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Atypical Resting State Functional Connectivity of Pain Regions in Chronic Migraine (S16.004)
... And yet, as far as we know, very little research has focused on the abnormal connections in people with VM. As a subcortical structure, the thalamus has been proved to play a crucial role in both vestibular and pain pathways, serving as a relay switching station to transmit information from the vestibular nucleus to the vestibular cortex, and to deliver nociceptive stimulus from the brainstem to the sensory cortex [15][16][17]. Previous task-state fMRI and Positron Emission Computed Tomography (PET) studies have already demonstrated thalamus abnormities in VM patients [10,11,18]. ...
... Rights reserved. [15][16][17]. The two seeds (bilateral thalamus) were extracted from the FSL Harvard-Oxford atlas included in the CONN toolbox. ...
... We found that VM patients had altered resting-state thalamocortical FC with a set of brain areas involved in pain, vestibular and visual processing. The thalamus is thought to be an important subcortical area of the trigemino-thalamo-cortical pain pathway, and has been regarded as a relay station for sensory conduction, participates in the transmission, projection and emotion-related pain responses, which has been proved by previous fMRI and DTI studies in migraine [15,16,20,21]. The thalamus also has an important role in central vestibular pathway as it receives vestibular input from the vestibular nuclei and the cerebellum and relays vestibular information to the vestibular cortex [17]. ...
PurposeTo explore the functional connectivity (FC) between the bilateral thalamus and the other brain regions in patients with vestibular migraine (VM).Methods
Resting-state fMRI and 3D-T1 data were collected from 37 patients with VM during the interictal period and 44 age-, gender-, and years of education-matched healthy controls (HC). The FC of the bilateral thalamus was analyzed using a standard seed-based whole-brain correlation method. Furthermore, the correlations between thalamus FC and clinical characteristics of patients were investigated using Pearson’s partial correlation.ResultsCompared with HC, VM patients showed decreased FC between the left thalamus and the left anterior cingulate cortex (ACC), bilateral insular and right supplementary motor cortex. We also observed decreased FC between the right thalamus and the left insular and ACC in VM patients. Furthermore, patients with VM also exhibited increased FC between the left thalamus and the right precuneus and middle frontal gyrus, between the right thalamus and superior parietal lobule. FC between the right thalamus and the left insular was negatively correlated with disease duration (p = 0.019, r = − 0.399), FC between the left thalamus and the left ACC was negatively correlated with HIT-6 score (p = 0.004, r = − 0.484).ConclusionVM patients showed altered FC between thalamus and brain regions involved in pain, vestibular and visual processing, which are associated with specific clinical features. Specifically, VM patients showed reduced thalamo-pain and thallamo-vestibular pathways, while exhibited enhanced thalamo-visual pathway, which provided first insight into the underlying functional brain connectivity in VM patients.
... Alterations in rs-fMRI have been demonstrated in several studies [66][67][68][69][70][71][72]. For example, Lee et al. (2019) applied rs-fMRI and observed increased functional connectivity of the pain matrix in CM [73]. ...
... Comparable to our findings, inter-regional coupling was altered in CM in a particular (pain) network comprising anterior insula, thalamus, prefrontal cortex, precuneus and anterior cingulate cortex. Using a seed-based approach, Schwedt et al. (2013) reported rs-fMRI connectivity differences between CM and controls in the anterior insula, amygdala, pulvinar, thalamus, middle temporal cortex, and periaqueductal gray (PAG) [70]. Our study adds that not functional connectivity shows a correlation to migraine frequency [70] but also graph theoretical measures. ...
... Comparable to our findings, inter-regional coupling was altered in CM in a particular (pain) network comprising anterior insula, thalamus, prefrontal cortex, precuneus and anterior cingulate cortex. Using a seed-based approach, Schwedt et al. (2013) reported rs-fMRI connectivity differences between CM and controls in the anterior insula, amygdala, pulvinar, thalamus, middle temporal cortex, and periaqueductal gray (PAG) [70]. Our study adds that not functional connectivity shows a correlation to migraine frequency [70] but also graph theoretical measures. ...
Background
Migraine is a primary headache disorder that can be classified into an episodic (EM) and a chronic form (CM). Network analysis within the graph-theoretical framework based on connectivity patterns provides an approach to observe large-scale structural integrity. We test the hypothesis that migraineurs are characterized by a segregated network.
Methods
19 healthy controls (HC), 17 EM patients and 12 CM patients were included. Cortical thickness and subcortical volumes were computed, and topology was analyzed using a graph theory analytical framework and network-based statistics. We further used support vector machines regression (SVR) to identify whether these network measures were able to predict clinical parameters.
Results
Network based statistics revealed significantly lower interregional connectivity strength between anatomical compartments including the fronto-temporal, parietal and visual areas in EM and CM when compared to HC. Higher assortativity was seen in both patients’ group, with higher modularity for CM and higher transitivity for EM compared to HC. For subcortical networks, higher assortativity and transitivity were observed for both patients’ group with higher modularity for CM. SVR revealed that network measures could robustly predict clinical parameters for migraineurs.
Conclusion
We found global network disruption for EM and CM indicated by highly segregated network in migraine patients compared to HC. Higher modularity but lower clustering coefficient in CM is suggestive of more segregation in this group compared to EM. The presence of a segregated network could be a sign of maladaptive reorganization of headache related brain circuits, leading to migraine attacks or secondary alterations to pain.
... Alterations in rs-fMRI have been demonstrated in several studies (66)(67)(68)(69)(70)(71)(72). For example, Lee et al. (2019) applied rs-fMRI and observed increased functional connectivity of the pain matrix in CM (73). ...
... Comparable to our ndings, inter-regional coupling was altered in CM in a particular (pain) network comprising anterior insula, thalamus, prefrontal cortex, precuneus and anterior cingulate cortex. Using a seed-based approach, Schwedt et al. (2013) reported rs-fMRI connectivity differences between CM and controls in the anterior insula, amygdala, pulvinar, thalamus, middle temporal cortex, and periaqueductal gray (PAG) (70). Our study adds that not functional connectivity shows a correlation to migraine frequency (70) but also graph theoretical measures. ...
... Comparable to our ndings, inter-regional coupling was altered in CM in a particular (pain) network comprising anterior insula, thalamus, prefrontal cortex, precuneus and anterior cingulate cortex. Using a seed-based approach, Schwedt et al. (2013) reported rs-fMRI connectivity differences between CM and controls in the anterior insula, amygdala, pulvinar, thalamus, middle temporal cortex, and periaqueductal gray (PAG) (70). Our study adds that not functional connectivity shows a correlation to migraine frequency (70) but also graph theoretical measures. ...
Background: Migraine is a primary headache disorder that can be classified into an episodic (EM) and a chronic form (CM). Network analysis within the graph-theoretical framework based on connectivity patterns provides an approach to observe large-scale structural integrity. We test the hypothesis that migraineurs are characterized by a segregated network.
Methods: 19 healthy controls (HC), 17 EM patients and 12 CM patients were included. Cortical thickness and subcortical volumes were computed, and topology was analyzed using a graph theory analytical framework and network-based statistics. We further used support vector machines regression (SVR) to identify whether these network measures were able to predict clinical parameters.
Results: Network based statistics revealed significantly lower interregional connectivity strength between anatomical compartments including the fronto-temporal, parietal and visual areas in EM and CM when compared to HC. Higher assortativity was seen in both patients’ group, with higher modularity for CM and higher transitivity for EM compared to HC. For subcortical networks, higher assortativity and transitivity were observed for both patients’ group with higher modularity for CM. SVR revealed that network measures could robustly predict clinical parameters for migraineurs.
Conclusion: We found global network disruption for EM and CM indicated by highly segregated network in migraine patients compared to HC. Higher modularity but lower clustering coefficient in CM is suggestive of more segregation in this group compared to EM. The presence of a segregated network could be a sign of maladaptive reorganization of headache related brain circuits, leading to migraine attacks or secondary alterations to pain.
... As a first step we characterized differences in functional connectivity between patients with CM and medication overuse and a healthy population. Previous work on this topic has yielded inconclusive evidence (Schwedt et al., 2013;Chen et al., 2017;Androulakis et al., 2018;Coppola et al., 2019;Lee et al., 2019;Lerebours et al., 2019;Dai et al., 2021;Zou et al., 2021;Hu et al., 2023), possibly because of methodological limitations, such as small sample sizes, a focus on a limited number of brain areas or networks (differing across studies), or differences in choice of control groups. As a result of this lack of convergence between previous studies, the neural basis of CM is still poorly understood. ...
... Future research is needed to establish whether the visual hyperresponsivity of the visual system in CM is associated with the here reported alterations in functional connectivity with the visual system, as well as with the treatment-related reductions in functional connectivity in responders. Previous resting-state fMRI studies in CM patients have reported inconsistent evidence for altered functional connectivity of the visual cortex (Schwedt et al., 2013;Chen et al., 2017;Androulakis et al., 2018;Coppola et al., 2019;Lee et al., 2019;Lerebours et al., 2019;Dai et al., 2021;Zou et al., 2021). However, this is probably due to methodological limitations. ...
Acute withdrawal of headache medication in chronic migraine patients with medication overuse may lead to a dramatic reduction in headache frequency and severity. However, the brain networks underlying chronic migraine and a favorable response to acute withdrawal are still poorly understood. The goal of the present study was to characterize the pattern of intrinsic magnetic resonance imaging (MRI) functional connectivity (FC) specific to chronic migraine and to identify changes in FC that characterize subjects with CM reverting to less frequent headaches. Subjects with chronic migraine (N = 99) underwent a resting-state functional MRI scan before and after three months of medication withdrawal therapy. In addition, we included four control groups who were scanned once: healthy participants (N = 27), patients with episodic migraine (N = 25), patients with chronic back pain (N = 22), and patients with clinical depression (N = 17). Using dual regression analysis, we compared whole-brain voxel-level functional connectivity with ten well-known resting-state networks between chronic migraine and control groups, and between responders to treatment (≥50 % reduction in monthly headache days) and non-responders (<50 % reduction), before and after treatment. Subjects with chronic migraine showed differences in FC with a number of RS-networks, most of which involved the visual cortex, compared with healthy controls. A comparison with patients with episodic migraine, chronic pain and depression showed differences in the same direction, suggesting that altered patterns of functional connectivity in chronic migraine patients could to some extent be explained by shared symptomatology with other pain, depression, or migraine conditions. A comparison between responders and non-responders indicated that effective withdrawal reduced FC with the visual cortex for responders. Interestingly, responders already differed in functional connectivity of the visual cortex at baseline compared with non-responders. Altogether, we show that chronic migraine and successful medication withdrawal therapy are linked to changes in the functional connectivity of the visual cortex. These neuroimaging findings provide new insights into the pathways underlying migraine chronification and its reversibility.
... Chronic migraine (CM) signi cantly impacts the socioeconomic status and quality of life of affected individuals [4]. Many neuroimaging studies found structural and functional changes in the cortex [5][6][7][8][9][10][11][12], basal ganglia [7][8][9][10], thalamus [6,12], hypothalamus [13,14], brainstem [14,15] in patients with chronic migraine. However, studies investigating brain features of migraine chroni cation in animal models of CM [16,17], including the repeated dural application of in ammatory soup, chronic systemic infusion of nitroglycerin (NTG) remain scarce [18]. ...
