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Migraine is the second most prevalent disorder in the world; yet, its underlying mechanisms are still poorly understood. Cumulative studies have revealed pivotal roles of cerebral cortex in the initiation, propagation, and termination of migraine attacks as well as the interictal phase. Investigation of basic mechanisms of the cortex in migraine not only brings insight into the underlying pathophysiology but also provides the basis for designing novel treatments. We aim to summarize the current research literatures and give a brief overview of the cortex and its role in migraine, including the basic structure and function; structural, functional, and biochemical neuroimaging; migraine-related genes; and theories related to cortex in migraine pathophysiology. We propose that long-term plasticity of synaptic transmission in the cortex encodes migraine. [ABSTRACT FROM AUTHOR]

Background: The previous documents demonstrated that iron deposition was identified in brain deep nuclei and periaqueductal gray matter region in chronic migraine (CM), and less is known about the cerebral iron deposition in CM. The aim of this study is to investigate the cerebral iron deposition in CM using an advanced voxel-based quantitative susceptibility mapping. Methods: A multi-echo gradient echo MR sequence was obtained from 14 CM patients and 28 normal controls (NC), and quantitative susceptibility mapping images were reconstructed and voxel-based analysis was performed over the whole cerebrum. The susceptibility value of all the positive brain regions was extracted and correlation was calculated between the susceptibility value and the clinical variables. Results: The brain regions with increased susceptibility value in CM patients located in right precuneus, insula, supramarginal gyrus, dorsolateral superior frontal gyrus, postcentral gyrus, cuneus and left postcentral gyrus compared with NC. The correlation analysis demonstrated that a positive correlation was identified between susceptibility value of all the positive brain regions and VAS score. Conclusion: The current study demonstrated increased cerebral iron deposition presented in chronic patients, which suggested that increased cerebral iron deposition might play a role in the migraine chronicization. [ABSTRACT FROM AUTHOR]

Objective: This study aims to further assess the rates and risk factors for relapse in medication overuse headache (MOH) patients in China. Methods: The patients were admitted to neurology outpatient clinics at Chinese PLA General Hospital (primarily for headache) and diagnosed with MOH. They responded well to 2 months of preventive treatment and completed a 1-year consultation. General information was collected, including demographic characteristics (age, height, weight, and education level), the clinical features of the headache and the use of pain relievers (type, frequency and duration). Differences in each factor between the group with relapse and the group without relapse were analyzed by the chi-square test or Wilcoxon test. Variables with a p < 0.05 were included as independent variables in nonconditional logistic regression analysis. Results: In total, 129 patients were recruited for this retrospective study. The relapse rate of the MOH patients at the 1-year follow-up was 24.8%. The relapse rate was significantly higher in the patients with migraine (29/97, 29.9%) than in the patients with tension-type headache (3/32, 9.4%) and in the patients with low education levels (middle school or lower; 24/77, 31.6%) than in those with high education levels (high school or higher; 8/52, 15.4%). Nonconditional logistic regression analysis showed that the type of primary headache was an independent risk factor for MOH relapse (OR 3.719, p = 0.044). Conclusions: The relapse rate of MOH patients at the 1-year follow-up was 24.8% in China. The type of primary headache is an independent risk factor for MOH relapse, and patients with migraine as the primary headache are more prone to relapse. [ABSTRACT FROM AUTHOR]

It is believed than hypothalamus (HTH) might be involved in generation of migraine, and evidence from high resolution fMRI reported that the more anterior part of HTH seemed to play an important role in migraine chronification. The current study was aimed to identify the alteration of morphology and resting-state functional connectivity (FC) of the hypothalamus (HTH) in interictal episodic migraine (EM) and chronic migraine (CM). High-resolution structural and resting-state functional magnetic resonance images were acquired in 18 EM patients, 16 CM patients, and 21 normal controls (NC). The volume of HTH was calculated and voxel-based morphometry (VBM) was performed over the whole HTH. Receiver operating characteristics (ROC) curve analysis was applied to evaluate the diagnostic efficacy of HTH volume. Correlation analyses with clinical variables were performed and FC maps were generated for positive HTH regions according to VBM comparison. The volume of the HTH significantly decreased in both EM and CM patients compared with NC. The cut-off volume of HTH as 1.429 ml had a good diagnostic accuracy for CM with sensitivity of 81.25% and specificity of 100%. VBM analyses identified volume reduction of posterior HTH in EM vs. NC which was negatively correlated with headache frequency. The posterior HTH presented decreased FC with the left inferior temporal gyrus (Brodmann area 20) in EM. Decreased volume of anterior HTH was identified in CM vs. NC and CM vs. EM which was positively correlated with headache frequency in CM. The anterior HTH presented increased FC with the right anterior orbital gyrus (AOrG) (Brodmann area 11) in CM compared with NC and increased FC with the right medial orbital gyrus (MOrG) (Brodmann area 11) in CM compared with EM. Our study provided evidence of structural plasticity and FC changes of HTH in the pathogensis of migraine generation and chronification, supporting potential therapeutic target toward the HTH and its peptide. [ABSTRACT FROM AUTHOR]

