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Across vertebrate species, gonadal hormones coordinate physiology with behavior to facilitate social interactions essential for reproduction and survival. In adulthood, these hormones activate neural circuits that regulate behaviors presenting differently in females and males, such as parenting and territorial aggression. Yet long before sex-typical behaviors emerge at puberty, transient hormone production during sensitive periods of neurodevelopment establish the circuits upon which adult hormones act. How transitory waves of early-life hormone signaling exert lasting effects on the brain remains a central question. Here we discuss how perinatal estradiol signaling organizes cellular and molecular sex differences in the rodent brain. We review classic anatomic studies revealing sex differences in cell number, volume, and neuronal projections, and consider how single-cell sequencing methods enable distinction between sex-biased cell-type abundance and gene expression. Finally, we highlight the recent discovery of a gene regulatory program activated by estrogen receptor α (ERα) following the perinatal hormone surge. A subset of this program displays sustained sex-biased gene expression and chromatin accessibility throughout the postnatal sensitive period, demonstrating a bona fide epigenetic mechanism. We propose that ERα-expressing neurons throughout the social behavior network use similar gene regulatory programs to coordinate brain sexual differentiation.

This review highlights new concepts in vascular patterning in the last 10 years, with emphasis on its beauty and complexity. Endothelial cell signaling pathways that respond to molecular or mechanical signals are described, and examples of vascular patterning that use these pathways in brain, skin, heart, and kidney are highlighted. The pathological consequences of patterning loss are discussed in the context of arteriovenous malformations (AVMs), and prospects for the next 10 years presented.

We report a case of a preschool age girl, previously healthy, referred to our hospital on ventilatory support with a history of vomiting, headache, and rapid neurological worsening within 24 hours in the form of seizures, encephalopathy and loss of consciousness. On presentation, she was deeply comatose with dilated non-reactive pupils, absent brainstem reflexes and flaccid quadriplegia. Diagnosis of acute haemorrhagic leukoencephalitis was considered based on laboratory and neuroimaging findings. MRI of the brain showed fluffy white matter hyperintensities and microhaemorrhages in bilateral cerebral hemispheres and thalami. Aggressive treatment with methylprednisolone, plasmapheresis and intravenous immunoglobulin showed dramatic improvement with no neurological sequelae. Our case is unique in a way that despite the hyperacute onset and rapid deterioration, with a fulminant course in the intensive care unit, the child recovered dramatically with aggressive management.

Sex differences are commonly observed in behaviors that are closely linked to adaptive function, but sex differences can also be observed in behavioral "building blocks" such as locomotor activity and reward processing. Modern neuroscientific inquiry, in pursuit of generalizable principles of functioning across sexes, has often ignored these more subtle sex differences in behavioral building blocks that may result from differences in these behavioral building blocks. A frequent assumption is that there is a default (often male) way to perform a behavior. This approach misses fundamental drivers of individual variability within and between sexes. Incomplete behavioral descriptions of both sexes can lead to an overreliance on reduced "single-variable" readouts of complex behaviors, the design of which may be based on male-biased samples. Here, we advocate that the incorporation of new machine-learning tools for collecting and analyzing multimodal "big behavior" data allows for a more holistic and richer approach to the quantification of behavior in both sexes. These new tools make behavioral description more robust and replicable across laboratories and species, and may open up new lines of neuroscientific inquiry by facilitating the discovery of novel behavioral states. Having more accurate measures of behavioral diversity in males and females could serve as a hypothesis generator for where and when we should look in the brain for meaningful neural differences.

Cysticercosis is caused by the larvae ofTaenia soliumand is a significant health problem. Disseminated cysticercosis is an infrequent manifestation of the same. A woman in her 30s presented to us with a history of seizures, outward protrusion of both eyes and multiple soft-tissue swellings over the face and tongue for 3 years. Imaging studies revealed multiple cystic lesions in the brain parenchyma, extraocular muscles, subcutaneous tissue, muscles of mastication and tongue. A high index of suspicion and a planned therapeutic approach is required in such cases.

Hiccups are experienced by people of all ages. While acute hiccups are benign and self-limited, persistent and intractable hiccups can sometimes signal a serious disease. We present a young previously healthy man who complained of only hiccups for 4 months and later developed a severe headache and projectile vomiting. His systemic examination was within normal limits. Brain imaging revealed a diffuse pontine glioma with mild hydrocephalus.

A woman in her 30s was referred to our neurology outpatient clinic following an incidental finding of significant bilateral and symmetric basal ganglia, thalamic, cerebellar and subcortical white matter calcification on brain CT and MRI. A diagnosis of asymptomatic primary familial brain calcification (PFBC) was made. Targeted genetic testing revealed a likely pathogenic variant in the

Alzheimer disease (AD) is the most common cause of dementia, accounting for 50% to 60% of cases and affecting nearly 6 million people in the United States. Definitive diagnosis requires either antemortem brain biopsy or postmortem autopsy. However, clinical neuroimaging has been playing a greater role in the diagnosis and management of AD, and several PET tracers approach the sensitivity of tissue diagnosis in identifying AD pathologic condition. This review will focus on the utility of PET imaging in the setting of cognitive impairment, with an emphasis on its role in the diagnosis of AD.

