Relationship between SLC6A2 gene polymorphisms and brain volume in Han Chinese adults who lost their sole child.

BACKGROUND: Norepinephrine transporter (NET) is encoded by the SLC6A2 gene and is a potential target for studying the pathogenesis of PTSD. To the best of our knowledge, no prior investigations have examined SLC6A2 polymorphism-related neuroimaging abnormalities in PTSD patients. METHODS: In 218 Han Chinese adults who had lost their sole child, we investigated the association between the T-182 C SLC6A2 genotype and gray matter volume (GMV). Participants included 57 PTSD sufferers and 161 non-PTSD sufferers, and each group was further separated into three subgroups based on each participant's SLC6A2 genotype (TT, CT, and CC). All participants received magnetic resonance imaging (MRI) and clinical evaluation. To assess the effects of PTSD diagnosis, genotype, and genotype × diagnosis interaction on GMV, 2 × 3 full factorial designs were used. Pearson's correlations were used to examine the association between GMV and CAPS, HAMD, and HAMA. RESULTS: The SLC6A2 genotype showed significant main effects on GMV of the left superior parietal gyrus (SPG) and the bilateral middle cingulate gyrus (MCG). Additionally, impacts of the SLC6A2 genotype-diagnosis interaction were discovered in the left superior frontal gyrus (SFG). The CAPS, HAMA, and HAMD scores, as well as the genotype main effect and diagnostic SLC6A2 interaction, did not significantly correlate with each other. CONCLUSION: These findings indicate a modulatory effect that the SLC6A2 polymorphism exerts on the SPG and MCG, irrespective of PTSD diagnosis. We found evidence to suggest that the SLC6A2 genotype-diagnosis interaction on SFG may potentially contribute to PTSD pathogenesis in adults who lost their sole child.

Association Between MRI-Assessed Patterns of Connectome Gradient and Gene-Expression Profiles in Two Independent Patient Cohorts With Hepatitis B Virus-Related Cirrhosis.

BACKGROUND: Patients with hepatitis B virus-related cirrhosis (HBV-RC) exhibit progressive neurologic dysfunction from primary sensorimotor to high-order cognition, as their disease advances. However, the exact neurobiologic mechanisms and the potential association with gene-expression profiles are not fully understood. PURPOSE: To explore the hierarchical disorganization in the large-scale functional connectomes in HBV-RC patients and to investigate its potential underlying molecular basis. STUDY TYPE: Prospective. POPULATION: Fifty HBV-RC patients and 40 controls (Cohort 1) and 30 HBV-RC patients and 38 controls (Cohort 2). FIELD STRENGTH/SEQUENCE: Gradient-echo echo-planar and fast field echo sequences at 3.0 T (Cohort 1) and 1.5 T (Cohort 2). ASSESSMENT: Data were processed with Dpabi and the BrainSpace package. Gradient scores were evaluated from global to voxel level. Cognitive measurement and patients grouping were based on psychometric hepatic encephalopathy scores. The whole-brain microarray-based gene-expression data were obtained from the AIBS website. STATISTICAL TESTS: One-way ANOVA, chi-square test, two-sample t-test, Kruskal-Wallis test, Spearman's correlation coefficient (r), the gaussian random field correction, false discovery rate (FDR) correction and the Bonferroni correction. Significance level: P < 0.05. RESULTS: HBV-RC patients exhibited a robust and replicable connectome gradient dysfunction, which was significantly associated with the gene-expression profiles in both cohorts (r = 0.52 and r = 0.56, respectively). The most correlated genes were enriched in γ-aminobutyric acid (GABA) and GABA-related receptor genes (FDR q value <0.05). Moreover, the connectome gradient dysfunction at network level observed in HBV-RC patients correlated with their poor cognitive performance (Cohort 2: visual network, r = -0.56; subcortical network, r = 0.66; frontoparietal network, r = 0.51). DATA CONCLUSION: HBV-RC patients had hierarchical disorganization in the large-scale functional connectomes, which may underly their cognitive impairment. In addition, we showed the potential molecular mechanism of the connectome gradient dysfunction, which suggested the importance of GABA and GABA-related receptor genes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Evaluation of gray matter reduction in patients with typhoon-related posttraumatic stress disorder using causal network analysis of structural MRI.

