Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “brain”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19

4D Multimodal Co-attention Fusion Network with Latent Contrastive Alignment for Alzheimer’s Diagnosis

Multimodal neuroimaging provides complementary structural and functional insights into both human brain organization and disease-related dynamics. Recent studies demonstrate enhanced diagnostic sensitivity for Alzheimer’s disease (AD) through synergistic integration of neuroimaging data (e.g., sMRI, fMRI) with tabular data (e.g., behavioral and cognitive tests). However, the intrinsic heterogeneity across modalities (e.g., 4D spatiotemporal fMRI dynamics vs. 3D anatomical sMRI structure) presents critical challenges for discriminative feature fusion, often leading to information loss or biased fusion. To bridge this gap, we propose M2M-AlignNet: a multimodal co-attention network with latent alignment for early AD diagnosis using sMRI and fMRI. At the core of our approach is a multi-patch-to-multi-patch (M2M) contrastive loss function that quantifies and reduces representational discrepancies via weighted patch correspondence, explicitly aligning fMRI components across brain regions with their sMRI structural substrates without one-to-one constraints. Additionally, we propose a latent-as-query co-attention module to autonomously discover fusion patterns, circumventing modality prioritization biases while minimizing feature redundancy. We conduct extensive experiments to confirm the effectiveness of our method and highlight the correspondence between fMRI and sMRI as AD biomarkers.

Wei, Yuxiang [Georgia Institute of Technology]↗

Heterotrimeric G‐protein, Gi1, is involved in the regulation of proliferation, neuronal migration, and dendrite morphology during cortical development in vivo

Abstract Heterotrimeric G‐proteins are composed of α, β, and γ subunits, and function as signal transducers. Critical roles of the α‐subunits of Gi/o family heterotrimeric G‐proteins, Gαi2, and Gαo1, have so far been reported in brain development and neurodevelopmental disorders. In this study, we tried to clarify the role of Gαi1, α‐subunit of another Gi/o family member Gi1, during corticogenesis, based on the recent identification of its gene abnormalities in neurodevelopmental disorders. In western blot analyses, Gαi1 was found to be expressed in mouse brain in a developmental stage‐dependent manner. Morphological analyses revealed that Gαi1 was broadly distributed in cerebral cortex with relatively high expression in the ventricular zone (VZ) at embryonic day (E) 14. Meanwhile, Gαi1 was enriched in membrane area of yet unidentified early mitotic cells in the VZ and the marginal zone at E14. Acute knockdown of Gαi1 with in utero electroporation in cerebral cortex caused cell cycle elongation of the neural progenitor cells and promoted their cell cycle exit. Gαi1‐deficient cortical neurons also exhibited delayed radial migration during corticogenesis, with abnormally elongated leading processes and hampered nucleokinesis. In addition, silencing of Gαi1 prevented basal dendrite development. The migration and dendritic phenotypes were at least partially rescued by an RNAi‐resistant version of Gαi1. Collectively, these results strongly suggest a crucial role of Gi1 in cortical development, and disturbance of its function may cause deficits in synaptic network formation, leading to neurodevelopmental disorders. image

Hamada, Nanako↗

Retina-inspired narrowband perovskite sensor array for panchromatic imaging

The retina is the essential part of the human visual system that receives light, converts it to neural signal, and transmits to brain for visual recognition. The red, green, and blue (R/G/B) cone retina cells are natural narrowband photodetectors (PDs) sensitive to R/G/B lights. Connecting with these cone cells, a multilayer neuro-network in the retina provides neuromorphic preprocessing before transmitting to brain. Inspired by this sophistication, we develop the narrowband (NB) imaging sensor combining R/G/B perovskite NB sensor array (mimicking the R/G/B photoreceptors) with a neuromorphic algorithm (mimicking the intermediate neural network) for high-fidelity panchromatic imaging. Compared to commercial sensors, we use perovskite “intrinsic” NB PD to exempt the complex optical filter array. In addition, we use an asymmetric device configuration to collect photocurrent without external bias, enabling a power-free photodetection feature. These results display a promising design for efficient and intelligent panchromatic imaging.

42 ENGINEERING↗

Automated CT registration, segmentation, and quantification (AutoCT) v1.0

Processing and analyzing brain imaging is crucial in both scientific development and clinical field. In this software package, we build a pipeline that integrates automatic registration, segmentation, and quantitative analysis for subjects' CT scans. Leveraging diffeomorphic transformations, we enable optimized forward and inverse mappings between an image and the reference. Furthermore, we extract localized features from deformation field based on an online template process, which advances statistical learning downstream. The created templates, atlas as well as our methods provide the brain imaging community tools for AI implementations.

