Neuroimaging differences between chronic migraine with and without medication overuse headache: a 7 Tesla multimodal MRI study

BACKGROUND: Chronic migraine (CM) patients with medication overuse headache (MOH) exhibit distinct neurobiological alterations compared to those without MOH. However, prior studies, often limited to single imaging modalities, have yielded inconsistent findings. This study employs multimodal MRI-combining structural, diffusion tensor, and functional imaging-to characterize brain abnormalities in CM patients with and without MOH, while investigating the relationship between acute analgesic use frequency and these changes. METHODS: The study employed comparative analyses to examine differences in gray matter volume, white matter integrity, and spontaneous brain activity between CM patients with (CM + MOH) and without (CM - MOH) medication overuse headache, as well as healthy controls. Additionally, brain regions associated with the frequency of acute medication use were identified and further investigated. RESULTS: Nineteen CM - MOH patients, twenty-five CM + MOH patients, and nineteen healthy controls were enrolled. Compared to CM - MOH patients, CM + MOH patients exhibited significantly reduced gray matter volume in the parahippocampal gyrus and middle occipital gyrus, alongside markedly lower fractional anisotropy (FA) in the left cingulum bundle. Moreover, fractional amplitude of low-frequency fluctuations (fALFF) values in the right putamen were significantly decreased and demonstrated a negative correlation with the frequency of acute pain medication use. Functional connectivity analysis further revealed significantly enhanced connectivity between the right putamen and regions such as the frontal lobe, middle cingulate gyrus, lingual gyrus, and precuneus, which positively correlated with the frequency of acute analgesic use. CONCLUSION: Compared to CM - MOH patients, those with MOH exhibit distinct patterns of gray matter volume reduction in regions associated with memory and visual processing, accompanied by significant white matter disruption. Additionally, decreased spontaneous activity in the right putamen and heightened functional connectivity between the putamen and multiple brain regions are strongly correlated with the frequency of acute medication use. These results highlight the significant impact of medication overuse on brain structure and function, shedding light on the mechanisms of migraine chronification.