Iron Deposition and Functional Connectivity Differences in Females With Migraine Without Aura: A Comparative Study of Headache Sides.

BACKGROUND: The pathophysiological mechanisms underlying migraine without aura (MwoA) in females remain incompletely elucidated. Currently, the association between headache laterality and iron deposition (ID), and functional connectivity (FC) in female MwoA patients has not been fully studied. METHODS: We prospectively recruited 63 female patients with MwoA and 31 matched healthy controls (HC) from the hospital. ID and FC among the four groups were analyzed using two-sample t-tests (with cluster-wise family-wise error [FWE] correction). Pearson correlation analysis was used to evaluate the relationships between clinical variables and both ID and FC values. Significance level: p < 0.05. RESULTS: Compared to HC, left-sided MwoA exhibited differences in ID in various brain regions, including the cerebellum, left orbital inferior frontal gyrus, left calcarine gyrus, right putamen, and left caudate nucleus, as well as exhibited enhanced FC between the left lobule III of the cerebellum and the right superior temporal gyrus. Compared to bilateral MwoA, left-sided MwoA showed significantly enhanced in FC values in the left calcarine gyrus, the right precentral gyrus, the right postcentral gyrus, and the right lingual gyrus. Additionally, significant differences were observed in the Pearson correlations between clinical variables and both ID and FC in the female MwoA subgroups. CONCLUSION: Our study provided preliminary evidence indicating significant differences in ID, FC, and correlations among subgroups of female MwoA. This provides neuroimaging references for further subclassifying MwoA patients. This offers valuable insights into potential pathophysiological mechanisms linked to the brain functional impairment in female MwoA.

Reduced neurovascular coupling of the visual network in migraine patients with aura as revealed with arterial spin labeling MRI: is there a demand-supply mismatch behind the scenes?

BACKGROUND: Although neuroimaging investigations have consistently demonstrated that "hyperresponsive" and "hyperconnected" visual cortices may represent the functional substrate of cortical spreading depolarization in patients with migraine with aura, the mechanisms which underpin the brain "tendency" to ignite the cortical spreading depolarization and, consequently, aura phenomenon are still matter of debate. Considering that triggers able to induce aura phenomenon constrain brain to increase global (such as physical activity, stressors and sleep abnormalities) or local (such as bright light visual stimulations) energy demand, a vascular supply unable to satisfy the increased energy requirement could be hypothesized in these patients. METHODS: Twenty-three patients with migraine with aura, 25 patients with migraine without aura and 20 healthy controls underwent a 3-Tesla MRI study. Cerebral blood flow and local functional connectivity (regional homogeneity) maps were obtained and registered to the MNI space where 100 cortical regions were derived using a functional local-global normative parcellation. A surrogate estimate of the regional neurovascular coupling for each subject was obtained at each parcel from the correlation coefficient between the z-scored ReHo map and the z-scored cerebral blood flow maps. RESULTS: A significantly higher regional cerebral blood flow across the visual cortex of both hemispheres (i.e. fusiform and lingual gyri) was detected in migraine with aura patients when compared to patients with migraine without aura (p < 0.05, corrected for multiple comparisons). Concomitantly, a significantly reduced neurovascular coupling (p < 0.05, false discovery rate corrected) in the primary visual cortex parcel (VIS-4) of the large-scale visual network was observed in the left hemisphere of patients with migraine with aura (0.23±0.03), compared to both patients with migraine without aura (0.32±0.05) and healthy controls (0.29±0.05). CONCLUSIONS: Visual cortex neurovascular "decoupling" might represent the "link" between the exposure to trigger factors and aura phenomenon ignition. While physiological vascular oversupply may compensate neurovascular demand-supply at rest, it becomes inadequate in case of increased energy demand (e.g. when patients face with trigger factors) paving the way to the aura phenomenon ignition in patients with migraine with aura. Whether preventive treatments may exert their therapeutic activity on migraine with aura restoring the energy demands and cerebral blood flow trade-off within the visual network should be further investigated.

