Rongfeng Qi

Altered Resting-State Brain Activity at Functional MR Imaging during the Progression of Hepatic Encephalopathy

PURPOSE To explore the spatial patterns of the amplitude of low-frequency fluctuation (ALFF) in patients with hepatic encephalopathy (HE) of varying severity and to correlate these fluctuations with clinical markers of HE. MATERIALS AND METHODS This study was approved by the local ethics committee, and written informed consent was obtained from all participants. Twenty-nine patients with HE (15 with overt and 14 with minimal HE) and 17 healthy control subjects underwent resting-state functional magnetic resonance (MR) imaging. The ALFF, an index reflecting the amplitudes of spontaneous brain activity, was compared among patients with overt HE, patients with minimal HE, and control subjects with analysis of variance tests and t tests between each pair. Pearson correlation analysis was performed between the ALFF and the venous blood ammonia level and Child-Pugh score of all patients with HE. RESULTS Compared with control subjects, patients with overt and minimal HE showed decreased ALFF mainly in regions within the default-mode network (DMN) and increased ALFF in the cerebellum and middle temporal gyrus. Compared with patients with minimal HE, those with overt HE showed decreased ALFF in DMN regions and increased ALFF in the posterior insular cortex (P<.05, corrected for multiple comparisons). Both the venous blood ammonia levels and Child-Pugh scores of individual patients with HE showed negative correlation with ALFF within some DMN regions, whereas they showed positive correlation with ALFF in the posterior insular cortex (P<.05, corrected for multiple comparisons). CONCLUSION Patients with HE have diffuse abnormalities in intrinsic brain activity. The levels of decreased ALFF in the DMN and increased ALFF in the posterior insular cortex are dependent on the severity of HE, suggesting continuous impairment of the DMN and a compensatory role of the insula during the progression of HE. Resting-state functional MR imaging with ALFF analysis may be a noninvasive modality with which to detect the progression of HE.

Abnormalities in whole-brain functional connectivity observed in treatment-naive post-traumatic stress disorder patients following an earthquake

BACKGROUND Convergent studies have highlighted the dysfunction of the amygdala, prefrontal cortex and hippocampus in post-traumatic stress disorder (PTSD). However, only a few studies have investigated the functional connectivity between brain regions in PTSD patients during the resting state, which may improve our understanding of the neuropathophysiology of PTSD. The aim of this study was to investigate patterns of whole-brain functional connectivity in treatment-naive PTSD patients without co-morbid conditions who experienced the 8.0-magnitude earthquake in the Sichuan province of China. METHOD A total of 72 PTSD patients and 86 trauma-exposed non-PTSD controls participated in the resting-state functional magnetic resonance imaging study. All these subjects were recruited from the disaster zone of the 2008 Sichuan earthquake. Functional connectivities between 90 paired brain regions in PTSD patients were compared with those in trauma-exposed non-PTSD controls. Furthermore, Pearson correlation analysis was performed between significantly abnormal connectivities in PTSD patients and their clinician-administered PTSD scale (CAPS) scores. RESULTS Compared with non-PTSD controls, PTSD patients showed weaker positive connectivities between the middle prefrontal cortex (mPFC) and the amygdala, hippocampus, parahippocampal gyrus and rectus, as well as between the inferior orbitofrontal cortex and the hippocampus. In addition, PTSD patients showed stronger negative connectivity between the posterior cingulate cortex (PCC) and the insula. The CAPS scores in PTSD patients correlated negatively with the connectivity between the amygdala and the mPFC. CONCLUSIONS PTSD patients showed abnormalities in whole-brain functional connectivity, primarily affecting the connectivities between the mPFC and limbic system, and connectivity between the PCC and insula.

Altered Brain Functional Connectivity in Patients with Cirrhosis and Minimal Hepatic Encephalopathy: A Functional MR Imaging Study

