Search

Chronic neuropathic pain can result from nervous system injury and can persist in the absence of external stimuli. Although ongoing pain characterizes the disorder, in many individuals, the intensity of this ongoing pain fluctuates dramatically. Previously, it was identified that functional magnetic resonance imaging signal covariations between the midbrain periaqueductal gray (PAG) matter, rostral ventromedial medulla (RVM), and spinal trigeminal nucleus are associated with moment-to-moment fluctuations in pain intensity in individuals with painful trigeminal neuropathy (PTN). Since this brainstem circuit is modulated by higher brain input, we sought to determine which cortical sites might be influencing this brainstem network during spontaneous fluctuations in pain intensity. Over 12 min, we recorded the ongoing pain intensity in 24 PTN participants and classified them as fluctuating (n = 13) or stable (n = 11). Using a PAG seed, we identified connections between the PAG and emotional-affective sites such as the hippocampal and posterior cingulate cortices, the sensory-discriminative posterior insula, and cognitive-affective sites such as the dorsolateral prefrontal (dlPFC) and subgenual anterior cingulate cortices that were altered dependent on spontaneous high and low pain intensity. Additionally, sliding-window functional connectivity analysis revealed that the dlPFC-PAG connection anticorrelated with perceived pain intensity over the entire 12 min period. These findings reveal cortical systems underlying moment-to-moment changes in perceived pain in PTN, which likely cause dysregulation in the brainstem circuits previously identified, and consequently alter the appraisal of pain across time.

BACKGROUND: Sex-differential biology may contribute to the consistently male-biased prevalence of autism spectrum disorder (ASD). Gene expression differences between males and females in the brain can indicate possible molecular and cellular mechanisms involved, although transcriptomic sex differences during human prenatal cortical development have been incompletely characterized, primarily due to small sample sizes. METHODS: We performed a meta-analysis of sex-differential expression and co-expression network analysis in 2 independent bulk RNA sequencing datasets generated from cortex of 273 prenatal donors without known neuropsychiatric disorders. To assess the intersection between neurotypical sex differences and neuropsychiatric disorder biology, we tested for enrichment of ASD-associated risk genes and expression changes, neuropsychiatric disorder risk genes, and cell type markers within identified sex-differentially expressed genes (sex-DEGs) and sex-differential co-expression modules. RESULTS: We identified 101 significant sex-DEGs, including Y-chromosome genes, genes impacted by X-chromosome inactivation, and autosomal genes. Known ASD risk genes, implicated by either common or rare variants, did not preferentially overlap with sex-DEGs. We identified 1 male-specific co-expression module enriched for immune signaling that is unique to 1 input dataset. CONCLUSIONS: Sex-differential gene expression is limited in prenatal human cortex tissue, although meta-analysis of large datasets allows for the identification of sex-DEGs, including autosomal genes that encode proteins involved in neural development. Lack of sex-DEG overlap with ASD risk genes in the prenatal cortex suggests that sex-differential modulation of ASD symptoms may occur in other brain regions, at other developmental stages, or in specific cell types, or may involve mechanisms that act downstream from mutation-carrying genes.

Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. The highly dynamic nature of MS lesions has made them difficult to study using traditional histopathology due to the specificity of current stains. This requires numerous stains to track and study demyelinating activity in MS. Thus, we utilized Fourier transform infrared (FTIR) spectroscopy to generate holistic biomolecular profiles of demyelinating activities in MS brain tissue. Multivariate analysis can differentiate MS tissue from controls. Analysis of the absorbance spectra shows profound reductions of lipids, proteins, and phosphate in white matter lesions. Changes in unsaturated lipids and lipid chain length indicate oxidative damage in MS brain tissue. Altered lipid and protein structures suggest changes in MS membrane structure and organization. Unique carbohydrate signatures are seen in MS tissue compared to controls, indicating altered metabolic activities. Cortical lesions had increased olefinic lipid content and abnormal membrane structure in normal appearing MS cortex compared to controls. Our results suggest that FTIR spectroscopy can further our understanding of lesion evolution and disease mechanisms in MS paving the way towards improved diagnosis, prognosis, and development of novel therapeutics. [ABSTRACT FROM AUTHOR]

Cytoprotective and neurotoxic kynurenines formed along the kynurenine pathway (KP) were identified as possible therapeutic targets in various neuropsychiatric conditions. Memantine, an adamantane derivative modulating dopamine-, noradrenaline-, serotonin-, and glutamate-mediated neurotransmission is currently considered for therapy in dementia, psychiatric disorders, migraines, or ischemia. Previous studies have revealed that memantine potently stimulates the synthesis of neuroprotective kynurenic acid (KYNA) in vitro via a protein kinase A-dependent mechanism. Here, the effects of acute and prolonged administration of memantine on brain kynurenines and the functional changes in the cerebral KP were assessed in rats using chromatographic and enzymatic methods. Five-day but not single treatment with memantine selectively activated the cortical KP towards neuroprotective KYNA. KYNA increases were accompanied by a moderate decrease in cortical tryptophan (TRP) and L-kynurenine (L-KYN) concentrations without changes in 3-hydroxykynurenine (3-HK) levels. Enzymatic studies revealed that the activity of cortical KYNA biosynthetic enzymes ex vivo was stimulated after prolonged administration of memantine. As memantine does not directly stimulate the activity of KATs' proteins, the higher activity of KATs most probably results from the increased expression of the respective genes. Noteworthy, the concentrations of KYNA, 3-HK, TRP, and L-KYN in the striatum, hippocampus, and cerebellum were not affected. Selective cortical increase in KYNA seems to represent one of the mechanisms underlying the clinical efficacy of memantine. It is tempting to hypothesize that a combination of memantine and drugs could strongly boost cortical KYNA and provide a more effective option for treating cortical pathologies at early stages. Further studies should evaluate this issue in experimental animal models and under clinical scenarios. [ABSTRACT FROM AUTHOR]

Sound‐source localization is based on spatial cues arising due to interactions of sound waves with the torso, head and ears. Here, we evaluated neural responses to free‐field sound sources in the central nucleus of the inferior colliculus (CIC), the medial geniculate body (MGB) and the primary auditory cortex (A1) of Mongolian gerbils. Using silicon probes we recorded from anaesthetized gerbils positioned in the centre of a sound‐attenuating, anechoic chamber. We measured rate‐azimuth functions (RAFs) with broad‐band noise of varying levels presented from loudspeakers spanning 210° in azimuth and characterized RAFs by calculating spatial centroids, Equivalent Rectangular Receptive Fields (ERRFs), steepest slope locations and spatial‐separation thresholds. To compare neuronal responses with behavioural discrimination thresholds from the literature we performed a neurometric analysis based on signal‐detection theory. All structures demonstrated heterogeneous spatial tuning with a clear dominance of contralateral tuning. However, the relative amount of contralateral tuning decreased from the CIC to A1. In all three structures spatial tuning broadened with increasing sound‐level. This effect was strongest in CIC and weakest in A1. Neurometric spatial‐separation thresholds compared well with behavioural discrimination thresholds for locations directly in front of the animal. Our findings contrast with those reported for another rodent, the rat, which exhibits homogenous and sharply delimited contralateral spatial tuning. Spatial tuning in gerbils resembles more closely the tuning reported in A1 of cats, ferrets and non‐human primates. Interestingly, gerbils, in contrast to rats, share good low‐frequency hearing with carnivores and non‐human primates, which may account for the observed spatial tuning properties. [ABSTRACT FROM AUTHOR]

