Increased amygdala volume and functional connectivity with cognitive control networks in chronic migraine

ABSTRACT Objective To characterize the role of the amygdala in episodic (EM) and chronic (CM) migraine, we evaluated amygdala volumes, functional connectivity (FC), and associations with clinical and affective measures. Methods Eighty-eight patients (44 with EM and 44 age- and sex-matched patients with CM) completed anatomical and resting-state functional MRI scans. Amygdala volumes and resting-state FC to three core large-scale cognitive control networks (default mode (DMN), salience (SN), central executive (CEN)) were compared between groups. Associations between amygdala volume and FC, measures of headache severity (frequency and intensity), and cognitive-affective measures (depression, anxiety, pain catastrophizing) were evaluated. Results Compared to EM, patients with CM had larger amygdala volume bilaterally. Headache frequency and intensity were associated with increased left and right amygdala volume, and depression was associated with increased right amygdala volume. Patients with CM also demonstrated increased left amygdala FC with the DMN, which across patients was related to headache frequency. Left amygdala FC to the SN was correlated with headache intensity while right amygdala FC to the CEN was correlated with pain catastrophizing. Conclusion Our findings reveal increased amygdala volume and FC with large-scale neurocognitive networks in patients with CM compared to EM. Aberrant amygdala volume and FC measures were associated with increased migraine severity, depression, and pain catastrophizing, pointing to a link between emotion and pain in migraine. Our findings provide novel insights into amygdala involvement in chronic migraine and may inform future interventions aimed at preventing the progression of both headache and its negative cognitive-affective symptoms.