Cortical Regions Research Articles

Exploring the spatial distribution of interstitial cells in kidney tissue

Introduction: Interstitial cells are crucial to the development of kidney structure and function, although the mechanism underlying their role in it remains unclear to date. Our previous study identified cell clusters in human fetal kidney tissue, and we further analyzed the interstitial cell cluster within this context. Methods: We extracted the barcoded cDNA from tissue samples and prepared spatial transcriptome libraries. Sequencing data was quality-checked, normalized, and clusters were identified using Seurat. Single-cell and spatial data were integrated using MIA and cell types were deconvoluted. DEGs in interstitial cells were identified and functionally annotated using DAVID. CellPhoneDB was used to predict ligand-receptor interactions between cell types. Results: The results of the present study revealed that this cluster of interstitial cells appeared to be scattered in the junction between the cortical and medullary regions. The subsequent KEGG pathway analysis revealed that the differentially expressed genes (DEGs) in this cluster of interstitial cells were involved in the WNT signaling pathway. The Gene Ontology (GO) analysis revealed that these DEGs were involved in multiple pathways associated with kidney development, with six of the genes (NKD2, TCF21, WNT5A, WNT4, MDK, and SFRP1) associated with kidney development exhibiting significant upregulation. Accordingly, it was inferred that these interstitial cells might be involved in regulating epithelial cell differentiation, ureteral bud development, and morphogenesis. The subsequent cell-cell communication analysis revealed that the cellular crosstalk was primarily regulated mainly by ligand-receptor pairs. Additionally, 17 genes reported to be associated with kidney disease were focused on, and these genes were found to be predominantly expressed in a single cell type. Conclusion: In summary, the present study revealed the characteristics of a previously identified cluster of interstitial cells in the kidney tissue, thereby providing fresh insights into the process of kidney development.

Structural Brain Characteristics of Chronic Schizophrenia Patients with Different Types of Functional Outcome

Background: studies allowing to explore the neurobiological characteristics of the long-term schizophrenic process are of high significance for both clinical practice and biological psychiatry. Objective: to examine morphometric brain characteristics in chronic schizophrenia patients with different types of functional outcomes. Patients and methods: morphometric MRI characteristics of the cerebral cortex and subcortical structures are analysed in 46 patients with schizophrenia with a long disease durations (20.5 ± 6.7 years), and in 35 mentally healthy subjects matched by sex and age. Results and discussion: the whole group of patients showed decreased gray matter thickness in some cerebral cortex regions. When outcome was assessed using clinical-psychopathologic, clinical-catamnestic, and clinical-epidemiologic methods, bilateral increases in pallidum and putamen volumes were found to be a presumptive marker of worse functional outcome and remission poor quality. At the same time, when outcome was assessed on the basis of the current psychometric measures of social functioning and clinical symptomatology, patients with an unfavorable outcome were characterized by decreased gray matter thickness in the two cingulate cortex regions compared to both healthy controls and patients with a good outcome. However, the absence of correlations with clinical scales and functioning doesn’t allow a conclusion on the specificity of this decrease as a marker of outcome. Conclusion: the results may only presume beforehand the existence of different neuroanatomical subtypes (biotypes) associated with different functional outcomes in patients with chronic schizophrenia.

