Researchers' sex/gender identity influences how sex/gender question is investigated in neuroscience: an example from an OHBM meeting.

Gender inequality and diversity in STEM is a challenging field of research. Although the relation between the sex/gender of the researcher and the scientific research practices has been previously examined, less interest has been demonstrated towards the relation between sex/gender of the researcher and the way sex/gender as a variable is explored. Here, we examine, from a neurofeminist perspective, both questions: whether sex/gender identity is related to the examination of sex/gender as a variable and whether different approaches towards examining sex/gender are being used in different topics of study within neuroscience. Using the database of submitted posters to the Organization of Human Brain Mapping 2022 annual conference, we identified abstracts examining a sex/gender-related research question. Among these target abstracts, we identified four analytical categories, varying in their degree of content-related complexity: (1) sex/gender as a covariate, (2) sex/gender as a binary variable for the study of sex/gender differences, (3) sex/gender with additional biological information, and (4) sex/gender with additional social information. Statistical comparisons between sex/gender of researcher and the target abstract showed that the proportion of abstracts from Non-binary or Other first authors compared to both Women and Men was lower for all submitted abstracts than for the target abstracts; that more researchers with sex/gender-identity other than man implemented analytical category of sex/gender with additional social information; and, for instance, that research involving cognitive, affective, and behavioural neuroscience more frequently fit into the sex/gender with additional social information-category. Word cloud analysis confirmed the validity of the four exploratorily identified analytical categories. We conclude by discussing how raising awareness about contemporary neurofeminist approaches, including perspectives from the global south, is critical to neuroscientific and societal progress.

Generalising XTRACT tractography protocols across common macaque brain templates.

Non-human primates are extensively used in neuroscience research as models of the human brain, with the rhesus macaque being a prominent example. We have previously introduced a set of tractography protocols (XTRACT) for reconstructing 42 corresponding white matter (WM) bundles in the human and the macaque brain and have shown cross-species comparisons using such bundles as WM landmarks. Our original XTRACT protocols were developed using the F99 macaque brain template. However, additional macaque template brains are becoming increasingly common. Here, we generalise the XTRACT tractography protocol definitions across five macaque brain templates, including the F99, D99, INIA, Yerkes and NMT. We demonstrate equivalence of such protocols in two ways: (a) Firstly by comparing the bodies of the tracts derived using protocols defined across the different templates considered, (b) Secondly by comparing the projection patterns of the reconstructed tracts across the different templates in two cross-species (human-macaque) comparison tasks. The results confirm similarity of all predictions regardless of the macaque brain template used, providing direct evidence for the generalisability of these tractography protocols across the five considered templates.

Fermentation technology as a driver of human brain expansion.

Brain tissue is metabolically expensive. Consequently, the evolution of humans' large brains must have occurred via concomitant shifts in energy expenditure and intake. Proposed mechanisms include dietary shifts such as cooking. Importantly, though, any new food source must have been exploitable by hominids with brains a third the size of modern humans'. Here, we propose the initial metabolic trigger of hominid brain expansion was the consumption of externally fermented foods. We define "external fermentation" as occurring outside the body, as opposed to the internal fermentation in the gut. External fermentation could increase the bioavailability of macro- and micronutrients while reducing digestive energy expenditure and is supported by the relative reduction of the human colon. We discuss the explanatory power of our hypothesis and survey external fermentation practices across human cultures to demonstrate its viability across a range of environments and food sources. We close with suggestions for empirical tests.

A map of white matter tracts in a lesser ape, the lar gibbon.

The recent development of methods for constructing directly comparable white matter atlases in primate brains from diffusion MRI allows us to probe specializations unique to humans, great apes, and other primate taxa. Here, we constructed the first white matter atlas of a lesser ape using an ex vivo diffusion-weighted scan of a brain from a young adult (5.5 years) male lar gibbon. We find that white matter architecture of the gibbon temporal lobe suggests specializations that are reminiscent of those previously reported for great apes, specifically, the expansion of the arcuate fasciculus and the inferior longitudinal fasciculus in the temporal lobe. Our findings suggest these white matter expansions into the temporal lobe were present in the last common ancestor to hominoids approximately 16 million years ago and were further modified in the great ape and human lineages. White matter atlases provide a useful resource for identifying neuroanatomical differences and similarities between humans and other primate species and provide insight into the evolutionary variation and stasis of brain organization.

