CHAPTER 60 – STATE OF BRAIN ACTIVITY – SLEEP, BRAIN WAVES, EPILEPSY, PSYCHOSES, AND DEMENTIA

SLEEP
• Unconsciousness from which a person can be aroused by sensory or other stimuli.
o Distinction: Sleep is different from coma, where arousal is not possible.
• Stages: Vary from very light to very deep sleep.
• Types: Sleep is divided into two main types:
▪ Slow-Wave Sleep (NREM Sleep)
▪ Rapid Eye Movement Sleep (REM Sleep)

TWO TYPES OF SLEEP: SLOW-WAVE AND REM SLEEP

• Sleep alternates between two major types during the night:
1. REM Sleep
▪ Eyes undergo rapid movements even while asleep.
2. Slow-Wave Sleep (NREM)
▪ Brain waves are strong and of low frequency.

• REM Sleep Features:

o Accounts for 25% of sleep time in young adults.
o Episodes recur about every 90 minutes.
o Associated with vivid dreaming but is not very restful.

• Slow-Wave Sleep Features:

o Dominates most of the night.
o Deep, restful sleep, especially during the first hour of sleep after extended wakefulness.

REM (Paradoxical, Desynchronized) Sleep

• Last 5 to 30 minutes and appear about every 90 minutes in young adults.
o Short or absent when a person is extremely sleepy.
o Duration increases as the person becomes rested.

• IMPORTANT CHARACTERISTICS:
▪ It is an active form of sleep
▪ Harder to arouse than during deep slow-wave sleep.
• BUT, people often wake spontaneously during REM episodes in the morning.

▪ Muscle Tone - Severely depressed due to strong inhibition of spinal muscle control.
▪ Heart rate and respiratory rate become irregular, characteristic of the dream state.
▪ Despite inhibited peripheral muscles, irregular muscle movements and rapid eye
movements occur.
▪ HIGH BRAIN ACTIVITY
• Brain metabolism increasing by up to 20%.
• EEG patterns resemble wakefulness.
• Also called paradoxical sleep because of the coexistence of brain activity and
unconsciousness.
o the person not fully aware of surroundings but truly asleep.

SLOW-WAVE SLEEP
• Characteristics:
o Exceedingly restful and common after prolonged wakefulness.
o Associated with:
▪ Decreased peripheral vascular tone.
▪ 10–30% reduction in blood pressure, respiratory rate, and basal metabolic rate.

• Dreams and Nightmares:

o Can occur but are less vivid than those in REM sleep.
o Not remembered due to lack of consolidation in memory.
o Dreams involve less bodily muscle activity than REM dreams.

BASIC THEORIES OF SLEEP

Sleep Is Caused by an Active Inhibitory Process

• Previously, it was believed that excitatory areas of the upper brainstem (reticular activating system) became
fatigued during the day, leading to inactivity.
• Modern View: Sleep is caused by an active inhibitory process:
o Experiments showed that transection at the midpons causes the brain cortex to never sleep.

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 o A center located below the midpontile brainstem is required to inhibit other brain parts and induce
sleep.

NEURONAL CENTERS, NEUROHUMORAL SUBSTANCES, AND MECHANISMS THAT CAUSE SLEEP

1. Key Areas That Induce Sleep!!!!!!!!!!!!!
o Raphe Nuclei:
▪ Located in the lower pons and medulla; a thin sheet of neurons in the midline.
▪ Fibers spread locally in the brainstem and project to the thalamus, hypothalamus, limbic
system, neocortex, and spinal cord.
▪ These fibers secrete serotonin, crucial for sleep.
▪ Drugs blocking serotonin formation prevent sleep for several days.
▪ Associated with sleep production

o Nucleus of the Tractus Solitarius:

▪ Found in the medulla and pons; receives visceral sensory signals via the vagus and
glossopharyngeal nerves.

o Diencephalon Regions:
▪ Rostral hypothalamus, especially the supra-chiasmal area.
▪ Diffuse thalamic nuclei in specific areas.

2. Lesions in Sleep-Promoting Centers:

o Raphe nuclei lesions: Cause intense wakefulness by releasing excitatory reticular nuclei in the
mesencephalon and upper pons from inhibition.

o Anterior hypothalamus lesions: Severe wakefulness may lead to death from exhaustion.