BACKGROUND: The structural changes recent-onset posttraumatic stress disorder (PTSD) subjects were rarely investigated. This study was to compare temporal and causal relationships of structural changes in recent-onset PTSD with trauma-exposed control (TEC) subjects and non-TEC subjects. METHODS: T1-weighted magnetic resonance images of 27 PTSD, 33 TEC and 30 age- and sex-matched healthy control (HC) subjects were studied. The causal network of structural covariance was used to evaluate the causal relationships of structural changes in PTSD patients. RESULTS: Volumes of bilateral hippocampal and left lingual gyrus were significantly smaller in PTSD patients and TEC subjects than HC subjects. As symptom scores increase, reduction in gray matter volume began in the hippocampus and progressed to the frontal lobe, then to the temporal and occipital cortices (p < 0.05, false discovery rate corrected). The hippocampus might be the primary hub of the directional network and demonstrated positive causal effects on the frontal, temporal and occipital regions (p < 0.05, false discovery rate corrected). The frontal regions, which were identified to be transitional points, projected causal effects to the occipital lobe and temporal regions and received causal effects from the hippocampus (p < 0.05, false discovery rate corrected). CONCLUSIONS: The results offer evidence of localized abnormalities in the bilateral hippocampus and remote abnormalities in multiple temporal and frontal regions in typhoon-exposed PTSD patients.

Cortico-striato-thalamo-cerebellar networks of structural covariance underlying different epilepsy syndromes associated with generalized tonic-clonic seizures.

Generalized tonic-clonic seizures (GTCS) are the severest and most remarkable clinical expressions of human epilepsy. Cortical, subcortical, and cerebellar structures, organized with different network patterns, underlying the pathophysiological substrates of genetic associated epilepsy with GTCS (GE-GTCS) and focal epilepsy associated with focal to bilateral tonic-clonic seizure (FE-FBTS). Structural covariance analysis can delineate the features of epilepsy network related with long-term effects from seizure. Morphometric MRI data of 111 patients with GE-GTCS, 111 patients with FE-FBTS and 111 healthy controls were studied. Cortico-striato-thalao-cerebellar networks of structural covariance within the gray matter were constructed using a Winner-take-all strategy with five cortical parcellations. Comparisons of structural covariance networks were conducted using permutation tests, and module effects of disease duration on networks were conducted using GLM model. Both patient groups showed increased connectivity of structural covariance relative to controls, mainly within the striatum and thalamus, and mostly correlated with the frontal, motor, and somatosensory cortices. Connectivity changes increased as a function of epilepsy durations. FE-FBTS showed more intensive and extensive gray matter changes with volumetric loss and connectivity increment than GE-GTCS. Our findings implicated cortico-striato-thalamo-cerebellar network changes at a large temporal scale in GTCS, with FE-FBTS showing more severe network disruption. The study contributed novel imaging evidence for understanding the different epilepsy syndromes associated with generalized seizures.

Decreased functional connectivity of hippocampal subregions and methylation of the NR3C1 gene in Han Chinese adults who lost their only child.

BACKGROUND: Losing one's only child is a major traumatic life event that may lead to post-traumatic stress disorder (PTSD); however, the underlying mechanisms of its psychological consequences remain poorly understood. Here, we investigated subregional hippocampal functional connectivity (FC) networks based on resting-state functional magnetic resonance imaging and the deoxyribonucleic acid methylation of the human glucocorticoid receptor gene (NR3C1) in adults who had lost their only child. METHODS: A total of 144 Han Chinese adults who had lost their only child (51 adults with PTSD and 93 non-PTSD adults [trauma-exposed controls]) and 50 controls without trauma exposure were included in this fMRI study (age: 40-67 years). FCs between hippocampal subdivisions (four regions in each hemisphere: cornu ammonis1 [CA1], CA2, CA3, and dentate gyrus [DG]) and methylation levels of the NR3C1 gene were compared among the three groups. RESULTS: Trauma-exposed adults, regardless of PTSD diagnosis, had weaker positive FC between the left hippocampal CA1, left DG, and the posterior cingulate cortex, and weaker negative FC between the right CA1, right DG, and several frontal gyri, relative to healthy controls. Compared to non-PTSD adults, PTSD adults showed decreased negative FC between the right CA1 region and the right middle/inferior frontal gyri (MFG/IFG), and decreased negative FC between the right DG and the right superior frontal gyrus and left MFG. Both trauma-exposed groups showed lower methylation levels of the NR3C1 gene. CONCLUSIONS: Adults who had lost their only child may experience disrupted hippocampal network connectivity and NR3C1 methylation status, regardless of whether they have developed PTSD.

Similarity and diversity of spontaneous brain activity in functional dyspepsia subtypes.

