Neurology. 2026 Mar 10;106(5):e214656. doi: 10.1212/WNL.0000000000214656. Epub 2026 Feb 6.
ABSTRACT
BACKGROUND AND OBJECTIVES: fMRI has proven useful in dissecting the neurobiological underpinnings of migraine. However, the existing evidence is limited by small samples, use of suboptimal statistical thresholds, and different methods of clinical data acquisition. Given these limitations, we hypothesized that a large, well-characterized sample would allow a clearer distinction between resting-state functional connectivity (rs-FC) alterations specific to migraine and those related to migraine subtypes.
METHODS: Adults with migraine and age-matched and sex-matched healthy controls (HCs) underwent a single 3T rs-fMRI scan. We compared rs-FC between migraine and HCs, and across migraine subtypes, using multi-voxel pattern and seed-based analysis. General linear models and analysis of covariance tests with Bonferroni-adjusted cluster-wise family-wise error correction (pFWE-Bonferroni ≤0.001) were applied. rs-FC measures, expressed as Z scores, were also compared across migraine subtypes using general linear models (pBonferroni < 0.05).
RESULTS: We analyzed rs-fMRI data from 264 participants with migraine (mean age 42 ± 12 years, 234 women) and 151 HCs (mean age 41 ± 11 years, 130 women). The multi-voxel pattern analysis identified significant rs-FC differences in a cluster within the bilateral middle cingulate cortex when comparing participants with migraine to HCs (pFWE-Bonferroni <0.001). The seed-based analysis revealed that participants with migraine had increased rs-FC between the cluster in the bilateral middle cingulate cortex and both the right lateral occipital cortex and bilateral occipital pole (both pFWE-Bonferroni <0.001), compared with HCs. Furthermore, increased rs-FC was identified between the limbic lobe and the right occipital pole (pFWE-Bonferroni = 0.0014) and precuneus (pFWE-Bonferroni <0.001). The cingulate-occipital rs-FC was consistently increased in participants with migraine, irrespective of the migraine subtype (pBonferroni <0.001). In addition, ictal participants who were scanned during attacks exhibited an increased hypothalamic rs-FC with the bilateral precuneus, compared with HCs (pBonferroni <0.001). No significant associations emerged between rs-FC and clinical features in migraine.
DISCUSSION: The identified rs-FC alterations between the middle cingulate cortex and occipital regions might represent a migraine-specific trait, suggesting an integration of nociceptive and visual processing. This discovery provides novel insights into the neurobiological underpinnings of migraine and proposes that altered cingulate-occipital rs-FC might serve as a potential biomarker for migraine.
PMID:41650361 | DOI:10.1212/WNL.0000000000214656