Flexibly selecting appropriate actions in response to complex, ever-changing environments requires both cortical and subcortical regions, which are typically described as participating in a strict hierarchy. In this traditional view, highly specialized subcortical circuits allow for efficient responses to salient stimuli, at the cost of adaptability and context specificity, which are attributed to the neocortex. Their interactions are often described as the cortex providing top-down command signals for subcortical structures to implement; however, as available technologies develop, studies increasingly demonstrate that behavior is represented by brainwide activity and that even subcortical structures contain early signals of choice, suggesting that behavioral functions emerge as a result of different regions interacting as truly collaborative networks. In this review, we discuss the field’s evolving understanding of how cortical and subcortical regions in placental mammals interact cooperatively, not only via top-down cortical-subcortical inputs but through bottom-up interactions, especially via the thalamus. We describe our current understanding of the circuitry of both the cortex and two exemplar subcortical structures, the superior colliculus and striatum, to identify which information is prioritized by which regions. We then describe the functional circuits these regions form with one another, and the thalamus, to create parallel loops and complex networks for brainwide information flow. Finally, we challenge the classic view that functional modules are contained within specific brain regions; instead, we propose that certain regions prioritize specific types of information over others, but the subnetworks they form, defined by their anatomical connections and functional dynamics, are the basis of true specialization.

The mechanisms behind Alzheimer's disease are not yet fully described, and changes in the electrophysiology of patients across the continuum of the disease could help to understand them. In this work, we study the power spectral distribution of a set of 129 individuals from the Connectomics of Brian Aging and Dementia project. From this sample, we acquired task-free data, with eyes closed, and estimated the power spectral distribution in source space. We compared the spectral profiles of three groups of individuals: 70 healthy controls, 27 patients with amnestic MCI, and 32 individuals showing cognitive impairment without subjective complaints (IWOC). The results showed a slowing of the brain activity in the aMCI patients, when compared to both the healthy controls and the IWOC individuals. These differences appeared both as a decrease in power for high frequency oscillations and an increase in power in alpha oscillations. The slowing of the spectrum was significant mainly in parietal and medial frontal areas. We were able to validate the slowing of the brain activity in individuals with aMCI, appearing in our sample in areas related to the default mode network. However, this pattern did not appear in the IWOC individuals, suggesting that their condition is not part of the AD continuum. This work raises interesting questions about this group of individuals, and the underlying brain mechanisms behind their cognitive impairment.

Episodic counterfactual thoughts (eCFT) consist of imagining alternative outcomes to past experiences. A common sub-class of eCFT— upward eCFT—involves imagining how past negative experiences could have been better , either because one could have done something differently (internal) or because something about the circumstances could have been different (external). Although previous neuroimaging research has shown that the brain's default mode network (DMN) supports upward eCFT, it is unclear how it is differentially recruited during internal versus external upward eCFT. We collected functional magnetic resonance imaging data while participants remembered negative autobiographical memories, generated either internal or external upward eCFT for the memory, and then rated the plausibility, perceived control and difficulty of eCFT generation. Both internal and external eCFT engaged midline regions of cingulate cortex, a central node of the DMN. Most activity differentiating eCFT, however, occurred outside the DMN. External eCFT engaged cuneus, angular gyrus and precuneus, whereas internal eCFT engaged posterior cingulate and precentral gyrus. Angular gyrus and precuneus were additionally sensitive to perceived plausibility of external eCFT, while postcentral gyrus and insula activity scaled with perceived plausibility of internal eCFT. These results highlight the key brain regions that might be involved in cases of maladaptive mental simulations. This article is part of the theme issue ‘Thinking about possibilities: mechanisms, ontogeny, functions and phylogeny’.

Chemotherapy can result in toxic side effects in the brain. Intake of marine-based omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alter brain fatty acids, potentially improving brain function. However, it is unclear if alpha-linolenic acid (ALA), the plant-based n-3, affects brain PUFAs during chemotherapy. The objective of this study was to examine the effects of dietary ALA, EPA and DHA, with high or low sucrose, on brain PUFAs in a mouse model of chemotherapy. Secondarily, the use of liver PUFAs as surrogate measures of brain PUFAs was examined. Lipid peroxidation (4-HNE) and neurotrophic markers (BDNF) were assessed. Female C57Bl/6 mice (n = 90) were randomized to 1 of 5 diets (high EPA + DHA/high or low sucrose, high ALA/high or low sucrose, or control with no EPA + DHA/low ALA/low sucrose) and injected with doxorubicin-based chemotherapy or saline. Brain EPA and DHA were greater (p < 0.0001) with high EPA + DHA diets, regardless of sucrose; there were no significant differences in brain PUFAs between high ALA diets and control. Chemotherapy-treated mice had higher brain and liver DHA (p < 0.05) and lower brain and liver linoleic acid (p < 0.0001). Brain n-3 and n-6 PUFAs were strongly correlated with liver n-3 (r = 0.8214, p < 0.0001) and n-6 PUFAs (r = 0.7568, p < 0.0001). BDNF was correlated with brain total PUFAs (r = 0.36; p < 0.05). In conclusion, dietary ALA in proportions approximately two times greater than consumed by humans did not appreciably increase brain n-3 PUFAs compared to low ALA intake. Liver PUFAs may be a useful surrogate marker of brain PUFAs in this mouse model.