BACKGROUND: Functional dyspepsia (FD) subtypes may differ in terms of pathophysiology, but the underlying mechanisms remain poorly understood. PURPOSE: To explore spontaneous brain activity in two main FD subtypes, namely epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), using the amplitude of low-frequency fluctuation (ALFF). MATERIAL AND METHODS: Thirty-one FD patients (18 EPS and 13 PDS) and 22 matched healthy controls (HC) underwent resting-state functional MRI scanning. Spontaneous brain activity was evaluated by measuring the ALFF and then compared among the EPS, PDS, and HC groups with ANOVA test. Pearson correlation analysis was performed between the ALFF values and clinical indices. RESULTS: Compared to healthy controls, both EPS and PDS patients had increased ALFF in the bilateral precentral/postcentral gyri, insula, and thalami. Furthermore, only the EPS patients displayed increased ALFF in the right middle and inferior frontal gyri, and only the PDS patients showed increased ALFF in the left posterior cingulate cortex (PCC). The ALFF values in the left thalamus were positively correlated with the sleep disturbance in EPS patients, and the ALFF values in the right precentral/postcentral gyri showed a positive correlation with the symptom score in PDS patients. CONCLUSION: EPS and PDS had similarities of higher spontaneous brain activity in the primary motor/sensory areas and homeostatic-afferent network regions, and differences in the prefrontal region and PCC, providing evidence to suggest the similarity and diversity of pathophysiology in FD subtypes.

Deteriorated functional and structural brain networks and normally appearing functional-structural coupling in diabetic kidney disease: a graph theory-based magnetic resonance imaging study.

PURPOSE: This study was conducted in order to investigate the topological organization of functional and structural brain networks in diabetic kidney disease (DKD) and its potential clinical relevance. METHODS: Two hundred two subjects (62 DKD patients, 60 diabetes mellitus [DM] patients, and 80 healthy controls) underwent laboratory examination, neuropsychological test, and magnetic resonance imaging (MRI). Large-scale functional and structural brain networks were constructed and graph theoretical network analyses were performed. The effect of renal function on brain functional and structural networks in DKD patients was further evaluated. Correlations were performed between network properties and neuropsychological scores and clinical variables. RESULTS: Progressing deteriorated global and local network topology organizations (especially for functional network) were observed for DKD patients compared with control subjects (all p < 0.05, Bonferroni-corrected), with intermediate values for the patients with DM. DKD patients showed normally appearing functional-structural coupling compared with controls, while DM patients manifested functional-structural decoupling (p < 0.05, Bonferroni-corrected). Impaired kidney function markedly affected functional and structural network organization in DKD patients (all p < 0.05). Urea nitrogen correlated with global and local efficiency in the structural networks (r = - 0.551, p < 0.001; r = - 0.476, p < 0.001, respectively). Global and local efficiency in the structural networks and normalized characteristic path length in the functional networks were associated with information processing speed and/or psychomotor speed. CONCLUSION: DKD patients showed enhanced functional and structural brain network disruption and normally appearing functional-structural coupling compared with DM patients, which correlated with kidney function, renal toxins, and cognitive performance. KEY POINTS: • DKD patients showed markedly disrupted functional and structural brain network efficiency measures compared with DM patients and healthy controls. • Reduced kidney function clearly deteriorated functional and structural brain networks in DKD patients. • DKD patients displayed normally appearing functional-structural coupling compared with DM patients.

Disturbed effective connectivity patterns in an intrinsic triple network model are associated with posttraumatic stress disorder.

BACKGROUND: Disturbance of the triple network model was recently proposed to be associated with the occurrence of posttraumatic stress disorder (PTSD) symptoms. Based on resting-state dynamic causal modeling (rs-DCM) analysis, we investigated the neurobiological model at a neuronal level along with potential neuroimaging biomarkers for identifying individuals with PTSD. METHODS: We recruited survivors of a devastating typhoon including 27 PTSD patients, 33 trauma-exposed controls (TECs), and 30 healthy controls without trauma exposure. All subjects underwent resting-state functional magnetic resonance imaging. Independent components analysis was used to identify triple networks. Detailed effective connectivity patterns were estimated by rs-DCM analysis. Spearman correlation analysis was performed on aberrant DCM parameters with clinical assessment results relevant to PTSD diagnosis. We also carried out step-wise binary logistic regression and receiver operating characteristic curve (ROC) analysis to confirm the capacity of altered effective connectivity parameters to distinguish PTSD patients. RESULTS: Within the executive control network, enhanced positive connectivity from the left posterior parietal cortex to the left dorsolateral prefrontal cortex was correlated with intrusion symptoms and showed good performance (area under the receiver operating characteristic curve = 0.879) in detecting PTSD patients. In the salience network, we observed a decreased causal flow from the right amygdala to the right insula and a lower transit value for the right amygdala in PTSD patients relative to TECs. CONCLUSION: Altered effective connectivity patterns in the triple network may reflect the occurrence of PTSD symptoms, providing a potential biomarker for detecting patients. Our findings shed new insight into the neural pathophysiology of PTSD.