Background: Imaging studies have provided valuable information in understanding the headache neuromechanism for medication-overuse headache (MOH), and the aim of this study is to investigate altered texture features of MR structural images over the whole brain in MOH using a 3-dimentional texture analysis. Methods: Brain three-dimensional T1-weighted structural images were obtained from 44 MOH patients and 32 normal controls (NC). The imaging processing included two steps: gray matter (gray images) segment and a 3-dimensional texture features mapping. Voxel-based gray-level co-occurrence matrix (VGLCM) was performed to measure the texture parameters mapping including Contrast, Correlation, Energy, Entropy and inverse difference moment (IDM). Results: The texture parameters of increased Contrast and Entropy, decreased Energy and IDM were identified in cerebellar vermis of MOH patients compared to NCs. Increased Contrast and decreased Energy were found in left cerebellum. Increased Correlation located in left dorsolateral periaqueductal gray (L-dlPAG), right parahippocampal gyrus (R-PHG), and left middle frontal gyrus (L-MFG) and decreased Correlation located in right superior parietal lobule(R-SPL). Disease duration was positively correlated with Contrast of vermis and negatively correlated with Correlation of R-SPL.HAMD score was negatively correlated with Correlation of R-PHG. MoCA score was positively correlated with Correlation of R-SPL. Conclusion: The altered textures in gray matter related to pain discrimination and modulation, affective and cognitive processing were helpful in understanding the pathogenesis of MOH. Texture analysis using VGLCM is a sensitive and efficient method to detect subtle gray matter changes in MOH. [ABSTRACT FROM AUTHOR]

Background: The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the nonspecific PAG lesions were also observed in episodic migraine (EM) recently. However, the PAG volume change was not totally detected in EM up to now. Herein, the aim of this study was to investigate altered PAG volume in EM patients based on high resolution brain structural image. Methods: The brain structural images were obtained from 18 normal controls (NC), 18 EM patients and 16 chronic migraine (CM) on 3.0 T MR system. PAG template was created based on the ICBM152 gray matter template using MRIcron, and the individual PAG was created by applying the deformation field to the PAG template after structural image segment. One-way analysis of covariance, partial correlation analysis and Receiver operating characteristics (ROC) curve were applied. Results: EM had a larger PAG volume (0.35 ± 0.02 ml) than that (0.32 ± 0.02 ml) of NC ( P = 0.017). The PAG volume of CM (0.33 ± 0.02 ml) was negatively related to the VAS score ( P = 0.03). ROC analysis demonstrated that PAG volume has higher diagnostic efficacy (AUC, 0.731; Sensitivity, 0.556; Specificity, 0.889) for NC vs. EM compared with that NC vs. CM (AUC, 0.634; Sensitivity, 0.438; Specificity, 0.833) and EM vs. CM (AUC, 0.618; Sensitivity, 0.813; Specificity, 0.556). Conclusion: PAG volume expansion may be the direct impairment evidence on the brain in EM, and could be considered as a diagnostic and evaluated imaging biomarker in migraine. [ABSTRACT FROM AUTHOR]

