Download Lecture 7 Rhythms of the Brain

Attention & Brain Rhythms
Attention & Brain Rhythms
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Arousal
Attention
Body Rhythms
Rhythm Disorders
Arousal
• The Reticular Activating System (RAS), a diffuse
collection of various nuclei in the pons, medulla and
brainstem including:
– Locus coeruleus (pons, NE)
• Activated by novel & meaningful sensory stimuli.
• Excitory effect on rest of brain.
– Raphe nuclei (pons, medulla, 5-HT)
• Mostly inhibitory. Particularly important in sleep.
– Substantia Nigra, Ventral tegmental area (DA)
– Cholinergic basal forebrain and brainstem nuclei (ACh)
• Excitatory
Arousal
• The Reticular Activating System (RAS)
projects to the basal forebrain, which then
projects to the entire cortex.
– ACh – promotes behavioral arousal
• Adenosine (AMP metabolite) builds up during
waking, and acts to inhibit arousal. Caffeine inhibits
adenosine receptors, and acts like a stimulant.
• Histamine from hypothalamus excites arousal.
– GABA – inhibits the thalamus and cortex and
inhibits behavioral arousal.
Arousal
• Stimulation of the RAS in sleeping cats
(Moruzzi & Magoun, 1949) produced a
waking pattern of electrical activity in the
cerebral cortex. Lesions caused sleep state.
• RAS acts as the on/off switch for the brain.
– On = conscious
– Off = unconscious
– Prolonged off state = coma
Attention
• The ability to preferentially ignore some
distracting sensory inputs, i.e. the “cocktail
party effect.”
• Why do we have attention systems?
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We can’t possibly process every sensation.
To make optimal use of limited resources.
Detection is enhanced.
Reaction times are speeded.
Attention
• Attention is generally limited to one sensory
stream at a time.
• There is some evidence for independent
hemispherical attention, but the left
hemisphere is more attentive.
• Attention requires arousal (by RAS), but
just enough. Insufficient arousal leads to
inattention.
Attention
• Attention is a like a spotlight, highlighting
one somato- or enviro-topic area by
inhibiting surrounding areas.
• The pulvinar nucleus of the thalamus and
the parietal lobes help directs attention by
inhibiting irrelevant information.
• The cortex controls inhibition of ascending
sensory information to preferentially select
input from one particular side or feature
type (ex. particular audio frequencies).
ADD/ADHD
• Attention Deficit Hyperactivity Disorder
(ADHD)
– Inattentive type (~55%)
• Meso-libmic dopamine system, motivation
– Impulsive-hyperactive type (~15%)
• Meso-cortical dopamine system, disinhibition
– Combined type (~30%)
• Affects 7-8% of children (DSM-IV), 3:1 M:F
• Chronic – persists to 4-5% of adults, <2:1 M:F
• Strongly genetic: MZ=80-90%, DZ=25-35%
ADD/ADHD
• Comorbidities:
– CD (20-50%)
– OCD (40-80%,
Hyperactive only)
– Substance Abuse
(~35%)
– Anxiety (10-40%)
– Depression (0-45%)
ADD/ADHD
• Non-genetic predispositions
– Maternal smoking, drinking (2.5:1)
– Maternal anxiety or high phenylalanine
– Prematurity of birth (45%+ have ADHD)
• Post-Natal
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Hypoxia
Lead poisoning
Streptococcus infection (basal ganglia)
Frontal lobe trauma (inattention only)
ADD/ADHD
• Genetics
– DAT1 (5p15.3) 10-R dopamine transporter
polymorphisms are strongly related and highly
predictive of ADHD hyperactivity and
impulsivity, but not inattention. Dopamine is
reuptaken with increased efficiency.
– Dopamine-beta-hydroxylase (DBH) (9q34)
variants are related. More efficient enzyme.
– DRD4 receptor (11p15.5) 7-R subsensitive.
– All act to decrease arousal by dopamine.
ADD/ADHD
• Neuroanatomical correlates
– Filipek, et al (1997) reported 10% decreased
volume in anterior superior (posterior prefrontal,
motor association) and anterior inferior (basal
ganglia) areas.
– Castellanos, et al (1996) reported 10% decreased
volume in the right anterior frontal, caudate and
globus pallidus areas and loss of normal symmetry.
– No significant difference by gender
• “A hypofunctioning smaller brain”
ADD/ADHD
• Commonly treated with stimulants:
– amphetamines
• Benzedrine 1937, Dexadrine, Adderall
– methylphenidate
• Ritalin, Concerta, Metadate
• Ineffective in homozygous 10 repeat DAT1 allele
– pemoline (Cylert)
– buproprion (Wellbutrin)
– All these drugs inhibit dopamine reuptake
transporters in the basal ganglia, raising synaptic
dopamine levels.
Rhythms of the Brain
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Body rhythms
Brain rhythms
Ultradian rhythms
Circadian rhythms
Monthly rhythms
Seasonal/yearly rhythms
Rhythm disorders: epilepsy
Body Rhythms
• Heart has its own pacemaker.
