Tinnitus classification based on resting-state functional connectivity using a convolutional neural network architecture.

OBJECTIVES: Many studies have investigated aberrant functional connectivity (FC) using resting-state functional MRI (rs-fMRI) in subjective tinnitus patients. However, no studies have verified the efficacy of resting-state FC as a diagnostic imaging marker. We established a convolutional neural network (CNN) model based on rs-fMRI FC to distinguish tinnitus patients from healthy controls, providing guidance and fast diagnostic tools for the clinical diagnosis of subjective tinnitus. METHODS: A CNN architecture was trained on rs-fMRI data from 100 tinnitus patients and 100 healthy controls using an asymmetric convolutional layer. Additionally, a traditional machine learning model and a transfer learning model were included for comparison with the CNN, and each of the three models was tested on three different brain atlases. RESULTS: Of the three models, the CNN model outperformed the other two models with the highest area under the curve, especially on the Dos_160 atlas (AUC = 0.944). Meanwhile, the model with the best classification performance highlights the crucial role of the default mode network, salience network, and sensorimotor network in distinguishing between normal controls and patients with subjective tinnitus. CONCLUSION: Our CNN model could appropriately tackle the diagnosis of tinnitus patients using rs-fMRI and confirmed the diagnostic value of FC as measured by rs-fMRI.

Connectivity of the insular subdivisions differentiates posttraumatic headache-associated from nonheadache-associated mild traumatic brain injury: an arterial spin labelling study.

OBJECTIVE: The insula is an important part of the posttraumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) neuropathological activity pattern. It is composed of functionally different subdivisions and each of which plays different role in PTH neuropathology. METHODS: Ninety-four mTBI patients were included in this study. Based on perfusion imaging data obtained from arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI), this study evaluated the insular subregion perfusion-based functional connectivity (FC) and its correlation with clinical characteristic parameters in patients with PTH after mTBI and non-headache mTBI patients. RESULTS: The insular subregions of mTBI + PTH (mTBI patients with PTH) and mTBI-PTH (mTBI patients without PTH) group had positive perfusion-based functional connections with other insular nuclei and adjacent discrete cortical regions. Compared with mTBI-PTH group, significantly increased resting-state perfusion-based FC between the anterior insula (AI) and middle cingulate cortex (MCC)/Rolandic operculum (ROL), between posterior insula (PI) and supplementary motor area (SMA), and decreased perfusion-based FC between PI and thalamus were found in mTBI + PTH group. Changes in the perfusion-based FC of the left posterior insula/dorsal anterior insula with the thalamus/MCC were significant correlated with headache characteristics. CONCLUSIONS: Our findings provide new ASL-based evidence for changes in the perfusion-based FC of the insular subregion in PTH patients attributed to mTBI and the association with headache features, revealing the possibility of potential neuroplasticity after PTH. These findings may contribute to early diagnosis of the disease and follow-up of disease progression.

Reorganization of the cortical connectome functional gradient in age-related hearing loss.

Age-related hearing loss (ARHL), one of the most common sensory deficits in elderly individuals, is a risk factor for dementia; however, it is unclear how ARHL affects the decline in cognitive function. To address this issue, a connectome gradient framework was used to identify critical features of information integration between sensory and cognitive processing centers using resting-state functional magnetic resonance imaging (rs-fMRI) data from 40 individuals with ARHL and 36 healthy controls (HCs). The first three functional gradient alterations associated with ARHL were investigated at the global, network and regional levels. Using a support vector machine (SVM) model, our analysis distinguished individuals with ARHL with normal cognitive function from those with cognitive decline. Compared to HCs, individuals with ARHL had a contracted principal primary-to-transmodal gradient axis, especially in the visual and default mode networks, with an altered gradient explained ratio and variance. Among individuals with ARHL, cognitive decline was detected in the visual network in the principal gradient as well as in the limbic, salience and default mode networks in the third gradient (salience to frontoparietal/default mode). These results suggest that ARHL is associated with disrupted information processing from the primary sensory networks to higher-order cognitive networks and highlight the key nodes closely associated with cognitive decline during cognitive processing in ARHL, providing new insights into the mechanism of cognitive impairment and suggesting potential treatments related to ARHL.

Alteration in resting-state effective connectivity within the Papez circuit in Presbycusis.

