To explore resting state (RS) effective connectivity (EC) abnormalities between the pons and hypothalamus in episodic migraine patients during the interictal phase and investigate their value in predicting migraine progression over the years.

Functional magnetic resonance imaging (fMRI) studies showed a significant interaction between the pons and hypothalamus during the pain phase of migraine. However, how these regions interact with each other during the interictal phase and whether the pontine-hypothalamic RS EC could influence migraine disease activity has never been investigated.

Ninety patients with episodic migraine and seventy-two controls underwent baseline interictal RS fMRI. Clinical evaluation was performed after a median of 4.5 years in 23 patients. RS EC of bilateral pons and hypothalamus was performed using SPM12 and dynamic causal modelling. RS EC differences between groups at baseline were investigated using parametric empirical bayes models. Linear regression models were used to identify imaging predictors of disease progression, as measured by changes in migraine frequency.

At baseline, compared to controls, migraine patients had (posterior probability>0.75) higher inhibitory EC within the left pons and from the right and left pons to the ipsilateral and contralateral hypothalamus. Migraine patients experienced also a lower inhibitory EC from the left hypothalamus to the left pons, as well as a lower excitatory EC from the right pons to the left pons. During the follow-up, 35% of patients reported an increased number of migraine attacks. Higher inhibitory RS EC from the left pons to the left (β=0.4, p=0.04) and right (β=0.5, p=0.02) hypothalamus predicted clinically worsening.

During the interictal phase, migraine patients experience a prominent inhibitory influence of the pons over the hypothalamus, while the inhibitory influence of the hypothalamus over the pons is reduced. A higher pontine-hypothalamic inhibitory activity may be a prognostic marker for migraine progression over the years.