PURPOSE To investigate patterns of whole-brain functional connectivity in patients with minimal hepatic encephalopathy (HE) by using functional magnetic resonance (MR) imaging. MATERIALS AND METHODS This study was approved by the local institutional review board and was HIPAA compliant. All participants provided written informed consent. Neuropsychiatric tests including number connection test type A and digit symbol test were used to define minimal HE. Twenty-three patients with minimal HE and 25 age- and sex-matched healthy volunteers were included in this study. Resting-state functional MR imaging was performed by using a 3-T MR imaging unit. Functional connectivities between 90 pairs of cortical and subcortical regions in patients with minimal HE were compared with those in control participants, and significantly different connectivities were chosen as connectivities of interest (COIs). Correlations between neuropsychiatric tests and correlation coefficients of COIs were calculated. RESULTS Among the 51 COIs that were significantly different in patients with minimal HE from those in control participants, 44 connectivities were weaker in patients with minimal HE. All 22 COIs related to subcortical regions of interest (bilateral putamen, pallidum, and thalamus) were weaker in patients with minimal HE. Of 29 cortical COIs, 22 connectivities were weaker and seven were stronger in patients with minimal HE. Nearly all COIs with significant differences correlated with digital symbol test scores (P<.05, false discovery rate corrected). No correlation was found among blood ammonia level, Child-Pugh scores, or any COIs in patients with minimal HE (P>.05, false discovery rate corrected). CONCLUSION Widespread cortical and subcortical network connectivity changes that correlated with neuropsychologic impairment were found in patients with minimal HE. In particular, impairment in the basal ganglia-thalamocortical circuit could play an important role in mediating neurocognitive dysfunction, especially for psychomotor speed and attention deficits in patients with minimal HE.

Brain default-mode network abnormalities in hepatic encephalopathy: a resting-state functional MRI study.

Many neuroimaging investigations focus on hepatic encephalopathy (HE); however, few investigate default‐mode network (DMN) in the patients with HE and its underlying physiological relevance using resting‐state fMRI. In this study, independent component analysis was used to retrieve components representing the DMN of patients with HE (n = 14) and healthy volunteers (n = 14). Four patients were excluded because of head motion (n = 3) and the artifact from the artificial tooth (n = 1). Comparison results between the two groups revealed significantly reduced functional connectivity in the right middle frontal gyrus and left posterior cingulate cortex in the HE patients. A statistical t‐map from the comparison of venous blood ammonia levels and the z‐scores of the DMN obtained from independent component analysis was computed in the HE group, which showed negative correlation with the changes in left angular gyrus. In conclusions, resting‐state fMRI can be used to examine DMN changes in HE patients. Reduced functional connectivity in the right middle frontal gyrus and left posterior cingulate cortex consisting of the DMN and negative correlation between the functional connectivity changes in left AG and the venous blood ammonia levels support the notion of damages in functional organization of the central nervous system in HE patients. Hum Brain Mapp, 2011.

Selective Impairments of Resting-State Networks in Minimal Hepatic Encephalopathy

Background Minimal hepatic encephalopathy (MHE) is a neuro-cognitive dysfunction characterized by impairment in attention, vigilance and integrative functions, while the sensorimotor function was often unaffected. Little is known, so far, about the exact neuro-pathophysiological mechanisms of aberrant cognition function in this disease. Methodology/Principal Findings To investigate how the brain function is changed in MHE, we applied a resting-state fMRI approach with independent component analysis (ICA) to assess the differences of resting-state networks (RSNs) between MHE patients and healthy controls. Fourteen MHE patients and 14 age-and sex-matched healthy subjects underwent resting-state fMRI scans. ICA was used to identify six RSNs [dorsal attention network (DAN), default mode network (DMN), visual network (VN), auditory network (AN), sensorimotor network (SMN), self-referential network (SRN)] in each subject. Group maps of each RSN were compared between the MHE and healthy control groups. Pearson correlation analysis was performed between the RSNs functional connectivity (FC) and venous blood ammonia levels, and neuropsychological tests scores for all patients. Compared with the healthy controls, MHE patients showed significantly decreased FC in DAN, both decreased and increased FC in DMN, AN and VN. No significant differences were found in SRN and SMN between two groups. A relationship between FC and blood ammonia levels/neuropsychological tests scores were found in specific regions of RSNs, including middle and medial frontal gyrus, inferior parietal lobule, as well as anterior and posterior cingulate cortex/precuneus. Conclusions/Significance MHE patients have selective impairments of RSNs intrinsic functional connectivity, with aberrant functional connectivity in DAN, DMN, VN, AN, and spared SMN and SRN. Our fMRI study might supply a novel way to understand the neuropathophysiological mechanism of cognition function changes in MHE.

