Microstructural differences in migraine: A diffusion-tensor imaging study.

BACKGROUND: Diffusion-tensor imaging can be applied to describe the microstructural integrity of the whole brain. As findings about microstructural alterations in migraine are inconsistent, we aimed to replicate the most frequent results and assess a relationship between migraine parameters and changes in microstructure. METHODS: Diffusion-weighted MRI data of 37 migraine patients and 40 controls were collected. Two indices of diffusion of water molecules, fractional anisotropy and mean diffusivity were used in a voxel-wise analysis. Group comparisons were carried out in SPM12 using age and sex as covariates. Statistically significant results survived family-wise error correction (pFWE < 0.05). Migraine intensity, frequency, and duration were self-reported and correlated with mean fractional anisotropy and mean diffusivity values across clusters. RESULTS: Migraine patients showed significantly lower fractional anisotropy in occipital regions, and significantly higher fractional anisotropy in thirteen clusters across the brain. Mean diffusivity of migraine patients was significantly decreased in the cerebellum and pons, but it was not increased in any area. Correlation between migraine duration and fractional anisotropy was significantly positive in the frontal cortex and significantly negative in the superior parietal lobule. CONCLUSION: We suggest that microstructural integrity of the migraine brain is impaired in visual areas and shows duration-related alterations in regions of the default mode network.

A cross-sectional study on the quality of life in migraine and medication overuse headache in a Hungarian sample: understanding the effect of headache characteristics.

Background and purpose: Previous studies using generic and disease specific instruments showed that both migraine and medication overuse headache are associated with lower health-related quality of life (HRQoL). The aim of our study was to assess HRQoL differences in migraineurs and in patients with MOH and to examine how headache characteristics such as years with headache, aura symptoms, triptan use, headache pain severity and headache frequency are related to HRQoL. Methods: In this cross-sectional study 334 participants were examined (248 were recruited from a tertiary headache centre and 86 via advertisements). The Comp-rehensive Headache-related Quality of life Questionnaire (CHQQ) was used to measure the participants' HRQoL. Data showed normal distribution, therefore beside Chi-squared test parametric tests (e.g. independent samples t-test) were used with a two-tailed p<0.05 threshold. Linear regression models were used to determine the independent effects of sex, age, recruitment method, headache type (migraine vs. MOH) and headache characteristics (presence of aura symptoms, years with headache, headache pain severity, headache frequency and triptan use) separately for each domain and for the total score of CHQQ. Significance threshold was adopted to p0.0125 (0.05/4) to correct for multiple testing and avoid Type I error. Results: Independent samples t-tests showed that patients with MOH had significantly lower scores on all CHQQ domains than migraineurs, except on the social subscale. Results of a series of regression analyses showed that triptan use was inversely related to all the domains of HRQoL after correction for multiple testing (p<0.0125). In addition, headache pain severity was associated with lower physical (p=0.001) and total scores (p=0.002) on CHQQ subscales. Conclusion: Based on the results, different headache characteristics (but not the headache type, namely migraine or MOH) were associated with lower levels of HRQoL in patients with headache. Determining which factors play significant role in the deterioration of HRQoL is important to adequately manage different patient populations and to guide public health policies regarding health service utilization and health-care costs.

Circadian Variation of Migraine Attack Onset Affects fMRI Brain Response to Fearful Faces.

Background: Previous studies suggested a circadian variation of migraine attack onset, although, with contradictory results - possibly because of the existence of migraine subgroups with different circadian attack onset peaks. Migraine is primarily a brain disorder, and if the diversity in daily distribution of migraine attack onset reflects an important aspect of migraine, it may also associate with interictal brain activity. Our goal was to assess brain activity differences in episodic migraine subgroups who were classified according to their typical circadian peak of attack onset. Methods: Two fMRI studies were conducted with migraine without aura patients (n = 31 in Study 1, n = 48 in Study 2). Among them, three subgroups emerged with typical Morning, Evening, and Varying start of attack onset. Whole brain activity was compared between the groups in an implicit emotional processing fMRI task, comparing fearful, sad, and happy facial stimuli to neutral ones. Results: In both studies, significantly increased neural activation was detected to fearful (but not sad or happy) faces. In Study 1, the Evening start group showed increased activation compared to the Morning start group in regions involved in emotional, self-referential (left posterior cingulate gyrus, right precuneus), pain (including left middle cingulate, left postcentral, left supramarginal gyri, right Rolandic operculum) and sensory (including bilateral superior temporal gyrus, right Heschl's gyrus) processing. While in Study 2, the Morning start group showed increased activation compared to the Varying start group at a nominally significant level in regions with pain (right precentral gyrus, right supplementary motor area) and sensory processing (bilateral paracentral lobule) functions. Conclusion: Our fMRI studies suggest that different circadian attack onset peaks are associated with interictal brain activity differences indicating heterogeneity within migraine patients and alterations in sensitivity to threatening fearful stimuli. Circadian variation of migraine attack onset may be an important characteristic to address in future studies and migraine prophylaxis.

Association of plasma tryptophan concentration with periaqueductal gray matter functional connectivity in migraine patients.

