Biology subjects

Dudley, R.

Publications and source records attributed to Dudley, R..

9 recordsLinked to original sources

bioRxiv2026

Connectome-wide mega-analysis identifies a reproducible functional network signature of temporal lobe epilepsy

Resting-state functional magnetic resonance imaging (MRI) studies have reported abnormal intrinsic functional connectivity (FC) across distributed circuits in patients with temporal lobe epilepsy (TLE), indicating a system-level impact of the disorder. However, findings remain inconsistent due to limited sample sizes and methodological heterogeneity, leaving the structural determinants and clinical relevance of FC alterations unresolved. To identify a robust and reproducible FC signature, we conducted a data-driven, connectome-wide mega-analysis in a large multicentre cohort of 652 participants (297 TLE, 73 disease controls, and 282 healthy controls) with multimodal 3T MRI and deep clinical phenotyping. We identified convergent FC reconfigurations at both group and individual levels that preferentially involved densely connected hubs, manifesting as hyperconnectivity in frontoparietal association systems and hypoconnectivity in temporal and paralimbic systems. Integrating structural cortical wiring features further revealed that these extensive alterations were constrained by corticocortical proximity, microstructural similarity, and white matter connectivity. Clinically, the FC phenotype tracked symptom burden and disease progression, informed postsurgical seizure outcome, and distinguished TLE from other focal epilepsies. Collectively, these findings systematically delineate a neurobiologically grounded, hub-centric pattern of intrinsic network disruption in TLE, anchored in temporolimbic and adjacent transmodal systems, with potential utility for individualized phenotypic stratification and outcome prognostication.

neuroscience↗

bioRxiv2025

The Hemodynamic Response Function Varies Across Anatomical Location and Pathology in the Epileptic Brain

The hemodynamic response function (HRF) links neuronal activity to functional magnetic resonance imaging (fMRI) signals. While most fMRI studies use a "canonical" HRF, increasing evidence from studies of healthy subjects suggests that the HRF depends on anatomical location and disease states. Here, we investigate how HRF variability relates to anatomical location and pathology in the epileptic brain, using a large simultaneous electroencephalogram and fMRI dataset. Applying HRF deconvolution and temporal decomposition, we built the first whole-brain HRF library specific to epilepsy, identifying four distinct shape groups. We mapped HRF features across parcellations of two atlases using novel Bayesian hierarchical models. In non-epileptogenic regions, HRF shape and spatial distributions align with findings from healthy subjects. Within pathological regions, they vary significantly according to pathology. Our results indicate that HRF variability is associated with pathology, in addition to its dependence on anatomical location, motivating region- and pathology-based HRF modulation in epilepsy studies.

neuroscience↗

bioRxiv2025

The use of Artificial Intelligence in Magnetic Resonance Imaging of Epilepsy: A Systematic Review and Meta-Analysis

BackgroundThe application of artificial intelligence (AI)/machine learning (ML) to MRI can be a powerful tool to streamline clinical decision-making, yet variability amongst MRI sequences and algorithms have hindered appropriate assessment of reliability and generalizability. MethodsWe conducted a systematic review and meta-analysis of the ability of current AI/ML models operating on MRI data for: 1) epilepsy diagnosis, 2) temporal lobe epilepsy lateralization, 3) lesion localization, and 4) post-surgical outcome prediction. Searches were conducted across PubMed, Medline, and Embase databases from inception until January 1, 2025. We selected studies that employed AI/ML models trained on any MRI modality to classify at least ten patients across the four main objectives for qualitative assessment, and further included in the meta-analysis if they reported an accuracy rate. The primary outcome of the meta-analysis was the overall accuracy of AI/ML models trained on MRI data. The secondary outcome was the concomitant risk of bias evaluation using PROBAST. FindingsWe identified 158 studies for qualitative evaluation and 127 studies for inclusion in the meta-analysis. AI/ML on multimodal MRI could accurately distinguish epilepsy patients from healthy controls (overall accuracy: 88% [85-90]), lateralize temporal lobe epilepsy (90% [87-93]), localize epileptogenic lesions (82% [74-88]), and predict post-surgical seizure-freedom (83% [78-87]). Overall, a high risk of bias remains in the literature; participant bias remained high across all outcomes (64-87%), as well as predictor (88-100%) and analysis (83-100%) bias. Outcome bias was low only for AI/ML studies predicting post-surgical outcomes. InterpretationOur results support promising accuracy of AI/ML models in epilepsy diagnostics and prognostics but remain highly susceptible to bias in participants, predictors, outcome, and analysis domains which limits current translation to routine clinical practice. We encourage closer interdisciplinary collaboration between clinical and scientific groups to improve validation studies based on thorough study design, analysis, and reporting.

neuroscience↗

bioRxiv2025

Epigenomic regulation of human oligodendrocyte myelination properties, relation to age and lineage

