Number Connection Test Type Research Articles

Combining arterial-spin labeling with functional magnetic resonance imaging measurement for characterizing patients with minimal hepatic encephalopathy.

Our objective is to explore key changes in brain functions in relation to minimal hepatic encephalopathy (MHE). We incorporated both resting-state functional magnetic resonance imaging (fMRI) and arterial spin labeling (ASL) to enhance the detection of MHE. We undertook fMRI scanning for 56 MHE patients and 66 healthy controls. Region functional connectivity was carried out to assess the connectivity status between pairs of regions among 90 brain regions. Additionally, blood flow (BF) status was measured by ASL for all subjects. Spearman's correlation test was implemented to identify any correlation among z-values, results from number connection test type A, and digit symbol tests. Finally, the receiver operating characteristic curve was generated for assessing the accuracy of BF in MHE diagnosis. The corresponding functional connectivity was significantly different between MHE and control groups in 15 regions. For MHE patients, BF showed an increasing pattern in regions of interest. Blood flood in the putamen was positively correlated with number connection test type A neuropsychological performance, whereas it was negatively correlated with the digit symbol test. Blood flood in the right putamen showed the highest value of area under the curve with a sensitivity of 85.7% and specificity of 89.4%. Connectivity impairment resulting from ganglia-thalamo-cortical circuits may play important roles in mediating the development of MHE patients. An increase in the BF, particularly in the right putamen, may be considered as evidence for the presence of MHE.

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

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. 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. 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). 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.

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.

Disrupted small world networks in patients without overt hepatic encephalopathy: A resting state fMRI study

PurposeTo explore changes in functional connectivity and topological organization of brain functional networks in cirrhotic patients with minimal hepatic encephalopathy (MHE) and non hepatic encephalopathy (nonHE) and their relationship with clinical markers. Materials and methodsResting-state functional MR imaging was acquired in 22 MHE, 29 nonHE patients and 33 healthy controls. Functional connectivity networks were obtained by computing temporal correlations between any pairs of 90 cortical and subcortical regions. Graph analysis measures were quantitatively assessed for each subject. One-way analysis of covariance was applied to identify statistical differences of functional connectivity and network parameters among three groups. Correlations between clinical markers, such as Child–Pugh scores, venous blood ammonia level, and number connection test type A (NCT-A)/digit symbol test (DST) scores, and connectivity/graph metrics were calculated. ResultsThirty functional connectivities represented by edges were found to be abnormal (P<0.05, FDR corrected) in cirrhotic patients, in which 16 edges (53.3%) were related with sub-cortical regions. MHE patients showed abnormal small-world attributes in the functional connectivity networks. Cirrhotic patients had significantly reduced nodal degree in 8 cortical regions and increased nodal centrality in 3 cortical regions. Twenty edges were correlated with either NCT-A or DST scores, in which 13 edges were related with sub-cortical regions. No correlation was found between Child–Pugh scores and graph theoretical measures in cirrhotic patients. ConclusionDisturbances of brain functional connectivity and small world property loss are associated with neurocognitive impairment of cirrhotic patients. Reorganization of brain network occurred during disease progression from nonHE to MHE.

Altered brain functional connectivity in hemodialysis patients with end-stage renal disease: a resting-state functional MR imaging study.

The changes of whole brain functional connectivity in hemodialysis (HD) patients with end-stage renal disease (ESRD) are still unclear, which may be associated with multiple factors, such as elevated neurotoxins, anemia, and side effects of hemodialysis. Resting-state functional magnetic resonance imaging (rs-fMRI) data of 71 patients (43 males, 28 females; mean age, 33.4 ± 9.4 years) and 43 age- and gender-matched healthy volunteers (29 males, 14 females; mean age, 30.6 ± 8.8 years) were acquired. Neuropsychological tests including number connection test type A (NCT-A), digit symbol test (DST), line-tracing test (LTT), serial-dotting test (SDT), self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to evaluate cognitive and psychiatric conditions in all subjects. Blood biochemistry tests including serum creatinine levels, blood urea, hematocrit, and Ca(2+) level were taken in HD patients. Forty-two connections significantly different between HD patients with ESRD and controls were found (all P < 0.05, Bonferroni corrected) and identified as connectivities of interests (COIs), among which 39 connections (92.9%) were markedly decreased in patients. Of the 39 weaker connections, 24 were related to the frontal lobe regions. Widespread weakening of cortical and subcortical network connectivity in ESRD patients was more directly related with neuropsychological impairments and anemia rather than serum creatinine level, blood urea and dialysis duration. In particular, impairments in the medial prefrontal lobe could play an important role in mediating psychological dysfunctions.

