Disrupted Brain Functional Status in Patients with Reversible Cerebral Vasoconstriction Syndrome.

OBJECTIVES: The aim of this study was to investigate the functional networks in subjects with reversible cerebral vasoconstriction syndrome (RCVS) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: We prospectively recruited patients with RCVS and healthy controls (HCs) between February 2017 and April 2021. The rs-fMRI data were analyzed using graph theory methods. We compared node-based global and regional topological metrics (Bundle 1) and network-based intranetwork and internetwork connectivity (Bundle 2) between RCVS patients and HCs. We also explored the associations of clinical and vascular (ie, the Lindegaard index, LI) parameters with significant rs-fMRI metrics. RESULTS: A total of 104 RCVS patients and 93 HCs were included in the final analysis. We identified significantly decreased local efficiency of the left dorsal anterior insula (dAI; p = 0.0005) in RCVS patients within 30 days after disease onset as compared to HCs, which improved 1 month later. RCVS patients also had increased global efficiency (p = 0.009) and decreased average degree centrality (p = 0.045), clustering coefficient (p = 0.033), and assortativity values (p = 0.003) in node-based analysis. In addition, patients with RCVS had increased internetwork connectivity of the default mode network (DMN) with the salience (p = 0.027) and dorsal attention (p = 0.016) networks. Significant correlations between LI and regional local efficiency in left dAI (rs = -0.418, p = 0.042) was demonstrated. INTERPRETATION: The significantly lower local efficiency of the left dAI, suggestive of impaired central autonomic modulation, was negatively correlated with vasoconstriction severity, which is highly plausible for the pathogenesis of RCVS. ANN NEUROL 2023;94:772-784.

A YOLO-based AI system for classifying calcifications on spot magnification mammograms.

OBJECTIVES: Use of an AI system based on deep learning to investigate whether the system can aid in distinguishing malignant from benign calcifications on spot magnification mammograms, thus potentially reducing unnecessary biopsies. METHODS: In this retrospective study, we included public and in-house datasets with annotations for the calcifications on both craniocaudal and mediolateral oblique vies, or both craniocaudal and mediolateral views of each case of mammograms. All the lesions had pathological results for correlation. Our system comprised an algorithm based on You Only Look Once (YOLO) named adaptive multiscale decision fusion module. The algorithm was pre-trained on a public dataset, Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM), then re-trained and tested on the in-house dataset of spot magnification mammograms. The performance of the system was investigated by receiver operating characteristic (ROC) analysis. RESULTS: We included 1872 images from 753 calcification cases (414 benign and 339 malignant) from CBIS-DDSM. From the in-house dataset, 636 cases (432 benign and 204 malignant) with 1269 spot magnification mammograms were included, with all lesions being recommended for biopsy by radiologists. The area under the ROC curve for our system on the in-house testing dataset was 0.888 (95% CI 0.868-0.908), with a sensitivity of 88.4% (95% CI 86.9-8.99%), specificity of 80.8% (95% CI 77.6-84%), and an accuracy of 84.6% (95% CI 81.8-87.4%) at the optimal cutoff value. Using the system with two views of spot magnification mammograms, 80.8% benign biopsies could be avoided. CONCLUSION: The AI system showed good accuracy for classification of calcifications on spot magnification mammograms which were all categorized as suspicious by radiologists, thereby potentially reducing unnecessary biopsies.

Simple parameters of synthetic MRI for assessment of bone density in patients with spinal degenerative disease.

OBJECTIVE: Good bone quality is the key to avoiding osteoporotic fragility fractures and poor outcomes after lumbar instrumentation and fusion surgery. Although dual-energy x-ray absorptiometry (DEXA) screening is the current standard for evaluating osteoporosis, many patients lack DEXA measurements before undergoing lumbar spine surgery. The present study aimed to investigate the utility of using simple quantitative parameters generated with novel synthetic MRI to evaluate bone quality, as well as the correlations of these parameters with DEXA measurements. METHODS: This prospective study enrolled patients with symptomatic lumbar degenerative disease who underwent DEXA and conventional and synthetic MRI. The quantitative parameters generated with synthetic MRI were T1 map, T2 map, T1 intensity, proton density (PD), and vertebral bone quality (VBQ) score, and these parameters were correlated with T-score of the lumbar spine. RESULTS: There were 62 patients and 238 lumbar segments eligible for analysis. PD and VBQ score moderately correlated with T-score of the lumbar spine (r = -0.565 and -0.651, respectively; both p < 0.001). T1 intensity correlated fairly well with T-score (r = -0.411, p < 0.001). T1 and T2 correlated poorly with T-score. Receiver operating characteristic curve analysis demonstrated area under the curve values of 0.808 and 0.794 for detecting osteopenia/osteoporosis (T-score ≤ -1.0) and osteoporosis (T-score ≤ -2.5) with PD (both p < 0.001). CONCLUSIONS: PD and T1 intensity values generated with synthetic MRI demonstrated significant correlation with T-score. PD has excellent ability for predicting osteoporosis and osteopenia.