Previous studies have suggested that the Papez circuit may be involved in the cognitive impairment observed after hearing loss in presbycusis patients, yet relatively little is known about the pattern of changes in effective connectivity within the circuit. The aim of this study was to investigate abnormal alterations in resting-state effective connectivity within the Papez circuit and their association with cognitive decline in presbycusis patients. The spectral dynamic causal modelling (spDCM) approach was used for resting-state effective connectivity analysis in 61 presbycusis patients and 52 healthy controls (HCs) within the Papez circuit. The hippocampus (HPC), mamillary body (MB), anterior thalamic nuclei (ATN), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), entorhinal cortex (ERC), subiculum (Sub) and parahippocampal gyrus (PHG) were selected as the regions of interest (ROIs). The fully connected model difference in effective connectivity between the two groups was assessed, and the correlation between effective connectivity alteration and cognitive scale was analysed. We found that presbycusis patients demonstrated decreased effective connectivity from MB, PCC, and Sub to ACC relative to HCs, whereas higher effective connectivity strength was shown from HPC to MB, from ATN to PHG and from PHG to Sub. The effective connectivity from PHG to Sub was significantly negatively correlated with the complex figure test (CFT)-delay score (rho = -0.259, p = 0.044). The results support and reinforce the role of abnormal effective connectivity within the Papez circuit in the pathophysiology of presbycusis-related cognitive impairment and reveal its potential as a novel imaging marker.

Kinesin KIF15 regulates tubulin acetylation and spindle assembly checkpoint in mouse oocyte meiosis.

Microtubule dynamics ensure multiple cellular events during oocyte meiosis, which is critical for the fertilization and early embryo development. KIF15 (also termed Hklp2) is a member of kinesin-12 family motor proteins, which participates in Eg5-related bipolar spindle formation in mitosis. In present study, we explored the roles of KIF15 in mouse oocyte meiosis. KIF15 expressed during oocyte maturation and localized with microtubules. Depletion or inhibition of KIF15 disturbed meiotic cell cycle progression, and the oocytes which extruded the first polar body showed a high aneuploidy rate. Further analysis showed that disruption of KIF15 did not affect spindle morphology but resulted in chromosome misalignment. This might be due to the reduced stability of the K-fibers, which further induced the loss of kinetochore-microtubule attachment and activated spindle assembly checkpoint, showing with the failed release of Bub3 and BubR1. Based on mass spectroscopy analysis and coimmunoprecipitation data we showed that KIF15 was responsible for recruiting HDAC6, NAT10 and SIRT2 to maintain the acetylated tubulin level, which further affected tubulin acetylation for microtubule stability. Taken together, these results suggested that KIF15 was essential for the microtubule acetylation and cell cycle control during mouse oocyte meiosis.

Age-related SUMOylation of PLK1 is essential to meiosis progression in mouse oocytes.

Polo like kinase 1 (PLK1) is a protein kinase involved in regulating the spindle assembly and cell cycle control in mammalian oocytes. SUMOylation, one way of post-translational modification, regulates oocyte meiosis by controlling several substrates. However, the relation between PLK1 and SUMOylation in oocytes is still unknown. In this study, we investigated that whether PLK1 was modified by SUMOylation in oocytes and its potential relationship with age-related meiotic abnormalities. We showed that PLK1 had colocalization and protein interaction with Small Ubiquitin-Like Modifier (SUMO)-1 and SUMO-2/3 in mouse oocytes, indicating that PLK1 could be modified by SUMO-1 and SUMO-2/3. Overexpression of PLK1 SUMOylation site mutants PLK1K178R and PLK1K191R caused the increase of the abnormal spindle rate of oocytes and the decline of the first polar body extrusion rate with the abnormal localization of PLK1, suggesting that the SUMOylation modification of PLK1 is essential for normal meiosis in oocytes. Compared with young mice, the expression of PLK1 protein increased and the expression of SUMO-1 and SUMO-2/3 protein decreased in the oocytes of aged mice, indicating that the SUMOylation of PLK1 might be related to the mouse aging. Therefore, our data suggested that PLK1 could be SUMOylated by SUMO-1 and SUMO-2/3 in mouse oocytes and SUMOylation of PLK1 regulated the meiosis progression of oocytes which was related with aging.

Nivalenol affects spindle formation and organelle functions during mouse oocyte maturation.