Disturbed CNS zinc homeostasis is suggested as part of the pathophysiology of schizophrenia. Our data, from multiple studies, suggests levels of cortical RNA for the solute carrier family 39 member 12 (SLC39A12), a putative zinc transporter, is higher in people with schizophrenia and is more perturbed in a sub-group of people with the disorder that can be separated because they have very low levels of muscarinic M1 receptors (MRDS). In this study qPCR was used to measure levels of two RNA splice variants of SLC39A12 (a and b) in Brodmann's area (BA) 44 from new cohorts of controls and people with schizophrenia. For the first time, in our study cohort as a whole, we report levels of both splice variants of SLC39A12 are lower in females compared to males and there are correlations between levels of SLC39A12 a and b and CNS pH. Levels of both splice variants were also lower in people with schizophrenia who were suicide completers compared to those who were not. Accounting for these factors, we showed levels of SLC39A12 a and b were higher in BA 44 in schizophrenia compared to controls. In further analyses, with and without our previous data on SLC39A12 a and b , we confirmed changes in levels of SLC39A1 2 RNAs were more profound in MRDS. In conclusion, our study argues there are higher levels of SLC39A12 a and b in BA 44 in schizophrenia which could be contributing to the breakdown in CNS zinc homeostasis suggested as part of the pathophysiology of schizophrenia, particularly in those with MRDS. [ABSTRACT FROM AUTHOR]

Type-1 IFN (interferon)-associated innate immune response is increasingly getting attention in neurodegenerative and metabolic diseases like type 2 diabetes (T2DM). However, its significance in T2DM/lipotoxicity-induced neuroglia changes and cognitive impairment is missing. The present study aims to evaluate the involvement of cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon gene), IRF3 (interferon regulatory factor-3), TBK (TANK binding kinase)-mediated Type-1 IFN response in the diabetic brain, and lipotoxicity (palmitate-bovine serum albumin conjugate/PA-BSA)-induced changes in cells (neuro2a and BV2). T2DM was induced in C57/BL6 mice by feeding on a high-fat diet (HFD, 60% Kcal) for 16 weeks and injecting a single dose of streptozotocin (100 mg/kg, i.p) in the 12th week. Plasma biochemical parameter analysis, neurobehavioral assessment, protein expression, and quantitative polymerase chain reaction study were carried out to decipher the hypothesis. T2DM-associated metabolic and lipotoxic stress led to mitochondrial impairment causing leakage of mtDNA to the cytoplasm further commencing cGAS activation and its downstream signaling. The diseased hippocampus and cortex showed decreased expression of synaptophysin (p < 0.01) and PSD-95 (p < 0.01, p < 0.05) with increased expression of cGAS (p < 0.001), p-STING (p < 0.001), p-STAT1 (signal transducer and activator of transcription) (p < 0.01), and IFN-β (p < 0.001) compared to normal control. The IFN-β/p-STAT1-mediated microglia activation was executed employing a conditioned media approach. C-176, a selective STING inhibitor, alleviated cGAS/p-STING/IFN-β expression and proinflammatory microglia/M1-associated markers (CD16 expression, CXCL10, TNF-α, IL-1β mRNA fold change) in the diabetic brain. The present study suggests Type-1IFN response may result in neuroglia dyshomeostasis affecting normal brain function. Alleviating STING signaling has the potential to protect T2DM-associated central ailment. [ABSTRACT FROM AUTHOR]

External contamination of hair is the most significant challenge to it becoming an accepted matrix for monitoring endogenous metal exposure and nutritional deficiency. Here we use laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to quantify elemental concentrations in hair strands below and above the scalp in the cuticle and cortex layers to determine the extent of external contamination in a reference population. Evidence of hair strand contamination occurred for barium, calcium, iron, magnesium, and strontium in both the outer cuticle and the inner cortex layers, with increasing concentrations from root to tip. Aluminum, boron, copper, lead, and manganese showed significant contamination in the cuticle layer only, suggesting some protection of the inner cortex. Phosphorus and potassium decreased outside the scalp suggesting loss by washing, while chromium, mercury, selenium, sodium, titanium, and zinc showed no evidence of loss or external contamination above the scalp. The results clearly show that for most elements, hair chemistry above the scalp is unreliable for use in interpretation of endogenous exposures or deficiencies, and that the below-scalp portion provides a more accurate monitoring tool. This is the first paper to provide a reference range of elemental hair chemistry that is not impacted by the external environment. [ABSTRACT FROM AUTHOR]

The cerebral cortex contains multiple, distinct areas that individually perform specific computations. A particular strength of the cortex is the communication of signals between cortical areas that allows the outputs of these compartmentalized computations to influence and build on each other, thereby dramatically increasing the processing power of the cortex and its role in sensation, action, and cognition. Determining how the cortex communicates signals between individual areas is, therefore, critical for understanding cortical function. Historically, corticocortical communication was thought to occur exclusively by direct anatomical connections between areas that often sequentially linked cortical areas in a hierarchical fashion. More recently, anatomical, physiological, and behavioral evidence is accumulating indicating a role for the higher-order thalamus in corticocortical communication. Specifically, the transthalamic pathway involves projections from one area of the cortex to neurons in the higher-order thalamus that, in turn, project to another area of the cortex. Here, we consider the evidence for and implications of having two routes for corticocortical communication with an emphasis on unique processing available in the transthalamic pathway and the consequences of disorders and diseases that affect transthalamic communication. [ABSTRACT FROM AUTHOR]

Characterizing cortical plasticity becomes increasingly important for identifying compensatory mechanisms and structural reserve in the ageing population. While cortical thickness (CT) largely contributed to systems neuroscience, it incompletely informs about the underlying neuroplastic pathophysiology. In turn, microstructural characteristics may correspond to atrophy mechanisms in a more sensitive way. Fractional anisotropy, a diffusion tensor imaging (DTI) measure, is inversely related to cortical histologic complexity. Axial diffusivity and radial diffusivity are assumed to be linked to the density of structures oriented perpendicular and parallel to the cortical surface, respectively. We hypothesized (1) that cortical DTI will reveal microstructural correlates for hemispheric specialization, particularly in the language and motor systems, and (2) that lateralization of cortical DTI parameters will show an age effect, paralleling age‐related changes in activation, especially in the prefrontal cortex. We analysed data from healthy younger and older adult participants (N = 91). DTI and CT data were extracted from regions of the Destrieux atlas. Diffusion measures showed lateralization in specialized motor, language, visual, auditory and inferior parietal cortices. Age‐dependent increased lateralization for DTI measures was observed in the prefrontal, angular, superior temporal and lateral occipital cortex. CT did not show any age‐dependent alterations in lateralization. Our observations argue that cortical DTI can capture microstructural properties associated with functional specialization, resembling findings from histology. Age effects on diffusion measures in the integrative prefrontal and parietal areas may shed novel light on the atrophy‐related plasticity in healthy ageing. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the impact of exercise training modes on sensory and motor-related cortex excitability using functional near-infrared spectroscopy technology (fNIRS) and reveal specific cortical effects. Materials and methods: Twenty participants with no known health conditions took part in a study involving passive, active, and resistance tasks facilitated by an upper-limb robot, using a block design. The participants wore functional near-infrared spectroscopy (fNIRS) devices throughout the experiment to monitor changes in cortical blood oxygen levels during the tasks. The fNIRS optode coverage primarily targeted key areas of the brain cortex, including the primary motor cortex (M1), primary somatosensory cortex (S1), supplementary motor area (SMA), and premotor cortex (PMC) on both hemispheres. The study evaluated cortical activation areas, intensity, and lateralization values. Results: Passive movement primarily activates M1 and part of S1, while active movement mainly activates contralateral M1 and S1. Resistance training activates brain regions in both hemispheres, including contralateral M1, S1, SMA, and PMC, as well as ipsilateral M1, S1, SMA, and PMC. Resistance movement also activates the ipsilateral sensorimotor cortex (S1, SMA, PMC) more than active or passive movement. Active movement has higher contralateral activation in M1 compared to passive movement. Resistance and active movements increase brain activity more than passive movement. Different movements activate various cortical areas equally on both sides, but lateralization differs. The correlation between lateralization of brain regions is significant in the right cortex but not in the left cortex during three movement patterns. Conclusion: All types of exercise boost motor cortex excitability, but resistance exercise activates both sides of the motor cortex more extensively. The PMC is crucial for intense workouts. The right cortex shows better coordination during motor tasks than the left. fNIRS findings can help determine the length of treatment sessions. [ABSTRACT FROM AUTHOR]

