Large Brain Research Articles

Applied machine learning for stroke differentiation by electrical impedance tomography with realistic numerical models

Electrical impedance tomography (EIT) may have potential to overcome existing limitations in stroke differentiation, enabling low-cost, rapid, and mobile data collection. Combining bioimpedance measurement technologies such as EIT with machine learning classifiers to support decision-making can avoid commonly faced reconstruction challenges due to the nonlinear and ill-posed nature of EIT imaging. Therefore, in this work, we advance this field through a study integrating realistic head models with clinically relevant test scenarios, and a robust architecture consisting of nested cross-validation and principal component analysis. Specifically, realistic head models are designed which incorporate the highly conductive layers of cerebrospinal fluid in the subarachnoid space and ventricles. In total, 135 unique models are created to represent a large patient population, with normal, haemorrhagic, and ischemic brains. Simulated EIT voltage data generated from these models are used to assess the classification performance of support vector machines. Parameters explored include driving frequency, signal-to-noise ratio, kernel function, and composition of binary classes. Classifier accuracy at 60 dB signal-to-noise ratio, reported as mean and standard deviation, are (79.92% ± 10.82%) for lesion differentiation, (74.78% ± 3.79%) for lesion detection, (77.49% ± 15.90%) for bleed detection, and (60.31% ± 3.98%) for ischemia detection (after ruling out bleed). The results for each method were obtained with statistics from 3 independent runs with 17,280 observations, polynomial kernel functions, and feature reduction of 76% by PCA (from 208 to 50 features). While results of this study show promise for stroke differentiation using EIT data, our findings indicate that the achievable accuracy is highly dependent on the classification scenario and application-specific classifiers may be necessary to achieve acceptable accuracy.

Comparison of physics-based deformable registration methods for image-guided neurosurgery.

This paper compares three finite element-based methods used in a physics-based non-rigid registration approach and reports on the progress made over the last 15 years. Large brain shifts caused by brain tumor removal affect registration accuracy by creating point and element outliers. A combination of approximation- and geometry-based point and element outlier rejection improves the rigid registration error by 2.5 mm and meets the real-time constraints (4 min). In addition, the paper raises several questions and presents two open problems for the robust estimation and improvement of registration error in the presence of outliers due to sparse, noisy, and incomplete data. It concludes with preliminary results on leveraging Quantum Computing, a promising new technology for computationally intensive problems like Feature Detection and Block Matching in addition to finite element solver; all three account for 75% of computing time in deformable registration.

Alzheimer’s disease genetics and real‐world patient data fuel target and drug discovery in European and African American ancestries

AbstractBackgroundTranslation of massive genetic and genomic data into Alzheimer’s target and drug discovery has not materialized. One challenge in this process is ethnicity‐based differences in the field of Alzheimer’s disease (AD). For example, African Americans (AAs) and European Americans (EAs) differ in AD prevalence, risk factors, and symptomatic presentation, and AAs have historically been less frequently enrolled in AD clinical trials.MethodWe conducted ancestry genetic‐specific target and drug discovery by gathering large genetic data from a diverse population with real‐world patient data to boost the likelihood of identifying disease‐modifying drug targets and treatments for AD. We analyzed genetic data from 275,540 AD cases and 1.55 million controls across 7 AD genome‐wide association studies (GWAS) datasets for both EA and AA ancestries, using Mendelian randomization. We utilized the genetic instruments from 9 expression quantitative trait loci (eQTL) and 3 protein quantitative trait loci (pQTL) datasets from three large human brain biobanks: a) Mount Sinai Brain Bank (MSBB), b) Mayo clinic (Mayo), and c) Religious Orders Study (ROS) or the Rush Memory and Aging Project (MAP) (ROS/MAP).ResultWe identified 25 drug targets in EAs and 6 new drug targets in AAs among 1,176 investigated druggable targets. Notably, the inflammatory target of epoxide hydrolase 2 (EPHX2) emerged as a potent AD target in EAs, and treatment of transgenic TgF344‐AD rats with an EPHX2 inhibitor was therapeutic. Among 6 AA‐specific targets, we identified that TRPV3 is a potent drug target for AA individuals with AD, and further replicated our finding in AA‐specific eQTL data. We additionally identified 23 candidate drugs associated with reduced risk of AD in mild cognitive impairment (MCI) patients after analysis of ∼80 million electronic health records. Using a propensity score‐matched design, we identified that usage of either apixaban (hazard ratio [HR] = 0.74, 95% confidence interval [CI] 0.69 – 0.80) or amlodipine (HR = 0.91, 95% CI 0.88 – 0.94) were both significantly associated with reduced progression to AD in people with MCI.ConclusionCombining genetics and real‐world patient data has identified ancestry‐specific therapeutic targets and medicines for AD.

