FUNCTIONAL MRI ANALYSIS OF PAIN PROCESSING IN PATIENTS WITH CHRONIC MIGRAINE

Abstract

Chronic migraine remains a disabling condition lacking objective biomarkers to guide personalized treatment. In this problem‐based study, we combined resting‐state and task‐evoked functional MRI with qualitative pain‐experience interviews in 40 adults (mean age 42.3 ± 10.5 years; 12 men) meeting ICHD-3 criteria for chronic migraine. Participants reported a mean of 20.5 ± 3.4 headache days per month (VAS pain intensity 7.2 ± 1.1) and moderate anxiety (HADS-A 8.5 ± 3.2) and depression (HADS-D 7.1 ± 2.8). Resting-state analyses revealed elevated default mode network (DMN) connectivity (z = 0.42 ± 0.15) that correlated with headache frequency (r = 0.48, p = 0.003) and heightened salience-network (SN) coherence (z = 0.35 ± 0.12) that correlated with headache days (r = 0.52, p = 0.001). Sliding-window connectivity demonstrated dynamic SN and DMN fluctuations tracking migraine burden. During thermal nociceptive stimulation, we observed robust anterior insula (t = 6.2) and secondary somatosensory cortex (t = 5.8) activations, with insular responsivity strongly associated with patient-reported pain intensity (r = 0.60, p < 0.001). Qualitative thematic analysis identified catastrophizing as the predominant cognitive–affective theme (25/40 participants), suggesting maladaptive appraisal contributes to chronification. A modest inverse relationship between central executive network connectivity and anxiety scores (r = –0.30, p = 0.050) further implicated affective dysregulation in impaired top-down control. Together, these findings delineate a composite biomarker profile—hyperconnected DMN and SN circuits, exaggerated insular activation, and catastrophizing cognitions—that reliably predicts migraine severity and disability. Our multimodal framework offers translational targets for neuromodulation and cognitive–behavioral interventions and lays the groundwork for longitudinal validation of fMRI‐based biomarkers in chronic migraine management.