Cdc42-driven endosomal cholesterol transport promotes collateral resistance in HER2-positive gastric cancer.

Resistance to trastuzumab and the poor efficacy of subsequent chemotherapy have become major challenges for HER2-positive gastric cancer (GC). As resistance evolves, tumor cells may acquire a new drug susceptibility profile, profoundly impacting the subsequent treatment selection and patient survival. However, the interplay between trastuzumab and other types of drugs in HER2-positive GC remains elusive. In our study, we utilized resistant cell lines and tissue specimens to map the drug susceptibility profile of trastuzumab-resistant GC, discovering that resistance to trastuzumab induces collateral resistance to commonly used chemotherapeutic agents. Additionally, patients with collateral resistance distinguished by a 13-gene scoring model in HER2-positive GC cohorts are predicted to have a poor prognosis and may be sensitive to cholesterol-lowering drugs. Mechanistically, endosomal cholesterol transport is further confirmed to enrich cholesterol in the plasma membrane, contributing to collateral resistance through the Hedgehog-ABCB1 axis. As a driver for cholesterol, Cdc42 is activated by the formation of the NPC1-TßRI-Cdc42 complex to facilitate endosomal cholesterol transport. We demonstrated that inhibiting Cdc42 activation with ZCL278 reduces cholesterol levels in the plasma membrane and reverses collateral resistance between trastuzumab and chemotherapy in vitro and in vivo. Collectively, our findings verify the phenomena and mechanism of collateral resistance between trastuzumab and chemotherapy, and propose a potential therapeutic target and strategy in the second-line treatment for trastuzumab-resistant HER2-positive GC.

Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2-positive gastric cancer.

BACKGROUND: Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2 (HER2)-positive gastric cancer. However, the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit, and there is currently no effective reversal measure. Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves, while the understanding of the mechanisms of environment-mediated drug resistance is relatively lacking. This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients. METHODS: Trastuzumab-sensitive and trastuzumab-resistant HER2-positive tumor tissues and cells were collected for transcriptome sequencing. Bioinformatics were used to analyze cell subtypes, metabolic pathways, and molecular signaling pathways. Changes in microenvironmental indicators (such as macrophage, angiogenesis, and metabolism) were verified by immunofluorescence (IF) and immunohistochemical (IHC) analyses. Finally, a multi-scale agent-based model (ABM) was constructed. The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM. RESULTS: Based on transcriptome sequencing, molecular biology, and in vivo experiments, we found that the level of glutamine metabolism in trastuzumab-resistant HER2-positive cells was increased, and glutaminase 1 (GLS1) was significantly overexpressed. Meanwhile, tumor-derived GLS1 microvesicles drove M2 macrophage polarization. Furthermore, angiogenesis promoted trastuzumab resistance. IHC showed high glutamine metabolism, M2 macrophage polarization, and angiogenesis in trastuzumab-resistant HER2-positive tumor tissues from patients and nude mice. Mechanistically, the cell division cycle 42 (CDC42) promoted GLS1 expression in tumor cells by activating nuclear factor kappa-B (NF-κB) p65 and drove GLS1 microvesicle secretion through IQ motif-containing GTPase-activating protein 1 (IQGAP1). Based on the ABM and in vivo experiments, we confirmed that the combination of anti-glutamine metabolism, anti-angiogenesis, and pro-M1 polarization therapy had the best effect in reversing trastuzumab resistance in HER2-positive gastric cancer. CONCLUSIONS: This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism, M2 macrophage polarization, and pro-angiogenic function of macrophages, leading to acquired trastuzumab resistance in HER2-positive gastric cancer. A combination of anti-glutamine metabolism, anti-angiogenesis, and pro-M1 polarization therapy may provide a new insight into reversing trastuzumab resistance.

Disrupting Circadian Rhythm via the PER1-HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer.