Patients with obstructive sleep apnea (OSA) show brain injury in sites responsible for autonomic, cognitive, and respiratory functions. Brain changes in OSA may vary with disease severity as assessed by the apnea-hypopnea index (AHI), which does not provide information about the apnea depth and length in contrast to oxygen desaturation. Although significant associations with brain injury and AHI are known in OSA, it is unclear whether AHI or the extent of oxygen desaturations better correlate with brain damage. We evaluated associations between brain changes, AHI, and oxygen desaturation using diffusion tensor imaging-based measures.We acquired diffusion tensor imaging data from 19 patients with OSA using a 3.0-Tesla MRI scanner and calculated, normalized, and smoothed mean, axial, and radial diffusivity maps that were used for correlations between brain changes, oxygen desaturation, and AHI values.Positive correlations with extent of injury (mean, axial, and radial diffusivity values) and AHI appeared in the frontal areas, cingulate and insula, amygdala, hippocampus, and basal pons, and negative associations emerged in the putamen, internal-capsule, globus-pallidus, and cerebellar cortices. Regional diffusivity values and oxygen desaturation showed positive correlations in the cingulate, frontal, putamen, and cerebellar sites, and negative relationships in several areas, including the occipital cortex.Patients with OSA show negative and positive correlations, indicated by increased and decreased diffusivity values, resulting from chronic and acute changes in those areas. The extent of injury in OSA partially depends on the extent of AHI and oxygen desaturation, with the effects representing continued development from acute to chronic processes.Sahib A, Roy B, Kang D, Aysola RS, Wen E, Kumar R. Relationships between brain tissue damage, oxygen desaturation, and disease severity in obstructive sleep apnea evaluated by diffusion tensor imaging.

Background Histogram analysis is a texture analysis method that can be used in medical images. Quantitative values of the intensity of images can be obtained with histogram analysis. It aimed to evaluate corpus callosum in magnetic resonance images (MRIs) using histogram analysis of pediatric patients with autism spectrum disorder (ASD) to compare them with healthy controls. Methods This study included 29 children with ASD and 29 healthy children with normal brain MRI. High-resolution three-dimensional turbo field echo images were obtained with a 1.5 T scanner device for brain magnetic resonance imaging. On the corpus callosum in the sagittal T1-weighted images obtained, mean gray level density (mean), the standard deviation, median, minimum, maximum, entropy, variance, skewness, kurtosis, uniformity, size % L, size % M, size % U, and percentile parameters were measured. Results In ASD patients, mean, standard deviation, maximum, median, variance, entropy, 25%, 75%, 90%, 97%, and 99% values were found to be lower than the control group, and size % U value was higher. In addition, the corpus callosum area was significantly lower in the ASD compared to the controls. Conclusion According to our study, corpus callosum of patients with ASD showed differences compared to healthy controls by histogram analysis, even though they were seen as normal in brain MRI. We think that histogram analysis can be used to evaluate possibly affected areas of brain in ASD patients.

Background Point-of-care (POC) MRI is a bedside imaging technology with fewer than five units in clinical use in the United States and a paucity of scientific studies on clinical applications. Purpose To evaluate the clinical and operational impacts of deploying POC MRI in emergency department (ED) and intensive care unit (ICU) patient settings for bedside neuroimaging, including the turnaround time. Materials and Methods In this preliminary retrospective study, all patients in the ED and ICU at a single academic medical center who underwent noncontrast brain MRI from January 2021 to June 2021 were investigated to determine the number of patients who underwent bedside POC MRI. Turnaround time, examination limitations, relevant findings, and potential CT and fixed MRI findings were recorded for patients who underwent POC MRI. Descriptive statistics were used to describe clinical variables. The Mann-Whitney

With their exponentially rising computational power, digital platforms are heralding a new era of hybrid intelligence. There has recently been much enthusiasm and hype that the Metaverse has the potential to unlock hybrid intelligence. This is premised on the idea that the Metaverse represents an applied convergence of Artificial Intelligence of Things (AIoT) and Extended Reality (XR) that intersects with urbanism in terms of the distinctive features of platform-mediated everyday life experiences in cities. However, social interaction and its resulting social organization in the Metaverse are mediated and governed by algorithms and thus submitted to—a dream of—complete logical ordering. This raises a plethora of concerns related to the systemic collection and algorithmic processing of users’ personal, brain, and biometric data, i.e., profound societal—and the hardest to predict ethical—implications. Therefore, this study analyzes and synthesizes a large body of scientific literature on the unfolding convergence of AIoT and XR technologies, neurotechnology, and nanobiotechnology in the realm of the Metaverse in order to derive a novel conceptual framework for the Metaverse as an envisioned virtual model of platform urbanism. Further, it examines the key challenges and risks of these converging technologies in relation to the Metaverse and beyond. This study employs thematic analysis and synthesis to cope with multidisciplinary literature. The analysis identifies seven themes: (1) Platformization, (2) platform urbanism, (3) virtual urbanism, (4) XR technologies, (5) AIoT technologies, (6) neurotechnology, and (7) nanobiotechnology. The synthesized evidence reveals that, while neurotechnology and nanobiotechnology have numerous benefits and promising prospects, they raise contentions and controversies stemming from their potential use to inflict harm to human users—if left unchecked—through the black box of the algorithmic mediation underpinning the Metaverse. The findings serve to steer the Metaverse to contribute to human flourishing and wellbeing by adhering to and upholding ethical principles as well as leveraging its underlying disruptive technologies in meaningful ways. They also aid scholars, practitioners, and policymakers in assessing the pros and cons of these technologies, especially their inevitable ramifications.

