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Altered effective connectivity between the left amygdala and whole brain regions in MwoA compared with HC (first row). Altered effective connectivity between the right amygdala and whole brain regions in MwoA compared with HC (second row). Thresholds were set at a corrected p < 0.01, determined by Monte Carlo simulation. Red means increased functional connectivity; blue means decreased functional connectivity. L, left; R, right; MOG, middle occipital gyrus; SOFC, superior orbitofrontal cortex
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Aberrant functional connectivity of brain networks has been demonstrated in migraine sufferers. Functional magnetic resonance imaging (fMRI) may illustrate altered connectivity in patients suffering from migraine without aura (MwoA). Here, we applied a seed-based approach based on limbic regions to investigate disrupted functional connectivity betw...
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Background:
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Objective:
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Method:
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Citations
... This study showed significantly different connectivity between migraineurs with and without photophobia in the cerebellum, particularly in hemispheric cerebellar lobule VI. Several studies have previously examined the functional connectivity of the cerebellum in migraineurs [7][8][9][10][11][12][13][14][15]. However, few studies have investigated lobule IV, which is thought to be involved in voluntary movement control and cognitive functions [16,17]. ...
... These limitations unfortunately diminish the statistical robustness of the study, frequently necessitating suboptimal methods to establish significance and constraining the broader applicability of the findings [4]. This sample size limitation has also been observed in other functional MRI studies [10,12,14]. Further multicenter studies are required to address this issue. ...
Background: We have previously shown that static and dynamic resting-state functional connectivity differ between migraineurs with and without photophobia, phonophobia, or osmophobia. Furthermore, some patients with photophobia also experience phonophobia or osmophobia. To investigate the functional connectivity specific to migraineurs with photophobia, we examined the differences in static and dynamic resting-state functional connectivity between patients with and without photophobia, with no phonophobia or osmophobia. Methods: Fifteen migraineurs with photophobia but without phonophobia or osmophobia, as well as 15 sex- and age-matched migraineurs without photophobia, phonophobia, or osmophobia, underwent 3-T functional magnetic resonance imaging during the interictal phase. Static and dynamic resting-state functional connectivity were compared using region-of-interest analyses of 91 cortical, 15 subcortical, and 26 cerebellar areas. Results: Static resting-state functional connectivity analysis revealed ten significant connectivity pairs in patients with photophobia, while dynamic resting-state functional connectivity analysis revealed six significant connectivity pairs in patients with photophobia. Migraineurs with photophobia had significantly lower connectivity between the cerebellar hemisphere and the temporal region than those without photophobia in both static and dynamic studies. Conclusions: Our results show that lower resting-state functional connectivity between the cerebellar hemisphere and the temporal region is specific to migraineurs with photophobia.
... Numerous studies have indicated that the onset of migraines is linked with hyperexcitability in the hypothalamus and early reorganisation of ascending pain and central trigeminovascular pathways, including the insula, brainstem, limbic system, hypothalamus, thalamus, and certain functional networks. The methodology used in these studies included static and dynamic functional connectivity (FC), effective connectivity (EC), graph theory analysis, and local brain activity [8][9][10][11][12][13]. However, the reproducibility of the results of these studies is poor, and a direct comparison of these fMRI indices is lacking. ...
Background
Alterations in the static and dynamic characteristics of spontaneous brain activity have been extensively studied to investigate functional brain changes in migraine without aura (MwoA). However, alterations in concordance among the dynamics of spontaneous brain activity in MwoA remain largely unknown. This study aimed to determine the possibilities of diagnosis based on the concordance indices.
Methods
Resting-state functional MRI scans were performed on 32 patients with MwoA and 33 matched healthy controls (HCs) in the first cohort, as well as 36 patients with MwoA and 32 HCs in the validation cohort. The dynamic indices including fractional amplitude of low-frequency fluctuation, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity were analyzed. We calculated the concordance of grey matter volume-wise (across voxels) and voxel-wise (across time windows) to quantify the degree of integration among different functional levels represented by these dynamic indices. Subsequently, the voxel-wise concordance alterations were analyzed as features for multi-voxel pattern analysis (MVPA) utilizing the support vector machine.