Trastuzumab is the only approved targeted drug for first-line treatment of HER2-positive advanced gastric cancer, but the high rate of primary resistance and rapid emergence of secondary resistance limit its clinical benefits. We found that trastuzumab-resistant (TR) gastric cancer cells exhibited high glycolytic activity, which was controlled by hexokinase 2 (HK2)-dependent glycolysis with a circadian pattern [higher at zeitgeber time (ZT) 6, lower at ZT18]. Mechanistically, HK2 circadian oscillation was regulated by a transcriptional complex composed of PPARγ and the core clock gene PER1. In vivo and in vitro experiments demonstrated that silencing PER1 disrupted the circadian rhythm of PER1-HK2 and reversed trastuzumab resistance. Moreover, metformin, which inhibits glycolysis and PER1, combined with trastuzumab at ZT6, significantly improved trastuzumab efficacy in gastric cancer. Collectively, these data introduce the circadian clock into trastuzumab therapy and propose a potentially effective chronotherapy strategy to reverse trastuzumab resistance in gastric cancer. SIGNIFICANCE: In trastuzumab-resistant HER2-positive gastric cancer, glycolysis fluctuates with a circadian oscillation regulated by the BMAL1-CLOCK-PER1-HK2 axis, which can be disrupted with a metformin-based chronotherapy to overcome trastuzumab resistance.

Remodeling Chondroitin-6-Sulfate-Mediated Immune Exclusion Enhances Anti-PD-1 Response in Colorectal Cancer with Microsatellite Stability.

Metastatic microsatellite-stable (MSS) colorectal cancer rarely responds to immune checkpoint inhibitors (ICI). Metabolism heterogeneity in the tumor microenvironment (TME) presents obstacles to antitumor immune response. Combining transcriptome (The Cancer Genome Atlas MSS colorectal cancer, n = 383) and digital pathology (n = 96) analysis, we demonstrated a stroma metabolism-immune excluded subtype with poor prognosis in MSS colorectal cancer, which could be attributed to interaction between chondroitin-6-sulfate (C-6-S) metabolites and M2 macrophages, forming the "exclusion barrier" in the invasive margin. Furthermore, C-6-S derived from cancer-associated fibroblasts promoted co-nuclear translocation of pSTAT3 and GLI1, activating the JAK/STAT3 and Hedgehog pathways. In vivo experiments with C-6-S-targeted strategies decreased M2 macrophages and reprogrammed the immunosuppressive TME, leading to enhanced response to anti-PD-1 in MSS colorectal cancer. Therefore, C-6-S-induced immune exclusion represents an "immunometabolic checkpoint" that can be exploited for the application of combination strategies in MSS colorectal cancer ICI treatment.

Spontaneous Activity in Primary Visual Cortex Relates to Visual Creativity.

Cognitive and neural processes underlying visual creativity have attracted substantial attention. The current research uses a critical time point analysis (CTPA) to examine how spontaneous activity in the primary visual area (PVA) is related to visual creativity. We acquired the functional magnetic resonance imaging (fMRI) data of 16 participants at the resting state and during performing a visual creative synthesis task. According to the CTPA, we then classified spontaneous activity in the PVA into critical time points (CTPs), which reflect the most useful and important functional meaning of the entire resting-state condition, and the remaining time points (RTPs). We constructed functional brain networks based on the brain activity at two different time points and then subsequently based on the brain activity at the task state in a separate manner. We explore the relationship between resting-state and task-fMRI (T-fMRI) functional brain networks. Our results found that: (1) the pattern of spontaneous activity in the PVA may associate with mental imagery, which plays an important role in visual creativity; (2) in comparison with the RTPs-based brain network, the CTP-network showed an increase in global efficiency and a decrease in local efficiency; (3) the regional integrated properties of the CTP-network could predict the integrated properties of the creative-network while the RTP-network could not. Thus, our findings indicated that spontaneous activity in the PVA at CTPs was associated with a visual creative task-evoked brain response. Our findings may provide an insight into how the visual cortex is related to visual creativity.

MET transcriptional regulator/serine peptidase inhibitor kunitz type 1 panel operating through HGF/c-MET axis as a prognostic signature in pan-cancer.