Supporting reproductive health among birthing persons with chronic conditions in the United States: A qualitative multilevel study using systems thinking to inform action.

OBJECTIVE (STUDY QUESTION): To use systems thinking with diverse system actors to (a) characterize current problems at the intersection of chronic conditions (CCs) and reproductive health (RH) care and their determinants, (b) determine necessary system actors for change, and (c) document cross-system actions that can improve identified problems in the United States. DATA SOURCES/STUDY SETTING: Data were collected from six groups of system actors via online focus groups. STUDY DESIGN: This is a qualitative multilevel study using the iceberg systems thinking framework. DATA COLLECTION/EXTRACTION METHODS: Data were collected by note-taking and recording six focus groups; analysis incorporated perspective triangulation using the systems thinking iceberg and system mapping to visualize interconnected system challenges, actors, and action ideas. PRINCIPAL FINDINGS: Participants described eight necessary system actors: health care institutions, medical leaders, medical providers, patient advocates and foundations, patients and families, payors, policy makers, and research funders. Forty pain points were identified, spread across each of the four levels of the systems thinking iceberg: undesirable outcomes (6), concerning trends (9), system structure flaws (15), and problematic mental models (10). In response to these pain points, a set of 46 action ideas was generated by participants and mapped into nine action themes: (1) adjust QI metrics, incentives, and reimbursement, (2) bolster RH medical education and training, (3) break down medical silos, (4) enrich patient education, (5) expand the health care team, (6) improve holistic health care, (7) modify research and programmatic funding to prioritize RH and CC, (8) spur innovation for patient visits, and (9) support professional champions and leaders. CONCLUSIONS: By embracing system complexity, creating visual maps, and pushing participants to identify actionable strategies for improvement, this study generates a set of specific actions that can be used to address pain points across the multiple system levels that make improving reproductive care for people with CCs so challenging.

Comparing human and chimpanzee temporal lobe neuroanatomy reveals modifications to human language hubs beyond the frontotemporal arcuate fasciculus.

The biological foundation for the language-ready brain in the human lineage remains a debated subject. In humans, the arcuate fasciculus (AF) white matter and the posterior portions of the middle temporal gyrus are crucial for language. Compared with other primates, the human AF has been shown to dramatically extend into the posterior temporal lobe, which forms the basis of a number of models of the structural connectivity basis of language. Recent advances in both language research and comparative neuroimaging invite a reassessment of the anatomical differences in language streams between humans and our closest relatives. Here, we show that posterior temporal connectivity via the AF in humans compared with chimpanzees is expanded in terms of its connectivity not just to the ventral frontal cortex but also to the parietal cortex. At the same time, posterior temporal regions connect more strongly to the ventral white matter in chimpanzees as opposed to humans. This pattern is present in both brain hemispheres. Additionally, we show that the anterior temporal lobe harbors a combination of connections present in both species through the inferior fronto-occipital fascicle and human-unique expansions through the uncinate and middle and inferior longitudinal fascicles. These findings elucidate structural changes that are unique to humans and may underlie the anatomical foundations for full-fledged language capacity.

The Digital Brain Bank, an open access platform for post-mortem imaging datasets.