– Normally runs too fast.
– Vagus nerve (X) slows it down (parasympathetic).
– Epinephrine speeds it up (sympathetic).
• Breathing
– Controlled by pacemaker in the medulla.
• Temperature
– Controlled by its own circadian clock, usually
synced to the circadian clock. Also in medulla.
Rhythms of the Brain
• Pairs of excitatory and
inhibitory neurons can form
neural oscillators.
– Any network of strongly
interconnected neurons is
prone to oscillation.
• Some thalamic neurons
have special sets of voltagecontrolled ion channels that
allow it to self-modulate.
Rhythms of the Thalamus
• Large thalamic rhythms are generated
during sleep.
– These project to all areas of the cortex and are
thought to shut down all sensory information to
and motor information from the cortex.
• Cortical rhythms while awake are thought
to help synchronize and bind various kinds
of information which are to be associated.
Ultradian Rhythms
• “Faster than a day”
• 90 minutes
– Infants feed, urination, sleep sub-cycles.
– This clock appears to be in the medulla.
• 12 hour
– Most people have wakefulness lows at 6 and 18
hours after rising, and are most wakeful at 0 and 12
hours after rising.
Circadian Rhythms
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Circadian (= “about a day”).
Circadian behaviors are inborn, not learned.
Primarily control sleep/wake cycle.
Secondarily control temperature, enzyme
levels (i.e. liver enzymes), genetic
expression, etc.
Circadian Clock
• Located in the suprachiasmic nuclei of the
hypothalamus, directly above the optic chiasm.
– SCN lesions disrupt circadian cycles, fetal SCN
tissue transplants restore circadian cycles.
• SCN contains about 10,000 neurons, each with
its own clock, all synced to light/dark cycle.
• SCN projects to hypothalamus, midbrain, and
the pineal gland. The pineal gland releases the
hormone melatonin at night.
Circadian Clock Genetics
• SCN neurons use genetics to oscillate
on a long time period, just like two
interconnected neurons can oscillate.
– The production of the first protein
stimulates the increased production of the
second.
– The second protein inhibits the first.
• Cycle lasts about 26 hours in humans,
but is resynchronized by the onset of
daylight every 24 hours.
Circadian Clock
• The SCN clock is synchronized to the onset
of light, shortening cycle to 24 hours.
• Dilemma: some blind people still sync to
daylight.
• Melanopsin - newly discovered opsin
(chromophore / B2) in the inner ganglion
layer of the retina (NOT in rods or cones!).
• Frogs have photosensitive cells in skin,
maybe humans do too.
Circadian Clock
• All mammalian species show about the same
melatonin production cycle (high at night, low
during the day), so melatonin only tracks time, not
wakefulness.
• Nocturnal animals interpret or respond differently to
the melatonin cycles as diurnal animals.
• Teenagers have phase shift vs. adults.
• FASPS phase shift due to 2q point mutation. (affects
per2)
Monthly Rhythms
• Primarily sex-related modulations
– Hormonally controlled
• Hypothalamus tells pituitary to release hormones.
– Female ovulation cycle
• Follicle Stimulating Hormone (FSH) causes follicle
maturation. Maturing follicle produces estradiol. A
large estradiol buildup causes release of Lutinizing
Hormone (LH), which causes release of follicle. If egg
is fertilized, progesterone is released. If not,
prostaglandin causes menstruation.
– Males have minor modulations.
Seasonal Rhythms
• SCN->PVN->SNS->Pineal gland
implicated in seasonal patterns.
• SCN/PVN lesions disrupt seasonal
patterns.
• Fetal SCN cell implants restore
circadian patterns but not seasonal
patterns.
• Seasonal variations not generally
found in humans, except in severe
cases, like SAD.
Seasonal Affective Disorder
• The length of melatonin produced at night
remains constant all year in normal people.
• People with SAD produce melatonin for
about an hour longer during periods of
prolonged reduced photoperiod.
• Since melatonin and serotonin are both made
from the same precursor, more melatonin
generally means less serotonin. Lowered
serotonin is linked with depression.
Seasonal Affective Disorder
• SAD is about 70% genetic. There are both
predispositions and protections.
• SAD is geographical: almost unheard of in
equatorial areas, with increasing prevalence
towards the poles.
• Light therapy is usually an effective
treatment, and early morning light is much
more effective than evening light.
Sleep
• Must be important!
– Takes up 1/3 of our lives, more than any other
activity.
– Other than breathing, sleep is the most insistent
drive.
– What function does it serve?
– Why is it so important?
– What controls it?
Sleep Function and Need
• Sleep appears to let the brain rest.
– Possibly to allow regeneration of depleted
neurotransmitters.
• Sleep appears to be necessary for survival.
– All vertebrates and reptiles sleep, and fish and
amphibians show periods of quiescence.
– Sleep has not disappeared even where it interferes
with survival, but not without adaptations.
