Characteristics of pain empathic networks in healthy and primary dysmenorrhea women: an fMRI study.

Pain empathy enables us to understand and share how others feel pain. Few studies have investigated pain empathy-related functional interactions at the whole-brain level across all networks. Additionally, women with primary dysmenorrhea (PDM) have abnormal pain empathy, and the association among the whole-brain functional network, pain, and pain empathy remain unclear. Using resting-state functional magnetic resonance imaging (fMRI) and machine learning analysis, we identified the brain functional network connectivity (FNC)-based features that are associated with pain empathy in two studies. Specifically, Study 1 examined 41 healthy controls (HCs), while Study 2 investigated 45 women with PDM. Additionally, in Study 3, a classification analysis was performed to examine the differences in FNC between HCs and women with PDM. Pain empathy was evaluated using a visual stimuli experiment, and trait and state of menstrual pain were recorded. In Study 1, the results showed that pain empathy in HCs relied on dynamic interactions across whole-brain networks and was not concentrated in a single or two brain networks, suggesting the dynamic cooperation of networks for pain empathy in HCs. In Study 2, PDM exhibited a distinctive network for pain empathy. The features associated with pain empathy were concentrated in the sensorimotor network (SMN). In Study 3, the SMN-related dynamic FNC could accurately distinguish women with PDM from HCs and exhibited a significant association with trait menstrual pain. This study may deepen our understanding of the neural mechanisms underpinning pain empathy and suggest that menstrual pain may affect pain empathy through maladaptive dynamic interaction between brain networks.

Brain network dynamics in women with primary dysmenorrhea during the pain-free periovulation phase.

The human brain is a dynamic system that shows frequency-specific features. Neuroimaging studies have shown that both healthy individuals and those with chronic pain disorders experience pain influenced by various processes that fluctuate over time. Primary dysmenorrhea is a chronic visceral pain that disrupts the coordinated activity of brain's functional network. However, it remains unclear whether the dynamic interactions across the whole-brain network over time and their associations with neurobehavioral symptoms are dependent on the frequency bands in patients with primary dysmenorrhea during the pain-free periovulation phase. In this study, we used an energy landscape analysis to examine the interactions over time across the large-scale network in a sample of 59 patients with primary dysmenorrhea and 57 healthy controls at different frequency bands. Compared to healthy controls, patients with primary dysmenorrhea exhibit aberrant brain dynamics, with more significant differences in the slow-4 frequency band. Patients with primary dysmenorrhea show more indirect neural transition times due to an unstable intermediate state, whereas neurotypical brain activity frequently transitions between two major states. This data-driven approach further revealed that the brains of individuals with primary dysmenorrhea have more abnormal brain dynamics than healthy controls. Our results suggested that unstable brain dynamics were associated with the strength of brain functional segregation and the Pain Catastrophizing Scale (PCS) score. Our findings provide preliminary evidence that atypical dynamics in the functional network may serve as a potential key feature and biological marker of patients with PDM during the pain-free phase. PERSPECTIVE: We applied energy landscape analysis on brain-imaging data to identify relatively stable and dominant brain activity patterns for patients with primary dysmenorrhea(PDM). More atypical brain dynamics were found in the slow-4 band and were related to the strength of functional segregation, providing new insights into the dysfunction brain dynamics.

Individual differences of white matter characteristic along the anterior insula-based fiber tract circuit for pain empathy in healthy women and women with primary dysmenorrhea.

Pain empathy, defined as the ability of one person to understand another person's pain, shows large individual variations. The anterior insula is the core region of the pain empathy network. However, the relationship between white matter (WM) properties of the fiber tracts connecting the anterior insula with other cortical regions and an individual's ability to modulate pain empathy remains largely unclear. In this study, we outline an automatic seed-based fiber streamline (sFS) analysis method and multivariate pattern analysis (MVPA) to predict the levels of pain empathy in healthy women and women with primary dysmenorrhoea (PDM). Using the sFS method, the anterior insula-based fiber tract network was divided into five fiber cluster groups. In healthy women, interindividual differences in pain empathy were predicted only by the WM properties of the five fiber cluster groups, suggesting that interindividual differences in pain empathy may rely on the connectivity of the anterior insula-based fiber tract network. In women with PDM, pain empathy could be predicted by a single cluster group. The mean WM properties along the anterior insular-rostroventral area of the inferior parietal lobule further mediated the effect of pain on empathy in patients with PDM. Our results suggest that chronic periodic pain may lead to maladaptive plastic changes, which could further impair empathy by making women with PDM feel more pain when they see other people experiencing pain. Our study also addresses an important gap in the analysis of the microstructural characteristics of seed-based fiber tract network.

