Modular strategy for development of the hierarchical visual network in mice.

Hierarchical and parallel networks are fundamental structures of the mammalian brain1-8. During development, lower- and higher-order thalamic nuclei and many cortical areas in the visual system form interareal connections and build hierarchical dorsal and ventral streams9-13. One hypothesis for the development of visual network wiring involves a sequential strategy wherein neural connections are sequentially formed alongside hierarchical structures from lower to higher areas14-17. However, this sequential strategy would be inefficient for building the entire visual network comprising numerous interareal connections. We show that neural pathways from the mouse retina to primary visual cortex (V1) or dorsal/ventral higher visual areas (HVAs) through lower- or higher-order thalamic nuclei form as parallel modules before corticocortical connections. Subsequently, corticocortical connections among V1 and HVAs emerge to combine these modules. Retina-derived activity propagating the initial parallel modules is necessary to establish retinotopic inter-module connections. Thus, the visual network develops in a modular manner involving initial establishment of parallel modules and their subsequent concatenation. Findings in this study raise the possibility that parallel modules from higher-order thalamic nuclei to HVAs act as templates for cortical ventral and dorsal streams and suggest that the brain has an efficient strategy for the development of a hierarchical network comprising numerous areas.

Remaining Issues Related to Serum Cytokines in Patients with Unresectable Hepatocellular Carcinoma Treated by Atezolizumab plus Bevacizumab Combination Treatment.

INTRODUCTION: Atezolizumab plus bevacizumab (AteBev) combination treatment is widely used as first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC). We aimed to clarify therapeutic issues regarding serum cytokines and the immune reaction in patients with uHCC treated with AteBev. METHODS: We analyzed preserved serum from a previous prospective study on adult Japanese patients with chronic liver disease and uHCC who received AteBev treatment at our hospital. In that study, AteBev were administered intravenously every 3 weeks, and blood samples were collected before and after 3 weeks' treatment. Dynamic computed tomography was performed after 6 weeks of treatment to assess response. RESULTS: In the prospective study, 21 of the 59 patients showed partial response (PR) and 19 patients showed stable disease (SD), but 19 patients showed progressive disease (PD). We found that serum levels of tumor necrosis factor-alpha, interleukin (IL)-6, and soluble IL-2 receptor (IL-2R) increased significantly in the PR group, but only soluble IL-2R increased significantly in the PD group. Regulatory T cells decreased significantly in the PD group, but there was no significant change in Th1 or Th2 cells from before to after treatment in any group. As regards soluble MHC-class I, pre-treatment levels were significantly lower in the PD group than in the PR group, and serum levels increased significantly with treatment in the PD group. CONCLUSION: These findings reveal a need to further improve T-cell priming and to further make T-cells recognize tumor antigens in uHCC.

Ketamine-induced 1-Hz oscillation of spontaneous neural activity is not directly visible in the hemodynamics.

The extent to which resting-state hemodynamics reflects the underlying neural activity is still under debate. Especially in the delta frequency band (0.5-4 Hz), it is unclear whether the hemodynamics can directly track the dynamics of underlying neural activity. Based on a recent report showing that ketamine administration induced a 1-Hz neural activity oscillation in the retrosplenial cortex, we conducted simultaneous recordings of the calcium signal and hemodynamics in mice and examined whether the hemodynamics tracked the oscillatory neural activity. Although we observed that the oscillation induced by ketamine appeared in the calcium signal, no sign of oscillation was detected in the simultaneously recorded hemodynamics. Consistently, there was a notable decrease in the correlation between simultaneously recorded calcium signal and hemodynamics. However, on a much longer time scale (10-60 min), we unexpectedly observed an ultraslow increase of hemodynamic signals specifically in the same cortical region exhibiting the neural activity oscillation. These results indicated that hemodynamics cannot track the 1-Hz oscillation in neural activity, although the presence of neural activity oscillation was detectable on a longer timescale. Such ultraslow hemodynamics may be useful for detecting abnormal neural activity induced by psychotic drugs or mental disorders.

Effects of Lenvatinib on Skeletal Muscle Volume and Cardiac Function in Patients with Hepatocellular Carcinoma.

