Mechanisms of migraine aura revealed by functional MRI in human visual cortex

TLDR

Cortical spreading depression has been proposed to underlie migraine visual aura, yet direct evidence in human cortex has been difficult to obtain. High‑field fMRI with near‑continuous recording during aura in three subjects revealed BOLD changes that matched at least eight hallmarks of CSD and were time‑locked to aura onset. The BOLD signal first rose focally in extrastriate V3A, then spread slowly (~3.5 mm min⁻¹) across occipital cortex in a retinotopic pattern before declining, supporting CSD as the aura generator.

Abstract

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 ± 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex.