Optimization of structural connectomes and scaled patterns of structural-functional decoupling in Parkinson's disease.

Parkinson's disease (PD) is manifested with disrupted topology of the structural connection network (SCN) and the functional connection network (FCN). However, the SCN and its interactions with the FCN remain to be further investigated. This multimodality study attempted to precisely characterize the SCN using diffusion kurtosis imaging (DKI) and further identify the neuropathological pattern of SCN-FCN decoupling, underscoring the neurodegeneration of PD. Diffusion-weighted imaging and resting-state functional imaging were available for network constructions among sixty-nine patients with PD and seventy demographically matched healthy control (HC) participants. The classification performance and topological prosperities of both the SCN and the FCN were analyzed, followed by quantification of the SCN-FCN couplings across scales. The SCN constructed by kurtosis metrics achieved optimal classification performance (area under the curve 0.89, accuracy 80.55 %, sensitivity 78.40 %, and specificity 80.65 %). Along with diverse alterations of structural and functional network topology, the PD group exhibited decoupling across scales including: reduced global coupling; increased nodal coupling within the sensorimotor network (SMN) and subcortical network (SN); higher intramodular coupling within the SMN and SN and lower intramodular coupling of the default mode network (DMN); decreased coupling between the modules of DMN-fronto-parietal network and DMN-visual network, but increased coupling between the SMN-SN module. Several associations between the coupling coefficient and topological properties of the SCN, as well as between network values and clinical scores, were observed. These findings validated the clinical implementation of DKI for structural network construction with better differentiation ability and characterized the SCN-FCN decoupling as supplementary insight into the pathological process underlying PD.

Motor asymmetry related cerebral perfusion patterns in Parkinson's disease: An arterial spin labeling study.

Persisting asymmetry of motor symptoms are characteristic of Parkinson's disease (PD). We investigated the possible lateralized effects on regional cerebral blood flow (CBF), CBF-connectivity, and laterality index (LI) among PD subtypes using arterial spin labeling (ASL). Forty-four left-sided symptom dominance patients (PDL), forty-eight right-sided symptom dominance patients (PDR), and forty-five matched HCs were included. Group comparisons were performed for the regional normalized CBF, CBF-connectivity and LI of basal ganglia (BA) subregions. The PDL patients had lower CBF in right calcarine sulcus and right supramarginal gyrus compared to the PDR and the HC subjects. Regional perfusion alterations seemed more extensive in the PDL than in the PDR group. In the PDL, correlations were identified between right thalamus and motor severity, between right fusiform gyrus and global cognitive performance. None of correlations survived after multiple comparisons correction. The significantly altered CBF-connectivity among the three groups included: unilateral putamen, unilateral globus pallidus, and right thalamus. LI score in the putamen was significantly different among groups. Motor-symptom laterality in PD may exhibit asymmetric regional and interregional abnormalities of CBF properties, particularly in PDL patients. This preliminary study underlines the necessity of classifying PD subgroups based on asymmetric motor symptoms and the potential application of CBF properties underlying neuropathology in PD.

Can Hybrid Arterial Spin Labeling-Tagged Zero-Echo-Time Magnetic Resonance Angiography Be an Effective Candidate in the Evaluation of Intracranial Artery Diseases? A Clinical Feasibility Study.

BACKGROUND: Flow related artifacts in continuous arterial spin labeling (cASL) zero-echo-time (ZTE) magnetic resonance angiography (MRA) could influence the vasculature visualization. PURPOSE: To investigate the clinical feasibility for the intracranial artery diseases assessment by utilizing hybrid ASL-ZTE-MRA (hASL-ZTE-MRA). STUDY TYPE: Prospective, technical development. POPULATION: Sixty-seven subjects with known/suspected cerebrovascular diseases. FIELD STRENGTH/SEQUENCE: Gradient echo based cASL-/hASL- ZTE-MRA at 3.0 T. ASSESSMENT: Subjective/objective evaluation for sound-levels. Image quality (IQ), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were analyzed within artery segments. Stenotic grading, aneurysm measurement, and signal intensity of lesions were further analyzed. STATISTICAL TESTS: Kolmogorov-Smirnov test for data normality check. Between two MRAs: Wilcoxon signed-rank test for sound experience/IQ ratings analysis; Paired t test for SNR/CNR comparison. One-way analysis of variance for sound intensity comparison. For stenosis grading/aneurysm measurement: Kendall's W test/intraclass correlation coefficient (ICC) for interobserver agreement test within each modality, weighted kappa statistics/ICC for intermodality agreement test between each MRA and computed tomography angiography. RESULTS: Sound-level perception/intensity was similar (P = 0.86, P = 0.55) between MRAs. The mean IQ score for hASL-ZTE-MRA was on diagnostic scale and slightly higher (P < 0.05) than that of cASL-ZTE-MRA. hASL-ZTE-MRA provided higher (P < 0.05) SNR/CNR than that of cASL-ZTE-MRA. Signal uniformity was improved on hASL-ZTE-MRA, particularly among the anterior circulation (P < 0.05). Comparing to cASL-ZTE-MRA, on hASL-ZTE-MRA, stenotic lesions were accurately assessed; flow in the stent or aneurysm remnant was better depicted (P < 0.05); AVM nidus was preferred with increased SNR (P < 0.05). No significant differences for the aneurysm measurement were found between MRAs (P = 0.95), in addition to the slightly higher SNR (P < 0.05) on hASL-ZTE-MRA. DATA CONCLUSION: Comparing to cASL-ZTE-MRA, hASL-ZTE-MRA is robust and feasible for the evaluation of intracranial artery diseases with diagnostic IQ, improved vessel contrast, and better signal heterogeneity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: 2.

Alterations of brain network topology and structural connectivity-functional connectivity coupling in capsular versus pontine stroke.

BACKGROUND AND PURPOSE: This study was conducted to investigate whether capsular stroke (CS) and pontine stroke (PS) have different topological alterations of structural connectivity (SC) and functional connectivity (FC), as well as correlations of SC-FC coupling with movement assessment scores. METHODS: Resting-state functional magnetic resonance imaging and diffusion tensor imaging were prospectively acquired in 46 patients with CS, 36 with PS, and 29 healthy controls (HCs). Graph theoretical network analyses of SC and FC were performed. Patients with left and right lesions were analyzed separately. RESULTS: With regard to FC, the PS and CS groups both showed higher local efficiency than the HCs, and the CS group also had a higher clustering coefficient (Cp) than the HCs in the right lesion analysis. With regard to SC, the PS and CS groups both showed different normalized clustering coefficient (γ), small-worldness (σ), and characteristic path length (Lp) compared with the HC group. Additionally, the CS group showed higher normalized characteristic path length (λ) and a lower Cp than the HCs and the PS group showed higher λ and lower global efficiency than the HCs in the right-lesion analysis. However, γ, σ, Cp and Lp were only significantly different in the PS and CS groups compared with the HC group in the right-lesion analysis. Importantly, the CS group was found to have a weaker SC-FC coupling than the PS group and the HC group in the right-lesion analysis. In addition, both patient groups had weaker structural-functional connectome correlation than the HCs. CONCLUSIONS: The CS and PS groups both showed FC and SC disruption and the CS group had a weaker SC-FC coupling than the PS group in the right lesion analysis. This may provide useful information for individualized rehabilitative strategies.

Altered static and dynamic functional network connectivity in post-traumatic headache.

BACKGROUND: Post-traumatic headache (PTH) is a very common symptom following mild traumatic brain injury (mTBI), yet much remains unknown about the underlying pathophysiological mechanisms of PTH. Neuroimaging studies suggest that aberrant functional network connectivity (FNC) may be an important factor in pain disorders. The present study aimed to investigate the functional characteristics of static FNC (sFNC) and dynamic FNC (dFNC) in mTBI patients with PTH. METHODS: With Institutional Review Board (IRB) approval, we prospectively recruited 50 mTBI patients with PTH, who were diagnosed with ICHD-3 beta diagnostic criteria and 39 mTBI without PTH who were well matched for age, gender and education. Resting-state functional magnetic resonance imaging (fMRI) scanning (3.0 T, Philips Medical Systems, Netherlands), Montreal Cognitive Assessment (MoCA) and headache symptom measurement (headache frequency and headache intensity) were performed. The resting-state fMRI sequence took 8 min and 10 s. Independent component analysis and sliding window method were applied to examine the FNC on the basis of nine resting-state networks, namely, default mode network (DMN), sensorimotor network (SMN), executive control network (ECN), auditory network (AuN), attention network (AN), salience network (SN), visual network (VN), and cerebellum network (CN). The differences in sFNC and dFNC were determined and correlated with clinical variables using Pearson rank correlation. RESULTS: For sFNC, compared with mTBI patients without PTH, mTB with PTH group showed four altered interactions, including decreased interactions in SN-SMN and VN-DMN pairs, increased sFNC in SN-ECN and SMN-DMN pairs. For dFNC, significant group differences were found in State 2, including increased connectivity alteration in the DMN with CN, DMN with SMN, and AuN with CN. Significant reduced connectivity changes in the DMN with VN was found in State 4. Furthermore, the number of transitions (r=0.394, p=0.005) between states was positively associated with headache frequency. Additionally, dwell time (r=-0.320, p=0.025) in State 1 was negatively correlated with MoCA score. CONCLUSIONS: MTBI patients with PTH are characterized with altered sFNC and dFNC, which could provide new perspective to understand the neuropathological mechanism underlying the PTH to determine more appropriate management, and may be a useful imaging biomarker for identifying and predicting mTBI with PTH.

Cerebral Blood Flow and Its Connectivity Deficits in Mild Traumatic Brain Injury at the Acute Stage.

Objective: The influence of cognitive impairment after mild traumatic brain injury (mTBI) on cerebral vascular perfusion has been widely concerned, yet the resting-state cerebral blood flow (CBF) connectivity alterations based on arterial spin labeling (ASL) in mild traumatic brain injury (mTBI) remain unclear. This study investigated region CBF and CBF connectivity features in acute mTBI patients, as well as the associations between CBF changes and cognitive impairment. Materials and Methods: Forty-five acute mTBI patients and 42 health controls underwent pseudocontinuous arterial spin labeling (pCASL) perfusion magnetic resonance imaging (MRI). The alterations in regional CBF and relationship between the CBF changes and cognitive impairment were detected. The ASL-CBF connectivity of the brain regions with regional CBF significant differences was also compared between two groups. Neuropsychological tests covered seven cognitive domains. Associations between the CBF changes and cognitive impairment were further investigated. Results: Compared with the healthy controls, the acute mTBI patients exhibited increased CBF in the bilateral inferior temporal gyrus (ITG) and decreased CBF in the right middle frontal gyrus (MFG), the bilateral superior frontal gyrus (SFG), and the right cerebellum posterior lobe (CPL). In the mTBI patients, significant correlations were identified between the CBF changes and cognitive impairment. Importantly, the acute mTBI patients exhibited CBF disconnections between the right CPL and right fusiform gyrus (FG) as well as bilateral ITG, between the left SFG and left middle occipital gyrus (MOG), and between the right SFG and right FG as well as right parahippocampal gyrus. Conclusion: Our results suggest that acute mTBI patients exhibit both regional CBF abnormalities and CBF connectivity deficits, which may underlie the cognitive impairment of the acute mTBI patients.

Follow-up assessment of coiled intracranial aneurysms using zTE MRA as compared with TOF MRA: a preliminary image quality study.

OBJECTIVES: To prospectively assess coiled intracranial aneurysms using a novel non-contrast enhanced zero echo time (zTE) MR angiography (MRA) method, and compare its image quality with time-of-flight (TOF) MRA, using digital subtraction angiography (DSA) as reference. METHODS: Twenty-five patients (10 males and 15 females; age 53.96 ± 12.46 years) were enrolled in this monocentric study. MRA sequences were performed 24 h before DSA. Susceptibility artefact intensity and flow signal within the parent artery were carried out using a 4-point scale. Occlusion status was assessed using the 3-grade Montreal scale. RESULTS: Scores of zTE were higher than TOF for both susceptibility artefact intensity (3.42 ± 0.64, 2.92 ± 0.63, P = 0.01) and flow signal (3.66 ± 0.95, 3.24 ± 1.24, P = 0.01). DSA revealed 17 complete occlusions, five residual neck aneurysms and two residual aneurysms. Inter-observer agreement was excellent (weighted κ: 0.89) for zTE and good (weighted κ: 0.68) for TOF. Intermodality agreement was excellent for zTE (weighted κ: 0.95) and good for TOF (weighted κ: 0.80). Correlations of both MRA sequences with DSA were high (zTE, Spearman's ρ: 0.91; TOF, Spearman's ρ: 0.81). CONCLUSIONS: zTE MRA showed promising results for follow-up assessment of coiled intracranial aneurysms and was superior to TOF MRA for visualizing the parent artery and evaluating occlusion status. KEY POINTS: • Various MRA sequences were applied for follow-up assessment of coiled intracranial aneurysms. • zTE MRA was less sensitive to susceptibility artefacts and haemodynamics. • In this monocentric study, zTE MRA was equivalent to DSA. • zTE MRA maybe an alternative to TOF MRA for follow-up assessment.

