AbstractThe pathophysiology of migraine as a headache disorder is still undetermined. Diffusion tensor imaging (DTI) has significantly improved our knowledge about brain microstructure in this disease. Here, we aimed to systematically review DTI studies in migraine and survey the sources of heterogeneity by investigating diffusion parameter changes associated with clinical characteristics and migraine subtypes. Microstructural changes, as revealed by widespread alteration of diffusion metrics in white matter (WM) tracts, subcortical and cortical regions, were reported by several migraine DTI studies. Specifically, we reported changes in the corpus callosum, thalamic radiations, corona radiata, and brain stem. These alterations showed high variability across migraine cycle phases. Additionally, migraine associated with depressive/anxiety symptoms revealed significant changes in the corpus callosum, internal capsule, and superior longitudinal fasciculus. No significant WM microstructural differences were observed between migraine patients with and without aura. Overall, differences between chronic and episodic migraine showed inconsistency across studies. Migraine is associated with microstructural changes in widespread regions including thalamic radiations, corpus callosum, and brain stem. These alterations can highlight neuronal damage and neuronal plasticity mechanisms either following pain stimulations occurring in migraine cycle or as a compensatory response to pain in chronic migraine. Longitudinal studies applying advanced modalities may shed new light on the underlying microstructural changes in migraine subtypes.