Psychology 2401 Foundations of Biopsychology Alana Rawana 2013 RHYTHMIC ACTIVITY Environment is rhythmic Brains have evolved a variety of systems for rhythmic control • Mammalian rhythmicity: • • • • • • • Thirst and hunger States of arousal (alertness) Hormonal secretion Respiration Heart rate Electrical rhythms of the cortex THE SLEEP WAKE CYCLE ELECTROENCEPHALOGRAM EEG: Classic method of recording brain rhythms A measurement that enables us to take a generalized look at the activity of the cerebral cortex Richard Caton (England, 1875) • • Electrical recordings from the surface of dog and rabbit brains Hans Berger (Austria, 1929) • • First described the human EEG Observed differences in EEG activity What are EEG’s used for today? ELECTROENCEPHALOGRAM RECORDING BRAIN WAVES Method is non-invasive & painless Wire electrodes are taped to the scalp, along with a conductive paste to lower the resistance Electrodes are placed on standard positions on the head Electrodes are connected to banks of amplifiers and recording devices Small voltage fluctuations are measured between pairs of electrodes RECORDING BRAIN WAVES CONT’D • WHAT GENERATES THE OSCILLATIONS OF AN EEG? • An EEG measures voltages generated by dendritic synaptic excitation of pyramidal cells of the cortex • However, any single neuron does not contribute much to the electrical signals recorded by the EEG • Therefore, an EEG is a reflection of many thousands of neurons firing simultaneously EEG CONSEQUENCES OF SUMMATION • The amplitude of EEG signal strongly depends, in part, on how synchronous the activity of the underlying neurons is. • • Synchronous activity: when a group of cells are simultaneously excited and the “mini” individual signals summate to generate one large surface signal Irregular activity: when a group of cells receives the same amount of excitation but do not respond simultaneously the summation does not amount to much Synchronous activity Magnetocephalography (MEG) Wherever electrical current flows a magnetic field is generated Magnetic current detected by an array of 150 sensitive magnetic detectors MEG vs EEG What are MEG’s used for today? Magnetocephalography (MEG) EEG RHYTHMS • EEG rhythms vary drastically depending on particular states of behavior or pathology • e.g. level of attentiveness, arousal, sleeping, waking…coma, seizures • EEG rhythms are categorized according to their frequency range… TYPES OF RHYTHMS • • • • Beta rhythms: fastest, greater than 14Hz, signal activated, alert cortex Alpha rhythms: 8-13Hz, signal awake but quiet and relaxed states Theta rhythms: 4-7Hz, signal some of the deep sleep states Delta rhythms: very slow, very large in amplitude, less than 4Hz, hallmark of deep sleep Normal EEG Alpha & beta waves Both sides of brain show similar patterns of electrical activity No abnormal bursts of electrical activity & no slow brain waves Proper response to photic stimulation Abnormal EEG Abnormal EEG (Cont’d…) Sudden bursts of electrical activity or sudden slowing of brain waves Delta waves or too many theta waves in adults who are awake. a "flat" or "straight-line" EEG EEG Rhythms Cont’d… • • Obviously EEG recordings do not allow us to read a persons thoughts, but they do allow us to tell if a person is thinking frequency: amplitude rhythms are associated with alertness, waking, and dreaming sleep states frequency: amplitude rhythms are associated with non-dreaming sleep states and pathological states of coma Generation of Synchronous Rhythms Activity of a large set of neurons produce synchronized oscillations in one of two ways: (1) They may take cues from central clock (pacemaker) (2) Share or distribute the timing fcn among themselves by mutually exciting or inhibiting one another Synchronous Activity – Mammalian Brain Rhythmic synchronous activity is usually coordinated by a combination of the pacemaker & collective methods Thalamus Can generate very rhythmic action potential discharges How do thalamic neurons oscillate? How do thalamic neurons oscillate? How do thalamic neurons oscillate? (Cont’d…) Synaptic connections between excitatory and inhibitory thalamic neurons force each individual neuron to conform to the rhythm of the group Coordinated rhythms passed to cortex Function of Brain Rhythms • Why are there so many rhythms? • Do they serve a purpose? • Obviously there are no satisfactory answers to either of these questions… but there are a few decent hypotheses Functions of Brain Rhythms Cont’d… • “Disconnection Hypothesis”: • Sleep-related rhythms are the brain’s way of disconnecting the cortex from sensory input • AWAKE, sensory information is allowed to the cortex via the thalamus • ASLEEP, the thalamus goes on auto-pilot, the neurons enter a self-regulated state that prevents the relay of sensory input to the cortex Functions of Brain Rhythms