Abstract / Summary
Migraine aura is a heterogeneous phenomenon in which visual symptoms predominate, while a substantial proportion of patients also experience somatosensory and, more rarely, dysphasic or motor manifestations. While neurovascular coupling (NVC) abnormalities within the visual cortices in migraine with aura (MwA) have recently been implicated as a potential mechanism facilitating cortical spreading depression (CSD) ignition, it is still unclear whether impaired NVC extending beyond visual areas may contribute to CSD propagation and, therefore, to the broader symptomatology characterizing complex aura phenotypes. Forty patients with MwA (21 simple visual MwA, 19 complex MwA) and 30 patients with migraine without aura (MwoA) underwent multimodal 3T MRI during the interictal period, including resting-state functional MRI (fMRI) and multi-delay arterial spin labeling (ASL). Twenty-two healthy controls underwent the same MRI protocol. Regional NVC was estimated by computing the correlation coefficient between z-scored regional homogeneity (ReHo), a measure of local neural function, and z-scored cerebral blood flow (CBF), a measure of cerebral perfusion, derived from resting-state fMRI and multi-delay ASL imaging, respectively. Compared with both patients with MwoA and HC, patients with either simple or complex MwA showed a significant NVC reduction within left visual cortical parcels (VIS-4 and VIS-5). In addition, patients with complex aura exhibited a selective NVC reduction within the precuneus–posterior cingulate cortex compared with patients with simple visual aura, MwoA, and HC. Patients with MwA exhibit persistent reduced interictal NVC within the left visual cortical parcels (VIS-4 and VIS-5), irrespective of aura complexity, suggesting the changes in perfusion–function matching as potentially associated with susceptibility to CSD initiation. In patients with complex aura, the reduced NVC extends beyond the left visual cortical parcels (VIS-4 and VIS-5) to involve the precuneus–posterior cingulate cortex, a central hub of the default mode network characterized by exceptionally high baseline metabolic demand and extensive structural and functional connectivity with somatosensory and motor cortices. Such changes in perfusion–function matching within this multimodal hub may identify a network-level vulnerability which could facilitate CSD anterior propagation, thereby providing a plausible mechanistic substrate for the broader clinical manifestations of complex aura.