To adapt to threats in the environment, animals must predict them and engage in defensive behavior. While the representation of a prediction error signal for reward has been linked to dopamine, a neuromodulatory prediction error for aversive learning has not been identified. We measured and manipulated norepinephrine release during threat learning using optogenetics and a novel fluorescent norepinephrine sensor. We found that norepinephrine response to conditioned stimuli reflects aversive memory strength. When delays between auditory stimuli and footshock are introduced, norepinephrine acts as a prediction error signal. However, temporal difference prediction errors do not fully explain norepinephrine dynamics. To explain noradrenergic signaling, we used an updated reinforcement learning model with uncertainty about time and found that it explained norepinephrine dynamics across learning and variations in temporal and auditory task structure. Norepinephrine thus combines cognitive and affective information into a predictive signal and links time with the anticipation of danger. [ABSTRACT FROM AUTHOR]

It is a paradox of neurological rehabilitation that, in an era in which preclinical models have produced significant advances in our mechanistic understanding of neural plasticity, there is inadequate support for many therapies recommended for use in clinical practice. When the goal is to estimate the probability that a specific form of therapy will have a positive clinical effect, the integration of mechanistic knowledge (concerning ‘the structure or way of working of the parts in a natural system’) may improve the quality of inference. This is illustrated by analysis of three contemporary approaches to the rehabilitation of lateralized dysfunction affecting people living with stroke: constraint‐induced movement therapy; mental practice; and mirror therapy. Damage to ‘cross‐road’ regions of the structural (white matter) brain connectome generates deficits that span multiple domains (motor, language, attention and verbal/spatial memory). The structural integrity of these regions determines not only the initial functional status, but also the response to therapy. As structural disconnection constrains the recovery of functional capability, ‘disconnectome’ modelling provides a basis for personalized prognosis and precision rehabilitation. It is now feasible to refer a lesion delineated using a standard clinical scan to a (dis)connectivity atlas derived from the brains of other stroke survivors. As the individual disconnection pattern thus obtained suggests the functional domains most likely be compromised, a therapeutic regimen can be tailored accordingly. Stroke is a complex disorder that burdens individuals with distinct constellations of brain damage. Mechanistic knowledge is indispensable when seeking to ameliorate the behavioural impairments to which such damage gives rise. [ABSTRACT FROM AUTHOR]

In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs; Pdgfrα-CreER transgenic mice) or mature OLs (Plp-CreER transgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre-existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ~ 471 µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs, increased the number of surviving OLs that supported internodes in the corpus callosum (CC), and increased the proportion of axons that were myelinated. The ability of LI-rTMS to modify cortical neuronal activity and the behaviour of new and surviving OLs, suggests that it may be a suitable adjunct intervention to enhance remyelination in people with MS. [ABSTRACT FROM AUTHOR]

The cGAS-STING pathway is a pivotal element of the innate immune system, recognizing cytosolic DNA to initiate the production of type I interferons and pro-inflammatory cytokines. This study investigates the alterations of the cGASSTING signaling components in the cortex and hippocampus of mice aged 24 and 108 weeks. In the cortex of old mice, an increase in the dsDNA sensor protein cGAS and its product 2030-cGAMP was observed, without corresponding activation of downstream signaling, suggesting an uncoupling of cGAS activity from STING activation. This phenomenon may be attributed to increased dsDNA concentrations in the EC neurons, potentially arising from nuclear DNA damage. Contrastingly, the hippocampus did not exhibit increased cGAS activity with aging, but there was a notable elevation in STING levels, particularly in microglia, neurons and astrocytes. This increase in STING did not correlate with enhanced IRF3 activation, indicating that brain inflammation induced by the cGAS-STING pathway may manifest extremely late in the aging process. Furthermore, we highlight the role of autophagy and its interplay with the cGAS-STING pathway, with evidence of autophagy dysfunction in aged hippocampal neurons leading to STING accumulation. These findings underscore the complexity of the cGASSTING pathway's involvement in brain aging, with regional variations in activity and potential implications for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

GABAergic interneurons (INs) in the mammalian forebrain represent a diverse population of cells that provide specialized forms of local inhibition to regulate neural circuit activity. Over the last few decades, the development of a palette of genetic tools along with the generation of single-cell transcriptomic data has begun to reveal the molecular basis of IN diversity, thereby providing deep insights into how different IN subtypes function in the forebrain. In this review, we outline the emerging picture of cortical and hippocampal IN speciation as defined by transcriptomics and developmental origin and summarize the genetic strategies that have been utilized to target specific IN subtypes, along with the technical considerations inherent to each approach. Collectively, these methods have greatly facilitated our understanding of how IN subtypes regulate forebrain circuitry via cell type and compartment-specific inhibition and thus have illuminated a path toward potential therapeutic interventions for a variety of neurocognitive disorders. [ABSTRACT FROM AUTHOR]

Ooids are coated grains composed of a tangential or radial cortex growing around a nucleus. They are common in carbonate deposits of almost any geological age and provide insights into environmental conditions. However, abiotic or biotic factors influencing their formation remain unclear. This study aims to advance current understanding of ooid formation with a multi‐analytical approach (for example, field emission scanning electron microscopy, Raman spectroscopy and micro X‐ray fluorescence) to classic examples from Great Salt Lake, USA, and the Lower Triassic Germanic Buntsandstein Basin, Germany. Both of these deposits represent hypersaline shallow‐water environments where ooids are closely associated with microbial mats. Great Salt Lake ooids are dominantly 0.2 to 1.0 mm in size, ellipsoidal to subspherical in shape, composed of aragonite and contain organic matter. Germanic Buntsandstein Basin ooids are mainly ≤4 mm in size, spherical to subspherical in shape, composed of calcite and currently contain little organic matter. Despite the differences, both ooids have the same cortex structures, likely reflecting similar formation processes. Some Great Salt Lake ooids formed around detrital grains while others exhibit micritic particles in their nuclei. In Germanic Basin ooids, detrital nuclei are rare, despite the abundance of siliciclastic particles of various sizes in the host rocks. Germanic Basin deposits also include 'compound ooids', i.e. adjacent ooids that coalesced with one another during growth, suggesting static in situ development, which is supported by the lack of detrital grains as nuclei. Germanic Basin ooids also grew into laminated microbial crusts with identical microstructures, further indicating a static formation. Such microbial crusts typically form through mineral precipitation associated with organic matter (for example, extracellular polymeric substances), suggesting a similar formation pathway for ooids. The inferred key‐role of organic matter is further supported by features in radial ooids from the Great Salt Lake, which commonly exhibit, from their nuclei towards their surface, increasing organic matter contents and decreasing calcification. [ABSTRACT FROM AUTHOR]