Dysregulations in transcription factors (TFs) and their genetic products play important roles in tumorigenesis, tumor progression and metastasis. However, prognostic value of the transcriptional regulatory networks in different cancers has not been investigated in depth. The purpose of our study was to identify and validate a potential predictive signature that combines TFs and their regulatory products in eight solid tumors. We used bioinformatics analysis to identify MET Transcriptional Regulator (MACC1) and Serine Peptidase Inhibitor Kunitz Type 1 (SPINT1) as candidate TFs with the respective downstream regulatory proteins for patient prognosis in pan-cancer. Subsequent molecular analysis of clinical gastric cancer tissue samples further verified the negative correlation between MACC1 and SPINT1. Further, we showed that mechanistically, MACC1/SPINT1 mediated the pro-HGF proteolysis and c-Met phosphorylation in HGF/c-MET signaling pathway. Kaplan-Meier plots and receiver operating characteristics analysis revealed that the two-gene signature combining MACC1 with SPINT1 was effective in predicting survival in all eight cancer cohorts tested. In conclusion, our study clarified the regulatory relationship between MACC1 and SPINT1 in the context of the HGF/c-MET signaling pathway and determined MACC1/SPINT1 panel as a valuable signature for the prediction of prognosis in patients for multiple solid cancer types.

Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation.

BACKGROUND: Metastasis and recurrence, wherein circulating tumour cells (CTCs) play an important role, are the leading causes of death in colorectal cancer (CRC). Metastasis-initiating CTCs manage to maintain intravascular survival under anoikis, immune attack, and importantly shear stress; however, the underlying mechanisms remain poorly understood. METHODS: In view of the scarcity of CTCs in the bloodstream, suspended colorectal cancer cells were flowed into the cyclic laminar shear stress (LSS) according to previous studies. Then, we detected these suspended cells with a CK8+/CD45-/DAPI+ phenotype and named them mimic circulating tumour cells (m-CTCs) for subsequent CTCs related researches. Quantitative polymerase chain reaction, western blotting, and immunofluorescence were utilised to analyse gene expression change of m-CTCs sensitive to LSS stimulation. Additionally, we examined atonal bHLH transcription factor 8 (ATOH8) expressions in CTCs among 156 CRC patients and mice by fluorescence in situ hybridisation and flow cytometry. The pro-metabolic and pro-survival functions of ATOH8 were determined by glycolysis assay, live/dead cell vitality assay, anoikis assay, and immunohistochemistry. Further, the concrete up-and-down mechanisms of m-CTC survival promotion by ATOH8 were explored. RESULTS: The m-CTCs actively responded to LSS by triggering the expression of ATOH8, a fluid mechanosensor, with executive roles in intravascular survival and metabolism plasticity. Specifically, ATOH8 was upregulated via activation of VEGFR2/AKT signalling pathway mediated by LSS induced VEGF release. ATOH8 then transcriptionally activated HK2-mediated glycolysis, thus promoting the intravascular survival of colorectal cancer cells in the circulation. CONCLUSIONS: This study elucidates a novel mechanism that an LSS triggered VEGF-VEGFR2-AKT-ATOH8 signal axis mediates m-CTCs survival, thus providing a potential target for the prevention and treatment of hematogenous metastasis in CRC.

MSC-regulated lncRNA MACC1-AS1 promotes stemness and chemoresistance through fatty acid oxidation in gastric cancer.

Chemotherapy is the preferred treatment for advanced stage gastric cancer (GC) patients and chemotherapy resistance is the major obstacle to effective cancer therapy. Increasing evidence suggests that mesenchymal stem cells (MSCs) make important contributions to development of drug resistance. However, the underlying mechanism remains elusive. In this study, we discovered that abundant MSCs in tumor tissues predicted a poor prognosis in GC patients. MSCs promoted stemness and chemoresistance in GC cells through fatty acid oxidation (FAO) in vitro and in vivo. Mechanically, transforming growth factor ß1 (TGF-ß1) secretion by MSCs activated SMAD2/3 through TGF-ß receptors and induced long non-coding RNA (lncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p. Moreover, pharmacologic inhibition of FAO with etomoxir (ETX) attenuated MSC-induced FOLFOX regiment resistance in vivo. These results suggest that FAO plays an important role in MSC-mediated stemness and chemotherapy resistance in GC and FAO inhibitors in combination with chemotherapeutic drugs present as a promising strategy to overcome chemoresistance.