Post-mortem magnetic resonance imaging (MRI) provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), a data release platform providing open access to curated, multimodal post-mortem neuroimaging datasets. Datasets span three themes-Digital Neuroanatomist: datasets for detailed neuroanatomical investigations; Digital Brain Zoo: datasets for comparative neuroanatomy; and Digital Pathologist: datasets for neuropathology investigations. The first Digital Brain Bank data release includes 21 distinctive whole-brain diffusion MRI datasets for structural connectivity investigations, alongside microscopy and complementary MRI modalities. This includes one of the highest-resolution whole-brain human diffusion MRI datasets ever acquired, whole-brain diffusion MRI in fourteen nonhuman primate species, and one of the largest post-mortem whole-brain cohort imaging studies in neurodegeneration. The Digital Brain Bank is the culmination of our lab's investment into post-mortem MRI methodology and MRI-microscopy analysis techniques. This manuscript provides a detailed overview of our work with post-mortem imaging to date, including the development of diffusion MRI methods to image large post-mortem samples, including whole, human brains. Taken together, the Digital Brain Bank provides cross-scale, cross-species datasets facilitating the incorporation of post-mortem data into neuroimaging studies.

Postpartum Health Experiences of Women with Newborns in Intensive Care: The Desire to Be by the Infant Bedside as a Driver of Postpartum Health.

INTRODUCTION: Women with infants in a neonatal intensive care unit (NICU) encounter multiple challenges following childbirth, including greater burden of chronic disease and increased risk for depression, compared with women with well infants. At the same time, they are confronted with the trauma of a hospitalized infant while also managing their postpartum recovery. Limited research exists describing the health needs of these women, despite the many numbers living this experience daily. This study aimed to better understand postpartum health needs of women with infants in the NICU in the 90 days following birth and to propose actionable system improvements to address identified needs. METHODS: The authors conducted in-depth individual interviews with 50 postpartum women of infants admitted to the NICU at a quaternary care hospital. Eligible women were aged at least 18 years, spoke English or Spanish, and had infants in the NICU longer than 3 days. Interview topics included NICU experience, recommended and desired health care, and suggestions for improvement. Interviews were audiotaped and transcribed verbatim. The authors used qualitative description techniques including memo-writing, coding, matrices, diagramming, and team discussion to analyze the data. RESULTS: Women reported significant intrapartum health conditions and concerns (eg, preeclampsia, emergency cesarean birth, anxiety) and described unmet social, emotional, mental, and physical health needs. Unmet practical needs while in the NICU (eg, a place to rest, affordable parking, access to food, childcare) caused considerable burden. Despite disease burden and emergent health needs, few women reported regular monitoring of their postpartum health by maternal health care providers. Women frequently minimized and delayed care for their health needs so as to remain by the infant bedside. DISCUSSION: Women with infants in the NICU would benefit from patient-centered care that provides greater attention to their postpartum health and recovery while also supporting their drive to remain close to their hospitalized infant.

Cortical Morphology and White Matter Tractography of Three Phylogenetically Distant Primates: Evidence for a Simian Elaboration.

Comparative neuroimaging has been used to identify changes in white matter architecture across primate species phylogenetically close to humans, but few have compared the phylogenetically distant species. Here, we acquired postmortem diffusion imaging data from ring-tailed lemurs (Lemur catta), black-capped squirrel monkeys (Saimiri boliviensis), and rhesus macaques (Macaca mulatta). We were able to establish templates and surfaces allowing us to investigate sulcal, cortical, and white matter anatomy. The results demonstrate an expansion of the frontal projections of the superior longitudinal fasciculus complex in squirrel monkeys and rhesus macaques compared to ring-tailed lemurs, which correlates with sulcal anatomy and the lemur's smaller prefrontal granular cortex. The connectivity of the ventral pathway in the parietal region is also comparatively reduced in ring-tailed lemurs, with the posterior projections of the inferior longitudinal fasciculus not extending toward parietal cortical areas as in the other species. In the squirrel monkeys we note a very specific occipito-parietal anatomy that is apparent in their surface anatomy and the expansion of the posterior projections of the optical radiation. Our study supports the hypothesis that the connectivity of the prefrontal-parietal regions became relatively elaborated in the simian lineage after divergence from the prosimian lineage.

Perinatal morbidity and health utilization among mothers of medically fragile infants.

