fMRI Insights into Visual Cortex Dysfunction as a Biomarker for Migraine with Aura

Migraine with aura (MwA) is a common and severely disabling neurological disorder, characterised by transient yet recurrent visual disturbances, including scintillating scotomas, flickering photopsias, and complex geometric patterns. These episodic visual phenomena significantly compromise daily functioning, productivity, and overall quality of life. Despite extensive research, the underlying pathophysiological mechanisms remain only partially understood. Cortical spreading depression (CSD), a propagating wave of neuronal and glial depolarisation, has been identified as a central process in MwA. This phenomenon is triggered by ion channel dysfunction, leading to elevated intracellular calcium levels and excessive glutamate release, which contribute to widespread cortical hyperexcitability. Genetic studies, particularly involving the CACNA gene family, further implicate dysregulation of calcium channels in the pathogenesis of MwA. Recent advances in neuroimaging, particularly functional magnetic resonance imaging (fMRI), have provided critical insights into the neurophysiology of MwA. These results support the central role of CSD as a basic mechanism behind MwA and imply that cortical dysfunction endures beyond brief episodes, possibly due to chronic neuronal dysregulation or hyperexcitability. The visual cortex of MwA patients exhibits activation patterns in comparison to other neuroimaging studies, supporting the possibility that it is a disease-specific biomarker. Its distinctive sensory and cognitive characteristics are influenced by a complex interplay of cortical, vascular, and genetic factors, demonstrating the multifactorial nature of MwA. We now know much more about the pathophysiology of MwA thanks to the combination of molecular and genetic research with sophisticated neuroimaging techniques like arterial spin labelling (ASL) and fMRI. This review aims to synthesize current knowledge and analyse molecular and neurophysiological targets, providing a foundation for developing targeted therapies to modulate cortical excitability, restore neural network stability, and alleviate the burden of migraine with aura. The most important and impactful research in our field has been the focus of this review, which highlights important developments and their contributions to the knowledge and treatment of migraine with aura.