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This study aimed to investigate the molecular mechanism under the pathophysiology of subarachnoid hemorrhage (SAH) and identify the potential biomarkers for predicting the risk of SAH. Differentially expressed mRNAs (DEGs), microRNAs, and lncRNAs were screened. Protein–protein interaction (PPI), drug–gene, and competing endogenous RNA (ceRNA) networks were constructed to determine candidate RNAs. The optimized RNAs signature was established using least absolute shrinkage and selection operator and recursive feature elimination algorithms. A total of 124 SAH-related DEGs were identified, and were enriched in inflammatory response, TNF signaling pathway, and others. PPI network revealed 118 hub genes such as TNF, MMP9, and TLR4. Drug–gene network revealed that chrysin targeted more genes, such as TNF and MMP9. JMJD1C-AS-hsa-miR-204-HDAC4/SIRT1 and LINC01144-hsa-miR-128-ADRB2/TGFBR3 regulatory axes were found from ceRNA network. From these networks, 125 candidate RNAs were obtained. Of which, an optimal 38 RNAs signatures (2 lncRNAs, 1 miRNA, and 35 genes) were identified to construct a Support Vector Machine classifier. The predictive value of 38 biomarkers had an AUC of 0.990. Similar predictive performance was found in external validation dataset (AUC of 0.845). Our findings provided the potential for 38 RNAs to serve as biomarkers for predicting the risk of SAH. However, their application values should be further validated in clinical.

Background: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. Materials and Methods: Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. Results: Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. Conclusions: The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients. [ABSTRACT FROM AUTHOR]

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data—derived from diffusion MRI tractography from each subject—into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and interindividual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain. [ABSTRACT FROM AUTHOR]

Objective: Leveraging an integrative multimodal MRI paradigm to elaborate on the hippocampus-derived structural and functional changes in children and adolescents with juvenile idiopathic arthritis (JIA) and to explore potential correlations within the "joint-inflammation-brain" axis during the period of central neural system (CNS) development. Methods: Twenty-one patients with JIA all completed the multimodal MRI scanning, laboratory tests, and neuropsychological assessments; meanwhile, 23 matched controls were recruited. We then harnessed the spherical harmonics with a point distribution model (SPHARM-PDM) and the ROI-to-voxel functional connectivity (FC) to measure the hippocampal shape and hippocampo-cortical FC patterns. Correlation analysis was performed to explore the potential links in neuroimaging features with disease-related indices. Results: Compared to controls, JIA patients only presented an atrophic tendency in the posterior part of the bilateral hippocampus. The hippocampo-cortical FC revealed the between-group divergences mainly located at the pain matrix, striatum, and temporal lobe. Remarkably, the enhanced FC between the right hippocampus and postcentral cortex is positively correlated with the disability index, while the weakened FC of right anterior hippocampus with right insula and that of left posterior hippocampus with left superior temporal gyrus was inversely related to the erythrocyte sedimentation rate and anxiety status, separately. Conclusion: As with macroscopic damages, the altered functional-connectome patterns of the hippocampus in JIA patients might be more sensitive to detect the early neuropathological changes. Moreover, the functional disturbances were demonstrated associated with the physical disability, inflammation, and emotional status. These findings may enlighten us on the underlying neuropathological mechanism of CNS comorbidities in JIA. [ABSTRACT FROM AUTHOR]

Background: Losing one's only child is a major traumatic life event that may lead to post-traumatic stress disorder (PTSD); however, the underlying mechanisms of its psychological consequences remain poorly understood. Here, we investigated subregional hippocampal functional connectivity (FC) networks based on resting-state functional magnetic resonance imaging and the deoxyribonucleic acid methylation of the human glucocorticoid receptor gene (NR3C1) in adults who had lost their only child. Methods: A total of 144 Han Chinese adults who had lost their only child (51 adults with PTSD and 93 non-PTSD adults [trauma-exposed controls]) and 50 controls without trauma exposure were included in this fMRI study (age: 40–67 years). FCs between hippocampal subdivisions (four regions in each hemisphere: cornu ammonis1 [CA1], CA2, CA3, and dentate gyrus [DG]) and methylation levels of the NR3C1 gene were compared among the three groups. Results: Trauma-exposed adults, regardless of PTSD diagnosis, had weaker positive FC between the left hippocampal CA1, left DG, and the posterior cingulate cortex, and weaker negative FC between the right CA1, right DG, and several frontal gyri, relative to healthy controls. Compared to non-PTSD adults, PTSD adults showed decreased negative FC between the right CA1 region and the right middle/inferior frontal gyri (MFG/IFG), and decreased negative FC between the right DG and the right superior frontal gyrus and left MFG. Both trauma-exposed groups showed lower methylation levels of the NR3C1 gene. Conclusions: Adults who had lost their only child may experience disrupted hippocampal network connectivity and NR3C1 methylation status, regardless of whether they have developed PTSD. [ABSTRACT FROM AUTHOR]

Background : Losing one's only child may lead to post-traumatic stress disorder (PTSD), of which re-experiencing is the core symptom. However, neuroimaging studies of sex differences in re-experiencing in the context of the trauma of losing one's only child and PTSD are scarce; comparisons of the functional networks from the hippocampal subfields to the thalamus might clarify the neural basis. Methods : Thirty couples without any psychiatric disorder who lost their only child (non-PTSD group), 55 patients with PTSD, and 50 normal controls underwent resting-state functional magnetic resonance imaging. The functional connectivity (FC) from the hippocampal subregions to the thalamus and the correlations of FC with re-experiencing symptoms were analyzed within and between the sexes. Results : Compared with husbands without PTSD, wives without PTSD had higher re-experiencing symptoms and weaker FC between the right hippocampal cornu ammonis 3 (RCA3) and the right thalamus (RT; RCA3-RT). Moreover, only the correlation between the RCA3-RT FC and re-experiencing in wives without PTSD was significant. Among the three groups, only the RCA3-RT FC in female subjects was markedly different. Additionally, the RCA3-RT FC in wives without PTSD was remarkably lower relative to female patients with PTSD. Conclusion : Wives without PTSD who lost their only child had worse re-experiencing symptoms relative to their husbands, which was associated with the FC alteration between the hippocampal subregions and the thalamus. Importantly, the low level of the RCA3-RT FC may play a potentially protective role against the development of PTSD in wives who have lost their only child. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to find out the distributed functional connectome of white matter in patients with functional dyspepsia (FD). Methods: 20 patients with FD and 24 age- and gender-matched healthy controls were included into the study. The functional connectome of white matter and graph theory were used to these participants. Two-sample t -test was used for the detection the abnormal graph properties in FD. Pearson correlation was used for the relationship between properties and the clinical and neuropshychological information. Results: Patients with FD and healthy controls showed small-world properties in functional connectome of white matter. Compared with healthy controls, the FD group showed decreased global properties (Cp, S, Eglobal, and Elocal). Four pairs of fiber bundles that are connected to the frontal lobe, insula, and thalamus were affected in the FD group. Duration and Pittsburgh Sleep Quality Index positively correlated with the betweenness centrality of white matter regions of interest. Conclusion: FD patients turned to a non-optimized functional organization of WM brain network. Frontal lobe, insula, and thalamus were key regions in brain information exchange of FD. It provided some novel imaging evidences for the mechanism of FD. [ABSTRACT FROM AUTHOR]

Generalized tonic–clonic seizures (GTCS) are the severest and most remarkable clinical expressions of human epilepsy. Cortical, subcortical, and cerebellar structures, organized with different network patterns, underlying the pathophysiological substrates of genetic associated epilepsy with GTCS (GE‐GTCS) and focal epilepsy associated with focal to bilateral tonic–clonic seizure (FE‐FBTS). Structural covariance analysis can delineate the features of epilepsy network related with long‐term effects from seizure. Morphometric MRI data of 111 patients with GE‐GTCS, 111 patients with FE‐FBTS and 111 healthy controls were studied. Cortico‐striato‐thalao‐cerebellar networks of structural covariance within the gray matter were constructed using a Winner‐take‐all strategy with five cortical parcellations. Comparisons of structural covariance networks were conducted using permutation tests, and module effects of disease duration on networks were conducted using GLM model. Both patient groups showed increased connectivity of structural covariance relative to controls, mainly within the striatum and thalamus, and mostly correlated with the frontal, motor, and somatosensory cortices. Connectivity changes increased as a function of epilepsy durations. FE‐FBTS showed more intensive and extensive gray matter changes with volumetric loss and connectivity increment than GE‐GTCS. Our findings implicated cortico‐striato‐thalamo‐cerebellar network changes at a large temporal scale in GTCS, with FE‐FBTS showing more severe network disruption. The study contributed novel imaging evidence for understanding the different epilepsy syndromes associated with generalized seizures. [ABSTRACT FROM AUTHOR]

