Sleep, memory and speech
Higher functions: sleep stages, EEG, memory, speech areas, limbic system and hypothalamus
EEG rhythms change with alertness and sleep stage; REM sleep brings dreams and muscle atonia. Covers memory and the hippocampus, Papez circuit, amnesia, aphasias, frontal lobe damage, reward pathways, hypothalamic feeding and temperature centres, and melatonin.
One of the most tested topics in past papers
EEG rhythms
| Wave | Frequency | When |
|---|---|---|
| Beta | > 13 Hz | Alert, eyes open, concentrating; benzodiazepines (lorazepam) and barbiturates increase frontal beta |
| Alpha | 8–13 Hz | Awake, relaxed, eyes closed; occipital; blocked by eye opening (alpha block) |
| Theta | 4–7 Hz | Drowsiness and light sleep; normal in children |
| Delta | < 4 Hz | Deep (slow-wave) sleep, infants; in an awake adult indicates brain dysfunction |
| Pattern | Meaning |
|---|---|
| 3 Hz spike-and-wave | Absence seizures |
| Hypsarrhythmia (chaotic high-voltage slow waves and spikes) | Infantile spasms (West syndrome): clusters of flexion spasms on waking, developmental regression |
| Diffuse slowing with triphasic waves | Metabolic encephalopathy, classically hepatic encephalopathy (raised ammonia, flapping tremor) |
| Flat (isoelectric) | Very deep anaesthesia, brain death (clinical diagnosis) |
Depth of anaesthesia: processed EEG indices such as the bispectral index (0 = no activity, 100 = awake) are kept at about 40–60 during general anaesthesia to reduce awareness; ketamine and nitrous oxide make the number unreliable.
Sleep stages
| Stage | EEG | Features |
|---|---|---|
| N1 | Theta | Drowsiness; easily woken |
| N2 | Sleep spindles and K complexes | Most of total sleep (about 45–55%) |
| N3 (slow-wave sleep) | Delta | Deepest; hardest to wake; GH pulse; sleepwalking, night terrors, bedwetting |
| REM | Low-voltage fast activity resembling waking ("paradoxical") | Vivid dreaming, rapid eye movements, atonia of skeletal muscle (except eye muscles and diaphragm), irregular pulse and breathing, penile erection; about 20–25% of sleep |
- Cycles last about 90 minutes; slow-wave sleep dominates early in the night, REM later. Hormones rising in sleep: GH (slow-wave sleep) and prolactin; cortisol rises towards morning.
- REM is generated in the pons (cholinergic neurones); atonia comes from brainstem inhibition of motor neurones.
- Obstructive sleep apnoea is worst in REM: atonia of pharyngeal dilator muscles produces the longest apnoeas and deepest desaturations (opioids after surgery add to this). First-line treatment of severe OSA is nightly CPAP.
- Sleep paralysis: REM atonia persists for a minute after waking, often with hallucinated figures. With daytime sleepiness and cataplexy it suggests narcolepsy, caused by loss of orexin (hypocretin) neurones in the lateral hypothalamus, with early-onset REM.
- Depression: early-morning waking, shortened REM latency, more REM early in the night, less slow-wave sleep.
- Wakefulness depends on the ascending reticular activating system, orexin, histamine (tuberomammillary nucleus), noradrenaline and serotonin. Sedating antihistamines (chlorphenamine) cross the blood–brain barrier and block central H1 receptors; they also have antimuscarinic effects.
Circadian rhythm and melatonin
The suprachiasmatic nucleus receives retinal light input and drives the pineal gland. Its pathway is long: hypothalamus, down the spinal cord to the intermediolateral column at T1, superior cervical ganglion, then sympathetic fibres back to the pineal. Melatonin rises in darkness. A complete cervical cord injury cuts this pathway, abolishing the night-time melatonin rise; beta-blockers also lower it.
