Structural Gray Matter Alterations in Chronic Migraine: Implications for a Progressive Disease?

Neeb, Lars; Bastian, Kaili; Villringer, Kersten; Israel, Heike; Reuter, Uwe; Fiebach, Jochen B.

doi:10.1111/head.13012

Cited by 84 publications

(81 citation statements)

References 57 publications

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“…Contrary to the current findings, several studies have found more hippocampal volume in migraine patients and in patients with chronic pain relative to control populations. Hubbard et al 37 and Neeb et al 38 reported more hippocampal volume in migraine patients and more hippocampal volume was reported in a study that investigated the brain morphology in patients with burning mouth syndrome. 39 Results of a meta-analysis of chronic pain studies found the hippocampus to be the only region that had larger volumes in patients compared to controls.…”

Section: Discussionmentioning

confidence: 93%

Structural Co‐Variance Patterns in Migraine: A Cross‐Sectional Study Exploring the Role of the Hippocampus

2017

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Objective To interrogate hippocampal morphology and structural co-variance patterns in migraine patients and to investigate whether structural co-variance patterns relate to migraine disease characteristics. Background Migraine is associated with structural alterations in widespread cortical and subcortical regions associated with the sensory, cognitive, and affective components of pain processing. Recent studies have shown that migraine patients have differences in hippocampal structure and function relative to healthy control subjects, but whether hippocampal structure relates to disease characteristics including frequency of attacks, years lived with migraine and symptoms of allodynia remains unknown. Furthermore, this study investigated hippocampal volume co-variance patterns in migraineurs, an indirect measure of brain network connectivity. Here, we explore differences in hippocampal volume and structural co-variance patterns in migraine patients relative to healthy controls and examine whether these hippocampal measures relate to migraine disease burden. Methods This study included 61 migraine patients and 57 healthy control subjects (healthy controls: median age=34.0, IQR=19.0; migraine patients: median age=35.0, IQR=17.5; p=0.65). Regional brain volumes were automatically calculated using FreeSurfer version 5.3. Symptoms of allodynia were determined using the Allodynia Symptom Checklist 12 (ASC-12). Structural covariance patterns were interrogated using pairwise correlations and group differences in correlation strength were estimated using Euclidian distance. A stepwise regression was used to investigate the relationship between structural co-variance patterns with migraine burden. Results Migraine patients had less left hippocampal volume (healthy controls: left hippocampal volume = 4276.8mm3, SD= 425.3mm3, migraine patients: left hippocampal volume= 4089.5mm3, SD= 453.9mm3, p= 0.02) and less total (right plus left) hippocampal volume (healthy controls: total hippocampal volume= 8690.8mm3, SD= 855.1mm3; migraine patients: total hippocampal volume= 8341.8mm3, SD=917.9mm3; p= 0.03) compared to healthy controls. Migraineurs had stronger structural covariance between the hippocampi and cortico-limbic regions in the frontal lobe (inferior opercular gyrus), temporal lobe (planum temporale, amygdala), parietal lobe (angular gyrus, precuneus,) and the cerebellar white matter. Results of a stepwise regression showed that hippocampal volumes and the interactions between hippocampal volumes with the volumes of other cortico-limbic regions associate with migraine-related allodynia but not with headache frequency or years lived with migraine. Conclusion Migraineurs have less hippocampal volume and stronger hippocampal-cortico-limbic connectivity compared to healthy controls. Hippocampal volumes and measures of hippocampal volume connectivity with other cortico-limbic network regions associate with symptoms of allodynia.