Background: Functional dyspepsia (FD) subtypes may differ in terms of pathophysiology, but the underlying mechanisms remain poorly understood.Purpose: To explore spontaneous brain activity in two main FD subtypes, namely epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), using the amplitude of low-frequency fluctuation (ALFF).Material and Methods: Thirty-one FD patients (18 EPS and 13 PDS) and 22 matched healthy controls (HC) underwent resting-state functional MRI scanning. Spontaneous brain activity was evaluated by measuring the ALFF and then compared among the EPS, PDS, and HC groups with ANOVA test. Pearson correlation analysis was performed between the ALFF values and clinical indices.Results: Compared to healthy controls, both EPS and PDS patients had increased ALFF in the bilateral precentral/postcentral gyri, insula, and thalami. Furthermore, only the EPS patients displayed increased ALFF in the right middle and inferior frontal gyri, and only the PDS patients showed increased ALFF in the left posterior cingulate cortex (PCC). The ALFF values in the left thalamus were positively correlated with the sleep disturbance in EPS patients, and the ALFF values in the right precentral/postcentral gyri showed a positive correlation with the symptom score in PDS patients.Conclusion: EPS and PDS had similarities of higher spontaneous brain activity in the primary motor/sensory areas and homeostatic-afferent network regions, and differences in the prefrontal region and PCC, providing evidence to suggest the similarity and diversity of pathophysiology in FD subtypes. [ABSTRACT FROM AUTHOR]

Objective: Temporal lobe epilepsy (TLE) is the most common drug‐resistant epilepsy in adults. Although it is commonly related to hippocampal pathology, increasing evidence suggests structural changes beyond the mesiotemporal lobe. Functional anomalies and their link to underlying structural alterations, however, remain incompletely understood. Methods: We studied 30 drug‐resistant TLE patients and 57 healthy controls using multimodal magnetic resonance imaging (MRI) analyses. All patients had histologically verified hippocampal sclerosis and underwent postoperative imaging to outline the extent of their surgical resection. Our analysis leveraged a novel resting‐state functional MRI framework that parameterizes functional connectivity distance, consolidating topological and physical properties of macroscale brain networks. Functional findings were integrated with morphological and microstructural metrics, and utility for surgical outcome prediction was assessed using machine learning techniques. Results: Compared to controls, TLE patients showed connectivity distance reductions in temporoinsular and prefrontal networks, indicating topological segregation of functional networks. Testing for morphological and microstructural associations, we observed that functional connectivity contractions occurred independently from TLE‐related cortical atrophy but were mediated by microstructural changes in the underlying white matter. Following our imaging study, all patients underwent an anterior temporal lobectomy as a treatment of their seizures, and postsurgical seizure outcome was determined at a follow‐up at least 1 year after surgery. Using a regularized supervised machine learning paradigm with fivefold cross‐validation, we demonstrated that patient‐specific functional anomalies predicted postsurgical seizure outcome with 76 ± 4% accuracy, outperforming classifiers operating on clinical and structural imaging features. Significance: Our findings suggest connectivity distance contractions as a macroscale substrate of TLE. Functional topological isolation may represent a microstructurally mediated network mechanism that tilts the balance toward epileptogenesis in affected networks and that may assist in patient‐specific surgical prognostication. [ABSTRACT FROM AUTHOR]

