Background: The objective of this study was to identify functional and structural alterations that differentiate cluster headache (CH) from migraine and address their aberrant imaging features to distinguish from healthy controls.
Methods: Clinical and MRI data were obtained from 87 CH patients, 166 migraineurs (26 with aura and 140 without aura) and 115 healthy controls using a 7T MR system. Between-group differences in the resting-state functional MRI, DTI and T1-weighted structural images were analyzed. Furthermore, the correlation between imaging features and clinical characteristics were explored.
Results: Independent component analysis showed that, compared to controls, CH patients presented decreased fluctuation within auditory network, whereas migraineurs presented decreased fluctuation within default mode network and lateral visual network, and increased fluctuation within salience network (FDR corrected p < 0.05). In comparison with controls, both CH patients and migraineurs had increased connectivity between medial visual network and lateral visual network, and CH patients also had increased connectivity between visual network and somatomotor network (MAFDR corrected p < 0.05). Consistent with inter-network findings, functional connectivity analysis based on anatomical atlas revealed that both CH patients and migraineurs had increased connectivity between brain areas mediating sensory-motor and perceptual information processing. Compared to migraineurs, CH patients had increased functional connectivity among limbic brain regions (FDR corrected p < 0.05). Structural connectivity analysis found that CH patients had increased fiber number between right lentiform nucleus and right cerebellum, and generally decreased fiber number among cerebellar regions (FDR corrected p < 0.05). The vertex-wise analysis showed that CH patients presented reduced cortical thickness in clusters located in the left pericalcarine and right lateraloccipital, compared to both controls and migraineurs (Monte-Carlo cluster corrected p < 0.05). In CH patients, attack duration was negatively correlated with the functional connectivity between medial visual network and lateral visual network, as well as functional connectivity between right calcarine gyrus and right fusiform gyrus. In headache patients, cortical thickness in the left pericalcarine was positively correlated with attack duration and negatively correlated with NRS score (the absolute value of r > 0.2 and p < 0.05).
Conclusions: Generally increased functional connectivity, including between functional networks and between anatomical brain regions, is shared by CH patients and migraineurs. The increased functional connectivity among limbic brain regions and reduced cortical thickness in associated areas may differentiate CH from migraine, potentially reflecting their distinct nociceptive mechanisms.
Keywords: 7T MRI; Biomarkers; Cluster headache; Migraine; Neuroimaging.
© 2026. The Author(s).