Essiari, Abdelilah↗

Automated CT registration, segmentation, and quantification (AutoCT) v1.1

Processing and analyzing brain imaging is crucial in both scientific development and clinical field. In this software package, we build a pipeline that integrates automatic registration, segmentation, and quantitative analysis for subjects' CT scans. Leveraging diffeomorphic transofrmations, we enable optimized forward and inverse mappings between an image and the reference. Furthermore, we extract localized features from deformation field based on an online template process, which advances statistical learning downstream. The created templates, atlas as well as our methods provide the brain imaging community tools for AI implementations

Bai, Zhe↗

Lipoprotein Particles in Cerebrospinal Fluid

The brain is the most lipid-rich organ in the body, and the intricate interplay between lipid metabolism and pathologies associated with neurodegenerative disorders is being increasingly recognized. The brain is bathed in cerebrospinal fluid (CSF), which, like plasma, contains lipid-protein complexes called lipoproteins that are responsible for extracellular lipid transport. Multiple CSF lipoprotein populations exist, some of which are produced de novo in the central nervous system and others that appear to be generated from protein constituents that are produced in the periphery. These CSF lipoproteins are thought to play key roles in maintaining lipid homeostasis in the central nervous system, while little else is known due to their limited accessibility and their low abundance in CSF. Recent work has provided new insights into the compositional complexity of CSF lipoprotein families and their metabolism in cerebral circulation. Finally, the purpose of this review is to summarize our current state of knowledge on the composition, origin, and metabolism of CSF lipoproteins.

59 BASIC BIOLOGICAL SCIENCES↗

Second passage of chronic wasting disease of mule deer to sheep by intracranial inoculation compared to classical scrapie

The origin of chronic wasting disease (CWD) in cervids is unclear. One hypothesis suggests that CWD originated from scrapie in sheep. We compared the disease phenotype of sheep-adapted CWD to classical scrapie in sheep. We inoculated sheep intracranially with brain homogenate from first-passage mule deer CWD in sheep (sCWD md ). The attack rate in second-passage sheep was 100% (12 of 12). Sheep had prominent lymphoid accumulations of PrP Sc reminiscent of classical scrapie. The pattern and distribution of PrP Sc in the brains of sheep with CWD md was similar to scrapie strain 13-7 but different from scrapie strain x124. The western blot glycoprofiles of sCWD md were indistinguishable from scrapie strain 13-7; however, independent of sheep genotype, glycoprofiles of sCWD md were different than x124. When sheep genotypes were evaluated individually, there was considerable overlap in the glycoprofiles that precluded significant discrimination between sheep CWD and scrapie strains. Our data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given our results, current detection techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally. It is unknown if sheep are naturally vulnerable to CWD; however, the susceptibility of sheep after intracranial inoculation and lymphoid accumulation indicates that the species barrier is not absolute.

Cassmann, Eric D.↗

Deletion of a non-canonical regulatory sequence causes loss of Scn1a expression and epileptic phenotypes in mice

Abstract Background Genes with multiple co-active promoters appear common in brain, yet little is known about functional requirements for these potentially redundant genomic regulatory elements. SCN1A, which encodes the Na V 1.1 sodium channel alpha subunit, is one such gene with two co-active promoters. Mutations in SCN1A are associated with epilepsy, including Dravet syndrome (DS). The majority of DS patients harbor coding mutations causing SCN1A haploinsufficiency; however, putative causal non-coding promoter mutations have been identified. Methods To determine the functional role of one of these potentially redundant Scn1a promoters, we focused on the non-coding Scn1a 1b regulatory region, previously described as a non-canonical alternative transcriptional start site. We generated a transgenic mouse line with deletion of the extended evolutionarily conserved 1b non-coding interval and characterized changes in gene and protein expression, and assessed seizure activity and alterations in behavior. Results Mice harboring a deletion of the 1b non-coding interval exhibited surprisingly severe reductions of Scn1a and Na V 1.1 expression throughout the brain. This was accompanied by electroencephalographic and thermal-evoked seizures, and behavioral deficits. Conclusions This work contributes to functional dissection of the regulatory wiring of a major epilepsy risk gene, SCN1A . We identified the 1b region as a critical disease-relevant regulatory element and provide evidence that non-canonical and seemingly redundant promoters can have essential function.

