Attention

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Attention Brain Rhythms
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Attention Brain Rhythms

• Arousal
• Attention
• Body Rhythms
• Rhythm Disorders

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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

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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.

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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

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Attention

• The ability to preferentially ignore some
  distracting sensory inputs, i.e. the cocktail
  party effect.
• Why do we have attention systems?
• We cant possibly process every sensation.
• To make optimal use of limited resources.
• Detection is enhanced.
• Reaction times are speeded.

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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.

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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).

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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), 31 MF
• Chronic persists to 4-5 of adults, lt21 MF
• Strongly genetic MZ80-90, DZ25-35

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ADD/ADHD

• Comorbidities
• CD (20-50)
• OCD (40-80, Hyperactive only)
• Substance Abuse (35)
• Anxiety (10-40)
• Depression (0-45)

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ADD/ADHD

• Non-genetic predispositions
• Maternal smoking, drinking (2.51)
• Maternal anxiety or high phenylalanine
• Prematurity of birth (45 have ADHD)
• Post-Natal
• Hypoxia
• Lead poisoning
• Streptococcus infection (basal ganglia)
• Frontal lobe trauma (inattention only)

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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.

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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

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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.

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Rhythms of the Brain

• Body rhythms
• Brain rhythms
• Ultradian rhythms
• Circadian rhythms
• Monthly rhythms
• Seasonal/yearly rhythms
• Rhythm disorders epilepsy

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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.

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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
  voltage-controlled ion channels that allow it to
  self-modulate.

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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.

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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.

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Circadian Rhythms

• 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.

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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.

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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.

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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.

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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)

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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.

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Seasonal Rhythms

• SCN-gtPVN-gtSNS-gtPineal 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.

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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.

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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.

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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?

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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.

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(Beta 13-30 Hz, awake, alert) Alpha (8-12
Hz) Theta (3.5-7.5 Hz) Theta spindles and K
complexes Delta (lt3.5 Hz) Delta REM (like beta)
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Sleep Stages
Dement REM (1) a hallucinating brain in a
paralyzed body. Delta (4) an idling brain in
a moveable body.
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• REM (Rapid Eye Movement)
• 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.

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• 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.

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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.

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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.
• Brocas area is activated during speech.
• Wernickes area is activated during listening.
• Motor areas are activated during movement.

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Sleep Theories

• Recuperation Theory
• Body needs time to rebuild after a hard days
  work.
• Circadian Theory
• Animals are active at the best times of the day
  to promote their survival.
• Mostly circadian with some recuperation.

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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.

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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
  brains temperature (and metabolic rate) seem to
  cause increased need for slow wave sleep.

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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.

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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.

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Sleep Deprivation

• Sleep deprivation increases sleep efficiency.
• 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.

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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.

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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.

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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

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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