reticular formation
Accumulation of Adenosine? – Yes.
Conclusion: all of the above with the Orexin
switch
What is the natural period of one circadian cycle (a natural day duration)?
• The natural period of one
circadian cycle in this
experiments = 25.3h
• This might explain why it is
easier to travel west,
compared to jetlag problems
associated with traveling east.
• Optimal travel: go west and
cross one time zone a day
• Photosensitive cells in the
retina control the 24-hour
cycle of several subcortical
nuclei, that, in turn, control
the pineal gland.
• Interestingly: most organs,
even individual cells in the
body have their own 24hours clocks
• Melatonin anticipates the
daily onset of darkness –
central control of local
circadian rhythms
• Melatonin is safe aid for
falling into sleep. Jetlag –
take melatonin to help you
fall asleep
Disorders of sleep
• Slow-wave deep sleep
– Sleep-talking
– Bedwetting
– Sleepwalking
• Can be triggered by stress, alcohol, sleep deprivation
• Individuals engage in complex behavior while sleepwalking
• REM Sleep Behavior Disorder
– Muscles are NOT inhibited  physical activity during REM sleep:
• Dream about diving and dive from bed
• Dream about playing football and tackle a bed partner
– Often associated with a neurological disorder or a tumor
• REM Sleep paralysis:
– Muscles are inhibited but the brain is almost awake
• Some people think they are abducted by aliens and strapped down for probing.
• Narcolepsy
– Narcolepsy results in excessive daytime sleepiness, inability to
consolidate wakefulness in the day (and sleep at night), and cataplexy
when individual suddenly falls asleep (into REM sleep, with all their
skeletal muscles paralyzed)
Sleep apnea
• is a sleep disorder characterized
by pauses in breathing during sleep.
• Each pause in breathing for several seconds can wake
you up.
• Result: lack of normal continuous sleep  sleepiness
during the day, lack of attention, spontaneous nap.
• Common in middle aged overweight people
(prevalence in men over 25%), very high in truck
drivers.
micro-sleep
• Sleep-deprived humans will fall into micro-sleep.
One part of the brain falls asleep, while the rest
of the brain is active.
• While driving you might miss sensory
information from the red light or a car in front of
you, even when the rest of the brain (motor
cortex) is not sleeping and is able to drive the
car.
REM is essential
Barbituric
acid, the
basic
structure of
all
barbiturates
The core structure of
benzodiazepines.
•
•
•
•
During 1970s the main hypnotic (from Greek
Hypnos =sleep: drugs that induce sleep)
•
drugs were barbiturates
Prescribed to treat insomnia, barbiturates •
are agonists of ionotropic GABA receptor
Ethanol, barbiturates, benzodiazepines all
increase conductance of ionotropic GABA
receptor
Barbiturates significantly reduce the amount
of REM sleep 
Abrupt withdrawal of barbiturates results in
REM rebound in terrible nightmares
Barbiturates have now largely been replaced
by safer benzodiazepines (triazolam,
flurazepam)
Short daytime naps
• Consist of primarily of deep
slow wave sleep,
• In the early phase there is short
REM-like period:
– people report vivid
hallucinations that are shorter,
more static and more
thoughtlike than the dreams that
normally occur during REM
sleep.
– These visions are typically more
like snapshots than narratives
and do not include a self.
• Even a short nap can really
improve memory
Dreams
• Dreams are vivid, sensorimotor hallucinations with a narrative structure
• lateral PFC (the puppeteer) is inhibited and puppets (neuronal ensembles in
posterior cortex) activate spontaneously. As a result the brain looses its
normal sense of logic: during dreaming we could fly or meet somebody long
dead; things happen, and we go along for the ride…
• Although we often have trouble remembering dreams, our dreaming selves
have full access to our pasts. In dreams we recall earlier episodes from our
lives, and we often experience intense feelings of sadness, fear, anxiety or
joy (increased activity in the medial PFC).
• REM sleep behavior disorder = lack the muscle paralysis (known as atonia).
Patients act out their dreams: their actions match their dream reports. For
example, when they say they have dreamed about walking, they moved
their legs during REM sleep.