60 APPLIED LIFE SCIENCES↗

Association of AK4 Protein From Stem Cell–Derived Neurons With Cognitive Reserve

Background and Objectives: Identifying protein targets that provide cognitive reserve is a strategy to prevent and treat Alzheimer disease and Alzheimer disease related dementias (AD/ADRD). Previous studies using bulk human brain tissue reported 12 proteins associated with cognitive reserve. This study examined whether the same proteins from induced neurons (iNs) are associated with cognitive reserve of their human donors. Methods: Here, induced pluripotent stem cell (iPSC) lines were generated from cryopreserved peripheral blood mononuclear cells of older adults who were autopsied as part of the Religious Orders Study or Rush Memory and Aging Project. Neurons were induced from iPSCs using a standard neurogenin2 protocol. Tandem mass tag proteomics analyses were conducted on iNs day 21. Cognitive reserve of their human donors was measured as person-specific slopes of cognitive change not accounted for by common neuropathologies. Results: The 53 human donors died at a mean age of 91 years, all were non-Latino White, and 36 (67.9%) were female. Eighteen were diagnosed with Alzheimer dementia proximate to death, and 34 had pathologic AD diagnosis at autopsy. Approximately 60% of the donors had above-average cognitive reserve such that their cognition declined slower than an average person with comparable burdens of neuropathologies. Eight of the 12 candidate proteins were quantified in iNs proteomics analyses. Higher adenylate kinase 4 (AK4) expression in iNs was associated with lower cognitive reserve, consistent with the previous report for brain AK4 expression. Discussion: By replicating cortical protein associations with cognitive reserve in human iNs, these data provide a valuable molecular readout for studying complex clinical phenotypes such as cognitive reserve in a dish.

59 BASIC BIOLOGICAL SCIENCES↗

RatXcan: A framework for cross-species integration of genome-wide association and gene expression data

Genome-wide association studies (GWAS) have implicated specific alleles and genes as risk factors for numerous complex traits. However, translating GWAS results into biologically and therapeutically meaningful discoveries remains extremely challenging. Most GWAS results identify noncoding regions of the genome, suggesting that differences in gene regulation are the major driver of trait variability. To better integrate GWAS results with gene regulatory polymorphisms, we previously developed PrediXcan (also known as “transcriptome-wide association studies” orTWAS), which maps SNPs to predicted gene expression using GWAS data. In this study, we developed RatXcan, a framework that extends this methodology to outbred heterogeneous stock (HS) rats. RatXcan accounts for the close familial relationships among HS rats by modeling the relatedness with a random effect that encodes the genetic relatedness. RatXcan also corrects for polygenic-driven inflation because of the equivalence between a relatedness random effect and the infinitesimal polygenic model. To develop RatXcan, we trained transcript predictors for 8,934 genes using reference genotype and expression data from five rat brain regions. We found that the cis genetic architecture of gene expression in both rats and humans was sparse and similar across brain tissues. We tested the association between predicted expression in rats and two example traits (body length and BMI) using phenotype and genotype data from 5,401 densely genotyped HS rats and identified a significant enrichment between the genes associated with rat and human body length and BMI. Thus, RatXcan represents a valuable tool for identifying the relationship between gene expression and phenotypes across species and paves the way to explore shared biological mechanisms of complex traits.

Genetics & Heredity↗

A pilot study: Auditory steady-state responses (ASSR) can be measured in human fetuses using fetal magnetoencephalography (fMEG)

Auditory steady-state responses (ASSRs) are ongoing evoked brain responses to continuous auditory stimuli that play a role for auditory processing of complex sounds and speech perception. Transient auditory event-related responses (AERRs) have previously been recorded using fetal magnetoencephalography (fMEG) but involve different neurological pathways. Previous studies in children and adults demonstrated that the cortical components of the ASSR are significantly affected by state of consciousness and by maturational changes in neonates and young infants. To our knowledge, this is the first study to investigate ASSRs in human fetuses. 47 fMEG sessions were conducted with 24 healthy pregnant women in three gestational age groups (30–32 weeks, 33–35 weeks and 36–39 weeks). The stimulation consisted of amplitude-modulated (AM) tones with a duration of one second, a carrier frequency (CF) of 500 Hz and a modulation frequency (MF) of 27 Hz or 42 Hz. Both tones were presented in a random order with equal probability adding up to 80–100 repetitions per tone. The ASSR across trials was quantified by assessing phase synchrony in the cortical signals at the stimulation frequency. Ten out of 47 recordings were excluded due to technical problems or maternal movements. Analysis of the included 37 fetal recordings revealed a statistically significant response for the phase coherence between trials for the MF of 27 Hz but not for 42 Hz. An exploratory subgroup analysis moreover suggested an advantage in detectability for fetal behavioral state 2F (active asleep) compared to 1F (quiet asleep) detected using fetal heart rate. In conclusion, this pilot study is the first description of a method to detect human ASSRs in fetuses. The findings warrant further investigations of the developing fetal brain.