Short-term efficacy of stenting as a rescue therapy for acute atherosclerotic occlusion in anterior cerebral circulation.

Purpose: The study aimed to explore the efficacy and safety of the Neuroform EZ stent in treating acute anterior circulation large artery occlusion. Methods: The clinical data of 42 consecutive patients with acute anterior circulation large atherosclerotic occlusion who were treated with the Neuroform EZ stent from January 2018 to August 2019 in our stroke care center, including baseline characteristics, images, therapeutic condition, and follow-up data were retrospectively analyzed. Results: There were 42 mechanical thrombectomy (MT) failure cases of intracranial atherosclerotic stenosis with rescue Neuroform EZ stent implantation, of which 78.6% (33/42) had a good prognosis and 88.1% (37/42) showed no re-stenosis at follow-up. The average time from puncture to recanalization is 79.50 ± 14.19 min. The successful rate of intraoperative stent release is 97.6%, while there is one case of stent displacement, three cases of thrombus escape, and six cases of hemorrhage. Conclusion: Rescue therapy of the Neuroform EZ stent for acute anterior circulation large atherosclerotic occlusion can archive good short-term imaging and clinical results, while long-term follow-up is still needed to verify.

White matter changes in young and middle-aged males with chronic prostatitis/chronic pelvic pain syndrome: Tract-based spatial statistics analysis.

The supraspinal mechanism plays a key role in developing and maintaining chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, it is not clear how white matter changes in young and middle-aged males with CP/CPPS. In this cross-sectional study, 23 CP/CPPS patients and 22 healthy controls (HCs) were recruited. Tract-based spatial statistics was applied to investigate the differences in diffusion tensor imaging metrics, including fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD) and axial diffusion (AD), between CP/CPPS patients and HCs. The study also examined the association between white matter alterations and clinical variables in patients using correlation analysis. Compared with HCs, patients showed decreased FA, MD, RD and AD in the body and genu of the corpus callosum and right anterior corona radiata. In addition, they showed increased FA along with decreased MD, RD and AD in the left posterior limb of the internal capsule (PLIC-L), left external capsule and left cerebral peduncle. The FA of PLIC-L was negatively correlated with disease duration (r = -.54, corrected p = .017), while MD and RD were positively correlated (r = .45, corrected p = .042; r = .57, corrected p = .017). These results suggest that CP/CPPS is associated with extensive changes in white matter tracts, which are involved in pain processing. In particular, the FA, MD and RD values in the PLIC-L were correlated with the disease duration, indicating that the long-term course of CP/CPPS may have effects on the white matter microstructure of the pain perception pathways.

The functional connectivity of the basal ganglia subregions changed in mid-aged and young males with chronic prostatitis/chronic pelvic pain syndrome.

Background: The Basal ganglia (BG) played a crucial role in the brain-level mechanisms of chronic pain disorders. However, the functional changes of BG in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still poorly understood. This study investigated the BG subregions' resting-state functional connectivity (rs-FC) in CP/CPPS patients compared with healthy controls. Methods: Twenty eight patients with CP/CPPS and 28 age- and education-matched healthy males underwent clinical measurements and 3T brain MR imaging, including T1-weighted structural images and resting-state functional imaging. The data were analyzed by the seeded-based rs-FC analysis. Then, a machine learning method was applied to assess the feasibility of detecting CP/CPPS patients through the changed rs-FC. Results: Compared with healthy males, patients presented decreased rs-FC between the BG subregions and right middle cingulate cortex, and correlated with pain (r = 0.51, p-uncorrected = 0.005) and urinary symptoms (r = -0.4, p-uncorrected = 0.034). The left superior temporal gyrus and right supramarginal gyrus showed decreased rs-FC with the BG subregions as well. The area under the receiver operating characteristic curve of 0.943 (accuracy = 80%, F1-score = 80.6%) was achieved for the classification of CP/CPPS patients and healthy males with support vector machine (SVM) based on the changed rs-FC. Conclusion: These findings provide evidence of altered BG subregions' rs-FC in CP/CPPS, which may contribute to our understanding of the BG's role in CP/CPPS.

The effects of long-term menstrual pain on pain empathy in women with primary dysmenorrhea.