An eccentricity gradient reversal across high-level visual cortex

Human visual cortex contains regions selectively involved in perceiving and recognizing ecologically important visual stimuli such as people and places. Located in the ventral temporal lobe, these regions are organized consistently relative to cortical folding, a phenomenon thought to be inherited from how centrally or peripherally these stimuli are viewed with the retina. While this eccentricity theory of visual cortex has been one of the best descriptions of its functional organization, whether or not it accurately describes visual processing in all category-selective regions is not yet clear. Through a combination of behavioral and functional MRI measurements in 27 participants (17 females), we demonstrate that a limb-selective region neighboring well-studied face-selective regions shows tuning for the visual periphery in a cortical region originally thought to be centrally-biased. We demonstrate that the spatial computations performed by the limb-selective region are consistent with visual experience, and in doing so, make the novel observation that there may in fact be two eccentricity gradients, forming an eccentricity reversal across high-level visual cortex. These data expand the current theory of cortical organization to provide a unifying principle that explains the broad functional features of many visual regions, showing that viewing experience interacts with innate wiring principles to drive the location of cortical specialization.Significance StatementWhat is the organizing principle of high-level visual cortex? Visual stimuli experienced extensively during childhood, like faces or scenes, give rise to specialized regions in visual cortex. These regions emerge in consistent locations across individuals, thought to result from the retinotopic input of earlier visual cortex. The field has quantified this input as a medial-lateral gradient of retinotopic eccentricity in ventrotemporal cortex that has not yet been mapped beyond the fusiform gyrus. By performing receptive field mapping in limb-selective cortex for the first time we uncover a u-shaped eccentricity gradient which reverses near the lateral Fusiform. These findings produce a parsimonious model of cortical organization incorporating previously uncharacterized regions, offering a new organizing principle of high-level vision.

Molecular signatures of cortical expansion in the human foetal brain

The third trimester of human gestation is characterised by rapid increases in brain volume and cortical surface area. Recent studies have revealed a remarkable molecular diversity across the prenatal cortex but little is known about how this diversity translates into the differential rates of cortical expansion observed during gestation. We present a digital resource, μBrain, to facilitate knowledge translation between molecular and anatomical descriptions of the prenatal brain. Using μBrain, we evaluate the molecular signatures of preferentially-expanded cortical regions, quantified in utero using magnetic resonance imaging. Our findings demonstrate a spatial coupling between areal differences in the timing of neurogenesis and rates of neocortical expansion during gestation. We identify genes, upregulated from mid-gestation, that are highly expressed in rapidly expanding neocortex and implicated in genetic disorders with cognitive sequelae. The μBrain atlas provides a tool to comprehensively map early brain development across domains, model systems and resolution scales.

Magnetic resonance diffusion tensor imaging for detecting the cerebral microstructure changes in patients with CSVD -induced mild cognitive impairment.

Cerebral small vessel disease (CSVD)-induced mild cognitive impairment (MCI) has been linked to cognitive decline. Brain atrophy is considered the most common change in MCI patients, which can be measured by diffusion tensor imaging (DTI). The study aimed to explore the relationship between DTI parameters and cognitive function in CSVD patients with MCI. This retrospective analysis involved 185 patients with CSVD, comprising 87 cases with MCI and 98 cases without MCI (NMCI). Analyses of demographic and clinical characteristics were conducted. DTI-measured fractional anisotropy (FA) and mean diffusivity (MD) in the hippocampus and entorhinal cortex regions were examined. The diagnostic values were determined using receiver-operative-curve (ROC) analysis, with the Youden Index identifying optimum sensitivity and specificity. Correlations between Montreal cognitive assessment (MoCA) scores and FA or MD in MCI patients were further assessed. No significant differences were observed in demographic and clinical characteristics between MCI and NMCI groups (all p>0.05), except for diabetes prevalence (p=0.011). Notably, the ROC analysis highlighted the diagnostic potential of FA, showing the maximum area under the curve values (Hippocampus-Left: 0.76; Hippocampus-Right: 0.66; Entorhinal cortex-Left: 0.62; Entorhinal cortex-Right: 0.64). MD exhibited a significant negative correlation with MoCA scores (Hippocampus-Left: r=-0.58, p<0.001; Hippocampus-Right: r=-0.41, p<0.001; Entorhinal cortex-Left: r=-0.49, p<0.001; Entorhinal cortex-Right: r=-0.27, p<0.001), while FA showed a significant positive correlation (Hippocampus-Left: r=0.51, p<0.001; Hippocampus-Right: r=0.31, p=0.004; Entorhinal cortex-Left: r=0.35, p<0.001; Entorhinal cortex-Right: r=0.38, p<0.001). The study demonstrates the diagnostic value of DTI parameters in CSVD patients with MCI, emphasizing the associations between microstructural brain changes and cognitive function.