... In NTG-induced migraine mice, the activation of ACC was consistent with clinical imaging studies and the nding of other genetic mice migraine models. For instance, in CM patients, stronger structural connectivity was found between the caudal anterior cingulate cortex (ACC) and other brain regions [5,10] and the N-acetylaspartate of bilateral thalami and right anterior cingulate decreased [6]. In the familial hemiplegic migraine type 2 (FHM2) mouse model, migraine-relevant hypersensitivity triggered by NTG has been attributed to altered neural function in the cingulate cortex [45] and CGRP receptors distributed in the cingulate cortex [39]. ...
Background
Chronic migraine is a common and disabling disorder. Functional MRI has established that abnormal brain region activation is present in chronic migraine. Drugs targeting the calcitonin gene-related peptide (CGRP) or its receptor have been reported to be efficient for treating chronic migraine. The CGRP signaling pathway has been documented in two types of preclinical migraine mouse models. However, it remains unclear how an active specific brain region develops migraine-like pain and whether CGRP receptor antagonists can alter specific brain region activation and relieve migraine-like pain. Therefore, we sought to investigate brain activation and the effect of olcegepant treatment on brain activation in two chronic migraine models and provide a reference for future research on neural circuits.
Methods
Repeated administration of nitroglycerin (NTG) or levcromakalim(LEV) was conducted to establish two types of preclinical migraine mouse models to stimulate human migraine-like pain. Mechanical hypersensitivity was evaluated using the von Frey filament test. Then, we evaluated the activation of different brain regions using c-Fos and NeuN staining. Olcegepant, a CGRP receptor-specific antagonist, was administered to explore its countering effect on brain region activation and mechanical hyperalgesia.
Results
After treatment with NTG and LEV, acute and chronic basal mechanical hyperalgesia was observed in the migraine models. Olcegepant, a CGRP receptor selective antagonist, significantly alleviated mechanical hyperalgesia in both models. In NTG-induced chronic migraine mice, the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and caudal part of the spinal trigeminal nucleus (Sp5c) showed a significant increase in c-Fos expression, while olcegepant reduced c-Fos expression. No change in c-Fos expression was found in the paraventricular thalamic nucleus (PVT) and ventrolateral periaqueductal gray (vlPAG). In LEV-induced migraine mice, mPFC, PVT and Sp5c showed a significant increase in c-Fos expression and olcegepant reduced c-Fos expression. No change in c-Fos expression was found in vlPAG and ACC.
Conclusions
Our study demonstrated activation of the medial prefrontal cortex and caudal part of the spinal trigeminal nucleus in both chronic migraine models. Olcegepant may alleviate hyperalgesia of the hind paw and periorbital area by attenuating brain activation in chronic migraine.
... The amygdala is one brain region that has been implicated in nociceptive processing, 16,17 migraine pathophysiology, [18][19][20] and sleep disturbance. [21][22][23][24] In adult patients with migraine, amygdalar functional connectivity with the whole brain is related to the severity of sleep disturbances (measured as categorical four-grade sleep disturbance scale ranging from normal to serious sleep disturbance). ...
... A potential explanation is the methodological differences between the studies, such as age range of participants, usage of medications, and analysis methods (seed-based connectivity vs. network connectivity). Nevertheless, our results are similar to the results of studies conducted in adults with migraine in which increased functional connectivity between the amygdala (left and right) and the secondary somatosensory cortex, 20 as well as between the left amygdala and the middle cingulate and precuneus 25 and superior frontal cortex19 are observed in adults with migraine compared to adult healthy controls. ...
Objective:
This case-control study examines if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents.
Background:
Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Sleep is often disturbed in adolescents with migraine, and could contribute to the alterations in functional connectivity.
Methods:
Twenty adolescents with migraine and 20 healthy controls were recruited from Cincinnati Children's Hospital. Participants completed surveys about their headaches and overall sleep quality, sleep hygiene, and perceived sleep difficulties (Insomnia Severity Scale [ISI]); completed wrist-worn actigraphy; and underwent a magnetic resonance imaging scan.
Results:
Adolescents with migraine differed from healthy controls only in perceived difficulty in sleep initiation and maintenance (ISI: 8.5 ± 4.7 and 4.5 ± 3.7 [mean ± standard deviation], -4.00 [95% confidence: -6.7 to -1.3], p = 0.005) and had greater functional connectivity between the amygdala and the posterior cingulate cortex, precuneus, dorsolateral prefrontal, sensorimotor, and the occipital cortexes. The differences in functional connectivity of the amygdala were not mediated by the subjective/objective sleep measures (ISI/wake minutes after sleep onset).
Conclusions:
Adolescents with migraine have greater connectivity between the amygdala and areas involved in sensory, affective, and cognitive aspects of pain. These alterations may not be due to higher levels of sleep difficulties in adolescents with migraine, suggesting that both amygdala and sleep alterations may play an independent role in migraine pathophysiology. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.
... 70 In patients with migraine, the neurophysiological characteristics in the ACC suggest the crucial role of diminished blood oxygen level-dependent response to noxious trigeminal stimulation, 49 altered N-acetyl aspartate or creatinine concentration, 9,41,45 decreased gray matter volume, 33,46,52 and atypical resting-state functional connectivity. 32,55 In the suboccipital stimulation of patients with CM, rCBF changes in the ACC were associated with headache improvement and correlated with pain scores. 38 The current findings support that the critical hub for affective pain in the ACC plays a pivotal role in migraine neuropathology in the resting-state condition. ...
... In functional connectivity measurements using fMRI, ACC connectivity also exhibited prominent alterations in patients with migraine. 32,55 Given the role of the ACC in affective and cognitive pain processing, the aforementioned findings suggest that migraine chronification is linked to neuroplasticity in the pain areas of higher-level processing rather than those involved in basic sensory discrimination (ie, SI and SII). This notion was supported by one recent work showed that ACC connectivity in migraine patients was able to predict the development of cutaneous allodynia, a well-known negative prognostic factor for migraine chronification. ...
Pain disorders are associated with aberrant oscillations in the pain-related cortical regions; however, few studies have investigated the relationship between the functional cortical network and migraine chronification through direct neural signals. Magnetoencephalography was used to record the resting-state brain activity of healthy controls as well as patients with episodic migraine (EM) and chronic migraine (CM). The source-based oscillatory dynamics of the pain-related cortical regions, which comprises 10 node regions (the bilateral primary [SI] and secondary somatosensory cortices, insula, medial frontal cortex, and anterior cingulate cortex [ACC]), were calculated to determine the intrinsic connectivity and node strength at 1 to 40 Hz. The total node strength within the pain-related cortical regions was smaller in the beta band in patients with migraine (70 EM and 80 CM) than in controls (n = 65). In the beta band, the node strength and functional connectivity values of patients with CM and patients with EM differed from those of controls in specific cortical areas, notably the left SI (EM < control) and bilateral ACC (CM < control); moreover, the node strength was lower in patients with CM than in those with EM. In all patients with migraine, negative correlations were observed between headache frequency and node strength in the bilateral ACC. In conclusion, migraine is characterized by reduced beta oscillatory connectivity within the pain-related cortical regions. Reduced beta connectivity in the ACC is linked to migraine chronification. Longitudinal studies should verify whether this oscillation change is a brain signature and a potential neuromodulation target for migraine.
... In gray matter volume studies, FM has been reported to significantly reduce gray matter volume in the amygdala [10] and exhibit an age-associated reduction in gray matter volume by 3.3 times compared with healthy controls [12], whereas gray matter volume exhibited structural plasticity that was nonlinearly linked to headache frequency in CM [54]. In functional connectivity studies, FM has been associated with reduced amygdala-ACC connectivity [11]; by contrast, increased connectivity between the amygdala and other pain-related regions has been observed in CM [55,56]. Additional studies directly comparing patients with FM and CM (without comorbidity with each other) in terms of limbic structural and functional changes and thus elucidating the reasons of the discrepancies in fear habituation are warranted. ...
... Amygdala fear habituation predicted pregabalin treatment outcomes in patients with FM. Previous studies indicating an association between the amygdala and sensory areas [55,56] have provided a theoretical basis for the intermediation of amygdala activity on bodily pain in FM. Some interventional studies have further demonstrated the modulatory effect of pregabalin on amygdala activity. ...
IntroductionFibromyalgia (FM) is a chronic pain condition characterized by impaired emotional regulation. This study explored the brain response to pain-related fear as a potential brain signature of FM.Methods
We used a conditioned fear task and magnetoencephalography to record pain-related fear responses in patients with FM. Two blocks of 30 fear responses were collected to compute the response strength in the first block and the strength difference between the first and second blocks (fear habituation). These measurements were investigated for their clinical relevance and compared with measurements obtained from healthy controls and patients with chronic migraine (CM), a different chronic pain condition often comorbid with FM.ResultsPain-related fear clearly activated the bilateral amygdala and anterior insula in patients with FM (n = 52), patients with CM (n = 50), and the controls (n = 30); the response strength in the first block was consistent across groups. However, fear habituation in the right amygdala decreased in the FM group (vs. CM and control groups, both p ≤ 0.001, no difference between CM and control groups). At the 3-month follow-up, the patients with FM reporting < 30% improvement in pain severity (n = 15) after pregabalin treatment exhibited lower fear habituation in the left amygdala at baseline (vs. ≥ 30% improvement, n = 22, p = 0.019). Receiver operating characteristic analysis confirmed that amygdala fear habituation is a suitable predictor of diagnosis and treatment outcomes of FM (area under the curve > 0.7).Conclusions
Amygdala activation to pain-related fear is maladaptive and linked to treatment outcomes in patients with FM. Because the aberrant amygdala response was not observed in the CM group, this response is a potential brain signature of FM.Trial RegistrationClinicalTrials.gov Identifier, NCT02747940.
... 11,12 There were significant correlations between the number of years with CM and the strength of functional connectivity (FC) between the anterior insula and mediodorsal thalamus, as well as between anterior insula and periaqueductal gray matter. 13 Migraineurs with severe allodynia had stronger FC between the periaqueductal gray matter and the insula, as well as between the nucleus cuneiform and the insula. 14 All these findings indirectly suggest that the insula has an important role in the pathophysiology of migraine of migraine. ...
... Consistent with the results of human CM studies, we found increased FC between the insula and the pons, between the insula and the midbrain, and between the insula and the thalamus in the interictal stage in the HF-IS group; these findings suggested that the insula participates in the sensory-discriminative, cognitive, and integrative domains of the pain experience. 13 Moreover, increased FC between the insula and the sensory cortex, as well as between the insula and the visual cortex, was found in the HF-IS group, implying that the chronification of migraine is due to the abnormal processing of sensory information and dysfunctional pain modulation. Due to its multidimensional link, the insula affects the pain experience by affecting the recognition or valence of a given sensory input, but not by altering sensory perception thresholds. ...