Oocyte maturation is essential for fertilization and early embryo development, and proper organelle functions guarantee this process to maintain high-quality oocytes. The type B trichothecene nivalenol (NIV) is a mycotoxin produced by Fusarium oxysporum and is commonly found in contaminated food. NIV intake affect growth, the immune system, and the female reproductive system. Here, we investigated NIV toxicity on mouse oocyte quality. Transcriptome analysis results showed that NIV exposure altered the expression of multiple genes involved in spindle formation and organelle function in mouse oocytes, indicating its toxicity on mouse oocyte maturation. Further analysis indicated that NIV exposure disrupted spindle structure and chromosome alignment, possibly through tubulin acetylation. NIV exposure induced aberrant mitochondria distribution and reduced mitochondria number, mitochondria membrane potential (MMP), and ATP levels. In addition, NIV caused the abnormal distribution of the Golgi apparatus and altered the expression of the vesicle trafficking protein Rab11. ER distribution was also disturbed under NIV exposure, indicating the effects of NIV on protein modification and transport in oocytes. Thus, our results demonstrated that NIV exposure affected spindle structure and organelles function in mouse oocytes.

Exposure to nivalenol declines mouse oocyte quality via inducing oxidative stress-related apoptosis and DNA damage†.

Mammalian oocyte quality is critical for fertilization and early embryo development. The type B trichothecene nivalenol (NIV) is a mycotoxin produced by Fusarium oxysporum, and it is commonly found with deoxynivalenol in contaminated food or feed. NIV has been shown to affect the immune system and female reproductive system, cause emesis and growth retardation. Here, we investigated the toxicity of NIV on mouse oocyte quality, as well as the protective effects of melatonin on the NIV-exposed oocytes. We found NIV exposure caused meiotic arrest and further induced the failure of polar body extrusion in mouse oocytes. Transcriptome analysis data showed that NIV exposure altered the expression of multiple pathway-related genes in oocytes, indicating its wide toxicity on oocyte maturation. Based on the RNA-seq data, we showed that NIV exposure induced oxidative stress and caused DNA damage in oocytes. Besides, autophagy, and early apoptosis were also found in NIV-exposed oocytes. Treatment with melatonin significantly ameliorated these defects through its effects on ROS level. Thus, our results demonstrated that exposure to NIV affected oocyte quality and melatonin treatment could reduce the defects caused by NIV in mouse oocytes.

Melatonin reverses mitochondria dysfunction and oxidative stress-induced apoptosis of Sudan I-exposed mouse oocytes.

Sudan I is one of the industry dyes and widely used in cosmetics, wax agent, solvent and textile. Sudan I has multiple toxicity such as carcinogenicity, mutagenicity, genotoxicity and oxidative damage. However, Sudan I has been illegally used as colorant in food products, triggering worldwide attention about food safety. Nevertheless, the toxicity of Sudan I on reproduction, particularly on oocyte maturation is still unclear. In the present study, using mouse in vivo models, we report the toxicity effects of Sudan I on mouse oocyte. The results reflect that Sudan I exposure disrupts spindle organization and chromosomes alignment as well as cortical actin distribution, thus leading to the failure of polar body extrusion. Based on the transcriptome results, it is found that the exposure of Sudan I leads to the change in expression of 764 genes. Moreover, it's further reflected that the damaging effects of Sudan I are mediated by the destruction of mitochondrial functions, which induces the accumulated ROS to stimulate oxidative stress-induced apoptosis. As an endogenous hormone, melatonin within the ovarian follicle plays function on improving oocyte quality and female reproduction by efficiently suppressing oxidative stress. Moreover, melatonin supplementation also improves oocyte quality and increases fertilization rate during in vitro culture. Consistent with these, we find that in vivo supplementation of melatonin efficaciously suppresses mitochondrial dysfunction and the accompanying apoptosis, thus reverses oocyte meiotic deteriorations. Collectively, our results prove the reproduction toxicity of Sudan I for the exposure of Sudan I reduces the oocyte quality, and demonstrate the protective effects of melatonin against Sudan I-induced meiotic deteriorations.

Evaluation of glymphatic system activity by diffusion tensor image analysis along the perivascular space in presbycusis.