Eyes Closed Elevates Brain Intrinsic Activity of Sensory Dominance Networks: A Classifier Discrimination Analysis.

Brain neocortex is usually dominated by visual input (with eyes open [EO]), whereas this visual predominance could be reduced by closing eyes. Cutting off visual input from the eyes (with eyes closed [EC]) would also benefit other sensory performance; however, the neural basis underlying the state-switching remains unclear. In this study, we investigated the brain intrinsic activity of either the EO or EC states by using the resting-state functional magnetic resonance imaging data from 22 healthy participants. The 10 resting-state networks (RSNs) of these participants were explored by the independent component analysis method. Within each RSN, various network parameters (i.e., the amplitude of low-frequency fluctuation, the voxel-wise weighted degree centrality, and the RSN-wise functional connectivity) were measured to depict the brain intrinsic activity properties underlying the EO and EC states. Taking these brain intrinsic activity properties as discriminative features in a linear classifier, we found that the EO and EC states could be effectively classified using the intrinsic properties of the sensory dominance networks and the salience network (SN). Further analysis showed that the brain intrinsic activity within the sensory dominance networks was constantly overwhelmed during the EC state relative to that in the EO state. The SN might play a key role as a switcher between state-switching. Therefore, this study indicated that the brain intrinsic activity in the sensory dominance networks would be enhanced with EC, which might improve other sensory-relative task performance.

Adipocytes fuel gastric cancer omental metastasis via PITPNC1-mediated fatty acid metabolic reprogramming.

Omental metastasis occurs frequently in gastric cancer (GC) and is considered one of the major causes of gastric cancer-related mortality. Recent research indicated that omental adipocytes might mediate this metastatic predilection. Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) was identified to have a crucial role in metastasis. However, whether PITPNC1 participates in the interaction between adipocytes and GC omental metastasis is unclear. Methods: We profiled and analyzed the expression of PITPNC1 through analysis of the TCGA database as well as immunohistochemistry staining using matched GC tissues, adjacent normal gastric mucosa tissues (ANTs), and omental metastatic tissues. The regulation of PITPNC1 by adipocytes was explored by co-culture systems. By using both PITPNC1 overexpression and silencing methods, the role of PITPNC1 in anoikis resistance and metastasis was determined through in vitro and in vivo experiments. Results: PITPNC1 was expressed at higher rates in GC tissues than in ANTs; notably, it was higher in omental metastatic lesions. Elevated expression of PITPNC1 predicted higher rates of omental metastasis and a poor prognosis. PITPNC1 promoted anoikis resistance through fatty acid metabolism by upregulating CD36 and CPT1B expression. Further, PITPNC1 was elevated by adipocytes and facilitated GC omental metastasis. Lastly, in vivo studies showed that PITPNC1 was a therapeutic indicator of fatty acid oxidation (FAO) inhibition. Conclusion: Elevated expression of PITPNC1 in GC is correlated with an advanced clinical stage and a poor prognosis. PITPNC1 promotes anoikis resistance through enhanced FAO, which is regulated by omental adipocytes and consequently facilitates GC omental metastasis. Targeting PITPNC1 might present a promising strategy to treat omental metastasis.

A metagenome-wide association study of gut microbiota in asthma in UK adults.

BACKGROUND: Asthma, one of the most common chronic respiratory disorders, is associated with the hyper-activation of the T-cell subset of adaptive immunity. The gut microbiota may be involved in the development of asthma through the production of short-chain fatty acids (SCFAs), exhibiting modulatory effects on Th. So, we performed a metagenome-wide association study (MWAS) of the fecal microbiota from individuals with asthma and healthy controls. And that was the first case to resolve the relationship between asthma and microbiome among UK adults. RESULTS: The microbiota of the individuals with asthma consisted of fewer microbial entities than the microbiota of healthy individuals. Faecalibacterium prausnitzii, Sutterella wadsworthensis and Bacteroides stercoris were depleted in cases, whereas Clostridiums with Eggerthella lenta were over-represented in individuals with asthma. Functional analysis shows that the SCFAs might be altered in the microbiota of asthma patients. CONCLUSION: In all, the adult human gut microbiome of asthma patients is clearly different from healthy controls. The functional and taxa results showed that the change of asthma patients might related to SCFAs.

