Sleep & Attention June 23, 2011

Sleep Architechture

Why Do We Sleep? Who knows?!? It’s not entirely clear. Who knows?!? It’s not entirely clear. However, we do know that all organisms, from fruit flies to humans, show some form of sleep-like behavior. However, we do know that all organisms, from fruit flies to humans, show some form of sleep-like behavior. Sleep is ESSENTIAL Sleep is ESSENTIAL –Sleep deprived humans can become paranoid and have hallucinations. –Sleep deprived rats can die after 2-3 weeks. We do have some ideas… We do have some ideas…

Proposed functions of sleep Function Brain or body restoration, or both Replenishment of cerebral glycogen Replenishment of cerebral glycogen Tissue synthesis and cell mitosis Tissue synthesis and cell mitosis Protein synthesis Protein synthesis Growth hormone release Growth hormone release Thermo regulation Energy conservation Regulation of noradrenergic activity Memory consolidation and information processing Brain development Cell maturation Development of oculomotor control Programming of genetically determined behaviors Neural stimulation REM sleep + NREM sleep + From Lecture at Emory University, 2006

What is Sleep?

Awake State Alpha Waves Alpha Waves –Smooth, synchronous activity from 8-12 Hz –Relaxation Beta Waves Beta Waves –Irregular, desynchronous activity from Hz –Arousal & Wakefulness

Stage 1 & 2 Sleep Theta Waves Theta Waves – Hz EEG activity –Early slow-wave sleep and REM sleep Stage 2 sleep is also characterized by sleep spindles and K complexes (short bursts of waves that may help person fall into deeper sleep by decreasing sensitivity to outer stimuli) Stage 2 sleep is also characterized by sleep spindles and K complexes (short bursts of waves that may help person fall into deeper sleep by decreasing sensitivity to outer stimuli)

Stage 3 & 4 Sleep Delta Activity Delta Activity –High-amplitude (less than 3.5 Hz) Stage 3 consists of approx 20-50% delta activity Stage 3 consists of approx 20-50% delta activity Stage 4 consists of more than 50% delta activity Stage 4 consists of more than 50% delta activity

REM Sleep Desynchronized EEG movement accompanied by Rapid Eye Movement Desynchronized EEG movement accompanied by Rapid Eye Movement Hz waves Hz waves Also characterized by inability to move your muscles (paradoxical sleep) Also characterized by inability to move your muscles (paradoxical sleep) This is the stage when dreams occur. This is the stage when dreams occur.

Sleep Progression and Cycle

Astronaut Sleep Activity

Neurobiology of Sleep

Sleep in the Brain

Ventrolateral Preoptic Area Releases GABA to inhibit wake- promoting regions of the brain and thereby promote sleep Releases GABA to inhibit wake- promoting regions of the brain and thereby promote sleep –Destruction of the VLPA causes insomnia in rats –Electrical stimulation causes sleepiness From Lecture at Emory University, 2006

Sleep Promotion Sleep promoting regions in the VLPA release inhibitory GABA signals to Sleep promoting regions in the VLPA release inhibitory GABA signals to –Acetylcholine neurons in basal forebrain –Histaminergic neurons in the tuberomammillary nucleus –Hypocretin neurons –Noreprinephrine neurons in the Locus Ceruleus –Serotonin in the Dorsal Raphe Inhibition of these regions decreases wakefulness and increases sleepiness Inhibition of these regions decreases wakefulness and increases sleepiness

REM Sleep Promotion During REM sleep, the ACh and hypocretin neurons remain active. During REM sleep, the ACh and hypocretin neurons remain active. Projections from the Medial Pontine Reticular Formation activate ACh neurons in the cerebral cortex to keep them active. Projections from the Medial Pontine Reticular Formation activate ACh neurons in the cerebral cortex to keep them active.

Models of sleep-waking regulation Thalamus,CortexTMLCDRACh Hcrt HcrtHA NE 5-HTACh Waking From Lecture at Emory University, 2006

Models of sleep-waking regulation Thalamus,Cortex TMLCDRACh Hcrt HcrtHA NE 5-HTAChWakingThalamus,Cortex GABA NREM sleep POA From Lecture at Emory University, 2006

Models of sleep-waking regulation Thalamus,Cortex TMLCDRACh Hcrt HcrtHA NE 5-HTAChWakingThalamus,Cortex GABA REM sleep POA+PAG Hcrt ACh From Lecture at Emory University, 2006

Dream Journal Analysis

Nova Science NOW

Sleepiness Log Analysis

Discussion Did you find any rhythms or patterns in your sleep log? Did you find any rhythms or patterns in your sleep log? What do these rhythms mean? What do these rhythms mean?

