Spreading depression is basically an electrical change of brain, much like a seizure in that it is transient. Like a seizure, spreading depression is may not be evident in normal brain activity (1). But then, a flurry of increased neuronal activity (2) can result in synchronized neuronal firing over an expanse of brain that evokes the spreading depression (3). Unlike a seizure that shows a transient increase in brain activity, spreading depression triggers a transient loss of brain activity (4) before al returns to normal. The ion current changes responsible for spreading depression are shown as 1-4 and show the key change — a loss of inhibition. In the brain, synapses are areas where neurons communicate and there are two key types at play in migraine: The excitatory and inhibitory synapses. Excitatory synapses increase brain activity by directing ions into cells (blue). Inhibitory synapses decrease brain activity by directing ions out of cells (red). This in-and-out flow among neuronal dendrites (D) makes brain activity (1) which can be increased by various triggers of migraine (2). The ion flow of normally is outward at cell bodies (CB). Importantly with triggering of spreading depression (i.e., the most likely cause of migraine), this normal cell body outward ion movement is reversed for seconds (3). This means that spreading depression begins because of a loss of neuronal inhibition that makes the brain more excitable. Then, spreading depression moves across the brain with slow, normally distributed in-and-out ion currents (4) not associated with typical communication between synapses (gray) before all returns to normal. (This video was created with the assistance of Mr. Dale Mertes from the University of Chicago.)