INTRODUCTION: Previously, we reported that the tyrosine kinase inhibitor (TKI) sorafenib decreases serum levels of carnitine and reduces skeletal muscle volume. Moreover, others reported that TKIs might lead to cardiomyopathy or heart failure. Therefore, this study aimed to evaluate the effects of lenvatinib (LEN) on skeletal muscle volume and cardiac function in patients with hepatocellular carcinoma (HCC). METHODS: This retrospective study included 58 adult Japanese patients with chronic liver diseases and HCC treated with LEN. Blood samples were collected before and after 4 weeks of treatment, and serum carnitine fraction and myostatin levels were measured. Before and after 4-6 weeks of treatment, the skeletal muscle index (SMI) was evaluated from computed tomography images and cardiac function was assessed by ultrasound cardiography. RESULTS: After treatment, SMI, serum levels of total carnitine, and global longitudinal strain were significantly lower, but serum levels of myostatin were significantly higher. Left ventricular ejection fraction showed no significant change. CONCLUSION: In patients with HCC, LEN decreases serum levels of carnitine, skeletal muscle volume, and worsens cardiac function.

Lenvatinib Might Induce Activation of Host Immunity in Patients with Hepatocellular Carcinoma.

INTRODUCTION: Atezolizumab, an immune checkpoint inhibitor, plus bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), is an approved first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Immune checkpoint inhibitors are more effective in patients with HCC when administered with anti-VEGF drugs; however, these drugs affect host immunity. Lenvatinib is an anti-VEGF agent used to treat HCC; therefore, this study evaluated the effect of treatment of HCC with lenvatinib on host immunity in patients with chronic liver disease (CLD). METHODS: We studied adult Japanese patients with CLD and unresectable HCC treated with lenvatinib at our hospital. Lenvatinib was administered for 4 weeks (8 mg/day for bodyweight <60 kg; 12 mg/day for bodyweight >60 kg). Blood samples were collected at baseline and at 4 weeks of treatment and examined for immune-related changes. RESULTS: Forty-three patients were enrolled in this study. We found a significant increase in T helper (Th) 1 cells following 4 weeks of lenvatinib treatment, although there was no significant difference in Th2 cells and regulatory T cells. We also found a significant increase in serum levels of TNF-alpha, soluble TNF-alpha receptor I, and endothelial growth factor following 4 weeks of lenvatinib treatment. Furthermore, an increase in Th1 cells and serum levels of TNF-alpha was found in patients with partial response. CONCLUSION: Lenvatinib might induce Th1-dominant host immunity in patients with CLD and unresectable HCC treatment in patients who showed a partial response. These changes in host immunity may be a biomarker in HCC patients treated with lenvatinib.

On co-activation pattern analysis and non-stationarity of resting brain activity.

The non-stationarity of resting-state brain activity has received increasing attention in recent years. Functional connectivity (FC) analysis with short sliding windows and coactivation pattern (CAP) analysis are two widely used methods for assessing the dynamic characteristics of brain activity observed with functional magnetic resonance imaging (fMRI). However, the statistical nature of the dynamics captured by these techniques needs to be verified. In this study, we found that the results of CAP analysis were similar for real fMRI data and simulated stationary data with matching covariance structures and spectral contents. We also found that, for both the real and simulated data, CAPs were clustered into spatially heterogeneous modules. Moreover, for each of the modules in the real data, a spatially similar module was found in the simulated data. The present results suggest that care needs to be taken when interpreting observations drawn from CAP analysis as it does not necessarily reflect non-stationarity or a mixture of states in resting brain activity.

Executive control by fronto-parietal activity explains counterintuitive decision behavior in complex value-based decision-making.

In real life, humans make decisions by taking into account multiple independent factors, such as delay and probability. Cognitive psychology suggests that cognitive control mechanisms play a key role when facing such complex task conditions. However, in value-based decision-making, it still remains unclear to what extent cognitive control mechanisms become essential when the task condition is complex. In this study, we investigated decision-making behaviors and underlying neural mechanisms using a multifactor gambling task where participants simultaneously considered probability and delay. Decision-making behavior in the multifactor task was modulated by both probability and delay. The behavioral effect of probability was stronger than delay, consistent with previous studies. Furthermore, in a subset of conditions that recruited fronto-parietal activations, reaction times were paradoxically elongated despite lower probabilistic uncertainty. Notably, such a reaction time elongation did not occur in control tasks involving single factors. Meta-analysis of brain activations suggested an interpretation that the paradoxical increase of reaction time may be associated with strategy switching. Consistent with this interpretation, logistic regression analysis of the behavioral data suggested a presence of multiple decision strategies. Taken together, we found that a novel complex value-based decision-making task cause prominent activations in fronto-parietal cortex. Furthermore, we propose that these activations can be interpreted as recruitment of cognitive control system in complex situations.