Neural stem cells (NSCs) present attractive natural drug delivery systems (DDSs). Their migratory potential enables crossing of the blood-brain barrier and efficient and selective accumulation near malignant cells. Here, we present the potential of NSCs as DDSs for nucleoside analogue conjugated nanogels (NGs). Two different approaches were investigated: the intracellular loading and extracellular cell surface decoration with NGs. For both designs, the tumor-specific migratory potentials of NSCs remained unchanged; however, the intracellular loading showed a shorter NG retention. The cell surface decoration protocol yielded a high loading capacity of 100% after 1 h and a prolonged drug retention. A redox-sensitive linker between NGs and the nucleoside analogue 5-ethynyl-2 '-deoxycytidine (EdC) allowed a tumor environment-specific drug release and its efficient and preferential incorporation into the DNA of the tumor cells. Interestingly, the tumor-trafficking potentials of NSCs were significantly potentiated by irradiation of tumor cells. In conclusion, this study indicates the potentials of cell surface-decorated NSCs as DDSs for tumor specific release, cellular uptake, and incorporation of EdC into DNA.

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Twin and family studies have historically aimed to partition phenotypic variance into components corresponding to additive genetic effects (A), common environment (C), and unique environment (E). Here we present the ACE Model and several extensions in the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), employed using the new Fast Efficient Mixed Effects Analysis (FEMA) package. In the twin sub-sample (n = 924; 462 twin pairs), heritability estimates were similar to those reported by prior studies for height (twin heritability = 0.86) and cognition (twin heritability between 0.00 and 0.61), respectively. Incorporating SNP-derived genetic relatedness and using the full ABCD Study® sample (n = 9,742) led to narrower confidence intervals for all parameter estimates. By leveraging the sparse clustering method used by FEMA to handle genetic relatedness only for participants within families, we were able to take advantage of the diverse distribution of genetic relatedness within the ABCD Study® sample.

A significant proportion of brains with Alzheimer's disease pathology are obtained from patients that were cognitively normal, suggesting that differences within the brains of these individuals made them resilient to the disease. Here, we describe recent approaches that specifically increase synaptic resilience, as loss of synapses is considered to be the first change in the brains of Alzheimer's patients. We start by discussing studies showing benefit from increased expression of neurotrophic factors and protective genes. Methods that effectively make dendritic spines stronger, specifically by acting through actin network proteins, scaffolding proteins and inhibition of phosphatases are described next. Importantly, the therapeutic strategies presented in this review tackle Alzheimer's disease not by targeting plaques and tangles, but instead by making synapses resilient to the pathology associated with Alzheimer's disease, which has tremendous potential.

Previous studies have identified bilingualism as a protective factor against dementia. Here we aimed to test whether being bilingual at different life stages impacts cognition and brain structure in older adulthood. We included 746 participants from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Assessment of bilingualism at 3 life stages (early: 13-30, middle: 30-65 and late: over 65 years old) was determined with the Lifetime of Experiences Questionnaire. Individuals reporting bilingualism (i.e., daily use of L2) in the early life stage outperformed monolinguals on learning & memory, working-memory, executive functions and language. Bilingualism in middle life stage showed a significant advantage on learning & memory, while no effect of bilingualism in old life stage was identified. Brain gray matter volume was not associated with L2 use and did not differ between groups. However, stronger correlations between brain gray matter volume in selected brain regions and cognitive performance were found in bilingual participants in the early and middle life stages. Our results indicate that bilingualism in early life might provide a long-lasting protective effect on cognition and shape the brain to sustain cognitive performance in older adulthood.

Several GWAS reported Myocyte Enhancer Factor 2 C (MEF2C) gene associations with white matter microstructure and psychiatric disorders, and MEF2C involvement in pathways related to neuronal development suggests a common biological factor underlying these phenotypes. We aim to refine the MEF2C effects in the brain relying on an integrated analysis of white matter and psychiatric phenotypes in an extensively characterized sample. This study included 870 Brazilian adults (47% from an attention-deficit/hyperactivity disorder outpatient clinic) assessed through standardized psychiatric interviews, 139 of which underwent a magnetic resonance imaging scan. We evaluated variants in the MEF2C region using two approaches: 1) a gene-wide analysis, which uses the sum of polymorphism effects, and 2) SNP analyses, restricted to the independent variants within the gene. The outcomes included psychiatric phenotypes and fractional anisotropy for brain images. Results: The gene-wide analyses pointed to a nominal association between MEF2C and the Temporal Portion of the Superior Longitudinal Fasciculus (SLFTEMP). The SNP analysis identified four independent variants significantly associated with SLFTEMP and one (rs4218438) with Substance Use Disorder. Our findings showing specific associations of MEF2C variants with temporal-frontal circuitry components may help to elucidate how the MEF2C gene underlies a broad range of psychiatric phenotypes since these regions are relevant to executive and cognitive functions.

