Structural and Functional Reorganization of the Brain in Migraine Without Aura.
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ABSTRACT:
SUBMITTER: Soheili-Nezhad S
PROVIDER: S-EPMC6515892 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
Structural and Functional Reorganization of the Brain in Migraine Without Aura.
Soheili-Nezhad Sourena S Sedghi Alireza A Schweser Ferdinand F Eslami Shahr Babaki Amir A Jahanshad Neda N Thompson Paul M PM Beckmann Christian F CF Sprooten Emma E Toghae Mansoureh M
Frontiers in neurology 20190507
It remains unknown whether migraine headache has a progressive component in its pathophysiology. Quantitative MRI may provide valuable insight into abnormal changes in the migraine interictum and assist in identifying disrupted brain networks. We carried out a data-driven study of structural integrity and functional connectivity of the resting brain in migraine without aura. MRI scanning was performed in 36 patients suffering from episodic migraine without aura and 33 age-matched healthy subject ...[more]
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Project description:ObjectivesTo explore the possible concurrent brain functional and structural alterations in patients with migraine without aura (MwoA) patients compared to healthy subjects (HS).MethodsSeventy-two MwoA patients and forty-six HS were recruited. 3D-T1 and resting state fMRI data were collected during the interictal period for MwoA and HS. Voxel-based morphometry (VBM) for structure analysis and regional homogeneity (Reho) for fMRI analysis were applied. The VBM and Reho maps were overlapped to determine a possible brain region with concurrent functional and structural alteration in MwoA patients. Further analysis of resting state functional connectivity (FC) alteration was applied with this brain region as the seed.ResultsCompared with HS, MwoA patients showed decreased volume in the bilateral superior and inferior colliculus, periaqueductal gray matter (PAG), locus ceruleus, median raphe nuclei (MRN) and dorsal pons medulla junction. MwoA patients showed decreased Reho values in the middle occipital gyrus and inferior occipital gyrus, and increased Reho values in the MRN. Only a region in the MRN showed both structural and functional alteration in MwoA patients. Pearson correlation analysis showed that there was no association between volume or Reho values of the MRN and headache frequency, headache intensity, disease duration, self-rating anxiety scale or self-rating depression scale in MwoA patients. Resting state functional connectivity (FC) with the MRN as the seed showed that MwoA patients had increased FC between the MRN and PAG.ConclusionsMRN are involved in the pathophysiology of migraine during the interictal period. This study may help to better understand the migraine symptoms.Trial registrationNCT01152632 . Registered 27 June 2010.
| S-EPMC7720576 | biostudies-literature
Project description:Previous studies have reported abnormal amplitude of low-frequency fluctuation and regional homogeneity in patients with migraine without aura using resting-state functional magnetic resonance imaging. However, how whole brain functional connectivity pattern homogeneity and its corresponding functional connectivity changes in patients with migraine without aura is unknown. In the current study, we employed a recently developed whole brain functional connectivity homogeneity (FcHo) method to identify the voxel-wise changes of functional connectivity patterns in 21 patients with migraine without aura and 21 gender and age matched healthy controls. Moreover, resting-state functional connectivity analysis was used to reveal the changes of corresponding functional connectivities. FcHo analyses identified significantly decreased FcHo values in the posterior cingulate cortex (PCC), thalamus (THA), and left anterior insula (AI) in patients with migraine without aura compared to healthy controls. Functional connectivity analyses further found decreased functional connectivities between PCC and medial prefrontal cortex (MPFC), between AI and anterior cingulate cortex, and between THA and left precentral gyrus (PCG). The functional connectivities between THA and PCG were negatively correlated with pain intensity. Our findings indicated that whole brain FcHo and connectivity abnormalities of these regions may be associated with functional impairments in pain processing in patients with migraine without aura.