PURPOSE: Previous studies have suggested that presbycusis (age-related hearing loss) is accompanied with cognitive decline and dementia. However, the neural mechanism underlying the cognitive decline in presbycusis remains unclear. This study aimed to evaluate the glymphatic system function in presbycusis patients compared to healthy controls using diffusion tensor imaging (DTI) with the perivascular space (DTI-ALPS) method. METHODS: DTI scans were obtained from 30 presbycusis patients with cognitive decline (PCD), 30 presbycusis patients with no cognitive decline (PNCD) and 40 age-, gender-, and education-matched healthy controls (HCs). The DTI-ALPS index was calculated for each group. We evaluated the differences in the DTI-ALPS index among PCD, PNCD and HCs. In addition, we conducted a correlation analysis between the DTI-ALPS index and cognitive performance. RESULTS: There were significant differences of the DTI-ALPS index among three groups. Post-hoc analysis suggested that the DTI-ALPS index in PCD was significantly lower patients in relative to PNCD and HCs (1.49147 vs. 1.57441 vs. 1.62020, p < 0.001). After correcting for age, gender, and education, the DTI-ALPS index is positively correlated with the MoCA scores (rho = 0.426, p = 0.026). CONCLUSION: Presbycusis patients with cognitive impairment exhibited decreased glymphatic activity than those without cognitive impairment and HCs. The DTI-ALPS index may provide useful disease progression or treatment biomarkers for patients with presbycusis as an indicator of modulation of glymphatic activity.

Loss of AMPK activity induces organelle dysfunction and oxidative stress during oocyte aging.

BACKGROUND: Oocyte quality is critical for the mammalian reproduction due to its necessity on fertilization and early development. During aging, the declined oocytes showing with organelle dysfunction and oxidative stress lead to infertility. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase which is important for energy homeostasis for metabolism. Little is known about the potential relationship between AMPK with oocyte aging. RESULTS: In present study we reported that AMPK was related with low quality of oocytes under post ovulatory aging and the potential mechanism. We showed the altered AMPK level during aging and inhibition of AMPK activity induced mouse oocyte maturation defect. Further analysis indicated that similar with its upstream regulator PKD1, AMPK could reduce ROS level to avoid oxidative stress in oocytes, and this might be due to its regulation on mitochondria function, since loss of AMPK activity induced abnormal distribution, reduced ATP production and mtDNA copy number of mitochondria. Besides, we also found that the ER and Golgi apparatus distribution was aberrant after AMPK inhibition, and enhanced lysosome function was also observed. CONCLUSIONS: Taken together, these data indicated that AMPK is important for the organelle function to reduce oxidative stress during oocyte meiotic maturation.

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.

Neurovascular coupling dysfunction associated with cognitive impairment in presbycusis.

The neuropathological mechanism underlying presbycusis remains unclear. This study aimed to illustrate the mechanism of neurovascular coupling associated with cognitive impairment in patients with presbycusis. We assessed the coupling of cerebral blood perfusion with spontaneous neuronal activity by calculating the correlation coefficients between cerebral blood flow and blood oxygen level-dependent-derived quantitative maps (amplitude of low-frequency fluctuation, fractional amplitude of low-frequency fluctuation, regional homogeneity, degree centrality). Four neurovascular coupling metrics (cerebral blood flow-amplitude of low-frequency fluctuation, cerebral blood flow-fractional amplitude of low-frequency fluctuation, cerebral blood flow-regional homogeneity and cerebral blood flow-degree centrality) were compared at the global and regional levels between the presbycusis group and the healthy control group, and the intrinsic association between the altered neurovascular coupling metrics and the neuropsychological scale was further analysed in the presbycusis group. At the global level, neurovascular coupling was significantly lower in the presbycusis group than in the control group and partially related to cognitive level. At the regional level, neurovascular biomarkers were significantly elevated in three brain regions and significantly decreased in one brain region, all of which involved the Papez circuit. Regional neurovascular coupling provides more information than global neurovascular coupling, and neurovascular coupling dysfunction within the Papez circuit has been shown to reveal the causes of poor cognitive and emotional responses in age-related hearing loss patients.

Zearalenone exposure impairs organelle function during porcine oocyte meiotic maturation.