Funder: Aarhus Universitets Forskningsfond; Id: http://dx.doi.org/10.13039/501100002739, Funder: Health Data Research UK; Id: http://dx.doi.org/10.13039/501100023699, Funder: Jabbs Foundation; Id: http://dx.doi.org/10.13039/501100016132, Funder: National Institute of Health Research Biomedical Research Centre, Interoception is the sensation, perception, and integration of signals from within the body. It has been associated with a broad range of physiological and psychological processes. Further, interoceptive variables are related to specific regions and networks in the human brain. However, it is not clear whether or how these networks relate empirically to different domains of physiological and psychological health at the population level. We analysed a data set of 19,020 individuals (10,055 females, 8965 males; mean age: 63 years, age range: 45-81 years), who have participated in the UK Biobank Study, a very large-scale prospective epidemiological health study. Using canonical correlation analysis (CCA), allowing for the examination of associations between two sets of variables, we related the functional connectome of brain regions implicated in interoception to a selection of nonimaging health and lifestyle related phenotypes, exploring their relationship within modes of population co-variation. In one integrated and data driven analysis, we obtained four statistically significant modes. Modes could be categorised into domains of arousal and affect and cardiovascular health, respiratory health, body mass, and subjective health (all p < .0001) and were meaningfully associated with distinct neural circuits. Circuits represent specific neural "fingerprints" of functional domains and set the scope for future studies on the neurobiology of interoceptive involvement in different lifestyle and health-related phenotypes. Therefore, our research contributes to the conceptualisation of interoception and may lead to a better understanding of co-morbid conditions in the light of shared interoceptive structures.

Neurological symptoms, in particular cognitive deficits, are common in post-COVID-19 syndrome (PCS). There is no approved therapy available, and the underlying disease mechanisms are largely unknown. Besides others, autoimmune processes may play a key role.We here present data of a prospective study conducted between September 2020 and December 2021 and performed at two German University hospitals with specialized Neurology outpatient clinics. Fifty patients with self-reported cognitive deficits as main complaint of PCS and available serum and CSF samples were included. Cell-based assays and indirect immunofluorescence on murine brain sections were used to detect autoantibodies against intracellular and surface antigens in serum and CSF and analyzed for associations with cognitive screening assessment.Clearly abnormal cognitive status (MoCA ≤ 25/30 points) was only seen in 18/50 patients with self-reported cognitive deficits. Most patients (46/50) had normal routine CSF parameters. Anti-neuronal autoantibodies were found in 52% of all patients: n=9 in serum only, n=3 in CSF only and n=14 in both, including those against myelin, Yo, Ma2/Ta, GAD65 and NMDA receptor, but also a variety of undetermined epitopes on brain sections. These included cerebral vessel endothelium, Purkinje neurons, granule cells, axon initial segments, astrocytic proteins and neuropil of basal ganglia or hippocampus as well as a formerly unknown perinuclear rim pattern. Pathological MoCA results were associated with the presence of anti-neuronal antibodies in CSF (p=0.0004).Autoantibodies targeting brain epitopes are common in PCS patients and strongly associate with pathological cognitive screening tests, in particular when found in CSF. Several underlying autoantigens still await experimental identification. Further research is needed to inform on the clinical relevance of these autoantibodies, including controlled studies that explore the potential efficacy of antibody-depleting immunotherapy in PCS.

Abstract: Adult neurogenesis deficiency has been proposed to be a common hallmark in different age-related neurodegenerative diseases. The administration of flavonoids is currently reported as a potentially beneficial strategy for preventing brain aging alterations, including adult neurogenesis decline. Flavonoids are a class of plant-derived dietary polyphenols that have drawn attention for their neuroprotective and pro-cognitive effects. Although they undergo extensive metabolism and localize in the brain at low concentrations, flavonoids are now believed to improve cerebral vasculature and interact with signal transduction cascades involved in the regulation of adult neurogenesis. Further-more, many dietary flavonoids have been shown to reduce oxidative stress and neuroinflammation, improving the neuronal microenvironment where adult neurogenesis occurs. The overall goal of this review is to summarize the evidence supporting the role of flavonoids in modulating adult neurogene-sis as well as to highlight how these dietary agents may be promising candidates in restoring healthy brain function during physiological and pathological aging.

Appraisals can be influenced by cultural beliefs and stereotypes. In line with this, past research has shown that judgments about the emotional expression of a face are influenced by the face's sex, and vice versa that judgments about the sex of a person somewhat depend on the person's facial expression. For example, participants associate anger with male faces, and female faces with happiness or sadness. However, the strength and the bidirectionality of these effects remain debated. Moreover, the interplay of a stimulus' emotion and sex remains mostly unknown in the auditory domain. To investigate these questions, we created a novel stimulus set of 121 avatar faces and 121 human voices (available at https://bit.ly/2JkXrpy) with matched, fine-scale changes along the emotional (happy to angry) and sexual (male to female) dimensions. In a first experiment (N = 76), we found clear evidence for the mutual influence of facial emotion and sex cues on ratings, and moreover for larger implicit (task-irrelevant) effects of stimulus' emotion than of sex. These findings were replicated and extended in two preregistered studies-one laboratory categorization study using the same face stimuli (N = 108; https://osf.io/ve9an), and one online study with vocalizations (N = 72; https://osf.io/vhc9g). Overall, results show that the associations of maleness-anger and femaleness-happiness exist across sensory modalities, and suggest that emotions expressed in the face and voice cannot be entirely disregarded, even when attention is mainly focused on determining stimulus' sex. We discuss the relevance of these findings for cognitive and neural models of face and voice processing.