Memory
| Type | Example | Main structures |
|---|---|---|
| Declarative (explicit): episodic and semantic | Facts and events | Hippocampus and medial temporal lobe to form; neocortex to store |
| Non-declarative (implicit): procedural, priming, conditioning | Riding a bicycle | Basal ganglia, cerebellum |
| Working memory | Holding a phone number | Prefrontal cortex |
- Consolidation turns short-term into long-term memory over minutes to years; long-term potentiation (glutamate on NMDA receptors) in the hippocampus is its cellular basis.
- Bilateral hippocampal damage causes anterograde amnesia: no new declarative memories, while old memories and new motor skills are preserved.
- After concussion, the minutes before injury are lost because those memories were not yet consolidated (retrograde amnesia); post-traumatic amnesia length better reflects severity.
- Hippocampal CA1 pyramidal cells are the neurones most vulnerable to global hypoxia–ischaemia (cardiac arrest), with cortical layers and Purkinje cells.
- Papez circuit: hippocampus, fornix, mammillary bodies, mammillothalamic tract, anterior thalamic nucleus, cingulate gyrus, parahippocampal gyrus, back to hippocampus. Bilateral fornix damage (for example during removal of a colloid cyst of the third ventricle) causes anterograde amnesia.
- Wernicke encephalopathy (thiamine deficiency from alcohol, hyperemesis or persistent vomiting after bariatric surgery): confusion, ataxia, nystagmus and ophthalmoplegia. Give IV thiamine first, before glucose. Untreated it leads to Korsakoff syndrome: damage to the mammillary bodies and dorsomedial thalamus, with anterograde and retrograde amnesia and confabulation.
- Mesial temporal lobe epilepsy: after prolonged febrile convulsions in childhood, hippocampal sclerosis causes seizures starting with a rising epigastric sensation and déjà vu, then lip-smacking and fumbling automatisms; drug-resistant cases may need surgery.
- Alzheimer disease: loss of cholinergic neurones (nucleus basalis of Meynert) and early hippocampal involvement.
Speech
| Area | Location (dominant, usually left) | Lesion |
|---|---|---|
| Broca | Inferior frontal gyrus (44, 45) | Expressive (non-fluent) aphasia: effortful speech, good comprehension, frustrated patient |
| Wernicke | Posterior superior temporal gyrus (22) | Receptive (fluent) aphasia: fluent meaningless speech, poor comprehension, often unaware |
| Arcuate fasciculus | Links the two | Conduction aphasia: fluent, good comprehension, poor repetition |
| Angular gyrus | Inferior parietal | Alexia with agraphia; Gerstmann syndrome |
The left hemisphere is dominant for language in almost all right-handers and most left-handers.
Limbic system, frontal lobes and reward
- Amygdala: fear and emotional memory. Bilateral damage causes Klüver–Bucy syndrome: docility, hyperorality, hypersexuality and visual agnosia.
- Orbitofrontal cortex: social behaviour and judgement. Contusions on the undersurface of the frontal lobes make a previously polite man impulsive, tactless and disinhibited, with normal power, memory and IQ scores.
- Dorsolateral prefrontal cortex: planning, working memory; damage causes apathy and poor executive function.
- Reward pathway: the mesolimbic dopamine projection from the ventral tegmental area to the nucleus accumbens underlies the euphoria and craving of drugs of abuse. Other dopamine pathways explain antipsychotic side effects: nigrostriatal (parkinsonism), tuberoinfundibular (raised prolactin).
Hypothalamic control of feeding and temperature
| Area | Function | Lesion |
|---|---|---|
| Ventromedial nucleus | Satiety centre (leptin acts here) | Hyperphagia and obesity |
| Lateral hypothalamus | Feeding centre; orexin | Refusal to eat, weight loss |
| Anterior hypothalamus | Heat loss (sweating, vasodilatation) | Hyperthermia |
| Posterior hypothalamus | Heat conservation and production (shivering, vasoconstriction) | Poikilothermia: temperature drifts with the environment, because the lesion also cuts descending pathways from the anterior centre |
Obesity is usually a state of leptin resistance, not leptin lack.
Learning
- Classical conditioning: a neutral stimulus paired with an unconditioned one comes to produce the response.
- Operant conditioning: behaviour shaped by reward or punishment.