Altered resting-state dorsal anterior cingulate cortex functional connectivity in patients with post-traumatic stress disorder.

OBJECTIVE: The brain functional alterations at regional and network levels in post-traumatic stress disorder patients are still unclear. This study explored brain functional alterations at regional and network levels in post-traumatic stress disorder patients with resting-state functional magnetic resonance imaging and evaluated the relationship between brain function and clinical indices in post-traumatic stress disorder. METHODS: Amplitude of low-frequency fluctuation and seed-based functional connectivity analyses were conducted among typhoon survivors with ( n = 27) and without post-traumatic stress disorder ( n = 33) and healthy controls ( n = 30) to assess the spontaneous brain activity and network-level brain function. Pearson correlation analyses were performed to examine the association of brain function with clinical symptom and social support. RESULTS: Both the post-traumatic stress disorder group and the trauma-exposed control group showed decreased amplitude of low-frequency fluctuation in the dorsal anterior cingulate cortex relative to the healthy control group. The post-traumatic stress disorder group showed increased dorsal anterior cingulate cortex functional connectivity with the right paracentral lobule and bilateral precentral gyrus/postcentral gyrus relative to both control groups. Both traumatized groups exhibited decreased dorsal anterior cingulate cortex functional connectivity with the right hippocampus and left cerebellum relative to the healthy control group. More decreased dorsal anterior cingulate cortex functional connectivity with the right hippocampus was found in the post-traumatic stress disorder group. The Checklist-Civilian Version score positively correlated with functional connectivity between the dorsal anterior cingulate cortex and the right paracentral lobule as well as between the dorsal anterior cingulate cortex and the right precentral gyrus/postcentral gyrus. The social support was associated with functional connectivity between the dorsal anterior cingulate cortex and the bilateral precentral gyrus/postcentral gyrus as well as the dorsal anterior cingulate cortex and the left middle frontal gyrus. CONCLUSION: Trauma exposure may result in aberrant local and network-level functional connectivity in individuals with or without post-traumatic stress disorder. Altered amplitude of low-frequency fluctuation in the dorsal anterior cingulate cortex may be a predisposing risk factor for post-traumatic stress disorder development following trauma exposure. More prominent decreased dorsal anterior cingulate cortex functional connectivity with the right hippocampus might be specific in the post-traumatic stress disorder group. Improvement of social support might possibly be significant for post-traumatic stress disorder patients.

Typhoon-Related Post-Traumatic Stress Disorder and Trauma Might Lead to Functional Integration Abnormalities in Intra- and Inter-Resting State Networks: a Resting-State Fmri Independent Component Analysis.

BACKGROUND/AIMS: Functional connectivity studies based on region of interest approach suggest altered functional connectivity of the default mode network (DMN), executive control network (ECN), and salience network (SN). The aim of this study is to determine whether intranetwork and internetwork brain connectivity are altered in both post-traumatic stress disorder (PTSD) patients and traumatized subjects without PTSD using a data-driven approach. METHODS: Resting-state functional MRI data were acquired for 27 patients with typhoon-related PTSD, 33 trauma-exposed controls (TEC), and 30 healthy controls (HC). Functional connectivity within the DMN, ECN, and SN as well as functional and effective connectivity between these resting-state networks were examined with independent component analysis (ICA), and then compared between groups by conducting analysis of variance. RESULTS: Within the DMN, the TEC group showed decreased and increased functional connectivity in the superior frontal gyrus compared with the PTSD group and the HC group, respectively. The TEC group showed increased angular functional connectivity within the DMN and decreased functional connectivity in the superior temporal gyrus/posterior insula within the SN relative to the HC group. Compared with the TEC group, the PTSD group showed increased functional connectivity in the middle frontal gyrus and supplementary motor area within the ECN as well as in the inferior frontal gyrus/anterior insula within the SN. The PTSD group showed decreased functional connectivity in the supplementary motor area within the SN relative to both control groups. Moreover, the PTSD showed increased excitatory influence from the ECN to DMN compared with both control groups, while the TEC group showed increased inhibitory influence from the DMN to ECN compared with the HC group. Intranetwork functional connectivity within the DMN and SN is altered in traumatized subjects irrespective of PTSD diagnosis. PTSD patients also showed altered intranetwork functional connectivity within the ECN. CONCLUSIONS: Distinct changes of effective connectivity between the DMN and ECN in the PTSD group and TEC group may reflect different compensatory mechanisms for rebalance of resting-state networks in the two groups.

