Uncovering longitudinal changes in the brain functional connectome along the migraine cycle: a multilevel clinical connectome fingerprinting framework

Background: Changes in large-scale brain networks have been reported in migraine patients, but it remains unclear how these manifest in the various phases of the migraine cycle. Case-control fMRI studies spanning the entire migraine cycle are lacking, precluding a complete assessment of brain functional connectivity in migraine. Such studies are essential for understanding the inherent changes in the brain of migraine patients as well as transient changes along the cycle. Here, we leverage the concept of functional connectome (FC) fingerprinting, whereby individual subjects may be identified based on their FC, to investigate changes in FC and its stability across different phases of the migraine cycle. Methods: 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 functional magnetic resonance imaging (fMRI). We propose a novel multilevel clinical connectome fingerprinting approach to analyse the FC identifiability not only within-subject, but also within-session and within-group. Results: This approach allowed us to obtain individual FC fingerprints by reconstructing the data using the first 19 principal components to maximize identifiability at all levels. We found decreased FC identifiability for patients in the preictal phase relative to controls, which increased with the progression of the attack and became comparable to controls in the interictal phase. Using Network-Based Statistic analysis, we found increased FC strength across several brain networks for patients in the ictal and postictal phases relative to controls. Conclusion: Our novel multilevel clinical connectome fingerprinting approach captured FC variations along the migraine cycle in a case-control longitudinal study, bringing new insights into the cyclic nature of the disorder.