Cont’d… Walter Freeman Neural rhythms coordinate activity between regions of the NS Gamma rhythms Momentarily synchronizing fast oscillations generated by different regions of cortex brain binds neural components into a single perceptual construction Another plausible reason? Seizures of Epilepsy Most extreme form of synchronous brain activity Generalized seizure: involves the entire cortex of both hemispheres Partial seizure: involves a particular area of the cortex Commonalities between the two? Epilepsy: a condition defined by repeated seizure experiences ~ 1% of the American population has epilepsy Seizures and Epilepsy (Cont’d…) The cause of seizures can sometimes be identified Examples Different types of seizures have different underlying mechanisms Genetic predisposition Convulsants & Anticonvulsants GABA receptor antagonists are very potent convulsants: Block GABA receptors Seizure-promoting agents Common uses? GABA receptor agonists are very potent anticonvulsants: Suppresses seizures by countering excitability in various ways… E.g., prolong inhibitory influence of GABA Behavioural Features of Seizures During more forms of generalized seizures: All cortical neurons are engaged Unconscious Muscles – tonic or clonic activity John Hughlings Jackson - Partial Seizures Pathological Brain Activity: Seizures & Epilepsy Sleep • • • • We spend about one-third of our lives sleeping • One-quarter of this time is spent dreaming Sleep is universal among higher vertebrates Sleep is essential to our lives, like eating and breathing Prolonged sleep deprivation can devastate proper functioning and in some animals, lead to death Sleep (Cont’d…) • DEFINITION OF SLEEP: • Sleep is a readily reversible state of reduced responsiveness to, and interaction with, the environment (anesthesia and coma do not count since they are not readily reversible) Rapid Eye Movement Sleep REM sleep When EEG looks more awake than asleep Your body (except eye and respiratory muscles) is immobilized Dreaming sleep Non-REM sleep a.k.a., slow-wave sleep Period of rest Temperature and energy consumption lowered Heart rate, respiration, and kidney fcn all slow down Digestive processes speed up Brain rests REM AND NON-REM SLEEP William Dement (Stanford University): REM SLEEP: “An active, hallucinating brain in a paralyzed body” NON-REM SLEEP: “An idling brain in a movable body” • ultradian rhythms How are sleep spindles generated? Sleep Related Disorders Insomnia Affects at least 20% of population at some time Example case One of the most important causes of insomnia seems to be sleeping medication Sleep Apnea Sleep-Related Disorders (Cont’d…) Why do we sleep? All birds, reptiles, and mammals appear to sleep Although only mammals and some birds have REM phases Cool Animal Sleep Facts The Bottlenose Dolphin • Have more reason not to sleep • Live in deep water and must breathe air every minute or so (no napping) • However, they still manage to get as much sleep as humans do • How??? Bottlenose Dolphin • They sleep with one cerebral hemisphere at a time! • About 2 hours asleep on one side, then 1 hour awake on both sides, then 2 hours asleep on the other side… • For a grand total of 12 hours a night • Do not seem to have REM sleep Indus River Dolphin Sleep Theories Theories of restoration vs. theories of adaptation We sleep to rest and recover We sleep to keep us out of trouble Does sleep renew us the same way eating and drinking do? Functions of Dreaming and REM Sleep Dreams are difficult to study • Modern studies tend to look at REM sleep rather than dreams…REM sleep can be measured objectively • Remember, REM sleep and dreaming are not synonymous • • Dreams can occur during non-REM sleep and many peculiar things occur during REM sleep that have nothing to do with dreaming Dreaming and REM sleep (cont’d…) • • Do we need to dream? Who knows. But, we do need REM sleep • If people are deprived of REM sleep for a few days they will experience REM rebound • Sleepers will attempt to enter REM more rapidly and will spend more time in REM proportional to the duration of their deprivation • Studies have found that REM deprivation does not cause any psychological harm during the daytime Dream Theories Sigmund Freud • Dreams are disguised wish-fulfillment, an unconscious way for us to express our sexual and aggressive fantasies, which are forbidden to us when we are awake • Hobson & McCarley (Harvard University) • More biologically based theories • “activation-synthesis hypothesis” • Dreams are seen as associations and memories of the cortex that are elicited by the random discharges of the pons during REM sleep • Activation Synthesis Hypothesis The pontine nucleus, via the thalamus, activate different areas of the cortex, elicit images/emotions, and the cortex attempts to synthesize the disparate images