Results
Compared with that of HCs, patients with MwoA had lower whole-grey matter volume-wise concordance, and the mean value of volume-wise concordance was negatively correlated with the frequency of migraine attacks. The MVPA results revealed that the most discriminative brain regions were the right thalamus, right cerebellar Crus II, left insula, left precentral gyrus, right cuneus, and left inferior occipital gyrus.
Conclusions
Concordance alterations in the dynamics of spontaneous brain activity in brain regions could be an important feature in the identification of patients with MwoA.
... Total intracranial volume (TIV) was the total of GM, WM, and CSF volumes. The volume of the amygdala was calculated by extracting mean voxel values in a region of interest (ROI), as defined by the AAL brain atlas, using WFU PickAtlas software as described in previous studies (Foell et al., 2019;Wei et al., 2020) (http://www.ansir.wfubmc.edu) ( Figure 1a). ...
Objective
The comorbid relationship between migraine and depression has been well recognized, but its underlying pathophysiology is unclear. Here, we aimed to explore the structural changes of the amygdala and the abnormal functional connectivity of the centromedial amygdala (CMA) in migraineurs with depression.
Methods
High‐resolution T1‐weighted and functional magnetic resonance images were acquired from 22 episodic migraineurs with comorbid depression (EMwD), 21 episodic migraineurs without depression (EM), and 17 healthy controls (HC). Voxel‐based morphometry and resting‐state functional connectivity (rsFC) were applied to examine the intergroup differences in amygdala volume.
Results
The bilateral amygdala volume was increased in the EMwD and EM groups compared with the HC group, but there were no differences between the EMwD and EM groups. The right CMA exhibited decreased rsFC in the left dorsolateral prefrontal cortex (DLPFC) in the EMwD group compared with the EM group, while rsFC increased between the CMA and the contralateral DLPFC in the EM group compared with the HC group. In addition, the EM group showed decreased rsFC between the left CMA and the left pallidum compared with the HC group.
Conclusions
Enlarged amygdala is an imaging feature of EM and EMwD. The inconsistency of rsFC between CMA and DLPFC between migraineurs with and without depression might indicate that decreased rsFC between CMA and DLPFC is a neuropathologic marker for the comorbidity of migraine and depression. The core regions might be a potential intervention target for the treatment of EMwD in the future.
... The role of the occipital lobe in migraine is thought to be related to visual aura (Bridge et al., 2015;Lai et al., 2016;Niddam et al., 2016). However, recent studies have showed that alterations in the occipital lobe can also be observed in migraines without aura (MWoA) Wei et al., 2020;Yin et al., 2020). As a center for auditory and visual integration, it may contribute to photophobia and phonophobia onset (Beauchamp, 2005). ...
Objectives:
Migraine is often combined with vestibular dysfunction, particularly in patients with chronic migraine (CM). However, the pathogenesis of migraine chronification leading to vestibular dysfunction is not fully understood. The current study investigated whether structural or functional impairments to the brain during migraine chronification could be associated with vestibular dysfunction development.
Methods:
The eligible participants underwent clinical assessment and magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) determined structural impairment by evaluating alterations in gray matter volume (GMV). Functional impairment was assessed by the mean amplitude of low-frequency fluctuation (mALFF). Furthermore, the resting-state functional connectivity (rsFC) of regions possessing impairment was examined with a seed-based approach. We also analyzed the correlations between altered neuroimaging features with clinical variables and performed multiple linear regression.
