Consciousness, Unconsciousness, Sleep & EEG PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn CONSCIOUSNESS, UNCONSCIOUSNESS, SLEEP & EEG Class Year 2 Semester 1 Course CNS Code CNS Title Consciousness, Unconsciousness, Sleep & EEG Lecturer Dr. Melanie Föcking (RCSI-IE): Dr. Colin Greengrass...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn CONSCIOUSNESS, UNCONSCIOUSNESS, SLEEP & EEG Class Year 2 Semester 1 Course CNS Code CNS Title Consciousness, Unconsciousness, Sleep & EEG Lecturer Dr. Melanie Föcking (RCSI-IE): Dr. Colin Greengrass (RCSI-BH) Date 08.11.2023 ALO167 Define consciousness and unconsciousness and describe coma, vegetative state and brain death ALO168 Characterise circadian rhythms, ultradian rhythms and sleep stages ALO169 List neurophysiological measurements to characterise sleep stages ALO170 Recall benefits of sleep ALO171 Describe the regulation of sleep-wakefulness cycle ALO172 List sleep disorders Defining Consciousness, Unconsciousness, Coma, Vegetative State, and Brain Death ALO 167 – Define consciousness and unconsciousness and describe coma, vegetative state and brain death  O-PET fMRI Cerebral metabolism in Conscious healthy individuals Patients in vegetative state Patients in locked-in syndrome Patients in a minimally conscious state. Colour scale represents mg glucose metabolised per 100 g of brain tissue per minute. 1.1 Consciousness Definition: A state of self-awareness, perception, ability to respond to stimuli, ability to act with judgement Features: A state characterised by an individual’s awareness of their surroundings, thoughts, feelings, and memories Awareness of their own internal sensations, thoughts, and experiences. It encompasses the ability to perceive, communicate, and exhibit purposeful behaviour. Sleep Sleep is a state of changed consciousness from which a person can be aroused by stimulation, Alternating in a 24-hour cycle (circadian rhythm) with wakefulness Sleep is a physiological state 1.2 Unconsciousness Definition: A temporary or prolonged state in which there's a lack of responsiveness to external stimuli and an absence of voluntary actions. Features: Absence or disruption of consciousness where an individual cannot respond to external stimuli. 1.3 Coma Definition: A state of profound unconsciousness characterised by inability to sense and respond to external stimuli and loss of sleep- wake-cycle Features: A profound state of unresponsiveness caused by injury, disease, or toxins where an individual shows no spontaneous movements, does not respond to painful stimuli, and cannot be awakened. Mechanism: Often involves injury to both cerebral hemispheres or the reticular activating system in the brainstem. 1.3 Coma Causes: Intoxication, acute neurologic injuries, metabolic disorders, CNS infection, stroke, hypoxia Duration: Generally, few days to few weeks (2 - 5 weeks). Some patients progress to a vegetative state or die. Traumatic brain injury is graded as mild, moderate, or severe on the basis of the level of consciousness or Glasgow coma scale (GCS). https://reference.medscape.com/calcula tor/glasgow-coma-scale The relationship between the GCS Score and outcome is the basis for a common classification of acute traumatic brain injury: Severe GCS 3 – 8 Moderate GCS 9 – 12 Mild GCS 13 – 15 Web Viewer: Glasgow Coma scale  Spectrum of Consciousness Fully Alert Minimally Persistent Locked-in Acute Prolonged Brain and Delirium Conscious Vegetative Syndrome Coma Coma Death Attentive State State Behavioural Responsivity – refers to behavioural reaction to environmental stimuli Neurological Responsiveness – Measurable change in brain activity in response to external stimuli Spectrum of Consciousness Fully Alert and Attentive Neurological Responsiveness: Brain Activity (EEG/PET/fMRI): Consciously Aware: Yes Behavioural Responsivity: Yes Actively and appropriately Normal and active Delirium Behavioural Responsivity: Yes, Neurological Responsiveness: Brain Activity (EEG/PET/fMRI): Consciously Aware: but often inappropriate or Inconsistently; may show Disrupted patterns; Fluctuating; often confused confused abnormal responses abnormalities present Behavioural Responsivity – refers to behavioural reaction to external stimuli Neurological