• Uni-hemisphere sleep, multiple naps, etc.
(Beta 13-30 Hz,
awake, alert)
Alpha (8-12 Hz)
Theta (3.5-7.5 Hz)
Theta + spindles
and K complexes
Delta (<3.5 Hz)
Delta
REM (like beta)
Sleep Stages
Dement:
REM (1): a “hallucinating brain in a paralyzed body.”
Delta (4) : an “idling brain in a moveable body.”
• REM (Rapid Eye Movement)
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Dement: “hallucinating brain in a paralyzed body.”
Dreaming occurs during this phase.
Complete muscle relaxation/paralysis.
“Paradoxical Sleep” because of beta activity.
Can be easily awakened by meaningful stimuli (i.e.
their name) and will appear alert and attentive.
– Physical arousal of the sexual organs.
• REM sleep is important to learning.
– Periods of REM are longer following intense
learning episodes.
– REM deprivation interferes with learning tasks.
– Non-REM deprivation does not interfere with
the same learning tasks.
Dreams
• Dreams seem to be the cortex trying to
make sense of random lower brain firings.
• Dreams are usually high in visual imagery,
but poorly organized with respect to time.
• Madsen, et al (1991) found high cortical
activation in the visual association cortex
and low activation of the frontal lobes.
Dreams
• REMs seems to be related to visual
scanning of a scene - EEG patterns match
visual scanning, not just eye movements.
• Cortical and subcortical brain mechanisms
that would be involved if the dream were
real seem to be activated during dreaming.
– Broca’s area is activated during “speech.”
– Wernicke’s area is activated during “listening.”
– Motor areas are activated during “movement.”
Sleep Theories
• Recuperation Theory
– Body needs time to “rebuild” after a hard
day’s work.
• Circadian Theory
– Animals are active at the best times of the day
to promote their survival.
• Mostly circadian with some recuperation.
Recuperation Theory Pros
• REM sleep seems to be necessary.
• REM sleep is made up if deprived,
non-REM is not.
• Function seems to be memory housekeeping:
flush useless clutter and consolidate new
memories and information with existing
memories.
Recuperation Theory Cons
• There is a problem with recuperation theory:
• Lack of sleep does not seem to interfere with
human capacity for physical exercise.
– Quadriplegics and forced bed rest subjects do
not show decreased or altered sleep.
– Exception: exercise that significantly raises the
brain’s temperature (and metabolic rate) seem to
cause increased need for slow wave sleep.
Sleep Deprivation Predictions
• Recuperation:
– Missed sleep will cause physiological and
psychological disturbances, which will get
worse with time.
– Much of missed sleep will be made up.
• Circadian:
– No ill effects, except due to falling asleep.
– Sleep desire will display circadian cycle.
– Little or no sleep compensation.
Sleep Deprivation Studies
• Kleitman (1963)
– Sleep deprived lab subjects functioned
normally during the day, with greatest
drowsiness between 3-6 AM.
• Gardner/Dement (1978)
– Randy Gardner, 17, decided to break world
record for staying awake, lasting 11+ days.
– Only slept 14 hours for one night, then 8.
• Both support circadian theory.
Sleep Deprivation
• Sleep deprivation increases sleep efficiency.
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Increased percentage of REM sleep.
Increased slow wave sleep.
As much time in stages 3 & 4 as with longer sleep.
Seems to indicate slow wave sleep has some sort
of recuperative features.
– Protein synthesis seems to be accelerated during
slow wave sleep.
Sleep and Affective Disorders
• New research shows:
– Sleep deprivation can bring a person out of
depression.
– Sleep deprivation can cause a stable bipolar
patient to go (hypo)manic.
– Prolonged sleep intensifies a depression.
– Children with early onset bipolar disorder show
marked ultradian cycles.
Epilepsy
• Epilepsy
– Oldest known brain
disorder (over 2000 years)
– Def: repetitive seizures
(abnormally synchronous
brain activity)
– 7-10% have at least one
seizure. 1% have epilepsy.
– More a symptom than a
disease.
Epilepsy
• Seizures
– Undamped oscillation between hemispheres
– Generalized (grand-mal)
• Involves the entire cortex of both hemispheres.
• Split-brain procedure used in the worst cases.
– Partial (petite-mal)
• Only a circumscribed area of the cortex is involved.
• Often treated with drugs, or by removal of the area.
– Often preceded by auras (minor, partial seizures)
• Tension, smell, sound, temperature, visual
Epilepsy
• Treatment
– GABA antagonists are good convulsants.
– Anticonvulsants:
• barbiturates and benzodiazapenes prolong the inhibitory
effects of GABA.
– (barbiturate and alcohol withdrawal can trigger seizures)
• gabapentin (Neurontin) increases brain GABA.
• phenytoin (Dilantin), carbamazapine (Tegretol),
valproate (Depakote), clonazepam (Klonopin) and
oxycarbazapine (Trileptal) decrease high-frequency
firing by nerves.
– Surgical resection or splitting