In the model organism Bacillus subtilis, a signaling protease produced in the forespore, SpoIVB, is essential for the activation of the sigma factor σK, which is produced in the mother cell as an inactive pro‐protein, pro‐σK. SpoIVB has a second function essential to sporulation, most likely during cortex synthesis. The cortex is composed of peptidoglycan (PG) and is essential for the spore's heat resistance and dormancy. Surprisingly, the genome of the intestinal pathogen Clostridioides difficile, in which σK is produced without a pro‐sequence, encodes two SpoIVB paralogs, SpoIVB1 and SpoIVB2. Here, we show that spoIVB1 is dispensable for sporulation, while a spoIVB2 in‐frame deletion mutant fails to produce heat‐resistant spores. The spoIVB2 mutant enters sporulation, undergoes asymmetric division, and completes engulfment of the forespore by the mother cell but fails to synthesize the spore cortex. We show that SpoIIP, a PG hydrolase and part of the engulfasome, the machinery essential for engulfment, is cleaved by SpoIVB2 into an inactive form. Within the engulfasome, the SpoIIP amidase activity generates the substrates for the SpoIID lytic transglycosylase. Thus, following engulfment completion, the cleavage and inactivation of SpoIIP by SpoIVB2 curtails the engulfasome hydrolytic activity, at a time when synthesis of the spore cortex peptidoglycan begins. SpoIVB2 is also required for normal late gene expression in the forespore by a currently unknown mechanism. Together, these observations suggest a role for SpoIVB2 in coordinating late morphological and gene expression events between the forespore and the mother cell. [ABSTRACT FROM AUTHOR]

In this article, we, for the first time, provide a comprehensive overview and unified framework of the impact of poverty and low socioeconomic status (SES) on the brain and behaviour. While there are many studies on the impact of low SES on the brain (including cortex, hippocampus, amygdala, and even neurotransmitters) and behaviours (including educational attainment, language development, development of psychopathological disorders), prior studies did not integrate behavioural, educational, and neural findings in one framework. Here, we argue that the impact of poverty and low SES on the brain and behaviour are interrelated. Specifically, based on prior studies, due to a lack of resources, poverty and low SES are associated with poor nutrition, high levels of stress in caregivers and their children, and exposure to socio-environmental hazards. These psychological and physical injuries impact the normal development of several brain areas and neurotransmitters. Impaired functioning of the amygdala can lead to the development of psychopathological disorders, while impaired hippocampus and cortex functions are associated with a delay in learning and language development as well as poor academic performance. This in turn perpetuates poverty in children, leading to a vicious cycle of poverty and psychological/physical impairments. In addition to providing economic aid to economically disadvantaged families, interventions should aim to tackle neural abnormalities caused by poverty and low SES in early childhood. Importantly, acknowledging brain abnormalities due to poverty in early childhood can help increase economic equity. In the current study, we provide a comprehensive list of future studies to help understand the impact of poverty on the brain. [ABSTRACT FROM AUTHOR]

Cells exist in different phenotypes and can transition between them. A phenotype may be characterized by many different aspects. Here, we focus on the example of whether the cell is adhered or suspended and choose particular parameters related to the structure and mechanics of the actin cortex. The cortex is essential to cell mechanics, morphology, and function, such as for adhesion, migration, and division of animal cells. To predict and control cellular functions and prevent malfunctioning, it is necessary to understand the actin cortex. The structure of the cortex governs cell mechanics; however, the relationship between the architecture and mechanics of the cortex is not yet well enough understood to be able to predict one from the other. Therefore, we quantitatively measured structural and mechanical cortex parameters, including cortical thickness, cortex mesh size, actin bundling, and cortex stiffness. These measurements required developing a combination of measurement techniques in scanning electron, expansion, confocal, and atomic force microscopy. We found that the structure and mechanics of the cortex of cells in interphase are different depending on whether the cell is suspended or adhered. We deduced general correlations between structural and mechanical properties and show how these findings can be explained within the framework of semiflexible polymer network theory. We tested the model predictions by perturbing the properties of the actin within the cortex using compounds. Our work provides an important step toward predictions of cell mechanics from cortical structures and suggests how cortex remodeling between different phenotypes impacts the mechanical properties of cells. [ABSTRACT FROM AUTHOR]

The extent to which evolution is repeatable has been a debated topic among evolutionary biologists. Although rewinding the tape of life perhaps would not lead to the same outcome every time, repeated evolution of analogous genes for similar functions has been extensively reported. Wing phenotypes of butterflies and moths have provided a wealth of examples of gene re-use, with certain 'hotspot loci' controlling wing patterns across diverse taxa. Here, we present an example of convergent evolution in the molecular genetic basis of Batesian wing mimicry in two Hypolimnas butterfly species. We show that mimicry is controlled by variation near cortex/ivory/mir-193, a known butterfly hotspot locus. By dissecting the genetic architecture of mimicry in Hypolimnas misippus and Hypolimnas bolina, we present evidence that distinct non-coding regions control the development of white pattern elements in the forewing and hindwing of the two species, suggesting independent evolution, and that no structural variation is found at the locus. Finally, we also show that orange coloration in H. bolina is associated with optix, a well-known patterning gene. Overall, our study once again implicates variation near the hotspot loci cortex/ivory/mir-193 and optix in butterfly wing mimicry and thereby highlights the repeatability of adaptive evolution. [ABSTRACT FROM AUTHOR]

Introduction: Complex neuronal interactions underlie cortical information processing that can be compromised in altered states of consciousness. Here intracortical microstimulation was applied to investigate anesthetic statedependent effective connectivity of neurons in rat visual cortex in vivo. Methods: Extracellular activity was recorded at 32 sites in layers 5/6 while stimulating with charge-balanced discrete pulses at each electrode in random order. The same stimulation pattern was applied at three levels of anesthesia with desflurane and in wakefulness. Spikes were sorted and classified by their waveform features as putative excitatory and inhibitory neurons. Network motifs were identified in graphs of effective connectivity constructed from monosynaptic cross-correlograms. Results: Microstimulation caused early (<10 ms) increase followed by prolonged (11-100 ms) decrease in spiking of all neurons throughout the electrode array. The early response of excitatory but not inhibitory neurons decayed rapidly with distance from the stimulation site over 1 mm. Effective connectivity of neurons with significant stimulus response was dense in wakefulness and sparse under anesthesia. The number of network motifs, especially those of higher order, increased rapidly as the anesthesia was withdrawn indicating a substantial increase in network connectivity as the animals woke up. Conclusion: The results illuminate the impact of anesthesia on functional integrity of local cortical circuits affecting the state of consciousness. [ABSTRACT FROM AUTHOR]

The claustrum is structurally connected with many cortical areas. A major hurdle standing in the way of understanding claustrum function is the difficulty in assessing the global functional connectivity (FC) of this structure. The primary issues lie in the inability to isolate claustrum signal from the adjacent insular cortex (Ins), caudate/putamen (CPu), and endopiriform nucleus (Endo). To address this issue, we used (7T) fMRI in the rat and describe a novel analytic method to study claustrum without signal contamination from the surrounding structures. Using this approach, we acquired claustrum signal distinct from Ins, CPu, and Endo, and used this claustrum signal to determine whole brain resting state functional connectivity (RSFC). Claustrum RSFC was distinct from the adjacent structures and displayed extensive connections with sensory cortices and the cingulate cortex, consistent with known structural connectivity of the claustrum. These results suggest fMRI and improved analysis can be combined to accurately assay claustrum function. [ABSTRACT FROM AUTHOR]