A key goal for cognitive neuroscience is to understand the neurocognitive systems that support semantic memory. Recent multivariate analyses of neuroimaging data have contributed greatly to this effort, but the rapid development of these novel approaches has made it difficult to track the diversity of findings and to understand how and why they sometimes lead to contradictory conclusions. We address this challenge by reviewing cognitive theories of semantic representation and their neural instantiation. We then consider contemporary approaches to neural decoding and assess which types of representation each can possibly detect. The analysis suggests why the results are heterogeneous and identifies crucial links between cognitive theory, data collection, and analysis that can help to better connect neuroimaging to mechanistic theories of semantic cognition.

International audience; Background & aimsIn most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut–brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control.MethodsAn integrative study was performed after SHAM (n = 8) or RYGBP (n = 8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis.ResultsWe showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP.ConclusionThis longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance.

Women who contract a viral or bacterial infection during pregnancy have an increased risk of giving birth to a child with a neurodevelopmental or psychiatric disorder. The effects of maternal infection are likely mediated by the maternal immune response, as preclinical animal models have confirmed that maternal immune activation (MIA) leads to long lasting changes in offspring brain and behavior development. The present study sought to determine the impact of MIA-exposure during the first or second trimester on neuronal morphology in dorsolateral prefrontal cortex (DLPFC) and hippocampus from brain tissue obtained from MIA-exposed and control male rhesus monkey (Macaca mulatta) during late adolescence. MIA-exposed offspring display increased neuronal dendritic branching in pyramidal cells in DLPFC infra- and supragranular layers relative to controls, with no significant differences observed between offspring exposed to maternal infection in the first and second trimester. In addition, the diameter of apical dendrites in DLPFC infragranular layer is significantly decreased in MIA-exposed offspring relative to controls, irrespective of trimester exposure. In contrast, alterations in hippocampal neuronal morphology of MIA-exposed offspring were not evident. These findings demonstrate that a maternal immune challenge during pregnancy has long-term consequences for primate offspring dendritic structure, selectively in a brain region vital for socioemotional and cognitive development.

Here we characterize 6 cases (4 autopsies and 2 biopsies) of histiocytic sarcoma in the CNS of cats. All affected cats had chronic, progressive clinical signs. Three autopsied cats were euthanized because of a poor prognosis, and one died. The clinical outcome for the biopsy cases remains unknown. Tumors occurred in the brain (4 cases), spinal cord (1 case), and brain and spinal cord (1 case). Neoplasms were restricted to the CNS in 3 cases. Reported gross changes in the 4 autopsy cases consisted of neuroparenchymal swelling with or without tissue pallor or gray discoloration (2 cases) and a yellow or dark-gray mass (2 cases). Histologically, pleomorphic, round-to-elongate neoplastic cells with typical histiocytic morphology effaced the neuroparenchyma and leptomeninges. Multinucleate neoplastic cells were observed in all cases. The mitotic count was 1–24 in 2.37 mm2 (10 FN22 40× fields). Neoplastic cells in all cases had positive immunolabeling for Iba1; immunolabeling was negative for E-cadherin, CD3, CD79, and MUM1, confirming their histiocytic origin.

The present study investigates the effectiveness of a deep learning neural network for non-invasively localizing the seizure onset zone (SOZ) using multi-modal MRI data that are clinically acquired from children with drug-resistant epilepsy. A cortical parcellation was applied to localize the SOZ in cortical nodes of the epileptogenic hemisphere. At each node, the laminar surface analysis was followed to sample 1) the relative intensity of gray matter and white matter in multi-modal MRI and 2) the neighboring white matter connectivity using diffusion tractography edge strengths. A cross-validation was employed to train and test all layers of a multi-scale residual neural network (msResNet) that can classify SOZ node in an end-to-end fashion. A prediction probability of a given node belonging to the SOZ class was proposed as a non-invasive MRI marker of seizure onset likelihood. In an independent validation cohort, the proposed MRI marker provided a very large effect size of Cohen's d = 1.21 between SOZ and non-SOZ, and classified SOZ with a balanced accuracy of 0.75 in lesional and 0.67 in non-lesional MRI groups. The subsequent multi-variate logistic regression found the incorporation of the proposed MRI marker into interictal intracranial EEG (iEEG) markers further improves the differentiation between the epileptogenic focus (defined as SOZ resected during surgery) and non-epileptogenic sites (i.e., non-SOZ sites preserved during surgery) up to 15 % in non-lesional MRI group, suggesting that the proposed MRI marker could improve the localization of epileptogenic foci for successful pediatric epilepsy surgery.

