Abstract
BACKGROUND: Migraine is a complex sensory processing disorder marked by dysfunctions in both exteroception and interoception. The high frequency of emotional comorbidities suggests significant abnormalities in emotional processing. Persistent interoceptive abnormalities, indicated by widespread homeostatic disturbances, may be a crucial link between migraine and its associated emotional disorders. However, the specific neural mechanism underlying this altered interoception and abnormal emotional function remains under-explored. This study used task-based functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms of interoceptive dysfunction and aberrant emotional processing in migraine and to examine their potential interplay. METHODS: We recruited 29 patients with episodic migraine (EMs) and 31 healthy controls (HCs). Participants underwent fMRI while performing two interoceptive attention tasks (focusing on heartbeat and breathing) and two negative emotion recall tasks (involving pain and anxiety). Statistical analyses included group-level activation mapping, between-group comparisons, generalized psychophysiological interaction (gPPI) for task-modulated functional connectivity, and correlations with clinical characteristics. RESULTS: Migraine patients exhibited dysfunction within the prefrontal cortex (PFC) during both interoceptive and emotional tasks. During heartbeat attention, patients showed significant hypoactivation in the right superior frontal gyrus (SFG) and reduced functional connectivity between the SFG and frontal pole (FP) compared to controls. This SFG hypoactivation was correlated with greater headache intensity. Conversely, during anxiety recall, patients displayed hyperactivation in the left medial orbitofrontal cortex (mOFC) and enhanced functional connectivity from the mOFC to the SFG. Notably, the degree of mOFC hyperactivation was negatively correlated with depression and anxiety scores. CONCLUSIONS: Our results provide experimental fMRI evidence that migraine involves abnormal interoceptive and emotional processing, with a core dysfunction localized to circuits within the prefrontal cortex. This disrupted PFC activity suggests a fundamental dysregulation in the transformation of bodily signals into conscious awareness. Furthermore, the mOFC-SFG pathway may serve as a key neural substrate mediating the interplay between these interoceptive and emotional abnormalities. CLINICAL TRIAL NUMBER: Not applicable.