Static and dynamic functional connectivity of the bilateral insula in patients with migraine without aura: a resting-state fMRI study
Abstract
Objective To investigate alterations in resting-state functional connectivity (rs-FC) and the standard deviation of dynamic functional connectivity (dFCstd) of the bilateral insula in patients with migraine without aura (MwoA), and to examine their associations with clinical symptoms. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) was conducted on 45 patients with MwoA and 45 healthy controls (HCs). The left and right insulae were defined as seed regions according to the AAL116 atlas. rs-FC and dFCstd were calculated between each insular seed and the remaining 115 brain regions, with dFCstd defined as the standard deviation of Fisher-z transformed connectivity estimates across sliding windows. Group differences were evaluated with general linear models adjusted for age and sex, with false discovery rate (FDR) correction applied for multiple comparisons. Associations between altered functional connectivity and clinical measures were further examined within the MwoA group. Results Patients with MwoA had higher rs-FC than HCs for the left and right insulae with the right hippocampus. Dynamic connectivity analysis identified lower dFCstd involving the left insula and ipsilateral caudate nucleus and higher dFCstd involving the left insula and ipsilateral superior frontal gyrus, orbital part. All group differences survived FDR correction. Exploratory correlation analyses showed that several altered connectivity measures were associated with monthly migraine attack frequency, visual analog scale (VAS) scores, and Self-Rating Depression Scale (SDS) standard scores. Conclusion Combined rs-FC and dFCstd analyses revealed altered functional connectivity involving the insula in patients with MwoA. These connectivity patterns may reflect disturbances in neural circuits supporting pain processing, emotion regulation, and cognitive control, providing complementary imaging evidence for brain network dysfunction in MwoA.