Simple Summary: Feathers are remarkable skin appendages that serve various ecological functions due to their complex structure and composition. This study focuses on frizzling feathers, which are known for their unique curling patterns. By examining frizzle chickens, both those with two copies of the frizzling gene and those with one, we analyzed how soft and stiff keratin materials are distributed in the shafts of their flight feathers. Our findings show that the way these keratins are arranged affects the internal structure and biomechanics of the feathers, causing them to curl naturally. Specifically, we discovered that a reduction in soft keratin in the core of the feather shaft changes the internal stresses and leads to frizzling. This research enhances our understanding of how curl feather structures develop and adapt to different ecological needs, providing valuable insights into the diversity of feather forms in nature. The morphological and compositional complexities of keratinized components make feathers ingenious skin appendages adapted to diverse ecological needs. Frizzling feathers, characterized by their distinct curling phenotypes, offer a unique model to explore the intricate morphogenesis in developing a keratin-based bioarchitecture over a wide range of morphospace. Here, we investigated the heterogeneous allocation of α- and β-keratins in flight feather shafts of homozygous and heterozygous frizzle chickens by analyzing the medulla–cortex integrations using quantitative morphology characterizations across scales. Our results reveal the intriguing construction of the frizzling feather shaft through the modified medulla development, leading to a perturbed balance of the internal biomechanics and, therefore, introducing the inherent natural frizzling compared to those from wild-type chickens. We elucidate how the localized developmental suppression of the α-keratin in the medulla interferes with the growth of the hierarchical keratin organization by changing the internal stress in the frizzling feather shaft. This research not only offers insights into the morphogenetic origin of the inherent bending of frizzling feathers but also facilitates our in-depth understanding of the developmental strategies toward the diverse integuments adapted for ecological needs. [ABSTRACT FROM AUTHOR]

Schizophrenia and autism spectrum disorders (ASD) were considered as two neurodevelopmental disorders and had shared clinical features. we hypothesized that they have some common atypical brain functions and the purpose of this study was to explored the shared brain spontaneous activity strength alterations in early onset schizophrenia (EOS) and ASD in the children and adolescents with a multi-center large-sample study. A total of 171 EOS patients (aged 14.25 ± 1.87), 188 ASD patients (aged 9.52 ± 5.13), and 107 healthy controls (aged 11.52 ± 2.82) had scanned with Resting-fMRI and analyzed surface-based amplitude of low-frequency fluctuations (ALFF). Results showed that both EOS and ASD had hypoactivity in the primary sensorimotor regions (bilateral primary and early visual cortex, left ventral visual stream, left primary auditory cortex) and hyperactivity in the high-order transmodal regions (bilateral SFL, bilateral DLPFC, right frontal eye fields), and bilateral thalamus. EOS had more severe abnormality than ASD. This study revealed shared functional abnormalities in the primary sensorimotor regions and the high-order transmodal regions in EOS and ASD, which provided neuroimaging evidence of common changes in EOS and ASD, and may help with better early recognition and precise treatment for EOS and ASD. [ABSTRACT FROM AUTHOR]

This article addresses the discrepancy between Edouard Hitzig's and David Ferrier's findings on the cortical localization of movements in animals and Jean-Martin Charcot's findings in humans. The results of Hitzig's and Ferrier's vivisections were criticized by experimentalists in England and France as discordant, irreproducible, and inconclusive, and they were rejected by clinicians as irrelevant. Charcot addressed the gap between animal and human motor function by correlating motor deficits and focal epileptic seizures in patients to their autopsy findings. By this method he discovered the functional organization of the human motor cortex and produced the first accurate human motor brain map. Ferrier, William Osler, and Hughlings Jackson acknowledged Charcot's findings, and his findings guided the first neurosurgeons in localizing and resecting intracranial mass lesions presenting with focal epileptic seizures. Although his contributions in these fields have been neglected by modern historians, Charcot made significant contributions to the neurobiology of the human motor system, to epileptology, and to the birth of modern neurosurgery. [ABSTRACT FROM AUTHOR]

Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18 kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry. Forty-nine multiple sclerosis patients (21 with secondary progressive and 28 with relapsing-remitting multiple sclerosis) with mixed or high affinity binding for 11C-PBR28 underwent 90-min 11C-PBR28 simultaneous MR-PET. Tracer binding was measured using 60–90 min normalized standardized uptake value ratios sampled at mid-cortical depth and ∼3 mm above the pial surface. Data in multiple sclerosis patients were compared to 21 age-matched healthy controls. To characterize the nature of 11C-PBR28 PET uptake, the meningeal and cortical lesion cellular expression of TSPO was further described in post-mortem brain tissue from 20 cases with secondary progressive multiple sclerosis and five age-matched healthy donors. Relative to healthy controls, patients with multiple sclerosis exhibited abnormally increased TSPO signal in the cortex and meningeal tissue, diffusively in progressive disease and more localized in relapsing-remitting multiple sclerosis. In multiple sclerosis, increased meningeal TSPO levels were associated with increased Expanded Disability Status Scale scores (P = 0.007, by linear regression). Immunohistochemistry, validated using in situ sequencing analysis, revealed increased TSPO expression in the meninges and adjacent subpial cortical lesions of post-mortem secondary progressive multiple sclerosis cases relative to control tissue. In these cases, increased TSPO expression was related to meningeal inflammation. Translocator protein immunostaining was detected on meningeal MHC-class II+ macrophages and cortical-activated MHC-class II+ TMEM119+ microglia. In vivo arterial blood data and neuropathology showed that endothelial binding did not significantly account for increased TSPO cortico-meningeal expression in multiple sclerosis. Our findings support the use of TSPO-PET in multiple sclerosis for imaging in vivo inflammation in the cortico-meningeal brain tissue compartment and provide in vivo evidence implicating meningeal inflammation in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Gene regulatory regions are poorly conserved across evolution and contribute to interindividual differences as well as species diversification. While mammals share general stages of brain development and gross anatomical organization, the cortex has undergone substantial expansion in humans, necessitating molecular, cellular, and circuit-level adaptations of neural cell types, including pyramidal neurons, GABAergic interneurons, and astrocytes. Numerous studies have shown that human cortical pyramidal neurons diverge from tractable rodent models in synaptic density, synaptic volume, synaptic protein composition, neurite length, and maturation time-course, as well as in ion channel composition, membrane capacitance, and computational capacities. Molecular signatures across species differ in spatiotemporal expression patterns, including neuropsychiatric and neurodegenerative disease-associated genes. While many core biological processes are conserved across species, the human brain has evolved with unique capacities. Current understanding of the neurobiological mechanisms that endow human traits as well as associated vulnerabilities remains limited. However, emerging data have illuminated species divergence in DNA elements and genome organization, in molecular, morphological, and functional features of conserved neural cell types, as well as temporal differences in brain development. Here, we summarize recent data on unique features of the human brain and their complex implications for the study and treatment of brain diseases. We also consider key outstanding questions in the field and discuss the technologies and foundational knowledge that will be required to accelerate understanding of human neurobiology. [ABSTRACT FROM AUTHOR]