Results:
Eighteen CM patients, 18 episodic migraine (EM) patients, and 18 healthy controls (HCs) were included in this study. A one-way ANOVA indicated the group differences in mALFF. These were located within right supramarginal gyrus (SMG), left angular gyrus (AG), middle frontal gyrus (MFG), left middle occipital gyrus (MOG), right rolandic operculum (Rol) and left superior parietal gyrus (SPG). During rsFC analysis, the CM group had more enhanced rsFC of left SPG with left MOG than the EM and HC groups. The EM group revealed enhanced rsFC of left SPG with left AG than the CM and HC groups. In multiple linear regression, after controlling for age, body mass index (BMI) and disease duration, the rsFC of left SPG with left MOG (β = 48.896, p = 0.021) was found to predict the total Dizziness Handicap Inventory (DHI) score with an explained variance of 25.1%. Moreover, the rsFC of left SPG with left MOG (β = 1.253, p = 0.003) and right SMG (β = -1.571, p = 0.049) were significant predictors of migraine frequency, accounting for a total explained variance of 73.8%.
Conclusion:
The functional impairments due to migraine chronification are primarily concentrated in the multisensory integration-related brain regions. Additionally, the rsFC of SPG with MOG can predict the frequency of migraine and the degree of vestibular dysfunction. Therefore, these neuroimaging features could be potential mechanisms and therapeutic targets for developing vestibular dysfunction in migraine.
... High VAS scores were another determinant factor when classifying patients into diagnostic zones in our study. In recent clinical and functional magnetic resonance imaging (f-MRI) studies, disrupted limbic system (both amygdala and hippocampus) functional connectivity to pain-related cortex regions of modulation and encoding was reported (52,53). Resting-state functional abnormalities of the limbic system may lead to impairment of the pain process in patients with MwoA, resulting in increased pain intensity and hypersensitive response to external stimuli (52,54). ...
... In recent clinical and functional magnetic resonance imaging (f-MRI) studies, disrupted limbic system (both amygdala and hippocampus) functional connectivity to pain-related cortex regions of modulation and encoding was reported (52,53). Resting-state functional abnormalities of the limbic system may lead to impairment of the pain process in patients with MwoA, resulting in increased pain intensity and hypersensitive response to external stimuli (52,54). The magnitude of the neural responses in the complex network regulating pain (pain matrix) is correlated with the intensity of the perceived pain in migraine attacks (55,56). ...
... It is shown that cortico-limbic interactions mediate maladaptive responses relevant to psychopathology (Kovner et al., 2019) and pain progression with peripheral inflammation (Ma et al., 2019). Furthermore, abnormal functional patterns of the limbic system were significantly associated with pain-related characteristics and psychiatric disorders (Huang et al., 2021;Wei et al., 2020), and had the potential for predicting NSAIDs efficacy in migraine treatment (Wei et al., 2022). Therefore, our findings suggest that the effectiveness of known treatments that managing both migraine and psychiatric conditions should be considered in the clinical strategy. ...
Objectives:
To explore potential predictors of the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with migraine.
Methods:
Consecutive migraine patients were recruited and divided into responders and non-responders to NSAIDs according to follow-up for at least three months. Demographic data, migraine-related disabilities and characteristics, and psychiatric comorbidities were evaluated and used to build multivariable logistic regression models. Subsequently, we generated receiver operating characteristic (ROC) curves to explore the performance of these traits in predicting NSAIDs efficacy.
Results:
A total of 567 patients with migraine who completed at least three months of follow-up were enrolled. In the multivariate regression analysis, five factors were identified as potential predictors for NSAIDs efficacy in treating migraine. Namely, attack duration (odds ratio (OR) = 0.959; p < 0.001), headache impact (OR = 0.966; p = 0.015), depression (OR = 0.889; p < 0.001), anxiety (OR = 0.748; p < 0.001), and education level (OR = 1.362; p < 0.001) were associated with response to NSAIDs treatment. The area under the curve, sensitivity, and specificity combining these five factors for predicting the efficacy of NSAIDs were 0.834, 0.909 and 0.676.
