Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues
Ontology highlight
ABSTRACT:
SUBMITTER: Atherton E
PROVIDER: S-EPMC8595892 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control for contributions of brain volume. Task performance was positively correlated with strength of task-based functional connectivity (tFC) between brain regions of the frontoparietal working memory network. However, higher cortical iron concentration was associated with lower tFC within this frontoparietal network and with poorer working memory performance after controlling for both cerebral blood flow and brain volume. Our results suggest that high cortical iron concentration disrupts communication within frontoparietal networks supporting working memory and is associated with reduced working memory performance in older adults.
| S-EPMC7821351 | biostudies-literature
Project description:Recently, EEG recording techniques and source analysis have improved, making it feasible to tap into fast network dynamics. Yet, analyzing whole-cortex EEG signals in source space is not standard, partly because EEG suffers from volume conduction: Functional connectivity (FC) reflecting genuine functional relationships is impossible to disentangle from spurious FC introduced by volume conduction. Here, we investigate the relationship between white matter structural connectivity (SC) and large-scale network structure encoded in EEG-FC. We start by confirming that FC (power envelope correlations) is predicted by SC beyond the impact of Euclidean distance, in line with the assumption that SC mediates genuine FC. We then use information from white matter structural connectivity in order to smooth the EEG signal in the space spanned by graphs derived from SC. Thereby, FC between nearby, structurally connected brain regions increases while FC between nonconnected regions remains unchanged, resulting in an increase in genuine, SC-mediated FC. We analyze the induced changes in FC, assessing the resemblance between EEG-FC and volume-conduction- free fMRI-FC, and find that smoothing increases resemblance in terms of overall correlation and community structure. This result suggests that our method boosts genuine FC, an outcome that is of interest for many EEG network neuroscience questions.
| S-EPMC7462431 | biostudies-literature
Project description:As their illness progresses, patients with the semantic variant of Primary Progressive Aphasia (svPPA) frequently exhibit peculiar behaviors indicative of altered visual attention or an increased interest in artistic endeavors. In the present study, we examined changes within and between large-scale functional brain networks that may explain this altered visual behavior. We first examined the connectivity of the visual association network, the dorsal attention network, and the default mode network in healthy young adults (n = 89) to understand the typical architecture of these networks in the healthy brain. We then compared the large-scale functional connectivity of these networks in a group of svPPA patients (n = 12) to a group of age-matched cognitively normal controls (n = 30). Our results showed that the between-network connectivity of the dorsal attention and visual association networks was elevated in svPPA patients relative to controls. We further showed that this heightened between-network connectivity was associated with a decrease in the within-network connectivity of the default mode network, possibly due to progressive degeneration of the anterior temporal lobes in svPPA. These results suggest that focal neurodegeneration can lead to the reorganization of large-scale cognitive networks beyond the primarily affected network(s), possibly contributing to cognitive or behavioral changes that are commonly present as part of the clinical phenotype of svPPA.
| S-EPMC7708956 | biostudies-literature
Project description:Autism spectrum disorders (ASD) represent a complex group of neurodevelopmental conditions characterized by deficits in communication and social behaviors. We examined the functional connectivity (FC) of the default mode network (DMN) and its relation to multimodal morphometry to investigate superregional, system-level alterations in a group of 22 adolescents and young adults with high-functioning autism compared to age-, and intelligence quotient-matched 29 healthy controls. The main findings were that ASD patients had gray matter (GM) reduction, decreased cortical thickness and larger cortical surface areas in several brain regions, including the cingulate, temporal lobes, and amygdala, as well as increased gyrification in regions associated with encoding visual memories and areas of the sensorimotor component of the DMN, more pronounced in the left hemisphere. Moreover, patients with ASD had decreased connectivity between the posterior cingulate cortex, and areas of the executive control component of the DMN and increased FC between the anteromedial prefrontal cortex and areas of the sensorimotor component of the DMN. Reduced cortical thickness in the right inferior frontal lobe correlated with higher social impairment according to the scores of the Autism Diagnostic Interview-Revised (ADI-R). Reduced cortical thickness in left frontal regions, as well as an increased cortical thickness in the right temporal pole and posterior cingulate, were associated with worse scores on the communication domain of the ADI-R. We found no association between scores on the restrictive and repetitive behaviors domain of ADI-R with structural measures or FC. The combination of these structural and connectivity abnormalities may help to explain some of the core behaviors in high-functioning ASD and need to be investigated further.
| S-EPMC6048242 | biostudies-literature
Project description:The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow. Here we extend functional connectivity analysis from hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in glutamatergic neurons were imaged transcranially in both anesthetized (using ketamine/xylazine) and awake states. Sequential LED illumination (λ = 454, 523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity network maps were constructed for infraslow (0.009-0.08Hz), intermediate (0.08-0.4Hz), and high (0.4-4.0Hz) frequency bands. At infraslow and intermediate frequencies, commonly used in BOLD fMRI and fcOIS studies of functional connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2 functional connectivity structures were in high agreement, both qualitatively and also quantitatively through a measure of spatial similarity. The spontaneous dynamics of both contrasts had the highest correlation when the GCaMP6 signal was delayed with a ~0.6-1.5s temporal offset. Within the higher-frequency delta band, sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we evaluate the speed with which the connectivity analysis stabilized and found that the functional connectivity maps captured putative network structure within time window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity maps at 0.4-4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke.