Zearalenone (ZEN) is one of the secondary metabolites of Fusarium and is regarded as a common contaminant of foodstuffs especially corn products. ZEN is considered to be cytotoxic, tissue toxic, genotoxic and reproductive toxic, which acts as a serious threat for humans and animals. In this study, we investigated the effects of ZEN on organelle function during porcine oocyte meiotic maturation. Our results showed that the expansion of cumulus granulosa cells and the extrusion of oocyte polar body were disturbed after ZEN exposure. Besides the aberrant mitochondrial distribution and impaired mitochondrial membrane potential after ZEN treatment during porcine oocyte maturation. We also found the fluorescence intensity of ER was decreased, and ZEN exposure altered ER stress level, showing with the reduced expression of GRP78. We also found that the spindle cortex distribution of Golgi apparatus was disrupted in ZEN-exposed oocytes, which was confirmed by the decreased level of GM130, moreover, our data also showed that Rab11-based vesical transport was disturbed, indicating the Golgi apparatus function was disrupted. Besides, the fluorescence intensity of lysosome was significantly increased, indicating the protein degradation and the potential autophagy occurrence after ZEN treatment. Thus, our results demonstrated that exposure to ZEN affected porcine oocyte meiotic maturation through its wide effects on organelle function for protein synthesis, transport and degradation.

Glyphosate exposure deteriorates oocyte meiotic maturation via induction of organelle dysfunctions in pigs.

BACKGROUND: Recently, defects in mammalian oocytes maturation induced by environmental pollution results in the decreasing animal reproduction. Animal exposed to glyphosate is largely unavoidable because glyphosate is one of the most widely used herbicide worldwide due to its high-efficiency and broad-spectrum effects, which causes glyphosate an environmental contaminant found in soil, water and food. During the last few years, the growing and wider use of glyphosate has raised great concerns about its effects of reproductive toxicity. In this study, using porcine models, we investigated effects of glyphosate on organelle functions during oocyte meiosis. RESULTS: The results showed glyphosate exposure disrupted porcine oocyte maturation. Expression levels of cumulus expansion-related genes were interfered, further indicating the meiotic defects. The damaging effects were mediated by destruction of mitochondrial distribution and functions, which induced ROS accumulation and oxidative stress, also indicated by the decreased mRNA expression of related antioxidant enzyme genes. We also found an interference of endoplasmic reticulum (ER) distribution, disturbance of Ca2+ homeostasis, as well as fluctuation of ER stress, showing with the reduced ER stress-related mRNA or protein expression, which could indicate the dysfunction of ER for protein processing and signal transduction in glyphosate-exposed oocytes. Moreover, glyphosate exposure induced the disruption of lysosome function for autophagy, showing with the decrease of LAMP2 expression and autophagy-related genes mRNA expression. Additionally, our data showed the distribution of Golgi apparatus and the functions of ribosome were disturbed after glyphosate exposure, which might affect protein synthesis and transport. CONCLUSIONS: Collectively, our study showed that exposed to glyphosate could affect animal reproduction by compromising the quality of oocytes through its wide toxic effects on organelle functions.

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.

Disrupted Topological Organization of Resting-State Functional Brain Networks in Age-Related Hearing Loss.

Purpose: Age-related hearing loss (ARHL), associated with the function of speech perception decreases characterized by bilateral sensorineural hearing loss at high frequencies, has become an increasingly critical public health problem. This study aimed to investigate the topological features of the brain functional network and structural dysfunction of the central nervous system in ARHL using graph theory. Methods: Forty-six patients with ARHL and forty-five age, sex, and education-matched healthy controls were recruited to undergo a resting-state functional magnetic resonance imaging (fMRI) scan in this study. Graph theory was applied to analyze the topological properties of the functional connectomes by studying the local and global organization of neural networks. Results: Compared with healthy controls, the patient group showed increased local efficiency (Eloc) and clustering coefficient (Cp) of the small-world network. Besides, the degree centrality (Dc) and nodal efficiency (Ne) values of the left inferior occipital gyrus (IOG) in the patient group showed a decrease in contrast with the healthy control group. In addition, the intra-modular interaction of the occipital lobe module and the inter-modular interaction of the parietal occipital module decreased in the patient group, which was positively correlated with Dc and Ne. The intra-modular interaction of the occipital lobe module decreased in the patient group, which was negatively correlated with the Eloc. Conclusion: Based on fMRI and graph theory, we indicate the aberrant small-world network topology in ARHL and dysfunctional interaction of the occipital lobe and parietal lobe, emphasizing the importance of dysfunctional left IOG. These results suggest that early diagnosis and treatment of patients with ARHL is necessary, which can avoid the transformation of brain topology and decreased brain function.