| S-EPMC7759668 | biostudies-literature
Project description:BackgroundIncreasing evidence has suggested that the cerebellum is associated with pain and migraine. In addition, the descending pain system of the brainstem is the major site of trigeminal pain processing and modulation and has been discussed as a main player in the pathophysiology of migraine. Cerebellar and brainstem structural changes associated with migraineurs remain to be further investigated.MethodsVoxel-based morphometry (VBM) (50 controls, 50 migraineurs without aura (MWoAs)) and diffusion tensor imaging (DTI) (46 controls, 46 MWoAs) were used to assess cerebellum and brainstem anatomical alterations associated with MWoAs. We utilized a spatially unbiased infratentorial template toolbox (SUIT) to perform cerebellum and brainstem optimized VBM and DTI analysis. We extracted the average diffusion values from a probabilistic cerebellar white matter atlas to investigate whether MWoAs exhibited microstructure alterations in the cerebellar peduncle tracts.ResultsMWoAs showed decreased fractional anisotropy (FA) in the vermis VI extending to the bilateral lobules V and VI of the cerebellum. We also found higher axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in the right inferior cerebellum peduncle tract in MWoAs. MWoAs exhibited both reduced gray matter volume and increased AD, MD and RD in the spinal trigeminal nucleus (SpV).ConclusionMWoAs exhibited microstructural changes in the cerebellum and the local brainstem. These structural differences might contribute to dysfunction of the transmission and modulation of noxious information, trigeminal nociception, and conduction and integration of multimodal information in MWoAs. These findings further suggest involvement of the cerebellum and the brainstem in the pathology of migraine without aura.
| S-EPMC6734280 | biostudies-literature
Project description:IntroductionIt is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.AimUsing a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO.MethodsGene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.ResultsWe found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.ConclusionsOur results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.
| S-EPMC5541777 | biostudies-literature
Project description:Magnetic resonance imaging (MRI) is by nature a multi-modality technique that provides complementary information about different aspects of diseases. So far no attempts have been reported to assess the potential of multi-modal MRI in discriminating individuals with and without migraine, so in this study, we proposed a classification approach to examine whether or not the integration of multiple MRI features could improve the classification performance between migraine patients without aura (MWoA) and healthy controls. Twenty-one MWoA patients and 28 healthy controls participated in this study. Resting-state functional MRI data was acquired to derive three functional measures: the amplitude of low-frequency fluctuations, regional homogeneity and regional functional correlation strength; and structural MRI data was obtained to measure the regional gray matter volume. For each measure, the values of 116 pre-defined regions of interest were extracted as classification features. Features were first selected and combined by a multi-kernel strategy; then a support vector machine classifier was trained to distinguish the subjects at individual level. The performance of the classifier was evaluated using a leave-one-out cross-validation method, and the final classification accuracy obtained was 83.67% (with a sensitivity of 92.86% and a specificity of 71.43%). The anterior cingulate cortex, prefrontal cortex, orbitofrontal cortex and the insula contributed the most discriminative features. In general, our proposed framework shows a promising classification capability for MWoA by integrating information from multiple MRI features.
| S-EPMC5045214 | biostudies-literature
Project description:Transcutaneous auricular vagus nerve stimulation (taVNS) shows excellent effects on relieving clinical symptoms in migraine patients. Nevertheless, the neurological mechanisms of taVNS for migraineurs remain unclear. In recent years, voxel-wise degree centrality (DC) and functional connectivity (FC) methods were extensively utilized for exploring alterations in patterns of FC in the resting-state brain. In the present study, thirty-five migraine patients without aura and thirty-eight healthy controls (HCs) were recruited for magnetic resonance imaging scans. Firstly, this study used voxel-wise DC analysis to explore brain regions where abnormalities were present in migraine patients. Secondly, for elucidating neurological mechanisms underlying taVNS in migraine, seed-based resting-state functional connectivity analysis was employed to the taVNS treatment group. Finally, correlation analysis was performed to explore the relationship between alterations in neurological mechanisms and clinical symptoms. Our findings indicated that migraineurs have lower DC values in the inferior temporal gyrus (ITG) and paracentral lobule than in healthy controls (HCs). In addition, migraineurs have higher DC values in the cerebellar lobule VIII and the fusiform gyrus than HCs. Moreover, after taVNS treatment (post-taVNS), patients displayed increased FC between the ITG with the inferior parietal lobule (IPL), orbitofrontal gyrus, angular gyrus, and posterior cingulate gyrus than before taVNS treatment (pre-taVNS). Besides, the post-taVNS patients showed decreased FC between the cerebellar lobule VIII with the supplementary motor area and postcentral gyrus compared with the pre-taVNS patients. The changed FC of ITG-IPL was significantly related to changes in headache intensity. Our study suggested that migraine patients without aura have altered brain connectivity patterns in several hub regions involving multisensory integration, pain perception, and cognitive function. More importantly, taVNS modulated the default mode network and the vestibular cortical network related to the dysfunctions in migraineurs. This paper provides a new perspective on the potential neurological mechanisms and therapeutic targets of taVNS for treating migraine.