Background: The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the altered dysfunction of PAG subregions were not totally detected up to now. The aim of this study is to investigate the altered functional connectivity of PAG subregions in EM patients. Methods: The brain structural images and resting state functional MR imaging (rs-fMRI) data were obtained from 18 normal controls (NC) and 18 EM patients on 3.0 T MR system. Seven subregions of PAG were classified as bilateral ventrolateral PAG (vlPAG), lateral PAG (lPAG), dorsolateral PAG (dlPAG) and dorsomedial PAG (dmPAG). The functional connectivity maps of each PAG subregion were calculated, and Two sample t-test was applied with age and sex as covariables. Results: Bilateral vlPAG and left dlPAG presented decreased functional connectivity, and the other subregions (bilateral lPAGs, right dlPAG and dmPAG) showed no significant altered functional connectivity in EM compared with NC. The brain regions with decreased functional connectivity mainly located in bilateral prefrontal cortex(PFC), middle temporal gyrus, primary motor area (PMA) and supplementary motor area (SMA) and right ventrolateral PFC (vlPFC) in EM patients in this study. Disease duration was positively related to the functional connectivity of bilateral vlPAG on the bilateral thalamus and putamen, left pallidum and right medial orbitofrontal gyrus in EM patients. Conclusion: The present study suggested that the dysfunction of bilateral vlPAG and left dlPAG presented in EM, and functional evaluation of PAG subregions may be help for the diagnosis and understanding of EM pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Functional connectivity density (FCD) could identify the abnormal intrinsic and spontaneous activity over the whole brain, and a seed-based resting-state functional connectivity (RSFC) could further reveal the altered functional network with the identified brain regions. This may be an effective assessment strategy for headache research. This study is to investigate the RSFC architecture changes of the brain in the patients with medication overuse headache (MOH) using FCD and RSFC methods. Methods: 3D structure images and resting-state functional MRI data were obtained from 37 MOH patients, 18 episodic migraine (EM) patients and 32 normal controls (NCs). FCD was calculated to detect the brain regions with abnormal functional activity over the whole brain, and the seed-based RSFC was performed to explore the functional network changes in MOH and EM. Results: The decreased FCD located in right parahippocampal gyrus, and the increased FCD located in left inferior parietal gyrus and right supramarginal gyrus in MOH compared with NC, and in right caudate and left insula in MOH compared with EM. RSFC revealed that decreased functional connectivity of the brain regions with decreased FCD anchored in the right dorsal-lateral prefrontal cortex, right frontopolar cortex in MOH, and in left temporopolar cortex and bilateral visual cortices in EM compared with NC, and in frontal-temporal-parietal pattern in MOH compared with EM. Conclusions: These results provided evidence that MOH and EM suffered from altered intrinsic functional connectivity architecture, and the current study presented a new perspective for understanding the neuromechanism of MOH and EM pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The specific periaqueductal gray (PAG) lesions with migraine-like headache were easily identified on conventional MR images in clinical practice, and the aim of this study is to investigate the nonspecific periaqueductal gray (PAG) lesions in episodic migraine (EM) patients based on T2 weighted imaging (T2WI). Methods: T2WI images were obtained from 18 EM patients and 18 normal controls (NC) on 3.0 T MR system. The images were observed by two experienced radiologists, and the lesions were identified on T2WI by consensus by 2 experienced neuroradiologists blinded to the patient identity. Chi-Square test was performed for the significance test. Results: Ring-like hyperintensity lesions (HILs) around the PAG region were observed in 14 EM patients and in 5 NCs on T2WI. Four EM patients and 13 NCs were normal in PAG region. The significance was revealed by Chi-Square test ( P = 0.003). Conclusion: HIL of PAG may be the direct evidence of the EM genesis, and the further structural and functional study should be performed to elucidate the neuromechanism of migraine pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: To observe the prevalence and characteristics of premonitory symptoms in Chinese migraineurs and explore their associations with migraine-related factors. Method: Migraineurs who visited a tertiary headache clinic and one of nine neurology clinics between May 2014 and November 2019 were studied. Result: Among the 4821 patients meeting the migraine criteria (International Classification of Headache Disorders, 3rd edition), 1038 (21.5%) patients experienced at least one premonitory symptom. The most common premonitory symptoms were neck stiffness, dizziness, yawning and drowsiness. The logistic regression analysis demonstrated that aura, photophobia, aggravation by routine physical activity, triggers, family history, depression, coffee consumption and physical exercise were associated with an increased probability of experiencing premonitory symptoms (p ≤ 0.001). The premonitory symptoms of migraine with and without aura differ in prevalence and most common symptoms. The cluster analysis revealed pairwise clustering of the following premonitory symptoms: Photophobia/phonophobia, concentration change/dysesthesia, loquacity/overactivity, yawning/drowsiness, fatigue/dizziness, and mood change/irritability. The correlation analysis of triggers and premonitory symptoms revealed that temperature change, environment change, sleep disorder, activity and stress were related to multiple premonitory symptoms, and that food, light, menstruation, alcohol and odor were related to special premonitory symptoms (p ≤ 0.001). Conclusion: The prevalence of premonitory symptoms among migraineurs in China is 21.5%. Some factors influence the probability of experiencing premonitory symptoms. Paired premonitory symptoms in the clustering analysis may share similar origins. Certain triggers associated with multiple premonitory symptoms may induce brain dysfunction; however, other triggers that overlap with corresponding special premonitory symptoms may be premonitory symptoms or a form of premonitory symptom. [ABSTRACT FROM AUTHOR]

