1 Psychophysiology of day/night cycleNetania Interesting site: org/publications/letsleepwork.cfm#1

2 We change with time What is changing ? Linear changes ? Cyclic changes ? Source of changes?

3 Exogenous clocks: Environment as a source of cyclic changesEnvironment is cyclic… we are sensitive to environment, therefore…. we live in cycles. “The Calendar” describes life timed by nature. /4 days around the sun: cycles of depression, suicide, susceptibility to schizophrenia… 28-31 days: Gregorian timing in honor of Caesar? No environmental cycle. 1 day spin: light/dark cycle of biological & mental functions.

4 Endogenous clocks: Biology as a source of cyclic changesAnnual clock: not known. Monthly clock: female menstrual cycle. Circadian clock: > 24 hrs, why not = 24 hrs? 8 hrs clock: when the pilots are most fit? 90 min clock: when do you dream? < seconds range: localized biological processes like sand clocks, HR, biochemistry.

5

6 Chronobiology research is being conducted by:Allergists Animal and plant physiologists Cardiologists Cell and molecular biologists Chronobiologists Endocrinologists Environmental scientists Gastroenterologists Immunologists Nephrologists Neuroscientists Obstetricians/gynecologists Pharmaceutical scientists Psychiatrists Toxicologists Epidemiologists Do you see the psychologists ???

7 Complex cycles: Interaction between exogenous & endogenous clocksMonthly: Synchronization of monthly cycle in ladies’ dormitories. Circadian: > 24 hrs in isolation, but 24 hrs in normal conditions. 90 min: easy to detect in boring but not in exciting conditions.

8 Complex cycles: 24 + 8 cycles in phase24 hrs 8 hrs result

9 Complex cycles: 24 + 8 out of phase24 hrs 8 hrs result

10 Cyclic changes: conclusionsContinuous change rather than stability Change in response to exogenous clocks Change in response to endogenous clocks Asynchronous cycles Models of adaptation (e.g., arousal) Models of pathology??? (e.g., arousal)

11 Sleep (2) External clock: Light through eyes & skin Biological clock: Suprachiasmatic n. Pineal Gland (melatonin)

12 Spectrum of Arousal Coma Sleep - Wakefulness Excitation - Anxiety Drugs Epilepsy Circadian cycles of arousal Momentary changes of arousal

13 Arousal and PerformanceArousal is a major aspect of behavior and is closely related to other concepts such as anxiety, attention, agitation, stress, and motivation. The arousal level can be thought of as how much capacity you have available to work with. One finding with respect to arousal is the Yerkes-Dodson law which predicts an inverted U-shaped function between arousal and performance. 

14 Arousal and HomeostasisMaintaining a single level of adaptive arousal

15 Arousal and AllostasisAllostasis rather than homeostasis: Stable level of arousal is not adaptive

16 Allostasis and PerformanceAllostasis: maintaining stability of performance through change of arousal, as a fundamental process by which organisms actively adjust to both predictable and unpredictable events. i.e., stay maximally adaptive by changing the arousal Allostatic overload being a state in which serious pathophysiology can occur.

17 Allostasis and Poor PerformanceCatastrophic conditions are possible

18 Alertness daily cycle

19 Sleep Needs over the Life CycleToddlers/Children yrs: hours yrs: hours yrs: hours yrs: hours Adolescents hours Adults/Older Persons hours

20 Sleep Needs over the Life Cycle

21 Circadian sleep distribution

22 Sleep cycles and stagesSleep like wakefulness, is not homogenous.

23 Sleep cycles and stages (again)

24 Sleep stages NREM: 75% of night sleep; composed of Stages 1-4.Stage 1: Light sleep; between being awake and entering sleep. Stage 2: Becoming disengaged with the environment; breathing and heart rate are regular and body temperature goes down. Stage 3 & 4: Deepest sleep; blood pressure drops; breathing slower; energy regained; hormones are released. REM: 25% of night sleep. 1st about 90 min after falling asleep; length increases over the subsequent cycles; cortex is active and dreams occur as eyes dart back and forth; bodies become immobile and relaxed; muscles shut down; breathing and heart rate may become irregular.

25 EEG in sleep Beta: > 13 Hz Alpha: 8-13 Hz Theta: 4-8 HzDelta: < 4 Hz

26 EEG in sleep (3)

27 REM dream The painting suggests Delvaux was not optimistic about either approach, preferring to celebrate rather than resolve the central mystery. A dream and its investigators in a painting by Paul Delvaux. The dream Neurologist examines… Psychologist inquires…

28 Sleep & response to environmentOvert – awakening Covert – dream Sleep & selective attention

29 Sleep and learning Sleep & Learning: Dawkins – “The selfish gene” The song of Don Juan "The zebra finch appears to store the neuronal firing pattern of song production during the day and reads it out at night, rehearsing the song, and, perhaps, improvising variations. The match is remarkably good."