| S-EPMC10264378 | biostudies-literature
Project description:BackgroundMenstrual migraine without aura (MRM) is common in female migraineurs and is closely related to cerebral functional abnormalities. However, whether the whole brain networks and directional functional connectivity of MRM patients are altered remains unclear. The purpose of this study was to detect the alterations of resting-state functional networks and directional functional connectivity between MRM and non-menstrual migraine without aura (NMM) patients using functional magnetic resonance imaging (fMRI) with degree centrality (DC) and Granger causality analysis (GCA) methods.MethodsIn this retrospective and cross-sectional study, 45 MRM and 40 NMM patients (matched in age, gender, and years of education) were recruited in the study between May 2018 and June 2022. All participants had undergone resting-state fMRI scanning at the Neurology and Pain Outpatient Department of Nanjing First Hospital. Their brain functions were analyzed in terms of DC and GCA, with the significant threshold at voxel level P<0.01 and cluster level P<0.05, Gaussian random field corrected. Correlation analysis was adopted to assess the relationships between the fMRI results and clinical features (P<0.05, Bonferroni corrected).ResultsCompared with those in the NMM group, MRM patients showed decreased DC in the right insula (T=-4.253). Using the right insula as the seed region, patients with MRM demonstrated enhanced effective connectivity from the right insula to the ipsilateral middle temporal gyrus (T=4.138) and contralateral superior temporal gyrus (T=3.523). Furthermore, the MRM group also showed decreased effective connectivity from several brain regions to the right insula, which included the right inferior occipital gyrus (T=-4.498), left middle frontal gyrus (T=-4.879), right precuneus (T=-4.644), and left inferior parietal gyrus (T=-4.113). The average Self-rating Anxiety Scale score of the MRM group was significantly higher than that of the NMM group [P=0.032, 95% confidence interval (CI): 0.363-7.761]. In the MRM group, disease duration was negatively correlated with the mean value of DC in right insula (r=-0.428, P=0.01).ConclusionsThe present research demonstrated that patients with MRM have disruption in insula resting-state functional networks. Disrupted networks contained regions associated with cognitive processes, emotional perception, and migraine attack in MRM patients. These results may improve our comprehension of the neuromechanism of menstrually-related migraine.
| S-EPMC10783996 | biostudies-literature
Project description:BackgroundCortical spreading depression (CSD) has been considered the prominent theory for migraine with aura (MwA). However, it is also argued that CSD can exist in patients in a silent state, and not manifest as aura. Thus, the MwA classification based on aura may be questionable. This study aimed to capture whole-brain connectome-based imaging markers with identifiable signatures for MwA and migraine without aura (MwoA).MethodsA total of 88 migraine patients (32 MwA) and 49 healthy controls (HC) underwent a diffusion tensor imaging and resting-state functional magnetic resonance imaging scan. The whole-brain structural connectivity (SC) and functional connectivity (FC) analysis was employed to extract imaging features. The extracted features were subjected to an all-relevant feature selection process within cross-validation loops to pinpoint attributes demonstrating substantial efficacy for patient categorization. Based on the identified features, the predictive ability of the random forest classifiers constructed with the 88 migraine patients' sample was tested using an independent sample of 32 migraine patients (eight MwA).ResultsCompared to MwoA and HC, MwA showed two reduced SC and six FC (five increased and one reduced) features [all P<0.01, after false discovery rate (FDR) correction], involving frontal areas, temporal areas, visual areas, amygdala, and thalamus. A total of four imaging features were significantly correlated with clinical rating scales in all patients (r=-0.38 to 0.47, P<0.01, after FDR correction). The predictive ability of the random forest classifiers achieved an accuracy of 78.1% in the external sample to identify MwA.ConclusionsThe whole-brain connectivity features in our results may serve as connectome-based imaging markers for MwA identification. The alterations of SC and FC strength provide possible evidence in further understanding the heterogeneity and mechanism of MwA which may help for patient-specific decision-making.