Responsiveness – Measurable change in brain activity in response to external stimuli Spectrum of Consciousness Locked-in Syndrome Behavioural Responsivity Very Neurological Responsiveness Brain Activity (EEG/PET/fMRI) Consciously Aware: Yes limited; mainly through eye Yes, but physical response is Normal or near-normal but with movements limited due to paralysis motor pathway disruption Minimally Conscious State Consciously Aware: Partially; minimal Behavioural Responsivity Limited; might Neurological Responsiveness Yes, but in a signs of awareness follow simple commands or make gestures limited and inconsistent manner Behavioural Responsivity – refers to behavioural reaction to external stimuli Neurological Responsiveness – Measurable change in brain activity in response to external stimuli Spectrum of Consciousness Persistent Vegetative State Behavioural Responsivity No; Neurological Responsiveness Brain Activity (EEG/PET/fMRI) Consciously Aware: No? might have reflexes but no Minimal to none; mostly Minimal; primarily autonomic purposeful behaviour autonomic reflexes functions Acute Coma Neurological Responsiveness Brain Activity (EEG/PET/fMRI) Consciously Aware: No Behavioural Responsivity No Generally non-responsive; no Very low; non-specific patterns typical reactions to stimuli or isoelectric (flat) Behavioural Responsivity – refers to behavioural reaction to external stimuli Neurological Responsiveness – Measurable change in brain activity in response to external stimuli 1.4 Vegetative State Definition: A condition of wakefulness without awareness. Individuals have sleep- wake cycles but show no signs of conscious awareness or purposeful activity. Mechanism: Damage to the cerebral cortex but retention of some brainstem functions. Features: A condition where a person is awake but showing no signs of awareness. They may have periods of wakefulness and even some reflexive actions but no meaningful response to the environment. 1.5 Brain Death Definition: A state of irreversible cessation of all cerebral and brainstem activities. It is the irreversible end of all brain activity due to total necrosis of the cerebral neurons following loss of blood flow and oxygenation. Mechanism: Total brain anoxia leading to neuronal death. Features: Used as a clinical and legal definition of death. Loss of pain responses and cranial nerve reflexes (pupillary response (fixed pupils), corneal reflex), loss of spontaneous respiration. Cerebral metabolism in patient with brain death Colour scale represents mg glucose metabolised per 100 g of brain tissue per minute. Spectrum of Consciousness – Coma and Brain Death Acute Coma (short duration) Consciously Aware: No Behavioural Responsivity: No Neurological Responsiveness: Brain Activity (EEG/PET/fMRI): Generally non-responsive; no Very low; non-specific patterns typical reactions to stimuli or isoelectric (flat) Prolonged Coma (long duration) Consciously Aware: No Behavioural Responsivity: No Neurological Responsiveness: Brain Activity (EEG/PET/fMRI): Generally non-responsive; no Very low; non-specific patterns typical reactions to stimuli or isoelectric (flat) Brain Death Consciously Aware: No Behavioural Responsivity: No Neurological Responsiveness: Brain Activity (EEG/PET/fMRI): Absent; no detectable reactions Absent; no detectable activity Biological Rhythms Infradian rhythms are Circadian rhythm is a naturally occurring Ultradian rhythm occurs cycle that lasts cycles in the human many times within the approximately a day/24 body that last longer span of a day. hours. than 24 hours but shorter than 1 year. EXAMPLE EXAMPLE EXAMPLE Feeding cycle Sleep-Wakefulness Cycle menstrual cycle is an Sleep REM|NREM cycle Body Temperature Infradian rhythm Hormone secretion (e.g. cortisol) 2.1 Circadian Rhythms Definition: Biological processes that display an endogenous oscillation of about 24 hours. Mechanism: Regulated primarily by the suprachiasmatic nucleus (SCN) of the hypothalamus. Features: Roughly 24-hour cycles regulating physiological processes, influenced by the natural environment (e.g., light-dark cycles). Changing the time of the day of the signal (light-dark timings) can alter the timing of the biological process, e.g. seasons, jetlag 2.2 Ultradian