OBJECTIVE: To determine the burden of perinatal morbidity among mothers of medically fragile infants. STUDY DESIGN: We conducted a retrospective cohort study of 6849 mothers who delivered liveborn infants at a quaternary care hospital during a two-year period. We compared mothers of well babies with mothers of infants admitted to the Neonatal Intensive Care Unit (NICU), and we used logistic regression to model predictors of postpartum acute care utilization among NICU mothers. RESULTS: Rates of obstetric morbidity were highest for mothers of infants staying ≥72 h in the NICU; 54.2% underwent cesarean birth, 7.5% experienced severe maternal morbidity, and 6.6% required a blood transfusion. Factors independently associated with postpartum acute care use included gestational age <28 weeks, ever smoking, non-Hispanic Black race, temperature >38 °C and receiving psychiatric medication during the birth hospitalization. CONCLUSION: Focused support for mothers of NICU infants has the potential to reduce maternal morbidity and improve health.

Human Group IIA Phospholipase A2-Three Decades on from Its Discovery.

Phospholipase A2 (PLA2) enzymes were first recognized as an enzyme activity class in 1961. The secreted (sPLA2) enzymes were the first of the five major classes of human PLA2s to be identified and now number nine catalytically-active structurally homologous proteins. The best-studied of these, group IIA sPLA2, has a clear role in the physiological response to infection and minor injury and acts as an amplifier of pathological inflammation. The enzyme has been a target for anti-inflammatory drug development in multiple disorders where chronic inflammation is a driver of pathology since its cloning in 1989. Despite intensive effort, no clinically approved medicines targeting the enzyme activity have yet been developed. This review catalogues the major discoveries in the human group IIA sPLA2 field, focusing on features of enzyme function that may explain this lack of success and discusses future research that may assist in realizing the potential benefit of targeting this enzyme. Functionally-selective inhibitors together with isoform-selective inhibitors are necessary to limit the apparent toxicity of previous drugs. There is also a need to define the relevance of the catalytic function of hGIIA to human inflammatory pathology relative to its recently-discovered catalysis-independent function.

The Anticipatory and Task-Driven Nature of Visual Perception.

Humans have a remarkable capacity to arrange and rearrange perceptual input according to different categorizations. This begs the question whether the categorization is exclusively a higher visual or amodal process, or whether categorization processes influence early visual areas as well. To investigate this we scanned healthy participants in a magnetic resonance imaging scanner during a conceptual decision task in which participants had to answer questions about upcoming images of animals. Early visual cortices (V1 and V2) contained information about the current visual input, about the granularity of the forthcoming categorical decision, as well as perceptual expectations about the upcoming visual stimulus. The middle temporal gyrus, the anterior temporal lobe, and the inferior frontal gyrus were also involved in the categorization process, constituting an attention and control network that modulates perceptual processing. These findings provide further evidence that early visual processes are driven by conceptual expectations and task demands.

Does the temporal cortex make us human? A review of structural and functional diversity of the primate temporal lobe.

Temporal cortex is a primate specialization that shows considerable variation in size, morphology, and connectivity across species. Human temporal cortex is involved in many behaviors that are considered especially well developed in humans, including semantic processing, language, and theory of mind. Here, we ask whether the involvement of temporal cortex in these behaviors can be explained in the context of the 'general' primate organization of the temporal lobe or whether the human temporal lobe contains unique specializations indicative of a 'step change' in the lineage leading to modern humans. We propose that many human behaviors can be explained as elaborations of temporal cortex functions observed in other primates. However, changes in temporal lobe white matter suggest increased integration of information within temporal cortex and between posterior temporal cortex and other association areas, which likely enable behaviors not possible in other species.

Targeting the eicosanoid pathway in hepatocellular carcinoma.

