Disruption of Periaqueductal Gray-default Mode Network Functional Connectivity in Patients with Crohn's Disease with Abdominal Pain.

Abdominal pain in Crohn's disease (CD) has been known to be associated with changes in the central nervous system. The periaqueductal gray (PAG) plays a well-established role in pain processing. However, the role of PAG-related network and the effect of pain on the network in CD remain unclear.Resting-state functional magnetic imaging (fMRI) data were collected from 24 CD patients in remission with abdominal pain, 24 CD patients without abdominal pain and 28 healthy controls (HCs). Using the subregions of PAG (dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG)) as seeds, the seed-based FC maps were calculated and one-way analysis of variance (ANOVA) was performed to investigate the differences among the three groups.Results showed that the group differences were mainly involved in the FC of the vlPAG with the precuneus, medial prefrontal cortex (mPFC) as well as orbitofrontal cortex (OFC), and the FC of the right lateral PAG (lPAG) with the precuneus, inferior parietal lobule (IPL), angular gyrus and premotor cortex. The FC values of all these regions decreased successively in the order of HCs, CD without abdominal pain and CD with abdominal pain. The pain score was negatively correlated with the FC of the l/vlPAG with the precuneus, angular gyrus and mPFC in CD patients with abdominal pain.This study implicated the disrupt communication between the PAG and the default mode network (DMN). These findings complemented neuroimaging evidence for the pathophysiology of visceral pain in CD patients.

Altered functional connectivity density and structural covariance networks in women with premenstrual syndrome.

Background: Premenstrual syndrome (PMS) is a menstrual-related disorder, characterized by physical, emotional, behavioral and cognitive symptoms. However, the neuropathological mechanisms of PMS remain unclear. This study aimed to investigate the frequency-specific functional connectivity density (FCD) and structural covariance in PMS. Methods: Functional and T1-weighted structural data were obtained from 35 PMS patients and 36 healthy controls (HCs). This study was a cross-sectional and prospective design. The local/long-range FCD (LFCD/LRFCD) across slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands were computed, and two-way analysis of variance (ANOVA) was performed to ascertain the main effects of group and interaction effects between group and frequency band. Receiver operating characteristic (ROC) curve was performed to investigate reliable biomarkers for identifying PMS from HCs. Based on the ROC results, characterized the changes of whole-brain structural covariance patterns of striatum subregions in two groups. Correlation analysis was applied to examine relationships between the clinical symptoms and abnormal brain regions. Results: Compared with HCs, PMS patients exhibited: (I) aberrant functional communication in the middle cingulate cortex and precentral gyrus; (II) significant frequency band-by-group interaction effects of the striatum, thalamus and orbitofrontal cortex; (III) the better classification ability of the LFCD in the striatum in ROC analysis (slow-5); (IV) decreased gray matter volumes in the caudate subregions and decreased structural associations of between the caudate subregions and frontal cortex; (V) the LFCD value in thalamus were significantly negatively correlated with the sleep problems (slow-5). Conclusions: Based on multi-modal magnetic resonance imaging (MRI) analysis, this study might imply the aberrant emotional regulation and cognitive function related to menstrual cycle in PMS and improve our understanding of the pathophysiologic mechanism in PMS from novel perspective.

Multivariate Pattern Analysis of Lifelong Premature Ejaculation Based on Multiple Kernel Support Vector Machine.

Objective: This study aimed to develop an effective support vector machine (SVM) classifier based on the multi-modal data for detecting the main brain networks involved in group separation of premature ejaculation (PE). Methods: A total of fifty-two patients with lifelong PE and 36 matched healthy controls were enrolled in this study. Structural MRI data, functional MRI data, and diffusion tensor imaging (DTI) data were used to process SPM12, DPABI4.5, and PANDA, respectively. A total of 12,735 features were reduced by the Mann-Whitney U test. The resilience nets method was further used to select features. Results: Finally, 36 features (3 structural MRI, 7 functional MRI, and 26 DTI) were chosen in the training dataset. We got the best SVM model with an accuracy of 97.5% and an area under the curve (AUC) of 0.986 in the training dataset as well as an accuracy of 91.4% and an AUC of 0.966 in the testing dataset. Conclusion: Our findings showed that the majority of the brain abnormalities for the classification was located within or across several networks. This study may contribute to the neural mechanisms of PE and provide new insights into the pathophysiology of patients with lifelong PE.