into a coherent whole • This process can account for the often bizarre and nonsensical nature of many dreams; since they are triggered by the semi-random activity of the pons • Evidence • No definitive evidence but some intriguing hints indicating the role of REM sleep and memory consolidation What many suggest: • REM sleep deprivation in humans and rats can impair their ability to learn new tasks • Karni and colleagues found that people’s performance on a visual task improved with REM sleep • • Interesting to note that non-REM sleep deprivation actually enhanced their performances • Karni hypothesized that this kind of visual memory requires a period of time to strengthen, specifically via REM sleep Sleep Learning? Neural Mechanisms of Sleep • • • Until the 1940s sleep was thought to be a passive process…without sensory input, the brain will fall asleep However, experiments blocking sensory afferents in animals did not eradicate their sleep/wake cycles We now know that sleeping is an active process that includes the participation of a variety of brain regions Neural Mechanisms of Sleep (Cont’d…) 1. 2. 3. 4. The diffuse modulatory NT systems are the most critical to the control of sleeping and waking During waking, the locus coeruleus (NE) and the raphe nuclei (5-HT) fire and enhance awake states (some ACh neurons also participate as well) These diffuse modulatory systems control rhythmic behaviors of the thalamus, which controls many EEG rhythms of the cortex (remember slow wave rhythms…block flow of sensory information via the thalamus to cortex) Descending branches of these systems are involved in inhibition of motor neurons Localization of Sleep Mechanisms in the Brain • • • Lesions of the brainstem of human can cause sleep and coma suggesting the brain stem must play a role in keeping us awake Moruzzi (1940s) attempted to sort out the brain stem’s control of waking and arousal • Lesions in the midline structures of the brain stem caused a state similar to non-REM sleep • Lesions in the lateral tegmentum did not (this area interrupts ascending sensory inputs) • Stimulation of the lateral tegmentum transformed the cortex from slow EEGs to awake EEGs (a more alert and aroused state) Called this area ASCENDING RETICULAR ACTIVATING SYSTEM (ARAS) Falling Asleep and the Non-REM State Decrease in the firing rates of most brain stem modulatory neurons Sleep spindles disappear Synchronization of activity due to neural interconnections Mechanisms of REM Sleep • • • • • • Neurons of the motor cortex continue to fire rapidly and attempt to command the muscles of the body but only succeed with the eye, ear, and respiratory muscles V1 is equally active in REM and non-REM Extrastriate areas and limbic areas more active during REM Frontal lobe activity less active in REM sleep The firing rates of the locus coeruleus and raphe nuclei decrease to almost nothing Sharp increase in firing rate of ACh neurons in the pons PET Imaging Why don’t we act out our dreams? Same core brain stem systems inhibit our spinal motor neurons Adaptive REM sleep behaviour disorder Disruption of brain stem systems Lesions studies Sleep-Promoting Factors John Pappenheimer (Harvard U.) Muramyl dipeptide facilitated no-REM sleep Found in spinal fluid of sleep-deprived goats Usually peptides are only produced by cell walls of bacteria Maybe synthesized by bacteria in the intestines Interleukin-1 Synthesized by brain Sleep-Promoting Factors (Cont’d…) Adenosine Acts as a neuromodulator at synapses throughout brain Antagonists of adenosine (e.g., caffeine and theophylline) Administration of adenosine or its agonists increase sleep Extracellular adenosine levels are higher during waking Adenosine levels throughout the day How does adenosine promote sleep? Inhibitory effect on modulatory systems for Ach, NE, and 5-HT Neural activity in the awake brain increases adenosine levels Brain will fall into the slow-wave synchronous activity SIDE NOTE: How does caffeine promote wakefulness? Four different adenosine receptor subtypes have been identified: A1, A2A, A2B, A3 Which one does caffeine most potently block? Another Sleep-Promoting Factor Melatonin Located just above tectum Derivative of tryptophan “Dracula of hormones” Circadian Rhythms Circadian rhythms: the daily cycles of daylight and darkness that result from the spin of the earth • The precise schedules vary from species to species (some are active at night… some in the day) • Many physiological and biochemical processes fluctuate with the daily/monthly/yearly rhythms • • Body temperature, blood flow, urine production, hormonal levels, hair growth, and metabolic rate Zeitgebers (from the German zeit=time and geber=giver): environmental time cues Light/dark, temperature, humidity… In their presence, animals become entrained to the day/night rhythm