Alterations in Effective Connectivity of the Hippocampus in Migraine without Aura

Purpose: Neuroimaging studies on migraine have revealed structural and functional altera-tions in the hippocampus, a region involved in pain processing and stress response. This study was designed to investigate whether effective connectivity of this region is disrupted in migraine and relates to chronicity of this disease. Patients and Methods: In 39 episodic migraine (EM) patients, 17 chronic migraine (CM) patients, and 35 healthy controls, we investigated differences in the directional influences between the hippocampus and the rest of the brain by combining resting-state functional magnetic resonance imaging and Granger causality analysis (GCA), with bilateral hippo-campus as seed regions. The associations between directional influences and the clinical variables were also examined. Results: Comparing each patient group to the control group, we found increased and decreased negative influence on the hippocampus exerted by the bilateral visual areas and right dorsolateral prefrontal cortex (dlPFC), respectively. The hippocampus showed increased positive influence on the right posterior insula and medial prefrontal cortex (mPFC), as well as increased negative influence on the left cerebellum in CM patients relative to EM patients and healthy controls. Furthermore, across all patients, the migraine frequency exhibited a positive and negative association with causal influence from the hippocampus to mPFC and left cerebellum, respectively. Conclusion: Migraine patients have abnormal effective connectivity between the hippo-campus and multiple brain regions involved in the sensory and cognitive processing of pain. Disrupted directional influences to the hippocampus exerted by dlPFC and bilateral visual areas were common features of EM and CM patients. Directional influences from the hippocampus to mPFC and left cerebellum may be useful imaging biomarkers for assessing migraine frequency.