Neuronal Origin of the Temporal Dynamics of Spontaneous BOLD Activity Correlation.

Resting-state functional connectivity (FC) has become a major functional magnetic resonance imaging method to study network organization of human brains. There has been recent interest in the temporal fluctuations of FC calculated using short time windows ("dynamic FC") because this method could provide information inaccessible with conventional "static" FC, which is typically calculated using the entire scan lasting several tens of minutes. Although multiple studies have revealed considerable temporal fluctuations in FC, it is still unclear whether the fluctuations of FC measured in hemodynamics reflect the dynamics of underlying neural activity. We addressed this question using simultaneous imaging of neuronal calcium and hemodynamic signals in mice and found coordinated temporal dynamics of calcium FC and hemodynamic FC measured in the same short time windows. Moreover, we found that variation in transient neuronal coactivation patterns was significantly related to temporal fluctuations of sliding window FC in hemodynamics. Finally, we show that the observed dynamics of FC cannot be fully accounted for by simulated data assuming stationary FC. These results provide evidence for the neuronal origin of dynamic FC and further suggest that information relevant to FC is condensed in temporally sparse events that can be extracted using a small number of time points.

Tivantinib Decreases Hepatocyte Growth Factor-Induced BCRP Expression in Hepatocellular Carcinoma HepG2 Cells.

Tivantinib, a mesenchymal-epithelial transition factor (cMET) inhibitor, is a molecular targeting drug that kills hepatocellular carcinoma (HCC) cells. Tivantinib alone does not affect the overall survival of patients with HCC, and combination treatment with tivantinib and other therapies has not been evaluated. This study was conducted to clarify the effect of the tivantinib in regulating breast cancer therapy-resistant protein (BCRP), a key transporter of 5-fluorouracil (5-FU), and dihydropyridine dehydrogenase (DPYD), a major metabolic enzyme of 5-FU. To this end, cMET gene expression was determined by RT-PCR in HepG2 (human hepatoma) cells. The transcriptional start sites of BCRP were determined by 5'-rapid amplification of cDNA ends (5'-RACE). BCRP and DPYD mRNA levels were determined by real-time RT-PCR, and promoter activities were measured by dual-luciferase assays. Results show that hepatocyte growth factor (HGF) upregulated the mRNA level of BCRP, but not DPYD, in HepG2 cells. The upregulation of BCRP expression by HGF was down-regulated by tivantinib. We also identified two transcriptional start sites (E1α, E1ß) in BCRP by 5'-RACE. The transcriptional activity of the region -287 to E1α of BCRP was upregulated by HGF, which was decreased by tivantinib, whereas activity of the region -297 to E1ßo f BCRP was not affected by tivantinib. Therefore, tivantinib regulates BCRP expression upstream of exon 1α. Combination treatment of tivantinib and 5-FU should be further evaluated for HCC therapy.

Transient neuronal coactivations embedded in globally propagating waves underlie resting-state functional connectivity.

Resting-state functional connectivity (FC), which measures the correlation of spontaneous hemodynamic signals (HemoS) between brain areas, is widely used to study brain networks noninvasively. It is commonly assumed that spatial patterns of HemoS-based FC (Hemo-FC) reflect large-scale dynamics of underlying neuronal activity. To date, studies of spontaneous neuronal activity cataloged heterogeneous types of events ranging from waves of activity spanning the entire neocortex to flash-like activations of a set of anatomically connected cortical areas. However, it remains unclear how these various types of large-scale dynamics are interrelated. More importantly, whether each type of large-scale dynamics contributes to Hemo-FC has not been explored. Here, we addressed these questions by simultaneously monitoring neuronal calcium signals (CaS) and HemoS in the entire neocortex of mice at high spatiotemporal resolution. We found a significant relationship between two seemingly different types of large-scale spontaneous neuronal activity-namely, global waves propagating across the neocortex and transient coactivations among cortical areas sharing high FC. Different sets of cortical areas, sharing high FC within each set, were coactivated at different timings of the propagating global waves, suggesting that spatial information of cortical network characterized by FC was embedded in the phase of the global waves. Furthermore, we confirmed that such transient coactivations in CaS were indeed converted into spatially similar coactivations in HemoS and were necessary to sustain the spatial structure of Hemo-FC. These results explain how global waves of spontaneous neuronal activity propagating across large-scale cortical network contribute to Hemo-FC in the resting state.

Functional Segregation and Development of Mouse Higher Visual Areas.

