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Evans, C. J.

Publications and source records attributed to Evans, C. J..

9 recordsLinked to original sources

Breathlessness catastrophising after COVID-19 involves both interoceptive and visceromotor connectivity

Persistent breathlessness is common after COVID-19, yet its severity typically correlates weakly with objective clinical measures. This discordance is often attributed to perceptual inference amplified by anxiety. Because breathing involves a closed perception-action loop, breathlessness may also reflect alterations in interoceptive and visceromotor pathways. We acquired 7-tesla resting-state functional MRI in 53 post-COVID patients with varying breathlessness and estimated functional connectivity across 18 pre-defined interoceptive and visceromotor regions. Linear regression identified two connections associated with breathlessness catastrophising: reduced dorsal periaqueductal grey-posterior insula (dPAG-PoI1) and increased basolateral amygdala-dorsal anterior cingulate (BLA-dACC) connectivity. The dPAG-PoI1 association was stronger in patients who had required mechanical ventilation, whereas the BLA-dACC association was attenuated at higher generalised anxiety. These findings are consistent with two potentially separable contributions to symptom burden: weakened interoceptive signalling between brainstem and sensory cortex, and heightened visceromotor influence of threat processing on autonomic control, rather than anxiety-driven misperception alone.

neuroscience↗

Open-Source Framework for Measurement of the Gradient Impulse Response Function

The Gradient Impulse Response Function (GIRF) is widely used to model and correct gradient system imperfections in MRI, but scanner-specific GIRF measurement remains inaccessible to many research groups because existing approaches rely on specialised field monitoring hardware or fragmented and non-reproducible software workflows. To address this limitation, an open-source, end-to-end framework for phantom-based GIRF measurement is presented, providing a reproducible workflow requiring only standard MRI hardware and a spherical water phantom. The framework integrates vendor-independent pulse sequence generation, phantom-based data acquisition, automated data processing, and GIRF estimation. The framework was validated by comparing GIRF-predicted non-Cartesian k-space trajectories with independent measurements acquired using NMR field probes, which served as the gold-standard for trajectory characterization. Accurate prediction of rosette and spiral trajectories was demonstrated across multiple imaging orientations, with substantially lower trajectory error than the corresponding nominal trajectories. By providing the first openly available end-to-end implementation for phantom-based GIRF measurement, the barrier to routine scanner-specific GIRF characterisation is reduced, facilitating broader adoption of GIRF-based methods across the MRI community.

bioengineering↗

Cardiac diffusion kurtosis imaging in the human heart in vivo using 300mT/m gradients

PurposeDiffusion tensor imaging (DTI) is commonly used in cardiac diffusion magnetic resonance imaging (dMRI). However, the tissues microstructure (cells, membranes, etc.) restricts the movement of the water molecules, making the spin displacements deviate from Gaussian behaviour. This effect may be observed with diffusion kurtosis imaging (DKI) using sufficiently high b-values (b > 450 s/mm2), which are presently outside the realm of routine cardiac dMRI due to the limited gradient strength of clinical scanners. The Connectom scanner with Gmax = 300 mT/m enables high b-values at echo times (TE) similar to DTI on standard clinical scanners, therefore facilitating cardiac DKI in humans. MethodsCardiac-gated, second-order motion-compensated dMRI was performed with bmax = 1350 s/mm2 in 10 healthy volunteers on a 3T MRI scanner with Gmax = 300 mT/m. The signal was fitted to a cumulant expansion up to and including the kurtosis term and diffusion metrics such as fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) were calculated. ResultsWe demonstrate deviation of the signal from monoexponential decay for b-values > 450 s/mm2 (MK = 0.32 {+/-} 0.03). Radial kurtosis (RK = 0.35 {+/-} 0.04) was observed slightly larger than axial kurtosis (AK = 0.27 {+/-} 0.02), and the difference is statistically significant (RK - AK = 0.08 {+/-} 0.04, p = 2e - 4). ConclusionThis work demonstrates the feasibility of quantifying kurtosis effect in the human heart in vivo (at an echo time shorter than typical TEs reported for cardiac DTI), using high-performance gradient systems (which are 4-8 times stronger than on standard clinical scanners). Our work lays the foundation for exploring new biomarkers in cardiac dMRI beyond DTI.

biophysics↗

Multimodal MEG and microstructure-MRI investigations of the human hippocampal scene network