Conclusions:
These findings suggest that migraine-related and psychiatric factors are associated with the response to NSAIDs in migraine management. Identifying such key factors may help to optimize individualized migraine management strategy.
... The limbic system is a functional system and works as an umbrella term for a set of anatomical structures (generally taken to include the cingulate gyri, amygdalae, hippocampi, hypothalamus, and septal areas) that function in close relation to each other and are involved in governing of many vegetative, emotional, and cognitive functions (141). Various components of the limbic system were identified as relevant in migraine (Table 3), with a strong focus on the amygdala (26,55,85,100,127,130), cingulate cortex (27,40,48,55,69,70,83,130,132), and hippocampus (26,31,55,81,108,123). ...
... The limbic system is a functional system and works as an umbrella term for a set of anatomical structures (generally taken to include the cingulate gyri, amygdalae, hippocampi, hypothalamus, and septal areas) that function in close relation to each other and are involved in governing of many vegetative, emotional, and cognitive functions (141). Various components of the limbic system were identified as relevant in migraine (Table 3), with a strong focus on the amygdala (26,55,85,100,127,130), cingulate cortex (27,40,48,55,69,70,83,130,132), and hippocampus (26,31,55,81,108,123). ...
... Hippocampus. The rs-FC of hippocampus was decreased to some areas (hypothalamus [31], right nucleus accumbens [119], inferior parietal gyrus and supplementary motor area [26]) and increased to other areas (hypothalamus [53], cerebellar and occipital areas [26]) compared to HC. rs-FCD of hippocampus was found increased in chronic migraine (123) as well as decreased in migraine without aura (55) compared to HC. The hippocampus was found to show altered rs-EC with frontal areas, visual areas, insula, and cerebellum between migraine without aura, chronic migraine, and HC (81). ...
Background:
Migraine is a highly prevalent primary headache disorder. Despite a high burden of disease, key disease mechanisms are not entirely understood. Functional magnetic resonance imaging is an imaging method using the blood-oxygen-level-dependent signal, which has been increasingly used in migraine research over recent years. This systematic review summarizes recent findings employing functional magnetic resonance imaging for the investigation of migraine.
Methods:
We conducted a systematic search and selection of functional magnetic resonance imaging applications in migraine from April 2014 to December 2021 (PubMed and references of identified articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines). Methodological details and main findings were extracted and synthesized.
Results:
Out of 224 articles identified, 114 were included after selection. Repeatedly emerging structures of interest included the insula, brainstem, limbic system, hypothalamus, thalamus, and functional networks. Assessment of functional brain changes in response to treatment is emerging, and machine learning has been used to investigate potential functional magnetic resonance imaging-based markers of migraine.
Conclusions:
A wide variety of functional magnetic resonance imaging-based metrics were found altered across the brain for heterogeneous migraine cohorts, partially correlating with clinical parameters and supporting the concept to conceive migraine as a brain state. However, a majority of findings from previous studies have not been replicated, and studies varied considerably regarding image acquisition and analyses techniques. Thus, while functional magnetic resonance imaging appears to have the potential to advance our understanding of migraine pathophysiology, replication of findings in large representative datasets and precise, standardized reporting of clinical data would likely benefit the field and further increase the value of observations
... High VAS scores were another determinant factor when classifying patients into diagnostic zones in our study. In recent clinical and functional magnetic resonance imaging (f-MRI) studies, disrupted limbic system (both amygdala and hippocampus) functional connectivity to pain-related cortex regions of modulation and encoding was reported (52,53). Resting-state functional abnormalities of the limbic system may lead to impairment of the pain process in patients with MwoA, resulting in increased pain intensity and hypersensitive response to external stimuli (52,54). ...