Magnetic resonance and near-infrared imaging using a novel dual-modality nano-probe for dendritic cell tracking in vivo.

BACKGROUND AIMS: The effect of cellular-based immunotherapy is highly correlated with the success of dendritic cells (DCs) homing to the draining lymph nodes (LNs) and interacting with antigen-specific CD4(+) T cells. In this study, a novel magneto-fluorescent nano-probe was used to track the in vivo migration of DCs to the draining LNs. METHODS: A dual-modality nano-probe composed of superparamagnetic iron oxide (SPIO) and near-infrared fluorescent (NIRF) dye (NIR797) was developed, and its magnetic and optical contrasting properties were characterized. DCs generated from mouse bone marrow were co-cultured with the probe at a lower concentration of 10 µg/mL. The cell phenotype and function of DCs were also investigated by fluorescence-activated cell sorting analysis and mixed leukocyte reactivity assay. Labeled DCs were injected into the footpad of C57BL/6 mice. Afterward, magnetic resonance imaging, NIRF imaging, Perls staining and CD11c immunofluorescence were used to observe the migration of the labeled DCs into draining LNs. RESULTS: The synthetic SPIO-NIR797 nano-probe had a desirable superparamagnetic and near-infrared behavior. Perls staining showed perfect labeling efficiency. The cell phenotypes, including CD11c, CD80, CD86 and major histocompatibility complex class II, as well as the T-cell activation potential of the mature DCs were insignificantly affected after incubation (P > 0.05). Labeled DCs migrating into LNs could be detected by both magnetic resonance imaging and NIRF imaging simultaneously, which was further confirmed by Perls staining and immunofluorescence. CONCLUSIONS: The novel dual-modality SPIO-NIR797 nano-probe has highly biocompatible characteristics for labeling and tracking DCs, which can be used to evaluate cancer immunotherapy in clinical applications.

Effect of maternal cigarette smoke exposure on COPD progression in offspring mice.

OBJECTIVE: To investigate the impact of maternal smoking on chronic obstructive pulmonary disease (COPD) progression in offspring. METHODS: Using female C57BL/6 J mice, a maternal cigarette smoke exposure (CSE) model was established. Mice were exposed to cigarette smoke for 2 hours/day, 7 days/week, with a minimum 4-hour interval between exposures. Experimental groups included control (Con), pregnancy exposure (AS), pre-pregnancy exposure (SA), and pre-pregnancy + pregnancy exposure (SS). Lung function tests (Penh, PAU, TVb, EF50, Tr) were conducted on male offspring at 7 weeks. Histopathology, electron microscopy, and protein level changes were examined. RESULTS: Lung function tests revealed significant impairments in Penh, PAU, TVb, EF50, and Tr in offspring across all exposure scenarios. Specifically, AS experienced significant lung function impairment and mitochondrial dysfunction in offspring, with noticeable pulmonary lesions and increased apoptosis. SA showed similar or even more severe lung function impairment and cellular apoptosis. SS exhibited the most pronounced effects, with the highest levels of lung dysfunction, mitochondrial damage, and apoptosis. Histopathological analysis showed pulmonary lesions in offspring exposed to maternal CSE. Flow cytometry revealed increased apoptosis and reduced mitochondrial membrane potential in offspring lung cells. Electron microscopy confirmed mitochondrial dysfunction. Upregulation of apoptotic proteins and downregulation of anti-apoptotic protein Bcl-2 were found in offspring lung tissue exposed to maternal CSE. CONCLUSION: Maternal smoking induces impaired lung function, pulmonary lesions, and mitochondrial dysfunction in offspring, regardless of exposure timing and duration. Additionally, it alters expression of apoptosis-related proteins in offspring lung tissue, potentially contributing to COPD susceptibility.

Intracerebral hemodynamic abnormalities in patients with Parkinson's disease: Comparison between multi-delay arterial spin labelling and conventional single-delay arterial spin labelling.