Circadian Rhythms Daily 24-hour rhythms in several chemicals, like melatonin, help control our sleep/wake cycles. Daily 24-hour rhythms in several chemicals, like melatonin, help control our sleep/wake cycles. Melatonin is secreted by the pineal gland. Melatonin is secreted by the pineal gland.

What Regulates Circadian Rhythms? The Suprachiasmatic Nucleus (SCN) is our primary biological clock that organizes these rhythms. The Suprachiasmatic Nucleus (SCN) is our primary biological clock that organizes these rhythms. It does this through its projections to the midbrain and hypothalamic nuclei. It does this through its projections to the midbrain and hypothalamic nuclei.

The Michael Siffre Story

Sleep Difficulties

Sleep Disorder Quiz 1. Do you snore loudly and/or heavily while asleep? 2. Are you excessively sleepy or do you lack energy in the daytime? 3. Do you have trouble with concentration or memory loss? 4. Do you fall asleep while driving, in meetings, while reading a book, or while watching television? 5. Do you have occasional morning headaches? 6. Do you sleepwalk, have nightmares, or have night terrors? 7. Do you suffer from depression or mood changes? 8. Do you have trouble going to sleep or staying asleep? 9. Have you experienced recent weight gain or high blood pressure? 10. Have you been told you hold your breath when you sleep?

Narcolepsy Characterized by suddenly falling asleep at an inappropriate time Characterized by suddenly falling asleep at an inappropriate time Cataplexy, a common symptom, involves complete paralysis during a narcoleptic attack. Cataplexy, a common symptom, involves complete paralysis during a narcoleptic attack. Likely caused by activation of REM sleep promoting brain areas at inappropriate times Likely caused by activation of REM sleep promoting brain areas at inappropriate times –Mutations in the gene responsible for producing hypocretin are also involved Successfully treated by stimulants that increase serotonergic and noradrenergic activity Successfully treated by stimulants that increase serotonergic and noradrenergic activity

Night Terrors Terrifying period of screaming, trembling, and racing heart Terrifying period of screaming, trembling, and racing heart Usually does not remember what caused the night terror Usually does not remember what caused the night terror Associated with slow-wave sleep Associated with slow-wave sleep Most common in children, these are usually out-grown with age and do not require treatment Most common in children, these are usually out-grown with age and do not require treatment

Restless Leg Syndrome Insatiable urge to move ones legs in order to escape a tingling feeling or an “itch you can’t scratch” Insatiable urge to move ones legs in order to escape a tingling feeling or an “itch you can’t scratch” Can also occur to arms, torso, etc Can also occur to arms, torso, etc Worsens while relaxing and is relieved by movement or activity Worsens while relaxing and is relieved by movement or activity Dopamine and iron deficiency have been implicated Dopamine and iron deficiency have been implicated

Sleep Apnea Temporary cessation of breathing during sleep Temporary cessation of breathing during sleep Results in daytime sleepiness and fatigue Results in daytime sleepiness and fatigue May occur when the muscle paralysis of REM sleep extends into the throat muscles May occur when the muscle paralysis of REM sleep extends into the throat muscles Treatment often includes a CPAP (continuous positive airway pressure) machine to help with breathing during sleep Treatment often includes a CPAP (continuous positive airway pressure) machine to help with breathing during sleep

REM without Atonia What happens if a person in REM sleep DOESN’T have muscle paralysis? What happens if a person in REM sleep DOESN’T have muscle paralysis? Motor cortex and subcortical motor systems remain active, and without the atonia induced by REM, a person will be able to wake up and act out their dreams. Motor cortex and subcortical motor systems remain active, and without the atonia induced by REM, a person will be able to wake up and act out their dreams. Morrison, A. R., L. D. Sanford, et al. (1995). "Stimulus- elicited behavior in rapid eye movement sleep without atonia." Behavioral neuroscience 109(5):

Sample Case “I was a halfback playing football, and after the quarterback reeived the ball from the center he lateraled it sideways to me and I’m supposed to go around end and cut back over tack and—this is very vivid— as I cut back over tackle there is this big 280-pound tackle waiting, so I, according to football rules, was to give him my shoulder and bounce him out of the way…” “I was a halfback playing football, and after the quarterback reeived the ball from the center he lateraled it sideways to me and I’m supposed to go around end and cut back over tack and—this is very vivid— as I cut back over tackle there is this big 280-pound tackle waiting, so I, according to football rules, was to give him my shoulder and bounce him out of the way…”

Sample Case, Cont’d “…When I came to, I was standing in front of our dresser and I had [gotten up out of bed and run and] knocked lamps, mirrors, and everything off the dresser, hit my head against the wall, and my knee against the dresser.” “…When I came to, I was standing in front of our dresser and I had [gotten up out of bed and run and] knocked lamps, mirrors, and everything off the dresser, hit my head against the wall, and my knee against the dresser.” Schenk et al, 1986, p. 294

Why Am I So Sleepy or Hyper?