Migraine is a pain disorder accompanied by various symptoms. The insula, a “cortical hub,” is involved in many functions. Few studies have focused on the insula in migraine. We explored the resting-state functional connectivity between the insula and other brain areas in rats subjected to repeated meningeal nociception which was commonly used as animal model of migraine. Inflammatory soup was infused through supradural catheters in conscious rats. The rats were subdivided based on the frequency of the inflammatory soup infusions. Magnetic resonance imaging data were acquired on rats 21 days after inflammatory soup infusion and functional connectivity seeded on the insula was analyzed. In the low-frequency inflammatory soup group, magnetic resonance imaging was performed again 1 h after the glyceryl trinitrate injection following baseline scanning. The cerebellum showed increased functional connectivity with the insula in the inflammatory soup groups. The insula showed increased functional connectivity with the medulla and thalamus in the ictal period in the low-frequency inflammatory soup rats. In the high-frequency inflammatory soup group, several areas showed increased functional connectivity with the insula, including the pons, midbrain, thalamus, temporal association cortex, and retrosplenial, visual, and sensory cortices. Our findings support the hypothesis that the headache phase of migraine depends on the activation and sensitization of the trigeminovascular system, and that the chronification of migraine may be related to higher brain centers and limbic cortices. The insula may be a new target for treatment of migraine.
... Alterations in amygdalar function and structure are observed in adult participants with migraine. [43][44][45] Moreover, connectivity of the amygdala was identified as a key factor in classifying adult migraine participants vs healthy controls. 46 Previous studies have demonstrated changes in amygdalar connectivity after CBT. ...
... 54 In adult migraine patients but not in healthy controls, a negative connectivity between the right amygdala and the left occipital cortex was found. 45 However, the involvement of the lateral occipital cortex in CBT effects on pain is not clear. In rats, electrical stimulation of the occipital cortex had an antinociceptive effect on the tail-flick latency 55 or paw-withdrawal thresholds to mechanical stimulation in an incision pain model. ...
Objectives:
This basic mechanistic study examined the changes in brain activation and resting-state connectivity after 8 weeks of CBT in youth with migraine.
Background:
Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known.
Methods:
Eighteen adolescents with migraine (15 females, age 15.1 ± 2.1 years [mean ± SD]) completed 8 weekly CBT sessions. Before the first and after the final CBT session, participants underwent structural and resting-state blood-oxygen-level-dependent contrast MRI scans. Arterial spin labeling was also used to examine brain activation during the resting state. For connectivity analyses, the right and left amygdala were chosen as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated.
Results:
Headache frequency decreased from 15 ± 7.4 headaches per month before CBT to 10 ± 7.4 after CBT (P < .001). After CBT, greater brain activations in frontal regions involved in cognitive regulation of pain were found. In addition, after CBT increased connectivity between the amygdala and frontal regions was observed. Associations between brain activation and amygdalar connectivity with a reduction in headache frequency were also observed.
Conclusions:
Alterations in brain function and amygdalar connectivity with areas involved in nociceptive processing, cognitive function, and emotional regulation may underlie the ability of CBT to aid in the prevention of headaches in migraine patients.
... When comparing migraine patient to controls, the functional connectivity was changed within or with a number of different networks or seed areas: periaqueductal gray network [1,23], left [3,7] dorsal [5] and right [3,25] anterior cingulate cortex, fronto-parietal-network [4], right occipital lobe [5], left medial [5] and bilateral [7] prefrontal cortex, right cerebellum [5], brainstem [5], bilateral central executive network [6,20], left [16] salience network [6,20], default mode network [6,8,14,15,20,21], right thalamus [7], right [7] and anterior [9] insula, amygdala [9,10,24], bilateral caudate [11], right nucleus accumbens [11], hypothalamus [12], right executive control network [13], left dorsal attention network [16], right cuneus [16], visual network [17], marginal division of neostriatum [18], primary visual cortex [19], primary auditory cortex [19] and bilateral primary somatosensory cortex [26]. All areas with abnormal connectivity to the above-mentioned networks are shown in Table 1 and Additional file 1 and Fig. 2. ...
... When comparing migraine patient to controls, the functional connectivity was changed within or with a number of different networks or seed areas: periaqueductal gray network [1,23], left [3,7] dorsal [5] and right [3,25] anterior cingulate cortex, fronto-parietal-network [4], right occipital lobe [5], left medial [5] and bilateral [7] prefrontal cortex, right cerebellum [5], brainstem [5], bilateral central executive network [6,20], left [16] salience network [6,20], default mode network [6,8,14,15,20,21], right thalamus [7], right [7] and anterior [9] insula, amygdala [9,10,24], bilateral caudate [11], right nucleus accumbens [11], hypothalamus [12], right executive control network [13], left dorsal attention network [16], right cuneus [16], visual network [17], marginal division of neostriatum [18], primary visual cortex [19], primary auditory cortex [19] and bilateral primary somatosensory cortex [26]. All areas with abnormal connectivity to the above-mentioned networks are shown in Table 1 and Additional file 1 and Fig. 2. ...
Background:
Resting-state functional connectivity (FC) MRI has widely been used to understand migraine pathophysiology and to identify an imaging marker of the disorder. Here, we review what we have learned from FC studies.
Methods:
We performed a literature search on the PubMed website for original articles reporting data obtained from conventional resting-state FC recording in migraine patients compared with healthy controls or during and outside of migraine attacks in the same patients.
Results:
We found 219 articles and included 28 in this review after screening for inclusion and exclusion criteria. Twenty-five studies compared migraine patients with healthy controls, whereas three studies investigated migraine patients during and outside of attacks. In the studies of interictal migraine more alterations of more than 20 FC networks (including amygdala, caudate nucleus, central executive, cerebellum, cuneus, dorsal attention network, default mode, executive control, fronto-parietal, hypothalamus, insula, neostriatum, nucleus accumbens, occipital lobe, periaqueductal grey, prefrontal cortex, salience, somatosensory cortex I, thalamus and visual) were reported. We found a poor level of reproducibility and no migraine specific pattern across these studies.
Conclusion:
Based on the findings in the present review, it seems very difficult to extract knowledge of migraine pathophysiology or to identify a biomarker of migraine. There is an unmet need of guidelines for resting-state FC studies in migraine, which promote the use of homogenous terminology, public availability of protocol and the a priori hypothesis in line with for instance randomized clinical trial guidelines.
... Moreover, in a social threat task in which angry, fearful, or happy faces are presented, amygdala activation is heightened after exogenous testosterone is given to healthy women (Hermans et al., 2008, van Wingen et al., 2009. For migraine, differences in amygdala structure and functional connectivity with various brain regions, including the somatosensory, prefrontal, cingulate, and insular cortices, are found in patients with migraine compared to healthy controls (Hadjikhani et al., 2013, Schwedt et al., 2013, Faria et al., 2015, Chen et al., 2017, Chong et al., 2017, Zhang et al., 2023, Kosuge et al., 2024. Amygdala connectivity is also related to the response to migraine treatment. ...
Migraine affects ∼12 % of the worldwide population and is more prevalent in females, which suggests a role of sex hormones in migraine pathophysiology. Most studies have focused on estrogen and progesterone, and the involvement of androgens has been less studied. However, due to the recent advances in androgen interventions, which could advance new androgen-based migraine treatments, it is critical to better understand the role of androgens in migraine. Testosterone, the most studied androgen, was found to have an antinociceptive effect in various animal and human pain studies. Thus, it could also have a protective effect related to lower migraine severity and prevalence. In this review, we discuss studies examining the role of androgens on migraine-related symptoms in migraine animal models. Additionally, we summarize the results of human studies comparing androgen levels between patients with migraine and healthy controls, studies assessing the relationships between androgen levels and migraine severity, and intervention studies examining the impact of testosterone treatment on migraine severity. Many of the studies have limitations, however, the results suggest that androgens may have a minor effect on migraine. Still, it is possible that androgens are involved in migraine pathophysiology in a sub-group of patients such as in adolescents or postmenopausal women. We discuss potential mechanisms in which testosterone, as the main androgen tested, can impact migraine. These mechanisms range from the cellular level to systems and behavior and include the effect of testosterone on sensory neurons, the immune and vascular systems, the stress response, brain function, and mood. Lastly, we suggest future directions to advance this line of research.
... An increasing number of studies have shown that the IC also participates in pain perceptions as the anterior cingulate cortex (ACC) does by influencing synaptic transmission, such as in neuropathic pain, inflammatory pain and phantom limb pain [10][11][12][13][14][15][16], which leading these two area into major cortical areas for regulating chronic pain perception, especially for neuropathic pain [17][18][19][20][21][22][23]. A brain functional imaging study also has shown that the number of years of CM is significantly correlated with the strength of functional connections between the anterior IC and the medial dorsal thalamus, as well as between the anterior IC and periaqueductal gray matter [24]. Besides, the insular cortical thickness in women with migraine did not thin with age as it does in healthy individuals [25]. ...
Background
Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood.
Methods
The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats.
Results
The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application.
Conclusions
Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future.
... 2 Certain brain areas like entorhinal cortex, medial orbital frontal gyrus, pars triangularis and anterior cingulate cortex are involved in cognitive and affective processing of pain and many previous studies have suggested their role in migraine patients in terms of connectivity and activation. [3][4][5][6][7][8][9] Migraine affects patient's personal, family and social quality of life along with the financial loss in the form of missing duties and paying for consultation and medicine charges(an old estimated >$13 billion/year). Sufferers of migraine seldom get satisfied so almost 50% of them stop medications after consultation although 28% show satisfaction over therapeutic measures. ...
Methods: Data was collected on developed profoma, the same was analyzed on SPSS 22 nd version. Results: Out of 238 patients, 61 (25.6%) were male 177 (74.4%) were female patients. Age group distribution of study population ranged from 04-65 years with mean age was 31.66 with standard deviation of12.72. Out of 238 patients 170 (71.4%) were diagnosed as primary headache disorders, 56 (17%) were secondary headache while 12 (%) were labeled as cranial neuropathies and facial pains. Migraine without aura 113(65.3%) followed by tension type headache 35(20.2%) were most common primary headache disorder. Among secondary headaches Cervicogenic headache 16(30.2%) was most common cause followed by headache secondary to sinusitis, hypertension and trauma 8(15.1%), 7 (13.2%) and 6(11.3%) respectively. Trigeminal Neuralgia 9 (75.0%) was most common painful cranial neuropathies. Conclusion: Primary as well as secondary headache disorders are most prevalent in female at an age range of 21-40 years with majority of them suffering from migraine followed by tension and Cervical origin respectively. Article Citation: Lakhiar MA, Bughio AH, Arain AA, Lakhiar MA. Migraine; the most common headache disorders a neurology clinical perspective. Professional Med J 2019; 26(2):264-268.
... This neuropeptide is currently thought to play a role in nociception and cause vasodilation. 22 Functional magnetic resonance imaging has identified that chronic migraineurs have abnormal activity at the amygdala, thalamus, and temporal cortex, even when not experiencing an attack, 23 suggesting pathology regarding nociceptive processing. ...
Objective
To characterize migraine pathophysiology, presentation, and current treatment strategies, specifically in regard to vestibulocochlear manifestations of migraine.
Methods
Narrative review of available literature.