Recent studies suggest that higher visual areas (HVAs) in the mouse visual cortex are segregated anatomically into two visual streams, likely analogous to the ventral and dorsal streams in primates. However, HVAs in mice have yet to be characterized functionally. Moreover, it is unknown when the functional segregation of HVAs occurs during development. Here, we investigated spatiotemporal selectivity of HVAs and their development using wide-field calcium imaging. We found that lateral HVAs in the anatomical ventral stream shared similar spatiotemporal selectivity, whereas the spatiotemporal selectivity of anterior and medial HVAs in the anatomical dorsal stream was not uniform and these areas were segregated functionally into multiple groups. This functional segregation of HVAs developed and reached an adult-like pattern ∼10 d after eye opening (EO). These results suggest, not only the functional segregation of ventral and dorsal streams, but also the presence of multiple substreams in the dorsal stream, and indicate that the functional segregation of visual streams occurs gradually after EO.SIGNIFICANCE STATEMENT Investigation of the spatiotemporal selectivity of nine higher visual areas (HVAs) in adult and developing mice revealed that lateral HVAs belonging to the putative ventral stream shared similar spatiotemporal selectivity, whereas the spatiotemporal selectivity of anterior and medial HVAs belonging to the putative dorsal stream was not uniform and these areas were segregated functionally into multiple groups. These results suggest the presence of multiple substreams within the putative dorsal stream for visuospatial processing. Furthermore, we found that initially immature functional segregation among HVAs developed to an adult-like pattern ∼10 d after eye opening. These results provide a foundation for using mouse HVAs as a model to understand parallel processing and its developmental mechanism.

Astrocytes in the mouse visual cortex reliably respond to visual stimulation.

Astrocytes are known to contact with a great number of synapses and may integrate sensory inputs. In the ferret primary visual cortex, astrocytes respond to a visual stimulus with a delay of several seconds with respect to the surrounding neurons. However, in the mouse visual cortex, it remains unclear whether astrocytes respond to visual stimulations. In this study, using dual-color simultaneous in vivo two-photon calcium imaging of neurons and astrocytes in the awake mouse visual cortex, we examined the visual response of astrocytes and their precise response timing relative to the surrounding neurons. Neurons reliably responded to visual stimulations, whereas astrocytes often showed neuromodulator-mediated global activities, which largely masked small visual responses. Administration of the selective α1-adrenergic receptor antagonist prazosin substantially reduced such global astrocytic activities without affecting the neuronal visual responses. In the presence of prazosin, astrocytes showed weak but consistent visual responses mostly at their somata. Cross-correlation analysis estimated that the astrocytic visual responses were delayed by approximately 5 seconds relative to the surrounding neuronal responses. In conclusion, our research demonstrated that astrocytes in the primary visual cortex of awake mice responded to visual stimuli with a delay of several seconds relative to the surrounding neurons, which may indicate the existence of a common mechanism of neuron-astrocyte communication across species.

Comparison of Sorafenib and Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Study.

BACKGROUND/AIMS: This prospective non-randomized controlled trial aimed to compare the efficacy of sorafenib vs hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma. METHODOLOGY: Forty-seven patients treated with sorafenib (sorafenib group) and 77 patients treated with HAIC (HAIC group) were investigated retrospectively using propensity score matching (PSM) to minimize selection bias. The cumulative survival rate was investigated before and after PSM in each of the sorafenib and HAIC groups. The cumulative survival rate was compared between the sorafenib and HAIC groups, and among the TNM stage by the Liver Cancer Study Group of Japan (LCSGJ TNM stage). RESULTS: No significant difference was noted in overall survival (OS) between the sorafenib and HAIC groups regardless of before or after PSM. On comparison of the cumulative survival rate between the groups by the same LCSGJ TNM stage, significant prolongation of OS was noted in stage IVB only in the sorafenib group (p = 0.032) after PSM. CONCLUSIONS: It may be better to actively introduce sorafenib for stage IVB, i.e., patients with extrahepatic metastasis.

Host Immunity Influences the Efficacy of Combined Intra-Arterial Chemotherapy for Advanced Hepatocellular Carcinoma in Liver Cirrhosis Patients.