Herpes Simplex Virus‐1 Proteins Drive Alzheimer’s Disease Pathologies in Humans

AbstractBackgroundDNA and RNA of Herpes Simplex Virus 1 (HSV‐1) were found in the brains and serological samples of Alzheimer’s disease (AD) patients. Such molecular presence of HSV‐1 in AD patients is especially intriguing as HSV‐1 virions are rarely detected in AD brains.MethodsTo follow the molecular footsteps detected, we imaged viral proteins in postmortem human AD brains at superior resolution using expansion microscopy, a tissue manipulation method that physically expands the samples by a factor of 4.5x, allowing a 40 nm imaging resolution, and immunolabeled herpetic proteins, AD pathologies and cell markers.ResultsWe found an abundance of herpetic proteins, previously undetectable with standard methods, across large brain areas. Importantly, we found that HSV‐1 proteins strongly co‐localized with AD pathologies. Consequently, we hypothesized that expression of HSV‐1 proteins during latency may be linked to AD pathology. We are now in the process of characterizing the HSV‐1 proteome in AD brains by imaging key proteins in expanded AD brain slices and examining their colocalization with AD pathologies across brain areas and disease stages. As a complementary system to the fixed human brain slices, we introduced HSV‐1 in human derived brain organoids and imaged the relationships between viral proteins and the formation of AD pathologies via expansion microscopy. We found that HSV‐1 infection triggered these pathologies, pointing out that viruses may be triggers of immune responses driving AD.Conclusionsthis study sheds light on one common pathogen, HSV‐1, while serving as a framework to unveiling molecular causation between infectious agents and AD hallmarks.

Clinical Manifestations.

Individuals diagnosed with mild cognitive impairment and dementia (MCI/Dem) are excluded from research on intervention for acute ischemic stroke; This research gap places stroke physicians worldwide in dilemmas while treating patients with cognitive decline. One example is acute stroke of large brain arteries, typically manifesting as immediate onset of severe neurological disability. Endovascular treatment (EVT), aka catheter-base clot removal, is considered the gold-standard treatment and when applied within hours after onset, can mitigate or reverse deficits and dramatically improve outcomes. Our goal was to evaluate efficacy and safety of EVT for acute stroke in MCI/Dem. This is a single site retrospective study from Rabin Medical Center,2019-2021. Inclusion criteria was new onset acute large vessel stroke receiving EVT treatment, ages 18-85 years. Pre-stroke cognitive status was assessed using previous diagnosis, assessments in geriatric / occupational therapy clinics, nurse functional questionnaire and rehabilitation interview. Individuals were dichotomized to MCI/Dem (any severity) and unimpaired via consensus between two behavioural neurologists. The MCI/Dem group was matched to unimpaired individuals for sex, age, pre-stroke functional independence, and stroke arterial territory, severity and time to EVT. The outcomes were retrospectively assessed 90 days after stroke and included mortality, intracranial haemorrhage, and pre to post stroke difference in the modified Rankin scale (mRS), commonly used instrument for stroke functional independence. We identified 306 individuals with acute large vessel stroke who underwent EVT, of which 32 with pre-stroke MCI/Dem. After matching, we saw no differences between non impaired group to MCI/Dem group in functional outcome measured by mRS change, (56% vs.53%, p = 0.8), brain hemorrhage(22% vs. 9%, p = 0.68) and mortality (25% vs. 12%,p = 0.2). To our knowledge this is the first study to report on EVT outcomes in individuals with MCI/Dem. Our results suggest interventions for acute large vessel stroke may have similar efficacy and safety profile in individuals with pre-stroke MCI/Dementia and thus challenge previous recommendations to exclude them from therapy. Our data is retrospective and thus of inadequate design to suggest change to clinical guidelines. Further research on stroke interventions in MCI/Dem is urgently needed to guide day-to-day clinical decision making.