A 7T fMRI investigation of hand and tool areas in the lateral and ventral occipitotemporal cortex.

Previous studies demonstrated the existence of hand and tool areas in lateral and ventral occipitotemporal cortex (OTC), as well as an overlap between them. We reinvestigated this organization using 7T fMRI, benefiting from a higher signal-to-noise ratio than 3T. This enabled us to include a wider array of categories to achieve a more holistic perspective, and to omit certain spatial preprocessing steps. Despite these improvements, univariate analysis confirmed the existence of hand-tool overlap across OTC, which is striking given the omission of the spatial preprocessing steps that can influence overlap. There was significantly more overlap between hands and tools, compared to other overlap types in the left hemisphere of OTC. The overlap was also larger in the left lateral OTC as compared to the right lateral OTC. We found in all hand areas a differentiation between tools and other types of objects, although they still responded more to bodies than to tools. Regarding the tool areas, we observed a differentiation between hands and other categories such as faces and non-tool objects. Left hemisphere tool areas also differentiated between hands and bodies. When excluding the overlapping voxels from the hand and tool areas, they still showed a significant response to tools or hands (compared to objects or faces) respectively. Multi-voxel pattern analysis indicated that neural representations in the hand areas showed greater similarity between hands and tools than between hands and other objects. In the tool areas, the neural representations between tools and hands and between tools and other type of objects were all equally similar. To summarize, capitalizing on the benefits of 7T fMRI, we further substantiate the evidence in favor of hand-tool overlap in several regions of occipitotemporal cortex.

Role of the medial posterior parietal cortex in orchestrating attention and reaching.

The interplay between attention, alertness and motor planning is crucial for our manual interactions. To investigate the neural bases of this interaction, and challenging the views that attention cannot be disentangled from motor planning, we instructed human volunteers of both sexes to plan and execute reaching movements while attending to the target, while attending elsewhere, or without constraining attention. We recorded reaction times to reach initiation and pupil diameter and interfered with the functions of the medial posterior parietal cortex (mPPC) with online repetitive transcranial magnetic stimulation to test the causal role of this cortical region in the interplay between spatial attention and reaching. We found that mPPC plays a key role in the spatial association of reach planning and covert attention. Moreover, we have found that alertness, measured by pupil size, is a good predictor of the promptness of reach initiation only if we plan a reach to attended targets, and mPPC is causally involved in this coupling. Different from previous understanding, we suggest that mPPC is neither involved in reach planning per se, nor in sustained covert attention in absence of a reach plan, but it is specifically involved in attention functional to reaching.Significance Statement Attention is required to perform dexterous arm movements. In this work we show the neural bases of the interplay between attention and reaching preparation, with the aim to provide information useful to address effective rehabilitation strategies to treat functional deficits observed in attention-related diseases. We discuss how brain areas are involved in orchestrating attention and reaching by signaling the alignment of their spatial coordinates. Moreover, we found that pupil size changes during reach preparation are related to reach initiation, suggesting a coordination between vigilance and reach promptness when preparing a reach to attended targets.

A dynamical systems approach to optimal foraging

Foraging for resources in an environment is a fundamental activity that must be addressed by any biological agent. Modelling this phenomenon in simulations can enhance our understanding of the characteristics of natural intelligence. In this work, we present a novel approach to model foraging in-silico using a continuous coupled dynamical system. The dynamical system is composed of three differential equations, representing the position of the agent, the agent’s control policy, and the environmental resource dynamics. Crucially, the control policy is implemented as a parameterized differential equation which allows the control policy to adapt in order to solve the foraging task. Using this setup, we show that when these dynamics are coupled and the controller parameters are optimized to maximize the rate of reward collected, adaptive foraging emerges in the agent. We further show that the internal dynamics of the controller, as a surrogate brain model, closely resemble the dynamics of the evidence accumulation mechanism, which may be used by certain neurons of the dorsal anterior cingulate cortex region in non-human primates, for deciding when to migrate from one patch to another. We show that by modulating the resource growth rates of the environment, the emergent behaviour of the artificial agent agrees with the predictions of the optimal foraging theory. Finally, we demonstrate how the framework can be extended to stochastic and multi-agent settings.