PURPOSE: The purpose of this study was to analyze the intracerebral abnormalities of hemodynamics in patients with Parkinson's disease (PD) through arterial spin labelling (ASL) technique with multi-delay ASL (MDASL) and conventional single-delay ASL (SDASL) protocols and to verify the potential clinical application of these features for the diagnosis of PD. MATERIALS AND METHODS: Perfusion data of the brain obtained using MDASL and SDASL in patients with PD were compared to those obtained in healthy control (HC) subjects. Intergroup comparisons of z-scored cerebral blood flow (zCBF), arterial transit time (zATT) and cerebral blood volume (zCBV) were performed via voxel-based analysis. Performance of these perfusion metrics were estimated using area under the receiver operating characteristic curve (AUC) and compared using Delong test. RESULTS: A total of 47 patients with PD (29 men; 18 women; mean age, 69.0 ± 7.6 (standard deviation, [SD]) years; range: 50.0-84.0 years) and 50 HC subjects (28 men; 22 women; mean age, 70.1 ± 6.2 [SD] years; range: 50.0-93.0 years) were included. Relative to the uncorrected-zCBF map, the corrected-zCBF map further refined the distributed brain regions in the PD group versus the HC group, manifested as the extension of motor-related regions (PFWE < 0.001). Compared to the HC subjects, patients with PD had elevated zATT and zCBV in the right putamen, a shortened zATT in the superior frontal gyrus, and specific zCBV variations in the left precuneus and the right supplementary motor area (PFWE < 0.001). The corrected-zCBF (AUC, 0.90; 95% confidence interval [CI]: 0.84-0.96) showed better classification performance than uncorrected-zCBF (AUC, 0.84; 95% CI: 0.75-0.92) (P = 0.035). zCBV achieved an AUC of 0.89 (95% CI: 0.82-0.96) and zATT achieved an AUC of 0.66 (95% CI: 0.55-0.77). The integration model of hemodynamic features from MDASL provided improved performance (AUC, 0.97; 95% CI: 0.95-0.98) for the diagnosis of PD by comparison with each perfusion model (P < 0.001). CONCLUSION: ASL identifies impaired hemodynamics in patients with PD including regional abnormalities of CBF, CBV and ATT, which can better be mapped with MDASL compared to SDASL. These findings provide complementary depictions of perfusion abnormalities in patients with PD and highlight the clinical feasibility of MDASL.

Molecular subtype identification and prognosis stratification by a immunogenic cell death-related gene expression signature in colorectal cancer.

OBJECTIVES: This study intended to develop a new immunogenic cell death (ICD)-related prognostic signature for colorectal cancer (CRC) patients. RESEARCH DESIGN AND METHODS: The Non-Negative Matrix Factorization (NMF) algorithm was adopted to cluster tumor samples based on ICD gene expression to obtain ICD-related subtypes. Survival analysis and immune microenvironment analysis were conducted among different subtypes. Regression analysis was used to construct the model. Based on riskscore median, cancer patients were classified into high and low risk groups, and independent prognostic ability of the model was analyzed. The CIBERSORT algorithm was adopted to determine the immune infiltration level of both groups. RESULTS: We analyzed the differential genes between cluster 4 and cluster 1-3 and obtained 12 genes with the best prognostic features finally (NLGN1, SLC30A3, C3orf20, ADAD2, ATOH1, ATP6V1B1, KCNQ2, MUCL3, RGCC, CLEC17A, COL6A5, and INSL4). In addition, patients with lower risk had higher levels of infiltration of most immune cells, lower Tumor Immune Dysfunction and Exclusion (TIDE) level and higher immunophenscore (IPS) level than those with higher risk. CONCLUSIONS: This study constructed and validated the ICD feature signature predicting CRC prognosis and provide a reference criteria for guiding the prognosis and immunotherapy of CRC cancer patients.

Topological disruption of low- and high-order functional networks in presbycusis.

Prior efforts have manifested that functional connectivity (FC) network disruptions are concerned with cognitive disorder in presbycusis. The present research was designed to investigate the topological reorganization and classification performance of low-order functional connectivity (LOFC) and high-order functional connectivity (HOFC) networks in patients with presbycusis. Resting-state functional magnetic resonance imaging (Rs-fMRI) data were obtained in 60 patients with presbycusis and 50 matched healthy control subjects (HCs). LOFC and HOFC networks were then constructed, and the topological metrics obtained from the constructed networks were compared to evaluate topological differences in global, nodal network metrics, modularity and rich-club organization between patients with presbycusis and HCs. The use of HOFC profiles boosted presbycusis classification accuracy, sensitivity and specificity compared to that using LOFC profiles. The brain networks in both patients with presbycusis and HCs exhibited small-world properties within the given threshold range, and striking differences between groups in topological metrics were discovered in the constructed networks (LOFC and HOFC). NBS analysis identified a subnetwork involving 26 nodes and 23 signally altered internodal connections in patients with presbycusis in comparison to HCs in HOFC networks. This study highlighted the topological differences between LOFC and HOFC networks in patients with presbycusis, suggesting that HOFC profiles may help to further identify brain network abnormalities in presbycusis.