Laughter is a contagious prosocial signal that conveys bonding motivation; adult crying conversely communicates desire for social proximity by signalling distress. Endogenous mu-opioid receptors (MORs) modulate sociability in humans and non-human primates. In this combined PET–fMRI study ( n = 17), we tested whether central MOR tone is associated with regional brain responses to social signals of laughter and crying. MOR availability was measured with positron emission tomography (PET) using the high-affinity agonist radioligand [ 11 C]carfentanil. Haemodynamic responses to social laughter and crying vocalizations were measured using functional magnetic resonance imaging (fMRI). Social laughter evoked activation in the auditory cortex, insula, cingulate cortex, amygdala, primary and secondary somatosensory cortex, and primary and secondary motor cortex; crying sounds led to more restricted activation in the auditory cortex and nearby areas. MOR availability was negatively correlated with the haemodynamic responses to social laughter in the primary and secondary somatosensory cortex, primary and secondary motor cortex, posterior insula, posterior cingulate cortex, precuneus, cuneus, temporal gyri and lingual gyrus. For crying-evoked activations, MOR availability was negatively correlated with medial and lateral prefrontal haemodynamic responses. Altogether our findings highlight the role of the MOR system in modulating acute brain responses to both positive and negative social signals. This article is part of the theme issue ‘Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience’.

High-resolution functional MRI (fMRI) is largely hindered by random thermal noise. Random matrix theory (RMT)-based principal component analysis (PCA) is promising to reduce such noise in fMRI data. However, there is no consensus about the optimal strategy and practice in implementation. In this work, we propose a comprehensive RMT-based denoising method that consists of 1) rank and noise estimation based on a set of newly derived multiple criteria, and 2) optimal singular value shrinkage, with each module explained and implemented based on the RMT. By incorporating the variance stabilizing approach, the denoising method can deal with low signal-to-noise ratio (SNR) (such as5) magnitude fMRI data with favorable performance compared to other state-of-the-art methods. Results from both simulation and in-vivo high-resolution fMRI data show that the proposed denoising method dramatically improves image restoration quality, promoting functional sensitivity at the same level of functional mapping blurring compared to existing denoising methods. Moreover, the denoising method can serve as a drop-in step in data preprocessing pipelines along with other procedures aimed at removal of structured physiological noises. We expect that the proposed denoising method will play an important role in leveraging high-quality, high-resolution task fMRI, which is desirable in many neuroscience and clinical applications.

This review focuses on the physiology of glymphatic solute transport and waste clearance, using evidence from experimental animal models as well as from human studies. Specific topics addressed include the biophysical characteristics of fluid and solute transport in the central nervous system, glymphatic-lymphatic coupling, as well as the role of cerebrospinal fluid movement for brain waste clearance. We also discuss the current understanding of mechanisms underlying increased waste clearance during sleep.

Human brain is a complex yet economically organized system, where a small portion of critical hub regions support the majority of brain functions. The identification of common hub nodes in a population of networks is often simplified as a voting procedure on the set of identified hub nodes across individual brain networks, which ignores the intrinsic data geometry and partially lacks the reproducible findings in neuroscience. Hence, we propose a first-ever group-wise hub identification method to identify hub nodes that are common across a population of individual brain networks. Specifically, the backbone of our method is to learn common graph embedding that can represent the majority of local topological profiles. By requiring orthogonality among the graph embedding vectors, each graph embedding as a data element is residing on the Grassmannian manifold. We present a novel Grassmannian manifold optimization scheme that allows us to find the common graph embeddings, which not only identify the most reliable hub nodes in each network but also yield a population-based common hub node map. Results of the accuracy and replicability on both synthetic and real network data show that the proposed manifold learning approach outperforms all hub identification methods employed in this evaluation.

ImportanceIt is not clear how common pure vascular cognitive impairment (VCI) is in the absence of Alzheimer disease (AD) and/or other neurodegenerative pathologies.ObjectiveTo identify participants without AD and other neurodegenerative pathologies and determine the extent to which cerebrovascular disease pathologies were associated with cognitive impairment.Design, Setting, and ParticipantsThis clinical pathological study included participants from 2 ongoing community-based cohorts that began enrollment in 1994 and 1997. Prior to death, participants were observed for a mean (SD) of 8.4 (5.3) years with annual assessments. From 2096 participants who died, 1799 (85.8%) underwent autopsy and 1767 had complete postmortem pathological examination data at the time of data analyses. To identify participants without neurodegenerative pathologies, we categorized them in 3 subgroups. A vascular subgroup was composed of participants without significant levels of neurodegenerative brain pathologies. A neurodegenerative subgroup was composed of participants without significant levels of cerebrovascular disease pathologies. A mixed subgroup was composed of the rest of the participants. Data were analyzed from May 2021 to July 2022.ExposuresBrain pathology indices obtained by postmortem pathological assessments.Main Outcomes and MeasuresThe primary outcome was cognitive impairment defined by presence of mild cognitive impairment or dementia. The secondary outcome was cognition assessed by 19 neuropsychological tests.ResultsOf 1767 included participants, 1189 (67.3%) were women, and the mean (SD) age at death was 89.4 (6.6) years. In the vascular subgroup (n = 369), cognitive impairment was present in 156 participants (42.3%) and was associated with cerebrovascular disease pathologies (macroinfarcts: odds ratio [OR], 2.05; 95% CI, 1.49-2.82; P P = .03) but not AD or other neurodegenerative pathologies, an indication of pure VCI. In mixed-effects models including all the pathologies, only macroinfarcts were associated with a faster cognitive decline rate (estimate, −0.019; SE, 0.005; P Conclusions and RelevanceIn this study, pure VCI was not rare. Macroinfarcts, specifically in frontal white matter, were the main cerebrovascular disease pathologies associated with cognitive decline in pure VCI.