Metabolic networks in ferroptosis.

Ferroptosis is an iron-dependent and peroxidation-driven form of cell death associated with multiple metabolic disorders and disrupted homeostasis. A number of metabolic processes and homeostasis are affected by ferroptosis. The molecules that regulate ferroptosis are involved in metabolic pathways that regulate cysteine exploitation, glutathione state, nicotinamide adenine dinucleotide phosphate function, lipid peroxidation and iron homeostasis. The present review summarizes the metabolic networks involved in ferroptosis based on previous studies, and discusses the function of ferroptosis in pathological processes, including cancer. Finally, the clinical significance of ferroptosis is highlighted, to provide evidence for further studies.

Relation of visual creative imagery manipulation to resting-state brain oscillations.

Visual creative imagery (VCI) manipulation is the key component of visual creativity; however, it remains largely unclear how it occurs in the brain. The present study investigated the brain neural response to VCI manipulation and its relation to intrinsic brain activity. We collected functional magnetic resonance imaging (fMRI) datasets related to a VCI task and a control task as well as pre- and post-task resting states in sequential sessions. A general linear model (GLM) was subsequently used to assess the specific activation of the VCI task compared with the control task. The changes in brain oscillation amplitudes across the pre-, on-, and post-task states were measured to investigate the modulation of the VCI task. Furthermore, we applied a Granger causal analysis (GCA) to demonstrate the dynamic neural interactions that underlie the modulation effect. We determined that the VCI task specifically activated the left inferior frontal gyrus pars triangularis (IFGtriang) and the right superior frontal gyrus (SFG), as well as the temporoparietal areas, including the left inferior temporal gyrus, right precuneus, and bilateral superior parietal gyrus. Furthermore, the VCI task modulated the intrinsic brain activity of the right IFGtriang (0.01-0.08 Hz) and the left caudate nucleus (0.2-0.25 Hz). Importantly, an inhibitory effect (negative) may exist from the left SFG to the right IFGtriang in the on-VCI task state, in the frequency of 0.01-0.08 Hz, whereas this effect shifted to an excitatory effect (positive) in the subsequent post-task resting state. Taken together, the present findings provide experimental evidence for the existence of a common mechanism that governs the brain activity of many regions at resting state and whose neural activity may engage during the VCI manipulation task, which may facilitate an understanding of the neural substrate of visual creativity.

Cysteine Dioxygenase 1 Mediates Erastin-Induced Ferroptosis in Human Gastric Cancer Cells.

BACKGROUND: Ferroptosis is a recently discovered form of iron-dependent nonapoptotic cell death. It is characterized by loss of the activity of the lipid repair enzyme, glutathione peroxidase 4 (GPX4), and accumulation of lethal reactive lipid oxygen species. However, we still know relatively little about ferroptosis and its molecular mechanism in gastric cancer (GC) cells. Here, we demonstrate that erastin, a classic inducer of ferroptosis, induces this form of cell death in GC cells and that cysteine dioxygenase 1 (CDO1) plays an important role in this process. METHODS: We performed quantitative real-time polymerase chain reaction, Western blotting, cell viability assay, reactive oxygen species (ROS) assay, glutathione assay, lipid peroxidation assay, RNAi and gene transfection, immunofluorescent staining, dual-luciferase reporter assay, transmission electron microscopy, and chromatin immunoprecipitation assay to study the regulation of ferroptosis in GC cells. Mouse xenograft assay was used to figure out the mechanism in vivo. RESULTS: Silencing CDO1 inhibited erastin-induced ferroptosis in GC cells both in vitro and in vivo. Suppression of CDO1 restored cellular GSH levels, prevented ROS generation, and reduced malondialdehyde, one of the end products of lipid peroxidation. In addition, silencing COO1 maintained mitochondrial morphologic stability in erastin-treated cells. Mechanistically, c-Myb transcriptionally regulated CDO1, and inhibition of CDO1 expression upregulated GPX4 expression. CONCLUSIONS: Our findings give a better understanding of ferroptosis and its molecular mechanism in GC cells, gaining insight into ferroptosis-mediated cancer treatment.