Although several studies have demonstrated that perceptual discrimination of complex scenes relies on an extended hippocampal network, distinct from an anterotemporal network supporting the perceptual discrimination of faces, we currently have limited insight into the specific functional and structural properties of these networks. Here, combining electrophysiological (magnetoencephalography, MEG) and microstructural (multi-shell diffusion MRI, dMRI) imaging in healthy human adults (30 female/10 male), we show that both hippocampal theta power modulation and fibre restriction of the fornix (a major input/output pathway of the hippocampus) independently related to accuracy during scene, but not face, perceptual discrimination. Conversely, microstructural features of the inferior longitudinal fasciculus (a long-range occipito- anterotemporal tract) correlated with face, but not scene, perceptual discrimination accuracy. Our results provide new mechanistic insight into the neurocognitive systems underpinning complex scene and face perception, providing support for multiple-system representation-based accounts of the medial temporal lobe. Significance StatementIn contrast to theories positing segregated cortical areas for perception and memory, the specialized representations of the hippocampus may support both the perception and memory of visual scenes. To investigate, we utilised the unique window into hippocampal electrophysiological activity offered by Magnetoencephalography (MEG). We found hippocampal theta activity modulations in the hippocampus and posteromedial cortex during scene, versus face and shape-size, perceptual oddity discrimination, the magnitude of which correlated with scene, but not face or shape- size, discrimination accuracy. Moreover, multimodal white matter imaging revealed that tissue restriction of the fornix - the major hippocampal output tract - independently predicted scene discrimination performance. Our multimodal MEG-microstructure study provides novel evidence that the hippocampus and connected structures conjointly support online scene processing.

neuroscience↗

Fly-CURE, a Multi-institutional CURE using Drosophila, Increases Students' Confidence, Sense of Belonging, and Persistence in Research

The Fly-CURE is a genetics-focused multi-institutional Course-Based Undergraduate Research Experience (CURE) that provides undergraduate students with hands-on research experiences within a course. Through the Fly-CURE, undergraduate students at diverse types of higher education institutions across the United States map and characterize novel mutants isolated from a genetic screen in Drosophila melanogaster. To evaluate the impact of the Fly-CURE experience on students, we developed and validated assessment tools to identify students perceived research self-efficacy, sense of belonging in science, and intent to pursue additional research opportunities. Our data show gains in these metrics after completion of the Fly-CURE across all student subgroups analyzed, including comparisons of gender, academic status, racial and ethnic groups, and parents educational background. Importantly, our data also show differential gains in the areas of self-efficacy and interest in seeking additional research opportunities between Fly-CURE students with and without prior research experience, illustrating the positive impact of research exposure (dosage) on student outcomes. Altogether, our data indicate that the Fly-CURE experience has a significant impact on students efficacy with research methods, sense of belonging to the scientific community, and interest in pursuing additional research experiences.

scientific communication and education↗

Methacrylate-Modified Gold Nanoparticles Enable Non-Invasive Monitoring of Photocrosslinked Hydrogel Scaffolds

Photocrosslinked hydrogels, such as methacrylate-modified gelatin (gelMA) and hyaluronic acid (HAMA), are widely utilized as tissue engineering scaffolds and/or drug delivery vehicles, but lack a suitable means for non-invasive, longitudinal monitoring of surgical placement, biodegradation, and drug release. Therefore, we developed a novel photopolymerizable X-ray contrast agent, methacrylate-modified gold nanoparticles (AuMA NPs), to enable covalent-linking to methacrylate-modified hydrogels (gelMA and HAMA) in one-step during photocrosslinking and non-invasive monitoring by X-ray micro-computed tomography (micro-CT). Hydrogels exhibited a linear increase in X-ray attenuation with increased Au NP concentration to enable quantitative imaging by contrast-enhanced micro-CT. The enzymatic and hydrolytic degradation kinetics of gelMA-Au NP hydrogels were longitudinally monitored by micro-CT for up to one month in vitro, yielding results that were consistent with concurrent measurements by optical spectroscopy and gravimetric analysis. Importantly, AuMA NPs did not disrupt the hydrogel network, rheology, mechanical properties, and hydrolytic stability compared with gelMA alone. GelMA-Au NP hydrogels were thus able to be bioprinted into well-defined three-dimensional architectures supporting endothelial cell viability and growth. Overall, AuMA NPs enabled the preparation of both conventional photopolymerized hydrogels and bioprinted scaffolds with tunable X-ray contrast for noninvasive, longitudinal monitoring of placement, degradation, and NP release by micro-CT.

bioengineering↗

Injury-induced inflammatory signaling and hematopoiesis in Drosophila

Inflammatory response in Drosophila to sterile (axenic) injury in embryos and adults has received some attention in recent years, and most concentrate on the events at the injury site. Here we focus on the effect sterile injury has on the hematopoietic organ, the lymph gland, and the circulating blood cells in the larva, the developmental stage at which major events of hematopoiesis are evident. In mammals, injury activates Toll-like receptor (TLR)/NF{kappa}B signaling in macrophages, which then express and secrete secondary, pro-inflammatory cytokines. In Drosophila larvae, distal puncture injury of the body wall epidermis causes a rapid activation of Toll and Jun kinase (JNK) signaling throughout the hematopoietic system and the differentiation of a unique blood cell type, the lamellocyte. Furthermore, we find that Toll and JNK signaling are coupled in their activation. Secondary to this Toll/JNK response, a cytokine, Upd3, is induced as a Toll pathway transcriptional target, which then promotes JAK/STAT signaling within the blood cells. Toll and JAK/STAT signaling are required for the emergence of the injury-induced lamellocytes. This is akin to the derivation of specialized macrophages in mammalian systems. Upstream, at the injury site, a Duox- and peroxide-dependent signal causes the activation of the proteases Grass and SPE needed for the activation of the Toll-ligand Spz, but microbial sensors or the proteases most closely associated with them during septic injury are not involved in the axenic inflammatory response.