Structural brain characteristics of epilepsy patients with comorbid migraine without aura.

Migraine is a common bi-directional comorbidity of epilepsy, indicating potential complex interactions between the two conditions. However, no previous studies have used brain morphology analysis to assess possible interactions between epilepsy and migraine. Voxel-based morphometry (VBM), surface-based morphometry (SBM), and structural covariance networks (SCNs) can be used to detect morphological changes with high accuracy. We recruited 30 individuals with epilepsy and comorbid migraine without aura (EM), along with 20 healthy controls (HC) and 30 epilepsy controls (EC) without migraine. We used VBM, SBM, and SCN analysis to compare differences in gray matter volume, cortical thickness, and global level and local level graph theory indexes between the EM, EC, and HC groups to investigate structural brain changes in the EM patients. VBM analysis showed that the EM group had gray matter atrophy in the right temporal pole compared with the HC group (p < 0.001, false discovery rate correction [FDR]). Furthermore, the headache duration in the EM group was negatively correlated with the gray matter volume of the right temporal pole (p < 0.05). SBM analysis showed cortical atrophy in the left insula, left posterior cingulate gyrus, left postcentral gyrus, left middle temporal gyrus, and left fusiform gyrus in the EM compared with the HC group (p < 0.001, family wise error correction). We found a positive correlation between headache frequency and the cortical thickness of the left middle temporal gyrus (p < 0.05). SCN analysis revealed no differences in global parameters between the three groups. The area under the curve (AUC) of the nodal betweenness centrality in the right postcentral gyrus was lower in the EM group compared with the HC group (p < 0.001, FDR correction), and the AUC of the nodal degree in the right fusiform gyrus was lower in the EM group compared with the EC group (p < 0.001, FDR correction). We found clear differences in brain structure in the EM patients compared with the HC group. Accordingly, migraine episodes may influence brain structure in epilepsy patients. Conversely, abnormal brain structure may be an important factor in the development of epilepsy with comorbid migraine without aura. Further studies are needed to investigate the role of brain structure in individuals with epilepsy and comorbid migraine without aura.

[Altered functional connectivity of parietal opercular 2 in patients with vestibular migraine: a resting-state fMRI study].

Objective: To investigate the differences in resting-state functional connectivity (FC) between patients with vestibular migraine (VM) and migraine without aura (MwoA) in order to infer the possible neuroimaging mechanisms of VM. Methods: Thirty VM patients admitted to the Department of Neurology of the Second Affiliated Hospital of Xuzhou Medical University from December 2019 to December 2022 were selected as the experimental group (EG) (6 males and 24 females, with mean age of 38.3 years) and 26 MwoA patients as the control group (7 males and 19 females, mean age 35.5 years). General demographic and clinical data such as gender, age, year of education, course of disease and frequency of attacks were collected for all the patients, as well as data of Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), headache Visual Arialogue Scale (VAS), Headache Impact Test 6 (HIT-6) and Migraine Disability Assessment Questionnaire (MIDAS). VM patients were also assessed by Dizziness Handicap Inventory (DHI), dizziness VAS and Vestibular Disorders Activities of Daily Living (VADL) scales. All patients underwent resting-sate functional Magnetic Resonance Imaging (fMRI) scans. Bilateral parietal opercular cortex 2 (OP2) and primary visual cortex (V1) were used as regions of interests (ROIs). Differences in FC between ROIs and other brain regions were calculated between the two groups. In view of the brain regions with significant differences, z-values of FC were extracted for each subject in the EG, and Pearson partial correlation analysis was conducted between z-values of FC and clinical characteristics of patients, P<0.05 was considered to have significant correlation. SPSS 22.0 was used for statistical analysis. Results: There was no significant difference in gender, age, years of education, course of disease, frequency of attack and scores of MoCA, HAMA and HAMD between the two groups (P>0.05). Headache VAS, HIT-6 and MIDAS scores in VM patients were significantly lower than those in MwoA patients (P<0.05). Compared with MwoA patients, the FC between left OP2 and bilateral precuneus and left thalamus was significantly increased in VM patients, and the FC between right OP2 and left thalamus and right anterior cingulate gyrus were significantly increased (P<0.05, False Discovery Rate correction). Correlation analysis showed that the FC between left OP2 and left precuneus was positively correlated with DHI score in VM patients (P=0.007, r=0.480), and the FC between right OP2 and left thalamus was positively correlated with the disease course in VM patients (P=0.015, r=0.439). Conclusions: The pathogenesis of VM may be related to the altered FC of vestibular, pain and visual-motor networks, abnormalities of these neural pathways may be important imaging biomarkers of VM pathogenesis.