... In recent clinical and functional magnetic resonance imaging (f-MRI) studies, disrupted limbic system (both amygdala and hippocampus) functional connectivity to pain-related cortex regions of modulation and encoding was reported (52,53). Resting-state functional abnormalities of the limbic system may lead to impairment of the pain process in patients with MwoA, resulting in increased pain intensity and hypersensitive response to external stimuli (52,54). The magnitude of the neural responses in the complex network regulating pain (pain matrix) is correlated with the intensity of the perceived pain in migraine attacks (55,56). ...
Background
Migraine without aura (MwoA) is a very frequent and remarkable comorbidity in patients with idiopathic/genetic epilepsy (I/GE). Frequently in clinical practice, diagnosis of MwoA may be challenging despite the guidance of current diagnostic criteria of the International Classification of Headache Disorders 3 (ICHD-3). In this study, we aimed to disclose the diagnostic gaps in the diagnosis of comorbid MwoA, using a zone concept, in patients with I/GEs with headaches who were diagnosed by an experienced headache expert.
Methods
In this multicenter study including 809 consecutive patients with a diagnosis of I/GE with or without headache, 163 patients who were diagnosed by an experienced headache expert as having a comorbid MwoA were reevaluated. Eligible patients were divided into three subgroups, namely, full diagnosis, zone I, and zone II according to their status of fulfilling the ICHD-3 criteria. A Classification and Regression Tree (CART) analysis was performed to bring out the meaningful predictors when evaluating patients with I/GEs for MwoA comorbidity, using the variables that were significant in the univariate analysis.
Results
Longer headache duration (<4 h) followed by throbbing pain, higher visual analog scale (VAS) scores, increase of pain by physical activity, nausea/vomiting, and photophobia and/or phonophobia are the main distinguishing clinical characteristics of comorbid MwoA in patients with I/GE, for being classified in the full diagnosis group. Despite being not a part of the main ICHD-3 criteria, the presence of associated symptoms mainly osmophobia and also vertigo/dizziness had the distinguishing capability of being classified into zone subgroups. The most common epilepsy syndromes fulfilling full diagnosis criteria (n = 62) in the CART analysis were 48.39% Juvenile myoclonic epilepsy followed by 25.81% epilepsy with generalized tonic-clonic seizures alone.
Conclusion
Longer headache duration, throbbing pain, increase of pain by physical activity, photophobia and/or phonophobia, presence of vertigo/dizziness, osmophobia, and higher VAS scores are the main supportive associated factors when applying the ICHD-3 criteria for the comorbid MwoA diagnosis in patients with I/GEs. Evaluating these characteristics could be helpful to close the diagnostic gaps in everyday clinical practice and fasten the diagnostic process of comorbid MwoA in patients with I/GEs.
... Recent studies (38, 39) have argued that the dysfunction of the visual cortical neurons may also be an important factor in primary insomnia. Several studies (40)(41)(42)(43) have shown some degree of brain dysfunction in the visual central brain regions such as the lingual gyrus or occipital lobe, including migraines, anxiety symptoms, apnea syndrome, and cognitive impairment in patients with Parkinson's disease and hepatic encephalopathy, also indicating that the visual cortex is associated with cognitive and anxiety states. In a study of children with obstructive sleep apnea (44), the patient group showed significantly decreased ReHo values in the right lingual gyrus and left precuneus. ...
Objective
This study aimed to explore the abnormality of local brain function in patients with post-stroke insomnia (PSI) based on fMRI and explore the possible neuropathological mechanisms of insomnia in patients with PSI in combination with the Pittsburgh sleep quality index (PSQI) score and provide an objective evaluation index for the follow-up study of acupuncture treatment of PSI.
Methods
A total of 27 patients with insomnia after stroke were enrolled, and the PSQI was used to evaluate their sleep status. Twenty-seven healthy participants who underwent physical examinations during the same period were selected as controls. Resting-state brain function images and structural images of the two groups of participants were collected, and the abnormal changes in the regional brain function in patients with PSI were analyzed using three methods: regional homogeneity (ReHo), the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF), and a correlation analysis with the PSQI scale score.