Interrogating the impact of metabolism during development is important for understanding cellular and tissue formation, organ and systemic homeostasis, and dysregulation in disease states. To evaluate the vital functions metabolism coordinates during human brain development and disease, pluripotent stem cell-derived models, such as organoids, provide tractable access to neurodevelopmental processes. Despite many strengths of neural organoid models, the extent of their replication of endogenous metabolic programs is currently unclear and requires direct investigation. Studies in intestinal and cancer organoids that functionally evaluate dynamic bioenergetic changes provide a framework that can be adapted for the study of neural metabolism. Validation of in vitro models remains a significant challenge; investigation using in vivo models and primary tissue samples is required to improve our in vitro model systems and, concomitantly, improve our understanding of human development.

This review on brain multiparametric quantitative MRI (MP-qMRI) focuses on the primary subset of quantitative MRI (qMRI) parameters that represent the mobile ("free") and bound ("motion-restricted") proton pools. Such primary parameters are the proton densities, relaxation times, and magnetization transfer parameters. Diffusion qMRI is also included because of its wide implementation in complete clinical MP-qMRI application. MP-qMRI advances were reviewed over the past 2 decades, with substantial progress observed toward accelerating image acquisition and increasing mapping accuracy. Areas that need further investigation and refinement are identified as follows

The cerebrofacial metameric syndromes are a group of congenital syndromes that result in vascular malformations throughout specific anatomical distributions of the brain, cranium and face. Multiple reports of patients with high-flow or low-flow vascular malformations following a metameric distribution have supported this idea. There has been much advancement in understanding of segmental organization and cell migration since the concept of metameric vascular syndromes was first proposed. We aim to give an updated review of these embryological considerations and then propose a more detailed classification system for these syndromes, predominately incorporating the contribution of neural crest cells and somitomeres to the pharyngeal arches.

There is growing interest in developing training programs to mitigate cognitive decline associated with normal aging. Here, we assessed the effect of 3-month music and visual art training programs on the oscillatory brain activity of older adults using a partially randomized intervention design. High-density electroencephalography (EEG) was measured during the pre- and post-training sessions while participants completed a visual GoNoGo task. Time-frequency representations were calculated in regions of interest encompassing the visual, parietal, and prefrontal cortices. Before training, NoGo trials generated greater theta power than Go trials from 300 to 500 ms post-stimulus in mid-central and frontal brain areas. Theta power indexing response suppression was significantly reduced after music training. There was no significant difference between pre- and post-test for the visual art or the control group. The effect of music training on theta power indexing response suppression was associated with reduced functional connectivity between prefrontal, visual, and auditory regions. These results suggest that theta power indexes executive control mechanisms in older adults. Music training affects theta power and functional connectivity associated with response suppression. These findings contribute to a better understanding of inhibitory control ability in older adults and the neuroplastic effects of music interventions.

Professor Hans H. Ussing (1911–2000) was one of the founding members of the field of epithelial cell biology. He is most famous for the electrophysiological technique that he developed to measure electrogenic ion flux across epithelial tissues. Ussing-style electrophysiology has been applied to multiple tissues and has informed fields as diverse as amphibian biology and medicine. In the latter, this technique has contributed to a basic understanding of maladies such as hypertension, polycystic kidney disease, cystic fibrosis, and diarrheal diseases to mention but a few. In addition to this valuable contribution to biological methods, Prof. Ussing also provided strong evidence for the concept of active transport several years before the elucidation of Na+K+ATPase. In addition, he provided cell biologists with the important concept of polarized epithelia with specific and different transporters found in the apical and basolateral membranes, thus providing these cells with the ability to conduct directional, active and passive transepithelial transport. My studies have used Ussing chamber electrophysiology to study the toad urinary bladder, an amphibian cell line, renal cell lines, and, most recently, choroid plexus cell lines. This technique has formed the basis of our in vitro mechanistic studies that are used in an iterative manner with animal models to better understand disease progress and treatment. I was honored to be invited to deliver the 2022 Hans Ussing Lecture sponsored by the Epithelial Transport Group of the American Physiological Society. This manuscript is a version of the material presented in that lecture.

Resting-state functional magnetic resonance imaging (rs-fMRI)-derived functional connectivity (FC) patterns have been extensively used to delineate global functional organization of the human brain in healthy development and neuropsychiatric disorders. In this paper, we investigate how FC in males and females differs in an age prediction framework.We first estimate FC between regions-of-interest (ROIs) using distance correlation instead of Pearson's correlation. Distance correlation, as a multivariate statistical method, explores spatial relations of voxel-wise time courses within individual ROIs and measures both linear and nonlinear dependence, capturing more complex between-ROI interactions. Then, we propose a novel non-convex multi-task learning (NC-MTL) model to study age-related gender differences in FC, where age prediction for each gender group is viewed as one task, and a composite regularizer with a combination of the non-convex lWe validate the effectiveness of our NC-MTL model with distance correlation-based FC derived from rs-fMRI for predicting ages of both genders. The experimental results on the Philadelphia Neurodevelopmental Cohort demonstrate that our NC-MTL model outperforms several other competing MTL models in age prediction. We also compare the age prediction performance of our NC-MTL model using FC estimated by Pearson's correlation and distance correlation, which shows that distance correlation-based FC is more discriminative for age prediction than Pearson's correlation-based FC.This paper presents a novel framework for functional connectome developmental studies, characterizing developmental gender differences in FC patterns.