Why we do not remember our dreams?
• ACh is 50% of its awake level in slow wave sleep
• ACh is 200% of its awake level in REM sleep
• High ACh is known to break communication between cortex and
hippocampus. Without hippocampus the spontaneously generated
neuronal ensembles are NOT consolidated and we do not
remember our dreams.
• Everyone dreams, but sleep lab data reveal that people
consistently underreport how often and how much. The reason is
that dreams are ephemeral. Memory for dreams is very limited
and largely restricted to the short period before awakening
(hippocampus is virtually disconnected – Recall patient HM he
could only remember the last few minutes).
• The only way to remember a dream is to immediately recall it on
waking and then write it down or describe it to another person.
Only then does its content become encoded in memory.
Brain regions critical to dreaming
• Most dreaming occurs during REM, but…
• When a part of the brain stem known as the Pons
is destroyed, people no longer experience REM sleep.
• But only one in 26 of such patients reports a loss
of dreaming, and nobody has ever reported loss
of dreaming from limited Pons damage.
• The regions critical for dreaming are cortical sensory areas where
neuronal ensembles containing memory reside.
– Loss of visual dreaming 2 weeks after bilateral damage to V1
– Destruction (a stroke, tumor) of the cortical region necessary for color
will delete color from dreams.
– Destruction of V5/MT will delete movement from dreams
• Medications that manipulate dopamine levels strongly affect
dreaming while leaving the REM sleep cycle unaffected:
– L-dopa (dopamine precursor given to Parkinson’s disease patients)
increases the frequency and vividness of dreams
– Antipsychotic drugs that block dopamine reduce dreaming.
• REM is NOT essential for dreaming, but the sensory cortex is!
Fetus is asleep
• The thalamo-cortical connections are in place
by 7th month of gestation.
• After that the fetus is in one of the two sleep states
95% of the time, separated by brief transitions.
• In the uterus fetus is actively sedated by
– the low oxygen pressure (equivalent to that at the top of
Mount Everest),
– the warm and cushioned uterine environment
– a range of neuroinhibitory and sleep-inducing substances
produced by the placenta and the fetus itself:
• adenosine;
• two steroidal anesthetics, allopregnanolone and pregnanolone;
• one potent hormone, prostaglandin D2; and others.
• the fetus is asleep while its brain matures.
• REM sleep appears to be important for
development of the brain. REM sleep occupies
the majority of time of sleep of infants, who
spend most of their time sleeping.
Hallucinations
• In a classical example of a schizophrenic hallucination, the patient may be
convinced that a real small homunculus is sitting on the table giving orders to the
patient.
• It is likely that animals can also hallucinate. Several substances including marijuana,
nutmeg, and peyote are known to produce delusional behavior in cats: hunting for
nonexistent objects or running away from non-existent danger.
• In humans: Mescaline (from peyote cactus), LSD (synthetic) and psilocybin (from
magic mushrooms) among others trigger hallucinations
• The Doors of Perception by Aldous Huxley (mescaline): profound changes in the
visual world, colors that induce sound, the telescoping of time and space, the loss
of the notion of self, and feelings of oneness, peacefulness and bliss more
commonly associated with religious visions or an exultant state: “A moment later a
clump of Red Hot Pokers, in full bloom, had exploded into my field of vision. So
passionately alive that they seemed to be standing on the very brink of utterance,
the flowers strained upwards into the blue.... I looked down at the leaves and
discovered a cavernous intricacy of the most delicate green lights and shadows,
pulsing with undecipherable mystery.”
• Hallucinations can be explained by a spontaneous activation of neuronal
ensembles. Moreover, several neuronal ensembles can fire in synch to create
never-before-seen images.
• Would you expect increased or decreased activity in the PFC?
RH
Midline
LH
Study by David
Nutt from
Imperial College
London:
• injected either a saltwater (a placebo) or two milligrams of
psilocybin into the veins of 30 volunteers inside fMRI.
• subjects experienced within a minute or two the short “trip”
• Brain activity was reduced by up to 20 percent in the
thalamus, the medial PFC, the cingulate cortex.