Transcription factors in microcephaly.

Higher cognition in humans, compared to other primates, is often attributed to an increased brain size, especially forebrain cortical surface area. Brain size is determined through highly orchestrated developmental processes, including neural stem cell proliferation, differentiation, migration, lamination, arborization, and apoptosis. Disruption in these processes often results in either a small (microcephaly) or large (megalencephaly) brain. One of the key mechanisms controlling these developmental processes is the spatial and temporal transcriptional regulation of critical genes. In humans, microcephaly is defined as a condition with a significantly smaller head circumference compared to the average head size of a given age and sex group. A growing number of genes are identified as associated with microcephaly, and among them are those involved in transcriptional regulation. In this review, a subset of genes encoding transcription factors (e.g., homeobox-, basic helix-loop-helix-, forkhead box-, high mobility group box-, and zinc finger domain-containing transcription factors), whose functions are important for cortical development and implicated in microcephaly, are discussed.

HBO aftereffect on lipid peroxidation and enzyme antioxidants of the brain: prospective experiental study

OBJECTIVE. Study the effect of a single and multiple administration of hyperbaric oxygenation (HBO) in the therapeutic regime on the processes of lipid peroxidation (LPO) and enzyme of antioxidative defense in phylogenetically various structures of the brain in the period of the immediate and remote aftereffect of expositions.
 MATERIALS AND METHODS. Experiments were carried out on 87 nonlinear white male rats weighing 180-230 grams. Hyperbaric oxygenation was conducted by medical oxygen in the experimental pressure chamber in the “mild” mode (2 ata, 50 min isopression), 1 session per day in the morning. The study was carried out after 1, 5, 10 sessions, in 5 and 10 days after 1 session and in 5 days after 5 sessions of HBO. The content of malondialdehyde (MDA) was determined in the brain stem, cerebellum and large brain hemispheres. The state of an enzyme element of antioxidant defense was evaluated by superoxide dismutase (SOD) and catalase.
 RESULTS. It was found that exposure to oxygen under high pressure caused increased intensity of LPO processes in the brain that progresses from 1 to 5 sessions. While MDA changes in the brain stem were detected later than in the hemispheres and cerebellum. LPO intensification in the brain proceeded against the background of increased activity of SOD. After 10 sessions of HBO LPO intensity decreased that was confirmed by reduced MDA content and SOD activity in examined brain tissue. Catalase activity reduced in the stem after 5 sessions and increased in the cerebellum and hemispheres after 10 sessions of HBO. Aftereffect of 1 HBO session was characterized by persistent increase in MDA concentration in the brain regions, detected in 5 and 10 days after exposure and was accompanied by increased SOD activity against the background of reduced catalase activity. In 5 days after 5 sessions the increase in MDA content and SOD activation was observed only in the tissue of the cerebral hemispheres.
 DISCUSSION. The use of HBO in the mode 2 ata, 50 min stimulates reactions of free radical oxidation (FRO) in the brain. The dynamics of their development with continued exposure shows that there are enough resources of the brain antioxidant defense to compensate hyperoxic load, including 10-fold exposure and no depletion of the reserves of enzyme antioxidant element in the brain is observed. After a single exposure of hyperbaric oxygen FRO activation remains during 10 days that can be concluded from an increased level of MDA and an increased activity of SOD in all the brain regions against the background of reduced catalase activity of stem structures and cerebellum. Repeated 5-fold exposures have a shorter metabolic “footprint”: in 5 days LPO effect and SOD activation are less pronounced than in the period of 1 session aftereffect both in 5 and 10 days.
 CONCLUSION. The therapeutic “mild” mode of HBO (2 ata, 50 min, 1 session per day) causes FRO activation in the brain tissue of experimental animals. Its intensity is controlled by the activation of enzyme protection mechanisms that is enough to compensate FRO changes with this mode of hyperoxic load. After ending exposures more pronounced aftereffect of HBO in the brain regions is found after 1 session compared to 5 sessions.

