Structural connectivity changes in migraine involving the cerebellum

Objective: Although the pathophysiology of migraine remains poorly understood, structural disruptions across brain networks have been reported. Migraine connectivity studies primarily focus on cortical networks, neglecting crucial subcortical (SC) regions like the thalamus and the cerebellum (CB), which are known to play a significant role in migraine pathophysiology. Here, we investigate structural connectivity in a group of episodic migraine patients without aura compared to controls using diffusion-weighted MRI (dMRI). Methods: Multi-shell dMRI data was acquired in Hospital da Luz Lisboa and structural connectivity was determined using two brain parcellations (Schaefer+SC+CB and AAL116). The connectivity was assessed using the network-based statistics (NBS) toolbox and graph metrics were calculated including the global efficiency (GE) and the characteristic path length (L) and their correlation with clinical data. Groups were compared using the Wilcoxon Rank Sum Test. A p-value of 0.05 was considered significant. Results: Results showed significant connectome differences in patients, with increased structural connectivity between the left crus and left posterior lobe of the cerebellum (PLC) and between the occipital lobe/ visual network and cerebellar regions (Figure 1). Patients showed decreased L and increased GE in both parcellations (Figure 2), with a positive correlation (r=0.56) between L and disease duration (Figure 3). The cerebellum plays an inhibitory role in pain processing, having several connections to the prefrontal cortex (via the thalamus). The increased connectivity between the cerebellum and other regions may indicate a dysfunctional negative feedback loop where the inhibitory signal is not sensed by the thalamus. The decreased L and increased GE can be indicative of higher pain information dissemination in the brain circuitry. Conclusion: These results showcase cerebellum’s importance in migraine pathophysiology, highlighting the necessity of including it in connectome studies.