Evaluation of retinal perfusion density and foveal avascular zone in migraine subjects with and without aura.

Migraine, classified as a neurovascular disease, has been identified as a potential risk factor for ocular vascular complications. Our study aimed to compare retinal vessel density and perfusion density between subjects with migraine and healthy subjects using optical coherence tomography angiography (OCTA). In this cross-sectional case-control study, we enrolled 30 migraine subjects with aura (MWA), 30 migraine subjects without aura (MWOA) and 30 age and gender-matched healthy controls (HC). The foveal avascular zone (FAZ) in superficial capillary plexus (SCP), Vessel density (VD) and perfusion density (PD) in SCP and deep capillary plexus (DCP) were assessed in a 3 × 3 mm scan of the macula with the swept source OCT. Results indicated that the FAZ of MWA and MWOA subjects was significantly larger from HC. Also, FAZ of MWA was larger from MWOA. VD and PD in both SCP and DCP were significantly reduced in both MWA and MWOA groups compared to HC. However, VD and PD did not show significant differences among MWA and MWOA. Additionally, the duration of disease was the main determinant of the FAZ. In conclusion, the FAZ in the SCP, VD and PD in the SCP and DCP of the macula were affected in both MWA and MWOA. FAZ, specifically, was increased with the evolution of the disease. These findings might contribute to an increased risk of ocular vascular complications among subjects with migraine and could potentially use OCTA as a biomarker for this population.

Association between patent foramen ovale and migraine: evidence from a resting-state fMRI study.

A relationship between migraine without aura (MO) and patent foramen ovale (PFO) has been observed, but the neural basis underlying this relationship remains elusive. Utilizing independent component analysis via functional magnetic resonance imaging, we examined functional connectivity (FC) within and across networks in 146 patients with MO (75 patients with and 71 patients without PFO) and 70 healthy controls (35 patients each with and without PFO) to elucidate the individual effects of MO and PFO, as well as their interaction, on brain functional networks. The main effect of PFO manifested exclusively in the FC among the visual, auditory, default mode, dorsal attention and salience networks. Furthermore, the interaction effect between MO and PFO was discerned in brain clusters of the left frontoparietal network and lingual gyrus network, as well as the internetwork FC between the left frontoparietal network and the default mode network (DMN), the occipital pole and medial visual networks, and the dorsal attention and salience networks. Our findings suggest that the presence of a PFO shunt in patients with MO is accompanied by various FC changes within and across networks. These changes elucidate the intricate mechanisms linked to PFO-associated migraines and provide a basis for identifying novel noninvasive biomarkers.

Patients with episodic migraine without aura have an increased rate of delayed discounting.