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Section: Discussionmentioning

confidence: 93%

Structural Co‐Variance Patterns in Migraine: A Cross‐Sectional Study Exploring the Role of the Hippocampus

2017

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“…In addition, repeated and long-term migraine attacks may induce functional and structural plastic changes that may underlie the progression of the disorder [8, 9]. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) are advantageous for evaluating structural alterations (such as gray matter volume, cortical thickness and gyrification index [GI]) of the gray matter due to their ability to localize abnormal brain regions in patients without a priori hypothesis [10–12].…”

Section: Introductionmentioning

confidence: 99%

Assessment of gray and white matter structural alterations in migraineurs without aura

Zhang

et al. 2017

J Headache Pain

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BackgroundMigraine constitute a disorder characterized by recurrent headaches, and have a high prevalence, a high socio-economic burden and severe effects on quality of life. Our previous fMRI study demonstrated that some brain regions are functional alterations in migraineurs. As the function of the human brain is related to its structure, we further investigated white and gray matter structural alterations in migraineurs.MethodsIn current study, we used surface-based morphometry, voxel-based morphometry and diffusion tensor imaging analyses to detect structural alterations of the white matter and gray matter in 32 migraineurs without aura compared with 32 age- and gender-matched healthy controls.ResultsWe found that migraineurs without aura exhibited significantly increased gray matter volume in the bilateral cerebellar culmen, increased cortical thickness in the lateral occipital-temporal cortex, decreased cortical thickness in the right insula, increased gyrification index in left postcentral gyrus, superior parietal lobule and right lateral occipital cortex, and decreased gyrification index in the left rostral middle frontal gyrus compared with controls. No significant change in white matter microstructure was found in DTI analyses.ConclusionThe significantly altered gray matter brain regions were known to be associated with sensory discrimination of pain, multi-sensory integration and nociceptive information processing and were consistent with our previous fMRI study, and may be involved in the pathological mechanism of migraine without aura.

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“…It has repeatedly been demonstrated how the migraine brain differs morphologically from the healthy brain in several brain regions. Moreover, these alterations appear to progress over time and with attack frequency [25,28,[31][32][33][34][35]. However, there may well be alterations at the level of structural synaptic plasticity that cannot be detected in vivo in humans with available methods.…”

Section: Discussionmentioning

confidence: 99%

“…Results from these investigations have identified differences between control and migraine brains with regard to resting state activity and structure of gray and white matter. Differences have been detected in the frontal lobes, corpus callosum, the limbic system, cerebellum, the brainstem and nociceptive regions, although findings are not consistent across studies [22,24,25,[27][28][29][30][31][32][33][34][35][36]. In addition to regional differences, cortical thickness has been reported to differ between migraine patients and controls, and even correlate to attack frequency [37].…”

Section: Introductionmentioning

confidence: 94%

Genetic Screening of Plasticity Regulating Nogo-Type Signaling Genes in Migraine

et al. 2019

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Migraine is the sixth most prevalent disease in the world and a substantial number of experiments have been conducted to analyze potential differences between the migraine brain and the healthy brain. Results from these investigations point to the possibility that development and aggravation of migraine may include grey matter plasticity. Nogo-type signaling is a potent plasticity regulating system in the CNS and consists of ligands, receptors, co-receptors and modulators with a dynamic age- and activity-related expression in cortical and subcortical regions. Here we investigated a potential link between migraine and five key Nogo-type signaling genes: RTN4, OMGP, MAG, RTN4R and LINGO1, by screening 15 single nucleotide polymorphisms (SNPs) within these genes. In a large Swedish migraine cohort (749 migraine patients and 4032 controls), using a logistic regression with sex as covariate, we found that there was no such association. In addition, a haplotype analysis was performed which revealed three haplotype blocks. These blocks had no significant association with migraine. However, to robustly conclude that Nogo-type genotypes signaling do not influence the prevalence of migraine, further studies are encouraged.

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Structural Gray Matter Alterations in Chronic Migraine: Implications for a Progressive Disease?

Cited by 84 publications

References 57 publications

Structural Co‐Variance Patterns in Migraine: A Cross‐Sectional Study Exploring the Role of the Hippocampus

Structural Co‐Variance Patterns in Migraine: A Cross‐Sectional Study Exploring the Role of the Hippocampus

Assessment of gray and white matter structural alterations in migraineurs without aura

Genetic Screening of Plasticity Regulating Nogo-Type Signaling Genes in Migraine

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