3. Other Substances Promoting Sleep:

o Substances accumulate in cerebrospinal fluid (CSF), blood, or urine after prolonged wakefulness.

▪ Example: Muramyl Peptide (MAP)

▪ Induces sleep when injected into the brain ventricles.

▪ Example: Delta Sleep-Inducing Peptide

▪ Nonapeptide found in CSF after thalamic stimulation for sleep.

▪ Other sleep-promoting peptides may accumulate in CSF or brainstem tissues after prolonged
wakefulness.

Possible Cause of REM Sleep

• Acetylcholine (ACh) Role:
o Drugs mimicking ACh increase REM sleep.
o Large ACh-secreting neurons in the upper brainstem reticular formation may activate many brain
areas during REM sleep.
o The signals from these neurons may not channel correctly, preventing conscious awareness.

CYCLE BETWEEN SLEEP AND WAKEFULNESS

1. Mechanism:
o When sleep centers are inactive, the reticular activating nuclei (mesencephalic and upper pontile)
are released from inhibition, becoming spontaneously active.
▪ These nuclei excite the cerebral cortex and peripheral nervous system, creating a positive
feedback loop.
o After prolonged activity, the activating neurons fatigue, positive feedback fades, and sleep-
promoting effects take over, transitioning to sleep.

o Explains rapid transitions between sleep and wakefulness.

o Accounts for arousal during insomnia (preoccupation with thoughts) or wakefulness due to physical
activity.

ROLE OF OREXIN NEURONS IN AROUSAL AND WAKEFULNESS

• Orexin (Hypocretin): Produced by neurons in the hypothalamus, providing excitatory input to orexin
receptor areas.
o Active During Wakefulness
o Almost ceases during slow-wave and REM sleep.
o Loss of Orexin Signaling:
▪ Narcolepsy:
▪ Overwhelming daytime drowsiness.
▪ Sudden sleep attacks during activities.

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 ▪ Cataplexy:
▪ Sudden loss of muscle tone, leading to partial or complete paralysis during attacks.

Sleep's Important Physiological Functions

• General Importance
o Sleep exists in all mammals.
o Deprivation causes "catch-up" or "rebound" sleep, emphasizing its essential role.
o Mild sleep restriction impairs cognitive and physical performance.
o Total deprivation (2-3 weeks) in rats can result in death, underscoring its critical role.

• 2 major types of Physiological Effects of sleep

o CENTRAL Nervous System:
▪ Lack of sleep leads to cognitive dysfunction, irritability, and possible psychosis.
▪ Sleep is believed to restore normal brain activity and balance.

o Other Systems:
▪ Sleep is considered an adaptive response to conserve energy for combating infections or
injuries.
• Postulated Functions
▪ Neural maturation.
▪ Facilitation of learning or memory.
▪ Targeted synaptic erasure to "forget" unimportant information.
▪ Cognition improvement.
▪ Clearance of metabolic waste from the brain.
▪ Conservation of metabolic energy.

BRAIN WAVES AND THE EEG!!!!!!!!!!!!!!!

• Brain Wave Types
o Alpha Waves:
▪ Frequency: 8-13 cycles/sec.
▪ Found in resting states; disappear during deep sleep.

o Beta Waves:
▪ Frequency: >14 cycles/sec.
▪ Occur during active mental engagement.
▪ Asynchronous, higher frequency than alpha (low voltage but irregular and high frequency)
▪ Recorded mainly in parietal and frontal regions (PF)
▪ Intense mental activity and FRIGHT

o Theta Waves:
▪ Frequency: 4-7 cycles/sec.
▪ Found in children or during emotional stress in adults.
▪ Recorded mostly in part parietal and temporal (PT)
▪ Additional: present in psychomotor states

o Delta Waves:
▪ Frequency: <3.5 cycles/sec.
▪ Associated with deep sleep in infancy and certain brain disorders.
▪ Present in surgical anesthesia

• Origins of Wave
- note synchronous stimulation ang need for waves to be detected
- strong non-synchronized forces = nullified
o Alpha Waves: Result from oscillations in the thalamocortical system.
o Delta Waves: from the cortical neuronal system itself, independent of thalamic input.

