Biology subjects

Edwards, L. J.

Publications and source records attributed to Edwards, L. J..

10 recordsLinked to original sources

bioRxiv2026

Inter- and intra-individual variability in structure-function coupling in human brain

Microstructure shapes functional brain dynamics. Yet this notion has remained largely untested for human brain signals measured with electroencephalography and magnetoencephalography (EEG/MEG). In this study, we related functional activity variance to microstructural variance across brain regions and across participants. Across regions, we used multiple independent datasets: EEG (n=209), MEG (n=507), high-resolution MRI (n=10), and the human post-mortem brain. Across participants, we used a multimodal dataset including MEG and high-resolution MRI (n=31). Between regions, alpha power correlated positively with layer IV thickness and with myelin and iron estimates at mid-cortical depth. By contrast, between participants, alpha power correlated negatively with mid-cortical myelin and iron estimates. Using computational modeling, we demonstrated that regional effects are consistent with excitatory changes, whereas inter-individual effects may be driven by inhibitory influence. This dissociation reveals distinct underlying mechanisms and indicates that different factors influence intra-versus inter-individual variations in alpha activity.

neuroscience↗

bioRxiv2026

Longitudinal whole-human-brain quantitative MRI study on autolysis, fixation, rehydration, and shrinkage effects

Postmortem MRI links in vivo MRI contrast to microstructure measured with ex vivo histology, yet fixation systematically alters relevant physical MRI parameters. We quantified these effects by longitudinally characterizing multi-parametric mapping (MPM) measures - longitudinal (R1) and effective transverse (R2*) relaxation rates, normalized proton density proxy (NA), and magnetization transfer saturation (MTsat) - and tissue-volume change in five whole human brains scanned unfixed ex vivo in situ, during formaldehyde immersion fixation, and, when available, after transfer to phosphate buffered saline solution. We included an independent in vivo cohort of 25 younger healthy participants to provide a qualitative in vivo reference. The largest changes were found for R1 during fixation relative to in situ values (up to 351% in dGM), followed by R2* (up to 60% in WM). NA was largely unchanged during fixation. Although MTsat decreased by up to 25% in gray matter from in vivo to in situ, it largely preserved tissue contrast during fixation and PBS immersion, making it an ideal candidate for longitudinal registration across tissue conditions. Phenomenological models characterized fixation-induced parameter changes and relative tissue-volume change. R1 and fixation-associated volume loss evolved under broadly similar timescales, consistent with a contribution from fixation-related water loss or redistribution. This densely sampled dataset and analyses provide a resource for linking in vivo MRI to postmortem fixed-tissue MRI and ex vivo histology under a standardized immersion-fixation protocol.

neuroscience↗

bioRxiv2024

Lifespan trajectory of chimpanzee brains characterized by magnetic resonance imaging histology

Chimpanzee brain maturation provides an invaluable framework for understanding the evolution of the human brain. We performed ultra-high resolution quantitative magnetic resonance imaging (qMRI) with histological validation on post mortem brains from captive and wild chimpanzees with a broad age range. We mapped developmental myelination and age-related iron accumulation across regions and layers of the neocortex. Compared to humans, chimpanzees showed more myelination and iron deposition in motor and premotor cortices, while the auditory cortex was more strongly myelinated in humans. Our model suggests that chimpanzees cortical myelination was largely completed by the age of nine years, while iron accumulation continued throughout the lifespan. The regions with highest adult levels of myelin and iron took the longest to mature, challenging the widespread assumption that highly myelinated regions complete their development first. The reported maps and developmental curves provide a foundation for comparative neuroscience research and understanding of human brain evolution.

neuroscience↗

bioRxiv2024

Connectivity at fine scale: mapping structural connective fields by tractography of short association fibres in vivo