Acrylamide Exposure Destroys the Distribution and Functions of Organelles in Mouse Oocytes.

Acrylamide (ACR) is a common industrial ingredient which is also found in foods that are cooked at high temperatures. ACR has been shown to have multiple toxicities including reproductive toxicity. Previous studies reported that ACR caused oocyte maturation defects through the induction of apoptosis and oxidative stress. In the present study, we showed that ACR exposure affected oocyte organelle functions, which might be the reason for oocyte toxicity. We found that exposure to 5 mM ACR reduced oocyte maturation. ACR caused abnormal mitochondrial distribution away from spindle periphery and reduced mitochondrial membrane potential. Further analysis showed that ACR exposure reduced the fluorescence intensity of Rps3 and abnormal distribution of the endoplasmic reticulum, indicating that ACR affected protein synthesis and modification in mouse oocytes. We found the negative effects of ACR on the distribution of the Golgi apparatus; in addition, fluorescence intensity of vesicle transporter Rab8A decreased, suggesting the decrease in protein transport capacity of oocytes. Furthermore, the simultaneous increase in lysosomes and LAMP2 fluorescence intensity was also observed, suggesting that ACR affected protein degradation in oocytes. In conclusion, our results indicated that ACR exposure disrupted the distribution and functions of organelles, which further affected oocyte developmental competence in mice.

Causal interactions with an insular-cortical network in mild traumatic brain injury.

PURPOSE: This study aimed to investigate the insula-based directional effective connectivity in mild traumatic brain injury (mTBI) using resting-state functional magnetic resonance imaging (fMRI) and to explore its relationship with cognitive performance. METHODS: Sixty mTBI patients and 55 age-, gender- and years of education- matched healthy controls (HC) were recruited in this study. Using granger causality analysis (GCA), we selected bilateral insula as two individual seed regions to compare the difference of directional effective connectivity of insula between mTBI group and HC group, and analyze its relationship with cognitive performance. RESULTS: Compared with HC, acute mTBI group showed decreased outflows from the left insula to the left middle frontal gyrus (MFG) and right rolandic operculum (Rol), increased inflow from the left supplementary motor area (SMA) to the left insula, decreased outflows from the right insula to the left superior frontal gyrus (SFG), as well as increased outflows from the right insula to the left superior temporal gyrus (STG). No significantly different inflows to the right insula from other regions were found. Correlation analyses revealed that the abnormal connectivity between insula and MFG, as well as insula and STG were associated with the cognitive function score. CONCLUSIONS: Our data demonstrated abnormalities in the effective connection pathways of insula in acute mTBI patients, while abnormal effective connectivity significantly correlated with cognitive function score. These findings may shed light on the pathophysiological mechanisms of cognitive impairment after mTBI.

Abnormal Static and Dynamic Functional Network Connectivity in Patients With Presbycusis.

Aim: This study aimed to investigate abnormal static and dynamic functional network connectivity (FNC) and its association with cognitive function in patients with presbycusis. Methods: In total, 60 patients with presbycusis and 60 age-, sex-, and education-matched healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) and cognitive assessments. Group independent component analysis (ICA) was carried out on the rs-fMRI data, and eight resting-state networks (RSNs) were identified. Static and dynamic FNCs (sFNC and dFNC) were then constructed to evaluate differences in RSN connectivity between the patients with presbycusis and the HCs. Furthermore, the correlations between these differences and cognitive scores were analyzed. Results: Patients with presbycusis had differences in sFNC compared with HCs, mainly reflected in decreased sFNC in the default mode network (DMN)-left frontoparietal network (LFPN) and attention network (AN)-cerebellum network (CN) pairs, but they had increased sFNC in the auditory network (AUN) between DMN domains. The decreased sFNC in the DMN-LFPN pair was negatively correlated with their TMT-B score (r = -0.441, p = 0.002). Patients with presbycusis exhibited aberrant dFNCs in State 2 and decreased dFNCs between the CN and AN and the visual network (VN). Moreover, the presbycusis group had a shorter mean dwell time (MDT) and fraction time (FT) in State 3 (p = 0.0027; p = 0.0031, respectively). Conclusion: This study highlighted differences in static and dynamic functional connectivity in patients with presbycusis and suggested that FNC may serve as an important biomarker of cognitive performance since abnormal alterations can better track cognitive impairment in presbycusis.