Design a Public Service Announcement

Neurobiology of Attention & Arousal

You Are Getting Very Sleepy… Remember from this morning: Sleep occurs when the VLPA is activated and then inhibits: Remember from this morning: Sleep occurs when the VLPA is activated and then inhibits: –Acetylcholine neurons in basal forebrain –Histaminergic neurons in the tuberomammillary nucleus –Hypocretin neurons –Noreprinephrine neurons in the Locus Ceruleus –Serotonin in the Dorsal Raphe So what do you think might happen when you need to wake up? So what do you think might happen when you need to wake up?

Rise And Shine! Stimulation of the Brain Stem Reticular Formation leads to arousal and a wake state. Stimulation of the Brain Stem Reticular Formation leads to arousal and a wake state. The reticular formation then follows 2 pathways: The reticular formation then follows 2 pathways: –Dorsal: Projects through the thalamus to the cerebral cortex –Ventral: Projects through the lateral hypothalamus, basal ganglia, and basal forebrain regions to the cortex & hippocampus

Anatomy of the arousal systems Histamine, serotonin, norepinephrine, acetylcholine, hypocretin TM DR LC PPT MS LDT NBM DBB Hcrt From Lecture at Emory University, 2006

Reticular Formation and Beyond Activation of the Reticular Formation results in release of: Activation of the Reticular Formation results in release of: –Histamine from the tuberomammillary nucleus (TMN) –Norepinephrine in the locus ceruleus (LC) –Serotonin from the dorsal raphe (DR) –Hypocretin from the Lateral hypothalamic area (LHA) Together, this helps you become awake! Together, this helps you become awake!

Arousal Systems - Histamine - NREM sleep Waking tuberomammillary nucleus (TMN) c-fos activity From Lecture at Emory University, 2006

Arousal Systems - Norepinephrine - locus coeruleus (LC) Waking c-fos activity From Lecture at Emory University, 2006

Arousal Systems - Serotonin - dorsal raphe (DR) From Lecture at Emory University, 2006

Arousal Systems - Hypocretin (orexin) - NREM sleep Waking Lateral hypothalamic area (LHA)c-fos activity From Lecture at Emory University, 2006

Models of sleep-waking regulation Thalamus,CortexTMLCDRACh Hcrt HcrtHA NE 5-HTACh Waking From Lecture at Emory University, 2006

The Results Are In!

Hyperactivity and Behavioral Disorders

Attention Deficit & Hyperactivity Disorder Excess hyperactivity and inability to pay attention beyond that expected for one’s developmental stage Excess hyperactivity and inability to pay attention beyond that expected for one’s developmental stage Medications typically target norepinephrine and/or dopamine levels Medications typically target norepinephrine and/or dopamine levels –Should they increase or decrease these levels? –DA may help to decrease inappropriate network signals and NE may increase appropriate ones.

How Do These Pathways Compare to Sleep/Wake? How Do These Pathways Compare to Sleep/Wake? Neurobiology of Attention Deficit/Hyperactivity Disorder PURPER-OUAKIL, DIANE; RAMOZ, NICOLAS; LEPAGNOL-BESTEL, AUDE-MARIE; GORWOOD, PHILIP; SIMONNEAU, MICHEL. Pediatric Research. 69(5 Part 2):69R-76R, May doi: /PDR.0b013e318212b40f

Conduct Disorder Persistent behaviors that violate the basic rights of others or societal conventions of behavior Persistent behaviors that violate the basic rights of others or societal conventions of behavior May include: May include: –Aggressive behaviors that threaten the well being of others –Vandalism, arson, or related property-damaging behaviors –Lying or stealing –Serious rule violations, skipping school, running away, etc. Linked with decreased temporal lobe volume and decreased serotonin levels Linked with decreased temporal lobe volume and decreased serotonin levels

Oppositional-Defiant Disorder Repeated pattern of defiant and rebellious behavior, which may include: Repeated pattern of defiant and rebellious behavior, which may include: –Frequent temper tantrums –Spiteful, mean behavior and revenge attempts –Resentment and hateful talking –Highly argumentative Possible alterations in serotonin, differences in genes for dopaminergic and noradrenergic signaling Possible alterations in serotonin, differences in genes for dopaminergic and noradrenergic signaling

Attention Experiments

Find the two Ts

Find the Red T

Find the tilted line on the left, vertical on the right