Altered structural covariance and functional connectivity of the insula in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a clinically chronic inflammatory bowel disease, which has been shown to be closely related to the brain-gut axis dysfunction. Although traditionally considered to be a limbic region, the insula has also been commonly identified as an abnormal brain region in previous CD-related studies. METHODS: Structural magnetic resonance imaging (MRI) and resting-state functional MRI images were acquired from 45 CD patients in remission and 40 healthy controls (HCs). Three neuroimaging analysis methods including voxel-based morphometry (VBM), structural covariance, and functional connectivity (FC) were applied to investigate structural and functional alterations of the insulae between the CD patients and HCs. Pearson correlation was then used to examine the relationships between neuroimaging findings and clinical symptoms. RESULTS: Compared with the HCs, CD patients exhibited decreased gray matter volume (GMV) in the left dorsal anterior insula (dAI) and bilateral posterior insula (PI). Taking these three areas including the left dAI, right PI, and left PI as regions of interest (ROIs), differences were observed in the structural covariance and FC of the ROI with several regions between the two groups. After controlling for psychological factors, the differences of several regions involved in emotional processing in GMV in the left dAI, the FC of the dAI, and the right PI were not significant. The FC of the parahippocampus/hippocampus with dAI and PI were negatively correlated with the CD activity index (CDAI). CONCLUSIONS: We suggest that the insula-centered structural and/or functional changes may be associated with abnormal visceral sensory processing and related emotional responses in CD patients.

Functional Connectivity of Nucleus Accumbens Is Associated with Lifelong Premature Ejaculation in Male Adults : A Resting-state fMRI Study.

PURPOSE: Ejaculation represents a crucial component of sexual behavior in men, which is involved in reward functions of certain brain areas including the nucleus accumbens (NAcc). Lifelong premature ejaculation (PE) is one of the most prevalent sexual dysfunctions in men. It is suggested to be related to abnormal brain function. This study aimed to explore changes of the functional connectivity patterns of NAcc and possible correlations of the neuroimaging abnormalities with clinical features in lifelong PE patients. METHODS: The sample consisted with 42 lifelong PE patients and 30 healthy controls. All participants underwent functional magnetic resonance imaging scans and clinical symptoms. The functional connectivity (FC) approach was applied to investigate differences of NAcc-seed intrinsic connectivity between two groups and correlation analysis was used to access possible relationships between the imaging findings and clinical features, such as premature ejaculation diagnostic tool (PEDT) or intravaginal ejaculatory latency time (IELT). RESULTS: Results showed that lifelong PE patients had decreased FC between the NAcc and thalamus, superior temporal pole, superior temporal cortex (STC), inferior frontal gyrus (IFG), orbitofrontal cortex, caudate and putamen. A significantly negative correlation between the PEDT score and NAcc-STC connectivity (r = -0.46) was found in lifelong PE patients, while IELT score positively correlated with the NAcc-IFG connectivity (r = 0.48) and NAcc-thalamus connectivity (r = 0.46). CONCLUSION: The findings may facilitate a more sophisticated understanding of neural mechanisms of lifelong PE, particularly associated with the NAcc-related intrinsic connectivity during the resting state.

Regional Gray Matter Volume Changes in Brains of Patients With Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are 2 subtypes of inflammatory bowel disease (IBD). Several studies have reported brain abnormalities in IBD patients. This study aims to identify differences of gray matter volume (GMV) between patients with UC and healthy controls (HCs). METHODS: Fifty-seven patients with UC and 40 HCs underwent structural magnetic resonance imaging. Voxel-based morphometry method was used to detect GMV differences. Receiver operating characteristic (ROC) curve was applied to investigate reliable biomarkers for identifying patients with UC from HCs. Regression analysis was used to examine relationships between the structure alternations and clinical symptoms. RESULTS: Compared with HCs, patients with UC showed decreased GMV in the insula, thalamus, pregenual anterior cingulate cortex, hippocampus/parahippocampus, amygdala, and temporal pole; they showed increased GMV in the putamen, supplementary motor area, periaqueductal gray, hypothalamus, and precentral gyrus. Receiver operating characteristic analysis showed the highest classification power of thalamus. The inclusion of anxiety and depression as covariates eliminated the differences in the right insula, pregenual anterior cingulate cortex, supplementary motor area, and precentral gyrus. Most of the GMV changes were found in active patients with UC, with few changes in patients with UC in remission. We also found significantly negative correlation between UC duration and GMV in several regions. CONCLUSION: The current neuroimaging findings were involved in visceral sensory pathways and were partially associated with the levels of anxiety and depression and clinical stage of patients with UC. This study might provide evidence for possible neuromechanisms of UC.