Structural and Functional Abnormalities of Default Mode Network in Minimal Hepatic Encephalopathy: A Study Combining DTI and fMRI

Background and Purpose Live failure can cause brain edema and aberrant brain function in cirrhotic patients. In particular, decreased functional connectivity within the brain default-mode network (DMN) has been recently reported in overt hepatic encephalopathy (HE) patients. However, so far, little is known about the connectivity among the DMN in the minimal HE (MHE), the mildest form of HE. Here, we combined diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to test our hypothesis that both structural and functional connectivity within the DMN were disturbed in MHE. Materials and Methods Twenty MHE patients and 20 healthy controls participated in the study. We explored the changes of structural (path length, tracts count, fractional anisotropy [FA] and mean diffusivity [MD] derived from DTI tractography) and functional (temporal correlation coefficient derived from rs-fMRI) connectivity of the DMN in MHE patients. Pearson correlation analysis was performed between the structural/functional indices and venous blood ammonia levels/neuropsychological tests scores of patients. All thresholds were set at P<0.05, Bonferroni corrected. Results Compared to the healthy controls, MHE patients showed both decreased FA and increased MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN) to left parahippocampal gyrus (PHG), and decreased functional connectivity between the PCC/PCUN and left PHG, and medial prefrontal cortex (MPFC). MD values of the tract connecting PCC/PCUN to the left PHG positively correlated to the ammonia levels, the temporal correlation coefficients between the PCC/PCUN and the MPFC showed positive correlation to the digital symbol tests scores of patients. Conclusion MHE patients have both disturbed structural and functional connectivity within the DMN. The decreased functional connectivity was also detected between some regions without abnormal structural connectivity, suggesting that the former may be more sensitive in detecting the early abnormalities of MHE. This study extends our understanding of the pathophysiology of MHE.

Altered Regional Homogeneity in the Development of Minimal Hepatic Encephalopathy: A Resting-State Functional MRI Study

Background Little is known about how spontaneous brain activity progresses from non-hepatic encephalopathy (non-HE) to minimal HE (MHE). The purpose of this study was to evaluate the evolution pattern of spontaneous brain activities in cirrhotic patients using resting-state fMRI with a regional homogeneity (ReHo) method. Methodology/Principal Findings Resting-state fMRI data were acquired in 47 cirrhotic patients (minimal HE [MHE], n = 20, and non-HE, n = 27) and 25 age-and sex-matched healthy controls. The Kendall’s coefficient of concordance (KCC) was used to measure the regional homogeneity. The regional homogeneity maps were compared with ANOVA tests among MHE, non-HE, and healthy control groups and t-tests between each pair in a voxel-wise way. Correlation analyses were performed to explore the relationships between regional ReHo values and Child-Pugh scores, number connection test type A (NCT-A), digit symbol test (DST) scores, venous blood ammonia levels. Compared with healthy controls, both MHE and non-HE patients showed decreased ReHo in the bilateral frontal, parietal and temporal lobes and increased ReHo in the bilateral caudate. Compared with the non-HE, MHE patients showed decreased ReHo in the bilateral precuneus, cuneus and supplementary motor area (SMA). The NCT-A of cirrhotic patients negatively correlated with ReHo values in the precuneus, cuneus and lingual gyrus. DST scores positively correlated with ReHo values in the cuneus, precuneus and lingual gyrus, and negatively correlated with ReHo values in the bilateral caudate (P<0.05, AlphaSim corrected). Conclusions/Significance Diffused abnormal homogeneity of baseline brain activity was nonspecific for MHE, and only the progressively decreased ReHo in the SMA and the cuneus, especially for the latter, might be associated with the development of MHE. The ReHo analysis may be potentially valuable for detecting the development from non-HE to MHE.

Combined analyses of gray matter voxel-based morphometry and white matter tract-based spatial statistics in pediatric bipolar mania

BACKGROUND Ample evidence has suggested the presence of gray matter (GM) and white matter (WM) abnormalities in bipolar disorder (BD) patients, including pediatric bipolar disorder (PBD). However, little research has been done in PBD patients that carefully classify the mood states. The aim of the present study is to investigate the brain structural changes in PBD-mania children and adolescents. METHODS Eighteen children and adolescents with bipolar mania (male/female, 6/12) aged 10-18 years old and 18 age- and sex-matched healthy controls were included in the present study. The 3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data were obtained on a Siemens 3.0 T scanner. Voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) analysis were conducted to compare the gray matter volume and white matter fractional anisotropy (FA) value between patients and controls. Correlations of the MRI data of each survived area with clinical characteristics in PBD patients were further analyzed. RESULTS As compared with the control group, PBD-mania children showed decreased gray matter volume in the left hippocampus. Meanwhile, significant lower FA value was detected in the right anterior cingulate (AC) in the patient group. No region of increased gray matter volume or FA value was observed in PBD-mania. The hippocampal volume was negatively associated with the Young Mania Rating Scale (YMRS) score when controlling for clinical characteristics in PBD-mania patients, however, there was no significant correlation of FA value of the survived area with illness duration, the onset age, number of episodes, or the YMRS score in PBD-mania patients. LIMITATION The present outcomes require replication in larger samples and verification in medication free subjects. CONCLUSIONS Our findings highlighted that extensive brain structural lesions (including GM and WM) were existed in PBD-mania. The widespread occurrence of structural abnormalities mainly located in the anterior limbic network (ALN) which suggested that this network might contribute to emotional and cognitive dysregulations in PBD.

