Abnormal neurovascular coupling in the precuneus associated with migraine chronification: A multimodal magnetic resonance imaging study

Background Neurovascular coupling (NVC) reflects the interaction between cerebral blood flow (CBF) and functional activity. However, the relationship between NVC and migraine chronification remains unclear. This study investigated the state of NVC in migraine patients and evaluated its potential as an imaging feature for migraine chronification using arterial spin labeling (ASL) combined with resting-state functional magnetic resonance imaging (rs-fMRI). Methods This was a cross-sectional study. Thirty-nine episodic migraine (EM), 61 chronic migraine (CM) patients (25 with medication overuse headache, MOH) and 42 healthy controls (HCs) were recruited in the same period. Imaging data were acquired using a 3.0 T MRI. Regional homogeneity (ReHo) represented functional activity, whereas CBF was quantified via ASL. Correlation coefficient between CBF and ReHo values of each participant in voxel level represented the whole-brain NVC status, whereas the CBF/ReHo ratio represented regional NVC status. Correlations between NVC metrics and clinical characteristics were analyzed in CM patients. Exploratory mediation analysis was conducted to identify mediators between NVC alterations and the clinical characteristics of CM patients. Finally, receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic performance of NVC metrics for migraine chronification. Results Compared to HCs, both EM and CM patients presented significantly reduced whole-brain CBF-ReHo coupling. Compared to EM patients, CM patients presented a decreased CBF/ReHo ratio in the right precuneus. Correlation analysis revealed that z value of the CBF/ReHo ratio in the right precuneus was negatively correlated with both HIT-6 score and PHQ-9 score; HIT-6 score was positively correlated with PHQ-9 score in CM group. Exploratory mediation analysis indicated that depression mediated the relationship between abnormal NVC and clinical characteristics in CM patients. Finally, ROC curve indicated that the CBF/ReHo ratio in the right precuneus (AUC = 0.75) exhibited high sensitivity and specificity in distinguishing CM from EM patients. Conclusion Abnormal NVC in the precuneus was involved in migraine chronification, with depression potentially serving as a mediator in this process. NVC metric may serve as an imaging feature for migraine chronification in the future.