Brain regional homogeneity changes following transjugular intrahepatic portosystemic shunt in cirrhotic patients support cerebral adaptability theory—A resting-state functional MRI study

PurposeThe exact neuro-pathophysiological effect of transjugular intrahepatic portosystemic shunt (TIPS) on brain function remains unclear. The purpose of this study was to investigate the longitudinal brain activity changes in cirrhotic patients with TIPS insertion using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. MethodsFifteen cirrhotic patients without overt hepatic encephalopathy (OHE) planned for TIPS procedure and 15 age- and gender-matched healthy controls were included in this study. Eleven of the 15 patients underwent repeated fMRI examinations at median 7-day following TIPS, 8 patients in median 3-month, and 7 patients in median 1-year follow-up duration, respectively. Regional homogeneity was calculated by the Kendall's coefficient of concordance (KCC) and compared between patients before TIPS and healthy controls with two-sample t test as well as pre-and post-TIPS patients with paired t test. Correlations between the pre- and post-TIPS changes of ReHo and the changes of venous blood ammonia level and number connection test type A (NCT-A)/digit symbol test (DST) scores were calculated by crossing subjects. ResultsCompared with healthy controls, 15 cirrhotic patients before TIPS procedure showed decreased ReHo in the bilateral frontal, parietal, temporal and occipital lobes and increased ReHo in the bilateral caudate. Compared with the pre-TIPS patients, 11 post-TIPS patients in the median 7-day follow-up examinations demonstrated decreased ReHo in the medial frontal gyrus (MFG), superior parietal gyrus (SPG), middle/superior temporal gyrus (M/STG), anterior cingulate cortex (ACC), caudate, and increased ReHo in the insula. Eight post-TIPS patients in the median 3-month follow-up examinations showed widespread decreased ReHo in the bilateral frontal and parietal lobes, ACC, caudate, and increased ReHo in the insula and precuneus/cuneus. In the median 1-year follow-up studies, seven post-TIPS patients displayed decreased ReHo in the bilateral frontal and parietal lobes, ACC, supplementary motor area (SMA), posterior cingulate cortex (PCC), and increased ReHo in the caudate and insula (P<0.05, Alphasim corrected). The changes of ReHo values in bilateral IPL, MFG, caudate and SMA were correlated with changes of DST scores during the median 3-month follow-up (all P<0.05). ConclusionThe TIPS implantation had a persistent effect on brain function in cirrhotic patients including both predominant impairment and compensation mechanisms, with the most significant alterations in the median 3-month period after TIPS. The ReHo analysis may be potentially valuable for uncovering the mechanism of TIPS’ effects on brain function.

Altered Pattern of Spontaneous Brain Activity in the Patients with End-Stage Renal Disease: A Resting-State Functional MRI Study with Regional Homogeneity Analysis

PurposeTo investigate the pattern of spontaneous neural activity in patients with end-stage renal disease (ESRD) with and without neurocognitive dysfunction using resting-state functional magnetic resonance imaging (rs-fMRI) with a regional homogeneity (ReHo) algorithm.Materials and Methodsrs-fMRI data were acquired in 36 ESRD patients (minimal nephro-encephalopathy [MNE], n = 19, 13 male, 37±12.07 years; non-nephro-encephalopathy [non-NE], n = 17, 11 male, 38±12.13 years) and 20 healthy controls (13 male, 7 female, 36±10.27 years). Neuropsychological (number connection test type A [NCT-A], digit symbol test [DST]) and laboratory tests were performed in all patients. The Kendall's coefficient of concordance (KCC) was used to measure the regional homogeneity for each subject. The regional homogeneity maps were compared using ANOVA tests among MNE, non-NE, and healthy control groups and post hoc t -tests between each pair in a voxel-wise way. A multiple regression analysis was performed to evaluate the relationships between ReHo index and NCT-A, DST scores, serum creatinine and urea levels, disease and dialysis duration.ResultsCompared with healthy controls, both MNE and non-NE patients showed decreased ReHo in the multiple areas of bilateral frontal, parietal and temporal lobes. Compared with the non-NE, MNE patients showed decreased ReHo in the right inferior parietal lobe (IPL), medial frontal cortex (MFC) and left precuneus (PCu). The NCT-A scores and serum urea levels of ESRD patients negatively correlated with ReHo values in the frontal and parietal lobes, while DST scores positively correlated with ReHo values in the bilateral PCC/precuneus, MFC and inferior parietal lobe (IPL) (all P<0.05, AlphaSim corrected). No significant correlations were found between any regional ReHo values and disease duration, dialysis duration and serum creatinine values in ESRD patients (all P>0.05, AlphaSim corrected).ConclusionDiffused decreased ReHo values were found in both MNE and non-NE patients. The progressively decreased ReHo in the default mode network (DMN), frontal and parietal lobes might be trait-related in MNE. The ReHo analysis may be potentially valuable for elucidating neurocognitive abnormalities of ESRD patients and detecting the development from non-NE to MNE.