OBJECTIVE: This study aimed to explore decision-making impulsivity and its neural mechanisms in patients with episodic migraine without aura (EMoA). BACKGROUND: Previous evidence indicates increased impulsivity and altered reward processing in patients with chronic migraine and medication overuse; however, whether the same holds true for those with EMoA is unclear. METHODS: Patients newly diagnosed with EMoA (n = 51) and healthy controls (HC, n = 45) were recruited. All participants completed delay discounting task, cognitive assessments, a questionnaire for headache profile, and resting-state function magnetic resonance imaging scans. Resting-state functional connectivity (RSFC) between the regions of interest and the entire brain was explored. RESULTS: Patients with EMoA showed a steeper subjective discount rate than HCs (F = 4.74, p = .032), which was positively related to a history of migraines (r = .742, p < .001). RSFC among the ventral striatum (vSTR), ventromedial prefrontal cortex, and occipital cortex was lower in patients with EMoA than in control groups, which was correlated with history (r' = .294, p = .036) and subjective discount rate (r' = .380, p = .006). Additionally, discounting rates and RSFC between the vSTR and occipital regions were significantly abnormal in the triptan group than the non-triptan group. Mediating effect analysis indicated a significant mediating effect in the change in RSFC between the vSTR and occipital status, history of triptan use, and subjective discount rate. CONCLUSION: This study further elucidated that an increase in delayed discounting rate exists in patients with EMoA and is related to the abnormality of the value processing network.

Structural and functional changes of anterior cingulate cortex subregions in migraine without aura: relationships with pain sensation and pain emotion.

Migraine without aura is a multidimensional neurological disorder characterized by sensory, emotional, and cognitive symptoms linked to structural and functional abnormalities in the anterior cingulate cortex. Anterior cingulate cortex subregions play differential roles in the clinical symptoms of migraine without aura; however, the specific patterns and mechanisms remain unclear. In this study, voxel-based morphometry and seed-based functional connectivity were used to investigate structural and functional alterations in the anterior cingulate cortex subdivisions in 50 patients with migraine without aura and 50 matched healthy controls. Compared with healthy controls, patients exhibited (1) decreased gray matter volume in the subgenual anterior cingulate cortex, (2) increased functional connectivity between the bilateral subgenual anterior cingulate cortex and right middle frontal gyrus, and between the posterior part of anterior cingulate cortex and right middle frontal gyrus, orbital part, and (3) decreased functional connectivity between the anterior cingulate cortex and left anterior cingulate and paracingulate gyri. Notably, left subgenual anterior cingulate cortex was correlated with the duration of each attack, whereas the right subgenual anterior cingulate cortex was associated with migraine-specific quality-of-life questionnaire (emotion) and self-rating anxiety scale scores. Our findings provide new evidence supporting the hypothesis of abnormal anterior cingulate cortex subcircuitry, revealing structural and functional abnormalities in its subregions and emphasizing the potential involvement of the left subgenual anterior cingulate cortex-related pain sensation subcircuit and right subgenual anterior cingulate cortex -related pain emotion subcircuit in migraine.

Altered neurovascular coupling in migraine without aura.

Neurovascular coupling (NVC) provides new insights into migraine, a neurological disorder impacting over one billion people worldwide. This study compared NVC and cerebral blood flow (CBF) in patients with migraine without aura (MwoA) and healthy controls. About 55 MwoA patients in the interictal phase and 40 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging and arterial spin-labeling perfusion imaging scans. The CBF and resting-state neuronal activity indicators, including the amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC), were calculated for each participant. The global and regional NVCs were assessed using cross-voxel CBF-neuronal activity correlations and CBF/neuronal activity ratios. Patients with MwoA showed increased CBF/ALFF ratios in the left media, superior and inferior frontal gyri, and anterior cingulate gyrus, increased CBF/DC ratios in the left middle and inferior frontal gyri, and increased CBF/ReHo ratios in the right corpus callosum and right posterior cingulate gyrus. Lower CBF/ALFF ratios in the right rectal gyrus, the left orbital gyrus, the right inferior frontal gyrus, and the right superior temporal gyrus were also found in the MwoA patients. Furthermore, the CBF/ALFF ratios in the inferior frontal and superior temporal gyri were positively correlated with the Headache Impact Test scores and Hamilton anxiety scale scores in the MwoA patients. These findings provide evidence for the theory that abnormal NVC contributes to MwoA.

Volumetric alteration of brainstem in female migraineurs with and without aura.