| S-EPMC5648115 | biostudies-literature
Project description:Neuroinflammation has been recognized as a major cause for neurocognitive diseases. Although the hippocampus has been considered an important region for cognitive dysfunction, the influence of hippocampal neuroinflammation on brain functional connectivity (FC) has been rarely studied. In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment. Systemic and hippocampal inflammation were determined using ELISA, while astrocyte responses during hippocampal neuroinflammation were determined by interleukin 1 beta (IL-1β)/tumor necrosis factor alpha (TNFα) double staining immunofluorescence. Oxidative stress was determined by reactive oxidative species (ROS), electron transport chain (ETC) complex, and superoxide dismutase (SOD). Short- (<7 days) and long-term (>30 days) learning and spatial working memory were tested by the Morris water maze (MWM). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyze the brain FC by placing seed voxels on the left and right hippocampus. Compared with the vehicle group, rats with the LPS exposure showed an impaired MWM performance, higher oxidative stress, higher levels of inflammatory cytokines, and astrocyte activation in the hippocampus. The neuroimaging examination showed decreased FC on the right orbital cortex, right olfactory bulb, and left hippocampus on day 3, 7, and 31, respectively, after treatment. In contrast, rats with SS-31 treatment showed lower levels of inflammatory cytokines, less astrocyte activation in the hippocampus, and improved MWM performance. Neuroimaging examination showed increased FC on the left-parietal association cortex (L-PAC), left sensory cortex, and left motor cortex on day 7 with the right flocculonodular lobe on day 31 as compared with those without SS-31 treatment. Our study demonstrated that inhibiting neuroinflammation in the hippocampus not only reduces inflammatory responses in the hippocampus but also improves the brain FC in regions related to the hippocampus. Furthermore, early anti-inflammatory treatment with SS-31 has a long-lasting effect on reducing the impact of LPS-induced neuroinflammation.
| S-EPMC7956963 | biostudies-literature
Project description:Major depression is a prevalent disorder that imposes a significant burden on society, yet objective laboratory-style tests to assist in diagnosis are lacking. We employed network-based analyses of "resting state" functional neuroimaging data to ascertain group differences in the endogenous cortical activity between healthy and depressed subjects.We additionally sought to use machine learning techniques to explore the ability of these network-based measures of resting state activity to provide diagnostic information for depression. Resting state fMRI data were acquired from twenty two depressed outpatients and twenty two healthy subjects matched for age and gender. These data were anatomically parcellated and functional connectivity matrices were then derived using the linear correlations between the BOLD signal fluctuations of all pairs of cortical and subcortical regions.We characterised the hierarchical organization of these matrices using network-based matrics, with an emphasis on their mid-scale "modularity" arrangement. Whilst whole brain measures of organization did not differ between groups, a significant rearrangement of their community structure was observed. Furthermore we were able to classify individuals with a high level of accuracy using a support vector machine, primarily through the use of a modularity-based metric known as the participation index.In conclusion, the application of machine learning techniques to features of resting state fMRI network activity shows promising potential to assist in the diagnosis of major depression, now suggesting the need for validation in independent data sets.
| S-EPMC3423402 | biostudies-literature
Project description:Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.
| S-EPMC3221675 | biostudies-literature
Project description:BackgroundDepression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [(18)F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging.MethodsThe Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [(18)F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [(18)F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS.ResultsPatients with MS had an increased hippocampal [(18)F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [(18)F]PBR111 distribution volume ratio.ConclusionsOur results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of the role of inflammatory processes in the pathogenesis of depression more generally.
| S-EPMC4918731 | biostudies-literature
Project description:Fibromyalgia (FM) is a generalized chronic pain condition whose pathophysiology is poorly understood, and both basic and translational research are needed to advance the field. Here we used the Sluka model to test whether FM-like pain in mice would produce detectable brain modifications using resting-state (rs) functional Magnetic Resonance Imaging (fMRI). Mice received intramuscular acid saline treatment, images were acquired at 7 T 5 days post-treatment, and pain thresholds tested 3 weeks post-scanning. Data-driven Independent Component Analysis revealed significant reduction of functional connectivity (FC) across several component pairs, with major changes for the Retrosplenial cortex (RSP) central to the default mode network, and to a lesser extent the Periaqueductal gray (PAG), a key pain processing area. Seed-to-seed analysis focused on 14 pain-related areas showed strongest FC reduction for RSP with several cortical areas (somatosensory, prefrontal and insular), and for PAG with both cortical (somatosensory) and subcortical (habenula, thalamus, parabrachial nucleus) areas. RSP-PAG FC was also reduced, and this decreased FC tended to be positively correlated with pain levels at individual subject level. Finally, seed-voxelwise analysis focused on PAG confirmed seed-to-seed findings and, also detected reduced PAG FC with the anterior cingulate cortex, increasingly studied in aversive pain effects. In conclusion, FM-like pain triggers FC alterations in the mouse, which are detected by rs-fMRI and are reminiscent of some human findings. The study reveals the causal fingerprint of FM-like pain in rodents, and indicates that both RSP and PAG connectional patterns could be suitable biomarkers, with mechanistic and translational value, for further investigations.
| S-EPMC8272737 | biostudies-literature