Disrupted metabolic connectivity in dopaminergic and cholinergic networks at different stages of dementia from 18F-FDG PET brain persistent homology network.

Dementia is related to the cellular accumulation of ß-amyloid plaques, tau aggregates, or α-synuclein aggregates, or to neurotransmitter deficiencies in the dopaminergic and cholinergic pathways. Cellular and neurochemical changes are both involved in dementia pathology. However, the role of dopaminergic and cholinergic networks in metabolic connectivity at different stages of dementia remains unclear. The altered network organisation of the human brain characteristic of many neuropsychiatric and neurodegenerative disorders can be detected using persistent homology network (PHN) analysis and algebraic topology. We used 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging data to construct dopaminergic and cholinergic metabolism networks, and used PHN analysis to track the evolution of these networks in patients with different stages of dementia. The sums of the network distances revealed significant differences between the network connectivity evident in the Alzheimer's disease and mild cognitive impairment cohorts. A larger distance between brain regions can indicate poorer efficiency in the integration of information. PHN analysis revealed the structural properties of and changes in the dopaminergic and cholinergic metabolism networks in patients with different stages of dementia at a range of thresholds. This method was thus able to identify dysregulation of dopaminergic and cholinergic networks in the pathology of dementia.

Alterations in sympathetic and parasympathetic brain networks in obstructive sleep apnea.

OBJECTIVE/BACKGROUND: Obstructive sleep apnea (OSA) patients experience hypoxia and, potentially, autonomic impairments stemming from neural damage. In this study, the executive control networks (ECNs), salience networks (SNs), and default mode networks (DMNs) of adult OSA patients, as well as their relationships with autonomic impairment, were investigated through independent component analysis (ICA). PATIENTS/METHODS: A total of 41 OSA patients and 19 healthy controls volunteers were recruited and subjected to polysomnography to ascertain their degree, if any, of sleep apnea. Each participant also underwent a cardiovascular autonomic survey, with the participant's baroreflex sensitivity (BRS) being determined based on heart rate and blood pressure alterations. The resting fMRI data of the participants was separated using probabilistic ICA, and six autonomic resting-state networks were established for group comparisons. The differences in autonomic parameters, autonomic functional connectivity (FC), and clinical severity were then correlated. RESULTS: The OSA group had significantly worse BRS values than the controls, as well as lower FC in the posterior and anterior SNs, bilateral ECNs, and the ventral DMN, and higher FC in the left ECN. These intrinsic connectivity networks showed dissociable correlations with greater baroreflex impairment and clinical disease severity. The higher FC in the left ECN was associated with the lower FC in the ventral DMN. CONCLUSIONS: Our findings suggest that autonomic dysfunction in OSA might be accompanied by central autonomic network alterations. The stronger sympathetic-associated regions in ECNs and the weaker parasympathetic-associated regions in DMNs may represent intrinsic neural architecture fluctuations underlining their consequent processes in OSA.

Comparison of Multivendor Single-Voxel MR Spectroscopy Data Acquired in Healthy Brain at 26 Sites.

Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model. P values were derived through parametric bootstrapping of the linear mixed-effects models (denoted Pboot). Results In total, 296 participants (mean age, 26 years ± 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of N-acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (≤5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol (Pboot > .90), N-acetylaspartate and N-acetylaspartylglutamate (Pboot = .13), or glutamate and glutamine (Pboot = .11). Among the smaller resonances, no vendor effects were found for ascorbate (Pboot = .08), aspartate (Pboot > .90), glutathione (Pboot > .90), or lactate (Pboot = .28). Conclusion Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols. © RSNA, 2020 Online supplemental material is available for this article.

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites.

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.

Interaction of systemic oxidative stress and mesial temporal network degeneration in Parkinson's disease with and without cognitive impairment.

