attention & brain rhythms. arousal attention body rhythms rhythm disorders

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Attention & Brain Rhythms

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Page 1: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

Attention & Brain Rhythms

Page 2: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

Attention & Brain Rhythms

• Arousal• Attention• Body Rhythms• Rhythm Disorders

Page 3: Attention & Brain Rhythms. 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

Page 4: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders
Page 5: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 6: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders
Page 7: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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

Page 8: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

Attention

• The ability to preferentially ignore some distracting sensory inputs, i.e. the “cocktail party effect.”

• Why do we have attention systems?– We can’t possibly process every sensation.– To make optimal use of limited resources.– Detection is enhanced.– Reaction times are speeded.

Page 9: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 10: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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).

Page 11: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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%

Page 12: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

ADD/ADHD

• Comorbidities:– CD (20-50%)

– OCD (40-80%, Hyperactive only)

– Substance Abuse (~35%)

– Anxiety (10-40%)

– Depression (0-45%)

Page 13: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

ADD/ADHD

• Non-genetic predispositions– Maternal smoking, drinking (2.5:1)– 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)

Page 14: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 15: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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”

Page 16: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 17: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

Rhythms of the Brain

• Body rhythms

• Brain rhythms

• Ultradian rhythms

• Circadian rhythms

• Monthly rhythms

• Seasonal/yearly rhythms

• Rhythm disorders: epilepsy

Page 18: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 19: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 20: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 21: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 22: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 23: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 24: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 25: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 26: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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)

Page 27: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 28: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 29: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 30: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 31: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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?

Page 32: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 33: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

(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)

Page 34: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

Sleep Stages

Dement: REM (1): a “hallucinating brain in a paralyzed body.”Delta (4) : an “idling brain in a moveable body.”

Page 35: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

• 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.

Page 36: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

• 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.

Page 37: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 38: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.”

Page 39: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 40: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 41: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 42: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 43: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 44: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 45: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 46: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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.

Page 47: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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

Page 48: Attention & Brain Rhythms. Arousal Attention Body Rhythms Rhythm Disorders

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