ABSTRACT: Primary dysmenorrhea (PDM) is not only a painful experience but also affects the psychological and affective states of women. Neuroimaging studies have revealed shared neural substrates for somatic and empathic pains in healthy subjects. However, little is known about the relationship between pain intensity and pain empathy in pain disorders. The cyclic nature of PDM makes it a unique model for investigating this issue during a patients' pain phase. To study how long-term pain modulates empathy for pain, T1-weighted magnetic resonance imaging scans were obtained in 39 PDM patients and 41 matched female healthy controls during menstruation. Subjects viewed static visual stimuli of the limbs submitted to painful and nonpainful stimulation to solicit empathy. The visual analogue scale for pain intensity and the Interpersonal Reactivity Index for empathic ability were also obtained. We found that women with PDM exhibited higher pain empathy compared with controls. The anterior insula and brain regions related to sensory discrimination with decreased gray matter volumes were not only shared but also acted as a mediator between pain intensity and pain empathy in PDM patients. In addition, the general linear modeling analysis revealed that long-term pain experience was a more important factor to pain empathy compared with pain intensity. This indicated that long-term pain may cause maladaptive brain structural plasticity, which may further affect psychological adjustment to bring patients more vivid pain when they witness suffering and distress in others.

Prediction of pain intensity with uterine morphological features and brain microstructural and functional properties in women with primary dysmenorrhea.

Primary dysmenorrhea (PDM), defined as painful menstrual cramps of uterine origin, could cause brain structural and functional changes after long-term menstrual pain. Here, we aimed to investigate the predictive value of uterine morphological features and microstructural/functional properties of the brain extracted from periovulatory phases for the intensity of menstrual pain as rated by women with PDM during their subsequent menstrual period. Forty-five women with PDM were recruited and classified into the high and mild pain intensity groups. Pelvic MRI was employed to extract the uterine texture features. White matter diffusion properties, grey matter and functional connectivity features were extracted as brain features. Multivariate logistic regression models with iteration optimization were built for classifying different pain intensity groups. Texture features from myometrium and uterine junction zone had outstanding prediction performance with an area under the receiver operating characteristic (AUC) of 0.96 (P < 0.05, permutation test), and diffusion properties along the thalamic fiber bundles were the most discriminative features with AUC of 0.95. Applying features from uterus and brain together, we could gain better prediction performance. Our results indicated that accumulated differences in menstrual pain were associated not only with uterine structure but also diffusion properties of thalamic-related fiber tracts, suggesting that treatment options of PDM patients may be expanded from only being able to manage pain in the uterus focusing on the functional/structural modifications of the pain processing system.

Effects of repeated menstrual pain on empathic neural responses in women with primary dysmenorrhea across the menstrual cycle.

Primary dysmenorrhea (PDM) is cyclic menstrual pain in the absence of pelvic anomalies, and it is thought to be a sex-hormone related disorder. Existing study has focused on the effects of menstrual cramps on brain function and structure, ignoring the psychological changes associated with menstrual pain. Here we examined whether pain empathy in PDM differs from healthy controls (HC) using task-based functional magnetic resonance imaging (fMRI). Fifty-seven PDM women and 53 matched HC were recruited, and data were collected at the luteal and menstruation phases, respectively. During fMRI scans, participants viewed pictures displaying exposure to painful situations and pictures without any pain cues and assessed the level of pain experienced by the person in the picture. Regarding the main effect of the pain pictures, our results showed that compared to viewing neutral pictures, viewing pain pictures caused significantly higher activation in the anterior insula (AI), anterior cingulate cortex, and the left inferior parietal lobule; and only the right AI exhibited a significant interaction effect (group × picture). Post-hoc analyses confirmed that, relative to neutral pictures, the right AI failed to be activated in PDM women viewing painsss pictures. Additionally, there was no significant interaction effect between the luteal and menstruation phases. It suggests that intermittent pain can lead to abnormal empathy in PDM women, which does not vary with the pain or pain-free phase. Our study may deepen the understanding of the relationship between recurrent spontaneous pain and empathy in a clinical disorder characterized by cyclic episodes of pain.

Abnormal white matter microstructure along the thalamus fiber pathways in women with primary dysmenorrhea.