BACKGROUND AND AIM: Brainstem descending modulatory circuits have been postulated to be involved in migraine. Differences in brainstem volume between migraineurs and healthy controls have been demonstrated in previous research, nevertheless, the effect of migraine aura on brainstem volume is still uncertain. The aim of this study was to investigate the brainstem volume in migraineurs and examine the effect of migraine aura on brainstem volume. METHODS: Our study included 90 female migraine patients without white matter lesions. (29 migraine patients with aura (MwA) and 61 migraine patients without aura (MwoA) and 32 age-matched female healthy controls (HC). Using the FreeSurfer image analysis suite, the volumes of the entire brainstem and its subfields (medulla, pons, and midbrain) were measured and compared between migraine subgroups (MwA vs. MwoA) and the healthy control group. The possible effects of migraine characteristics (i.e., disease duration and migraine attack frequency) on brainstem volume were also investigated. RESULTS: Migraineurs had greater medulla volume (MwoA 3552 ± 459 mm3, MwA 3424 ± 448 mm3) than healthy controls (3236 ± 411 mm3). Statistically, MwA vs. HC p = 0.040, MwoA vs. HC p = 0.002, MwA vs. MwoA p = 0.555. A significant positive correlation was found between disease duration and the volume of medulla in the whole migraine group (r = 0.334, p = 0.001). Neither the whole brainstem nor its subfields were significantly different in volume between migraine subgroups. CONCLUSION: Brainstem volume changes in migraine are mainly localized to the medulla and not specific to the presence of aura.

Lack of reproducibility of resting-state functional MRI findings in migraine with aura.

BACKGROUND: Several studies have applied resting-state functional MRI to examine whether functional brain connectivity is altered in migraine with aura patients. These studies had multiple limitations, including small sample sizes, and reported conflicting results. Here, we performed a large, cross-sectional brain imaging study to reproduce previous findings. METHODS: We recruited women aged 30-60 years from the nationwide Danish Twin Registry. Resting-state functional MRI of women with migraine with aura, their co-twins, and unrelated migraine-free twins was performed at a single centre. We carried out an extensive series of brain connectivity data analyses. Patients were compared to migraine-free controls and to co-twins. RESULTS: Comparisons were based on data from 160 patients, 30 co-twins, and 136 controls. Patients were similar to controls with regard to age, and several lifestyle characteristics. We replicated clear effects of age on resting-state networks. In contrast, we failed to detect any differences, and to replicate previously reported differences, in functional connectivity between migraine patients with aura and non-migraine controls or their co-twins in any of the analyses. CONCLUSION: Given the large sample size and the unbiased population-based design of our study, we conclude that women with migraine with aura have normal resting-state brain connectivity outside of migraine attacks.

Retinal and peripapillary vascular density in episodic and chronic migraine cases without aura.

BACKGROUND: Migraine is a neurovascular disease that can cause ocular and systemic ischemic damage. Despite from aura, a limited number of studies have considered the effect of the chronic migraine in cases without aura. Our aim was to evaluate the differences in the retinal and optic disk microvasculature among episodic and chronic migraine cases without aura using optical coherence tomography angiography (OCTA) imaging. METHODS: 45 cases with migraine, and 25 control subjects were included in this prospective, cross-sectional study. OCTA was performed at 3 × 3 mm and 6 × 6 mm of the macula and at 4.5 × 4.5 mm of the optic disk. Retinal nerve fiber layer (RNFL) thickness, ganglion cell complex thickness, and vessel densities of the optic nerve and macula were compared among the three groups: a control group, an episodic migraine without aura (EMWOA) group, and a chronic migraine without aura (CMWOA) group. RESULTS: In EMWOA group, circumpapillary vascular density (cpVD) was not decreased significantly in any quadrants (all, p>0.05). Compared to the control group, CMWOA group had significantly lower RNFL thickness in superior-temporal quadrants (p = 0.002 and 0.006, respectively), while cpVD differed only in the temporal quadrant and temporal inferior sector (p = 0.002 and p = 0.009, respectively). CONCLUSIONS: Temporal peripapillary perfusion is valuable in the follow-up of chronic migraine cases. Longitudinal studies are needed to determine the place of OCTA in the follow-up of migraine.