| S-EPMC10784058 | biostudies-literature
Project description:IntroductionMigraine without aura (MwoA) is a primary type of migraine, a common disabling disorder, and a disabling neurological condition. The headache is a complex experience, a common form of pain, in which multiple sensory information dimensions are combined to provide a unified conscious event. Migraine ictal have unique neuroimage biomarkers, but the brain is also affected during the inter-ictal phase. According to the current studies, a hypothesis was constructed that the altered integration of pain spatial and intensity information impacts headache intensity in the inter-ictal period.MethodsIn this study, we applied theory-based region-to-region functional connectivity (FC) analyses to compare the differences in resting-state FC between MwoA participants and healthy controls with the pain integration hypothesis. After the correlation matrices between FC edges and clinical symptoms were constructed, the moderating effect and simple slope tests were investigated to explain whether and how the dysfunction of pain features discrimination affects the clinical symptoms.ResultsFunctional connectivity analyses showed significantly decreased FC edges between the left dorsolateral superior frontal gyrus (SFGdor) and left insula, and an increased FC edge between the left SFGdor and bilateral angular gyrus. The correlation matrix showed no significant correlation between significantly altered FC edge and headache duration, frequency, Zung self-rating anxiety scale, and Zung self-rating depression scale. Only one significantly altered edge in the MwoA condition was significantly correlated with headache intensity. Moderating Module 1 and 2 manifested the moderator variable (altered rs-FC edge) moderated the link between the normal edges and headache intensity.ConclusionThe pain features integration processes in migraineurs vary from HCs, related to the clinical symptoms during a migraine attack. Moreover, the clinical symptoms will be affected by one or more discrimination modules. And the spatial or intensity discrimination modules have a higher impact when combined with another module on clinical symptoms than the single module.
| S-EPMC7969893 | biostudies-literature
Project description:ObjectiveTo identify and validate an fMRI-based neural marker for migraine without aura (MwoA) and to examine its association with treatment response.MethodsWe conducted cross-sectional studies with resting-state fMRI data from 230 participants and machine learning analyses. In studies 1 through 3, we identified, cross-validated, independently validated, and cross-sectionally validated an fMRI-based neural marker for MwoA. In study 4, we assessed the relationship between the neural marker and treatment responses in migraineurs who received a 4-week real or sham acupuncture treatment, or were waitlisted, in a registered clinical trial.ResultsIn study 1 (n = 116), we identified a neural marker with abnormal functional connectivity within the visual, default mode, sensorimotor, and frontal-parietal networks that could discriminate migraineurs from healthy controls (HCs) with 93% sensitivity and 89% specificity. In study 2 (n = 38), we investigated the generalizability of the marker by applying it to an independent cohort of migraineurs and HCs and achieved 84% sensitivity and specificity. In study 3 (n = 76), we verified the specificity of the marker with new datasets of migraineurs and patients with other chronic pain disorders (chronic low back pain and fibromyalgia) and demonstrated 78% sensitivity and 76% specificity for discriminating migraineurs from nonmigraineurs. In study 4 (n = 116), we found that the changes in the marker responses showed significant correlation with the changes in headache frequency in response to real acupuncture.ConclusionWe identified an fMRI-based neural marker that captures distinct characteristics of MwoA and can link disease pattern changes to brain changes.
| S-EPMC7176301 | biostudies-literature