and maintain an activity of exactly 24 hours In their absence, animals will settle into a rhythm of activity/rest within 24 hours (more or less)…these rhythms are free run Free running period of mice (23 hours), hamsters (24 hours), and humans (24.5 - 25.5 hours) Relationship Between Behaviour and Physiology Problems occur when behaviour and physiology are desynchronized When can this happen? Best cure? Brain Clocks • Biological clocks consist of a few components: Light-sensitive input pathway Clock Output pathway Input pathways entrain the clock to keep it in rhythm with the environment • The clock will continue to function if the input pathway is removed • Output pathway control brain/body functions according to the timing of the clock • Suprachiasmatic nuclei (SCN) SCN (Cont’d…) • Since behavior is synchronized with light/dark cycles, there must be a photosensitive mechanism involved Retinal ganglion cells via retinohypothalamic tract Synapse directly on SCN neurons The SCN Cont’d… This retinal input is necessary and sufficient to entrain waking/sleeping cycles with light/dark cycles • SCN neurons have very large receptive fields and respond to luminance changes (not motion or orientation) • Surprisingly, the retinal cells that aid in synchronizing the SCN are not rods or cones • • Eyeless mice cannot reset their clocks, but mice with intact retinas lacking rods and cones can SCN Mechanisms • • • SCN cells communicate with the rest of the brain using action potentials Rates of firing vary with circadian rhythm However, action potentials are not necessary for SCN neurons to maintain their rhythm • Tetrodotoxin (TTX) blocks action potentials but does not affect the rhythmicity of their metabolism and biochemical functions • SCN action potentials are like the hands of a clock; removing them does not stop the clock from working, but it does make telling time difficult Seasonal Affective Disorder (SAD) Seasonal Affective Disorder (SAD) A clinical condition characterized by regular onset and remission of depressive episodes that follow a seasonal pattern Etiology Models Melatonin Hypothesis and Circadian Models Monoamine Hypothesis The Dual Vulnerability Hypothesis Melatonin Hypothesis and Circadian Models Phase delay Circadian Rhythms Monoamine Hypothesis Serotonin Controls appetite & sleep Precursor of melatonin Dopamine The Dual-Vulnerability Hypothesis DVH 2 vulnerability dimensions in SAD Seasonal vs. nonseasonal depression Seasonality Study Seasonality Study Changes in mood, eating patterns, energy levels, socialization, sleep patterns and weight, which occur in response to the changing seasons, are referred to as seasonality (Kasper, Wehr, Bartko, Gaist & Rosenthal, 1989) . Individuals with seasonal mood changes often report the atypical vegetative-somatic depressive symptoms such as increased carbohydrate craving and food intake during the winter (Rosenthal, Genhart, Sack, Skwere & Wehr, 1987). Seasonal affective disorder (SAD) Study Findings Higher levels of seasonality was linked to more severe depression symptoms, stress, dysfunctional eating behaviours, and over- eating. Seasonality predicted both disordering eating behaviours and overeating, particularly in the presence of stress. Study demonstrates support for a diathesis-stress model Jet Lag Disorder Jet Lag Disorder Circadian misalignment, the inevitable consequence of crossing time zones too rapidly for the circadian system to keep pace Possible Treatments: Prescribed Sleep Scheduling Circadian Phase Shifting Timed Melatonin Administration Promoting Sleep with Hypnotic Medication Promoting Alertness with Stimulant Medication Prescribed Sleep Scheduling Conclusion: One study supports staying on a home- based sleep schedule when time at destination is planned to be brief (i.e., two days or less) in order to limit jet lag symptoms. There are some data from jet lag studies to support altering the scheduled timing of sleep prior to eastward travel to help with entrainment, though the impact of this on jet lag symptoms is not entirely clear Timed Light Exposure Conclusion: In a jet lag simulation study, appropriately timed bright light exposure prior to travel was able to shift circadian rhythms in the desired direction but would require high motivation and strict compliance with the prescribed light-dark schedule if prescribed clinically. One trial with artificial light exposure upon arrival produced equivocal results. Timed Melatonin Administration The evidence is overall quite supportive that melatonin, administered at the appropriate time, can reduce the symptoms of jet lag and improve sleep following travel across multiple time zones. Immediate-release formulations in doses of 0.5 to 5 mg appear effective Promoting Sleep With Hypnotic Medication Although the number of studies is limited, the