BACKGROUND: To identify the vulnerable areas associated with systemic oxidative stress and further disruption of these vulnerable areas by measuring the associated morphology and functional network alterations in Parkinson's disease (PD) patients with and without cognitive impairment. METHODS: This prospective study was approved by the institutional review board of KCGMH, and written informed consent was obtained. Between December 2010 and May 2015, 41 PD patients with different levels of cognitive functions and 29 healthy volunteers underwent peripheral blood sampling to quantify systemic oxidative stress, as well as T1W volumetric and resting state functional MRI (rs-fMRI) scans. Rs-fMRI was used to derive the healthy intrinsic connectivity patterns seeded by the vulnerable areas associated with any of the significant oxidative stress markers. The two groups were compared in terms of the functional connectivity correlation coefficient (fc-CC) and gray matter volume (GMV) of the network seeded by the vulnerable areas. RESULTS: The levels of oxidative stress markers, including leukocyte apoptosis and adhesion molecules, were significantly higher in the PD group. Using whole-brain VBM-based correlation analysis, the bilateral mesial temporal lobes (MTLs) were identified as the most vulnerable areas associated with lymphocyte apoptosis (P < 0.005). We found that the MTL network of healthy subjects resembled the PD-associated atrophy pattern. Furthermore, reduced fc-CC and GMV were further associated with the aggravated cognitive impairment. CONCLUSION: The MTLs are the vulnerable areas associated with peripheral lymphocyte infiltration, and disruptions of the MTL functional network in both architecture and functional connectivity might result in cognitive impairments in Parkinson's disease.

Clinical Effects and Differences in Neural Function Connectivity Revealed by MRI in Subacute Hemispheric and Brainstem Infarction Patients With Dysphagia After Swallowing Therapy.

Background: Early detection and intervention for post-stroke dysphagia could reduce the incidence of pulmonary complications and mortality. The aims of this study were to investigate the benefits of swallowing therapy in swallowing function and brain neuro-plasticity and to explore the relationship between swallowing function recovery and neuroplasticity after swallowing therapy in cerebral and brainstem stroke patients with dysphagia. Methods: We collected 17 subacute stroke patients with dysphagia (11 cerebral stroke patients with a median age of 76 years and 6 brainstem stroke patients with a median age of 70 years). Each patient received swallowing therapies during hospitalization. For each patient, functional oral intake scale (FOIS), functional dysphagia scale (FDS) and 8-point penetration-aspiration scale (PAS) in videofluoroscopy swallowing study (VFSS), and brain functional magnetic resonance imaging (fMRI) were evaluated before and after treatment. Results: FOIS (p = 0.003 in hemispheric group and p = 0.039 in brainstem group) and FDS (p = 0.006 in hemispheric group and p = 0.028 in brainstem group) were both significantly improved after treatment in hemispheric and brainstem stroke patients. In hemispheric stroke patients, changes in FOIS were related to changes of functional brain connectivity in the ventral default mode network (vDMN) of the precuneus in brain functional MRI (fMRI). In brainstem stroke patients, changes in FOIS were related to changes of functional brain connectivity in the left sensorimotor network (LSMN) of the left postcentral region characterized by brain fMRI. Conclusion: Both hemispheric and brainstem stroke patients with different swallowing difficulties showed improvements after swallowing training. For these two dysphagic stroke groups with corresponding etiologies, swallowing therapy could contribute to different functional neuroplasticity.

Correlation between Dopamine Transporter Degradation and Striatocortical Network Alteration in Parkinson's Disease.

The association between dopamine neuron loss and functional change in the striatocortical network was analyzed in 31 patients with Parkinson's disease (PD) [mean disease duration 4.03 ± 4.20 years; Hoehn and Yahr (HY) stage 2.2 ± 1.2] and 37 age-matched normal control subjects. We performed 99mTc-TRODAT-1 SPECT/CT imaging to detect neuron losses and resting-state functional magnetic resonance imaging to detect functional changes. Mean striatal dopamine transporter binding ratios were determined by region of interest analysis. The functional connectivity correlation coefficient (fc-cc) was determined in six striatal subregions, and interactions between these binding ratios and the striatocortical fc-cc values were analyzed. The PD patients had significant functional network alterations in all striatal subregions. Lower striatal dopamine transporter binding correlated significantly with lower fc-cc values in the superior medial frontal (SMF) lobe and superior frontal lobe and higher fc-cc values in the cerebellum and parahippocampus. The difference in fc-cc between the ventral inferior striatum and SMF lobe was significantly correlated with increased disease duration (r = -0.533, P = 0.004), higher HY stage (r = -0.431, P = 0.020), and lower activities of daily living score (r = 0.369, P = 0.049). The correlation of frontostriatal network changes with clinical manifestations suggests that fc-cc may serve as a surrogate marker of disease progression.