59 BASIC BIOLOGICAL SCIENCES↗

Naegleria fowleri: Protein structures to facilitate drug discovery for the deadly, pathogenic free-living amoeba

Naegleria fowleri is a pathogenic, thermophilic, free-living amoeba which causes primary amebic meningoencephalitis (PAM). Penetrating the olfactory mucosa, the brain-eating amoeba travels along the olfactory nerves, burrowing through the cribriform plate to its destination: the brain’s frontal lobes. The amoeba thrives in warm, freshwater environments, with peak infection rates in the summer months and has a mortality rate of approximately 97%. A major contributor to the pathogen’s high mortality is the lack of sensitivity of N . fowleri to current drug therapies, even in the face of combination-drug therapy. To enable rational drug discovery and design efforts we have pursued protein production and crystallography-based structure determination efforts for likely drug targets from N . fowleri . The genes were selected if they had homology to drug targets listed in Drug Bank or were nominated by primary investigators engaged in N . fowleri research. In 2017, 178 N . fowleri protein targets were queued to the Seattle Structural Genomics Center of Infectious Disease (SSGCID) pipeline, and to date 89 soluble recombinant proteins and 19 unique target structures have been produced. Many of the new protein structures are potential drug targets and contain structural differences compared to their human homologs, which could allow for the development of pathogen-specific inhibitors. Five of the structures were analyzed in more detail, and four of five show promise that selective inhibitors of the active site could be found. The 19 solved crystal structures build a foundation for future work in combating this devastating disease by encouraging further investigation to stimulate drug discovery for this neglected pathogen.

59 BASIC BIOLOGICAL SCIENCES↗

Fine-tuning TrailMap: The utility of transfer learning to improve the performance of deep learning in axon segmentation of light-sheet microscopy images

Light-sheet microscopy has made possible the 3D imaging of both fixed and live biological tissue, with samples as large as the entire mouse brain. However, segmentation and quantification of that data remains a time-consuming manual undertaking. Machine learning methods promise the possibility of automating this process. This study seeks to advance the performance of prior models through optimizing transfer learning. We fine-tuned the existing TrailMap model using expert-labeled data from noradrenergic axonal structures in the mouse brain. By changing the cross-entropy weights and using augmentation, we demonstrate a generally improved adjusted F1-score over using the originally trained TrailMap model within our test datasets.

97 MATHEMATICS AND COMPUTING↗

Whole nervous system expression of glutamate receptors reveals distinct receptor roles in sensorimotor circuits

A goal of connectomics is to reveal the links between neural circuits and behavior. Larvae of the primitive chordateCionaare well-suited to make contributions in this area. In addition to having a described connectome,Cionalarvae have a range of readily-quantified behaviors. Moreover, the small number of neurons in the larval CNS (∼180) holds the promise of a comprehensive characterization of individual neurons. We present single-neuron predictions for glutamate receptor (GlutR) expression based onin situhybridization. Included are both ionotropic receptors (AMPA, NMDA, and Kainate), and metabotropic receptors. The predicted glutamate receptor expression dataset is discussed in the context of known circuits driving behaviors such as phototaxis, mechanosensation, and looming shadow response. The predicted expression of AMPA and NMDA receptors may help to resolve issues regarding the co-production of GABA and glutamate by a subset of photoreceptors. The targets of these photoreceptors in the midbrain appear to express NMDA receptors, but not AMPA receptors. This is in agreement with previous results indicating that GABA is the primary neurotransmitter from the photoreceptors evoking a swimming response through a disinhibition mechanism, and that glutamate may, therefore, have only a modulatory action in this circuit. Other findings reported here are more unexpected. For example, many of the targets of glutamatergic epidermal sensory neurons (ESNs) do not express any of the ionotropic receptors, yet the ESNs themselves express metabotropic receptors. Thus, we speculate that their production of glutamate may be for communication with neighboring ESNs, rather than to their interneuron targets. Significance StatementSimple invertebrates offer a tractable alternative to complex vertebrate brains, facilitating holistic understanding of brain function. One such invertebrate is the marine chordateCiona, which has the benefit of a complete synaptic wiring diagram for its swimming larva. This “connectome” allowed identification of putative neural circuits driving defined behaviors. Fuller understanding of neural circuits, however, requires a description of the attributes of individual neurons. This study focuses on the excitatory neurotransmitter glutamate, which signals via a complex set of both ionotropic and metabotropic receptors. Here, we present a nervous system-wide prediction of GlutR expression inCionaat the individual neuron level, considered in the context of neural circuits, with emphasis on how GlutR expression accounts for function of neural circuits.