• Even more striking: the deeper the reduction in activity in the
cingulate cortex and medial PFC the stronger the subject
felt the effects of the hallucinogen.
• The cingulate cortex and medial PFC evaluate emotions 
lack of evaluation may be interpreted by a subject as
dissociation from reality…
• A team headed by Stuart C. Sealfon and Jay A. Gingrich
demonstrated that in mice, hallucinogens such as LSD,
psilocybin, and mescaline, act on a serotonin receptor
on the pyramidal cells.
• It is possible that mental images caused by
hallucinogenic compounds come from the direct
activation of the pyramidal cells via serotonin
receptors, which, in turn, trigger the self-organization
of neuronal ensembles.
Meditation
• Meditation effect on blood pressure example: my mom was
extremely stressed after she broke her leg. The stress resulted
in a hypertensive crisis (about 200/100mmHg) that lasted for
several days.
• Her doctor prescribed all possible blood pressure drugs (all
three types) at high dose. My mom was taking these drugs for
three days. Blood pressure did not decrease a bit.
• Meditation: 8 minutes of “swimming pool top to bottom
cleansing” visualization and 8 minutes of “sun energy flowing
throw the body” visualization.
Date
Before
After
2/25/2014
2/26/2014
2/27/2014
3/1/2014
3/2/2014
3/3/2014
190/97
176/87
170/75
157/76
150/68
131/73
186/92
145/76
139/64
150/70
135/66
Data for before and after meditation /
Comments
First day of meditation.
Second day of meditation.
Stopped taking amlodepine
Stopped taking amlodepine
Stopped taking amlodepine
Blood pressure measured in the doctor’s office
Normally we have
•
•
•
•
•
•
10 novice vs. 8 long-term meditators – energy in gamma-band
meditation
activity (relative to more slowly changing brain waves).
Asked to attain a state of “unconditional loving-kindness and compassion”
Experienced meditators produce increased high-frequency gamma waves in the brain (2542Hz) synchronized across the frontal and parietal cortices
Such activity is thought to be the hallmark of focusing attention that involves
synchronization of spatially dispersed groups of neurons.
gamma activity in monks is the largest seen in nonpathological conditions and 30 times
greater than in the novices. The more years the monks had been practicing meditation, the
stronger the gamma activity.
EXPLANATIONS: Normallym, all different departments activate spontaneously (most of them
subconsciously)  EEG waves cancelling each other. From time to time a neuronal ensemble
achieves greater synchronization and gets conscious attention to itself  this spontaneous
activation of neuronal ensembles produces thought clutter.
Experienced meditators can synchronize all departments  significant increase in EEG
amplitude  no thought clutter
Fadel Zeidan, Robert C. Coghill
and their colleagues at the Wake
Forest School of Medicine
anterior cingulate
cortex
insula
• A small metal plate was attached to right calf of
volunteers (n=15) lying in fMRI.
• As the plate’s temperature increased to 49 degrees
Celsius, subjects had to rate pain intensity.
• Predictably, the hot probe triggered increased
hemodynamic activity in structures that are known
to be involved in pain processing:
– the primary and secondary somatosensory cortices that
represent the leg,
– the anterior cingulate cortex and the insula.
After four days of 20 minutes’
daily practice of mindfulness
meditation involving focused
attention or the Buddhist mindcalming practice called shamatha
Lateral
PFC
thalamus
• Practicing mindfulness during the noxious stimulation
– reduced the unpleasantness of the pain by a 57%
– reduced pain intensity by 40%.
– Pain-related activity in the primary and secondary
somatosensory cortices was reduced by the meditation
• More strongly the meditation reduced the pain 
the higher the brain activity in lateral PFC and
the lower the activity in the thalamus
• This activity most likely gates, or reduces, the arriving
noxious information before it even reaches the cortex.
Lateral
PFC
thalamus
• Conclusion: we can control what
information reaches our conscious cortex!
• Lateral PFC in the practitioner’s brain reach all the way down to
the thalamus to reduce the flood of incoming information from
the periphery, leading to lessening of pain.