Rhythm Definition: Biological processes that display an endogenous oscillation several times within 24 hours. They have a cycle time shorter than a day but longer than an hour. Mechanism: Several – hormonal feedback loops, NREM|REM sleep cycle, Hunger Cycles Features: Occurring several times with a 24-hour period 2.3 Sleep Stages Definition: The distinct patterns of brain wave activity during sleep Sleep Stages typically broken down into: NREM (Non-Rapid Eye Movement) Sleep REM (Rapid Eye Movement) Sleep  Throughout then night, NREM sleep becomes less deep REM becoming more prolonged until waking occurs 90 min cycles, repeated 5 – 6 times per night The period of NREM sleep is made up of stages 1-4. Each stage can last from 5 to 15 minutes. A completed cycle of sleep consists of a progression from stages 1-4 before REM sleep is attained, then the cycle starts over again. 2.3 Sleep Stages: Non-REM Definition: Consists of four stages, each deeper than the last, characterised by slowing brain waves, reduced heart rate, and muscle relaxation. Features: autonomic stability - HR, BP, To fall Mechanism: Reduced activity in the reticular activating system.  Non-REM sleep has four stages. Stage 1 is characterized by a slight slowing of the EEG. Stage 2 has high-amplitude K complexes and spindles. Stages 3 and 4 have slow, high-amplitude delta waves. During NREM/slow wave sleep: neuronal activity in both cholinergic and monoaminergic pathways slows down  2.3 Sleep Stages: REM Definition: Characterised by rapid eye movements, muscle paralysis, and vivid dreams. Mechanism: Activation of the pons sends signals to the thalamus and cerebral cortex and inhibits motor neurons. During REM sleep: Cholinergic neurones fire rapidly Monoaminergic neurones stop firing REM sleep is characterized by a low-amplitude, high-frequency activity pattern. 2.3 Sleep Stages: REM sleep These variations in REM sleep over the course of the night are a fundamental aspect of the sleep architecture. REM sleep duration varies across sleep cycles. At the beginning of the night, REM sleep periods are relatively short, typically lasting about 10-20 minutes. As the night progresses, the duration of REM sleep tends to increase. reaching up to 30-45 minutes or more in later sleep cycles. The total amount of REM sleep during a night ranges from about 20-25% of total sleep time in adults.  MODEL MCQ 1 Biological rhythms are biological events with a pattern of activity that is repeated over and over again at a constant time interval. Which of the following represents an ultradian rhythm A.Body temperature B.Hormone secretion C.Menstrual cycle D.NREM/REM cycle E.Sleep/wakefulness cycle F.Appetite 3. Neurophysiological Measurements for Sleep Stages ALO 169 – List neurophysiological measurements to characterise sleep stages.  ELECTROENCEPHALOGRAM MEASURES ELECTRICAL ACTIVITY IS THE BRAIN IN DIFFERENT AREAS Main Clinical Applications of Electroencephalogram (EEG) Epilepsy: Diagnose, classify, and guide treatment. Sleep Disorders: Diagnose issues like sleep apnoea and narcolepsy. Coma/Altered State: Assess consciousness and non-convulsive seizures. Brain Death: Confirm absence of cerebral activity.  Alpha Alpha Beta EEG Waveforms  Monitors eye movements 3.2 Electrooculogram (EOG) which are especially relevant during REM phases. 3.3 Electromyogram (EMG) Assesses skeletal muscle activity which decreases as one enters deeper stages of sleep. Reduced muscle activity indicates deep NREM sleep, while almost no activity signifies REM sleep. EEG and muscle activity during various stages of the sleep– wake cycle REM sleep is characterized by: Greater eye movements, measured with electrooculogram (EOG); Loss of muscle tone – measured with decreased electromyogram (EMG) activity Low-amplitude, high-frequency EEG activity pattern. Autonomic instability: HR, BP, To vary GANONG 26th EEG OF WAKEFULNESS Alpha Beta Low amplitude, more irregular than alpha waves EEG β Awake with eyes open Rhythm of alert wakefulness waves desynchronised rhythm or alerting response EEG α Awake with eyes closed and Regular, rhythmic, and smooth waves inattentive to environment waves rhythm of drowsiness & NREM Called synchronised rhythms Sleep Stage 1 Light sleep, lasts