• EEG Correlation with Brain Activity

o Brain wave frequency increases with higher cerebral activity.
o Mental activity or stress often results in asynchronous waves (low voltage but high frequency). Not
synchronous!!!!

SLEEP STAGES AND EEG PATTERNS

• Wakefulness
o Alert Wakefulness: High-frequency beta waves.
o Quiet Wakefulness: Alpha waves dominate.

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 • Slow – Wave Sleep Stages
▪ Light Sleep (Stage 1): Low-voltage waves with occasional "sleep spindles." => slow burst of
alpha waves
▪ Stages 2, 3, and 4: Progressively slower frequencies with delta waves dominating in stage 4.
▪ Delta – only 1 to 3 waves per second
• REM Sleep
o EEG resembles wakefulness with irregular, high-frequency waves.
o Often called "desynchronized sleep" due to lack of neuronal synchrony.

SEIZURES AND EPILEPSY

SEIZURES
• Temporary brain function disruption caused by excessive, uncontrolled neuronal activity.
• Causes:
o Neurological/medical conditions (e.g., electrolyte imbalance, hypoglycemia, meningitis).
o External factors like drugs (e.g., cocaine) or systemic diseases (e.g., kidney failure, eclampsia).
• Prevalence: 5-10% of individuals experience at least one seizure in their lifetime.
• Types:
o Symptomatic seizures: Result from an underlying condition; cease when the condition is resolved.
o Epilepsy: A chronic condition involving recurrent seizures caused by various pathophysiological
mechanisms.

EPILEPSY
• A chronic condition of recurrent seizures with variable clinical symptoms.
• Causes: (note: it is not a single-cause disease!!!)
o Brain trauma, stroke, tumors, infection, degenerative conditions.
o Genetic predisposition and acquired brain pathology.
• Prevalence: Affects ~1% of the global population (~65 million people).
• Pathophysiology:
o Disruption in the balance of inhibitory and excitatory brain signals.
o Epileptogenic factors: Increased excitation or reduced inhibition in neuronal circuits. (opposite sa
antiepileptic = inhibition)
o Delay in seizure onset is common post-brain injury (months or years).

TYPES OF EPILEPTIC SEIZURES

1. Focal (Partial) Seizures

• Confined to one cerebral hemisphere or specific brain areas.
• Causes:
o Scar tissue
o Tumor
o Destroyed area
o Congenitally deranged local circuitry

• Mechanism:
o Localized reverberating circuits recruit adjacent cortical areas into the epileptic discharge zone
o Spread can be gradual (mm/min) or rapid (cm/sec).

• Jacksonian March:
o Progressive march of muscle contraction spreading from one body region to another (e.g., mouth to
legs). [CONTRALATERAL]

• Symptoms:
o Simple partial seizures:
▪ No major change in consciousness.
▪ Symptoms: Aura (e.g., fear), localized motor signs (e.g., rhythmic jerking).
o Complex partial seizures:
▪ Impaired consciousness.
▪ Included Automatisms = Repetitive movements (e.g., chewing or lip smacking).
▪ Aura may precede seizure; postictal amnesia common.

2. Generalized Seizures
• Localization: Involves both hemispheres of the cerebral cortex.
• Spread:
o From a focal region through connections to the thalamus and bilateral hemispheres.

Electroencephalogram (EEG) in Seizures

• EEG Findings:

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 o Synchronous discharges in focal regions for partial seizures.
o Complex patterns (e.g., low-frequency rectangular waves in psychomotor seizures).
• Postictal Period:
o Time between seizure and return to normal neurological function.

GENERALIZED SEIZURES
• Diffuse, excessive, and uncontrolled neuronal discharges spread rapidly and simultaneously to both
cerebral hemispheres through thalamocortical interconnections

Types of Generalized Seizures

1. Generalized Tonic-Clonic (Grand Mal) Seizures
• Characteristics:
o Abrupt loss of consciousness.
o Involves extreme neuronal discharges in the cerebral cortex, brainstem, and even the spinal cord.
o Phases:
1. Tonic phase: Sustained muscle contractions.
2. Clonic phase: Alternating contractions and relaxations.

o Symptoms:
▪ Tongue biting or swallowing the tongue.
▪ Difficulty breathing (cyanosis may occur).
▪ Involuntary urination or defecation.
o Duration: Ranges from a few seconds to 3–4 minutes.
o Post-Seizure Effects:
▪ Postictal depression: Depression of the entire nervous system, with stupor lasting minutes
to hours.
▪ Severe fatigue and prolonged sleep often follow.