Dynamic Network Analysis Reveals Altered Temporal Variability in Brain Regions after Stroke: A Longitudinal Resting-State fMRI Study.

Recent fMRI studies have demonstrated that resting-state functional connectivity (FC) is of nonstationarity. Temporal variability of FC reflects the dynamic nature of brain activity. Exploring temporal variability of FC offers a new approach to investigate reorganization and integration of brain networks after stroke. Here, we examined longitudinal alterations of FC temporal variability in brain networks after stroke. Nineteen stroke patients underwent resting fMRI scans across the acute stage (within-one-week after stroke), subacute stage (within-two-weeks after stroke), and early chronic stage (3-4 months after stroke). Nineteen age- and sex-matched healthy individuals were enrolled. Compared with the controls, stroke patients exhibited reduced regional temporal variability during the acute stages, which was recovered at the following two stages. Compared with the acute stage, the subacute stage exhibited increased temporal variability in the primary motor, auditory, and visual cortices. Across the three stages, the temporal variability in the ipsilesional precentral gyrus (PreCG) was increased first and then reduced. Increased temporal variability in the ipsilesional PreCG from the acute stage to the subacute stage was correlated with motor recovery from the acute stage to the early chronic stage. Our results demonstrated that temporal variability of brain network might be a potential tool for evaluating and predicting motor recovery after stroke.

Brain Default Mode Network Changes after Renal Transplantation: A Diffusion-Tensor Imaging and Resting-State Functional MR Imaging Study.

PURPOSE: To investigate structural and functional alterations of the default mode network (DMN) in the brain after renal transplantation in patients with end-stage renal disease by using diffusion-tensor imaging and resting-state functional MR imaging. MATERIALS AND METHODS: This prospective study was approved by the local medical research ethics committee, and written informed consent was obtained. Twenty-one patients with end-stage renal disease (15 men, six women; mean age ± standard deviation, 32 years ± 9.5) who were scheduled to undergo renal transplantation and 21 healthy control subjects (15 men, six women; mean age, 31 years ± 6.5) were included. Diffusion-tensor imaging and resting-state functional MR imaging were performed in all subjects. Patients were imaged both before and 1 month after renal transplantation. Structural (mean diffusivity, fractional anisotropy, path length, and number of tracts derived from diffusion-tensor imaging tractography) and functional (temporal correlation coefficient derived from resting-state functional MR imaging) connectivity of the DMN were quantitatively compared with two-sample t tests or paired t tests. Intergroup correlation analysis was performed to compare structural or functional indexes and results of neuropsychological or blood biochemistry tests. RESULTS: Mean diffusivity was decreased in the fiber bundles connecting the posterior cingulate cortex and the precuneus to the bilateral inferior parietal lobules in patients after renal transplantation compared with that in patients before transplantation (P < .05). Temporal correlation coefficients for patients after renal transplantation nearly reached the levels of those for control subjects (all, P > .05). The change in mean diffusivity of the fiber bundles connecting the posterior cingulate cortex and the precuneus to the right inferior parietal lobule positively correlated with the change in hematocrit levels (r = 0.522, P = .015), the change in temporal correlation coefficients between the posterior cingulate cortex or precuneus and left or right inferior parietal lobules correlated with changes in number connection test type A scores (r = -0.549, P = .010) and digit symbol test scores (r = 0.533, P = .013). CONCLUSION: Functional connectivity changes in the DMN, which were associated with improved hematocrit levels and cognitive function, may recover earlier than structural connectivity changes do 1 month after renal transplantation.

A longitudinal fMRI investigation in acute post-traumatic stress disorder (PTSD).