Topological disruption of high-order functional networks in cognitively preserved Parkinson's disease.

AIMS: This study aimed to characterize the topological alterations and classification performance of high-order functional connectivity (HOFC) networks in cognitively preserved patients with Parkinson's disease (PD), relative to low-order FC (LOFC) networks. METHODS: The topological metrics of the constructed networks (LOFC and HOFC) obtained from fifty-one cognitively normal patients with PD and 60 matched healthy control subjects were analyzed. The discriminative abilities were evaluated using machine learning approach. RESULTS: The HOFC networks in the PD group showed decreased segregation and integration. The normalized clustering coefficient and small-worldness in the HOFC networks were correlated to motor performance. The altered nodal centralities (distributed in the precuneus, putamen, lingual gyrus, supramarginal gyrus, motor area, postcentral gyrus and inferior occipital gyrus) and intermodular FC (frontoparietal and visual networks, sensorimotor and subcortical networks) were specific to HOFC networks. Several highly connected nodes (thalamus, paracentral lobule, calcarine fissure and precuneus) and improved classification performance were found based on HOFC profiles. CONCLUSION: This study identified disrupted topology of functional interactions at a high level with extensive alterations in topological properties and improved differentiation ability in patients with PD prior to clinical symptoms of cognitive impairment, providing complementary insights into complex neurodegeneration in PD.

Functional-structural large-scale brain networks are correlated with neurocognitive impairment in acute mild traumatic brain injury.

Background: This study was conducted to investigate topological changes in large-scale functional connectivity (FC) and structural connectivity (SC) networks in acute mild traumatic brain injury (mTBI) and determine their potential relevance to cognitive impairment. Methods: Seventy-one patients with acute mTBI (29 males, 42 females, mean age 43.54 years) from Nanjing First Hospital and 57 matched healthy controls (HC) (33 males, 24 females, mean age 46.16 years) from the local community were recruited in this prospective study. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were acquired within 14 days (mean 3.29 days) after the onset of mTBI. Then, large-scale FC and SC networks with 116 regions from the automated anatomical labeling (AAL) brain atlas were constructed. Graph theory analysis was used to analyze global and nodal metrics. Finally, correlations were assessed between topological properties and neurocognitive performances evaluated by the Montreal Cognitive Assessment (MoCA). Bonferroni correction was performed out for multiple comparisons in all involved analyses. Results: Compared with HC, acute mTBI patients had a higher normalized clustering coefficient (γ) for FC (Cohen's d=4.076), and higher γ and small worldness (σ) for SC (Cohen's d=0.390 and Cohen's d=0.395). The mTBI group showed aberrant nodal degree (Dc), nodal efficiency (Ne), and nodal local efficiency (Nloc) for FC and aberrant Dc, nodal betweenness (Bc), nodal clustering coefficient (NCp) and Ne for SC mainly in the frontal and temporal, cerebellum, and subcortical areas. Acute mTBI patients also had higher functional-structural coupling strength at both the group and individual levels (Cohen's d=0.415). These aberrant global and nodal topological properties at functional and structural levels were associated with attention, orientation, memory, and naming performances (all P<0.05). Conclusions: Our findings suggested that large-scale FC and SC network changes, higher correlation between FC and SC and cognitive impairment can be detected in the acute stage of mTBI. These network aberrances may be a compensatory mechanism for cognitive impairment in acute mTBI patients.

Drooling disrupts the brain functional connectivity network in Parkinson's disease.