Altered resting-state functional networks in patients with premenstrual syndrome: a graph-theoretical based study.

Premenstrual syndrome (PMS) is a menstrual cycle-related disorder. Previous studies have indicated alterations of brain functional connectivity in PMS patients. However, little is known about the overall organization of brain network in PMS patients. Functional magnetic resonance imaging data deriving from 20 PMS patients and 21 healthy controls (HCs). Pearson correlation between mean time-series was used to estimate connectivity matrix between each paired regions of interest, and the connectivity matrix for each participant was then binarized. Graph theory analysis was applied to assess each participant's global and local topological properties of brain functional network. Correlation analysis was performed to evaluate relationships between the daily rating of severity of problems (DRSP) and abnormal network properties. PMS patients had lower small-worldness values than HCs. PMS-related alterations of nodal properties were mainly found in the posterior cingulate cortex, precuneus and angular gyrus. The PMS-related abnormal connectivity components were mainly associated with the thalamus, putamen and middle cingulate cortex. In the PMS group, the DRSP score were negatively correlated with the area under the curves of nodal local efficiency in the posterior cingulate cortex. Our study suggests that the graph-theory method may be one potential tool to detect disruptions of brain connections and may provide important evidence for understanding the PMS from the disrupted network organization perspective.

Magnetic Resonance Imaging-Based Structural Covariance Changes of the Striatum in Lifelong Premature Ejaculation Patients.

BACKGROUND: The striatum has been reported to be implicated in various neurological diseases, including lifelong premature ejaculation (LPE). Altered striatum-related functional connectivity was investigated in LPE patients in previous studies; however, structural abnormalities in the striatum have been less studied in LPE. PURPOSE: To identify the gray matter volume (GMV) and structural covariance patterns of the striatum between LPE patients and healthy controls (HCs). STUDY TYPE: Prospective. SUBJECTS: Forty-three LPE patients and 31 male HCs. FIELD STRENGTH/SEQUENCE: 3.0 T magnetic resonance imaging (MRI) scanner; T1-weighted imaging using a spoiled gradient recalled echo sequence. ASSESSMENT: Preprocessing of structural MRI data and the striatum-seeded GMV computation were conducted using SPM12. STATISTICAL TESTS: Two sample t-test was used to compare differences in GMV of the striatum between patients and HCs. Regions showing altered between-group GMV were considered as seeds for structural covariance analysis in two groups. Additionally, correlations between GMV findings and clinical features were assessed with age and total intracranial volume (TIV) as covariates and with age, TIV, anxiety, and depression scores as covariates in the patient group, P < 0.05 was considered statistically significant. RESULTS: Compared to HCs, LPE patients had significantly decreased GMV in four regions located in the bilateral caudate and putamen. Distinct striatum-based structural covariance patterns in the two groups were mainly related to the thalamus, amygdala, insula, anterior cingulate cortex, middle cingulate cortex, medial prefrontal cortex, primary motor cortex, and precuneus/cuneus. LPE patients showed that GMV in the bilateral caudate negatively correlated with the premature ejaculation diagnostic tool (PEDT) scores (r = -0.369, r = -0.377, respectively). DATA CONCLUSION: Our findings indicated that LPE patients had altered GMV and structural covariance patterns in the striatum compared to HCs. The correlations between abnormal GMV and PEDT were also shown in the present findings. These findings may contribute to enhancing the understanding of the pathophysiology of LPE. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Altered functional connectivity density in mild cognitive impairment with moxibustion treatment: A resting-state fMRI study.

PURPOSE: Mild cognitive impairment (MCI) is a general neurodegenerative disease. Moxibustion has been shown to have remarkable effect on cognitive improvement, however, less is known about the effect of moxibustion on MCI and its underlying neural mechanism. This study aimed to investigate the ameliorative brain network in MCI after treatments of acupoint-related moxibustion. METHODS: Resting-state functional MRI were derived from 47 MCI patients and 30 healthy controls (HCs). Patients were randomized as Tiaoshen YiZhi (TSYZ, n = 27) and sham (SHAM, n = 20) acupoint moxibustion groups. Functional connectivity density (FCD) method and repeated-measures two-way analysis of variance (ANOVA) were performed to ascertain the interaction effects between groups (TSYZ and SHAM) and time (baseline and post-treatment). Abnormal FCD was examined between baseline and post-treatment in TSYZ and SHAM groups, respectively. RESULTS: Compared with HCs, MCI showed altered FCD in the middle frontal cortex (MFC), inferior frontal cortex, temporal pole, thalamus and middle cingulate cortex. After moxibustion treatment in MCI, 1) a significant time-by-groups interaction was observed in the medial prefrontal cortex (mPFC); 2) abnormal long-range FCD (lrFCD) in the mPFC and MFC were modulated in TSYZ group; 3) significantly improved clinical symptoms; 4) changed lrFCD in the MFC was significantly negatively correlated with the increased Montreal Cognitive Assessment scores in TSYZ group. CONCLUSIONS: These imaging findings suggest that treatments of acupoint-related moxibustion could improve lrFCD in certain regions related to self-related cognitive and decision making. Our study might promote understanding of MCI neural mechanisms and expand the clinical application of moxibustion in MCI.