Big GABA: Edited MR spectroscopy at 24 research sites.

Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.

Evolutional Characterization of Photochemically Induced Stroke in Rats: a Multimodality Imaging and Molecular Biological Study.

Photochemically induced cerebral ischemia is an easy-manipulated, reproducible, relatively noninvasive, and lesion controllable model for translational study of ischemic stroke. In order to longitudinally investigate the characterization of the model, magnetic resonance imaging, 18F-2-deoxy-glucose positron emission tomography, fluorescence, and bioluminescence imaging system were performed in correlation with triphenyl tetrazolium chloride (TTC), hematoxylin-eosin staining, and immunohistochemistry examinations of glial fibrillary acidic protein, CD68, NeuN, von willebrand factor, and α-smooth muscle actin in the infarct zone. The results suggested that the number of inflammatory cells, astrocytes, and neovascularization significantly elevated in peri-infarct region from day 7 and a belt of macrophage/microglial and astrocytes was formed surrounding infarct lesion at day 14. Both vasogenic and cytotoxic edema, as well as blood brain-barrier leakage, occurred since day 1 after stroke induction and gradually attenuated with time. Numerous cells other than neuronal cells infiltrated into infarct lesion, which resulted in no visible TTC negative regional existence at day 14. Furthermore, recovery of cerebral blood flow and glucose utilization in peri-infarct zone were noted and more remarkably than that in infarct core following the stroke progression. In conclusion, these characterizations may be highly beneficial to the development of therapeutic strategies for ischemic stroke.

Schizophrenia symptoms and brain network efficiency: A resting-state fMRI study.

Schizophrenia is a condition marked by a disrupted brain functional network. In schizophrenia, the brain network is characterized by reduced distributed information processing efficiency; however, the correlation between information processing efficiency and the symptomatology of schizophrenia remains unclear. Few studies have examined path length efficiencies in schizophrenia. In this study, we examined small-world network metrics computed from resting state functional magnetic resonance imaging data collected from 49 patients with schizophrenia and 28 healthy people. We calculated brain network efficiency using graph theoretical analysis of the networks of brain areas, as defined by the Automated Anatomical Labeling parcellation scheme, and investigated efficiency correlations by using the 5-factor model of psychopathology, which considers the various domains of schizophrenic symptoms and might also consider discrete pathogenetic processes. The global efficiency of the resting schizophrenic brains was lower than that of the healthy controls, but local efficiency did not differ between the groups. The severity of psychopathology, negative symptoms, and depression and anxiety symptoms were correlated with global efficiency in schizophrenic brains. The severity of psychopathology was correlated with increased network efficiency from short-range connections, but not networks from long-range connections. Our findings indicate that schizophrenic psychopathology is correlated with brain network information processing efficiency.

Resting State-fMRI with ReHo Analysis as a Non-Invasive Modality for the Prognosis of Cirrhotic Patients with Overt Hepatic Encephalopathy.

BACKGROUND: To investigate the relationships among regional activity abnormalities, clinical disease severity, and prognosis in cirrhotic patients with overt hepatic encephalopathy (OHE) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Regional homogeneity (ReHo) values of 12 cirrhotic patients with OHE and 12 age- and sex-matched healthy volunteers were calculated from rs-fMRI. Two-sample t-test was performed on individual ReHo maps between the two groups. The relationships between ReHo variation, disease severity, and prognosis were analyzed. RESULTS: Cirrhotic patients with OHE had significantly low ReHo values in the left middle cingulum, bilateral superior temporal, left inferior orbito-frontal, right calcarine, left inferior frontal gyrus, left post-central, left inferior temporal, and left lingual areas, and high ReHo in the right superior frontal, right inferior temporal, right caudate, and cerebellum. There was significant group difference in the right superior temporal lobe (p=0.016) and crus1 of the left cerebellum (p=0.015) between survivors and non-survivors in the OHE group. Worse Glasgow Coma Scale was associated with increased local connectivity in the left cerebellar crus I (r=-0.868, p=0.001). CONCLUSIONS: Information on the functional activity of cirrhotic patients with OHE suggests the use of rs-fMRI with ReHo analysis as a non-invasive prognosticating modality.

Reestablishing brain networks in patients without overt hepatic encephalopathy after liver transplantation.