• EG Findings:
o High-voltage, high-frequency discharges occur over the entire cortex during the tonic phase.
o Similar discharges recorded in the thalamus and reticular formation, indicating activation of the
subthalamic brainstem regions.

2. Absence Seizures (Petit Mal)

• Characteristics:
o Usually last 3–30 seconds and involve diminished consciousness or unconsciousness.
o Symptoms:
▪ Staring episodes and twitch-like muscle contractions, especially eyelid blinking.
▪ Rapid recovery with resumption of normal activities.
o Commonly appears during childhood or adolescence and typically resolves by age 30.
o Rarely, absence seizures may trigger a generalized tonic-clonic attack.

• EEG Findings:
o Spike-and-dome pattern over most of the cortex, reflecting activity in the thalamocortical system.
o Involves:
▪ Inhibitory thalamic reticular neurons (GABA-producing).
▪ Excitatory thalamocortical and corticothalamic neurons.

Treatment of Epilepsy
• Mechanisms of Antiepileptic Drugs:
1. Voltage-dependent sodium channel blockade (e.g., carbamazepine, phenytoin).
2. Calcium current modulation (e.g., ethosuximide).
3. Increased GABA activity (e.g., phenobarbital, benzodiazepines).
4. Glutamate receptor inhibition (e.g., perampanel).
5. Combination mechanisms (e.g., valproate, topiramate).

• Surgical Intervention:
o When epilepsy is medically intractable, EEG can localize abnormal spiking waves to guide surgical
excision of the focus, preventing future attacks.

ROLES OF SPECIFIC NEUROTRANSMITTER SYSTEMS IN BRAIN DISORDERS

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Parkinson’s Disease
• Caused by loss of neurons in the substantia nigra.
• Affects dopamine secretion in the caudate nucleus and putamen.

Huntington’s Disease
• Involves loss of GABA-secreting and acetylcholine-secreting neurons.
• Leads to abnormal motor patterns and dementia.

Depression and Manic-Depressive Psychoses

• Decreased activity of norepinephrine and serotonin neurotransmitter systems.
• Depressed patients may have diminished formation of these neurotransmitters.

Drug Treatments:
1. Monoamine oxidase inhibitors: Block the destruction of norepinephrine and serotonin.
2. Tricyclic antidepressants: Block the reuptake of these neurotransmitters, prolonging their activity.

Bipolar Disorder:
• Alternating depression and mania phases.
• Treated with lithium compounds to diminish norepinephrine and serotonin activity.

Schizophrenia
• Delusions, hallucinations, intense fear, and paranoia.
Hypotheses:
1. Dysfunction in the cerebral cortex (prefrontal lobes), likely due to synaptic abnormalities involving
glutamate.
2. Excessive activity of dopamine-secreting neurons in the mesolimbic system.
3. Abnormal function in the limbic behavioral control system, particularly the hippocampus.

Alzheimer’s Disease
• Progressive neurodegenerative disorder causing premature brain aging and memory impairment.
• Loss of neurons in the limbic pathway, critical for memory.
• Accumulation of beta-amyloid peptide in the brain, forming amyloid plaques in the cortex,
hippocampus, and other regions.

Key Observations:
1. Mutations increasing beta-amyloid production are linked to Alzheimer’s.
2. Patients with trisomy 21 (Down syndrome) develop Alzheimer’s-like pathology in midlife.
3. Genetic abnormalities affecting apolipoprotein E increase plaque deposition.
4. Anti-amyloid antibodies may attenuate disease progression.

Contributing Factors:
• Cerebrovascular disease (e.g., hypertension, diabetes, hyperlipidemia) exacerbates cognitive decline.
• Vascular dementia: 10–20% of dementia cases involve vascular causes alone.
• About 50% of Alzheimer’s patients exhibit silent strokes that may worsen cognitive impairment.

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