Attention & Brain Rhythms

1. Attention & Brain Rhythms

2. Attention & Brain Rhythms • Arousal • Attention • Body Rhythms • Rhythm Disorders

3. 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

5. 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.

7. 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

8. 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.

9. 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.

10. 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).

11. 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%

12. ADD/ADHD • Comorbidities: • CD (20-50%) • OCD (40-80%, Hyperactive only) • Substance Abuse (~35%) • Anxiety (10-40%) • Depression (0-45%)

13. 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)

14. 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.

15. 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”

16. 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.

17. Rhythms of the Brain • Body rhythms • Brain rhythms • Ultradian rhythms • Circadian rhythms • Monthly rhythms • Seasonal/yearly rhythms • Rhythm disorders: epilepsy

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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)

27. 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.

28. 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.

29. 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.

30. 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.

31. 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?

32. 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.

33. (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)

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

35. 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.

36. 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.

37. 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.

38. 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.”

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. 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.

45. 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.

46. 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.

47. 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

48. 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