Background The existence of an association between migraine and essential tremor has long been controversial. The prevalence of migraine in essential tremor patients was surveyed to explore the association between the two diseases. Methods A case–control clinical study was conducted to investigate the prevalence of migraine in 150 consecutive essential tremor patients and in 150 matched controls without tremor. Detailed information about essential tremor and migraine was obtained using a structured questionnaire at a face-to-face interview. Moreover, a functional variant of the dopamine receptor D3 gene (Ser9Gly, rs6280) was studied in 46 essential tremor patients with and without migraine using direct sequencing analysis. Results The prevalence of lifetime migraine in essential tremor patients was significantly higher than that in controls (22.0% vs. 12.7%; p = 0.035; odds ratio = 1.95; 95% confidence interval = 1.05–3.60). No significant difference was found in the migraine features between the essential tremor and control groups and most tremor characteristics were no different in essential tremor patients with and without migraine. A higher male prevalence of essential tremor patients without migraine was observed. Moreover, 44 of 46 (95.7%) essential tremor patients had the dopamine receptor D3 Ser9Gly variant, but no significant difference was found in the frequencies of the variant between essential tremor patients with and without migraine (87.5% vs. 100.0%; p = 0.22). Conclusion Our data suggest that essential tremor patients have a higher risk of lifetime migraine than do controls and the dopamine receptor D3 Ser9Gly variant may be lower in essential tremor with migraine than the general essential tremor patients. [ABSTRACT FROM AUTHOR]

Background: The existence of an association between migraine and essential tremor has long been controversial. The prevalence of migraine in essential tremor patients was surveyed to explore the association between the two diseases. Methods: A case-control clinical study was conducted to investigate the prevalence of migraine in 150 consecutive essential tremor patients and in 150 matched controls without tremor. Detailed information about essential tremor and migraine was obtained using a structured questionnaire at a face-to-face interview. Moreover, a functional variant of the dopamine receptor D3 gene (Ser9Gly, rs6280) was studied in 46 essential tremor patients with and without migraine using direct sequencing analysis. Results: The prevalence of lifetime migraine in essential tremor patients was significantly higher than that in controls (22.0% vs. 12.7%; p=0.035; odds ratio=1.95; 95% confidence interval=1.05-3.60). No significant difference was found in the migraine features between the essential tremor and control groups and most tremor characteristics were no different in essential tremor patients with and without migraine. A higher male prevalence of essential tremor patients without migraine was observed. Moreover, 44 of 46 (95.7%) essential tremor patients had the dopamine receptor D3 Ser9Gly variant, but no significant difference was found in the frequencies of the variant between essential tremor patients with and without migraine (87.5% vs. 100.0%; p=0.22). Conclusion: Our data suggest that essential tremor patients have a higher risk of lifetime migraine than do controls and the dopamine receptor D3 Ser9Gly variant may be lower in essential tremor with migraine than the general essential tremor patients. [ABSTRACT FROM AUTHOR]

Highlights: [•] Nociceptive behaviors were increased in the UCMS group. [•] One of nociceptive behaviors correlated with depressive-like behaviors. [•] No significant differences were observed in the plasma level of CGRP and SP after stimulation. [•] The impact of depression on migraines probably does not depend on the peripheral afferent pathway. [Copyright &y& Elsevier]

Abstract: A bi-directional relationship between depression and migraine has been widely reported in epidemiological and clinical studies, but the mechanisms of interaction between these disorders have not been fully examined using animal models. The aim of the present study was to investigate the effects of depression elicited by olfactory bulbectomy (OB) on trigeminovascular nociception in conscious rats. The nociception was induced by electrical stimulation of the dura mater surrounding the superior sagittal sinus (SSS); this procedure causes nociception similar to that experienced during vascular headaches such as migraine. We showed that nociceptive behaviors (grooming and head flicks) were significantly enhanced in OB rats as compared to sham-operation (Sham) rats and that these nociceptive behaviors were correlated with depressive-like behaviors. Systemic administration of the antidepressant amitriptyline (AMI) significantly alleviated nociceptive behaviors in both the OB rats and Sham rats. Plasma levels of substance P (SP), but not plasma calcitonin gene-related protein (CGRP), significantly increased in OB rats and plasma SP levels decreased to normal following AMI treatment. Furthermore, changes in plasma SP levels were associated with both depressive-like behaviors and nociceptive behaviors. In conclusion, our results indicate that OB-induced depression can exacerbate trigeminovascular nociception, which may be mediated by SP. Moreover, we demonstrate that inhibition of SP release may contribute to the antinociceptive effect of AMI. [Copyright &y& Elsevier]