Primary dysmenorrhea (PDM) is a cyclic menstrual pain in the absence of pelvic anomalies, and women with PDM have an increased sensitivity to pain than the internal and external areas associated with menstrual pain. However, the brain abnormality in the ascending pain pathways in dysmenorrhea remains largely unclear. As the thalamus plays a significant role in transmission of nociceptive input, we examined whether white matter microstructure of the thalamus-related fiber tracts obtained by DTI in women with PDM (n = 47) differs from healthy controls. A novel tractography atlas-based analysis method that detects tract integrity and altered microstructural properties along selected fibers was employed. The fiber bundles of interest contained the thalamus- primary somatosensory cortex (SI), thalamus- dorsal anterior cingulate cortex (dACC)/supplementary motor area (SMA), thalamus-insula, and thalamus-ACC. As compared with controls, abnormal white matter microstructures were found along the thalamus-related white matter fiber tracts. Additionally, the intensity of menstrual pain was significantly associated with diffusion measures of thalamus-SI fiber connections. Our study suggested that the thalamus-related pain processing pathways had altered white matter integrity that persisted beyond the time of menstruation, and the white matter microstructure of the thalamus-SI pathways was closely related to menstrual pain in the intensity by women with PDM.

Association Between Trait Empathy and Resting Brain Activity in Women With Primary Dysmenorrhea During the Pain and Pain-Free Phases.

Empathy refers to the ability to understand someone else's emotions and fluctuates with the current state in healthy individuals. However, little is known about the neural network of empathy in clinical populations at different pain states. The current study aimed to examine the effects of long-term pain on empathy-related networks and whether empathy varied at different pain states by studying primary dysmenorrhea (PDM) patients. Multivariate partial least squares was employed in 46 PDM women and 46 healthy controls (HC) during periovulatory, luteal, and menstruation phases. We identified neural networks associated with different aspects of empathy in both groups. Part of the obtained empathy-related network in PDM exhibited a similar activity compared with HC, including the right anterior insula and other regions, whereas others have an opposite activity in PDM, including the inferior frontal gyrus and right inferior parietal lobule. These results indicated an abnormal regulation to empathy in PDM. Furthermore, there was no difference in empathy association patterns in PDM between the pain and pain-free states. This study suggested that long-term pain experience may lead to an abnormal function of the brain network for empathy processing that did not vary with the pain or pain-free state across the menstrual cycle.

Correlation Between Thalamus-Related Functional Connectivity and Serum BDNF Levels During the Periovulatory Phase of Primary Dysmenorrhea.

The thalamus is a key region for the transmission of nociceptive information in the central modulation of pain and has been studied in the setting of numerous chronic pain conditions. Brain-derived neurotrophic factor (BDNF) is considered an important modulator for mediating nociceptive pathways in chronic pain. The present study aimed to investigate whether there was thalamus-related abnormal functional connectivity or relevant serum BDNF level alterations during periovulation in long-term primary dysmenorrhea (PDM). Thalamic subregions were defined according to the Human Brainnetome Atlas. Functional connectivity analyses were performed in 36 patients in the periovulatory phase and 29 age-, education-, and gender-matched healthy controls. Serum BDNF levels were evaluated by enzyme-linked immunosorbent assay and a significantly higher BDNF level was detected in PDM patients. Compared with HCs, PDM patients had abnormal functional connectivity of thalamic-subregions, mainly involving with prefrontal cortex, sensorimotor cortex, and temporal cortex. In addition, the functional connectivity of thalamic-subregions showed significant interactive effect correlated with serum BDNF level between PDM and HCs. It has been suggested that there were maladaptive or adoptive alteration associated with chronic menstrual pain even without the ongoing menstrual pain. BDNF might play a role in the development and chronicity of central nervous system dysfunction. These findings provided more accurate information about the involvement of the thalamus in the pathophysiology of PDM.

Altered amygdalar volume and functional connectivity in primary dysmenorrhoea during the menstrual cycle.

BACKGROUND: Primary dysmenorrhoea (PDM), characterized as menstrual pain without pelvic pathology, is associated with pain-related negative mood and hormone fluctuations. Previous studies strongly supported the link between pain and negative mood in affected individuals; however, it remains largely unknown in patients with PDM. METHODS: We focused on the effects how spontaneous pain, negative mood and hormone levels played on the central nervous system in 34 PDM women and 33 matched healthy controls across their cycles (periovulatory phase and menstruation phase) by using T1-weighted and functional imaging. Voxel-based morphometry and functional connectivity (FC) analyses were performed to evaluate brain structural and functional changes. Hormone concentrations (oestradiol, progesterone and cortisol) were also obtained. RESULTS: Abnormal state-related GM volume in the amygdala was found between periovulatory and menstruation phases in PDM. Furthermore, larger amygdalar volume was observed in patients' menstruation phase, which was significantly correlated with higher levels of cortisol. In addition, we found increased amygdala-seeded FC in vlPFC, which may be associated with pain intensity and negative mood in PDM women during the pain state. CONCLUSIONS: Taken together, we found women with PDM had structural and functional abnormalities in the amygdala, which associated with stress hormone levels, pain intensity and negative mood, may reflect disturbed emotional and pain modulation in women with PDM. SIGNIFICANCE: Our findings provide further evidence of amygdala-related abnormalities, which may be associated with pain-related affective distress and hormonal fluctuations in women with PDM, and complement the brain mechanism investigations for the pathophysiology of PDM.