The extraordinary number of short association fibres (SAF) connecting neighbouring cortical areas is a prominent feature of the large gyrified human brain. The contribution of SAF to the human connectome is largely unknown because of methodological challenges in mapping them. We present a method to characterise cortico-cortical connectivity mediated by SAF in topologically organised cortical areas. We introduce the structural connective fields (sCF) metric which specifically quantifies neuronal signal propagation and integration mediated by SAF. This new metric complements functional connective field metrics integrating across contributions from short- and long-range white matter and intracortical fibres. Applying the method in the human early visual processing stream, we show that SAF preserve cortical functional topology. Retinotopic maps of V2 and V3 could be predicted from retinotopy in V1 and SAF connectivity. The sCF sizes increased along the cortical hierarchy and were smaller than their functional counterparts, in line with the latter being additionally broadened by long-range and intracortical connections. In vivo sCF mapping provides insights into short-range cortico- cortical connectivity in humans comparable to tract tracing studies in animal research and is an essential step towards creating a complete human connectome. HighlightsO_LINon-invasive mapping of Short Association Fibre (SAF) connectivity via diffusion-weighted MRI-based probabilistic tractography accurately predicted cortical functional neuroanatomy. C_LIO_LIThe novel structural Connective Fields (sCF) concept provides a quantitative measure of cortico-cortical integration facilitated by SAF, complementing the existing functional Connective Field (CF) concept. C_LIO_LISub-millimeter resolution diffusion-weighted MRI enables tractography and connective field modeling of SAF, unlocking applications previously restricted to invasive tract tracing in animal studies. C_LI

neuroscience↗

bioRxiv2022

B1+-correction of MT saturation maps optimized for 7T postmortem MRI of the brain

PurposeMagnetization transfer saturation (MTsat) is a useful marker to probe tissue macromolecular content and myelination in the brain. The increased [Formula] -inhomogeneity at [≥] 7T and significantly larger saturation pulse flip angles which are often used for postmortem studies exceed the limits where previous MTsat [Formula] correction methods are applicable. Here, we develop a calibration-based correction model and procedure, and validate and evaluate it in postmortem 7T data of whole chimpanzee brains. TheoryThe [Formula] dependence of MTsat was investigated by varying the off-resonance saturation pulse flip angle. For the range of saturation pulse flip angles applied in typical experiments on postmortem tissue, the dependence was close to linear. A linear model with a single calibration constant C is proposed to correct bias in MTsat by mapping it to the reference value of the saturation pulse flip angle. MethodsC was estimated voxel-wise in five postmortem chimpanzee brains. "Individual-based global parameters" were obtained by calculating the mean C within individual specimen brains and "group-based global parameters" by calculating the means of the individual-based global parameters across the five brains. ResultsThe linear calibration model described the data well, though C was not entirely independent of the underlying tissue and [Formula]. Individual-based and group-based global correction parameters (C = 1.2) led to visible, quantifiable reductions of [Formula]-biases in high resolution MTsat maps. ConclusionThe presented model and calibration approach effectively corrects for [Formula] in-homogeneities in postmortem 7T data.

neuroscience↗

bioRxiv2022

High resolution quantitative and functional MRI indicate lower myelination of thin and thick stripes in human secondary visual cortex

The characterization of cortical myelination is essential for the study of structure-function relationships in the human brain. However, knowledge about cortical myelination is largely based on post mortem histology, which generally renders direct comparison to function impossible. The repeating pattern of pale-thin-pale-thick stripes of cytochrome oxidase (CO) activity in the primate secondary visual cortex (V2) is a prominent columnar system, in which histology also indicates different myelination of thin/thick versus pale stripes. We used quantitative magnetic resonance imaging (qMRI) in conjunction with functional magnetic resonance imaging (fMRI) at ultra-high field strength (7 T) to localize and study myelination of stripes in four human participants at sub-millimeter resolution in vivo. Thin and thick stripes were functionally localized by exploiting their sensitivity to color and binocular disparity, respectively. Resulting functional activation maps showed robust stripe patterns in V2 which enabled further comparison of quantitative relaxation parameters between stripe types. Thereby, we found lower longitudinal relaxation rates (R1) of thin and thick stripes compared to surrounding gray matter in the order of 1-2%, indicating higher myelination of pale stripes. No consistent differences were found for effective transverse relaxation rates [Formula]. The study demonstrates the feasibility to investigate structure-function relationships in living humans within one cortical area at the level of columnar systems using qMRI.