LPS-induced delirium-like behavior and microglial activation in mice correlate with bispectral electroencephalography (BSEEG).

Delirium is a multifactorial medical condition characterized by impairment across various mental functions and is one of the greatest risk factors for prolonged hospitalization, morbidity, and mortality. Research focused on delirium has proven to be challenging due to a lack of objective measures for diagnosing patients, and few laboratory models have been validated. Our recent studies report the efficacy of bispectral electroencephalography (BSEEG) in diagnosing delirium in patients and predicting patient outcomes. We applied BSEEG to validate a lipopolysaccharide (LPS)-induced mouse model of delirium. Moreover, we investigated the relationship between BSEEG score, delirium-like behaviors, and microglia activation in hippocampal dentate gyrus and cortex regions in young and aged mice. There was a significant correlation between BSEEG score and impairment of attention in young mice. Additionally, there was a significant correlation between BSEEG score and microglial activation in hippocampal dentate gyrus and cortex regions in young and aged mice. We have successfully validated the BSEEG method by showing its associations with a level of behavioral change and microglial activation in an LPS-induced mouse model of delirium. In addition, the BSEEG method was able to sensitively capture an LPS-induced delirium-like condition that behavioral tests could not capture because of a hypoactive state.

Genetic risk factors underlying white matter hyperintensities and cortical atrophy

White matter hyperintensities index structural abnormalities in the cerebral white matter, including axonal damage. The latter may promote atrophy of the cerebral cortex, a key feature of dementia. Here, we report a study of 51,065 individuals from 10 cohorts demonstrating that higher white matter hyperintensity volume associates with lower cortical thickness. The meta-GWAS of white matter hyperintensities-associated cortical ‘atrophy’ identifies 20 genome-wide significant loci, and enrichment in genes specific to vascular cell types, astrocytes, and oligodendrocytes. White matter hyperintensities-associated cortical ‘atrophy’ showed positive genetic correlations with vascular-risk traits and plasma biomarkers of neurodegeneration, and negative genetic correlations with cognitive functioning. 15 of the 20 loci regulated the expression of 54 genes in the cerebral cortex that, together with their co-expressed genes, were enriched in biological processes of axonal cytoskeleton and intracellular transport. The white matter hyperintensities-cortical thickness associations were most pronounced in cortical regions with higher expression of genes specific to excitatory neurons with long-range axons traversing through the white matter. The meta-GWAS-based polygenic risk score predicts vascular and all-cause dementia in an independent sample of 500,348 individuals. Thus, the genetics of white matter hyperintensities-related cortical atrophy involves vascular and neuronal processes and increases dementia risk.

Shifts in the spatiotemporal profile of inflammatory phenotypes of innate immune cells in the rat brain following acute intoxication with the organophosphate diisopropylfluorophosphate

Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication. Thus, the aim of this study was to characterize the natural history of microglial and astrocytic inflammatory phenotypes following acute intoxication with the OP, diisopropylfluorophosphate (DFP). Adult male and female Sprague–Dawley rats were administered a single dose of DFP (4 mg/kg, sc) followed by standard medical countermeasures. Within minutes, animals developed benzodiazepine-resistant SE as determined by monitoring seizures using a modified Racine scale. At 1, 3, 7, 14, and 28 d post-exposure (DPE), neuroinflammation was assessed using translocator protein (TSPO) positron emission tomography (PET) and magnetic resonance imaging (MRI). In both sexes, we observed consistently elevated radiotracer uptake across all examined brain regions and time points. A separate group of animals was euthanized at these same time points to collect tissues for immunohistochemical analyses. Colocalization of IBA-1, a marker for microglia, with iNOS or Arg1 was used to identify pro- and anti-inflammatory microglia, respectively; colocalization of GFAP, a marker for astrocytes, with C3 or S100A10, pro- and anti-inflammatory astrocytes, respectively. We observed shifts in the inflammatory profiles of microglia and astrocyte populations during the first month post-intoxication, largely in hyperintense inflammatory lesions in the piriform cortex and amygdala regions. In these areas, iNOS+ proinflammatory microglial cell density peaked at 3 and 7 DPE, while anti-inflammatory Arg1+ microglia cell density peaked at 14 DPE. Pro- and anti-inflammatory astrocytes emerged within 7 DPE, and roughly equal ratios of C3+ pro-inflammatory and S100A10+ anti-inflammatory astrocytes persisted at 28 DPE. In summary, microglia and astrocytes adopted mixed inflammatory phenotypes post-OP intoxication, which evolved over one month post exposure. These activated cell populations were most prominent in the piriform and amygdala areas and were more abundant in males compared to females. The temporal relationship between microglial and astrocytic responses suggests that initial microglial activity may influence delayed, persistent astrocytic responses. Further, our findings identify putative windows for inhibition of OP-induced neuroinflammatory responses in both sexes to evaluate the therapeutic benefit of anti-inflammation in this context.

Integrated strategy of mass spectrometry imaging and LC/MS-based GNPS for spatial characterization of alkaloids from Menispermi Rhizoma and study on potential anti-inflammatory mechanism by network pharmacology and molecular docking

Menispermi Rhizoma (MR) is the dried rhizome of Menispermum dauricum DC, which has been used to treat sore throat, enteritis, and rheumatic arthralgia. These therapeutic effects are attributed to its alkaloid ingredient. However, the chemical composition, anti-inflammatory mechanisms and the spatiotemporal distribution of the bioactive ingredients in MR have seldom been investigated. This study aims to clarify the anti-inflammation mechanism, material basis, and their spatial distribution of MR. Here, a LC/MS-based Global Natural Products Social Molecular Networking (GNPS) strategy was used to rapidly exhibit alkaloid molecular clusters that improve annotation accuracy and discover more unknown compounds. Then, a high-sensitive air flow-assisted ionization mass spectrometry imaging (AFAI-MSI) method was developed to visualize the spatial distributions alkaloids in different botanical parts of MR. The anti-inflammation mechanism was investigated based on network pharmacology and verified by molecular docking experiment. Finally, a total of 106 alkaloids including 24 aporphines, 23 monobenzylisoquinolines, 20 morphinanes, 20 proberberines, 12 bisbenzylisoquinolines, and 7 amides were identified in MR as well as 24 alkaloids were visualized in the medullary ray, cortex and epidermis regions. Moreover, the targets with a higher degree in the PPI network were TNF, GAPDH, AKT1, ALB, STAT3. GO and KEGG analysis revealed that MR in anti-inflammatory mechanism mainly involved plasma membrane, ATP binding, cytoplasm, identical protein binding and ATP binding. The signaling pathways mainly included NOD-like receptor signaling pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications. The molecular docking results indicated that stepharanine-2-O-glucoside, bianfugedine, bianfugecine, dehydrostephanine had excellent affinity with SRC, MMP9 AKT1, STAT3 and TNF. This study comprehensively characterized the alkaloid ingredients and spatial distribution of MR, and revealed potential mechanism of MR in inflammation, which provides a reference for development and application of MR and other Traditional Chinese medicines (TCMs).

Molecular Lineages and Spatial Distributions of Subplate Neurons in the Human Fetal Cerebral Cortex.