The telencephalon of reptiles has been suggested to be the key to understanding the evolution of the forebrain. Nevertheless, a meaningful framework to organize the telencephalon in any reptile has, with rare exception, yet to be presented. To address this gap in knowledge, the telencephalon was investigated in two species of crocodiles. A variety of morphological stains were used to examine tissue in transverse, horizontal, and sagittal planes of sections. Besides providing a description of individual nuclei, brain parts were organized based on two features. One was related to two fixed, internal structures: the lateral ventricle and the dorsal medullary lamina. The other was the alignment of neurons into either layers, cortex, or not, nucleus. Viewed from this perspective, all structures, with limited exceptions, could be accurately placed within the telencephalon regardless of the plane of section. Furthermore, this framework can be applied to other reptiles. A further extension of this scheme suggests that all structures in the telencephalon could be grouped into one of two categories: pallial or basal. [ABSTRACT FROM AUTHOR]

Endometriosis is a gynecological disease in the form of chronic inflammation characterized by the presence of tissue outside the uterine cavity that affects around 176 million women around the world. The pathogenesis of this disease is still unknown, resulting in a lack of standard treatment. People in East Nusa Tenggara, Indonesia, use boiled water from the cortex of Sterculia quadrifida R.Br. as a menstrual laxative and to treat menstrual pain, believed to be associated with endometriosis. The aim of this study was to investigate how a water extract of the S. quadrifida cortex prevents endometriosis lesions from growing in mice (Mus musculus) endometriosis models. This study was conducted as a true experimental research, dividing the mice into a control group and three SWE groups at doses of 200, 400, and 800 mg/kgBW. The findings showed that all SWE doses can significantly reduce endometriosis lesions and NF-κB expression compared to the negative control, with the optimal dose being 800 mg/kgBW. This activity was predicted due to its flavonoid compounds. These findings demonstrate the significant potential of S. quadrifida cortex as a developed herbal medicine for endometriosis treatment. [ABSTRACT FROM AUTHOR]

BackgroundThere has been increasing interest in cortical microstructure as a complementary and earlier measure of neurodegeneration than macrostructural atrophy, but few papers have related cortical diffusion imaging to post-mortem neuropathology. This study aimed to characterise the associations between the main Alzheimer's disease (AD) neuropathological hallmarks and multiple cortical microstructural measures from in vivo diffusion MRI. Comorbidities and co-pathologies were also investigated.MethodsForty-three autopsy cases (8 cognitively normal, 9 mild cognitive impairment, 26 AD) from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative databases were included. Structural and diffusion MRI scans were analysed to calculate cortical minicolumn-related measures (AngleR, PerpPD+, and ParlPD) and mean diffusivity (MD). Neuropathological hallmarks comprised Thal phase, Braak stage, neuritic plaques, and combined AD neuropathological changes (ADNC-the "ABC score" from NIA-AA recommendations). Regarding comorbidities, relationships between cortical microstructure and severity of white matter rarefaction (WMr), cerebral amyloid angiopathy (CAA), atherosclerosis of the circle of Willis (ACW), and locus coeruleus hypopigmentation (LCh) were investigated. Finally, the effect of coexistent pathologies-Lewy body disease and TAR DNA-binding protein 43 (TDP-43)-on cortical microstructure was assessed.ResultsCortical diffusivity measures were significantly associated with Thal phase, Braak stage, ADNC, and LCh. Thal phase was associated with AngleR in temporal areas, while Braak stage was associated with PerpPD+ in a wide cortical pattern, involving mainly temporal and limbic areas. A similar association was found between ADNC (ABC score) and PerpPD+. LCh was associated with PerpPD+, ParlPD, and MD. Co-existent neuropathologies of Lewy body disease and TDP-43 exhibited significantly reduced AngleR and MD compared to ADNC cases without co-pathology.ConclusionsCortical microstructural diffusion MRI is sensitive to AD neuropathology. The associations with the LCh suggest that cortical diffusion measures may indirectly reflect the severity of locus coeruleus neuron loss, perhaps mediated by the severity of microglial activation and tau spreading across the brain. Recognizing the impact of co-pathologies is important for diagnostic and therapeutic decision-making. Microstructural markers of neurodegeneration, sensitive to the range of histopathological features of amyloid, tau, and monoamine pathology, offer a more complete picture of cortical changes across AD than conventional structural atrophy.

Abstract Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. The highly dynamic nature of MS lesions has made them difficult to study using traditional histopathology due to the specificity of current stains. This requires numerous stains to track and study demyelinating activity in MS. Thus, we utilized Fourier transform infrared (FTIR) spectroscopy to generate holistic biomolecular profiles of demyelinating activities in MS brain tissue. Multivariate analysis can differentiate MS tissue from controls. Analysis of the absorbance spectra shows profound reductions of lipids, proteins, and phosphate in white matter lesions. Changes in unsaturated lipids and lipid chain length indicate oxidative damage in MS brain tissue. Altered lipid and protein structures suggest changes in MS membrane structure and organization. Unique carbohydrate signatures are seen in MS tissue compared to controls, indicating altered metabolic activities. Cortical lesions had increased olefinic lipid content and abnormal membrane structure in normal appearing MS cortex compared to controls. Our results suggest that FTIR spectroscopy can further our understanding of lesion evolution and disease mechanisms in MS paving the way towards improved diagnosis, prognosis, and development of novel therapeutics.

Background: Synaptic plasticity is an essential process encoding fine-tuned brain functions, but models to study this process in adult human systems are lacking. Objective: We aim to test whether ex vivo organotypic culture of post-mortem adult brain explants (OPABs) retain synaptic plasticity. Methods: OPABs were seeded on 3D microelectrode arrays to measure local field potential (LFP). Paired stimulation of distant electrodes was performed over three days to investigate our capacity to modulate specific neuronal connections. Results: Long-term potentiation (LTP) or depression (LTD) did not occur within a single day. In contrast, after two and three days of training, OPABs showed a significant modulation of the paired electrodes’ response compared to the non-paired electrodes from the same array. This response was alleviated upon treatment with dopamine. Conclusion: Our work highlights that adult human brain explants retain synaptic plasticity, offering novel approaches to neural circuitry in animal-free models.

Abstract This study aims to analyse the volumetric changes in brain MRI after cochlear implantation (CI), focusing on the speech perception in postlingually deaf adults. We conducted a prospective cohort study with 16 patients who had bilateral hearing loss and received unilateral CI. Based on the surgical side, patients were categorized into left and right CI groups. Volumetric T1-weighted brain MRI were obtained before and one year after the surgery. To overcome the artifact caused by the internal device in post-CI scan, image reconstruction method was newly devised and applied using the contralateral hemisphere of the pre-CI MRI data, to run FreeSurfer. We conducted within-subject template estimation for unbiased longitudinal image analysis, based on the linear mixed effect models. When analyzing the contralateral cerebral hemisphere before and after CI, a substantial increase in superior frontal gyrus and superior temporal gyrus (STG) volumes was observed in the left CI group. A positive correlation was observed in the STG and post-CI word recognition score in both groups. As far as we know, this is the first study attempting longitudinal brain volumetry based on post-CI MRI scans. We demonstrate that better auditory performance after CI is associated with structural restoration in central auditory structures.

