Reduced insula habituation associated with amplification of trigeminal brainstem input in migraine

Background Impaired sensory processing in migraine can reflect diminished habituation, increased activation, or even increased gain or amplification of activity from the primary synapse in the brainstem to higher cortical/subcortical brain regions. Methods We scanned 16 episodic migraine (interictal) and 16 healthy controls (cross-sectional study), and evaluated brain response to innocuous air-puff stimulation over the right forehead in the ophthalmic nerve (V₁) trigeminal territory. We further evaluated habituation, and cortical/subcortical amplification relative to spinal trigeminal nucleus (Sp5) activation. Results Migraine subjects showed greater amplification from Sp5 to the posterior insula and hypothalamus. In addition, while controls showed habituation to repetitive sensory stimulation in all activated cortical regions (e.g. the bilateral posterior insula and secondary somatosensory cortices), for migraine subjects, habituation was not found in the posterior insula. Moreover, in migraine, the habituation slope was correlated with the amplification ratio in the posterior insula and secondary somatosensory cortex, i.e. greater amplification was associated with reduced habituation in these regions. Conclusions These findings suggest that in episodic migraine, amplified information processing from spinal trigeminal relay nuclei is linked to an impaired habituation response. This phenomenon was localized in the posterior insula, highlighting the important role of this structure in mechanisms supporting altered sensory processing in episodic migraine.