Results
Migraine disorder can be described as a spectrum of otologic manifestations, with vestibular migraine now recognized with fully‐fledged diagnostic criteria. Otologic manifestations are theorized to be due, in part, to trigeminal innervation of the inner ear structures and calcitonin gene‐related peptide (CGRP) expression within the labyrinth. Patients can experience vertigo, aural fullness, enhanced tinnitus, and hearing loss without the characteristic migraine headache, leading to under recognition of these symptoms as migraine‐related. Meniere's disease, mal de débarquement syndrome, persistent postural perceptual dizziness, and recurrent benign paroxysmal positional vertigo have close associations to migraine and may exist on the migraine spectrum. Migraine treatment consists of two goals: halting acute attacks (abortive therapy) and preventing attacks (prophylactic therapy). Abortive medications include triptans, corticosteroids, anti‐histamines, and anti‐emetics. Pharmacologic prophylaxis in conjunction with lifestyle modifications can decrease frequency and severity of symptoms and include tricyclic antidepressants, calcium channel blockers, anti‐epileptic medications, selective serotonin reuptake inhibitors, serotonin‐norepinephrine reuptake inhibitors, beta‐blockers, gepants, and monoclonal antibodies to CGRP. Promising evidence is emerging regarding the ability of migraine medications to positively treat the various otologic symptoms of migraine.
Conclusion
Migraine disorder manifesting with primarily cochleovestibular symptoms can be challenging to diagnose and manage for practicing clinicians. Patients with various vestibulopathies that are closely related to migraine may benefit from migraine treatment. Lifestyle choices and prophylactic medications are key to satisfactorily preventing acute migrainous attacks and improve function.
... Moreover, CTM inhibits pain by stimulating mechanoreceptors, which closes the "pain gate'' inducing the release of endogenous opiates (Holey, 2000;Holey & Dixon, 2014;Holey et al., 2011;Kaada and Torsteinbø, 1989). It was stated that migraineurs had ANS dysfunction with increased sympathetic activity, dysfunction in the pain inhibition mechanism, and painful intolerances to somatosensory, visual, olfactory, and auditory stimuli (Miglis, 2018;Schwedt et al., 2013). The results of our study might be attributed to the restoration of the balance of ANS and the pain-inhibiting effects of CTM. ...
Introduction
To investigate the effects of connective tissue massage (CTM) on pain characteristics, accompanying symptoms, medication usage, disability, sleep quality, psychological status, and quality of life in women with migraine.
Method
The study was designed as a prospective controlled clinical trial. Women were allocated into the CTM (CTM + education (Ed) program, n = 8) and control groups (only Ed program, n = 8). One session of Ed and 12 sessions of CTM were performed for 4 weeks. They filled out a headache diary, including pain characteristics, accompanying symptoms, and medication usage, for the pre-, during-, and after-treatment periods. Disability, sleep quality, psychological status, quality of life, and disability were evaluated with the Migraine Disability Assessment Scale, the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Headache Impact Test-6, and the Nottingham Health Profile, respectively.
Results
The CTM group showed a significant change in pain, accompanying symptoms (except vomiting), medication usage, and Nottingham Health Profile, Headache Impact Test-6, and Disability with Migraine Disability Assessment Scale scores compared to the control group (p < 0.05). Only the CTM group showed a significant change over time in all parameters of the headache diary except vomiting (p < 0.05). Only Nottingham Health Profile, Headache Impact Test-6, and Migraine Disability Assessment Scale scores improved in the CTM group (p < 0.05).
Discussions
CTM was superior for reducing pain characteristics, accompanying symptoms, medication usage, disability, and improving quality of life. Conclusion: CTM may be considered as a non-pharmacological and complementary therapy for migraine.
... The impairment of structural network integrity increases with the presence of migraine attacks, indicating that CM causes the strongest structural abnormalities [25]. Affective, emotional and cognitive processing is also affected, specifically in the hippocampus, parahippocampal gyrus and orbitofrontal cortex, and other areas in which differences have been identified on functional magnetic resonance imaging (MRI) in CM patients [26][27][28][29][30]. These structural changes are already seen in patients with a migraine frequency of > 9 days per month [31]. ...
Objective
To study the impact of chronic migraine (CM) on the cognition and quality of life (QoL) of patients in the interictal period, and to analyse the degree of reversibility of any observed alterations following the use of preventive treatment.
Background
CM is a highly disabling disease, and migraineurs often have associated comorbidities, such as subjective memory problems, that are involved in the development of cognitive impairment. Our hypotheses are that patients suffering from chronic migraine experience objective cognitive alterations that are not only due to the pain that they suffer or their current emotional state. Furthermore, preventive treatment should be capable of reversing, or at least reducing, the impact of CM on the cognition and QoL of migraineurs.
Methods
The cognition and QoL of 50 control subjects and 46 patients with CM were assessed using a battery of tests, prior to the use of preventive treatment based on botulinum toxin or oral drugs and after 3 months of this treatment.
Results
Compared with controls, patients with CM had lower scores on the assessment of cognitive performance (Rey-Osterrieth Complex Figure test [ROCF] (p<0.05), Trail Making Test [TMT] B) (p < 0.05) and QoL (p < 0.05). Three months after the use of preventive treatment, improvement was observed in all cognitive parameters (p < 0.05) and QoL (p < 0.05), except the ROCF copy task (p = 0.79). No statistically significant differences were observed when these outcomes were compared based on treatment.
Conclusions
This study confirms poor cognitive performance that is not explained by migraine pain itself, as it occurs in the interictal period, irrespective of the patient’s emotional status. Our findings show that these effects are reversible in some cases with preventive treatment of CM, reaffirming the important impact of this condition on the QoL of these patients, and the need to establish preventive treatment guidelines.
... In high frequency migraine, defined by 8 to 14 monthly migraine days, compared to low frequency migraine, heat painful stimulations of the hand induced lower controlateral anterior insula and bilateral inferior insula activations, but a higher connectivity of bilateral insula with the left post central gyrus [14]. In chronic migraine, number of years of chronic migraine were correlated to the resting state FC between bilateral anterior insula and the right mediodorsal thalamus, as well as to the FC between the right anterior insula and the periaqueductal grey matter (PAG) [15]. Overall, the insula is posited to play a key role in migraine, acting as a « hub» of integration of autonomic, sensory, affective and cognitive functions [16]. ...
Introduction
Insula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA.
Methods
Twenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis.
Results
Seed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO.
Discussion
The anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA.
Conclusion
The anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA.
Trial registration
NCT02708797.
... However, the phenomena investigated in these studies may not be comparable with our findings; most connectivity studies on episodic migraine used a resting state design and tested in the interictal phase during the absence of any headache (Colombo et al., 2015;Maleki and Gollub, 2016;Russo et al., 2017). Although aberrant connectivity between pain-related structures has been found in CM (Hsiao et al., 2021;Lee et al., 2019;Schwedt et al., 2013), the widespread results, methods and study designs makes it difficult to infer hypotheses on the underlying deviant connections. Unfortunately, the demanding computational analysis allows the investigation of only a small number of preselected cortical regions. ...
Chronic migraine is characterised by persistent headaches for more than 15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 minutes). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients.
The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.
... In high frequency migraine, defined by 8 to 14 monthly migraine days, compared to low frequency migraine, heat painful stimulations of the hand induced lower controlateral anterior insula and bilateral inferior insula activations, but a higher connectivity of bilateral insula with the left post central gyrus [14]. In chronic migraine, number of years of chronic migraine were correlated to the resting state FC between bilateral anterior insula and the right mediodorsal thalamus, as well as to the FC between the right anterior insula and the periaqueductal grey matter (PAG) [15]. Overall, the insula is posited to play a key role in migraine, acting as a « hub» of integration of autonomic, sensory, affective and cognitive functions [16]. ...
Introduction: Insula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA.
Methods: Twenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis.
Results: Seed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO.
Discussion: The anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA.
Conclusion: The anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA.
Trial registration: NCT02708797
... Affective, emotional and cognitive processing is also affected, speci cally in the hippocampus, parahippocampal gyrus and orbitofrontal cortex, and other areas in which differences have been identi ed on functional magnetic resonance imaging (MRI) in CM patients. [21][22][23][24][25] These structural changes are already seen in patients with a migraine frequency of > 9 days per month. 26 Other cognitive domains affected in these patients include processing speed, attention span, memory, verbal skills, and executive function processes (working memory, divided attention, and planning). ...
Objective. To study the impact of chronic migraine (CM) on the cognition and quality of life (QoL) of patients in the interictal period, and to analyze the degree of reversibility of any observed alterations following the use of preventive treatment.
Background. CM is a highly disabling disease, and migraineurs often have associated comorbidities, such as subjective memory problems, that are involved in the development of cognitive impairment.
Methods. The cognition and QoL of 50 control subjects and 46 patients with CM were assessed using a battery of tests, prior to the use of preventive treatment based on botulinum toxin or oral drugs and after 3 months of this treatment.
Results. Compared with controls, patients with CM had lower scores on the assessment of cognitive performance (Rey-Osterrieth Complex Figure test [ROCF], Trail Making Test [TMT] B) (p < 0.05) and QoL (p < 0.05). Three months after the use of preventive treatment, improvement was observed in all cognitive parameters (p < 0.05) and QoL (p < 0.05), except the ROCF copy task (p = 0.79). No statistically significant differences were observed when these outcomes were compared based on treatment.
Conclusions. This study confirms poor cognitive performance that is not explained by migraine pain itself, as it occurs in the interictal period, irrespective of the patients’ emotional status. Our findings show that these effects are reversible in some cases with preventive treatment of CM, reaffirming the important impact of this condition on the QoL of these patients, and the need to establish preventive treatment guidelines.
... Dans la migraine chronique, l'insula antérieure est plus fortement connectée au sein d'un réseau de la douleur impliquant le thalamus, l'amygdale, le cortex temporal et la substance grise périaqueducale. De plus, l'anciennete de la migraine chronique est corrélée à la connectivité entre l'insula antérieure et le thalamus dorsomédian et la substance grise périaqueducale(191).Dans la migraine avec aura, une étude en TEP-IRM utilisant un marqueur de l'inflammation neurogliale, le [ C 11]PBR28, a montré une fixation de l'insula, ainsi que du thalamus, du cortex somato-sensoriel primaire et secondaire et du cortex vixuel, ...