Resting-state electroencephalography microstate dynamics altered in patients with migraine with and without aura-A pilot study.

OBJECTIVE: To evaluate electroencephalography (EEG) microstate differences between patients with migraine with aura (MWA), patients with migraine without aura (MWoA), and healthy controls (HC). BACKGROUND: Previous research employing microstate analysis found unique microstate alterations in patients with MWoA; however, it is uncertain how microstates appear in patients with MWA. METHODS: This study was conducted at the Headache Clinic of the First Affiliated Hospital of Xi'an Jiaotong University. In total, 30 patients with MWA, 30 with MWoA, and 30 HC were enrolled in this cross-sectional study. An EEG was recorded for all participants under resting state. The microstate parameters of four widely recognized microstate classes A-D were calculated and compared across the three groups. RESULTS: The occurrence of microstate B (MsB) in the MWoA group was significantly higher than in the HC (p = 0.006, Cohen's d = 0.72) and MWA (p = 0.016, Cohen's d = 0.57) groups, while the contribution of MsB was significantly increased in the MWoA group compared to the HC group (p = 0.016, Cohen's d = 0.64). Microstate A (MsA) displayed a longer duration in the MWA group compared to the MWoA group (p = 0.007, Cohen's d = 0.69). Furthermore, the transition probability between MsB and microstate D was significantly increased in the MWoA group compared to the HC group (p = 0.009, Cohen's d = 0.68 for B to D; p = 0.007, Cohen's d = 0.71 for D to B). Finally, the occurrence and contribution of MsB were positively related to headache characteristics in the MWoA group but negatively in the MWA group, whereas the duration of MsA was positively related to the visual analog scale in the MWA group (all p < 0.05). CONCLUSIONS: Patients with MWA and MWoA have altered microstate dynamics, indicating that resting-state brain network disorders may play a role in migraine pathogenesis. Microstate parameters may have the potential to aid clinical management, which needs to be investigated further.

Two distinct neuroanatomical subtypes of migraine without aura revealed by heterogeneity through discriminative analysis.

The neurobiological heterogeneity in migraine is poorly studied, resulting in conflicting neuroimaging findings. This study used a newly proposed method based on gray matter volumes (GMVs) to investigate objective neuroanatomical subtypes of migraine. Structural MRI and clinical measures of 31 migraine patients without aura and 33 matched healthy controls (HCs) were explored. Firstly, we investigated whether migraine patients exhibited higher interindividual variability than HCs in terms of GMVs. Then, heterogeneity through discriminative analysis (HYDRA) was applied to categorize migraine patients into distinct subtypes by regional volumetric measures of GMVs. Voxel-wise volume and clinical characteristics among different subtypes were also explored. Migraine patients without aura exhibited higher interindividual GMVs variability. Two distinct and reproducible neuroanatomical subtypes of migraine were revealed. These two subtypes exhibited opposite neuroanatomical aberrances compared to HCs. Subtype 1 showed widespread decreased GMVs, while Subtype 2 showed increased GMVs in limited regions. The total intracranial volume was significantly positively correlated with cognitive function in Subtype 2. Subtype 1 showed significantly longer illness duration and less cognitive scores compared to Subtype 2. The present study shows that migraine patients without aura have high structural heterogeneity and uncovers two distinct and robust neuroanatomical subtypes, which provide a possible explanation for conflicting neuroimaging findings.

Altered resting-state effective connectivity of trigeminal vascular system in migraine without aura: A spectral dynamic causal modeling study.