30 Sleep functions: The genetic prospectiveMolecular support for the concept that sleep is implicated in synaptic plasticity and memory (Mircea Steriade). Circadian genes differentially expressed during day and night. For some of the above, upregulation is attributable to sleep itself. Out of some 15,000 transcripts present in rat cerebral cortex, about 10% (1,564) were differentially expressed by day or night. For about half of these (752), the change was attributable to the waking or sleeping state, independent of time.

31 The body sleeps, but the genes do not.“Sleep genes” are upregulated specifically during sleep and suggest the following sleep's functions: genes involved in synaptic plasticity, memory consolidation. genes underlying translation, supporting observations that protein synthesis increases during sleep. genes regulating membrane, vesicle trafficking, vesicle recycling, exocytosis, docking of vesicles & neurotransmitter release. genes for synthesizing cholesterol, which may be crucial for synaptogenesis & membrane synthesis. Cirelli et al., "Extensive and divergent effects of sleep and wakefulness on brain gene expression," Neuron, 41:35-43, 2004.

32 SWS & REM builds memoriesResearchers recorded the electric signature of individual forebrain neurons firing during the two types of sleep. The firing pattern of recently captured memories are especially strong during slow-wave sleep and then decrease in force dramatically during REM. The neural plasticity genes turn on during REM sleep. It looks like a two-stage process: The memory echoes strongly during SWS, which stabilizes it. Then the gene expression machinery turns on during REM sleep to further consolidate it. You remember more when you have a combination of REM and SWS. Ribeiro et al., "Long-lasting novelty-induced neuronal reverberation during slow-wave sleep in multiple forebrain areas," PLoS Biol, 2: , 2004.

33 Sleep deprivation sleep pressure no full compensation on recovery night intrusion of sleep to wakefulness * compensation * mixture of mental processes * model of psychopathology ???

34 Sleep deprivation & drivingGetting less than 6 hours a night can affect coordination, reaction time and judgment, in continuous performance tasks, posing "a very serious risk.“ Drivers are especially vulnerable. Driving after 17 to 19 hrs of wakefulness is worse than after blood alcohol level of 0.8% which is the critical level in US.

35 America is asleep at the wheelThe 2002 National Sleep Foundation (NSF) Sleep in America poll revealed that one-half of all American adult drivers—particularly young males—admit to driving drowsy in the past year, and almost one in five admit to having fallen asleep behind the wheel. The results are appalling, and unless something is done, they may well get worse.

36 Sleep deprivation and hyperactivityInadequate sleep makes kids more moody, more impulsive, and less able to concentrate and learn (J. of Exp. Psychology, 1975). Recent research has verified that chronic poor sleep results in daytime tiredness, difficulties with focused attention, low threshold to express negative emotion (irritability and easy frustration), and difficulty modulating impulses and emotions (Seminars in Pediatric Neurology, Mar 1996). These are the same symptoms that can earn kids the diagnosis of attention deficit hyperactivity disorder.

37 Flies bred lacking their cycle gene tended to die after missing only 10 hours of sleep, found scientists from the Neurosciences Institute in San Diego, California. Scientists noticed that other genes in these mutated flies were less active after sleep deprivation. These genes, which produce "heat shock" proteins, were artificially stimulated prior to sleep deprivation by raising the fly's environment to human body temperature. "These 'heat shock' proteins protect cells when they are under stress. "Perhaps, if you can turn on these proteins in humans, it could be beneficial."

38 TIPS FOR GOOD SLEEP Avoid caffeine (coffee, tea, soft drinks, chocolate) and nicotine (cigarettes, tobacco products) close to bedtime. Avoid alcohol as it can lead to disrupted sleep. Exercise regularly, but complete your workout at least 3 hours before bedtime. Establish a regular relaxing, not alerting, bedtime routine (e.g. taking a bath or relaxing in a hot tub). Create a sleep-conducive environment that is dark, quiet and preferably cool and comfortable.

39 Consciousness (1) Consciousness Subconciousness Unconsciousness

40 Consciousness (2) Visual pathway

41 Consciousness (3) Reconstruction of natural scenes in thalamus

42

43 Consciousness: ConclusionsLocalization of consciousness: Consciousness not in the subcortical areas Consciousness not in the primary sensory cortex Consciousness in high cognitive cortex ???