genetics↗

Evidence against altered excitatory/inhibitory balance in the posteromedial cortex of young adult APOE E4 carriers: a resting state 1H-MRS study

A strategy to gain insight into early changes that may predispose people to Alzheimers disease is to study the brains of younger cognitively healthy people that are at increased genetic risk of AD. The Apolipoprotein (APOE) E4 allele is the strongest genetic risk factor for AD, and several neuroimaging studies comparing APOE E4 carriers with non-carriers at age ~20-30 have detected hyperactivity (or reduced deactivation) in posteromedial cortex (PMC), a key hub of the default network (DN) which has a high susceptibility to early amyloid deposition in AD. Transgenic mouse models suggest such early network activity alterations may result from altered excitatory/inhibitory (E/I) balance, but this is yet to be examined in humans. Here we test the hypothesis that PMC fMRI hyperactivity could be underpinned by altered levels of excitatory (glutamate) and/or inhibitory (GABA) neurotransmitters in this brain region. Forty-seven participants (20 APOE E4 carriers and 27 non-carriers) aged 18-25 underwent resting-state proton magnetic resonance spectroscopy (1H-MRS), a non-invasive neuroimaging technique to measure glutamate and GABA in vivo. Metabolites were measured in a PMC voxel of interest and in a comparison voxel in the occipital cortex (OCC). There was no difference in either glutamate or GABA between the E4 carriers and non-carriers in either MRS voxel, nor in the ratio of glutamate to GABA, a measure of E/I balance. Default Bayesian t-tests revealed evidence in support of this null finding. Results suggest that PMC hyperactivity in APOE E4 carriers is unlikely to be associated with, or indeed may precede, alterations in local resting-state PMC neurotransmitters, thus informing the spatio-temporal order and the cause/effect dynamic of neuroimaging differences in APOE E4 carriers. HighlightsO_LIHyperactivity in posteromedial (PM) network in people at AD genetic risk (APOE E4) C_LIO_LISuch PM network hyperactivity may initiate pathogenic cascade that triggers AD C_LIO_LIAPOE mouse models suggest hyperactivity driven by excitatory/inhibitory imbalance C_LIO_LIUsing 1H-MRS at 3T we studied PMC E/I balance in young adult APOE E4 carriers C_LIO_LIFound evidence against altered E/I balance in young adult APOE E4 carriers C_LI

neuroscience↗

Neurochemical correlates of scene processing in the precuneus/posterior cingulate cortex: a multimodal fMRI and 1H-MRS study

Precuneus/posterior cingulate cortex (PCu/PCC) are key components of a midline network, activated during rest but also in tasks that involve construction of scene or situation models. Despite growing interest in PCu/PCC functional alterations in disease, the underlying neurochemical modulators of PCu/PCCs task-induced activity are largely unstudied. Here, a multimodal imaging approach was applied to investigate whether inter-individual differences in PCu/PCC fMRI activity, elicited during perceptual discrimination of scene stimuli, were correlated with local brain metabolite levels, measured during resting-state 1H-MRS. Forty healthy young adult participants (12 male) completed an fMRI perceptual odd-one-out task for scenes, objects and faces. 1H-MRS metabolites N-acetyl-aspartate (tNAA), glutamate (Glx) and {gamma}-amino-butyric acid (GABA+) were quantified via PRESS and MEGA-PRESS scans in a PCu/PCC voxel and an occipital (OCC) control voxel. Whole brain fMRI revealed a cluster in right dorsal PCu/PCC that showed a greater BOLD response to scenes versus faces and objects. When extracted from an independently defined PCu/PCC region of interest, scene activity (versus faces and objects and also versus baseline) was positively correlated with PCu/PCC, but not OCC, tNAA. A complementary fMRI analysis restricted to the PCu/PCC MRS voxel area identified a significant PCu/PCC cluster, confirming the positive correlation between scene-related BOLD activity and PCu/PCC tNAA. There were no correlations between PCu/PCC fMRI activity and Glx or GABA+ levels. These results demonstrate, for the first time, that scene activity in PCu/PCC is linked to local tNAA levels, identifying a neurochemical influence on inter-individual differences in the task-driven activity of a key brain hub.

neuroscience↗