for a few minutes Frequency: 4-8 Hz Features: More irregular than alpha waves Easily awakened Slow eye movements (rolling) Muscle activity slows down EEG: Theta waves (high amplitude, low frequency) Occasional α waves SLEEP –STAGE 2 Eye movements cease EEG: Brain waves become slower Occasional burst of rapid waves called spindles and K complexes  SLEEP –STAGES 3 & 4 Stage 3: Extremely slow brain waves called delta waves appear, interrupted by smaller, faster waves Stage 4: Nearly exclusive production of delta waves Very difficult to awake person Last and deepest stages before REM (dream) sleep Frequency: 0.5-4 Hz Features: High amplitude, slowest waves  REM EEG: fast, small amplitude like wakefulness but behaviourally asleep, difficult to arouse, associated with dreaming EMG: hypotonicity or flaccidity EOG: rapid eye movements Features: Mixed frequencies MODEL MCQ2 An 18-year-old medical student attending a boring lecture on EEG patterns has lost all interest in what the lecturer is talking about. The student is awake but has his eyes closed and he is not thinking about anything in particular. If his EEG was recorded at that moment, what type of characteristic brain wave pattern would it show A. Alpha B. Beta C. Delta D. Gamma E. Theta DEVELOPMENTAL ASPECTS REM sleep occupies 50% of total sleep time in neonates; this proportion declines rapidly and plateaus at ∼25% until it falls further in the elderly. 4. Benefits of Sleep ALO 170 – Recall benefits of sleep Cognitive Benefits of Sleep 1.Memory Consolidation: REM and slow-wave sleep stages facilitate the reinforcement of synaptic connections. This process aids in transitioning memories from the hippocampus to more permanent regions in the cortex. 2.Glymphatic Clearance: During sleep, the brain's glymphatic system becomes more active, helping to clear out neurotoxic waste, including beta-amyloid. This may offer protection against neurodegenerative diseases. Cognitive Benefits of Sleep 3. Neurogenesis: Formation of new neurons in the brain, persistent in regions like the hippocampus. Hippocampus Role: Key for memory formation and associative learning. Impact of sleep: Boosts growth factors (e.g., BDNF) enhancing neuron survival and synaptic connectivity. Regulates cortisol levels, preventing neurogenesis suppression. New Neurons: integrate into neural circuits, aiding formation of new memory traces. Physiological Benefits of Sleep Cellular Regeneration: Active protein synthesis for tissue repair. Immune Modulation: Optimizes cytokine production and T-cell activity. cytokines can induce sleep Endocrine Homeostasis: Regulates secretion of insulin, cortisol, and growth hormone. Muscle Recovery: Promotes actin-myosin cross-bridge healing post-exertion. Energy Rebalance: Shifts metabolism to restorative anabolic processes. Glycaemic Control: Enhances insulin sensitivity and glucose metabolism. Cardiovascular Equilibrium: Modulates sympathetic tone, aiding BP and heart rate normalization. During NREM/slow wave sleep, growth hormone is secreted, in particular in, the “healing and repair” period between 10 pm and 2 am Effects of Sleep Deprivation Sleep deprivation is lethal in animal models Cognitive Impairment: Sleep is essential for synaptic pruning and memory consolidation. Deprivation interferes with these processes, affecting learning and memory, attention and decision-making. Mood Disturbances: Lack of sleep alters neurotransmitter levels and neural activation in the amygdala, leading to emotional instability. Physical Health Risks: Disruption in the circadian rhythm affects blood pressure regulation and inflammatory responses. Immune System Suppression: Sleep enhances immune memory. Lack of sleep reduces production of cytokines and T-cells, weakening defense against pathogens. Impaired Metabolism: Sleep modulates insulin secretion and carbohydrate metabolism. Deprivation reduces glucose tolerance and insulin sensitivity. Importance of REM Sleep 1.Memory Consolidation: REM sleep facilitates the integration of new information into the existing knowledge framework, a process termed synaptic consolidation. 2.Emotional Regulation: Studies suggest that REM sleep aids in processing emotional experiences, potentially helping with emotional resilience and reducing emotional reactivity. 