The expansion of neural progenitors and production of distinct neurons are crucial for architectural assembly and formation of connectivity in human brains. Subplate neurons (SPNs) are among the firstborn neurons in the human fetal cerebral cortex, and play a critical role in establishing intra- and extracortical connections. However, little is known about SPN origin and developmental lineages. In this study, spatial landscapes and molecular trajectories of SPNs in the human fetal cortices from gestational weeks (GW) 10 to 25 are created by performing spatial transcriptomics and single-cell RNA sequencing. Genes known to be evolutionarily human-specific and genes associated with extracellular matrices (ECMs) are found to maintain stable proportions of subplate neurons among other neuronal types. Enriched ECM gene expression in SPNs varies in distinct cortical regions, with the highest level in the frontal lobe of human fetal brains. This study reveals molecular origin and lineage specification of subplate neurons in the human fetal cerebral cortices, and highlights underpinnings of SPNs to cortical neurogenesis and early structural folding.

Metabolic pathways, pharmacokinetic, and brain neurochemicals effects of capsaicin: Comprehensively insights from in vivo studies

BackgroundCapsaicin (CAP), a prominent component of chili pepper known for its potent agonistic effects on TRPV1, has attracted significant attention for its diverse physiological effects. Nevertheless, there remains a paucity of data concerning its in vivo distribution, metabolism, pharmacodynamic properties, and influence on the metabolic profile of the brain. MethodsStable isotope tracing, in vitro enzyme incubation, microdialysis coupled with UHPLC-MS/MS techniques were employed to investigate the in vivo metabolic pathways, distribution, and pharmacokinetic properties of CAP, and the potential biases in metabolic pathways was elucidate through molecular docking. Furthermore, the effect of CAP on brain metabolic profiles was assessed using untargeted metabolomics, and spatial visualization analysis was conducted through mass spectrometry imaging. ResultsCAP was distributed predominantly in the kidneys, with lower content in the liver, heart, lungs, brain, and spleen following peripheral administration, and the absorption half-life in the body was about 20 minutes. CAP primarily underwent alkyl terminal dehydrogenation, hydroxylation, and macrocyclization metabolic pathways under the action of CYP2C9, CYP2C19 and CYP2D6, resulting in at least four metabolites. Among them, the hydroxylation products were main metabolites and the dehydrogenation product 16,17-dihydrocapsaicin could interact with the key binding sites Leu515 and Thr550 of TRPV1 like CAP. CAP quickly diffused to various brain regions and the metabolic characteristics in the striatum were relatively different from that in the blood. The distribution of CAP in the brain primarily triggered the release of neurotransmitters in areas associated with reward, cognition, and memory. Both acute and chronic exposure to CAP elevated amino acid levels in cortical regions, while producing contrasting effects on nucleotide metabolites. ConclusionThis study offers an initial in-depth analysis of the distribution patterns, metabolic pathways and pharmacodynamic properties of CAP in the body and brain. These findings established a basis for further studies on CAP's pharmacology properties and its influence on the central nervous system.

The Relationship between Event Boundary Strength and Pattern Shifts across the Cortical Hierarchy during Naturalistic Movie-viewing.

Our continuous experience is spontaneously segmented by the brain into discrete events. However, the beginning of a new event (an event boundary) is not always sharply identifiable: Phenomenologically, event boundaries vary in salience. How are the response profiles of cortical areas at event boundaries modulated by boundary strength during complex, naturalistic movie-viewing? Do cortical responses scale in a graded manner with boundary strength, or do they merely detect boundaries in a binary fashion? We measured "cortical boundary shifts" as transient changes in multivoxel patterns at event boundaries with different strengths (weak, moderate, and strong), determined by across-participant agreement. Cortical regions with different processing timescales were examined. In auditory areas, which have short timescales, cortical boundary shifts exhibited a clearly graded profile in both group-level and individual-level analyses. In cortical areas with long timescales, including the default mode network, boundary strength modulated pattern shift magnitude at the individual participant level. We also observed a positive relationship between boundary strength and the extent of temporal alignment of boundary shifts across different levels of the cortical hierarchy. In addition, hippocampal activity was highest at event boundaries for which cortical boundary shifts were most aligned across hierarchical levels. Overall, we found that event boundary strength modulated cortical pattern shifts strongly in sensory areas and more weakly in higher-level areas and that stronger boundaries were associated with greater alignment of these shifts across the cortical hierarchy.