Cirrhotic patients without overt hepatic encephalopathy (HE) have associated with widespread neuro-psychological impairment. Liver transplantation can restore metabolic abnormalities but the mechanisms are unclear. We investigate brain functional networks after transplantation using resting-state funtional magnetic resonance imaging (MRI). Twenty-six cirrhotic patients without overt HE completed neuro-psychological assessment before and 6 to 12 months after transplantation, and compared with 35 healthy controls. Five major functional brain networks, default mode (DMN), dorsal attention (DAN), executive control (ECN), salience (SN), and primary networks (PN), were assessed. Nodal efficiency and strength in different functional networks were weighed and their interaction metrics displayed. Granger causal analysis between pretransplantation and posttransplantation was performed. Before transplantation, the intrafunctional connectivity was decreased in DMN, DAN, ECN, and SN. After transplantation, cognitive functions improved with increased functional connectivity. The interaction metrics among large-scale networks in patients became similar to healthy controls. The increase in PN affected the decrease in SN, while the increase in DAN forced a decrease in DMN. There was a bidirectional balance between DMN and SN. Dynamic disruptions and reconstruction in intrinsic large-scale networks are associated with parallel patterns of cognitive information processing deficits and recovery. Remapping of SN, DMN, and DAN is essential for restoring cognition after transplantation.

Reduced neuro-integration from the dorsolateral prefrontal cortex to the whole brain and executive dysfunction in schizophrenia patients and their relatives.

Executive dysfunction is one of the core symptoms of schizophrenia. Functional neuro-imaging studies have suggested an association between deficits in activating the dorsolateral prefrontal cortex (DLPFC) and executive dysfunction, but neuro-integration from the DLPFC to the whole brain remains unclear. Studies investigating the neuro-integration from the DLPFC to the whole brain in unaffected but genetically liable family members are scant. In this study, we report DLPFC neuro-integrative deficits correlated with executive dysfunction and family history of schizophrenia using resting-state functional magnetic resonance imaging (fMRI). Using seed regions in DLPFC, we examined resting-state functional connectivity in 25 patients with schizophrenia, 25 unaffected first-degree relatives (UR), and 25 healthy control (HC) persons. Schizophrenia patients and UR have impaired connectivity from DLPFC to its coordinated regions (ANOVA: F=7.316-10.974, p<0.001). These coordinated brain regions are distributed in the bilateral caudate, left middle/inferior frontal gyrus, left precentral gyrus, and right cerebellum. The individual functional connectivity strength between the left DLPFC and its coordinated regions was correlated with individual executive function performance among whole persons. (Pearson's r=0.244-0.366, p=0.035-0.008) Our findings support that distributed neuro-integrative DLPFC deficits reflect a genetic risk for schizophrenia and that these deficits are present, to a lesser degree, in unaffected first-degree relatives. Our findings also support that neuro-integration might correlate with a patient's executive function performance.

Connectivity of default-mode network is associated with cerebral edema in hepatic encephalopathy.

Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC) of the default mode network (DMN) was determined by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from "without HE" or "minimal HE" to "overt HE", correlated with decreased anterior-posterior fc-CC in DMN [F(4.415), p = 0.000)]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis.

Impaired small-world network efficiency and dynamic functional distribution in patients with cirrhosis.

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome and a major complication of liver cirrhosis. Dysmetabolism of the brain, related to elevated ammonia levels, interferes with intercortical connectivity and cognitive function. For evaluation of network efficiency, a 'small-world' network model can quantify the effectiveness of information transfer within brain networks. This study aimed to use small-world topology to investigate abnormalities of neuronal connectivity among widely distributed brain regions in patients with liver cirrhosis using resting-state functional magnetic resonance imaging (rs-fMRI). Seventeen cirrhotic patients without HE, 9 with minimal HE, 9 with overt HE, and 35 healthy controls were compared. The interregional correlation matrix was obtained by averaging the rs-fMRI time series over all voxels in each of the 90 regions using the automated anatomical labeling model. Cost and correlation threshold values were then applied to construct the functional brain network. The absolute and relative network efficiencies were calculated; quantifying distinct aspects of the local and global topological network organization. Correlations between network topology parameters, ammonia levels, and the severity of HE were determined using linear regression and ANOVA. The local and global topological efficiencies of the functional connectivity network were significantly disrupted in HE patients; showing abnormal small-world properties. Alterations in regional characteristics, including nodal efficiency and nodal strength, occurred predominantly in the association, primary, and limbic/paralimbic regions. The degree of network organization disruption depended on the severity of HE. Ammonia levels were also significantly associated with the alterations in local network properties. Results indicated that alterations in the rs-fMRI network topology of the brain were associated with HE grade; and that focal or diffuse lesions disturbed the functional network to further alter the global topology and efficiency of the whole brain network. These findings provide insights into the functional changes in the human brain in HE.