use of hypnotic agents for jet lag-induced insomnia is a rational treatment and consistent with the standard recommendations for the treatment of short-term insomnia. However, the effects of hypnotics on daytime symptoms of jet lag have not been well-studied and are unknown. In addition, any benefits to using hypnotics must be weighed against the risk for side effects. Because alcohol intake is often high during international travel, the risk of interaction with hypnotics should be emphasized with patients. Promoting Alertness with Stimulant Medications Conclusion: The use of caffeine to counteract jet lag induced sleepiness seems rational, but the evidence is very limited (2 studies). The alerting effects of these agents must be weighed against their propensity to disrupt sleep. One study suggested that a slow-release caffeine formulation may enhance the rapidity of circadian entrainment following eastward travel. Therapeutic Sleep Deprivation Major Depressive Disorder Associated with high degree of subjective distress and psychosocial disability Lifetime prevalence rate of about 20% (Kessler et al., 2003) High relapse or recurrence rates (50–90%), especially if there has been prior depressive episodes (Piet & Hougaard,2011) Development of effective interventions is high priority Therapeutic Sleep Deprivation I.e., Wake therapy, induced-wakefulness therapy = chronobiological therapy Nonpharmacological therapy Counterintuitive Modes of SD Total sleep deprivation (TSD) 08:00 of day 1 until 22:00 of day 2 (38 hours) Partial sleep deprivation (PSD) Early: First half of night from 22:00 until 02:00 Late: Second half of night from 02:00 until 22:00 Supporting Evidence Pflug and Töille (1971): TSD can induce temporary remissions in depressed (unipolar) patients Responses within hours – shorter time lag than other drugs and psychotherapies (Wirz-Justice et al., 2005) PSD in second half of night shows similar effects (Schilgen and Töille, 1980) More than two thirds of unmedicated patients responded to SD with a 20-60% improvement in mood compared to baseline values (Rudolf & Töille, 1978; Giedke & Schwärzler, 2002) Meta-analysis of 61 studies by Wu and Bunney (1990): Marked antidepressive effect in 59% of patients Limitations 80% sink back into depression following one night of sleep (Wu & Bunney, 1990) 50% relapse into depressed mood after a nap (Wiegand et al., 1987) Early morning naps worse than naps later in day Microsleep – may prevent response or induce relapse (Hemmeter, Hemmeter-Spernal & Krieg, 2010) Approximately 1/3 of patients do not benefit from SD Increased tiredness May intensify depressive symptomatology Agitation and restlessness associated with exhaustion Occurs in 2-7% of therapeutic SDs (Giedke, Geilenkirchen, & Hauser, 1992) Stabilizing The Antidepressant Effect Recommendations of the Committee on Chronotherapeutics in Affective Disorders of the International Society for Affective Disorders + mood stabilizer (Goodwin & Jamison, 2007) Repeated = (two-[total sleep deprivation] or three-times [partial sleep deprivation] per week) Supporting Evidence: Predictors of SD Diurnal variation of mood Typical sleep disturbance Increased tiredness Frequent nocturnal awakenings Early morning awakening Un- or less-disturbed function of the hypothalamic- pituitary-adrenal axis and increased metabolic activity of the ventral anterior cingulate (Hemmeter, Hemmeter-Spernal & Krieg, 2010) More “activation” Less tired, more behavioural activation (Clark, Dupont, Golshan, & Gillin, 1997) Limitations: Side Effects of SD Vegetative symptoms i.e., increased appetite (Pflug, 1976) Fatigue (Pflug, 1976) Headaches (Bhanji & Roy, 1975) In epilepsy: high risk of inducing seizures (Nakken, Solaas, Kjeldsen, Friis, Pellock, & Corey, 2005) Nonspecific stress (Suh et al., 2007) Summary Sleep deprivation works as an antidepressant tx if paired with daily light therapy, administration of SSRIs, lithium (bipolar), or a short phase advance of sleep Combinations of these interventions show great promise in the treatment of depression. State of Research on Underlying Mechanisms Controversy: No conclusive explanation for rapid relief of depression and immediate relapse into depression after sleep Unlikely that psychological mechanisms can provide complete explanation – due to rapidity of changing mood Neuroimaging: Results indicated increased activity in ventral anterior cingulate cortex & medial prefrontal cortex in SD responders compared to nonresponders (Wu et al., 1992) Anterior cingulate is innervated by serotonin and dopamine systems (Wu, Buchsbaum, & Bunney, 2001). Mobilization: Decreased metabolism of serotonin and dopamine after SD as serotonin and dopamine are both enhanced after SD (Gardner, Fornal , & Jacobs, 1997)
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