Functional MRI and Diffusion Tensor Imaging in Migraine: A Review of Migraine Functional and White Matter Microstructural Changes

Abstract

Migraine is a complex and heterogenous disorder whose disease mechanisms remain disputed. This narrative review summarizes functional MRI (fMRI) and diffusion tensor imaging (DTI) findings and interprets their association with migraine symptoms and subtype to support and expand our current understanding of migraine pathophysiology. Our PubMed search evaluated and included fMRI and DTI studies involving comparisons between migraineurs vs healthy controls, migraineurs with vs without aura, and episodic vs chronic migraineurs. Migraineurs demonstrate changes in functional connectivity (FC) and regional activation in numerous pain-related networks depending on migraine phase, presence of aura, and chronicity. Changes to diffusion indices are observed in major cortical white matter tracts extending to the brainstem and cerebellum, more prominent in chronic migraine and associated with FC changes. Reported changes in FC and regional activation likely relate to pain processing and sensory hypersensitivities. Diffuse white matter microstructural changes in dysfunctional cortical pain and sensory pathways complement these functional differences. Interpretations of reported fMRI and DTI measure trends have not achieved a clear consensus due to inconsistencies in the migraine neuroimaging literature. Future fMRI and DTI studies should establish and implement a uniform methodology that reproduces existing results and directly compares migraineurs with different subtypes. Combined fMRI and DTI imaging may provide better pathophysiological explanations for nonspecific FC and white matter microstructural differences.

Keywords: Migraine; aura; chronic; diffusion tensor imaging; functional MRI.

Figure 1.

Flow chart of literature search performed for functional MRI and diffusion tensor imaging studies in migraine.

Figure 2.

Resting state functional MRI data comparing migraineurs without aura (MwoA) and healthy controls (HC). (A) Spatial group maps of 3 pain-related intrinsic connectivity networks (ICN), including the default mode network (DMN), central executive network (CEN) split into right (rCEN) and left (lCEN), and salience network (SN). (B) Group comparison maps of functional connectivity (FC) in the DMN, CEN, and SN (P < .05, family-wise error or FWE corrected). Against HCs, MwoA demonstrate DMN with increased FC to left and right anterior insula (lAI, rAI); rCEN with increased FC to right middle frontal gyrus (rMFG) and right anterior insula (rAI); lCEN with increased FC to left inferior frontal gyrus (lIFG); SN with decreased FC to right supplementary motor area (rSMA). Reprinted from “Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI,” by Xue T, Yuan K, Zhao L, et al, 2012, PLoS ONE, 7(12), e52927. DOI: 10.1371/journal.pone.0052927. Copyright (2012) by PLOS One. Permission under the Creative Commons CC BY license. http://creativecommons.org/licenses/by/4.0/.

Figure 3.

Group comparison of blood oxygen level-dependent (BOLD) response in advanced visual network (including lingual gyrus, inferior parietal lobe, inferior frontal gyrus, and medial frontal gyrus) between migraineurs with aura (MwA), migraineurs without aura (MwoA), and healthy controls during trigeminal heat stimulation. Increased BOLD activation observed in MwA. Reprinted from “Advanced visual network and cerebellar hyperresponsiveness to trigeminal nociception in migraine with aura,” by Russo A, Tessitore A, Silvestro M, et al, 2019, J Headache Pain, 20(1), 46. DOI: 10.1186/s10194-019-1002-3. Copyright (2019) by BioMed Central. Permission under the Creative Commons CC BY license. http://creativecommons.org/licenses/by/4.0/.

Figure 4.

Reduced fractional anisotropy is found in the genu and splenium of the corpus callosum in migraineurs without aura compared to healthy controls, using tract-based spatial statistics (TBSS) analysis. The normal white matter skeleton is shown in green, and voxels with significant differences are shown as red-yellow. Reprinted from “Reduced fractional anisotropy of corpus callosum modulates inter-hemispheric resting state functional connectivity in migraine patients without aura,” by Yuan K, Qin W, Liu P, et al, 2012, PLoS One, 7(9), e45476. DOI: 10.1371/journal.pone.0045476. Copyright (2012) by PLoS One. Original image cropped to include top half only. Permission under the Creative Commons CC BY license. http://creativecommons.org/licenses/by/4.0/.

Figure 5.

Reduced axial diffusivity (AD) is found in 44 regions in the Johns Hopkins University ICBM-DTI-81 White Matter Atlas and White-Matter Tractography Atlas in chronic migraineurs (CM) compared to episodic migraineurs (EM). The normal white matter skeleton is shown in green, and voxels with significant differences are shown as red-yellow. Reprinted from “White matter changes in chronic and episodic migraine: a diffusion tensor imaging study,” by Planchuelo-Gómez Á, García-Azorín D, Guerrero ÁL, et al, 2020, J Headache Pain, 21(1), 7. DOI: 10.1186/s10194-019-1071-3. Copyright (2020) by BioMed Central. Original image cropped to include top half only. Permission under the Creative Commons CC BY license. http://creativecommons.org/licenses/by/4.0/.