Sex-Specific Impacts of Early Life Sleep Disruption: Ethanol Seeking, Social Interaction, and Anxiety Are Differentially Altered in Adolescent Prairie Voles.

Early life sleep is important for neuronal development. Using the highly social prairie vole rodent model, we have previously reported that early life sleep disruption (ELSD) during the preweaning period results in interference with social bonding and increases ethanol consumption following a stressor in adulthood. Furthermore, ELSD increases parvalbumin expression and reduces glutamatergic neurotransmission in cortical regions in adult prairie voles. To understand the impact of ELSD on the lifespan, an examination of an earlier time in life is necessary. The aim of the present study was to examine behavioral outcomes of ELSD on adolescent prairie voles. Given the known effects of ELSD on development of neuronal systems involved in mood and social motivation, we hypothesized that anxiety, risk, and reward-related behaviors would be impacted by ELSD in adolescent prairie voles. We report that both male and female adolescent prairie voles that experienced ELSD showed heightened anxiety-like behavior compared to age-matched controls (CONs) as measured by a light-dark box. Additionally, both male and female ELSD voles showed reductions in both ethanol preference and consumption, and affiliative behavior compared to CONs. These results suggest that adolescent prairie voles of both sexes experience heightened anxiety-like behavior and reduced reward-seeking behaviors after ELSD. These results further suggest that early life sleep is critically important for neurotypical behaviors in adolescence.

A combined DTI-fMRI approach for optimizing the delineation of posteromedial versus anterolateral entorhinal cortex.

In the entorhinal cortex (EC), attempts have been made to identify the human homologue regions of the medial (MEC) and lateral (LEC) subregions using either functional magnetic resonance imaging (fMRI) or diffusion tensor imaging (DTI). However, there are still discrepancies between entorhinal subdivisions depending on the choice of connectivity seed regions and the imaging modality used. While DTI can be used to follow the white matter tracts of the brain, fMRI can identify functionally connected brain regions. In this study, we used both DTI and resting-state fMRI in 103 healthy adults to investigate both structural and functional connectivity between the EC and associated cortical brain regions. Differential connectivity with these regions was then used to predict the locations of the human homologues of MEC and LEC. Our results from combining DTI and fMRI support a subdivision into posteromedial (pmEC) and anterolateral (alEC) EC and reveal a confined border between the pmEC and alEC. Furthermore, the EC subregions obtained by either imaging modality showed similar distinct whole-brain connectivity profiles. Optimizing the delineation of the human homologues of MEC and LEC with a combined, cross-validated DTI-fMRI approach allows to define a likely border between the two subdivisions and has implications for both cognitive and translational neuroscience research.

Resting-state functional connectivity is correlated with peripheral inflammatory markers in patients with major depressive disorder and healthy controls

BackgroundRecent studies have highlighted the significant role of inflammation in the development and progression of major depressive disorder (MDD). Elevated levels of proinflammatory cytokines have consistently been observed in MDD, and these markers are shown to be linked to disruptions in brain networks. Therefore, we aimed to explore the relationship between inflammatory markers and resting-state functional connectivity (RSFC) in patients with MDD. MethodsThis study included 76 patients with MDD and 92 healthy controls (HCs). Seed-to-voxel RSFC analysis was performed using brain regions that have been identified in previous studies on the neural networks implicated in MDD. These regions served as key hubs in the default mode, salience, cognitive control, and frontostriatal networks and were used as seed regions. ResultsCompared with HCs, patients with MDD exhibited elevated levels of interleukin (IL)-6 and IL-8. The MDD group showed significant alterations of the RSFC between the prefrontal cortex (PFC), anterior cingulate cortex, visual cortex, postcentral gyrus, and striatal regions compared to the HC group. Additionally, within the MDD group, a positive correlation was observed between tumor necrosis factor (TNF)-α levels and the RSFC of the right dorsolateral prefrontal cortex (dlPFC) and visual cortex. Conversely, in the HC group, TNF-α levels were negatively correlated with the RSFC between the right dlPFC and bilateral dorsomedial prefrontal cortex, while positive correlations were noted between the RSFC of the right dlPFC with occipital regions and the levels of both IL-8 and TNF-α. ConclusionsThe present study confirmed that cytokine levels are linked to alterations in the RSFC, particularly in the prefrontal regions. Our findings suggest that systemic inflammation may contribute to functional disruptions in the brain networks involved in emotion regulation and cognitive control in MDD.