• Mindfulness practice over 8 week (30min a day) resulted in
reduction of amygdala size and increase in hippocampus size (2011
“Mindfulness practice leads to increases in regional brain gray
matter density”).
• These skills to steer the mind are not magical, they can be learned
by sufficiently intensive practice.
• Meditation is common in sports: Kobe Bryant (basketball player)
mediates every morning http://youtu.be/M6Bvb8NlNHw
• Meditation is much easier to learn when performed with a
teacher (at least initially)
Hypnosis
• Normally the motor cortex is listening to multiple
inputs in order to decide how many muscles to recruit.
Say, you are preparing to lift a car with your friends on the count 1-2-3….
• … and then you realize that the car is empty inside (just the shell) and
therefore it is very light and all this muscle recruitment was in vain.
• So the motor cortex always listens to the areas of the cortex capable of
predicting how much force you will need.
• Furthermore, motor cortex does not want to tear your tendons and
therefore it listens to Golgi tension sensors through sensory cortex.
• And so on … motor cortex is listening to a lot of inputs.
• Hypnotist gets access to these parts of cortex and convince them that “Your
hand is very heavy, it is stuck on the table, you can't move your hand.“
• In one experiment, the motor cortex appeared to be listening to a brain
region called the precuneus. The precuneus is involved in mental imagery.
And so precuneus seems to be able to convince the motor cortex that it
cannot move the hand.
Anesthesia
• Until the discovery of nitrous oxide (laughing gas, N2O) as an
anesthetic in the mid-19th century, surgery was an extreme and
dangerous intervention of last resort whose effects could, at best,
be blunted by opium or alcohol.
• Anesthesia: separately and independently eliminates:
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–
–
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pain (analgesia),
memory (amnesia),
muscle responsiveness to the cutting,
awareness (loss of consciousness).
• anesthetics activate inhibitory chemical synapses. All anesthetics
reduce brain activity.
• The greater the dose of the anesthetic, the bigger the activity
reduction in regions of the brain stem responsible for promoting
wakefulness, in the neocortex and the thalamus.
• most common anesthetic: Propofol (killed Michael Jackson)
Cortex Off  Consciousness Off
• Twenty-five patients with Parkinson’s disease were anesthetized
while the electrical activity of both cortex and thalamus were
monitored
• Their neocortex was monitored by a conventional
electroencephalograph (EEG)
• thalamic activity was recorded by an implanted electrode
• Experimenters assessed consciousness by tapping patients on the
shoulder and asking them every 20 seconds to open their eyes.
• When consciousness was lost after anesthesia was initiated—that
is, when the patients no longer opened their eyes following the
command—the cortical EEG changed dramatically, switching from
low amplitude and irregular activity into readings dominated by
large and slow brain waves that occur about once every second.
Such so-called delta band activity is characteristic of deep sleep.
• Only several minutes later the thalamic voltage signal matched
that of the cortex.
• Consciousness is driven by neocortex, the thalamus follows.
• stop
Theta waves in non-primate animals
• Inverse relationship between hippocampal and cortical
activity patterns, with hippocampal rhythmicity
occurring alongside desynchronized activity in the
cortex, whereas an irregular hippocampal activity
pattern was correlated with the appearance of large
slow waves in the cortical EEG.
• Brain stem neurons also initiate a sinusoidal wave 68Hz in the hippocampus. This brain signal is called
theta rhythm.
• Theta rhythm is apparently the natural means by which
the NMDA receptor is activated in neurons in the
hippocampus.
• Theta rhythm might produce long-lasting changes in
memory.
• In animals: no REM, no theta waves.
Hypnagogic jerk
• hypnagogic jerks are a natural part of the body's
transition from alertness to sleep, and occur when
nerves "misfire" during the process.
• as the body falls asleep it goes through mini-REMtype periods where dreamlike feelings might start.
Brainwaves occurring during hypnagogia resemble
brainwaves during REM sleep.
• Normally during REM muscles are paralyzed to
inhibit our ability to enact content of our dreams.
• as the body falls asleep it is likely that the muscle
paralysis mechanism was not activated yet and
dreaming stimulates movement…