AIMS: This study aimed to investigate the causal interaction between significant sensorimotor network (SMN) regions and other brain regions in Parkinson's disease patients with drooling (droolers). METHODS: Twenty-one droolers, 22 PD patients without drooling (non-droolers), and 22 matched healthy controls underwent 3T-MRI resting-state scans. We performed independent component analysis and Granger causality analysis to determine whether significant SMN regions help predict other brain areas. Pearson's correlation was computed between imaging characteristics and clinical characteristics. ROC curves were plotted to assess the diagnostic performance of effective connectivity (EC). RESULTS: Compared with non-droolers and healthy controls, droolers showed abnormal EC of the right caudate nucleus (CAU.R) and right postcentral gyrus to extensive brain regions. In droolers, increased EC from the CAU.R to the right middle temporal gyrus was positively correlated with MDS-UPDRS, MDS-UPDRS II, NMSS, and HAMD scores; increased EC from the right inferior parietal lobe to CAU.R was positively correlated with MDS-UPDRS score. ROC curve analysis showed that these abnormal ECs are of great significance in diagnosing drooling in PD. CONCLUSION: This study identified that PD patients with drooling have abnormal EC in the cortico-limbic-striatal-cerebellar and cortio-cortical networks, which could be potential biomarkers for drooling in PD.

Exosomal PD­L1 promotes the formation of an immunosuppressive microenvironment in gastric diffuse large B­cell lymphoma.

Gastric diffuse large B­cell lymphoma (GDLBCL) is a common disease with an increasing incidence. However, the regulatory effect of exosomal programmed death­ligand 1 (PD­L1) on the immune microenvironment in GDLBCL is unclear. In the present study, the protein expression levels of exosomal PD­L1 in the supernatants of cultured diffuse large B­cell lymphoma (DLBCL) cells and the plasma of patients with GDLBCL was assessed using immunoblotting. Exosomes derived from DLBCL cells were cocultured with T lymphocytes or injected into tumor xenograft mice by tail vein injection. The relationship between the protein expression level of exosomal PD­L1 in the plasma and the clinical characteristics and immune microenvironmental parameters of GDLBCL was evaluated using immunoblotting and immunohistochemistry. High levels of exosomal PD­L1 were found in the supernatants of cultured DLBCL cells. Exosomes with high levels of PD­L1 promoted growth of tumors formed by DLBCL cells in vivo and inhibited the proliferation of T lymphocytes. Notably, the protein expression level of PD­L1 in plasma exosomes derived from GDLBCL patients was significantly higher than that of healthy individuals. High levels of PD­L1 in plasma exosomes were significantly associated with international prognostic index score, pathological type and advanced Lugano stage, which might lead to the poor prognosis of GDLBCL. Moreover, a high level of PD­L1 in plasma exosomes was significantly associated with an immunosuppressive microenvironment in GDLBCL. Therefore, the results of the present study indicated that exosomal PD­L1 inhibited the proliferation of T lymphocytes and promoted the formation of an immunosuppressive microenvironment in GDLBCL. High expression of exosomal PD­L1 may suggest a poor prognosis of GDLBCL, and exosomal PD­L1 in plasma may be a new diagnostic indicator for GDLBCL.

Reorganized Brain Functional Network Topology in Presbycusis.

Purpose: Presbycusis is characterized by bilateral sensorineural hearing loss at high frequencies and is often accompanied by cognitive decline. This study aimed to identify the topological reorganization of brain functional network in presbycusis with/without cognitive decline by using graph theory analysis approaches based on resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Resting-state fMRI scans were obtained from 30 presbycusis patients with cognitive decline, 30 presbycusis patients without cognitive decline, and 50 age-, sex-, and education-matched healthy controls. Graph theory was applied to analyze the topological properties of brain functional networks including global and nodal metrics, modularity, and rich-club organization. Results: At the global level, the brain functional networks of all participants were found to possess small-world properties. Also, significant group differences in global network metrics were observed among the three groups such as clustering coefficient, characteristic path length, normalized characteristic path length, and small-worldness. At the nodal level, several nodes with abnormal betweenness centrality, degree centrality, nodal efficiency, and nodal local efficiency were detected in presbycusis patients with/without cognitive decline. Changes in intra-modular connections in frontal lobe module and inter-modular connections in prefrontal subcortical lobe module were found in presbycusis patients exposed to modularity analysis. Rich-club nodes were reorganized in presbycusis patients, while the connections among them had no significant group differences. Conclusion: Presbycusis patients exhibited topological reorganization of the whole-brain functional network, and presbycusis patients with cognitive decline showed more obvious changes in these topological properties than those without cognitive decline. Abnormal changes of these properties in presbycusis patients may compensate for cognitive impairment by mobilizing additional neural resources.

Rich-club reorganization of functional brain networks in acute mild traumatic brain injury with cognitive impairment.