Introduction : La migraine avec aura (MA) augmente le risque d'accident vasculaire cérébral (AVC). Parmi les hypothèses pouvant expliquer cette association, un défaut d'autorégulation cérébrale (AC) et un risque accru de fibrillation atriale sont évoqués. L'AC est en partie contrôlée par des noyaux du tronc cérébral tel que le locus coeruleus qui peut être exploré par une IRM de neuromélanine. La fibrillation atriale peut être déclenchée par des lésions de l'insula, qui est activée au cours des crises de migraine. Nous avons recherché des biomarqueurs du risque d'AVC dans la MA en étudiant d'une part le signal du locus coeruleus et l'AC et d'autre part la connectivité de l'insula et la régulation du rythme cardiaque. Méthodes : Dans une étude cas-contrôle, nous avons comparé 23 migraineux avec aura, âgés de 30 à 55 ans, à 23 contrôles. L'évaluation de l'AC a reposé sur le calcul d'indices de corrélations temporel et fréquentiel entre la vitesse circulatoire cérébrale mesurée par doppler transcrânien et la pression artérielle mesurée par photo-pléthysmographie. La variabilité de la fréquence cardiaque a été évaluée dans le domaine fréquentiel par une analyse spectrale. Le signal et le volume du locus coeruleus ont été mesurés grâce à une IRM de neuromélanine et la connectivité de l'insula grâce à une IRM fonctionnelle de repos. Résultats : Aucune différence d'AC ni de la variabilité de la fréquence cardiaque n'a été trouvée. Toutefois il existait une corrélation négative entre les performances d'AC et l'ancienneté de la migraine (rho = - 0.62 ; p = 0,002). Le LC ne différait pas en signal ni en volume entre migraineux avec aura et contrôles. Une faible corrélation entre les performances d'AC et le signal de LC a été identifiée (rho = 0,33 ; p = 0,030). L'insula antérieure dorsale et bilatérale était plus fortement corrélée avec le cervelet (vermis VI) dans la migraine avec aura (à droite : T = 6,24 ; p < 0,0001, à gauche : T = 5,02 ; p < 0,0001). Cependant, cette connectivité accrue n'était pas corrélée à la variabilité de la fréquence cardiaque. Discussion : La corrélation négative entre l'AC et l'ancienneté de la migraine avec aura suggérait une altération de l'AC au début de la maladie, ce qui est cohérent avec un risque d'AVC accru à un âge jeune dans la MA. L'AC n'était que faiblement corrélée à l'intensité de neuromélanine du locus coeruleus et aucune différence du locus coeruleus n'était trouvée dans la MA, ce qui ne fait pas du locus coeruleus un bon biomarqueur. L'insula antérieure dorsale droite et gauche étaient plus fortement connectée au vermis VI dans la MA. Les données de la littérature suggèrent un rôle du vermis supérieur dans le contrôle du système nerveux autonome cardiovasculaire. Des travaux ultérieurs pourraient chercher à explorer le lien entre cette connectivité accrue, la dysautonomie et le risque de fibrillation atriale dans la MA. Conclusion : Le signal de neuromélanine du LC ne semblait pas être un biomarqueur du défaut d'AC dans la MA. En revanche, la connectivité accrue de l'insula antérieure dorsale bilatérale avec le vermis VI justifierait des recherches complémentaires pour comprendre son lien avec le contrôle du système nerveux autonome.
... The thalamus, a critical cortical structure in the pain-related network, plays a key role in the development of pain. The thalamus is involved in the processing, perception, and modulation of pain [36]. A previous study found that paininduced neurotransmitter transmission of endogenous opioid-activated peptides was responsible for altered thalamic blood flow and the production of nociception [37]. ...
Introduction:
Migraine is a common headache disorder. Many studies have used magnetic resonance imaging (MRI) to explore the possible pathogenesis of migraine, but they have not reached consistent conclusions and lack rigorous multiple comparison correction. Thus, this study investigates the mechanisms of migraine development from the perspective of altered functional connectivity (FC) in brain regions by using data-driven and regions of interest (ROI)-based approaches.
Methods:
Resting-state functional MRI data were collected from 30 patients with migraine and 40 healthy controls (HCs) matched for age, gender, and years of education. For the data-driven method, we used a voxel-mirrored homotopic connectivity (VMHC) approach to compare the FC between the patients and HCs. For the ROI-based method, significant differences in VMHC maps between the patients and HCs were defined as ROI. The seed-based approach further revealed significant differences in FC between the seeds and the other brain regions. Furthermore, the correlations between abnormal FC and clinical characteristics of patients were investigated. A rigorous multiple comparison correction was used with false discovery rate and permutation test (5000 times).
Results:
In comparison with the controls group, patients showed enhanced VMHC in the bilateral thalamus. We also observed enhanced FC between the left thalamus and the left superior frontal gyrus, and increased FC between the right thalamus and the left middle frontal gyrus (Brodmann area 45 and Brodmann area 8) in patients. Further analysis showed that the FC values in the left superior frontal gyrus and left middle frontal gyrus were negatively corrected with visual analogue scale scores or attack times for headaches.
Conclusions:
Patients with migraine showed altered VMHC in the bilateral thalamus, and abnormal FC of bilateral thalamus and other brain regions. The abnormalities in thalamic FC are a likely mechanism for the development of migraine.
Trial registration:
Chinese Clinical Trial Registry, ChiCTR2000033995. Registered on 20 June 2020.
... However, the phenomena investigated in these studies may not be comparable with our findings; most connectivity studies on episodic migraine used a resting state design and tested in the interictal phase during the absence of any headache (Colombo et al., 2015;Maleki & Gollub, 2016;Russo et al., 2017). Although aberrant connectivity between pain-related structures has been found in CM (Hsiao et al., 2021;Lee et al., 2019;Schwedt et al., 2013), the widespread results, methods and study designs makes it difficult to infer hypotheses on the underlying deviant connections. Unfortunately, the demanding computational analysis allows the investigation of only a small number of preselected cortical regions. ...
Chronic migraine is characterised by persistent headaches for more than 15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 minutes). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients.
The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.
... CM is defined as a headache that occurs at least 15 days per month for more than three months and at least eight days per month with migraine characteristics. In CM during the inter-ictal period, the number of years of CM and the FC between the left anterior insula−right periaqueductal gray, the right anterior insula−right mediodorsal thalamus, and the right anterior insula-right periaqueductal gray showed significantly positive correlations [36]. In other words, the longer the duration of chronicity, the higher is the FC associated with pain. ...
Magnetic resonance imaging (MRI) has been used to investigate migraine pathophysiology because it is a non-invasive technique. The main aim of clinical imaging for patients with headaches is to exclude secondary headaches due to organic lesions. Conventional structural imaging techniques such as routine MRI demonstrate white matter lesions, changes in gray matter volume or cortical thickness, and cerebral blood flow in patients with migraine. Changes in metabolite levels are observed by magnetic resonance spectroscopy. Diffusion tensor imaging, neurite orientation dispersion, density imaging, and functional MRI reveal dynamic real-time functional changes in brain microstructures. These analyses have been applied not only for comparing patients with migraine and healthy controls but also for understanding the dynamic changes in brain function during the cyclic migraine ictal phase. Although these analyses have demonstrated migraine pathophysiology, there are still many limitations. Following the improvement in imaging technology, further research on this topic is in progress.
... e amygdala is regarded as a key region in nociceptive processing and is highly connected to other pain regions such as the PFC, thalamus, anterior cingulate cortex, insula, and PAG [65,66]. Changes in the amygdala function and structure have also been found in previous studies in adults suffering from migraine [67][68][69]. ...
Purpose. To review the recent neuroimaging studies on cognitive-behavioral therapy (CBT) for pain management, with the aim of exploring possible mechanisms of CBT. Recent Findings. Current studies can be divided into four categories, mixed pain, fibromyalgia, migraine, and experimental pain, based on the type of disease included, with the same or different changes of brain regions after CBT intervention. According to structural and functional MRI analyses, changes of brain gray matter volume, activation and deactivation of brain regions, and intrinsic connectivity between brain regions were observed after CBT sessions. The brain regions involved mainly included some areas related to cognitive and emotional regulation. After comparison, the DLPFC, OFC, VLPFC, PCC and amygdala were found to be recurrent in multiple studies and may be key regions for CBT intervention in pain management. In the treatment of mixed chronic pain, CBT may decrease the gray matter volume of DLPFC, reduce ICN connection of OFC within the DAN network, and increase fALFF of the PCC. For FM intervention, CBT may activate the bilateral OFC and VLPFC, while in migraine, only the right OFC, VLPFC, and DLPFC were found to be more activated after CBT. In addition, the differential action of the left and right amygdala has also been shown in the latest study of migraine. In heat-evoked pain, CBT may increase the deactivation of the PCC, the connectivity between the DMN and right VLPFC, while diminishing the deactivation of VLPFC. Summary. After CBT, the brain showed stronger top-down pain control, cognitive reassessment, and altered perception of stimulus signals (chronic pain and repeated acute pain). The DLPFC, OFC, VLPFC, PCC, and amygdala may be the key brain regions in CBT intervention of pain.
... Figure 4 further showed that susceptibility value could able to discriminate CM patients with a sensitivity of 77.78% and a specificity of 100% (AUC = 0.949), which could be considered as an optimal imaging biomarker for the diagnosis of CM. Previously, conventional, functional, 42 and structural MRI [15][16][17][18] had been used to understand the neuromechanism of CM and had limited clinical practice. However, quantitative assessment of iron deposition by QSM could be conveniently performed from a clinical perspective. ...
Background:
Prior studies identified iron deposition in deep brain nuclei and the periaqueductal gray matter region in chronic migraine (CM), and less is known about the cerebral iron deposition over the whole cerebral gray matter in CM. The aim of this case-control study is to investigate the cerebral iron deposition of gray matter in CM using an advanced quantitative susceptibility mapping.
Methods:
A multi-echo gradient echo MR sequence was used to obtain raw quantitative susceptibility mapping data from 12 CM patients and 18 normal controls (NC), and the quantitative susceptibility mapping were reconstructed. Three dimensional T1 images were segmented and the gray matter mask was generated to extract the susceptibility value of gray matter over the whole brain. The independent t test and receiver operating characteristic curve (ROC) was used to investigate the iron deposition changes in CM patients.
Results:
CM presented a higher susceptibility value (1.44×10-3 ppm) compared with NC group (0.47×10-3 ppm) (P < 0.0001) over the whole cerebral gray matter. There was no correlation between susceptibility value and the clinical variables including disease duration, Visual Analog Scale (VAS), Migraine Disability Assessment Scale (MIDAS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and Montreal Cognitive Assessment (MoCA) scores (P > 0.05). ROC analysis demonstrated the susceptibility had a high diagnostic efficacy (AUC 0.949, sensitivity 77.78% and specificity 100%) in distinguishing CM from NC.
Conclusion:
CM patients had increased iron deposition in total cerebral gray matter which could be considered as a potential diagnostic and evaluated imaging biomarker in CM.
... 36 The strength of functional connectivity between the anterior insula and the mediodorsal thalamus as well as the PAG was significantly related to the disease duration in chronic migraine. 37 In addition, migraineurs with aura were indicated to have more fluctuating functional connectivity within the salience network (mainly composed of dACC and anterior insula) compared with migraineurs without aura and healthy individuals. 38 Apart from alterations within the salience network, the insula as well showed enhanced connectivity with the default network and the central executive network in migraineurs. ...
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.
... Weaker connectivity was found between the right amygdala and occipital regions in CM compared to healthy subjects. Similar results were obtained by 16 , who were identifying atypical resting-state functional connectivity e.g. of the anterior insula, amygdala, thalamus and the periaqueductal grey (PAG) in CM compared to controls. In addition, disease duration correlated with the strength of connectivity between the anterior insula, thalamic nuclei, and the PAG. ...
Background. Chronic pain diseases are characterised by an ongoing and fluctuating endogenous pain, yet it remains to be elucidated how this is reflected by the dynamics of ongoing functional cortical connections. The present study addresses this disparity by taking the individual perspective of pain patients into account, which is the varying intensity of endogenous pain.
Methods. To this end, we investigated the cortical encoding of 20 chronic back pain patients and 20 chronic migraineurs in four repeated fMRI sessions. During the recording, the patients were asked to continuously rate their pain intensity. A brain parcellation approach subdivided the whole brain into 408 regions. A 10 s sliding-window connectivity analysis computed the pair-wise and time-varying connectivity between all brain regions across the entire recording period. Linear mixed effects models were fitted for each pair of brain regions to explore the relationship between cortical connectivity and the observed trajectory of the patients' fluctuating endogenous pain.
