Structural Aberrations of the Brain Associated With Migraine

A Narrative Review

Soo-Kyoung Kim MD, PhD; Simona Nikolova PhD; Todd J. Schwedt MD


Headache. 2021;61(8):1159-1179. 

In This Article

Abstract and Introduction


Objective: To summarize major results from imaging studies investigating brain structure in migraine.

Background: Neuroimaging studies, using several different imaging and analysis techniques, have demonstrated aberrations in brain structure associated with migraine. This narrative review summarizes key imaging findings and relates imaging findings with clinical features of migraine.

Methods: We searched PubMed for English language articles using the key words "neuroimaging" AND/OR "MRI" combined with "migraine" through August 20, 2020. The titles and abstracts of resulting articles were reviewed for their possible inclusion in this manuscript, followed by examination of the full texts and reference lists of relevant articles.

Results: Migraine is associated with structural brain aberrations within regions that participate in pain processing, the processing of other sensory stimuli, multisensory integration, and in white matter fiber tracts. Furthermore, migraine is associated with magnetic resonance imaging T2/fluid-attenuated inversion recovery white matter hyperintensities. Some structural aberrations are correlated with the severity and clinical features of migraine, whereas others are not. These findings suggest that some structural abnormalities are associated with or amplified by recurrent migraine attacks, whereas others are intrinsic to the migraine brain.

Conclusions: Migraine is associated with aberrant brain structure. Structural neuroimaging studies contribute to understanding migraine pathophysiology and identification of brain regions associated with migraine and its individual symptoms. Additional work is needed to determine the extent to which structural aberrations are a result of recurrent migraine attacks, and perhaps reversible with effective treatment or migraine resolution, versus being intrinsic traits of the migraine brain.


Neuroimaging is not indicated in patients who have symptoms consistent with migraine when there are no atypical features or warning signs and the neurological examination is normal.[1] When brain imaging is performed, it is done to exclude secondary causes of headache. Incidentally, white matter lesions that are attributed to migraine might be identified, most commonly as white matter hyperintensities (WMHs) on T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences. Even when visual inspection suggests the images are normal, advanced structural and functional analyses often identify subtle aberrations in brain structure and function.

Functional and structural neuroimaging aberrations in migraine are found in brain regions that participate in different aspects of pain processing, processing of other sensory stimuli (e.g., visual regions), and multisensory integration.[2–8] Functional imaging studies performed over the migraine cycle yield insights into which brain regions participate in different phases of the migraine attack, such as attack generation, the premonitory phase, aura, and the headache phase.[9,10] Between migraine attacks, imaging studies identify persistent aberrations in brain function and structure. Some imaging findings might be migraine brain states (e.g., aberrations due to migraine that are reversible with natural improvement in migraine or with migraine therapy), whereas other findings are likely migraine brain traits (e.g., irreversible aberrations).[11–15] Some studies demonstrate correlations between the presence and magnitude of imaging findings with migraine clinical characteristics such as headache frequency, number of years with migraine, and migraine subtypes.[3,16,17] Other structural aberrations seem to be independent from clinical features.[18] Longitudinal imaging studies are beginning to identify brain function and structure that correlate with changes in clinical patterns and with migraine treatment outcomes.[19–21] At the same time, there are also studies that show no structural differences in migraine, including longitudinal investigations.[22–24]

This review aims to provide a summary of the structural brain aberrations associated with migraine, including cross-sectional and longitudinal investigations of gray matter structure, white matter integrity, and WMH. When available, correlations of imaging findings with clinical characteristics are discussed.