Background: Mild traumatic brain injury (mTBI) is typically characterized by temporally limited cognitive impairment and regarded as a brain connectome disorder. Recent findings have suggested that a higher level of organization named the "rich-club" may play a central role in enabling the integration of information and efficient communication across different systems of the brain. However, the alterations in rich-club organization and hub topology in mTBI and its relationship with cognitive impairment after mTBI have been scarcely elucidated. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 88 patients with mTBI and 85 matched healthy controls (HCs). Large-scale functional brain networks were established for each participant. Rich-club organizations and network properties were assessed and analyzed between groups. Finally, we analyzed the correlations between the cognitive performance and changes in rich-club organization and network properties. Results: Both mTBI and HCs groups showed significant rich-club organization. Meanwhile, the rich-club organization was aberrant, with enhanced functional connectivity (FC) among rich-club nodes and peripheral regions in acute mTBI. In addition, significant differences in partial global and local network topological property measures were found between mTBI patients and HCs (P<0.01). In patients with mTBI, changes in rich-club organization and network properties were found to be related to early cognitive impairment after mTBI (P<0.05). Conclusions: Our findings suggest that such patterns of disruption and reorganization will provide the basic functional architecture for cognitive function, which may subsequently be used as an earlier biomarker for cognitive impairment after mTBI.

Cerebral Blood Flow and its Connectivity Deficits in Patients With Lung Cancer After Chemotherapy.

Purpose: This study was performed to investigate the regional cerebral blood flow (CBF) and CBF connectivity in the chemotherapy-induced cognitive impairment of patients with lung cancer by using arterial spin labeling. Methods: Pseudocontinuous arterial spin labeling perfusion magnetic resonance imaging and neuropsychological tests were performed for 21 patients with non-small cell lung cancer who had received chemotherapy CT (+) and 25 non-small cell lung cancer patients who need chemotherapy but did not yet received CT (-). The CT (+) group previously received platinum-based therapy for 3 months to 6 months (the time from their first chemotherapy to the MRI scan). Group comparisons were performed in the regional normalized CBF and CBF connectivity, and the relationship between the regional normalized CBF and cognitive impairment were detected. Results: The CT (+) group exhibited higher CBF in the left insula, right caudate, right superior occipital gyrus, left superior temporal gyrus (STG), and right middle frontal gyrus (MFG). MoCA scores as well as the memory scores were negatively correlated with the increased CBF in the right MFG (r = -0.492, p = 0.023; r = -0.497, p = 0.022). Alterations in the CBF connectivity were detected only in the CT (+) group between the following: right MFG and the right precentral gyrus; the right caudate and the right lingual gyrus; right caudate and right precuneus; left STG and the bilateral MFG; and the left STG and the right middle cingulum. Conclusion: These findings indicated that chemotherapy is associated with abnormalities in the CBF and connectivity alterations, which may contribute to the cognitive impairment in patients with lung cancer.

Topological features of limbic dysfunction in chronicity of tinnitus with intact hearing: New hypothesis for 'noise-cancellation' mechanism.

PURPOSE: The reorganization of the limbic regions extend to general cognitive network is believed to exist in the chronicity of tinnitus with particular 'hubs' contributing to a 'noise-cancellation' mechanism. To test this hypothesis, we investigated the topological brain network of tinnitus in different periods. METHODS: Resting-state functional magnetic resonance imaging were obtained from 32 patients with acute tinnitus, 41 patients with chronic tinnitus and 60 age- and gender- matched healthy controls (HC). The topological features of their brain networks were explored using graph theory analysis. RESULTS: Common small-world attributes were compared between the three groups, all showed a significantly increased values in Cp, Lp, λ (all p < 0.05). Significantly increased nodal centralities in the left superior frontal gyrus and the right precuneus, significantly decreased nodal centralities in the right inferior temporal gyrus were observed for acute tinnitus patients compared to HC. While for chronic tinnitus patients, there were significant increased nodal centralities in the left hippocampus, amygdala, and temporal pole, but decreased nodal centralities in the right inferior temporal gyrus. Additionally, significant higher nodal centralities were found in bilateral medial superior frontal gyrus for acute tinnitus patients compared to chronic tinnitus patients. Besides, alterations in rich-club organization were found in acute tinnitus patients and chronic tinnitus patients compared with HC, with increased functional connections among rich-club nodes and peripheral nodes in patients with tinnitus. CONCLUSIONS: Brain network topological properties altered across prefrontal-limbic-subcortical regions in tinnitus. The existed hubs in tinnitus might indicate an emotional and cognitive burden in 'noise-cancellation' mechanism.