Recent fMRI studies have demonstrated that resting-state functional connectivity (FC) is of nonstationarity. Temporal variability of FC reflects the dynamic nature of brain activity. Exploring temporal variability of FC offers a new approach to investigate reorganization and integration of brain networks after stroke. Here, we examined longitudinal alterations of FC temporal variability in brain networks after stroke. Nineteen stroke patients underwent resting fMRI scans across the acute stage (within-one-week after stroke), subacute stage (within-two-weeks after stroke), and early chronic stage (3-4 months after stroke). Nineteen age- and sex-matched healthy individuals were enrolled. Compared with the controls, stroke patients exhibited reduced regional temporal variability during the acute stages, which was recovered at the following two stages. Compared with the acute stage, the subacute stage exhibited increased temporal variability in the primary motor, auditory, and visual cortices. Across the three stages, the temporal variability in the ipsilesional precentral gyrus (PreCG) was increased first and then reduced. Increased temporal variability in the ipsilesional PreCG from the acute stage to the subacute stage was correlated with motor recovery from the acute stage to the early chronic stage. Our results demonstrated that temporal variability of brain network might be a potential tool for evaluating and predicting motor recovery after stroke. [ABSTRACT FROM AUTHOR]

Loss of cognitive function with age is devastating. EGL-30/GNAQ and G αq signaling pathways are highly conserved between C. elegans and mammals, and murine Gnaq is enriched in hippocampal neurons and declines with age. We found that activation of EGL-30 in aged worms triples memory span, and GNAQ gain of function significantly improved memory in aged mice: GNAQ(gf) in hippocampal neurons of 24-month-old mice (equivalent to 70- to 80-year-old humans) rescued age-related impairments in well-being and memory. Single-nucleus RNA sequencing revealed increased expression of genes regulating synaptic function, axon guidance, and memory in GNAQ-treated mice, and worm orthologs of these genes were required for long-term memory extension in worms. These experiments demonstrate that C. elegans is a powerful model to identify mammalian regulators of memory, leading to the identification of a pathway that improves memory in extremely old mice. To our knowledge, this is the oldest age at which an intervention has improved age-related cognitive decline. [Display omitted] • EGL-30/GNAQ and G αq signaling is highly conserved between worms and mammals • GNAQ gain of function in the hippocampus extends memory in 2-year-old mice • GNAQ gain of function also upregulates synaptic function, axon guidance, and memory genes • Worm orthologs of these genes are required for extended long-term memory Stevenson et al. find that activation of GNAQ and G αq signaling extends long-term memory in 2-year-old mice. GNAQ gain of function upregulates genes involved in plasticity, and worm orthologs were required for C. elegans memory. Invertebrates are a powerful model for identifying pathways that can improve memory in extremely old mammals. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder resulting from a dysregulation of the brain-gut axis. However, its exact neural substrate still remains unclear. This study investigated the changes of intrinsic whole brain functional connectivity pattern in IBS using functional connectivity density (FCD). We acquired resting-state functional magnetic resonance imaging (rs-fMRI) data from thirty-two IBS patients and thirty-two healthy controls. Functional connectivity density, a data-driven algorithm, was used to compute the long-range and short-range FCD values for each voxel in the brain of each subject, implying the amount of distant and local functional connections of cortical hubs. The FCD maps were compared between IBS patients and healthy controls. Pearson correlations analysis was also performed between abnormal FCD values and clinical/psychometric scores in patients. Compared to healthy controls, IBS patients showed concurrently decreased long- and short-range FCD in bilateral anterior midcingulate cortices (aMCC) and inferior parietal lobules (IPL), and decreased long-range FCD in right anterior insula, and decreased short-range FCD in bilateral prefrontal cortices, subgenual anterior cingulate cortices and caudates. IBS patients also had concurrently increased long- and short-range FCD mainly in primary sensorimotor cortices, as well as increased long-range FCD in right supplementary motor area and increased short-range FCD in occipital lobe. In addition, some regions with altered FCD showed abnormal functional connectivity in brain regions involved in pain matrix of IBS patients. Furthermore, the abnormal FCD values in right anterior insula and left caudate showed significant correlation with severity of symptoms and disease duration of IBS patients respectively. In conclusion, patients with IBS have widely disrupted FCD, which decreased in brain regions involved in homeostatic afferent network, emotional arouse, and cognitive regulation, while increased in regions associated with sensorimotor modulation. And the observed functional connectivity alterations unveiled complicated working patterns of pain matrix in IBS patients. This study may provide us with new insight into the underlying brain network topology of IBS. [ABSTRACT FROM AUTHOR]