The thymus gland is the primary lymphoid organ that undergoes postnatal growth followed by gradual atrophies and functional decline with age progress. The thymus gland has similar morphology across species, with a thoracic portion in the cranial mediastinum and a cervical portion along the trachea. Histologically, the thymus consists of an outer cortex populated with darkly stained T lymphocytes and a pale inner medulla. The medulla contains thymic Hassall's corpuscles (THC), which may function as sites for T cell maturation or as communication points between T cells and antigen-presenting cells. The thymus gland in camels has yet to be well studied, with limited research on its macroscopic and microscopic anatomy. In this study, the thymus glands of camel calves were examined. The thoracic portion was triangular and located in the cranioventral part of the mediastinum. The cervical portion extends cranially to the level of the thyroid gland and, in some cases, to the larynx. Histologically, the camel thymus had a fibrous capsule and connective tissue trabeculae, dividing the gland into incomplete lobules. The cortex was heavily populated with thymocytes, while the medulla contained epithelial reticular cells. A perivascular space (PVS) consisting of mature T lymphocytes surrounding blood vessels was also identified. THCs were present in the medulla, with variable shapes and forms ranging from small-sized to very large-sized with degenerative changes. Further research is needed to fully understand the role of the thymus gland in camels and its implications for vaccination programs and immune health.

• Postnatal inflammation causes evolving deficits in cortical neuronal dendritic maturation. • EEG was effective for identifying the early onset of cortical neuronal dysmaturation. • DTI and NODDI only detect established neuronal changes after postnatal inflammation. • EEG and MRI are complementary tools for assessing postnatal cortical dysmaturation. Exposure to postnatal systemic inflammation is associated with increased risk of brain injury in preterm infants, leading to impaired maturation of the cerebral cortex and adverse neurodevelopmental outcomes. However, the optimal method for identifying cortical dysmaturation is unclear. Herein, we compared the utility of electroencephalography (EEG), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) at different recovery times after systemic inflammation in newborn rats. Sprague Dawley rat pups of both sexes received single-daily lipopolysaccharide (LPS; 0.3 mg/kg i.p.; n = 51) or saline (n = 55) injections on postnatal days (P)1, 2, and 3. A subset of these animals were implanted with EEG electrodes. Cortical EEG was recorded for 30 min from unanesthetized, unrestrained pups at P7, P14, and P21, and in separate groups, brain tissues were collected at these ages for ex-vivo MRI analysis (9.4 T) and Golgi–Cox staining (to assess neuronal morphology) in the motor cortex. Postnatal inflammation was associated with reduced cortical pyramidal neuron arborization from P7, P14, and P21. These changes were associated with dysmature EEG features (e.g., persistence of delta waveforms, higher EEG amplitude, reduced spectral edge frequency) at P7 and P14, and higher EEG power in the theta and alpha ranges at P21. By contrast, there were no changes in cortical DTI or NODDI in LPS rats at P7 or P14, while there was an increase in cortical fractional anisotropy (FA) and decrease in orientation dispersion index (ODI) at P21. EEG may be useful for identifying the early evolution of impaired cortical development after early life postnatal systemic inflammation, while DTI and NODDI seem to be more suited to assessing established cortical changes. [ABSTRACT FROM AUTHOR]

• Autoimmune neuroinflammation induces aberrant astrocyte calcium signaling. • Astrocyte calcium signaling defects in multiple sclerosis are cell-autonomous. • Astrocyte malfunction exacerbates glutamate gliotransmission. • Reactive astrocytes promote synaptic potentiation in the brain cortex. Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in multiple sclerosis initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined. Here we unveil deregulation of astrocytic calcium signaling and astrocyte-to-neuron communication as key pathophysiological mechanisms of cortical dysfunction in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Using two-photon imaging ex vivo and fiber photometry in freely behaving mice, we found that acute EAE was associated with the emergence of spontaneously hyperactive cortical astrocytes exhibiting dysfunctional responses to cannabinoid, glutamate and purinoreceptor agonists. Abnormal astrocyte signaling by G i and G q protein coupled receptors was observed in the inflamed cortex. This was mirrored by treatments with pro-inflammatory factors both in vitro and ex vivo , suggesting cell-autonomous effects of the cortical neuroinflammatory environment. Finally, deregulated astrocyte calcium activity was associated with an enhancement of glutamatergic gliotransmission and a shift of astrocyte-mediated short-term and long-term plasticity mechanisms towards synaptic potentiation. Overall, our data identify astrocyte-neuronal network dysfunctions as key pathological features of gray matter inflammation in multiple sclerosis and potentially additional neuroimmunological disorders. [ABSTRACT FROM AUTHOR]

Industrialized environments, despite benefits such as higher levels of formal education and lower rates of infections, can also have pernicious impacts upon brain atrophy. Partly for this reason, comparing age-related brain volume trajectories between industrialized and non-industrialized populations can help to suggest lifestyle correlates of brain health. The Tsimane, indigenous to the Bolivian Amazon, derive their subsistence from foraging and horticulture and are physically active. The Moseten, a mixed-ethnicity farming population, are physically active but less than the Tsimane. Within both populations (N = 1024; age range = 46–83), we calculated regional brain volumes from computed tomography and compared their cross-sectional trends with age to those of UK Biobank (UKBB) participants (N = 19,973; same age range). Surprisingly among Tsimane and Moseten (T/M) males, some parietal and occipital structures mediating visuospatial abilities exhibit small but significant increases in regional volume with age. UKBB males exhibit a steeper negative trend of regional volume with age in frontal and temporal structures compared to T/M males. However, T/M females exhibit significantly steeper rates of brain volume decrease with age compared to UKBB females, particularly for some cerebro-cortical structures (e.g., left subparietal cortex). Across the three populations, observed trends exhibit no interhemispheric asymmetry. In conclusion, the age-related rate of regional brain volume change may differ by lifestyle and sex. The lack of brain volume reduction with age is not known to exist in other human population, highlighting the putative role of lifestyle in constraining regional brain atrophy and promoting elements of non-industrialized lifestyle like higher physical activity. [ABSTRACT FROM AUTHOR]

Adolescence is a crucial period for physical and psychological development. The impact of negative life events represents a risk factor for the onset of neuropsychiatric disorders. This study aims to investigate the relationship between negative life events and structural brain connectivity, considering both graph theory and connectivity strength. A group (n = 487) of adolescents from the IMAGEN Consortium was divided into Low and High Stress groups. Brain networks were extracted at an individual level, based on morphological similarity between grey matter regions with regions defined using an atlas-based region of interest (ROI) approach. Between-group comparisons were performed with global and local graph theory measures in a range of sparsity levels. The analysis was also performed in a larger sample of adolescents (n = 976) to examine linear correlations between stress level and network measures. Connectivity strength differences were investigated with network-based statistics. Negative life events were not found to be a factor influencing global network measures at any sparsity level. At local network level, between-group differences were found in centrality measures of the left somato-motor network (a decrease of betweenness centrality was seen at sparsity 5%), of the bilateral central visual and the left dorsal attention network (increase of degree at sparsity 10% at sparsity 30% respectively). Network-based statistics analysis showed an increase in connectivity strength in the High stress group in edges connecting the dorsal attention, limbic and salience networks. This study suggests negative life events alone do not alter structural connectivity globally, but they are associated to connectivity properties in areas involved in emotion and attention.