Results
Compared with the HCs, the ReHo values of the PSI group in the bilateral lingual gyrus, right cuneus, right precentral and postcentral gyri were significantly lower, and the ReHo values of the left supramarginal gyrus were significantly higher. In the PSI group, the ALFF values in the bilateral lingual gyrus were significantly decreased, whereas those in the bilateral middle temporal gyrus, right inferior temporal gyrus, right inferior frontal gyrus, right limbic lobe, right precuneus, left posterior cingulate gyrus, and left middle occipital gyrus were significantly increased. Compared with HCs, the fALFF values of the bilateral lingual gyrus, bilateral inferior occipital gyrus, and bilateral cuneus in the PSI group were significantly higher. The ReHo value of the left supramarginal gyrus in the PSI group was significantly negatively correlated with the total PSQI score.
Conclusion
Patients with PSI have abnormal local activities in multiple brain regions, including the visual processing-related cortex, sensorimotor cortex, and some default-mode network (DMN) regions. Over-arousal of the DMN and over-sensitivity of the audiovisual stimuli in patients with PSI may be the main mechanisms of insomnia and can lead to a decline in cognitive function and abnormalities in emotion regulation simultaneously.
... In addition, cerebellum activation may also be related to the transmission of negative emotional states caused by pain and mental stress (Wittbrodt et al., 2020). RS-fMRI studies have shown abnormal local brain activity in the cerebellum and increased FC between the cerebellum and hippocampus in patients with chronic pain, which are closely related to pain perception and emotion regulation (Wang et al., 2015(Wang et al., , 2016Wei et al., 2020;Gui et al., 2021). In this study, TMD patients showed decreased ALFF of the right cerebellum_crus2 and increased FC between the PHG and vermis, and associated with the degree of oral-facial pain and depressive symptoms. ...
Background and Purpose
Temporomandibular disorders (TMD), especially pain-related TMD, are closely related to social and psychological factors. We aimed to measure changes in spontaneous brain activity and its related functional connectivity (FC), as well as FC characteristics within the mood-regulating circuits (MRC) in TMD patients by resting-state functional magnetic resonance imaging (RS-fMRI), and to analyze the relationship between these parameters and emotional symptoms.
Materials and Methods
Twenty-one adult TMD patients and thirty demographically matched healthy controls (HCs) underwent clinical scale evaluation and RS-fMRI scanning. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) between the two groups were compared. Regions with abnormal ALFF values were selected as areas of interest (ROIs) to compare the differences of whole-brain seed-based FC between groups. The FCs between regions within MRC were also analyzed and compared. In addition, the relationships between RS-fMRI characteristics and pain and mood were explored by correlation and mediation analyses.
Results
Compared with HCs, TMD patients showed increased ALFF in the right parahippocampal gyrus (PHG), the right supplementary motor area, and the bilateral precentral gyrus, with decreased ALFF in the right cerebelum_crus2. Patients showed enhanced right PHG-related FC in the vermis and posterior cingulate cortex, orbitofrontal cortex (OFC)-related FC in the striatal-frontal regions, while decreased dorsolateral prefrontal cortex-related FC in the amygdala. In TMD patients, ALFF values in the right PHG and FC values between the right PHG and the vermis were positively correlated with depressive symptoms. Abnormal FCs in the left striatal-orbitofrontal pathway were correlated with pain and depressive symptoms. More importantly, mediation analysis revealed that chronic pain mediates the relationship between FC of right PHG with vermis and depressive symptoms, and abnormal FC in the left striatal-orbitofrontal pathway can mediate the association between pain and depressive symptoms.
Conclusion
TMD patients have dysregulated spontaneous activity and FC in the default mode network, sensorimotor network and pain-related regions, as well as dysfunction of the fronto-striatal-limbic circuits. The development of negative emotions in TMD may be related to the dysfunction of components within the reward system (especially hippocampus complex, OFC, striatum) due to chronic pain.