BACKGROUND: The trigeminal vascular system is an important part of the anatomical and physiological basis of migraine. The effective connectivity (EC) among the regions of interest (ROIs) in the trigeminal vascular system involved in migraine without aura (MWoA) remains unclear. METHODS: In this cross-sectional study, 48 patients (mean [SD] age 38.06 [10.35] years; male, 14/48 [29%]) with MWoA during the interictal phase and 48 healthy controls of similar age and sex (mean [SD] age 38.96 [10.96] years; male, 14/48 [29%]) underwent resting-state functional magnetic resonance imaging (fMRI). Dynamic causal modeling analysis was conducted to investigate directional EC among ROIs in the trigeminal vascular system including the bilateral brainstem, the primary somatosensory cortex (S1), the thalamus, and the insula. RESULTS: Compared with the healthy control group, MWoA represented significantly reduced EC from the left brainstem (Brainstem.L) to the left insula (MWoA: mean [SD] -0.16 [0.36]; healthy controls: mean [SD] 0.11 [0.41]; Pcorrected = 0.021), reduced EC from the Brainstem.L to the right insula (MWoA: mean [SD] -0.15 [0.39]; healthy controls: mean [SD] 0.03 [0.35]; Pcorrected = 0.021), and decreased EC from the left thalamus (Thalamus.L) to the Brainstem.L (MWoA: mean [SD] -0.13 [0.56]; healthy controls: mean [SD] 0.10 [0.45]; Pcorrected = 0.021). Altered EC parameters were not significantly correlated with MWoA clinical data. CONCLUSION: These results further provide increasing evidence that disturbed homeostasis of the trigeminovascular nociceptive pathway is involved in the pathophysiological mechanisms of migraine. Patients with MWoA exhibited a regional interaction distinct from healthy controls in the neural pathway of the Bilateral Insula-Brainstem.L-Thalamus.L, which may shed light on the future understanding of brain mechanisms for MWoA. Future brain-based interventions are suggested to consider the dysregulation in the Bilateral Insula-Brainstem.L-Thalamus.L circuits.

Altered functional brain network patterns in patients with migraine without aura after transcutaneous auricular vagus nerve stimulation.

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.

Parahippocampus hypertrophy drives gray matter morphological alterations in migraine patients without aura.

BACKGROUND: The aberrance of gray matter morphology in migraineurs has been widely investigated. However, it remains largely unknown whether there are illness duration-related hierarchical changes in the gray matter structure. METHODS: A total of 86 migraine without aura (MwoA) patients and 73 healthy controls were included. The Voxel-Based Morphometry approach was utilized to compare the gray matter volume (GMV) differences between MwoA patients and healthy controls. The Structural Covariance Network analysis was conducted to quantify the cross-regional synchronous alterations of gray matter structure in MwoA patients. The Causal Structural Covariance Network analysis was performed to describe the progressive and hierarchical changes in the gray matter network of patients in the pathological progression of migraine. RESULTS: MwoA patients had duration-stage related GMV hypertrophy in the left parahippocampus, as well as synergistic GMV aberrance in the parahippocampus and the medial inferior temporal gyrus and cerebellum. Moreover, the GMV alteration of the parahippocampus, and the surrounding hippocampus, amygdala, and bilateral anterior cerebellum, preceded and causally influenced the morphological changes of lateral parietal-temporal-occipital gyrus, as well as the motor cortex and prefrontal gyrus with the increasing illness duration in MwoA patients. CONCLUSION: The current study indicated that gray matter structural alterations in the medial inferior temporal gyrus, especially the parahippocampus, is a critical pathological characteristic in MwoA patients, which drives the gray matter structure alteration of other regions. These findings provide further evidence for understanding the progressive gray matter morphological changes in migraine and may facilitate the development of neuromodulation therapies targeting this procession.

Abnormally Increased Effective Connectivity of the Periaqueductal Gray in Migraine Without Aura Patients.