Higher inter-hemispheric homotopic connectivity in lifelong premature ejaculation patients: a pilot resting-state fMRI study.

BACKGROUND: Lifelong premature ejaculation (PE) is one common male sexual dysfunction and is implicated in widespread structural and functional abnormalities of bilateral hemispheres. However, whether the inter-hemisphere functional connectivity (FC) of lifelong PE patients was altered still remain unclear. METHODS: Thirty-four lifelong PE patients and 30 healthy controls (HCs) were enrolled in this study and all underwent T1-weighted and resting-state functional MRI (fMRI) scan. The voxel-mirrored homotopic connectivity (VMHC) measure and independent sample t-test were applied to examine the alterations of VMHC values in the patients relative to HCs with the significant threshold at P<0.05, false discovery rates corrected. Correlation analysis was adopted to calculate the relationships between the imaging results and clinical characteristics of patients (P<0.05, Bonferroni corrected). Receiver operating characteristic (ROC) curve analysis was performed to investigate the possible biomarkers for distinguishing the patients from the HCs using the VMHC values of inter-group differences. RESULTS: The results revealed that compared with HCs, lifelong PE patients had higher VMHC values in the precentral gyrus (PG), primary somatosensory cortex (S1), supplementary motor area (SMA), precuneus, middle temporal cortex (MTC), superior temporal pole (STP), thalamus, caudate and middle cingulate cortex (MCC). Correlation analysis showed that the mean VMHC values in the S1 negatively correlated with intravaginal ejaculation latency time (IELT) in the patient group. Furthermore, the caudate revealed the well classification power from the ROC analysis. CONCLUSIONS: The present study showed the abnormal inter-hemisphere interaction and integration of information involved in ejaculation inhibitory control, sensorimotor mediation and self-reference processing including the thalamus, caudate, MCC, widespread parietal cortex and temporal cortex in lifelong PE patients compared with HCs. Correlation analysis and ROC analysis revealed the importance of S1 and caudate in lifelong PE. Notably, the ROC result of caudate might show the core roles of caudate played in the pathophysiology of lifelong PE.

Smaller volume and altered functional connectivity of the amygdala in patients with lifelong premature ejaculation.

OBJECTIVES: To analyze the abnormal amygdala structure and function in lifelong premature ejaculation (PE) patients compared with healthy controls (HCs). METHODS: Forty-four lifelong PE patients and thirty-one HCs were enrolled in this study. Each subject was diagnosed with PE using a Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT) score. Based on t-tests and Pearson correlation analysis, the voxel-based morphometry and functional connectivity (FC) analyses were applied to evaluate brain structural and functional changes by using T1-weighted and resting-state functional magnetic resonance imaging scans. RESULTS: Lifelong PE patients had decreased gray matter volume in the bilateral amygdala and increased FC between the amygdala and precuneus, posterior cingulate cortex (PCC), and middle temporal cortex (MTC), as well as decreased FC between the amygdala and precentral gyrus, insula, and inferior frontal gyrus. Moreover, significantly negative correlations between the IELT score and the mean z-score from amygdala-MTC (r = -0.49) and amygdala-PCC (r = -0.48) FC were found in lifelong PE patients. CONCLUSIONS: Our study investigated the abnormal amygdala-related structure and connectivity patterns in PE patients, which might provide novel perspective for understanding the crucial role of the amygdala in the neural mechanism of PE. KEY POINTS: • As one of the most common diseases in men, PE may be related to abnormal brain mechanisms. • Functional and structural magnetic resonance imaging used to explore amygdala abnormalities in PE patients. • The correlation between clinical scores and functional connectivity was used to assess the reasonability of the results.