Whole-brain structural magnetic resonance imaging-based classification of primary dysmenorrhea in pain-free phase: a machine learning study.

To develop a machine learning model to investigate the discriminative power of whole-brain gray-matter (GM) images derived from primary dysmenorrhea (PDM) women and healthy controls (HCs) during the pain-free phase and further evaluate the predictive ability of contributing features in predicting the variance in menstrual pain intensity. Sixty patients with PDM and 54 matched female HCs were recruited from the local university. All participants underwent the head and pelvic magnetic resonance imaging scans to calculate GM volume and myometrium-apparent diffusion coefficient (ADC) during their periovulatory phase. Questionnaire assessment was also conducted. A support vector machine algorithm was used to develop the classification model. The significance of model performance was determined by the permutation test. Multiple regression analysis was implemented to explore the relationship between discriminative features and intensity of menstrual pain. Demographics and myometrium ADC-based classifications failed to pass the permutation tests. Brain-based classification results demonstrated that 75.44% of subjects were correctly classified, with 83.33% identification of the patients with PDM (P < 0.001). In the regression analysis, demographical indicators and myometrium ADC accounted for a total of 29.37% of the variance in pain intensity. After regressing out these factors, GM features explained 60.33% of the remaining variance. Our results suggested that GM volume can be used to discriminate patients with PDM and HCs during the pain-free phase, and neuroimaging features can further predict the variance in the intensity of menstrual pain, which may provide a potential imaging marker for the assessment of menstrual pain intervention.

The relationship between putamen-SMA functional connectivity and sensorimotor abnormality in ESRD patients.

The basal ganglia (BG) are composed of several nuclei involved in neural processing associated with integration of sensory and motor information. Recent neuroimaging studies implicated its key role in control of voluntary motor function. As the sensorimotor abnormality is common among the end-stage renal disease (ESRD) population, in the current study, we aimed to investigate the abnormal structure and functional connectivity patterns of BG in ESRD patients. Twenty-nine ESRD and twenty-nine age and gender-matched healthy controls (HC) were enrolled to compare the volume of the subsets in the BG (e.g., caudate nucleus, putamen and globus pallidus) by using the VBM analysis; resting-state functional connectivity was analyzed by a seed-based method. Compared with the HC group, ESRD patients had a smaller volume in the right putamen. Taking the right putamen as a seed region, we further found reduced functional connectivity in patients mainly between the putamen and supplementary motor area (SMA), insula, posterior mid-cingulate gyrus, and primary motor cortex. In ESRD group, the severity score of restless legs syndrome was negatively correlated with putamen-SMA functional connectivity, while the hemoglobin level was positively correlated with functional connectivity degree between the putamen and SMA. Our results revealed an abnormal volume of the putamen and its decreased functional connectivity patterns during resting state in ESRD with sensorimotor abnormalities. These preliminary results indicated that the decreased functional connectivity in putamen-SMA was associated with sensorimotor abnormalities, and anemia was correlated with this abnormal functional pattern in ESRD patients.

Integration of white matter network is associated with interindividual differences in psychologically mediated placebo response in migraine patients.

Individual differences of brain changes of neural communication and integration in the modular architecture of the human brain network exist for the repeated migraine attack and physical or psychological stressors. However, whether the interindividual variability in the migraine brain connectome predicts placebo response to placebo treatment is still unclear. Using DTI and graph theory approaches, we systematically investigated the topological organization of white matter networks in 71 patients with migraine without aura (MO) and 50 matched healthy controls at three levels: global network measure, nodal efficiency, and nodal intramodule/intermodule efficiency. All patients participated in an 8-week sham acupuncture treatment to induce analgesia. In our results, 30% (n = 21) of patients had 50% change in migraine days from baseline after placebo treatment. At baseline, abnormal increased network integration was found in MO patients as compared with the HC group, and the increased global efficiency before starting clinical treatment was associated with their following placebo response. For nodal efficiency, significantly increased within-subnetwork nodal efficiency and intersubnetwork connectivity of the hippocampus and middle frontal gyrus in patients' white matter network were correlated with the responses of follow-up placebo treatment. Our findings suggested that the trait-like individual differences in pain-related maladaptive stress interfered with and diminished the capacity of chronic pain modulation differently, and the placebo response for treatment could be predicted from a prior white matter network modular structure in migraineurs. Hum Brain Mapp 38:5250-5259, 2017. © 2017 Wiley Periodicals, Inc.