BACKGROUND/AIMS: It has been reported that Th2 cytokines down-regulate antitumor immunity, while activation of Th1 cells promotes such immunity. The aim of this study was to assess changes of host immunity in relation to efficacy in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC) treated by combined intra-arterial chemotherapy (CIAC). METHODOLOGY: Forty-three adult Japanese LC patients who had aHCC received CIAC. Blood samples were collected before and after CIAC. RESULTS: Eleven of the 43 patients showed a partial response (group PR) and 21 patients had stable disease (group SD), but 11 patients showed no response (group PD). There were no significant differences of Th1 or Th2 cells between before and after CIAC in each group. However, groups SD and PD had higher levels of Th2 cells than in group PR before and after CIAC. The percentage of regulatory T (Treg) cells in group PD was significantly increased after CIAC compared with before CIAC, whereas groups PR and SD showed significant decrease after CIAC. CONCLUSIONS: The percentage of Th2 cells is useful for predicting the response to CIAC and the percentage of Treg cells is useful for assessment of efficacy in LC patients with aHCC receiving CIAC.

Location analysis of presynaptically active and silent synapses in single-cultured hippocampal neurons.

A morphologically present but non-functioning synapse is termed a silent synapse. Silent synapses are categorized into "postsynaptically silent synapses," where AMPA receptors are either absent or non-functional, and "presynaptically silent synapses," where neurotransmitters cannot be released from nerve terminals. The presence of presynaptically silent synapses remains enigmatic, and their physiological significance is highly intriguing. In this study, we examined the distribution and developmental changes of presynaptically active and silent synapses in individual neurons. Our findings show a gradual increase in the number of excitatory synapses, along with a corresponding decrease in the percentage of presynaptically silent synapses during neuronal development. To pinpoint the distribution of presynaptically active and silent synapses, i.e., their positional information, we employed Sholl analysis. Our results indicate that the distribution of presynaptically silent synapses within a single neuron does not exhibit a distinct pattern during synapse development in different distance from the cell body. However, irrespective of neuronal development, the proportion of presynaptically silent synapses tends to rise as the projection site moves farther from the cell body, suggesting that synapses near the cell body may exhibit higher synaptic transmission efficiency. This study represents the first observation of changes in the distribution of presynaptically active and silent synapses within a single neuron.

LecT-Hepa, a glyco-marker derived from multiple lectins, as a predictor of liver fibrosis in chronic hepatitis C patients.

UNLABELLED: Assessment of liver fibrosis in patients with chronic hepatitis C (CHC) is critical for predicting disease progression and determining future antiviral therapy. LecT-Hepa, a new glyco-marker derived from fibrosis-related glyco-alteration of serum alpha 1-acid glycoprotein, was used to differentiate cirrhosis from chronic hepatitis in a single-center study. Herein, we aimed to validate this new glyco-marker for estimating liver fibrosis in a multicenter study. Overall, 183 CHC patients were recruited from 5 liver centers. The parameters Aspergillus oryzae lectin (AOL) / Dature stramonium lectin (DSA) and Maackia amurensis lectin (MAL)/DSA were measured using a bedside clinical chemistry analyzer in order to calculate LecT-Hepa levels. The data were compared with those of seven other noninvasive biochemical markers and tests (hyaluronic acid, tissue inhibitor of metalloproteases-1, platelet count, aspartate aminotransferase-to-platelet ratio index [APRI], Forns index, Fib-4 index, and Zeng's score) for assessing liver fibrosis using the receiver-operating characteristic curve. LecT-Hepa correlated well with the fibrosis stage as determined by liver biopsy. The area under the curve (AUC), sensitivity, and specificity of LecT-Hepa were 0.802, 59.6%, and 89.9%, respectively, for significant fibrosis; 0.882, 83.3%, and 80.0%, respectively, for severe fibrosis; and 0.929, 84.6%, and 88.5%, respectively, for cirrhosis. AUC scores of LecT-Hepa at each fibrosis stage were greater than those of the seven aforementioned noninvasive tests and markers. CONCLUSION: The efficacy of LecT-Hepa, a glyco-marker developed using glycoproteomics, for estimating liver fibrosis was demonstrated in a multicenter study. LecT-Hepa given by a combination of the two glyco-parameters is a reliable method for determining the fibrosis stage and is a potential substitute for liver biopsy.

Functional connectivity between anatomically unconnected areas is shaped by collective network-level effects in the macaque cortex.