- Habituation reduces the response to a repeated harmless stimulus; sensitisation increases it after a noxious one.
Remember Beta alert, alpha eyes closed, theta drowsy, delta deep; REM dreams with paralysed muscles; hippocampus makes memories, cortex keeps them.
Exam trap Muscle tone is lost in REM; sleepwalking and night terrors occur in slow-wave (N3) sleep.
Exam trap Conduction aphasia spares comprehension and fluency but ruins repetition.
How FCPS asks about this
- REM sleep: vivid dreams, atonia, rapid eye movements; sleep apnoea and sleep paralysis link to REM atonia.
- Cannot form new memories but remembers school days: bilateral hippocampal damage; after cardiac arrest CA1 cells die first.
- Docility, hyperorality, hypersexuality: bilateral amygdala damage (Klüver–Bucy).
- Lateral versus ventromedial hypothalamus: refusal to eat versus hyperphagia; posterior lesion causes poikilothermia.
- EEG in hepatic encephalopathy and infantile spasms: triphasic waves; hypsarrhythmia.
- Reward from heroin: dopamine from the VTA to the nucleus accumbens.
- Confusion, ataxia, nystagmus after bariatric surgery: Wernicke encephalopathy; IV thiamine first.
Test yourself on this topic
5 of the 75 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
Donepezil modestly improves a woman's memory in Alzheimer disease. Loss of which neurones does it partly compensate for?
Answer: Cholinergic neurones of the nucleus basalis
The nucleus basalis of Meynert in the basal forebrain supplies most of the cholinergic input to the cerebral cortex, and the septal nuclei supply the hippocampus. These neurones degenerate early in Alzheimer disease, and loss of cortical acetylcholine contributes to poor attention and memory. Donepezil inhibits acetylcholinesterase, so the acetylcholine still released stays longer in the synapse. Anticholinergic drugs worsen memory, especially in older people.
Acetylcholine and memory
- Nucleus basalis of Meynert: cortical ACh
- Lost early in Alzheimer disease
- Donepezil inhibits acetylcholinesterase
- Anticholinergics worsen memory
Remember Alzheimer memory loss is partly a cholinergic deficit.
Exam trap Cholinesterase inhibitors can cause bradycardia and syncope, so check the pulse and ECG in older patients.
Why the other options are wrong
- Dopaminergic neurones of the nigra Nigral loss causes Parkinson disease.
- Serotonergic neurones of the raphe Raphe neurones are affected but are not the target of donepezil.
- Noradrenergic neurones of the locus coeruleus Locus coeruleus neurones are also lost, but donepezil acts on acetylcholine.
- GABAergic neurones of the striatum Striatal GABA neurones die in Huntington disease.
A 45-year-old man who drank heavily every night stops drinking. For the next 2 weeks he has vivid, disturbing dreams and nightmares, though he has no tremor, confusion or hallucinations while awake. Which of the following explains his dreams?
Answer: Rebound of REM sleep after suppression
Alcohol, like benzodiazepines, barbiturates and many antidepressants, suppresses REM sleep. When regular use stops, the brain shows REM rebound: REM sleep comes earlier and is more intense and prolonged for days to weeks, with vivid dreams and nightmares. This disturbs sleep and is one reason people relapse by drinking 'to sleep'. Delirium tremens causes confusion, tremor and waking hallucinations within days of stopping, and night terrors arise from deep non-REM sleep with little dream recall.
REM rebound
- Alcohol and many drugs suppress REM
- On stopping: REM rebound
- Vivid dreams and nightmares
- Lasts days to weeks
Remember Take away a REM suppressant and dreams return with force.
Exam trap Alcohol speeds sleep onset but fragments the second half of the night, so it worsens insomnia overall.
Why the other options are wrong
- Delirium tremens He has no confusion, tremor or waking hallucinations.
- Wernicke encephalopathy There is no ataxia, confusion or eye movement palsy.
- Night terrors from deep non-REM sleep Night terrors occur early in the night with little recall.
- Hypoglycaemia during the night Nothing suggests nocturnal hypoglycaemia.