Liver cancer has variable incidence worldwide and high mortality. Histologically, the most common subtype of liver cancer is hepatocellular carcinoma (HCC). Approximately 30-40% of HCC patients are diagnosed at an advanced stage, and at present, there are limited treatment options for such patients. The current first-line therapy with tyrosine kinase inhibitors, sorafenib or lenvatinib, prolongs survival by a median of about 2.5-3 months after which the disease normally progresses. Additionally, many patients discontinue the use of tyrosine kinase inhibitors due to toxicity or may not be suitable candidates due to co-morbidity or frailty. It is, therefore, imperative to identify novel therapeutic targets for advanced HCC patients. Persistent injury to the liver as a result of insults such as hepatitis B or C viral (HBV or HCV) infections, alcohol abuse, and non-alcoholic fatty liver disease (NAFLD), results in chronic inflammation, which progresses to hepatic fibrosis and later, cirrhosis, provides the conditions for initiation of HCC. One of the key pathways studied for its role in inflammation and carcinogenesis is the eicosanoid pathway. In this review, we briefly outline the eicosanoid pathway, describe the mechanisms by which some pathway members either facilitate or counter the development of liver diseases, with the focus on NAFLD/hepatic fibrosis/cirrhosis, and HCC. We describe the link between the eicosanoid pathway, inflammation and these liver diseases, and identify components of the eicosanoid pathway that may be used as potential therapeutic targets in HCC.

Diffusion MRI data, sulcal anatomy, and tractography for eight species from the Primate Brain Bank.

Large-scale comparative neuroscience requires data from many species and, ideally, at multiple levels of description. Here, we contribute to this endeavor by presenting diffusion and structural MRI data from eight primate species that have not or rarely been described in the literature. The selected samples from the Primate Brain Bank cover a prosimian, New and Old World monkeys, and a great ape. We present preliminary labelling of the cortical sulci and tractography of the optic radiation, dorsal part of the cingulum bundle, and dorsal parietal-frontal and ventral temporal-frontal longitudinal white matter tracts. Both dorsal and ventral association fiber systems could be observed in all samples, with the dorsal tracts occupying much less relative volume in the prosimian than in other species. We discuss the results in the context of known primate specializations and present hypotheses for further research. All data and results presented here are available online as a resource for the scientific community.

Nuclear Leukocyte Immunoglobulin-like Receptor A3 Is Monomeric and Is Involved in Multiple Layers of Regulated Gene Expression and Translation.

The leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble protein primarily expressed by peripheral blood monocytes and is abundant in sera of healthy donors. Extracellular LILRA3 is anti-inflammatory and displays neuro-regenerative functions in vitro. However, its intracellular expression, distribution, and function(s) remain unknown. Using a combination of high-resolution confocal and super-resolution microscopy, we identified intracellular expression of native LILRA3 in the nucleus of peripheral blood monocytes and in vitro-derived macrophages. This unexpected nuclear localization of LILRA3 was confirmed in LILRA3-GFP-transfected HEK293T cells. Western blot of proteins fractionated from primary macrophages and the transfected HEK293T cells confirmed nuclear localization of the native and expressed LILRA3 proteins. Interestingly, most of the LILRA3 in the nucleus was in a monomeric form like the biologically active secreted protein, while that in the other cellular compartments was in mixed monomeric, dimeric, and oligomeric forms. The predominant presence of monomeric LILRA3 in the nucleus was independently corroborated in transfected live HEK293T cells using the number and molecular brightness (N&B) analysis method. Immunoprecipitation and mass spectrometric peptide sequencing studies revealed that nuclear LILRA3 co-immunoprecipitated with several nuclear proteins involved in host protein synthesis machinery via direct interactions to a key multifunctional RNA-binding protein, the Ewing sarcoma breakpoint region 1 protein (EWS) (data are available via ProteomeXchange with identifier PXD024602). The biological significance of the nuclear expression of LILRA3 and its interaction with these key proteins remain to be elucidated.

A comprehensive atlas of white matter tracts in the chimpanzee.