3.Dreaming: Most vivid dreams occur during REM sleep. While the exact purpose of dreaming is still debated, it may play role in emotional processing 4.Motor Skill Learning: REM sleep is thought to contribute to the brain's ability to learn motor skills, refining the neural pathways involved motor learning Reduction in REM occurs when consuming alcohol or nicotine or in response to certain medications (anti-depressants, anxiolytics) 5. Regulation of Sleep-Wakefulness Cycle ALO171 – Describe the regulation of sleep- wakefulness cycle. Reticular Activating System (RAS) The RAS, located in the brainstem, is a network of neurons that plays a crucial role in controlling arousal and wakefulness. It projects to various regions of the brain and plays a role in the transition between different states of consciousness.  Acetylcholine- Producing Neurons Cholinergic neurons promote cortical activation and wakefulness Monoamine- Producing Neurons Noradrenaline, Serotonin and Histamine release promotes wakefulness and alertness  Orexin-A and orexin-B (also known as hypocretin-1 and hypocretin-2) are produced by a cluster of neurons in the posterior lateral hypothalamus Orexin neurons help promote and sustain wakefulness by providing excitatory drive that govern arousal and alertness. In addition, orexins are essential regulators of REM sleep, the sleep stage characterized by vivid dreams and paralysis of nearly all muscles. Regulation of the Sleep-Wake Cycle The sleep-wake cycle, or circadian rhythm, is a crucial biological process that regulates our daily patterns of sleep and wakefulness. Key Regulator: The central regulator of the sleep-wake cycle is the Suprachiasmatic Nucleus (SCN), located in the hypothalamus of the brain.  Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) send signals to the suprachiasmatic nucleus (SCN) in response to light (appropriate to driving the circadian rhythm) These cells contain a photopigment called melanopsin, which responds more to blue light  The SCN receives input SCN and Melatonin from ipRG cells in the retina. The SCN regulates the production and release of melatonin, a hormone produced by the pineal gland. Melatonin levels typically rise in the evening, promoting sleepiness, and decrease in the morning, promoting wakefulness.  The sleep-wake cycle is regulated by a delicate balance between the SCN's Contributors to a Sleep State circadian rhythm and homeostatic sleep pressure. The SCN synchronises the timing of sleep and wakefulness based on the external light-dark cycle. Homeostatic sleep pressure gradually increases with time spent awake, creating a drive for sleep. Adenosine, a neurotransmitter, accumulates in the brain, contributing to sleep pressure. Regulation of the Sleep-Wake Cycle Synchronisation of Peripheral Clocks: The SCN also communicates with peripheral clocks found in other tissues and organs throughout the body. This synchronization ensures that various bodily functions, such as digestion and metabolism, are coordinated with the overall circadian rhythm. Temperature and Other Processes The SCN influences body temperature, hormone secretion, and other physiological activities related to the sleep-wake cycle. Regulation of the Sleep- Wake Cycle Melatonin Regulation The SCN controls the production and release of melatonin. Melatonin levels rise in the evening, promoting sleepiness, and decline in the morning, promoting wakefulness. The SCN receives input from light-sensitive cells in the retina. In the evening, as natural light levels decrease, the SCN signals the pineal gland to start producing and releasing melatonin. Melatonin and Sleep Melatonin acts as a signal to the body that it is time for sleep. Its increase in the bloodstream helps synchronize various physiological processes with the dark phase of the day-night cycle. Melatonin helps reset the body's internal biological clock, particularly when adjusting to changes in time zones or shift work.  