Results. Two pain processing entities were taken into account: pain intensity (high, middle, low pain) and the direction of pain intensity changes (rising vs. falling pain). Overall, we found that periods of high and increasing pain were predominantly related to low cortical connectivity. For chronic back pain this applies to the pain intensity-related connectivity for limbic and cingulate areas, and for the precuneus. The change of pain intensity was subserved by connections in left parietal opercular regions, right insular regions, as well as large parts of the parietal, cingular and motor cortices. The change of pain intensity direction in chronic migraine was reflected by decreasing connectivity between the anterior insular cortex and orbitofrontal areas, as well as between the PCC and frontal and ACC regions.
Conclusions. Interestingly, the group results were not mirrored by the individual patterns of pain-related connectivity, which is suggested to deny the idea of a common neuronal core problem for chronic pain diseases. In a similar vein, our findings are supported by the experience of clinicians, who encounter patients with a unique composition of characteristics: personality traits, various combinations of symptoms, and a wide range of individual responses to treatment. The diversity of the individual cortical signatures of chronic pain encoding results adds to the understanding of chronic pain as a complex and multifaceted disease. The present findings support recent developments for more personalised medicine.
... Both functional and structural studies have suggested that repeat migraine attacks can remodel the pain network, chiefly focusing on allodynia as a marker of central sensitization. [51][52][53][54] A recent imaging study showed increased connectivity in CM versus EM between the anterior cingulate cortex, anterior insula, thalami, dorsolateral prefrontal cortex, precuneus, supramarginal gyri, and cerebellum, which would also likely impact widespread pain. 55 Other COPCs (urologic chronic pelvic pain syndrome, FM) have also demonstrated significant changes in increased brain gray matter volume and functional connectivity involving sensorimotor and insular cortices (p < 0.05 corrected) compared with pain-free controls. ...
Objective:
Chronic overlapping pain conditions (COPCs) represent a co-aggregation of widespread pain disorders. We characterized differences in physical and psychosocial functioning in patients with chronic migraine (CM) and those with CM and COPCs.
Background:
Patients with CM and COPCs have been identified as a distinct subgroup of patients with CM, and these patients may be vulnerable to greater symptom severity and burden.
Methods:
Data were extracted from Collaborative Health Outcomes Information Registry (an open-source learning health-care system), completed at the patients' first visit at a large tertiary care pain management center and electronic medical records. In 1601 patients with CM, the number of non-cephalic areas of pain endorsed on a body map was used to examine the differences in pain, physical and psychosocial function, adverse life experience, and health-care utilization.
Results:
Patients endorsing more body map regions reported significantly worse symptoms and function across all domains. Scored on a t-score metric (mean = 50, SD = 10), endorsement of one additional body map region corresponded with a 0.69-point increase in pain interference (95% CI = 0.55, 0.82; p < 0.001; Cohen's f = 0.328), 1.15-point increase in fatigue (95% CI = 0.97, 1.32; p < 0.001; Cohen's f = 0.432), and 1.21-point decrease in physical function (95% CI = -1.39, -1.03; p < 0.001; Cohen's f = 0.560). Patients with more widespread pain reported approximately 5% more physician visits (95% CI = 0.03, 0.07; p < 0.001), and patients reporting adverse life events prior to age 17 endorsed 22% more body map regions (95% CI = 0.11, 0.32; p < 0.001).
Conclusions:
Patients with CM and other overlapping pain conditions as noted on the body map report significantly worse pain-related physical function, psychosocial functioning, increased health-care utilization, and greater association with adverse life experiences, compared with those with localized CM. This study provides further evidence that patients with CM and co-occurring pain conditions are a distinct subgroup of CM and can be easily identified through patient-reported outcome measures.
... 3,118 Further, our findings of altered ACC connectivity in PTH are similar to those seen in animal and human studies of chronic headache disorders. [119][120][121][122] A mTBI, therefore, seems to incite a shift from acute to chronic pain processing and supports the use of treatment and management strategies targeted toward chronic pain mechanisms. 23 Future research identifying the underlying mechanisms for this rapid shift from acute to chronic pain processing is likely to provide some valuable insights into potential therapeutic options for this clinically challenging problem. ...
Introduction
Post-traumatic headaches (PTH) are common following mild traumatic brain injury (mTBI). There is evidence of altered central pain processing in adult PTH; however, little is known about how children with PTH process pain. The anterior cingulate cortex (ACC) plays a critical role in descending central pain modulation. In this study, we explored whether the functional connectivity (FC) of the ACC is altered in children with PTH.
Methods
In this case-control study, we investigated resting-state FC of 5 ACC seeds (caudal, dorsal, rostral, perigenual, and subgenual) in children with PTH ( n = 73) and without PTH ( n = 29) following mTBI, and healthy controls ( n = 27). Post-concussion symptoms were assessed using the Post-Concussion Symptom Inventory and the Child Health Questionnaire. Resting-state functional Magnetic Resonance Imaging (fMRI) data were used to generate maps of ACC FC. Group-level comparisons were performed within a target mask comprised of pain-related regions using FSL Randomise.
Results
We found decreased FC between the right perigenual ACC and the left cerebellum, and increased FC between the right subgenual ACC and the left dorsolateral prefrontal cortex in children with PTH compared to healthy controls. The ACC FC in children without PTH following mTBI did not differ from the group with PTH or healthy controls. FC between rostral and perigenual ACC seeds and the cerebellum was increased in children with PTH with pre-injury headaches compared to those with PTH without pre-injury headaches. There was a positive relationship between PTH severity and rostral ACC FC with the bilateral thalamus, right hippocampus and periaqueductal gray.
Conclusions
Central pain processing is altered in children with PTH. Pre-existing headaches help to drive this process.
Trial registration
The PlayGame Trial was registered in ClinicalTrials.gov database ( ClinicalTrials.gov Identifier: NCT01874847).
... Overall, these results are not in line with the results of the present study; comparison between the studies is difficult due to the differences in analysis methods (functional connectivity vs. activation; seed-based connectivity vs. network connectivity). Nevertheless, our results are similar to the results of other studies conducted in adults with migraine in which increased functional connectivity between the amygdala (left and right) and the secondary somatosensory cortex (80), as well as between the left amygdala and the middle cingulate and precuneus (25) and superior frontal (81) are observed in those with migraine compared to adult healthy controls. ...
Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Considering that sleep is often disturbed in those adolescents with migrane, this study examined if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents. Twenty adolescents with migraine and 20 healthy controls completed surveys about their headaches and overall sleep quality, sleep hygiene and perceived sleep difficulties, wore a wrist-worn actigraphy, and underwent an MRI scan.
Adolescents with migraine differed from healthy controls only in perceived sleep difficulties related to sleep initiation and maintenance ( p <0.01) and had greater functional connectivity between the amygdala and the posterior cingulate cortex, precuneus, dorsolateral prefrontal, sensorimotor, and the occipital cortexes. While the mediation model showed group differences in subjective and actigraphic sleep difficulties, these did not mediate the differences in amygdalar connectivity found between the groups. Adolescents with migraine have greater connectivity between the amygdala and areas involved in sensory, affective, and cognitive aspects of pain. These alterations may not be due to higher levels of sleep difficulties in adolescents with migraine, suggesting that both amygdala and sleep alterations may play an independent role in migraine pathophysiology
Perspective
This article evaluates the role plays by sleep on neural alterations in adolescents with migraine. It indicates that neural alterations due to migraine are not related to alterations in subjective and actigraphic sleep difficulties. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.
... Previous studies have demonstrated that the S1, S2, PMC, M1 and SMA comprise the sensorimotor network (De Luca et al., 2005). In addition, an increasing body of literatures has shown that people with migraine have alterations in the functional connectivities (FCs) of regions which important for mediating sensory, affective, and cognitive components of pain (Smith et al., 2009;Russo et al., 2012aRusso et al., , 2012bSchwedt et al., 2013;Mathur et al., 2015). ...
Migraine is a chronic dysfunction characterized by recurrent pain, but its pathogenesis is still unclear. As a result, more and more methods have been focused on the study of migraine in recent years, including functional magnetic resonance imaging (fMRI), which is a mainstream technique for exploring the neural mechanisms of migraine. In this paper, we systematically investigated the fMRI functional connectivities (FCs) between large-scale brain networks in migraine patients from the perspective of multi-channel hierarchy, including static and dynamic FCs of group and individual levels, where the brain networks were obtained using group independent component analysis. Meanwhile, the corresponding topology properties of static and dynamic FCs networks in migraine patients were statistically compared with those in healthy controls. Furthermore, a graph metrics based method was used to detect the potential brain functional connectivity states in dynamic FCs at individual and group levels, and the corresponding topology properties and specificity of these brain functional connectivity states in migraine patients were explored compared with these in healthy controls. The results showed that the dynamic FCs and corresponding global topology properties among nine large-scale brain networks involved in this study have significant differences between migraine patients and healthy controls, while local topological properties and dynamic fluctuations were easily affected by window-widths. Moreover, the implicit dynamic functional connectivity patterns in migraine patients presented specificity and consistency under different window-widths, which suggested that the dynamic changes in FCs and topology structure between them played a key role in the brain functional activity of migraine. Therefore, it may be provided a new perspective for the clinical diagnosis of migraine.
... * Jun Ke fmrikej@126.com 1 functional MRI, CM patients were shown to have disrupted connectivity within and between several networks [5][6][7], including the default mode network (DMN), salience network, and central executive network. Schwedt et al. [8] revealed that functional connectivity of affective regions (anterior insula, amygdala, and periaqueductal gray) differed in CM patients and healthy controls (HCs). Disrupted functional connectivity has also been found in the amygdala [9], hypothalamus [10,11], and marginal division [12] in CM patients relative to HCs or patients with episodic migraine. ...
Purpose
Previous studies have indicated disrupted functional connectivity in multiple brain regions and resting-state networks in episodic migraine, but it is unclear how brain network property is disrupted in chronic migraine.
Methods
Using resting-state functional magnetic resonance imaging and voxel-wise functional connectivity density analysis, we examined the large-scale functional connectivity pattern over the whole brain in 17 patients with chronic migraine without medication overuse compared to 35 healthy controls. The associations between functional connectivity density and clinical variables were also explored.
Results
Compared with controls, chronic migraine patients showed decreased local and distant functional connectivity density in the dorsolateral and medial prefrontal cortexes and precuneus and increased local and distant functional connectivity density in the hippocampal complex. The patients also presented increased local functional connectivity density in the orbital frontal gyrus and cerebellum and increased distant functional connectivity density in the temporal pole. Moreover, local functional connectivity density in several brain regions, such as the left superior temporal gyrus and dorsal anterior cingulate cortex, was found to be correlated with headache frequency or pain intensity.
Conclusion
Chronic migraine is associated with functional connectivity alterations in regions involved in multisensory integration, affective and cognitive processing, and pain modulation. Both local and distant functional connectivity density are complementary biomarkers for investigating the neural mechanism of this disorder. Some local functional connectivity density alterations may be useful for assessing the disease burden of chronic migraine.