Background Neuroimaging studies have implicated limbic, paralimbic, and prefrontal cortex in the pathophysiology of chronic post-traumatic stress disorder (PTSD). However, little is known about the neural substrates of acute PTSD and how they change with symptom improvement. Purpose To examine the neural circuitry underlying acute PTSD and brain function changes during clinical recovery from this disorder. Material and Methods Nineteen acute PTSD patients and nine non-PTSD subjects who all experienced a devastating mining accident underwent clinical assessment as well as functional magnetic resonance imaging (fMRI) scanning while viewing trauma-related and neutral pictures. Two years after the accident, a subgroup of 17 patients completed a second clinical evaluation, of which 13 were given an identical follow-up scan. Results Acute PTSD patients demonstrated greater activation in the vermis and right posterior cingulate, and greater deactivation in the bilateral medial prefrontal cortex and inferior parietal lobules than controls in the traumatic versus neutral condition. At follow-up, PTSD patients showed symptom reduction and decreased activation in the right middle frontal gyrus, bilateral posterior cingulate/precuneus, and cerebellum. Correlation results confirmed these findings and indicated that brain activation in the posterior cingulate/precuneus and vermis was predictive of PTSD symptom improvement. Conclusion The findings support the involvement of the medial prefrontal cortex, inferior parietal lobule, posterior cingulate, and vermis in the pathogenesis of acute PTSD. Brain activation in the vermis and posterior cingulate/precuneus appears to be a biological marker of recovery potential from PTSD. Furthermore, decreased activation of the middle frontal gyrus, posterior cingulate/precuneus, and cerebellum may reflect symptom improvement.

Establishment of swine-penetrating craniocerebral gunshot wound model.

BACKGROUND: Bullet-induced brain wounds are common among military personnel in war zones and among civilians with gun accidents or crime-related gun injuries. The goal of this study was to develop a nonfatal porcine model of penetrating craniocerebral gunshot wound (PCGW) by firing a projectile in live swine to induce PCGW in such a realistic manner as to reconstruct their physical characteristics. MATERIALS AND METHODS: We established a nonfatal porcine model of PCGW based on a custom-designed experimental gun that emulates the shooting of a 5.56-mm NATO standard rifle at 800 m (317 m/s; 200.9 J). Commercial swine (n = 20) were subjected to a ballistic wound to the bilateral frontal lobe, and four swine were used as controls. Surviving swine were used in subsequent first-aid, management, and monitoring experiments for neurosurgeons. Various physiological variables were measured continuously. After computed tomography (CT) scanning and three-dimensional CT reconstructions, all pigs underwent primary lifesaving emergency interventions, including emergency decompressive craniotomies and hemorrhage control. RESULTS: In our nonfatal porcine model of PCGW, injuries were comparable in their morphology to real gunshot wounds, as evidenced by analysis of wound characteristics and CT scan images. The survival rates of the pigs were 100% within 2 h, 95% within 6 h, 85% within 12 h, and 85% within 24 h (P < 0.01). Hemodynamics, hematology, blood routine biochemistry, coagulation, and other physiological parameters also exhibited significant changes in the PCGW pigs. CONCLUSIONS: This model makes possible the laboratory reproduction of real ballistic wounds in a live large animal model that is close to humans.

The impact of hemodialysis on cognitive dysfunction in patients with end-stage renal disease: a resting-state functional MRI study.

To investigate the effect of hemodialysis (HD) on cognitive dysfunction in patients with end-stage renal disease (ESRD) using resting-state functional MR imaging (rs-fMRI) with regional homogeneity (ReHo) and functional connectivity algorithms. The rs-fMRI data were acquired in 58 ESRD patients (HD patients, n = 32, 22 male and 10 female, mean age 36.5 ± 9.6 years; non-HD ESRD patients, n = 26, 16 male and 10 female, mean years of 35.6 ± 8.2) and 32 healthy controls (22 male and 10 female, mean years of 32.7 ± 8.8). A battery of neuropsychological and blood laboratory tests were prescribed. The Kendall's coefficient of concordance (KCC) was used to measure ReHo for each subject. The ReHo maps were compared by using ANOVA tests among HD, non-HD, and healthy control groups. Regions showing ReHo differences between HD and non-HD patients were defined as seeds for further functional connectivity analysis. A multiple regression analysis was performed to evaluate the relationships between ReHo index and neuropsychological tests, serum creatinine and urea levels, disease and dialysis duration. Compared with healthy controls, both HD patients and non-HD patients showed decreased ReHo in the multiple areas of bilateral frontal, parietal and temporal lobes. Compared with the non-HD, HD patients showed decreased ReHo mainly in default mode network (DMN) including bilateral precuneus, posterior cingulate cortex, inferior parietal lobe, right postcentral gyrus, bilateral superior temporal gyri, right supramarginal gyrus and right angular gyrus. Some reduced ReHo brain regions correlated with some neuropsychological tests, serum creatinine and urea levels, and dialysis duration. Brain regions with ReHo reduction showed increased region-to-region functional network in HD patients compared with non-HD patients. Widespreadly decreased ReHo values were found in both HD and non-HD patients. Lower ReHo values mainly in the DMN correlated with cognition impairments were observed in HD patients compared with non-HD patients, while increased functional connectivity was found between these brain regions. HD might have an adverse effect on the cognitive function in ESRD patients.

