What causes migraines?

A migraine is not a bad headache. It is a neurological event lasting hours to days: often announced a day early by yawning, cravings, and mood shifts, sometimes preceded by an aura of shimmering geometry sliding across the visual field, then the pain, one-sided and pulsing, with light and sound turned unbearable and nausea for company. Hippocrates described the aura more than two thousand years ago. Roughly a billion people alive today know the sequence from inside, which makes migraine one of the commonest disabling conditions of the species, and its root cause is still not established.

Why it matters

The disability burden alone would justify the entry: migraine ranks among the world’s leading causes of years lived with disability, hitting hardest during working and caregiving years, and afflicting women about three times as often as men for reasons that remain unclear. But migraine is also a window into ordinary brains. Whatever periodically tips a migraine brain into an attack is some dial of excitability that all brains possess; finding it would illuminate how the organ regulates itself.

What has been tried

The old theory blamed blood vessels: constriction causing aura, rebound dilation causing pain. It has been largely dethroned by a neural account. The aura corresponds beautifully to cortical spreading depression, a slow electrical wave crawling across the cortex at millimeters per minute, silencing neurons as it goes, at exactly the speed the shimmer crosses vision. The pain involves the trigeminovascular system, the nerve network wrapping the brain’s coverings and vessels, and a neuropeptide called CGRP proved central: drugs designed to block it, arriving from 2018 onward, prevent or abort attacks in many patients, a rare case of mechanism-first medicine paying off. Genetics added dozens of risk variants, and rare familial forms traced to ion channel mutations tie migraine to neuronal excitability.

Where the edge is

The middle of the story is filling in; the beginning is not. What initiates an attack remains unknown, with imaging pointing suspiciously at the hypothalamus during the warning phase. Why attacks are episodic, how triggers actually trigger, why aura strikes some sufferers and not others, and why hormones modulate the whole disorder remain open, and a substantial minority of patients respond to none of the new drugs.

What would count as an answer

The generator identified: the circuit or state change that launches an attack, shown by predicting and preventing attacks from the origin rather than intercepting them downstream. The light show has a projectionist, still unidentified.