Disrupted Functional Connectivity of the Anterior Cingulate Cortex in Cirrhotic Patients without Overt Hepatic Encephalopathy: A Resting State fMRI Study

Background To evaluate the changes of functional connectivity of the anterior cingulate cortex (ACC) in patients with cirrhosis without overt hepatic encephalopathy (HE) using resting state functional MRI. Methodology/Principal Findings Participants included 67 cirrhotic patients (27 minimal hepatic encephalopathy (MHE) and 40 cirrhotic patients without MHE (non-HE)), and 40 age- and gender- matched healthy controls. rsfMRI were performed on 3 Telsa scanners. The pregenual ACC resting-state networks (RSNs) were characterized by using a standard seed-based whole-brain correlation method and compared between cirrhotic patients and healthy controls. Pearson correlation analysis was performed between the ACC RSNs and venous blood ammonia levels, neuropsychological tests (number connection test type A [NCT-A] and digit symbol test [DST]) scores in cirrhotic patients. All thresholds were set at P<0.05, with false discovery rate corrected. Compared with controls, non-HE and MHE patients showed significantly decreased functional connectivity in the bilateral ACC, bilateral middle frontal cortex (MFC), bilateral middle cingulate cortex (MCC), bilateral superior temporal gyri (STG)/middle temporal gyri (MTG), bilateral thalami, bilateral putamen and bilateral insula, and increased functional connectivity of bilateral precuneus and left temporo-occipital lobe and bilateral lingual gyri. Compared with non-HE patients, MHE showed the decreased functional connectivity of right MCC, bilateral STG/MTG and right putamen. This indicates decreased ACC functional connectivity predominated with the increasing severity of HE. NCT-A scores negatively correlated with ACC functional connectivity in the bilateral MCC, right temporal lobe, and DST scores positively correlated with functional connectivity in the bilateral ACC and the right putamen. No correlation was found between venous blood ammonia levels and functional connectivity in ACC in cirrhotic patients. Conclusions/Significance Disrupted functional connectivity in ACC was found in cirrhotic patients which further deteriorated with the increasing severity of HE and correlated cognitive dysfunction in cirrhotic patients.

The Effect of Hepatic Encephalopathy, Hepatic Failure, and Portosystemic Shunt on Brain Volume of Cirrhotic Patients: A Voxel-Based Morphometry Study

Purpose To evaluate the effect of hepatic encephalopathy (HE), hepatic failure, and portosystemic shunt (PS) on the brain volume alteration in cirrhotic patients with MRI voxel-based morphometry (VBM). Methods Sixty cirrhotic patients (overt HE [OHE], n = 11; minimal HE [MHE], n = 19; non HE [nHE], n = 30) including 12 with pre- and post-transjugular intrahepatic portosystemic shunt (TIPS) scanning and 40 healthy controls were recruited. Neuropsychological and laboratory tests were performed in all patients. VBM was analyzed with ANOVA test among 4 groups, and t-tests for patients with different hepatic function, PS scores, and TIPS. Multiple linear regression was performed to investigate the effect of venous blood ammonia levels, Child-Pugh scores, and PS on the brain volumes in all patients. Results Cirrhotic patients exhibited decreased volume in many areas of gray matter (GM), increased volume in thalamus, and increased whiter matter (WM) volume, with the extent of affected brain volume greater in HE patients than nHE patients. Hepatic failure also resulted in decreased GM volume. Patients with high PS scores and TIPS displayed decreased GM and increased WM volume in some regions. Post-TIPS patients displayed increased GM volume in the thalamus. Multiple covariate regression results suggested that Child-Pugh score was a major factor to affect GM volume, while PS mainly affected WM volume. Conclusion Brain structure abnormalities appeared bilaterally symmetrical in cirrhotic patients, and the impairment was more extensive in HE patients than those without HE. Increased thalamus volume was not associated with HE progression. Hepatic failure and PS altered cirrhotic patients’ brain structure.