Altered periaqueductal gray matter (PAG) functional connectivity contributes to brain hyperexcitability in migraine. Although tryptophan modulates neurotransmission in PAG projections through its metabolic pathways, the effect of plasma tryptophan on PAG functional connectivity (PAG-FC) in migraine has not been investigated yet. In this study, using a matched case-control design PAG-FC was measured during a resting-state functional magnetic resonance imaging session in migraine without aura patients (n = 27) and healthy controls (n = 27), and its relationship with plasma tryptophan concentration (TRP) was assessed. In addition, correlations of PAG-FC with age at migraine onset, migraine frequency, trait-anxiety and depressive symptoms were tested and the effect of TRP on these correlations was explored. Our results demonstrated that migraineurs had higher TRP compared to controls. In addition, altered PAG-FC in regions responsible for fear-cascade and pain modulation correlated with TRP only in migraineurs. There was no significant correlation in controls. It suggests increased sensitivity to TRP in migraine patients compared to controls. Trait-anxiety and depressive symptoms correlated with PAG-FC in migraine patients, and these correlations were modulated by TRP in regions responsible for emotional aspects of pain processing, but TRP did not interfere with processes that contribute to migraine attack generation or attack frequency.

Perceived stress in the time of COVID-19: the association with brooding and COVID-related rumination in adults with and without migraine.

BACKGROUND: The main goal of this research was to explore whether migraineurs had a higher level of perceived stress than healthy controls during the times of the coronavirus and related restrictive measures, and to examine the relationship between different subtypes of rumination and perceived stress in these groups. We measured two facets of depressive rumination, brooding and reflection, along with rumination about the current COVID-19 situation to see whether these different subtypes of rumination explained perceived stress among migraineurs and healthy controls. METHODS: Healthy adults (n = 64) and migraine patients (n = 73) filled out self-report questionnaires online. A multiple linear regression model was used to test whether depressive rumination (i.e. brooding and reflection) and COVID-related rumination explained perceived stress among adults with and without migraine during the times of COVID-19, after controlling for gender, age, migraine/control group status and migraine disability. RESULTS: Although we did not find any difference in the level of perceived stress among migraineurs and the control group, perceived stress was more strongly associated with brooding as well as COVID-related rumination among migraineurs than healthy controls. COVID-related rumination and brooding (but not reflection) explained the level of perceived stress after controlling for gender, age, migraine/control group status and migraine disability. CONCLUSIONS: The similar degree of perceived stress among migraineurs and the control group may imply that there is great variation in the personal experience of people regarding the pandemic, that may be determined by numerous other factors. Our results demonstrate that ruminating about the pandemic and related difficulties, as well as brooding (but not reflection) appear to be associated with higher level of perceived stress during the times of the coronavirus. This association was slightly stronger among migraineurs, hinting at the increased vulnerability of this patient group in stressful situations like the COVID-19 pandemic. Our results also suggest that ruminating about the pandemic and its consequences is weakly associated with trait-level depressive rumination, thus may be more contingent on specific factors.

Sex Differences of Periaqueductal Grey Matter Functional Connectivity in Migraine.

The existence of "sex phenotype" in migraine is a long-standing scientific question. Fluctuations of female sex hormones contribute to migraine attacks, and women also have enhanced brain activity during emotional processing and their functional brain networks seem to be more vulnerable to migraine-induced disruption compared to men. Periaqueductal grey matter (PAG) is a core region of pain processing and modulation networks with possible sex-related implications in migraine. In our study, sex differences of PAG functional resting-state connectivity were investigated in the interictal state in 32 episodic migraines without aura patients (16 women and 16 men). A significant main effect of sex was detected in PAG connectivity with postcentral, precentral, and inferior parietal gyri, and further differences were found between right PAG and visual areas (superior occipital gyrus, calcarine, and cuneus), supplementary motor area, and mid-cingulum connectivity. In all cases, PAG functional connectivity was stronger in female migraineurs compared to males. However, higher average pain intensity of migraine attacks correlated with stronger connectivity of PAG and middle temporal, superior occipital, and parietal gyri in male migraineurs compared to females. Migraine-related disability is also associated with PAG connectivity but without sex differences. Our results indicate that sex differences in PAG connectivity with brain regions involved in sensory and emotional aspects of pain might contribute to the "sex-phenotype" in migraine. The stronger functional connectivity between PAG and pain processing areas may be a sign of increased excitability of pain pathways even in resting-state in females compared to male migraineurs, which could contribute to female vulnerability for migraine. However, pain intensity experienced by male migraineurs correlated with increased connectivity between PAG and regions involved in the subjective experience of pain and pain-related unpleasantness. The demonstrated sex differences of PAG functional connectivity may support the notion that the female and male brain is differently affected by migraine.

Regular Practice of Autogenic Training Reduces Migraine Frequency and Is Associated With Brain Activity Changes in Response to Fearful Visual Stimuli.

Several factors can contribute to the development and chronification of migraines, including stress, which is undoubtedly a major trigger. Beyond pharmacotherapy, other treatment methods also exist, including behavioral techniques aiming at reducing patients' stress response. However, the exact brain mechanisms underlying the efficacy of such methods are poorly understood. Our pilot study examined whether the regular practice of autogenic training (AT) induces functional brain changes and if so, how it could be associated with the improvement of migraine parameters. By exploring neural changes through which AT exerts its effect, we can get closer to the pathomechanism of migraine. In particular, we investigated the effect of a headache-specific AT on brain activation using an implicit face emotion processing functional MRI (fMRI) task in female subjects with and without episodic migraine. Our focus was on migraine- and psychological stress-related brain regions. After a 16-week training course, migraineurs showed decreased activation in the migraine-associated dorsal pons to fearful compared with neutral visual stimuli. We also detected decreasing differences in supplementary motor area (SMA) activation to fearful stimuli, and in posterior insula activation to happy stimuli between healthy subjects and migraineurs. Furthermore, migraineurs reported significantly less migraine attacks. These brain activation changes suggest that AT may influence the activity of brain regions responsible for emotion perception, emotional and motor response integration, as well as cognitive control, while also being able to diminish the activation of regions that have an active role in migraine attacks. Improvements induced by the training and the underlying neurophysiological mechanisms are additional arguments in favor of evidence-based personalized behavioral therapies.