Multiple sclerosis (MS) is characterized by immune-mediated injury to myelin and oligodendrocytes (OLs). Repair depends on the ability of OL lineage cells to form new myelin and ensheathe axons. We previously showed that late progenitors (O4+A2B5+ cells) and mature human OLs exhibit age-related differences in ensheathment capacity and vulnerability to injury. Here, we test the hypothesis that differences in chromatin accessibility and specific histone marks may underlie transcriptional differences linked to these functional responses. Confocal imaging of cultured cells revealed higher levels of the transcriptionally permissive histone marks H3K27ac and H4K8ac in pediatric than adult derived late progenitors and mature OLs. Levels were higher in adult-derived progenitors versus mature cells from the same individuals. The majority of pathways and genes related to myelination and immune interactions were downregulated in adult cell samples when compared to pediatric samples. Analysis of publicly available datasets indicated that the chromatin accessibility for genes within these categories was more restricted in adult than pediatric OLs. There was less chromatin accessibility and lower H3K27ac chromatin occupancy also in more differentiated OL compared to progenitors. The levels of the transcriptionally repressive H3K27me3 histone mark in mature OLs were enriched in genomic regions encoding for transcriptional inhibitors of myelination and related signaling pathways, as compared to early progenitors. Restrictions in chromatin accessibility were more pronounced in human cells than in mouse cells. These results link the myelination capacity and immune-mediated injury susceptibility of human OLs to their epigenomic state, raising the issue of how epigenetic modulation could influence disease progression. Significance StatementNeurological disability in multiple sclerosis reflects a balance between the extent of tissue injury and repair. Human oligodendrocytes display distinct donor age- and maturity stage-related epigenomic profiles, which may influence both their myelination potential and vulnerability to immune-mediated injury. Our results emphasize that epigenomic status, particularly chromatin accessibility and specific histone modifications (H3K27ac and H3K27me3), may underlie these functional capacities. Thus, therapeutic strategies aimed at epigenomic modulation must be carefully considered, due to their net effect on these competing processes--promoting myelin repair while potentially altering susceptibility to further damage--to achieve beneficial clinical outcomes.

neuroscience↗

bioRxiv2022

Systematic comparison of culture media uncovers phenotypic shift of human microglia defined by reduced reliance to CSF1R signaling

Efforts to understand microglia function in health and diseases have been hindered by the lack of culture models that recapitulate in situ cellular properties. In recent years, the use of serum-free media with brain-derived growth factors (CSF1R ligands and TGF-{beta}1/2) have been favored for the maintenance of rodent microglia as they promote morphological features observed in situ. Here we study the functional and transcriptomic impacts of such media on human microglia. Media formulation had little impact on microglia transcriptome assessed by RNA sequencing which was sufficient to significantly alter microglia capacity to phagocytose myelin debris and to elicit an inflammatory response to lipopolysaccharide. When compared to immediately ex vivo microglia from the same donors, the addition of fetal bovine serum to culture media, but not growth factors, was found to aid in the maintenance of key signature genes including those involved in phagocytic processes. A phenotypic shift characterized by CSF1R downregulation in culture correlated with a lack of reliance on CSF1R signaling for survival. Consequently, no improvement in cell survival was observed following culture supplementation with CSF1R ligands. Our study provides better understanding of human microglia in culture, with observations that diverge from those previously made in rodent microglia. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/500101v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@16ea011org.highwire.dtl.DTLVardef@1cef01dorg.highwire.dtl.DTLVardef@f621aborg.highwire.dtl.DTLVardef@11c9f97_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Beyond winglets: evolution of flight-related morphology in stick insects (Phasmatodea)

The first winged insects evolved from a wingless ancestor, but details of the transition to a fully-winged morphology remain unclear. Studying extant pterygotes with partial wings, such as the stick insects (Order Phasmatodea), may help us to understand such a transition. Here, we address how a series of flight-related morphological parameters may correlate with flight evolution by studying different phasmids representing a volancy continuum ranging from miniaturized to full-sized wings. Variation in phasmid wing shape, venation, wing mass and the mass of flight muscle can be described by specific scaling laws referenced to wing length and wing loading. Also, the mass distribution of the body-leg system is conserved in spite of a wide range of variation in body shape. With reduced wing size and increased wing loading, the longitudinal position of the wing-bearing thoracic segments is shifted closer to the insects center of body mass. These results demonstrate complex reconfiguration of the flight system during wing morphological transitions in phasmids, with various anatomical features potentially correlated with reduced flight performance attained with partial wings. Although these data represent phasmid-specific features of the flight apparatus and body plan, the associated scaling relationships can provide insight into functionality of intermediate conditions between wingless and fully-winged insects more generally.