Adenosine is a neurotransmitter that Homeostatic Sleep accumulates in the brain during wakefulness. Regulation Sleep Pressure: Adenosine is often referred to as a "sleep pressure" molecule because its accumulation creates a biochemical signal that promotes the need for sleep. Inducing Sleepiness: As adenosine levels rise, it binds to adenosine receptors in the brain, causing a reduction in neural activity and promoting sleepiness. Homeostatic Sleep Drive: The longer one is awake, the greater the physiological urge to sleep. Homeostatic Sleep Regulation Clearance During Sleep: When you sleep, adenosine levels naturally decrease because the brain's metabolic activity decreases during this time. Caffeine is an antagonist at adenosine receptors, preventing adenosine from activating the receptors. This interaction promotes wakefulness, alertness, and a reduction in feelings of drowsiness. 6. Sleep Disorders ALO 172 – List sleep disorders SLEEP DISORDERS Insomnia Excessive daytime sleepiness Obstructive sleep apnoea Narcolepsy Parasomnias (Night terrors, sleep walking, sleep talking) Restless Leg Syndrome Insomnia Definition: Insomnia is a persistent difficulty in falling or staying asleep Types: Acute (short-term) and Chronic (long-term). Symptoms: Difficulty in falling asleep Difficulty in staying asleep Early wakening Not feeling refreshed after sleep. Daytime Symptoms: Fatigue or low energy, mood disturbances, reduced performance, and difficulties with attention or memory. Mechanism: Often associated with heightened brain activity or hormonal imbalances. Stress and medications Excessive daytime sleepiness (EDS) EDS: A persistent feeling of sleepiness during the day, even after adequate night-time sleep. It can result in unintentional periods of drowsiness or falling asleep during inappropriate times. Causes: Sleep disorders (e.g., sleep apnoea, narcolepsy, restless legs syndrome), medications, medical conditions, poor sleep habits. Sleep Apnoea Definition: Sleep apnoea is characterized by pauses in breathing or periods of shallow breathing during sleep. These interruptions can last from a few seconds to minutes and can occur 30 times or more an hour. Types: Obstructive (OSA) - throat muscles intermittently relax and block the airway during sleep Central (CSA) – the airway isn't blocked. Instead, the brain doesn't send proper signals to the muscles that control breathing. Complex - a combination of OSA and CSA Symptoms: Snoring, gasping, daytime sleepiness. Risk factors: Obesity, male gender, neck size, alcohol/sedatives. Diagnosis: Polysomnography. Treatments: CPAP, dental devices, lifestyle changes. NARCOLEPSY Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep-wake cycles. Experience: periods of extreme daytime sleepiness and sudden, irresistible bouts of sleep that can strike at any time. Symptoms: Excessive daytime sleepiness, cataplexy, sudden sleep paralysis, hallucinations. Cataplexy: Sudden loss of voluntary muscle control, can range from slight muscle weakness to full collapse. Types: Type 1 (with cataplexy) and Type 2 (without cataplexy). Orexin: Neurotransmitter for sleep-wake regulation. Causes: Genetic predisposition, brain chemical imbalances. Deficiency in Type 1 Narcolepsy. Potential cause: Autoimmune response. Diagnostic tool: Orexin levels in cerebrospinal fluid. Parasomnias (Night terrors, sleep-walking, sleep talking) Definition: A group of sleep disorders that involve unwanted events or experiences that occur while falling asleep, sleeping, or waking up. Types: NREM-related : Sleepwalking, sleep terrors, confusional arousals. REM-related : REM sleep behaviour disorder, recurrent isolated sleep paralysis, nightmare disorder. Pathophysiology: - Disruption in the normal transitions between wakefulness, REM sleep, and NREM sleep. - Can be associated with genetic, environmental, psychological, and physiological factors. MODEL MCQ A very overweight male patient who is treated for high blood pressure is complaining about excessive daytime sleepiness, lack of concentration and phases of lost memory. You recommend further evaluation and diagnostic testing for A.Allodynia B.Alzheimer’s disease C.Burnout D.Depression E.Obstructive sleep apnoea MODERN SOCIETY We tend to override basic biorhythms 24-h culture with stimulation available around the clock 20% decrease in night’s sleep in the past 100 years Sleep disorders are common health This may be you in 4 years… problems and have major economic implications Bibliography