A patient can learn a skill perfectly
and deny ever having practised it.

The minimum high-yield framework

1. Classify twice. By duration: short-term/working against long-term. By content: declarative (explicit) against non-declarative (implicit).
2. Declarative — facts and events, conscious. Requires the medial temporal lobe and hippocampus for encoding.
3. Non-declarative — skills, habits, conditioning, unconscious. Depends on basal ganglia, cerebellum and amygdala.
4. Working memory is a prefrontal function, limited in capacity, and requires ongoing neural activity rather than a structural change.
5. Long-term potentiation is the cellular model of memory, and the NMDA receptor is what makes it associative — it needs both glutamate and depolarisation to relieve its magnesium block.
6. The limbic system — hippocampus, amygdala, cingulate gyrus, hypothalamus, fornix, mammillary bodies — handles emotion and memory.
7. Broca (inferior frontal, dominant) = expression; Wernicke (superior temporal, dominant) = comprehension.
8. Amnesia occurs at lower anaesthetic concentrations than unconsciousness — the reason explicit recall after awareness is uncommon.

1. The magnesium block. At the resting potential the NMDA receptor channel is plugged by Mg²⁺. Glutamate binding alone does not open it.
2. AMPA first. Ordinary glutamatergic transmission acts on AMPA receptors, admitting Na⁺ and depolarising the postsynaptic membrane.
3. Coincidence detection. Sufficient depolarisation expels the Mg²⁺. Only if glutamate is present and the cell is depolarised does the NMDA channel conduct — so it fires only when pre- and postsynaptic activity coincide. This is exactly the property association requires, and it is why the NMDA receptor is the molecular basis of Hebbian learning.
4. Calcium entry. The open NMDA channel admits Ca²⁺, which activates calcium/calmodulin-dependent protein kinase II and protein kinase C.
5. Expression. Early phase — phosphorylation and insertion of additional AMPA receptors into the postsynaptic membrane, strengthening the synapse. Late phase — gene transcription, protein synthesis and structural growth of new dendritic spines, which is what makes the change durable.

The amygdala deserves separate treatment because it is the structure most often asked about. It receives sensory input by two routes: a fast, coarse subcortical route direct from the thalamus, and a slower, detailed cortical route. The fast route allows a defensive response to begin before the stimulus has been identified — the startle before you know what startled you. Its outputs go to the hypothalamus for the autonomic response, the periaqueductal grey for freezing and analgesia, and the brainstem for the startle reflex. It also modulates hippocampal consolidation, which is why emotionally charged events are remembered vividly and why intraoperative awareness with distress carries a much higher risk of lasting psychological sequelae.

An emotion has a subjective component generated in the cortex and limbic system, and three expressed components, all coordinated by the hypothalamus:

1. Autonomic — tachycardia, hypertension, sweating, pupillary dilation, gut and bladder changes, by way of the descending autonomic pathways of lesson 16.
2. Endocrine — corticotropin-releasing hormone from the hypothalamus driving ACTH and cortisol, together with catecholamine release: the stress response.
3. Behavioural (somatic) — facial expression, posture, vocalisation, approach or withdrawal.

The hypothalamus is also the site of the homeostatic drives that share this machinery — thermoregulation, osmoregulation, hunger and satiety, circadian rhythm and the sleep-wake switch of lesson 19. This convergence is the physiological explanation for a familiar clinical observation: anxiety produces a measurable haemodynamic and endocrine response, which is why anxiolytic premedication has physiological effects and not merely psychological ones.

The language areas are in the dominant hemisphere, which is the left in essentially all right-handed people and in the majority of left-handed people. That asymmetry is the reason the left carotid territory and left-sided craniotomy carry a language risk that the right does not.

Anaesthesia and memory

The concentration-response relationships for the components of anaesthesia are separate, and the ordering is the clinically important part: amnesia occurs at concentrations well below those producing unconsciousness, which in turn are below those preventing movement. Two consequences follow. First, a patient may be conscious during an inadequate anaesthetic yet have no explicit recall of it, which is why the incidence of awareness measured by structured interview exceeds the incidence of spontaneous complaint. Second, benzodiazepines produce profound anterograde amnesia at doses that leave the patient conversant — the basis of their use for sedation, and a reason a patient may recall nothing of a procedure they appeared to tolerate awake.

The ageing central nervous system

Postoperative delirium is an acute, fluctuating disturbance of attention and cognition, typically appearing on the first to third postoperative day. Its recognised contributors are the ones this module has covered: reduced cholinergic transmission, disrupted sleep architecture, pain, sepsis, hypoxaemia, metabolic disturbance and deliriogenic drugs — anticholinergics and benzodiazepines in particular. Prevention is multicomponent and largely non-pharmacological: orientation, early mobilisation, restoring hearing aids and spectacles, protecting sleep, treating pain with opioid-sparing regimens, and avoiding the drugs that precipitate it.

Previously examinedApril 2025 — the physiological changes of ageing in the central nervous system and their anaesthetic implications. Worked answers in the library