Chimpanzees (Pan troglodytes) are, along with bonobos, humans' closest living relatives. The advent of diffusion MRI tractography in recent years has allowed a resurgence of comparative neuroanatomical studies in humans and other primate species. Here we offer, in comparative perspective, the first chimpanzee white matter atlas, constructed from in vivo chimpanzee diffusion-weighted scans. Comparative white matter atlases provide a useful tool for identifying neuroanatomical differences and similarities between humans and other primate species. Until now, comprehensive fascicular atlases have been created for humans (Homo sapiens), rhesus macaques (Macaca mulatta), and several other nonhuman primate species, but never in a nonhuman ape. Information on chimpanzee neuroanatomy is essential for understanding the anatomical specializations of white matter organization that are unique to the human lineage.

Identifying co-morbid fibromyalgia in patients with systemic lupus erythematosus using the Multi-Dimensional Health Assessment Questionnaire.

OBJECTIVE: Fibromyalgia (FM) is prevalent but often under-recognized in patients with systemic lupus erythematosus (SLE). Patient-reported outcomes (PROs) from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) can identify co-morbid FM in patients with rheumatic diseases. The present study examined the utility of the MDHAQ in recognizing FM in patients with SLE during routine consultations. METHODS: Patients with SLE completed an MDHAQ. FM status was determined by the validated 2016 revision of the ACR 2010/2011 preliminary FM criteria. Individual PROs from the MDHAQ and composite Fibromyalgia Assessment Tool (FAST) indices of the discriminatory PROs were compared between patients with and without FM using Student's unpaired t-test and receiver operating characteristic curve analysis to determine the area under the curve (AUC). The physician's clinical impression of FM was recorded, and the SLE Disease Activity Index was used to assess disease activity. RESULTS: Of 88 patients with SLE, 23 (26%) satisfied the 2016 FM criteria. The FAST3 composite measure of two out of three of pain (≥6/10), joint count (≥16/48) and symptom checklist (≥16/60) correctly classified 89% of patients (AUC=0.90, kappa=0.71). Physician diagnosis demonstrated moderate agreement with the 2016 FM criteria (kappa=0.43) but missed 43% of patients with FM. In the presence of active disease, the FAST3 correctly classified 91% of patients. CONCLUSIONS: Co-morbid FM is prevalent in SLE yet often underdiagnosed by physicians. The simple FAST3 index of the MDHAQ provides an easy-to-use self-reported tool to improve identification of FM in patients with SLE.

Longitudinal connections and the organization of the temporal cortex in macaques, great apes, and humans.

The temporal association cortex is considered a primate specialization and is involved in complex behaviors, with some, such as language, particularly characteristic of humans. The emergence of these behaviors has been linked to major differences in temporal lobe white matter in humans compared with monkeys. It is unknown, however, how the organization of the temporal lobe differs across several anthropoid primates. Therefore, we systematically compared the organization of the major temporal lobe white matter tracts in the human, gorilla, and chimpanzee great apes and in the macaque monkey. We show that humans and great apes, in particular the chimpanzee, exhibit an expanded and more complex occipital-temporal white matter system; additionally, in humans, the invasion of dorsal tracts into the temporal lobe provides a further specialization. We demonstrate the reorganization of different tracts along the primate evolutionary tree, including distinctive connectivity of human temporal gray matter.

XTRACT - Standardised protocols for automated tractography in the human and macaque brain.

We present a new software package with a library of standardised tractography protocols devised for the robust automated extraction of white matter tracts both in the human and the macaque brain. Using in vivo data from the Human Connectome Project (HCP) and the UK Biobank and ex vivo data for the macaque brain datasets, we obtain white matter atlases, as well as atlases for tract endpoints on the white-grey matter boundary, for both species. We illustrate that our protocols are robust against data quality, generalisable across two species and reflect the known anatomy. We further demonstrate that they capture inter-subject variability by preserving tract lateralisation in humans and tract similarities stemming from twinship in the HCP cohort. Our results demonstrate that the presented toolbox will be useful for generating imaging-derived features in large cohorts, and in facilitating comparative neuroanatomy studies. The software, tractography protocols, and atlases are publicly released through FSL, allowing users to define their own tractography protocols in a standardised manner, further contributing to open science.