Abstract This study investigated brain responses during cybersickness in healthy adults using functional near-infrared spectroscopy (fNIRS). Thirty participants wore a head-mounted display and observed a virtual roller coaster scene that induced cybersickness. Cortical activation during the virtual roller coaster task was measured using fNIRS. Cybersickness symptoms were evaluated using a Simulator Sickness Questionnaire (SSQ) administered after the virtual rollercoaster. Pearson correlations were performed for cybersickness symptoms and the beta coefficients of hemodynamic responses. The group analysis of oxyhemoglobin (HbO) and total hemoglobin (HbT) levels revealed deactivation in the bilateral angular gyrus during cybersickness. In the Pearson correlation analyses, the HbO and HbT beta coefficients in the bilateral angular gyrus had a significant positive correlation with the total SSQ and disorientation. These results indicated that the angular gyrus was associated with cybersickness. These findings suggest that the hemodynamic response in the angular gyrus could be a biomarker for evaluating cybersickness symptoms.

Summary Single‐cell proteomics (SCP) is an emerging approach to resolve cellular heterogeneity within complex tissues of multi‐cellular organisms. Here, we demonstrate the feasibility of SCP on plant samples using the model plant Arabidopsis thaliana. Specifically, we focused on examining isolated single cells from the cortex and endodermis, which are two adjacent root cell types derived from a common stem cell lineage. From 756 root cells, we identified 3763 proteins and 1118 proteins/cell. Ultimately, we focus on 3217 proteins quantified following stringent filtering. Of these, we identified 596 proteins whose expression is enriched in either the cortex or endodermis and are able to differentiate these closely related plant cell types. Collectivity, this study demonstrates that SCP can resolve neighboring cell types with distinct functions, thereby facilitating the identification of biomarkers and candidate proteins to enable functional genomics. [ABSTRACT FROM AUTHOR]

Even in the absence of specific sensory input or a behavioral task, the brain produces structured patterns of activity. This organized activity is modulated by changes in arousal. Here, we use wide-field voltage imaging to establish how arousal relates to cortical network voltage and hemodynamic activity in spontaneously behaving head-fixed male and female mice expressing the voltage-sensitive fluorescent FRET sensor Butterfly 1.2. We find that global voltage and hemodynamic signals are both positively correlated with changes in arousal with amaximum correlation of 0.5 and 0.25, respectively, at a time lag of 0 s. We next show that arousal influences distinct cortical regions for both voltage and hemodynamic signals. These include a broad positive correlation across most sensorymotor cortices extending posteriorly to the primary visual cortex observed in both signals. In contrast, activity in the prefrontal cortex is positively correlated to changes in arousal for the voltage signal while it is a slight net negative correlation observed in the hemodynamic signal. Additionally, we show that coherence between voltage and hemodynamic signals relative to arousal is strongest for slow frequencies below 0.15 Hz and is near zero for frequencies >1 Hz. We finally show that coupling patterns are dependent on the behavioral state of the animal with correlations being driven by periods of increased orofacial movement. Our results indicate that while hemodynamic signals show strong relations to behavior and arousal, these relations are distinct from those observed by voltage activity. [ABSTRACT FROM AUTHOR]

As cells migrate through biological tissues, they must frequently squeeze through micron-sized constrictions in the form of interstitial pores between extracellular matrix fibers and/or other cells. Although it is now well recognized that such confined migration is limited by the nucleus, which is the largest and stiffest organelle, it remains incompletely understood how cells apply sufficient force to move their nucleus through small constrictions. Here, we report a mechanism by which contraction of the cell rear cortex pushes the nucleus forward to mediate nuclear transit through constrictions. Laser ablation of the rear cortex reveals that pushing forces behind the nucleus are the result of increased intracellular pressure in the rear compartment of the cell. The pushing forces behind the nucleus depend on accumulation of actomyosin in the rear cortex and require Rho kinase (ROCK) activity. Collectively, our results suggest a mechanism by which cells generate elevated intracellular pressure in the posterior compartment to facilitate nuclear transit through threedimensional (3D) constrictions. This mechanism might supplement or even substitute for other mechanisms supporting nuclear transit, ensuring robust cell migrations in confined 3D environments. [ABSTRACT FROM AUTHOR]

Pain management in neonates continues to be a challenge. Diverse therapies are available that cause loss of pain sensitivity. However, because of side effects, the search for better options remains open. Dexmedetomidine is a promising drug; it has shown high efficacy with a good safety profile in sedation and analgesia in the immature nervous system. Though dexmedetomidine is already in use for pain control in neonates (including premature neonates) and infants as an adjunct to other anesthetics, the question remains whether it affects the neuronal activity patterning that is critical for development of the immature nervous system. In this study, using the neonatal rat as a model, the pharmacodynamic effects of dexmedetomidine on the nervous and cardiorespiratory systems were studied. Our results showed that dexmedetomidine has pronounced analgesic effects in the neonatal rat pups, and also weakly modified both the immature network patterns of cortical and hippocampal activity and the physiology of sleep cycles. Though the respiration and heart rates were slightly reduced after dexmedetomidine administration, it might be considered as the preferential independent short-term therapy for pain management in the immature and developing brain. [ABSTRACT FROM AUTHOR]

In 1998, Jones suggested a classification of thalamocortical projections into core and matrix divisions (Jones, 1998). In this classification, core projections are specific, topographical, innervate middle cortical layers, and serve to transmit specific information to the cortex for further analysis; matrix projections, in contrast, are diffuse, much less topographic, innervate upper layers, especially Layer 1, and serve a more global, modulatory function, such as affecting levels of arousal. This classification has proven especially influential in studies of thalamocortical relationships. Whereas it may be the case that a clear subset of thalamocortical connections fit the core motif, since they are specific, topographic, and innervate middle layers, we argue that there is no clear evidence for any single class that encompasses the remainder of thalamocortical connections as is claimed for matrix. Instead, there is great morphological variation in connections made by thalamocortical projections fitting neither a core nor matrix classification. We thus conclude that the core/matrix classification should be abandoned, because its application is not helpful in providing insights into thalamocortical interactions and can even be misleading. As one example of the latter, recent suggestions indicate that core projections are equivalent to first-order thalamic relays (i.e., those that relay subcortical information to the cortex) and matrix to higher-order relays (i.e., those that relay information from one cortical area to another), but available evidence does not support this relationship. All of this points to a need to replace the core/matrix grouping with a more complete classification of thalamocortical projections. [ABSTRACT FROM AUTHOR]

Rodents rely on their whiskers as vital sensory tools for tactile perception, enabling them to distinguish textures and shapes. Ensuring the reliability and constancy of tactile perception under varying stimulus conditions remains a fascinating and fundamental inquiry. This study explores the impact of stimulus configurations, including whisker movement velocity and object spatial proximity, on texture discrimination and stability in rats. To address this issue, we employed three distinct approaches for our investigation. Stimulus configurations notably affected tactile inputs, altering whisker vibration's kinetic and kinematic aspects with consistent effects across various textures. Through a texture discrimination task, rats exhibited consistent discrimination performance irrespective of changes in stimulus configuration. However, alterations in stimulus configuration significantly affected the rats' ability to maintain stability in texture perception. Additionally, we investigated the influence of stimulus configurations on cortical neuronal responses by manipulating them experimentally. Notably, cortical neurons demonstrated substantial and intricate changes in firing rates without compromising the ability to discriminate between textures. Nevertheless, these changes resulted in a reduction in texture neuronal response stability. Stimulating multiple whiskers led to improved neuronal texture discrimination and maintained coding stability. These findings emphasize the importance of considering numerous factors and their interactions when studying the impact of stimulus configuration on neuronal responses and behavior. [ABSTRACT FROM AUTHOR]