Long non-coding RNAs H19 and NKILA are associated with the risk of death and lacunar stroke in the elderly population

IntroductionDifferential expression of long non-coding RNAs (lncRNAs) is a hallmark of cardiovascular aging, cerebrovascular diseases, and neurodegenerative disorders. This research article investigates the association between a panel of lncRNAs and the risk of death and ischemic stroke in a cohort of non-institutionalized elderly subjects. MethodA total of 361 healthy individuals aged 75 years old, prospectively recruited in the Vienna Transdanube Aging (VITA) cohort, were included. Expression of lncRNAs at baseline was assessed using quantitative polymerase chain reaction PCR with pre-amplification reaction, using 18S for normalization. The primary endpoint was all-cause mortality; the secondary endpoint was the incidence of new ischemic brain lesions. Death was assessed over a 14-year follow-up, and ischemic brain lesions were evaluated by magnetic resonance imaging (MRI) over a 90-month follow-up. Ischemic brain lesions were divided into large brain infarcts (Ø≥ 1.5 cm) or lacunes (Ø< 1.5 cm) ResultsThe primary endpoint occurred in 53.5 % of the study population. The incidence of the secondary endpoint was 16 %, with a 3.3 % being large brain infarcts, and a 12.7 % lacunes.After adjustment for potential confounders, the lncRNA H19 predicted the incidence of the primary endpoint (HR 1.194, 95 % C.I. 1.012–1.409, p = 0.036), whereas the lncRNA NKILA was associated with lacunar stroke (HR 0.571, 95 % C.I. 0.375–0.868, p = 0.006). ConclusionIn a prospective cohort of non-institutionalized elderly subjects, high levels of lncRNA H19 are associated with a higher risk of death, while low levels of lncRNA NKILA predict an increased risk of lacunar stroke.

CTNI-09. DOSE ESCALATION FOR NEOADJUVANT STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES: PHASE I RESULTS

Abstract BACKGROUND Surgical resection may be required for large and symptomatic brain metastases. Adjuvant radiotherapy or stereotactic radiosurgery (SRS) is needed to reduce local recurrence. Adjuvant radiosurgery has been associated with higher rates of leptomeningeal failure and radionecrosis. We conducted a phase I trial for brain metastases greater than 2 cm in size to determine the safety of preoperative SRS at escalating doses. METHODS Radiosurgery dose was escalated at 3 Gy increments starting with RTOG 90-05 dosing for 3 cohorts based on maximum tumor diameter: 18 Gy for &amp;gt;2-3 cm, 15 Gy for &amp;gt;3-4 cm, and 12 Gy &amp;gt;4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity. Patients underwent surgical resection within 2 weeks and were followed with imaging and physical evaluations every 3 months. RESULTS For tumor size &amp;gt;2-3 cm, patients were enrolled up to the second dose level (21 Gy); for &amp;gt;3-4 cm and &amp;gt;4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. 35 patients were enrolled with 36 brain metastases treated with preoperative radiosurgery. There were 2 DLT (wound issues) in the &amp;gt;3-4 cm arm at the third dose level and 1 DLT (hemorrhage) in the &amp;gt;4-6 cm arm at the third dose level. The maximal tolerated SRS dose (MTD) for &amp;gt;-2-3 cm arm was not reached, for &amp;gt;3-4 cm arm was 18 Gy and for &amp;gt;4-6 cm arm was 18 Gy. With a median follow-up of 64 months, the 6- and 12-month local control rates were 88.8% and 79.1%, respectively. The 2-year rate of LMD was 0%. CONCLUSION This Phase I preoperative SRS dose escalation trial found a MTD for brain metastases greater than 3 and up to 6 cm in size. The phase II trial will be conducted at the maximum tolerated SRS doses.