evolutionary biology↗

bioRxiv2022

Oxygen availability drives blood traits and the cell number-size tradeoff across Andean hummingbirds

Predictable trait variation across environmental gradients suggests that adaptive evolution repeatedly finds the same solution to a challenge. Trait-environment associations can reflect long-term, genetic evolution across phylogenies, or short-term, plastic responses of individuals. When phylogenetic and population-level patterns match, it implies consistency between the long timescale of adaptation and the short timescale of acclimatization. Alternatively, genetic adaptation can find solutions that break the rules of trait-environment covariation. For example, blood-hemoglobin concentration ([Hb]) increases at high elevations in animals, but genetic adaptations in some populations have been shown to augment tissue oxygenation while curtailing hemoglobin production, altering this predictable [Hb]-elevation association. Here, we tested whether species adaptation to elevation generally alters trait-environment relationships for blood. To do this, we measured blood traits of 1,217 individuals representing 77 species of Andean hummingbirds, across a 4,600 m elevational gradient. We used hierarchical Bayesian modeling to estimate blood trait responses to elevation, environmental temperature, precipitation, individual and species characteristics, and phylogeny. Strikingly, the effects of elevation on [Hb] and hematocrit (Hct) were nearly identical for individuals and species, implying that rules of elevational blood variation are set by physics of gas exchange in the hummingbird respiratory system and are unchanged by species adaptation. However, when we looked at mechanisms of [Hb] adjustment--by changes in red blood cell size or number--we did find a signal of species adaptation: To adjust [Hb], species at low and high elevations, respectively, tended to adjust cell size, whereas species at mid-elevations tended to adjust cell number. Despite scale-independent elevational variation in [Hb] and Hct, the species-specific balance of red blood cell size versus number appears to have been affected by adaptations that distinguish hummingbird species living at moderate versus high elevations.

evolutionary biology↗

bioRxiv2020

Canopy parkour: movement ecology of post-hatch dispersal in a gliding nymphal stick insect (Extatosoma tiaratum)

For flightless arboreal arthropods, moving from the understory into tree canopies is cognitively and energetically challenging because vegetational structures present complex three-dimensional landscapes with substantial gaps. Predation risk and wind-induced perturbations in the canopy may further impede the movement process. In the Australian stick insect Extatosoma tiaratum, first-instar nymphs hatch on the forest floor and disperse toward tree canopies in the daytime. Here, we address such vertical movements and associated sensory cues in E. tiaratum nymphs. Newly hatched nymphs ascend with high endurance, travelling >100 m within 60 minutes. Navigation toward open canopies is underpinned by negative gravitaxis, positive phototaxis, and visual responses to vertically oriented contrast patterns. Nymphal E. tiaratum also use directed jumping to cross air gaps, and respond to tactile stimulation and potential threat with a self-dropping reflex, resulting aerial descent. Post-hatch dispersal in E. tiaratum thus consists of visually mediated displacement both on vegetational structures and in the air; within the latter context, gliding is then an effective mechanism enabling recovery after predator- and perturbation-induced descent. These results further support the importance of a diurnal niche, in addition to the arboreal spatial niche, in the evolution of gliding in wingless arboreal invertebrates. Summary statementTo effectively disperse into canopies, ground-hatched stick insects use gravity and visual cues to navigate during midday, jump to cross air gaps and respond to threat or perturbation with self-dropping.

animal behavior and cognition↗

bioRxiv2019

A tale of winglets: evolution of flight morphology in stick insects

The evolutionary transition between winglessness and a full-winged morphology requires selective advantage for intermediate forms. Conversely, repeated secondary wing reductions among the pterygotes indicates relaxation of such selection. However, evolutionary trajectories of such transitions are not well characterized. The stick insects (Phasmatodea) exhibit diverse wing sizes at both interspecific and intersexual levels, and thus provide a system for examining how selection on flight capability, along with other selective forces, drives the evolution of flight-related morphology. Here, we examine variation in relevant morphology for stick insects using data from 1100+ individuals representing 765 species. Although wing size varies along a continuous spectrum, taxa with either long or miniaturized wings are the most common, whereas those with intermediate-sized wings are relatively rare. In a morphological space defined by wing and body size, the aerodynamically relevant parameter termed wing loading (the average pressure exerted on the air by the wings) varies according to sex-specific scaling laws; volant but also flightless forms are the most common outcomes in both sexes. Using phylogenetically-informed analyses, we show that relative wing size and body size are inversely correlated in long-winged insects regardless of sexual differences in morphology and ecology. These results demonstrate the diversity of flight-related morphology in stick insects, and also provide a general framework for addressing evolutionary coupling between wing and body dimensions. We also find indirect evidence for a fitness valley associated with intermediate-sized wings, suggesting relatively rapid evolutionary transitions between wingless and volant forms.

evolutionary biology↗