Which EEG rhythm is recorded over the occipital region in an awake, relaxed adult with eyes closed, and disappears when the eyes open?
Answer: Alpha waves (8–13 Hz)
EEG rhythms: alpha (8–13 Hz)—awake, relaxed, eyes closed, posterior; blocked by eye opening or mental effort ('alpha block'). Beta (> 13 Hz)—alert, eyes open, concentrating; increased by benzodiazepines. Theta (4–7 Hz)—drowsiness and light sleep, normal in children. Delta (< 4 Hz)—deep slow-wave sleep (N3), infancy, and in adults awake suggests structural brain disease or encephalopathy. Sleep spindles and K-complexes mark N2 sleep; REM sleep shows a low-voltage mixed (sawtooth) pattern resembling wakefulness.
EEG rhythms
- Beta > 13: alert
- Alpha 8–13: relaxed, eyes closed
- Theta 4–7: drowsy
- Delta < 4: deep sleep
- N2: spindles, K-complexes
Remember BATD: beta, alpha, theta, delta, from fast to slow.
Why the other options are wrong
- Beta waves (> 13 Hz) Alert, eyes open.
- Theta waves (4–7 Hz) Drowsiness; children.
- Delta waves (< 4 Hz) Deep sleep.
- Sleep spindles Stage N2 sleep.
A 45-year-old man has an upper GI endoscopy with IV midazolam. He answered questions and followed instructions during the procedure, but next day he cannot recall any of it, though he remembers arriving at the unit. Which of the following describes this effect?
Answer: Anterograde amnesia
Benzodiazepines such as midazolam enhance GABA-A receptor activity, including in the hippocampus, and block the consolidation of new information into long-term memory. Events after the dose are not stored even though the patient seemed awake and cooperative, which is anterograde amnesia. Memories formed before the drug was given, such as arriving at the unit, are kept. This effect is useful during unpleasant procedures but means instructions given afterwards should be written down.
Midazolam and memory
- Enhances GABA-A in hippocampus
- Blocks consolidation of new memories
- Anterograde amnesia
- Give discharge advice in writing
Remember After sedation, the patient may agree now and forget later.
Exam trap Consent and important advice should not be given only verbally after sedation; the patient will not remember it.
Why the other options are wrong
- Retrograde amnesia He remembers events before the drug was given.
- Loss of procedural memory Skills are not affected; the loss is for events.
- Transient global amnesia A spontaneous episode in older people, not drug-induced.
- Confabulation Filling memory gaps with invented stories, as in Korsakoff syndrome.
A man takes chlorphenamine for hay fever and becomes very drowsy at work. Why does this drug cause sedation?
Answer: It blocks central H1 receptors
Histamine-releasing neurones in the tuberomammillary nucleus of the posterior hypothalamus project widely and promote wakefulness through H1 receptors. First-generation antihistamines such as chlorphenamine and promethazine cross the blood–brain barrier and block these receptors, causing drowsiness and slowed reactions. Newer drugs such as cetirizine and loratadine enter the brain much less and sedate little.
Histamine and arousal
- Tuberomammillary nucleus makes histamine
- H1 receptors promote wakefulness
- Old antihistamines enter the brain
- Newer ones: little sedation
Remember Brain histamine keeps you awake.
Exam trap Sedating antihistamines also have antimuscarinic effects, causing dry mouth and urinary retention in older men.
Why the other options are wrong
- It blocks H2 receptors in the stomach H2 blockade reduces acid and does not sedate.
- It is a GABA-A agonist Chlorphenamine does not act on GABA-A.
- It blocks dopamine D2 receptors D2 blockade is not its main action.
- It stimulates melatonin release It does not act through melatonin.
Where this sits in the CPSP syllabus
- Paper 1: Nervous system, Higher functions: sleep, EEG, memory, learning, speech, limbic system
- Surgery & Allied, Paper 2: Nervous system, Higher functions: sleep, EEG, memory, learning, speech, limbic system
- Medicine & Allied, Paper 2: Nervous system, Higher functions: sleep, EEG, memory, learning, speech, limbic system
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