RADT-05. SINGLE VERSUS MULTI-FRACTION STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES: RATES OF LOCAL PROGRESSION AND NECROSIS

Abstract PURPOSE For large brain metastases, it is unknown whether single fraction stereotactic radiosurgery (sSRS) or multi-fraction stereotactic radiosurgery (fSRS) is optimal. We aimed to compare rates of local progression and necrosis between sSRS and fSRS for large brain metastases. METHODS Patients with intact or resected brain metastases with a target volume ≥ 4.2 cc (corresponding to a diameter ≥ 2 cm) treated with Gamma Knife (GK) or linear accelerator-based SRS from 2014-2022 were included in this retrospective review. RESULTS A total of 343 large brain metastases in 276 patients were included; 171 lesions were treated with sSRS (96% with GK) and 172 lesions with fSRS (100% with linear accelerator). Median lesion volume was 19.8 cc and 8.4 cc for fSRS and sSRS, respectively. Resection was performed prior to SRS in 228 (66%), with the remaining 115 metastases treated intact. There was no difference in rate of local progression between sSRS versus fSRS, or between resected versus intact targets (p &amp;gt;0.8 for both). Cumulative incidence of local progression (with death as a competing risk) at 1 and 3 years for patients receiving sSRS was 24% and 30%, respectively, compared to 22% and 34% for fSRS. FSRS was associated with significantly higher rates of necrosis than sSRS (HR 5.58, 2.38-13.08, p &amp;lt; 0.001). This association remained significant after controlling for target volume. Cumulative incidence of necrosis (with death as a competing risk) at 1 and 3 years for patients receiving sSRS was 1% and 3%, respectively, compared to 10% and 18% for fSRS. Necrosis rates were significantly higher with fSRS for both intact and resected targets (P &amp;lt; 0.02 for both). CONCLUSION While local control for large resected or intact brain metastases appears similar after sSRS or fSRS, this retrospective study shows higher rates of necrosis after fSRS. Prospective validation is needed.

A technology platform for standardized cryoprotection and freezing of large-volume brain tissues for high-resolution histology.

Understanding and mapping the human connectome is a long-standing endeavor of neuroscience, yet the significant challenges associated with the large size of the human brain during cryosectioning remain unsolved. While smaller brains, such as rodents and marmosets, have been the focus of previous connectomics projects, the processing of the larger human brain requires significant technological advancements. This study addresses the problem of freezing large brains in aligned neuroanatomical coordinates with minimal tissue damage, facilitating large-scale distortion-free cryosectioning. We report the most effective and stable freezing technique utilizing an appropriate choice of cryoprotection and leveraging engineering tools such as brain master patterns, custom-designed molds, and a continuous temperature monitoring system. This standardized approach to freezing enables high-quality, distortion-free histology, allowing researchers worldwide to explore the complexities of the human brain at a cellular level. Our approach combines neuroscience and engineering technologies to address this long-standing challenge with limited resources, enhancing accessibility of large-scale scientific endeavors beyond developed countries, promoting diverse approaches, and fostering collaborations.

Brain size predicts bees' tolerance to urban environments.

The rapid conversion of natural habitats to anthropogenic landscapes is threatening insect pollinators worldwide, raising concern regarding the negative consequences on their fundamental role as plant pollinators. However, not all pollinators are negatively affected by habitat conversion, as certain species find appropriate resources in anthropogenic landscapes to persist and proliferate. The reason why some species tolerate anthropogenic environments while most find them inhospitable remains poorly understood. The cognitive buffer hypothesis, widely supported in vertebrates but untested in insects, offers a potential explanation. This theory suggests that species with larger brains have enhanced behavioural plasticity, enabling them to confront and adapt to novel challenges. To investigate this hypothesis in insects, we measured brain size for 89 bee species, and evaluated their association with the degree of habitat occupancy. Our analyses revealed that bee species mainly found in urban habitats had larger brains relative to their body size than those that tend to occur in forested or agricultural habitats. Additionally, urban bees exhibited larger body sizes and, consequently, larger absolute brain sizes. Our results provide the first empirical support for the cognitive buffer hypothesis in invertebrates, suggesting that a large brain in bees could confer behavioural advantages to tolerate urban environments.

