Multilevel clinical fingerprinting: uncovering longitudinal changes in the functional connectome of the brain along the migraine cycle

Migraine is a common neurological disorder characterized by recurrent headache episodes alternating with symptom-free periods, which has been associated with alterations across large-scale functional brain networks albeit with variable findings. Critically, despite the cyclic nature of the disorder, longitudinal studies spanning the various phases of the migraine cycle are scarce. Here, we leverage the identifiability of individual functional connectomes (FC) to investigate changes along the migraine cycle. For this purpose, we employ a case-control longitudinal design to study a group of 10 patients with episodic menstrual or menstrual-related migraine without aura, in the 4 phases of their spontaneous migraine cycle (preictal, ictal, postictal, interictal), and a group of 14 healthy controls in corresponding phases of the menstrual cycle, using resting-state fMRI. We propose a novel multilevel clinical fingerprinting approach to analyse the differential FC identifiability within-subject, as well as within-session and within-group. The individual FC matrices are then reconstructed with 19 principal components maximizing identifiability at all levels, and analyzed with Network-Based Statistic to identify significant changes in FC strength. We observe decreased FC identifiability for patients in the preictal phase relative to controls, which increases with the progression of the attack and becomes comparable to controls in the interictal phase. Regarding the FC strength, is increased in the ictal and postictal phases relative to controls across several networks. Our novel multilevel clinical fingerprinting approach captures FC variations along the migraine cycle in a case-control longitudinal study, bringing new insights into the cyclic nature of the disorder.