Association between resting-state brain network topological organization and creative ability: Evidence from a multiple linear regression model.

Previous studies have indicated a tight linkage between resting-state functional connectivity of the human brain and creative ability. This study aimed to further investigate the association between the topological organization of resting-state brain networks and creativity. Therefore, we acquired resting-state fMRI data from 22 high-creativity participants and 22 low-creativity participants (as determined by their Torrance Tests of Creative Thinking scores). We then constructed functional brain networks for each participant and assessed group differences in network topological properties before exploring the relationships between respective network topological properties and creative ability. We identified an optimized organization of intrinsic brain networks in both groups. However, compared with low-creativity participants, high-creativity participants exhibited increased global efficiency and substantially decreased path length, suggesting increased efficiency of information transmission across brain networks in creative individuals. Using a multiple linear regression model, we further demonstrated that regional functional integration properties (i.e., the betweenness centrality and global efficiency) of brain networks, particularly the default mode network (DMN) and sensorimotor network (SMN), significantly predicted the individual differences in creative ability. Furthermore, the associations between network regional properties and creative performance were creativity-level dependent, where the difference in the resource control component may be important in explaining individual difference in creative performance. These findings provide novel insights into the neural substrate of creativity and may facilitate objective identification of creative ability.

Exploring the Associations Between Intrinsic Brain Connectivity and Creative Ability Using Functional Connectivity Strength and Connectome Analysis.

The present study aimed to explore the association between resting-state functional connectivity and creativity ability. Toward this end, the figural Torrance Tests of Creative Thinking (TTCT) scores were collected from 180 participants. Based on the figural TTCT measures, we collected resting-state functional magnetic resonance imaging data for participants with two different levels of creativity ability (a high-creativity group [HG, n = 22] and a low-creativity group [LG, n = 20]). For the aspect of group difference, this study combined voxel-wise functional connectivity strength (FCS) and seed-based functional connectivity to identify brain regions with group-change functional connectivity. Furthermore, the connectome properties of the identified regions and their associations with creativity were investigated using the permutation test, discriminative analysis, and brain-behavior correlation analysis. The results indicated that there were 4 regions with group differences in FCS, and these regions were linked to 30 other regions, demonstrating different functional connectivity between the groups. Together, these regions form a creativity-related network, and we observed higher network efficiency in the HG compared with the LG. The regions involved in the creativity network were widely distributed across the modality-specific/supramodality cerebral cortex, subcortex, and cerebellum. Notably, properties of regions in the supramodality networks (i.e., the default mode network and attention network) carried creativity-level discriminative information and were significantly correlated with the creativity performance. Together, these findings demonstrate a link between intrinsic brain connectivity and creative ability, which should provide new insights into the neural basis of creativity.

High transition frequencies of dynamic functional connectivity states in the creative brain.

Creativity is thought to require the flexible reconfiguration of multiple brain regions that interact in transient and complex communication patterns. In contrast to prior emphases on searching for specific regions or networks associated with creative performance, we focused on exploring the association between the reconfiguration of dynamic functional connectivity states and creative ability. We hypothesized that a high frequency of dynamic functional connectivity state transitions will be associated with creative ability. To test this hypothesis, we recruited a high-creative group (HCG) and a low-creative group (LCG) of participants and collected resting-state fMRI (R-fMRI) data and Torrance Tests of Creative Thinking (TTCT) scores from each participant. By combining an independent component analysis with a dynamic network analysis approach, we discovered the HCG had more frequent transitions between dynamic functional connectivity (dFC) states than the LCG. Moreover, a confirmatory analysis using multiplication of temporal derivatives also indicated that there were more frequent dFC state transitions in the HCG. Taken together, these results provided empirical evidence for a linkage between the flexible reconfiguration of dynamic functional connectivity states and creative ability. These findings have the potential to provide new insights into the neural basis of creativity.

Mental rotation task specifically modulates functional connectivity strength of intrinsic brain activity in low frequency domains: A maximum uncertainty linear discriminant analysis.