... Previous studies have suggested that global functional de cits in multisensory information processing is a characteristic feature of migraineurs during the interictal period [47]. In our study, we applied a component analysis to examine the activation and modulation of the auditory cortex in information transfer in MwoA. ...
Background: Resting-state functional magnetic resonance imaging has confirmed auditory network dysfunction in migraine without aura (MwoA). Epidemiological investigations have disclosed that migraine is comorbid with many psychiatric symptoms. However, the underlying mechanisms of auditory cortex dysfunction linked to psychiatric disorders in MwoA remain unclear. The present study aimed to explore associations between brain activation in the auditory cortex and clinical and psychiatric characteristics in patients with MwoA during interictal periods.
Methods: Resting-state data were acquired from patients with episodic MwoA (n=34) and healthy controls (n=30). Independent component analysis was used to extract and calculate the resting-state auditory network. Subsequently, we analyzed the correlations between spontaneous activation in the auditory cortex and clinical and psychiatric features in MwoA.
Results: Compared with healthy controls, patients with MwoA showed increased activation in the left auditory cortex (i.e., superior temporal gyrus (STG), postcentral gyrus (PoCG) and insula). Brain activation in the left STG was positively correlated with anxiety scores, and activation in the left PoCG was negatively correlated with anxiety and depression scores. No significant differences were found in intracranial volume between the two groups.
Conclusions: This study indicated that functional impairment and altered integration within the auditory cortex existed in patients with MwoA in the interictal period, suggesting that auditory cortex disruption as a biomarker may be implemented for the early diagnosis and prediction of neuropsychiatric impairment in MwoA.
... The WM ber bundles found to be microstructurally peculiar in the CM group of the present study interconnect numerous and widespread cortical areas, many of those in previous functional resting-state MRI studies in patients with CM, have shown an altered connectivity at rest, including cortical areas belonging to the default, salient, and executive control networks, and their connectivity with the descending pain control system [41][42][43][44]. Indeed, in a previous study using the same cohort of patients, we found distinct abnormal connectivity patterns between frontal executive, dorsal attentional, and prefrontal-parietal default networks in patients with CM, as well as a correlation between such structural aberrations and headache severity [45,46]. ...
Background: We investigated intracerebral fiber bundles using a tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) datato investigate microstructural integrity in patients with episodic (MO) and chronic migraine (CM).
Methods: We performed DTI in 19 patients with MO within interictal periods, 18 patients with CM without any history of drug abuse, and 18 healthy controls (HCs) using a 3T magnetic resonance imaging scanner. We calculated diffusion metrics, including fractional anisotropy (FA), axial diffusion (AD), radial diffusion (RD), and mean diffusion (MD).
Results: TBSS revealed no significant differences in the FA, MD, RD, and AD maps between the MO and HC groups. In comparison to the HC group, theCM group exhibited widespread increased RD (bilateral superior [SCR] and posterior corona radiata [PCR], bilateral genu of the corpus callosum [CC], bilateral posterior limb of internal capsule [IC], bilateral superior longitudinal fasciculus [LF]) and MD values (tracts of the right SCR and PCR, right superior LF, and right splenium of the CC). In comparison to theMO group, theCM group showed decreased FA (bilateral SCR and PCR, bilateral body of CC, right superior LF, right forceps minor) and increased MD values (bilateral SCR and right PCR, right body of CC, right superior LF, right splenium of CC, and right posterior limb of IC).
Conclusion: Our results suggest that chronic migraine can be associated withthe widespread disruption of normal white matter integrity in the brain.
... In the eld of neuroimage, altered brain volumes and activities have been demonstrated in patients with CM compared to the patients with episodic migraine or the healthy controls (HC). However, whether such changes re ect the current status of frequent attacks, the longitudinal consequences of migraine attacks, or are pathogenic and involved in headache chroni cation is not clearly understood [7][8][9]. ...
Background: The increase of headache frequency is associated with higher headache related disability and lower quality of life in patients with migraine. However, the pathophysiology of migraine progression, persistence, or remission is elusive. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10–30 headache days/month).
Methods: We prospectively enrolled patients with HFM and healthy controls and collected their baseline clinical profiles and brain-MRI data at first visit. We longitudinally followed the patients and determined their outcomes at 2-year follow-up. Good outcome was defined as ≥ 50% reduction of baseline headache days and poor outcome was defined as reduction < 50% or frequency increase. Voxel-based morphometry was used to study gray matter volume (GMV), and structural covariance was used to investigate structural connectivity.
Results: Among 56 patients with HFM, 37 had good outcome and 19 poor outcome. Compared to the healthy controls (n = 37), patients with poor outcome had decreased GMV over the left posterior cingulate gyrus, and increased GMV over the bilateral cerebellum and the right precentral gyrus. Further, patients with poor outcome had greater GMV over the right and the left cerebella compared to patients with good outcome, and the GMVs of the cerebella were correlated to 2-year headache frequencies (right: r = 0.38, P = 0.005; left: r = 0.35, P = 0.009). Structural connectivity were increased between the cerebellum and the cuneus, the calcarine cortex, and the temporal lobe, respectively, in patients with poor outcome, and was decreased between the cerebellum and the prefrontal cortex in patients with poor outcome. The structural covariance integrities between the right cerebellum and the right cuneus were correlated to 2-year headache frequencies (r = 0.36, P = 0.008).
Conclusions: Structural volume and connectivity changes of the cerebellum may underlie headache persistence in patients with HFM.
... In the field of neuroimage, altered brain volumes and activities have been demonstrated in patients with CM compared to the patients with episodic migraine or the healthy controls (HC). However, whether such changes reflect the current status of frequent attacks, the longitudinal consequences of migraine attacks, or are pathogenic and involved in headache chronification is not clearly understood [7][8][9]. ...
Background: The increase of headache frequency is associated with higher headache related disability and lower quality of life in patients with migraine. However, the pathophysiology of migraine progression, persistence, or remission is elusive. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10–30 headache days/month). Methods: We prospectively enrolled patients with HFM and healthy controls and collected their baseline clinical profiles and brain-MRI data at first visit. We longitudinally followed the patients and determined their outcomes at 2-year follow-up. Good outcome was defined as ≥ 50% reduction of baseline headache days and poor outcome was defined as reduction
... In the field of neuroimage, altered brain volumes and activities have been demonstrated in patients with CM compared to the patients with episodic migraine or the healthy controls (HC). However, whether such changes reflect the current status of frequent attacks, the longitudinal consequences of migraine attacks, or are pathogenic and involved in headache chronification is not clearly understood [7][8][9]. ...
Background:
The increase of headache frequency is associated with higher headache related disability and lower quality of life in patients with migraine. However, the pathophysiology of migraine progression, persistence, or remission is elusive. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10-30 headache days/month).
Methods:
We prospectively enrolled patients with HFM and healthy controls and collected their baseline clinical profiles and brain-MRI data at first visit. We longitudinally followed the patients and determined their outcomes at 2-year follow-up. Good outcome was defined as ≥50% reduction of baseline headache days and poor outcome was defined as reduction < 50% or frequency increase. Voxel-based morphometry was used to study gray matter volume (GMV), and structural covariance was used to investigate structural connectivity.
Results:
Among 56 patients with HFM, 37 had good outcome and 19 poor outcome. Compared to the healthy controls (n = 37), patients with poor outcome had decreased GMV over the left posterior cingulate gyrus, and increased GMV over the bilateral cerebellum and the right precentral gyrus. Further, patients with poor outcome had greater GMV over the right and the left cerebella compared to patients with good outcome, and the GMVs of the cerebella were correlated to 2-year headache frequencies (right: r = 0.38, P = 0.005; left: r = 0.35, P = 0.009). Structural connectivity were increased between the cerebellum and the cuneus, the calcarine cortex, and the temporal lobe, respectively, in patients with poor outcome, and was decreased between the cerebellum and the prefrontal cortex in patients with poor outcome. The structural covariance integrities between the right cerebellum and the right cuneus were correlated to 2-year headache frequencies (r = 0.36, P = 0.008).
Conclusions:
Structural volume and connectivity changes of the cerebellum may underlie headache persistence in patients with HFM.
... These regions are involved in sensorydiscriminative, cognitive, and integrative domains of the pain experience, and atypical rsFCs may relate to aberrant pain processing in migraine. 33 In particular, several previous studies have suggested that migraine is a disorder of multiple sensory processing and have highlighted that migraines interfere with the flow of information between the thalamus and cortex with consequent disturbances in sensory, cognitive, and motor neural processes. [34][35][36] While recent translational neuroimaging studies have provided a basis for identifying neuropathologic features of MwoA, the present study has achieved a significantly increased level of classification accuracy from 82.0% (without feature selection) to 91.4% compared to previous studies using machine learning to discriminate migraine from healthy brains. ...
Objective:
To identify and validate an fMRI-based neural marker for migraine without aura (MwoA) and to examine its association with treatment response.
Methods:
We conducted cross-sectional studies with resting-state fMRI data from 230 participants and machine learning analyses. In studies 1 through 3, we identified, cross-validated, independently validated, and cross-sectionally validated an fMRI-based neural marker for MwoA. In study 4, we assessed the relationship between the neural marker and treatment responses in migraineurs who received a 4-week real or sham acupuncture treatment, or were waitlisted, in a registered clinical trial.
Results:
In study 1 (n = 116), we identified a neural marker with abnormal functional connectivity within the visual, default mode, sensorimotor, and frontal-parietal networks that could discriminate migraineurs from healthy controls (HCs) with 93% sensitivity and 89% specificity. In study 2 (n = 38), we investigated the generalizability of the marker by applying it to an independent cohort of migraineurs and HCs and achieved 84% sensitivity and specificity. In study 3 (n = 76), we verified the specificity of the marker with new datasets of migraineurs and patients with other chronic pain disorders (chronic low back pain and fibromyalgia) and demonstrated 78% sensitivity and 76% specificity for discriminating migraineurs from nonmigraineurs. In study 4 (n = 116), we found that the changes in the marker responses showed significant correlation with the changes in headache frequency in response to real acupuncture.
Conclusion:
We identified an fMRI-based neural marker that captures distinct characteristics of MwoA and can link disease pattern changes to brain changes.
... * Chunhong Hu hch5305@163.com cortex (ACC), hippocampus, parahippocampal gyrus (PHG), orbitofrontal cortex, have been found to show aberrant regional brain activity or functional connectivity in migraine patients (Ma et al. 2018;Jixin Liu et al. 2012;Russo et al. 2012;Schwedt et al. 2014;Schwedt et al. 2013;Jin et al. 2013). By contrast, structural brain abnormality in migraine has not got the attention it deserves. ...
Neuroimaging studies have implicated abnormal brain microstructure in episodic migraine (EM), but whether the pattern is altered during migraine chronification is not well known. Fifty-six patients with migraine without aura, including 39 EM patients and 17 chronic migraine (CM) patients, and 35 healthy controls (HCs) were enrolled. Voxel-based morphometry analysis was performed to assess gray matter (GM) volume differences among groups and their association with clinical feature was examined. Compared with the HC group, both migraine groups showed increased GM volume in the periaqueductal grey matter (PAG) and decreased GM volume in the anterior cingulate cortex (ACC). The left hippocampus/parahippocampal gyrus (PHG) volume of the HC group was smaller than that of the EM group, but was larger than that of the CM group. For the dorsolateral prefrontal cortex (dlPFC), the EM group showed the smallest GM volume while the CM group had the largest volume. Higher headache frequency was associated with greater GM volume in the PAG and dlPFC, but was associated with smaller GM volume in the ACC and hippocampus/PHG across all patients. GM volume changes in regions involved in pain generation and control are potential neural mechanism underlying migraine, and are associated with migraine types and headache frequency.
