Hypothalamic connectivity strength is decreasing with polygenic risk in migraine without aura patients

Migraine is a heritable primary headache disorder which pathophysiology involves altered hypothalamic activity during migraine attacks. To explore the relationship between hypothalamic functional connectivity (HYPT FC) and genetic predisposition characterised by polygenic risk scores (PRS), in migraine, this research examines two types of PRS: one based on all migraine patients (PRS_ALL) regardless of their time of diagnosis and other disorders, and another on migraine-first patients (PRS_FIRST), whose first diagnosed condition was migraine in their lifetime. In an independent sample of 35 migraine patients and 38 healthy controls, using resting-state functional magnetic resonance (rfMRI, 3T) brain imaging, the study reveals significant hypoconnectivity of hypothalamus with the two investigated PRS scores but with different brain areas. While weakened hypothalamic connections in relations with PRS_ALL highlight regions involved in pain modulation, correlation with PRS_FIRST emphasizes decreased connections with sensory and integrative brain areas, suggesting a link between migraine-first genetic risk and cortical hyperexcitability. Our results demonstrate that the polygenic risk of different migraine subgroups may advance our insight into the specific genetic and neural underpinnings of migraine, advancing precision medicine approaches in this field.