Neuroimaging studies have highlighted that intrinsic brain activity is modified to implement task demands. However, the relation between mental rotation and intrinsic brain activity remains unclear. To answer this question, we collected functional MRI (fMRI) data from 30 healthy participants in two mental rotation task periods (1st-task state, 2nd-task state) and two rest periods before (pre-task resting state) and after the task (post-task resting state) respectively. By combining the spatial independent component analysis (ICA) and voxel-wise functional connectivity strength (FCS), we identified FCS maps of 10 brain resting state networks (RSNs) within six different bands (i.e., 0-0.05, 0.05-0.1, 0.1-0.15, 0.15-0.2, 0.2-0.25, and 0.01-0.08Hz) corresponding to the four states for each subject. The maximum uncertainty linear discriminant analysis (MLDA) method showed that the FCS within the low frequency bandwidth of 0.05-0.1Hz could effectively classify the mental rotation task state from pre-/post-task resting states but failed to discriminate the pre- and post-task resting states. Discriminative FCSs were observed in the cognitive executive-control network (central executive and attention) and the imagery-based internal mental manipulation network (default mode, primary sensorimotor, and primary visual). Imagery manipulation is a stable mental element of mental rotation, and the involvement of executive control is dependent on the degree of task familiarity. Together, the present study provides evidence that mental rotation task specifically modifies intrinsic brain activity to complement cognitive demands, which provides further insight into the neural basis of mental rotation manipulation.

Prediction of Biological Motion Perception Performance from Intrinsic Brain Network Regional Efficiency.

Biological motion perception (BMP) refers to the ability to perceive the moving form of a human figure from a limited amount of stimuli, such as from a few point lights located on the joints of a moving body. BMP is commonplace and important, but there is great inter-individual variability in this ability. This study used multiple regression model analysis to explore the association between BMP performance and intrinsic brain activity, in order to investigate the neural substrates underlying inter-individual variability of BMP performance. The resting-state functional magnetic resonance imaging (rs-fMRI) and BMP performance data were collected from 24 healthy participants, for whom intrinsic brain networks were constructed, and a graph-based network efficiency metric was measured. Then, a multiple linear regression model was used to explore the association between network regional efficiency and BMP performance. We found that the local and global network efficiency of many regions was significantly correlated with BMP performance. Further analysis showed that the local efficiency rather than global efficiency could be used to explain most of the BMP inter-individual variability, and the regions involved were predominately located in the Default Mode Network (DMN). Additionally, discrimination analysis showed that the local efficiency of certain regions such as the thalamus could be used to classify BMP performance across participants. Notably, the association pattern between network nodal efficiency and BMP was different from the association pattern of static directional/gender information perception. Overall, these findings show that intrinsic brain network efficiency may be considered a neural factor that explains BMP inter-individual variability.

Reconfiguration of the Brain Functional Network Associated with Visual Task Demands.

Neuroimaging studies have demonstrated that the topological properties of resting-state brain functional networks are modulated through task performances. However, the reconfiguration of functional networks associated with distinct degrees of task demands is not well understood. In the present study, we acquired fMRI data from 18 healthy adult volunteers during resting-state (RS) and two visual tasks (i.e., visual stimulus watching, VSW; and visual stimulus decision, VSD). Subsequently, we constructed the functional brain networks associated with these three conditions and analyzed the changes in the topological properties (e.g., network efficiency, wiring-cost, modularity, and robustness) among them. Although the small-world attributes were preserved qualitatively across the functional networks of the three conditions, changes in the topological properties were also observed. Compared with the resting-state, the functional networks associated with the visual tasks exhibited significantly increased network efficiency and wiring-cost, but decreased modularity and network robustness. The changes in the task-related topological properties were modulated according to the task complexity (i.e., from RS to VSW and VSD). Moreover, at the regional level, we observed that the increased nodal efficiencies in the visual and working memory regions were positively associated with the increase in task complexity. Together, these results suggest that the increased efficiency of the functional brain network and higher wiring-cost were observed to afford the demands of visual tasks. These observations provide further insights into the mechanisms underlying the reconfiguration of the brain network during task performance.