53 Change in Cerebral Metabolite Concentrations Following Bariatric Surgery

Objective:Obesity is associated with adverse effects on brain health, including increased risk for neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined change in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery.Participants and Methods:35 patients with obesity (BMI &gt; 35 kg/m2) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel 1H-proton magnetic resonance spectroscopy at baseline (pre-surgery) and within one year post-surgery. Spectra were obtained from a large medial frontal brain region. Tissue-corrected absolute concentrations for metabolites including choline-containing compounds (Cho), myo-inositol (mI), N-acetylaspartate (NAA), creatine (Cr), and glutamate and glutamine (Glx) were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycemic control.Results:Bariatric surgery was associated with a reduction in cerebral Cho (f[34j = -3.79, p &lt; 0.001, d = -0.64) and mI (f[34] = -2.81, p &lt; 0.01, d = -0.47) concentrations. There were no significant changes in NAA, Glx, or Cr concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p &lt; 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p &lt; 0.05).Conclusions:Participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

Retracted: Factors Associated with Cranial Nerve Injury after Radiotherapy for Large Brain Metastases.

[This retracts the article DOI: 10.1155/2021/1159145.].

Effects of parental mental health and family environment on impulsivity in preadolescents: a longitudinal ABCD study®.

Impulsivity is a known risk factor for the development of substance use disorders and other psychiatric conditions that is influenced by both genetics and environment. Although research has linked parental mental health to children's impulsivity, potential mediators of this relationship remain understudied. The current investigation leverages the large national Adolescent Brain Cognitive Development (ABCD) Study to assess the mediating role of family conflict - an important social context for youth development - in the relationship between parental mental health and youth impulsivity. Data were from the first three annual waves of the ABCD study (Baseline N = 11,876 children, Mage = 9.9 years; 48% female; 52% White). Parental mental health conditions were self-reported internalizing, externalizing, and total problems. Youth completed the family conflict scale, and Urgency, Planning (lack of), Perseverance (lack of), Sensation Seeking, and Positive Urgency (UPPS-P) scale to measure impulsivity. To determine if within-family change in conflict from baseline to year 1 explained changes in the strength of relations between baseline parental mental health and year 2 youth impulsivity, longitudinal causal mediation analyses were conducted, controlling for demographic factors (i.e., age, sex, race, household income, parental education, marital status), as well as baseline levels of family conflict and outcomes. Separate mediation models were run for each mental health condition and each UPPS-P subscale. Above and beyond bivariate relations, longitudinal mediation models, which included covariates, showed family conflict significantly (ps < 0.001) mediated relations between all three parental mental health conditions and all but one (i.e., sensation seeking) UPPS-P subscales. The proportion mediated through family conflict for internalizing problems and total problems on facets of impulsivity (except sensation seeking) ranged from 9% (for lack of perseverance) to 17% (for lack of planning). Proportion mediated via family conflict for externalizing problems on youth's impulsivity (except sensation seeking) was slightly higher, ranging between 13% (lack of perseverance) to 21% (lack of planning). Family conflict may be an important intergenerational factor linking parental mental health and youth's impulsivity. Addressing parental mental health and family conflict may help curb increased impulsivity in youth, and in turn reduce adolescent substance use disorders.

The Impact of the Nervous System on Arteries and the Heart: The Neuroimmune Cardiovascular Circuit Hypothesis.