Altered white matter microarchitecture in the cingulum bundle in women with primary dysmenorrhea: A tract-based analysis study.

Primary dysmenorrhea (PD), as characterized by painful menstrual cramps without organic causes, is associated with central sensitization and brain function changes. Previous studies showed the integrated role of the default mode network (DMN) in the pain connectome and its key contribution on how an individual perceives and copes with pain disorders. Here, we aimed to investigate whether the cingulum bundle connecting hub regions of the DMN was disrupted in young women with PD. Diffusion tensor imaging was obtained in 41 PD patients and 41 matched healthy controls (HC) during their periovulatory phase. The production of prostaglandins (PGs) was obtained in PD patients during their pain-free and pain phases. As compared with HC, PD patients had similar scores of pain intensity, anxiety, and depression in their pain-free phase. However, altered white matter properties mainly located in the posterior section of the cingulum bundle were observed in PD. Besides PGs being related to menstrual pain, a close relationship was found between the white matter properties of the cingulum bundle during the pain-free phase and the severity of the menstrual pain in PD patients. Our study suggested that PD had trait changes of white matter integrities in the cingulum bundle that persisted beyond the time of menstruation. We inferred that altered anatomical connections may lead to less-flexible communication within the DMN, and/or between the DMN and other pain-related brain networks, which may result in the central susceptibility to develop chronic pain conditions in PD's later life. Hum Brain Mapp 38:4430-4443, 2017. © 2017 Wiley Periodicals, Inc.

Brain structural properties predict psychologically mediated hypoalgesia in an 8-week sham acupuncture treatment for migraine.

Neuroimaging studies described brain structural changes that comprise the mechanisms underlying individual differences in migraine development and maintenance. However, whether such interindividual variability in migraine was observed in a pretreatment scan is a predisposition for subsequent hypoalgesia to placebo treatment that remains largely unclear. Using T1-weighted imaging, we investigated this issue in 50 healthy controls (HC) and 196 patients with migraine without aura (MO). An 8-week double-blinded, randomized, placebo-controlled acupuncture was used, and we only focused on the data from the sham acupuncture group. Eighty patients participated in an 8-weeks sham acupuncture treatment, and were subdivided (50% change in migraine days from baseline) into recovering (MOr) and persisting (MOp) patients. Optimized voxel-based morphometry (VBM) and functional connectivity analysis were performed to evaluate brain structural and functional changes. At baseline, MOp and MOr had similar migraine activity, anxiety and depression; reduced migraine days were accompanied by decreased anxiety in MOr. In our findings, the MOr group showed a smaller volume in the left medial prefrontal cortex (mPFC), and decreased mPFC-related functional connectivity was found in the default mode network. Additionally, the reduction in migraine days after placebo treatment was significantly associated with the baseline gray matter volume of the mPFC which could also predict post-treatment groups with high accuracy. It indicated that individual differences for the brain structure in the pain modulatory system at baseline served as a substrate on how an individual facilitated or diminished hypoalgesia responses to placebo treatment in migraineurs. Hum Brain Mapp 38:4386-4397, 2017. © 2017 Wiley Periodicals, Inc.

Abnormal rich club organization and impaired correlation between structural and functional connectivity in migraine sufferers.

Because of the unique position of the topologically central role of densely interconnected brain hubs, our study aimed to investigate whether these regions and their related connections would be particularly vulnerable to migraine. In our study, we explored the rich club structure and its role in global functional dynamics in 30 patients with migraine without aura and 30 healthy controls. DTI and resting fMRI were used to construct structural connectivity (SC) and functional connectivity (FC) networks. An independent replication data set of 26 patients and 26 controls was included to replicate and validate significant findings. As compared with the controls, the structural networks of patients exhibited altered rich club organization with higher level of feeder connection density, abnormal small-world organization with increased global efficiency and decreased strength of SC-FC coupling. As these abnormal topological properties and headache attack duration exhibited a significant association with increased density of feeder connections, our results indicated that migraine may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher 'bridgeness' with non-rich club regions, which may increase the integration among pain-related brain circuits with more excitability but less inhibition for the modulation of migraine.