... Atypical resting-state functional connectivity has been demonstrated in chronic migraine [72]; these functional changes may contribute to structural changes observed in a chronic migraine patient's visual (V5) areas [2] and also in areas involved in cognitive aspects of pain processing, such as the anterior cingulate cortex (affective and cognitive pain processing, pain anticipation, identification of relevant environmental stimuli), the orbital frontal cortex (affective response to pain and emotion-based decision-making), entorhinal cortex (modulating expectations), and pars triangularis (empathy) [73]. Such structural changes can already be noticed in patients with more than nine migraine days per month [73]. ...
Background
Migraine is a complex neurological disorder that affects a significant percentage of the human species, from all geographic areas and cultures. Cognitive symptoms and dysfunctions are interim and disabling components of this disorder and may be related to the brain processes underlying the pathophysiology. Yet they are often undervalued by clinicians. In this review, we present the different types of cognitive dysfunctions associated with migraine and the mechanisms that are potentially causing them.
Findings
While reversible attack-related cognitive dysfunction seems extremely consistent and likely related to functional cortical and subcortical brain changes occurring during attacks, interictal cognitive dysfunction is less consistent and might become more relevant as attack frequency and disease complexity increase. Migraine traits do not seem a predisposition to long-term cognitive decline.
Summary
Cognitive dysfunction is a frequent manifestation of migraine attacks and may be specific to this disorder; it is important to understand if it could be useful in migraine diagnosis. Attack-related cognitive dysfunction is clinically relevant and contributes to disability, so it should be perceived as a therapeutic target. While there is no evidence to support that migraine increases the risk of long-term or persistent cognitive dysfunction, the fact that it occurs during the attacks and may persist in subjects with frequent or complicated attacks should prompt the understanding of the mechanisms related to its pathophysiology for it may also clarify the processes underlying migraine.
... 26,40,42,43 Previous studies have suggested that global dysfunction in multisensory information processing and integration characterizes migraineurs in the interictal period. 44 In our study, we applied topologic measures to examine the global and local efficiencies of information transfer in migraine patients, thus providing direct evidence of disrupted functional segregation and integration in brain networks of migraine patients. ...
Objective:
To investigate the dynamic functional connectivity of thalamo-cortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity.
Methods:
We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model.
Results:
Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC.
Conclusion:
Our results demonstrated a transient pathologic state with atypical thalamo-cortical connectivity in migraineurs and extended current findings regarding abnormal thalamo-cortical networks and dysrhythmia in migraine.
... Accordingly, changes in functional connectivity (FC) from 'task negative', e.g. 'default mode' network (DMN) to 'task positive' networks, for example, the salience network (SN), including insula and anterior cingulate cortex (ACC)-have been reported in various chronic painful conditions (Baliki et al., 2014;(Schwedt et al., 2013;Seminowicz and Davis 2007a). Functional alterations in the periaqueductal grey (PAG), a crucial hub in descending pain control, have been reported in chronic pain, (Brooks and Tracey 2005;Hemington and Coulombe 2015), but reports of network perturbations vary between patient cohorts and are often inconsistent, for example, increased PAG-ventromedial PFC (vmPFC)/rostral ACC connectivity in low back pain (Yu et al., 2014), but reductions in the same regions in migraineurs (Jiang et al., 2016). ...
Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes is varied and inconsistent between cohorts. Increases and decreases in connectivity strength in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how other networks are effected, for example, descending pain control networks, remains unknown. Whether connectivity changes relate to peripherally mediated nociceptive afferent input, represent coping strategies or are sequelae of chronic pain, e.g. anxiety/depression, is also unknown. Here, we examined FC changes in response to experimentally-administered tonic cold pain in healthy volunteers as a means of disambiguating the nature of connectivity changes. We assessed FC prior to, during, and following tonic cold painful stimulation in four seed regions: ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG) and recorded subjectively reported pain using a computerised visual analogue scale. We saw DMN FC changes during painful stimulation and that internetwork communication between the rAI and sgACC seeds with the vmPFC became less anti-correlated during pain, whereas PAG-precuneus FC decreased. Pain-induced FC alterations largely persisted during a 6-minute recovery period following cessation of the painful stimulus. Observed FC changes related to the magnitude of individuals' subjectively reported pain. We provide new insights into FC changes during and following tonic coldpain and suggest that some FC changes observed in chronic pain patients may relate to the presence of an ongoing afferent peripheral drive.
Brain dynamics can be modeled by a sequence of transient, nonoverlapping patterns of quasi-stable electrical potentials named "microstates." While electroencephalographic (EEG) microstates among patients with chronic pain remained inconsistent in the literature, this study characterizes the temporal dynamics of EEG microstates among healthy individuals during experimental sustained pain. We applied capsaicin (pain condition) or control (no-pain condition) cream to 58 healthy participants in different sessions and recorded resting-state EEG 15 min after application. We identified 4 canonical microstates (A-D) that are related to auditory, visual, salience, and attentional networks. Microstate C had less occurrence, as were bidirectional transitions between microstate C and microstates A and B during sustained pain. In contrast, sustained pain was associated with more frequent and longer duration of microsite D, as well as more bidirectional transitions between microstate D and microstates A and B. Microstate D duration positively correlated with intensity of ongoing pain. Sustained pain improved global integration within microstate C functional network, but weakened global integration and efficiency within microstate D functional network. These results suggest that sustained pain leads to an imbalance between processes that load on saliency (microstate C) and processes related to switching and reorientation of attention (microstate D).
Trigeminal autonomic cephalalgias are a group of headache disorders not epidemiologically relevant but extremely demanding for their clinical expression. They include cluster headache, paroxysmal hemicrania, hemicrania continua, SUNCT and SUNA and have been studied a lot over the decades and only recently they have found an application of innovative drugs for prevention. As for the acute treatment, we are still on drugs from a few decades ago. The importance of these forms of headache is given precisely by their relative rarity, as the clinician is often challenged by diagnoses that are not complex, but an adequate background often leads diagnostic delays and errors. This chapter allows immediate access to relevant and referenced literature for clinical aspects and pathophysiology, and above all for an adequate and immediate management of these extremely painful and overwhelming forms of headache. Furthermore, a series of experimental approaches to the trigeminal autonomic cephalalgias are present and must be left at the disposal of researchers.
Background: Migraine is a common and disabling primary headache associated with a wide range of psychiatric comorbidities. However, the mechanisms of emotion processing in migraine are not fully understood yet. The present study was designed to investigate the neural network during neutral, positive，and negative emotional stimuli in migraine suffers.
Methods: We enrolled 24 migraine suffers and 24 age- and sex-matched controls in this study. Neuromagnetic brain activity was recorded by using a whole-head magnetoencephalography (MEG) system towards human faces expression pictures. MEG data were analyzed in the multi-frequency band of 1–100 Hz.
Results: Migraine patients exhibited significantly enhanced effective connectivity from the prefrontal lobe to the temporal cortex during negative emotional stimuli in the gamma band(30-90Hz). Graph theory analysis revealed that patients had (1) an increased degree and clustering coefficient of connectivity in the delta band(1-4Hz) during positive emotional stimuli; (2) an increased degree of connectivity in the delta band(1-4Hz) during negative emotional stimuli.
Conclusion: The results suggested individuals with migraine showed deviant effective connectivity when viewing human facial expressions in multi-frequency. The prefrontal-temporal pathway might be related to the altered negative emotion modulation in migraine. These findings may contribute to understanding the mechanism of the comorbidity of depression and anxiety in migraine and provide references for the comprehensive therapeutic plan.
Here we investigate brain functional connectivity in patients with visual snow syndrome (VSS). Our main objective was to understand more about the underlying pathophysiology of this neurological syndrome. Twenty‐four patients with VSS and an equal number of gender and age‐matched healthy volunteers attended MRI sessions in which whole‐brain maps of functional connectivity were acquired under two conditions: at rest while watching a blank screen and during a visual paradigm consisting of a visual‐snow like stimulus. Eight unilateral seed regions were selected a priori based on previous observations and hypotheses; four seeds were placed in key anatomical areas of the visual pathways and the remaining were derived from a pre‐existing functional analysis. The between‐group analysis showed that patients with VSS had hyper and hypoconnectivity between key visual areas and the rest of the brain, both in the resting state and during a visual stimulation, compared with controls. We found altered connectivity internally within the visual network; between the thalamus/basal ganglia and the lingual gyrus; between the visual motion network and both the default mode and attentional networks. Further, patients with VSS presented decreased connectivity during external sensory input within the salience network, and between V5 and precuneus. Our results suggest that VSS is characterised by a widespread disturbance in the functional connectivity of several brain systems. This dysfunction involves the pre‐cortical and cortical visual pathways, the visual motion network, the attentional networks and finally the salience network; further, it represents evidence of ongoing alterations both at rest and during visual stimulus processing.
Background
Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes varies between cohorts and may relate to the consequences of living with chronic‐pain related comorbidities, such as anxiety, and depression. Healthy volunteer studies provide opportunities to study the effects of tonic noxious stimulation independently of these sequelae. Connectivity changes in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how these and other connectivity networks, for example, those governing descending pain control are affected by the presence of tonic, noxious stimulation in healthy, pain‐free individuals remains unknown.
Method
In 20 healthy volunteers, we assessed FC prior to, during, and following tonic cold painful stimulation in the ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG). We also recorded subjectively reported pain using a computerised visual analogue scale. Results: We saw DMN FC changes during painful stimulation and that inter‐network connectivity between the rAI with the vmPFC increased during pain, whereas PAG‐precuneus FC decreased. Pain‐induced FC alterations persisted following noxious stimulation. FC changes related to the magnitude of individuals’ subjectively reported pain.
Conclusions
We demonstrate FC changes during and following tonic cold‐pain in healthy participants. Similarities between our findings and reports of patients with chronic pain suggest that some FC changes observed in these patients may relate to the presence of an ongoing afferent nociceptive drive.
Migraine and stroke are among the most prevalent and disabling neurological diseases. Epidemiologic studies showed that there is an association between migraine and stroke. Migraineurs, especially those with aura, are more likely to develop subclinical infarct‐like lesions in the brain and are at risk for cryptogenic or cardioembolic stroke. Migrainous headache can be found at the onset of acute ischemic stroke in some patients, and in rare instances, an infarction can be directly attributed to a prolonged migraine aura, ie, migrainous infarction. Importantly, recent studies suggest that in the event of cerebral artery occlusion, even a history of migraine is sufficient to accelerate infarct progression and worsen outcomes. The mechanisms underlying the migraine‐stroke connection are multifactorial, with genetic predisposition, aura‐related electrophysiological mechanisms (cortical spreading depolarization), and cerebral microembolism being the most convincing ones at this point. Here, we provide a comprehensive overview on recent imaging studies that have helped us better understand the complex association between migraine and stroke.
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