Coherent spontaneous blood oxygen level-dependent (BOLD) fluctuations have been intensely investigated as a measure of functional connectivity (FC) in the primate neocortex. BOLD-FC is commonly assumed to be constrained by the underlying anatomical connectivity (AC); however, cortical area pairs with no direct AC can also have strong BOLD-FC. On the mechanism generating FC in the absence of direct AC, there are 2 possibilities: 1) FC is determined by signal flows via short connection patterns, such as serial relays and common afferents mediated by a third area; 2) FC is shaped by collective effects governed by network properties of the cortex. In this study, we conducted functional magnetic resonance imaging in anesthetized macaque monkeys and found that BOLD-FC between unconnected areas depends less on serial relays through a third area than on common afferents and, unexpectedly, common efferents, which does not match the first possibility. By utilizing a computational model for interareal BOLD-FC network, we show that the empirically detected AC-FC relationships reflect the configuration of network building blocks (motifs) in the cortical anatomical network, which supports the second possibility. Our findings indicate that FC is not determined solely by interareal short connection patterns but instead is substantially influenced by the network-level cortical architecture.

Influence of etiology on host immunity in liver cirrhosis patients with advanced hepatocellular carcinoma receiving intra-arterial chemotherapy.

BACKGROUND/AIMS: We have shown that continuous intra-arterial combination chemotherapy (IACC) might be more effective for advanced HCC (aHCC) in patients with HCV-related (C-LC) or alcoholic (A-LC) liver cirrhosis (LC) patients than in patients with HBV-related LC (B-LC). This study retrospectively assesses the difference of etiology on host immunity in LC patients with aHCC treated by IACC. METHODOLOGY: Forty-seven adult LC patients with aHCC were treated by IACC between 2005 and 2008, with inoperable tumors according to CT findings. IACC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was delivered via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. The control group comprised 13 healthy volunteers. RESULTS: Twelve of the 47 patients with aHCC had B-LC, 27 had C-LC, and 8 had A-LC. In the B-LC group, 1 out of 12 patients had a Japan Integrated Staging (JIS) score of 2, 4 had a JIS score of 3, 7 had a JIS score of 4, and no patients had a JIS score of 5, while the respective numbers were 6, 9, 10 and 2 in the C-LC group, and 1, 1, 5 and 1 in the A-LC group. The response rates were 37.0%, 37.5% and 8.3% in the C-LC, A-LC and B-LC group, respectively. In the C-LC group, the percentage of Th1 cells before and after chemotherapy was significantly higher than in the control group. In the B-LC group, the percentage of Th2 cells after chemotherapy was significantly higher than that in the control group. However, there were no significant differences of Th1 and Th2 cells between the A-LC group and the control group. CONCLUSIONS: These results indicate that IACC was more effective for aHCC in A-LC patients with normal Th1/Th2 balance and in C-LC patients without Th2 dominance than in B-LC patients who showed Th2 dominance after chemotherapy.

[Primary adenosquamous carcinoma of the liver presenting with hematochezia due to tumor invasion of the colon].

A 69-year-old female was referred to our hospital with hematochezia. Dynamic computed tomography demonstrated a large tumor with rim enhancement and central necrosis that invaded into the transverse colon. The tumor was resected, and histopathological examination revealed mixed adenocarcinoma and squamous cell carcinoma with partial abscess formation. On the basis of a literature review and the findings from the present case, rim enhancement with central necrosis on imaging appears to be characteristic of this disease.

Static and Dynamic Functional Connectivity Alterations in Alzheimer's Disease and Neuropsychiatric Diseases.

Background: To date, numerous studies have documented various alterations in resting brain activity in Alzheimer's disease (AD) and other neuropsychiatric diseases. In particular, disease-related alterations of functional connectivity (FC) in the resting state networks (RSN) have been documented. Altered FC in RSN is useful not only for interpreting the phenotype of diseases but also for diagnosing the diseases. More recently, several studies proposed the dynamics of resting-brain activity as a useful marker for detecting altered RSNs related to AD and other diseases. Objectives: In this article, we review recent studies exploring alterations of static and dynamic functional connectivity in AD and other neuropsychiatric diseases. We then discuss how to utilize and interpret dynamics of FC for studying resting brain activity in diseases. Results: In contrast to previous studies, which focused on FC calculated using an entire fMRI scan (static FC), newer studies focused on the temporal dynamics of FC within the scan (dynamic FC) to provide more sensitive measures to characterize RSNs. However, despite the increasing popularity of dynamic FC, several statistical investigations of dynamic FC cautioned that the results obtained in commonly used analyses for dynamic FC require careful interpretation. Conclusions: Although static and dynamic FC are likely to be a useful tool to detect altered RSN in patients affected by AD and other neuropsychiatric disorders, interpretation of altered dynamic FC in patients require special care. Impact statement We review recent studies of static and dynamic functional connectivity (dFC) in Alzheimer's disease and discuss interpretation of dFC.