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Abstract Background Migraine is a complex disorder characterized by debilitating headaches. Despite its prevalence, its pathophysiology remains unknown, with subsequent gaps in diagnosis and treatment. We combined machine learning with connectivity analysis and applied a whole-brain network approach to identify potential targets for migraine diagnosis and treatment. Methods Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI(rfMRI), and diffusion weighted scans were obtained from 31 patients with migraine, and 17 controls. A recently developed machine learning technique, Hollow Tree Super (HoTS) was used to classify subjects into diagnostic groups based on functional connectivity (FC) and derive networks and parcels contributing to the model. PageRank centrality analysis was also performed on the structural connectome to identify changes in hubness. Results Our model attained an area under the receiver operating characteristic curve (AUC-ROC) of 0.68, which rose to 0.86 following hyperparameter tuning. FC of the language network was most predictive of the model’s classification, though patients with migraine also demonstrated differences in the accessory language, visual and medial temporal regions. Several analogous regions in the right hemisphere demonstrated changes in PageRank centrality, suggesting possible compensation. Conclusions Although our small sample size demands caution, our preliminary findings demonstrate the utility of our method in providing a network-based perspective to diagnosis and treatment of migraine.