Transjugular intrahepatic portosystemic shunt induced short- and long-term cerebral blood flow variations in cirrhotic patients: an arterial spin labeling MRI study

Short- and long-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on cerebral blood flow (CBF) in patients with cirrhosis are still unclear. The purpose of this longitudinal study was to explore CBF alteration patterns in cirrhotic patients after TIPS. Thirteen cirrhotic patients (7 male, 6 female, mean age 50.0 ± 9.3 years) underwent arterial-spin labeling (ASL) MRI 1-9 days (median 1 days) before TIPS. Follow-up MR examinations were performed about 1 week (median 6 days), 3 months (n = 6), 6-9 months (n = 5) and 12-18 months (n = 5) after TIPS. CBF, ammonia level, Child-Pugh score, number connection test type A (NCT-A) and digit symbol test (DST) scores were converted into relative values by dividing by his/her pre-TIPS values, and then, compared via one-way analysis of variance (ANOVA). Correlations between the pre- and post-TIPS changes of relative CBF (rCBF) and the changes of relative ammonia (rAmmonia), Child-Pugh (rChild-Pugh), and NCT-A/DST (rNCT-A/rDST) scores were calculated by crossing subjects. Compared with the pre-TIPS level, the global rCBF slightly increased by 10.9 % about 1 week later, then rapidly decreased by 14.2 % 3 months later, and flatly decreased by 17.2 % in 6-9 months and 18.0 % in 12-18 months following TIPS. The changes of 3-month rDST score were slightly correlated with 3-month rCBF rather than 1-week rCBF, (P < 0.1, FDR-corrected) No difference was found between the pre- and post-TIPS rAmmonia levels, rChild-Pugh and rNCT-A/rDST scores (Post-hoc P > 0.05). CBF measured at different time points after TIPS insertion showed different patterns, indicating varying longitudinal effects of TIPS on CBF. A sharp decline of rCBF was found in the 1 week to 3 months period after insertion, indicating that high event rate of hepatic encephalopathy might relate with the unadaptable CBF in patients undergoing TIPS insertion.

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

BackgroundTo 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 FindingsParticipants 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/SignificanceDisrupted 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.

Dynamic posturography findings among patients with liver cirrhosis in Egypt

Abstract Background Liver cirrhosis is a condition that destroys the normal function of the liver, leading to hepatic encephalopathy, which is associated with impairment in postural control and disturbance in balance. Aim of the study The aim of this study was to detect the disturbances in balance and postural control because of hepatic encephalopathy as a result of liver cirrhosis using dynamic posturography. Participants and methods Individuals were divided into two groups: 45 patients with liver cirrhosis and 45 controls. Both groups underwent dynamic posturography to evaluate balance control, number connection test-type A, line tracing test, and serum ammonia (NH3) level to assess encephalopathy. Results Dynamic posturography findings were significantly weaker in patients with liver cirrhosis than in the controls. They were also weaker in patients with high NH3 than in patients with low NH3. There were significant negative correlations between dynamic posturography findings and number connection test-type A, line tracing test, and NH3 levels. Conclusion Hepatic encephalopathy because if liver cirrhosis affects balance control and the degree of affection is related to the degree of encephalopathy.

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

To investigate patterns of whole-brain functional connectivity in patients with minimal hepatic encephalopathy (HE) by using functional magnetic resonance (MR) imaging. 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. 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). 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.

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

BackgroundLittle 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 FindingsResting-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/SignificanceDiffused 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.

Metabolic changes of anterior cingulate cortex in patients with hepatic cirrhosis: A magnetic resonance spectroscopy study

The anterior cingulate cortex (ACC) plays an important role in cognitive functions. The purpose of this study is to compare metabolite concentrations in the ACC of cirrhotic patients with normal controls, and to correlate metabolite changes with Child-Pugh class and with severity of hepatic encephalopathy (HE). Fifty-two cirrhotic patients and 30 healthy volunteers were included in this study. All subjects performed the number connection test type A (NCT-A) and digital symbol test (DST) before multiple resonance (MR) examinations. Single-voxel proton MR spectroscopy (MRS) data in the ACC were acquired on a 1.5-T scanner. The ratios of all metabolites to creatine and phosphocreatine (Cr) were obtained. Statistical analysis was performed to evaluate the difference between control and cirrhotic patients, with respect to metabolite ratios. The correlation between metabolite ratios and Child-Pugh scale, severity of HE, venous ammonia and neuropsychiatric test results was analyzed. The ratios of choline (Cho)/Cr and myo-inositol (mIns)/Cr were significantly lower, and the ratio of glutamine- glutamate (Glx)/Cr was significantly higher in cirrhotic patients than those in controls (P < 0.001). mIns/Cr correlated negatively with Child-Pugh scale (r = -0.496, P < 0.001) and HE degree (r = -0.313, P < 0.05). Venous ammonia had a significant correlation with Cho/Cr (r = -0.329, P < 0.05) and mIns/Cr (r = -0.347, P < 0.05). No statistical correlation between metabolite ratios and neuropsychological tests was found for cirrhotic patients, but mIns/Cr did have a statistical correlation with NCT-A (r = -0.270, P < 0.05) and DST (r = 0.463, P < 0.001) when all subjects were included in the analysis. Significant metabolite changes were seen in the ACC in cirrhotic patients. Of the metabolites examined, the mIns/Cr level in the ACC was most closely associated with the severity of HE and hepatic functional reserve reflected by Child-Pugh scale.