Neurosciences & Neurology↗

A Phenomenological Model for Cavitation

A phenomenological model of cavitation is presented, based on observations that both large relative negative pressures and large negative time derivatives of pressure are required for cavitation onset. We simulated two cavitation experiments to generate cavitation scaling parameters for relative pressure drop and rate of pressure drop. Our results show the model, while simple, is effective at reproducing results from laboratory experiments of cavitation. The parameters were then used in conjunction with a human surrogate computational model to predict, at any position within the head, the probability of intracranial cavitation caused by exposure to a blast event. The results suggest that the magnitude of blast overpressure observed in field data is sufficient to cause intracranial cavitation. Our analysis indicates that the helmeted head, when compared to the unhelmeted head configuration, results in a decrease but not elimination of cavitation exposure. When density functions of cavitation probability versus cumulative brain volume are combined with an injury severity model, the results show helmet efficacy at low and moderate risk levels. However, the convergence of unhelmeted and helmeted probability density functions at high-to-excessive risk thresholds indicates the helmet offers diminishing protection at elevated exposure levels, relative to the unhelmeted baseline. Future investigation and collaboration with neuroscience subject matter experts are needed to contextualize the current computational results. While the present work contributes specific and quantified predictions of intracranial cavitation location and severity, more research is required to apply our results to clinical settings with population-based brain injury subjects and controls. The relationship between our intracranial cavitation predictions with their anticipated clinical sequelae remains a topic in need of exploration.

60 APPLIED LIFE SCIENCES↗

Breakthrough MEG Technology [Slides]

LANL technology is a disruptive innovation to change market dynamics. For medical imaging experts who want to rapidly diagnose brain disorders, our LANL breakthrough MEG solution delivers faster and easier brain imaging without having to go to major urban medical centers.

59 BASIC BIOLOGICAL SCIENCES↗

Digital Twin + AI: Control Room of the Future [Slides]

The control room functions as the central brain of the grid, essential for balancing supply and demand and ensuring moment-to-moment grid reliability. Like the human brain, which processes sensory data to make decisions, control room operators analyze operational data from power generation, transmission, and distribution to make informed decisions. Currently, decision-making primarily rests with operators due to hardware and software limitations. However, with technological advancements, Digital Twins and AI are becoming high interest points in the control room's decision-making pilot programs. NREL is developing a comprehensive decision-making platform that integrates Digital Twins, AI, and advanced visualization techniques. As this integration progresses, the role of Digital Twins will evolve from conducting automated simulations to serving as a Trustworthy AI enabler, offering verification and validation of AI-generated response for power systems or providing physics-aware synthetic data of AI pre-training.

24 POWER TRANSMISSION AND DISTRIBUTION↗

High-Density, Actively Multiplexed µECoG Array on Reinforced Silicone Substrate

Simultaneous interrogation of electrical signals from wide areas of the brain is vital for neuroscience research and can aid in understanding the mechanisms of brain function and treatments for neurological disorders. There emerges a demand for development of devices with highly conformal interfaces that can span large cortical regions, have sufficient spatial resolution, and chronic recording capability while keeping a small implantation footprint. In this work, we have designed 61 channel and 48 channel high-density, cortical, micro-electrocorticographic electrode arrays with 400 µm pitch on an ultra-soft but durable substrate. We have also developed a custom multiplexing integrated circuit (IC), methods for packaging the IC in a water-tight liquid crystal polymer casing, and a micro-bonding method for attaching the electronics package to the electrode array. With the integrated multiplexer, the number of external wire connections can be reduced to 16 wires, thereby diminishing the invasive footprint of the device. Both the electrode array and IC were tested in vivo in a rat model to demonstrate the ability to sense finely-localized electrophysiological signals.

Rachinskiy, Iakov↗