Altered long- and short-range functional connectivity in the patients with end-stage renal disease: a resting-state functional MRI study.

To investigate alterations of functional connectivity density (FCD) in patients with end-stage renal disease (ESRD) by using resting-state functional magnetic resonance imaging (rs-fMRI). Medical research ethics committee approval from Jinling hospital and written informed consent from each subject were obtained. Forty six patients with ESRD, consisting of 21 patients minimal nephrotic encephalopathy (MNE) and 25 non-nephro-encephalopathy (non-NE), as well as 23 healthy controls underwent rs-fMRI. Neuropsychological tests were performed in all subjects, while laboratory tests were performed in ESRD patients. A voxel-wise whole brain functional connectivity analysis was used to generate long- and short-range FCD maps. The maps among MNE, non-NE, and healthy controls groups were compared by using one-way analysis of variance tests. A multiple regression analysis was performed to evaluate the correlations between FCD and the variables of neuropsychological or laboratory tests. Compared with healthy controls, non-NE showed decreased long-range FCD mainly in parietal lobe. Moreover, MNE showed further decreased long-range FCD in bilateral middle prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and right superior frontal gyrus. Meanwhile, non-NE showed decreased short-range FCD mainly in frontal cortex, and further reduction in bilateral ACC and right superior parietal gyrus in MNE. In addition, patients with ESRD mainly exhibited increased long-range FCD in left temporal lobe and caudate; and increased short-range FCD in bilateral orbitofrontal cortex and temporal gyri (P < 0.05, AlphaSim corrected). The number connection test type A score, serum creatinine, urea, and dialysis duration showed negative correlation with FCD in some brain regions, while the digital symbol test scores positively correlated with short-range FCD in left inferior parietal lobule (all P < 0.05, AlphaSim corrected). The prominent long- and short-range FCD reduction was found mainly in default mode network (DMN) and bilateral frontal and parietal lobes, while the progressively decreased long- and short-range FCD in ACC/MPFC and the long-range FCD in left superior frontal gyrus from non-NE to MNE was associated with cognition dysfunction in ESRD patients.

Altered cortical and subcortical local coherence in PTSD: evidence from resting-state fMRI.

BACKGROUND: Post-traumatic stress disorder (PTSD) is often characterized by region-specific brain activation/deactivation and functional abnormalities in corticolimbic circuitry, as elucidated by task-dependent functional neuroimaging. However, little is known about the abnormalities in the local coherence of cortical and subcortical activity occurring during the resting state. PURPOSE: To evaluate the functional discrepancy of local coherence between cortical and subcortical regions in PTSD patients using resting-state functional magnetic resonance imaging (fMRI). MATERIAL AND METHODS: Resting-state fMRI (RS-fMRI) was performed on 14 outpatients with PTSD, along with 14 age- and sex-matched normal control subjects. Regional homogeneity (ReHo), a measurement of the coherence of spontaneous RS-fMRI signal oscillations within spatially neighboring voxels, was examined. RESULTS: Compared with the normal controls, PTSD patients showed increased local coherence in subcortical regions, including amygdala, hippocampus, thalamus, and putamen, and decreased local coherence in cortical regions, including medial prefrontal cortex and dorsolateral prefrontal cortex. Moreover, a correlation analysis of the ReHo measurement versus the severity of the disorder was performed, and highly positive correlation were observed in the right amygdala. CONCLUSION: The present study identified a functional discrepancy of local coherence between cortical and subcortical regions in PTSD patients compared with normal controls. The findings revealed that resting-state abnormalities might lead to further improvement of the understanding of the neural substrates of cognitive impairment and symptoms in PTSD.

Aberrant default-mode functional connectivity in patients with end-stage renal disease: a resting-state functional MR imaging study.