Decoding Cortical Chronotopy - Comparing the Influence of Different Cortical Organizational Schemes

The brain's diverse intrinsic timescales enable us to perceive stimuli with varying temporal persistency. This study aimed to uncover the cortical organizational schemes underlying these variations, revealing the neural architecture for processing a wide range of sensory experiences. We collected resting-state fMRI, task-fMRI, and diffusion-weighted imaging data from 47 individuals. Based on this data, we extracted six organizational schemes: (1) the structural Rich Club (RC) architecture, shown to synchronize the connectome; (2) the structural Diverse Club architecture, as an alternative to the RC based on the network's module structure; (3) the functional uni-to-multimodal gradient, reflected in a wide range of structural and functional features; and (4) the spatial posterior/lateral-to-anterior/medial gradient, established for hierarchical levels of cognitive control. Also, we explored the effects of (5) structural graph theoretical measures of centrality and (6) cytoarchitectural differences. Using Bayesian model comparison, we contrasted the impact of these organizational schemes on (1) intrinsic resting-state timescales and (2) inter-subject correlation (ISC) from a task involving hierarchically nested digit sequences. As expected, resting-state timescales were slower in structural network hubs, hierarchically higher areas defined by the functional and spatial gradients, and thicker cortical regions. ISC analysis demonstrated hints for the engagement of higher cortical areas with more temporally persistent stimuli. Finally, the model comparison identified the uni-to-multimodal gradient as the best organizational scheme for explaining the chronotopy in both task and rest. Future research should explore the microarchitectural features that shape this gradient, elucidating how our brain adapts and evolves across different modes of processing.

Magnetoencephalographic brain activity evoked by the optic-flow task is correlated with β-amyloid burden and parahippocampal atrophy

Visuospatial perception is often impaired in people with Alzheimer’s disease (AD). Because visuospatial information is thought to be processed in the visual dorsal stream, it is believed that brain activities in the dorsal stream will be altered in AD patients. In this study, we investigated whether regional brain activity related to visuospatial perception were associated with AD progression markers. An optic-flow task, which activates the dorsal stream associated with visuospatial perception, was performed, and the brain activities evoked by the task were evaluated using magnetoencephalography (MEG). First, we evaluated the responses to optic-flow stimuli in 21 cognitively unimpaired participants and determined the regions of interest (ROIs) where optic-flow activities were activated. Task-related activations were observed in 14 cortical regions including the dorsal stream: the right and left medial ventral occipital cortex (MVOcC), lateral occipital cortex (LOcC), precuneus (Pcun), inferior parietal lobule (IPL), superior parietal lobule (SPL), posterior superior temporal sulcus (pSTS), and fusiform gyri (FuG). Next, we performed correlation analyses between task-related activity in each ROI and two AD progression markers, global amyloid burden and parahippocampal gyrus (PHG) volume, for 25 participants who underwent amyloid positron emission tomography (PET) scans. We found that the global amyloid burden was negatively correlated with task-related activity in the left MVOcC and right SPL [r = -0.488 (p = 0.013) and r = -0.421 (p = 0.038), respectively]. Furthermore, significant positive correlations were observed between PHG volume and task-related activity in both the left and right SPL [r = 0.500 (p = 0.011) and r = 0.549 (p = 0.005), respectively]. Since the SPL is known to be responsible for visuospatial perception, these results suggest that MEG neuronal activity of patients performing the optic-flow activity can detect changes in brain activity associated with visuospatial impairment related to AD.