neuroscience↗

bioRxiv2022

Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis

Quantitative MRI (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (R1), effective transverse relaxation rate (R2*), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (R2* at 3T, R1 at 7T), endothelial cells (R1 and MTsat at 3T), microglia (R1 and MTsat at 3T, R1 at 7T), and oligodendrocytes (R1 at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types.

neuroscience↗

bioRxiv2022

Mucociliary Transport Deficiency and Disease Progression in Syrian Hamsters with SARS-CoV-2 Infection

Substantial clinical evidence supports the notion that ciliary function in the airways plays an important role in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, consequent impaired mucociliary transport (MCT) remains unknown for the intact MCT apparatus from an in vivo model of disease. Using golden Syrian hamsters, a common animal model that recapitulates human COVID-19, we quantitatively followed the time course of physiological, virological, and pathological changes upon SARS-CoV-2 infection, as well as the deficiency of the MCT apparatus using micro-optical coherence tomography, a novel method to visualize and simultaneously quantitate multiple aspects of the functional microanatomy of intact airways. Corresponding to progressive weight loss up to 7 days post-infection (dpi), viral detection and histopathological analysis in both the trachea and lung revealed steadily descending infection from the upper airways, as the main target of viral invasion, to lower airways and parenchymal lung, which are likely injured through indirect mechanisms. SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 dpi, largely due to diminished motile ciliation coverage, but not airway surface liquid depth, periciliary liquid depth, or cilia beat frequency of residual motile cilia. Further analysis indicated that the fewer motile cilia combined with abnormal ciliary motion of residual cilia contributed to the delayed MCT. The time course of physiological, virological, and pathological progression suggest that functional deficits of the MCT apparatus predispose to COVID-19 pathogenesis by extending viral retention and may be a risk factor for secondary infection. As a consequence, therapies directed towards the MCT apparatus deserve further investigation as a treatment modality.

microbiology↗

bioRxiv2021

Naturalistic hyperscanning with wearable magnetoencephalography

The evolution of human cognitive function is reliant on complex social interactions which form the behavioural foundation of who we are. These social capacities are subject to dramatic change in disease and injury; yet their supporting neural substrates remain poorly understood. Hyperscanning employs functional neuroimaging to simultaneously assess brain activity in two individuals and offers the best means to understand the neural basis of social interaction. However, present technologies are limited, either by poor performance (low spatial/temporal precision) or unnatural scanning environment (claustrophobic scanners, with interactions via video). Here, we solve this problem by developing a new form of hyperscanning using wearable magnetoencephalography (MEG). This approach exploits quantum sensors for MEG signal detection, in combination with high-fidelity magnetic field control - afforded by a novel "matrix coil" system - to enable simultaneous scanning of two freely moving participants. We demonstrate our approach in a somatosensory task and an interactive ball game. Despite large and unpredictable subject motion, sensorimotor brain activity was delineated clearly in space and time, and correlation of the envelope of neuronal oscillations between people was demonstrated. In sum, unlike existing modalities, wearable-MEG combines high fidelity data acquisition and a naturalistic setting, which will facilitate a new generation of hyperscanning.

neuroscience↗

bioRxiv2020

Relating quantitative 7T MRI across cortical depths to cytoarchitectonics, gene expression and connectomics: a framework for tracking neurodegenerative disease

Cortical layer-specific ultra-high field MRI has the potential to provide anatomically precise biomarkers and mechanistic insights into neurodegenerative disease. Here we compare cortical layer-specificity for a 7T multi-parametric mapping (MPM) 500m whole brain acquisition to the von Economo and Big Brain post-mortem histology atlases. We also investigate the relationship between 7T MPMs, layer-specific gene expression and Huntingtons disease related genes, using the Allen Human Brain atlas. Finally we link MPM cortical depth measures with white matter connections using high-fidelity diffusion tractography from a 300mT/m Connectom MRI system. We show that R2* across cortical depths is highly correlated with layer-specific cell number, cell staining intensity and gene expression. Furthermore white matter connections were highly correlated with grey matter R1 and R2* across cortical depths. These findings demonstrate the potential of combining 7T MPMs, gene expression and white matter connections to provide an anatomically precise framework for tracking neurodegenerative disease.

neuroscience↗