PURPOSE: To investigate the functional connectivity of the default-mode network (DMN) in patients with end-stage renal disease (ESRD) by using independent component analysis of resting-state functional magnetic resonance (MR) imaging and to correlate these DMN connectivity changes with neuropsychological test results and clinical biomarkers. MATERIALS AND METHODS: Medical research ethics committee approval and written informed consent were obtained. Forty-six patients with ESRD, including 22 with minimal nephrotic encephalopathy (MNE) and 24 without nephrotic encephalopathy, and 23 healthy control subjects underwent resting-state functional MR imaging. All patients were asymptomatic and without history of neurologic or psychiatric disease. Independent component analysis was used to isolate the DMN. To display the voxels that contributed most strongly to an independent component, the intensity values in each spatial map were converted to z scores, which indirectly provided a measurement of functional connectivity in the DMN. Maps of the DMN were compared among the groups. Pearson correlation analysis was performed to correlate abnormal DMN functional connectivity with serum urea, creatinine, duration of dialysis, duration of disease, and neuropsychological test scores. RESULTS: Patients with ESRD showed significantly less functional connectivity in the posterior cingulate cortex, precuneus, and medial prefrontal cortex (MPFC) (P < .01) than did control subjects. Comparison of the two patient groups showed significantly reduced functional connectivity in the superior and MPFC in the MNE group (P < .01). The functional connectivity of the MPFC was positively correlated with digital symbol test score (R = 0.293, P = .048). Serum creatinine level was negatively correlated with functional connectivity of the posterior cingulate cortex and precuneus in patients with ESRD (R = -0.51, P = .002). CONCLUSION: Functional connectivity in the DMN was impaired in patients with ESRD, with further reduction in the MPFC with the development of MNE, which might explain the reduced performance of these patients on neurocognitive tests. Serum creatinine level might be associated with impairment of the DMN in patients with ESRD.

Alterations of regional homogeneity in pediatric bipolar depression: a resting-state fMRI study.

BACKGROUND: Pediatric bipolar disorder (PBD) has attracted increasing attentions due to its high prevalence and great influence on social functions of children and adolescents. However, the pathophysiology underlying PBD remains unclear. In the present study, the resting-state functional magnetic resonance imaging (fMRI) was used to detect abnormalities of baseline brain functions in depressed PBD youth. METHODS: Seventeen youth with PBD-depression aged 10 - 18 years old and 18 age- and sex-matched normal controls were recruited in this study. The fMRI data under resting state were obtained on a Siemens 3.0 Tesla scanner and were analyzed using the regional homogeneity (ReHo) method. Correlations between the ReHo values of each survived area and the severity of depression symptoms in patients were further analyzed. RESULTS: As compared with the control group, PBD-depression patients showed decreased ReHo in the medial frontal gyrus, bilateral middle frontal gyrus and middle temporal gyrus, and the right putamen. Significant negative correlations of the mood and feelings questionnaire scores with mean ReHo values in the medial frontal gyrus and the right middle frontal gyrus in PBD-depression patients were observed. CONCLUSION: Our results suggest that extensive regions with altered baseline brain activities are existed in PBD-depression and these brain regions mainly locate in the fronto-limbic circuit and associated striatal structures. Moreover, the present findings also add to our understanding that there could be unique neuropathophysiological mechanisms underlying PBD-depression.

Assessment of extracranial-intracranial bypass in Moyamoya disease using 3T time-of-flight MR angiography: comparison with CT angiography.

BACKGROUND: To evaluate the value of time-of-flight MR angiography (TOF MRA) for the assessment of extracranial-intracranial (EC-IC) bypass in Moyamoya disease in comparison with computed tomography angiography (CTA). PATIENTS AND METHODS: A consecutive series of 23 patients with Moyamoya disease were analyzed retrospectively. Twenty three patients underwent 25 procedures of extracranial-intracranial bypass. Cranial CTA was performed within one week after the surgery to assess bypass patency. Then TOF MRA was scanned within 24 h after CTA on a 3T MRI system. Using 5-point scales (0 = poor to 4 = excellent), two radiologists rated the image quality and vessel integrity of bypass for three segments (extracranial, trepanation, intracranial). RESULTS: Image quality was high in both CTA and TOF MRA (mean quality score 3.84 ± 0.37 and 3.8 ± 0.41), without statistical difference (p = 0.66). Mean scores of TOF MRA with respect to bypass visualization were higher than CTA in the intracranial segment (p = 0.026). No significant difference of bypass visualization regarding the extracranial and trepanation segments was found between TOF MRA and CTA (p = 0.66 and p = 0.34, respectively). For the trepanation segment, TOF MRA showed pseudo lesions in 2 of all 25 cases. CONCLUSIONS: 3T TOF MRA, a non-contrast technique not exposing the patients to radiation, proved to be at least equal to CTA for the assessment of EC-IC bypass, and even superior to CTA with respect to the intracranial segment. In addition, readers should be aware of a potential overestimation showing focal pseudo lesions of the bypass at the trepanation segment in TOF MRA.