Excitability landscape · Grey Matter

The excitability landscape is a working map, used in this section as a hypothesis, of where a patch of cortex sits relative to its two ways of failing, so that a disturbance in it can be predicted to fade, to become a slow wave of spreading depression, or to become a fast synchronous discharge.

Excitability landscape. The excitability landscape is a working map, used in this section as a hypothesis, of where a patch of cortex sits relative to its two ways of failing, so that a disturbance in it can be predicted to fade, to become a slow wave of spreading depression, or to become a fast synchronous discharge.

Picture the resting cortex as a ball in a valley. A small push (a flash, a burst of input, a brief imbalance of ions) moves it and it rolls back: inhibition catches the extra firing and pumps and astrocytes clear the potassium and glutamate it left. Beyond one ridge lies the seizure: neurons keep their gradients and fire too much and too synchronously because inhibition no longer contains them. Beyond another lies spreading depression: the gradients themselves collapse, cells depolarise passively from their surroundings and the tissue goes silent for minutes. The map is a simplification of real biophysics, useful for asking which variable moves the ball and which moves the ridges.

The variables that move the ridges are known in part. Extracellular potassium, energy supply for the pumps, the state of inhibition, the clearing capacity of astrocytes and the size of the extracellular space all shift which outcome a push leads to, and models of spreading depression and seizure use exactly these.

The two failures can follow each other. Seizures can set off spreading depression, and in some animal models the spreading depression then stops the seizure and prevents it from generalising.

The everyday factors are hypotheses with uneven support. Sleep loss and stress are among the precipitants people with epilepsy report most, and diary studies support both. Sustained mental effort raising the coupling between areas, and continuous visual stimulation keeping the visual cortex near its edge, are plausible mechanisms with little direct evidence. Emotional arousal releases noradrenaline, which raises cortical responsiveness, yet in animal models noradrenaline mostly protects against seizures, so the step from arousal to a lower threshold is not established.

The visual cortex is where the map is easiest to read. It is a frequent site for both auras and photosensitive seizures, and because it is a map of the visual field, all three outcomes show as visible symptoms with their own speed and shape.

The same tissue near its edge can fail in two opposite ways.

A seizure is too much firing with the gradients intact; spreading depression is the gradients lost and no firing at all, and what tips one way or the other is local and changes with state.

Questions: Can a spreading depression stop a seizure that set it off? In several animal models it can: a seizure raises extracellular potassium and glutamate until the tissue tips into spreading depression, and the depression immediately silences the seizure where it passes and keeps it from generalising. The two outcomes of the excitability map are therefore linked as well as opposed, since the collapse of the gradients removes the charge that the seizure needs. Whether the same sequence ends seizures in people, and whether it contributes to the confusion and weakness after some seizures, is still being studied. Does emotional arousal, through noradrenaline, push the cortex closer to a seizure? The evidence does not support the simple version of this hypothesis. Arousal releases noradrenaline from the locus coeruleus across the cortex, which raises responsiveness and could plausibly lower thresholds, yet in animal models noradrenaline mostly protects against seizures and damage to the locus coeruleus makes seizures worse. At the same time, people with epilepsy report stress as one of their most common triggers, and diary studies find more seizures after stressful days. The link between arousal and seizures is real at the level of reports and statistics, and the route, through noradrenaline, cortisol, lost sleep or something else, remains open.