OBJECTIVES: The periaqueductal gray (PAG) is a key region in the descending pain modulatory system. We applied a Granger causality analysis-based approach to examine resting-state effective connectivity of the bilateral PAG regions in migraine patients without aura (MwoA). MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging data were obtained from 28 MwoA patients and 17 healthy controls. The effective connectivity of the bilateral PAG was characterized using a voxel-wised Granger causality analysis method. The resulting effective connectivity measurements were assessed for correlations with other clinical features. RESULTS: Compared with the healthy controls, MwoA patients showed increased effective connectivity from the left PAG to the left anterior cingulate gyrus and right postcentral gyrus. Meanwhile, MwoA patients also showed increased effective connectivity from the right PAG to the left precentral gyrus and increased effective connectivity from the left caudate and right middle occipital gyrus to the right PAG. DISCUSSION: Abnormally increased effective connectivity between PAG and limbic system, primary sensorimotor cortex, and visual cortex may play a key role in neuropathological features, perception, and affection of MwoA. The current study provides further insights into the complex scenario of MwoA mechanisms.

Altered brain activity and functional connectivity in migraine without aura during and outside attack.

BACKGROUND: Migraine is commonly seen as a cyclic disorder with variable cortical excitability at different phases. Herein, we investigated the cortical excitability in migraine without aura patients during an attack (MWoA-DA) and interictal period (MWoA-DI) and further explored the functional connectivity (FC) in brain regions with cortical excitability abnormalities in patients. METHODS: Seven MWoA-DA patients, twenty-seven MWoA-DI patients, and twenty-nine healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuations (ALFF) was assessed to identify spontaneous brain activity. Then, brain regions showing significant differences across groups were identified as regions of interest (ROI) in FC analysis. RESULTS: Compared with MWoA-DI patients and HC, the ALFF in the trigeminocervical complex (TCC) was higher in the MWoA-DA patients. Decreased FC in MWoA-DA patients was found between TCC and left postcentral gyrus compared with MWoA-DI patients. Compared with HC, ALFF was lower in the right cuneus but higher in the right rolandic operculum of MWoA-DI patients. Additionally, the ALFF in the right cuneus was negatively correlated with the Migraine Disability Assessment Scale (MIDAS) in MWoA-DI patients. CONCLUSIONS: The trigeminovascular system and impairments in descending pain modulatory pathways participate in the pathophysiology of migraine during the ictal period. The defense effect exists in the interictal phase, and the dysfunction in the cuneus may be related to the disease severity. This dynamic change in different brain regions could deepen our understanding of the physiopathology underlying migraine.

Cerebral blood flow alterations in migraine patients with and without aura: An arterial spin labeling study.

BACKGROUND: Migraine aura is a transient, fully reversible visual, sensory, or other central nervous system symptom that classically precedes migraine headache. This study aimed to investigate cerebral blood flow (CBF) alterations of migraine with aura patients (MwA) and without aura patients (MwoA) during inter-ictal periods, using arterial spin labeling (ASL). METHODS: We evaluated 88 migraine patients (32 MwA) and 44 healthy control subjects (HC) who underwent a three-dimensional pseudo-continuous ASL MRI scanning. Voxel-based comparison of normalized CBF was conducted between MwA and MwoA. The relationship between CBF variation and clinical scale assessment was further analyzed. The mean CBF values in brain regions showed significant differences were calculated and considered as imaging features. Based on these features, different machine learning-based models were established to differentiate MwA and MwoA under five-fold cross validation. The predictive ability of the optimal model was further tested in an independent sample of 30 migraine patients (10 MwA). RESULTS: In comparison to MwoA and HC, MwA exhibited higher CBF levels in the bilateral superior frontal gyrus, bilateral postcentral gyrus and cerebellum, and lower CBF levels in the bilateral middle frontal gyrus, thalamus and medioventral occipital cortex (all p values < 0.05). These variations were also significantly correlated with multiple clinical rating scales about headache severity, quality of life and emotion. On basis of these CBF features, the accuracies and areas under curve of the final model in the training and testing samples were 84.3% and 0.872, 83.3% and 0.860 in discriminating patients with and without aura, respectively. CONCLUSION: In this study, CBF abnormalities of MwA were identified in multiple brain regions, which might help better understand migraine-stroke connection mechanisms and may guide patient-specific decision-making.