Three systemic biological systems, i.e., the nervous, the immune, and the cardiovascular systems, form a mutually responsive and forward-acting tissue network to regulate acute and chronic cardiovascular function in health and disease. Two sub-circuits within the cardiovascular system have been described, the artery brain circuit (ABC) and the heart brain circuit (HBC), forming a large cardiovascular brain circuit (CBC). Likewise, the nervous system consists of the peripheral nervous system and the central nervous system with their functional distinct sensory and effector arms. Moreover, the immune system with its constituents, i.e., the innate and the adaptive immune systems, interact with the CBC and the nervous system at multiple levels. As understanding the structure and inner workings of the CBC gains momentum, it becomes evident that further research into the CBC may lead to unprecedented classes of therapies to treat cardiovascular diseases as multiple new biologically active molecules are being discovered that likely affect cardiovascular disease progression. Here, we weigh the merits of integrating these recent observations in cardiovascular neurobiology into previous views of cardiovascular disease pathogeneses. These considerations lead us to propose the Neuroimmune Cardiovascular Circuit Hypothesis.

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium

BackgroundRecent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. MethodsWe analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. ResultsWe found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. ConclusionThese results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

How Intelligent is an Octopus or a Cuttlefish? Even Smarter Than You Might Think!

How smart is an octopus? Although we often associate intelligence with animals like dolphins, apes, elephants, parrots, and members of the crow family (jays and ravens), recent studies have revealed that octopuses and cuttlefish are also intelligent. These cephalopods have the largest brains amongst invertebrates, but their brains are completely different from our own human brains. Unlike many animals, an octopus grows up and learns on its own, without any instruction from its parents. An octopus quickly learns how to hide and camouflage itself to avoid predators. Octopuses have also been shown to use tools and sometimes they like to play. Cuttlefish, like their octopus cousins, are extremely intelligent. They are dazzling masters of camouflage, and have an excellent ability to remember past experiences, which helps guide their future behavior and decision-making. These clever cephalopods are revealing new insights that are helping scientists to understand how intelligence evolved.

Brown Bear Cognition and Welfare

Abstract The welfare of large-brained wide-roaming carnivores in captivity has been of longstanding public and professional concern. Bears are one such example. Ursids have unexpectedly large relative brain sizes, indeed showing brain size increases similar to those observed in canids. Bears also have considerable space requirements, with extensive home range sizes seen in the wild. Species with complex requirements often face difficulties when placed in artificial environments. Cognitive enrichment, however, may work to ameliorate this by providing stimulating mental challenges for individuals living in zoological settings. This case study explores the proposed benefits of cognitive trials. To do so, we exposed 17 captive European brown bears ( Ursus arctos arctos ) housed in UK zoos to two experimental tasks (1) a puzzle box and (2) an object-manipulation set-up. A total of 14 of the bears voluntarily engaged with the puzzle box, while 15 individuals interacted with the object-manipulation set-up. The bears that failed to interact with the tests were likely dissuaded due to the collective nature of testing, a lack of motivation or fear of novel objects. Cognitive stimulation, such as that provided in our study, offers one means of improving the welfare of captive bears. We advocate the use of cognition studies for zoo-housed bears to enrich their lived-experiences when housed in zoological settings. Information © The Authors 2023

A modified method to analyse cell proliferation using EdU labelling in large insect brains.

The study of neurogenesis is critical to understanding of the evolution of nervous systems. Within invertebrates, this process has been extensively studied in Drosophila melanogaster, which is the predominant model thanks to the availability of advanced genetic tools. However, insect nervous systems are extremely diverse, and by studying a range of taxa we can gain additional information about how nervous systems and their development evolve. One example of the high diversity of insect nervous system diversity is provided by the mushroom bodies. Mushroom bodies have critical roles in learning and memory and vary dramatically across species in relative size and the type(s) of sensory information they process. Heliconiini butterflies provide a useful snapshot of this diversity within a closely related clade. Within Heliconiini, the genus Heliconius contains species where mushroom bodies are 3-4 times larger than other closely related genera, relative to the rest of the brain. This variation in size is largely explained by increases in the number of Kenyon cells, the intrinsic neurons which form the mushroom body. Hence, variation in mushroom body size is the product of changes in cell proliferation during Kenyon cell neurogenesis. Studying this variation requires adapting labelling techniques for use in less commonly studied organisms, as methods developed for common laboratory insects often do not work. Here, we present a modified protocol for EdU staining to examine neurogenesis in large-brained insects, using Heliconiini butterflies as our primary case, but also demonstrating applicability to cockroaches, another large-brained insect.