Altered dorsal anterior insula functional connectivity underlying abnormal interoceptive accuracy awareness in migraine without aura

BACKGROUND: Abnormal interoception is increasingly recognized as a key feature of migraine. The dorsal anterior insula (dAI) is hypothesized to play a central role in interoceptive processing, yet the neural mechanisms underlying this abnormality remain unclear. We aimed to investigate interoceptive disturbances in migraine and to clarify the role of insula dysfunction, specifically dAI functional connectivity, in underlying these interoceptive alterations and potentially contributing to the pathophysiology of migraine. METHODS: We recruited 29 patients with migraine without aura and 32 matched healthy controls. All participants completed evaluations of interoceptive accuracy and resting-state functional magnetic resonance imaging scans. We applied a multivariate seed-based connectivity approach to examine the direct connectivity of the bilateral dAI and its link to interoceptive awareness in migraine patients. We conducted a simple mediation analysis to determine whether specific dAI connectivity mediated variations in interoceptive awareness across groups. Finally, serial multiple mediation analysis was applied to explore whether these effects were conveyed via subjective or objective accuracy metrics. RESULTS: Migraine patients showed significantly enhanced interoceptive accuracy awareness compared with controls. Across all participants, this awareness was positively associated with functional connectivity from the right dAI to the bilateral precentral gyrus (PreCG). Crucially, this specific right dAI-bilateral PreCG connectivity was markedly enhanced in migraine patients. Simple mediation results indicated that increased dAI connectivity substantially mediated the group difference in interoceptive accuracy awareness. Serial multiple mediation analysis revealed that this effect was predominantly driven by objective interoceptive processing. CONCLUSIONS: The observed altered dAI connectivity and its relationship with interoceptive awareness suggest that dysfunctions in interoceptive processes, particularly within the dAI-PreCG network, may be integral to the neuropathology of migraine.