Gray matter alteration in medication overuse headache: a coordinates-based activation likelihood estimation meta-analysis

Abstract

Medication overuse headache (MOH) is a prevalent secondary headache, bringing heavy economic burden and neuropsychological damage. Neuroimaging studies on the disease reported divergent results. To merge the reported neuroimaging alterations in MOH patients and explore a pathophysiological mechanism of this disorder. A meta-analytic activation likelihood estimation (ALE) analysis method was used. We systematically searched English and Chinese databases for both morphological and functional neuroimaging studies published before Nov 18, 2021. Reported altered brain regions and the stereotactic coordinates of their peaks were extracted and pooled by GingerALE using Gaussian probability distribution into brain maps, illustrating converged regions of alteration among studies. We identified 927 articles, of which five studies on gray matter changes, using voxel-based morphometry (VBM) were eventually included for ALE analysis, with 344 subjects and 54 coordinates put into GingerALE. No functional magnetic resonance imaging (fMRI) or positron emission topography (PET) studies were included for pooling. Compared with healthy controls (HCs), MOH featured increased gray matter density in midbrain, striatum, cingulate, inferior parietal cortex and cerebellum (P < 0.001 uncorrected), whereas decreased gray matter density in orbitofrontal cortex (P < 0.05, family-wise error), frontal, insular and parietal cortices (P < 0.001 uncorrected). Withdrawal of analgesics led to decreased gray matter density in superior temporal gyrus, cuneus, midbrain and cerebellum (P < 0.001 uncorrected). This meta-analysis confirmed that medication overuse headache is associated with morphologic alteration in the reward system, the prefrontal cortex and a reversible modification in the pain network. Further functional imaging paradigms and longitudinal studies are required for a more definite conclusion and a causal mechanism.

The Role of the Insula in Chronic Pain and Associated Structural Changes: An Integrative Review

“…The use of medication to treat chronic pain can lead to structural changes in the insula. Chen et al reported gray matter increases in the periaqueductal gray and the trigeminal afferent area in the midbrain, thalamus, and cerebellum, while a decrease in gray matter was noted in the insula in medication overuse for headache [ 44 ]. Research has indicated that migraine alters the activity of brain structures involved in memory processing and consolidation, including the insula [ 43 , 45 ].…”

A Survey of Deep Learning for Alzheimer’s Disease

“…After ROI extraction, the reviewed studies commonly use GM tissue mean intensities, or volumes, of brain ROIs as features from PET, MRI, fMRI or other modalities [198]. Other measures include subcortical volumes [199,200], grey matter densities [201,202], cortical thickness [203,204], brain glucose metabolism [205,206], cerebral amyloid-β accumulation [207,208], and the average regional CMRGlc [209] for PET. The hippocampus is of particular interest in the reviewed papers; ROI-based methods have used 3D data and morphological measurements of its cortical thickness, curvature, surface area, and volume.…”