Biology subjects

Roberts, G.

Publications and source records attributed to Roberts, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Structural Brain Network Alterations in Relation to Treatment and Illness Severity in Bipolar Disorder

BackgroundLarge-scale T1-weighted MRI studies have established grey-matter abnormalities in bipolar disorder (BD), with our group contributing to consensus findings. However, structural connectivity, particularly within emotion- and reward-related circuits, remains poorly understood. Diffusion-weighted MRI (dMRI) enables investigation of white-matter pathways, yet prior work is constrained by small samples, methodological heterogeneity, and unclear medication effects. We conducted the largest dMRI network analysis in BD, relating symptom burden and polypharmacy to tractography-derived connectivity and graph-theoretic metrics. MethodsCross-sectional structural and diffusion MRI scans from 449 individuals with BD (35.7{+/-}12.6 years) and 510 controls (33.3{+/-}12.6 years), aged 18-65, were analyzed across 16 ENIGMA-BD sites. Standardized segmentation/parcellation and constrained spherical deconvolution tractography generated individual structural connectivity matrices. Graph-theoretic metrics of global and subnetwork organization were related to symptom severity and medications. ResultsBD showed widespread network alterations (lower density and efficiency, longer path length, and higher betweenness centrality), altered microstructural organization in a limbic-basal ganglia circuit, and abnormal streamline counts in a default-mode/salience/fronto-limbic-basal ganglia network. Longer illness duration, later onset, and psychosis history were associated with greater abnormalities in network architecture, whereas more manic episodes were associated with greater fronto-limbic connectivity. Antidepressant (particularly SSRI), anticonvulsant, and antipsychotic use related to poorer global and fronto-limbic connectivity; no clear lithium effects emerged. ConclusionsAs the largest structural connectivity study in BD, we reveal widespread disruption in reward and emotion-regulation networks influenced by illness severity and medication use. Results show that multisite harmonization is feasible and highlight ENIGMA-BD as a scalable framework for identifying reproducible neurobiological markers.

neuroscience↗

bioRxiv2025

Intrinsic electrophysiological activity maps a latent dimension of poor sleep quality and reduced cognitive performance: a magnetoencephalography study using Cam-CAN data.

Sleep quality and cognition vary as functions of lifestyle, genetics, and health. However, poor sleep quality is prevalent, reportedly affecting approximately 38% of the adult population. Poor sleep quality is a significant risk factor for mood disorders, a predictive factor in cognitive decline in later life, and sleep disturbance is a putative precursor to severe cognitive impairment and is predictive of dementia onset. The direct relationship between these factors and intrinsic neural function is poorly understood. Integrating neurophysiology, cognition, and sleep quality to reveal latent factors would help understand the neurophysiology of sleep disturbances and their relation to cognitive performance. Here, we used data from the Cam-CAN dataset with a partial least squares (PLS) approach, producing a multivariate cross-decomposition model to map resting-state magnetoencephalography (MEG) data and cognitive/sleep scores of healthy controls (n = 490, age 18-86). Normative modelling was applied to MEG data, correcting for effects of age, sex, and handedness. We identify a significant relationship between poorer self-reported sleep quality and lower cognitive performance across multiple domains, characterised by excess low-frequency neural activity and reduced high-frequency activity, particularly in the alpha band. Moreover, globally increased low frequency and decreased alpha-beta functional connectivity - the dominant frequency channel in neural connectivity at rest across the brain - contribute significantly to this relationship. Our multivariate mapping approach enabled us to parse the electrophysiological signatures directly related to sleep quality and cognitive performance, independent of the confounding effects of age, and show that neural slowing and dysconnectivity are intrinsically linked to self-reported sleep quality and cognitive performance.

neuroscience↗

bioRxiv2025

A Scalable Toolkit for Modeling 3D Surface-based Brain Geometry

3D surface-based computational mapping is more sensitive to localized brain alterations in neurological, developmental and psychiatric conditions than traditional gross volumetric analysis, providing fine-scale 3D maps of a wide range of surface-based features. Here we introduce a scalable toolkit for large-scale computational surface analysis, with efficient algorithms for multisite data integration, statistical harmonization, accelerated multivariate statistics, and visualization. We showcase the utility of the toolkit by mapping subcortical shape variations and factors that affect them across 21 international samples from the ENIGMA Bipolar Disorder Working Group (N=3,373).

neuroscience↗

bioRxiv2024

Reciprocal cooperation can be stable when the presence of defectors selects for discrimination

Human cooperation among non-kin has long been accepted as being based on reciprocity - the idea that we return help from individuals that we re-meet. However, this paradigm has been challenged by Efferson et al. (Efferson, C., et al., Super-additive cooperation. Nature, 2024. 626, 1034-1041) who found that repeated interaction was insufficient to support cooperation without selection between groups. The authors based their conclusion on a model in which cooperative partners used a novel function to determine their response. In their system, cooperation through repeated interaction broke down. I point out here that the collapse of cooperation was not the result of the novel strategy set. Instead, it reflects a standard modelling result in which a cooperative environment allows drift towards unstable, undiscriminating strategies. I show how modifying model assumptions such as changing the implementation of mutation or allowing persistent defection maintain the variation which selects for discrimination. This discrimination in turn stabilizes reciprocity. I conclude that Efferson et al.s results can readily be explained by existing theory and that repeated interaction can support cooperation without requiring between-group competition.

evolutionary biology↗

bioRxiv2024

Predicting brain age across the adult lifespan with spontaneous oscillations and functional coupling in resting brain networks captured with magnetoencephalography

The functional repertoire of the human brain changes dramatically throughout the developmental trajectories of early life and even all the way throughout the adult lifespan into older age. Capturing this arc is important to understand healthy brain ageing, and conversely, how injury and diseased states can lead to accelerated brain ageing. Regression modelling using lifespan imaging data can reliably predict an individuals brain age based on expected arcs of ageing. One feature of brain function that is important in this respect, and understudied to date, is neural oscillations - the rhythmic fluctuations of brain activity that index neural cell assemblies and their functioning, as well as coordinating information flow around networks. Here, we analysed resting-state magnetoencephalography (MEG) recordings from 367 healthy participants aged 18 to 83, using two distinct statistical approaches to link neural oscillations & functional coupling with that of healthy ageing. Spectral power and leakage-corrected amplitude envelope correlations were calculated for each canonical frequency band from delta through gamma ranges. Spatially and spectrally consistent associations between healthy ageing and neurophysiological features were found across the applied methods, showing differential effects on neural oscillations, with decreasing amplitude of low frequencies throughout the adult lifespan, and increasing high frequency amplitude. Functional connectivity within and between resting-state brain networks mediated by alpha coupling generally decreased throughout adulthood and increased in the beta band. Predictive modelling of brain age via regression showed an age dependent prediction bias resulting in overestimating the age of younger people (<40 years old) and underestimating the age of older individuals. These findings evidence strong age-related neurophysiological changes in oscillatory activity and functional networks of the brain as measured by resting-state MEG and that cortical oscillations are moderately reliable markers for predictive modelling. For researchers in the field of predictive brain age modelling with neurophysiological data, we recommend attention is paid to predictive biases for younger and older age ranges and consider using specific models for different age brackets. Nevertheless, these results suggest brain age prediction from MEG data can be used to model arcs of ageing throughout the adult lifespan and predict accelerated ageing in pathological brain states.

neuroscience↗

bioRxiv2023

Multi-Site Statistical Mapping of Along-Tract Microstructural Abnormalities in Bipolar Disorder with Diffusion MRI Tractometry

Investigating alterations in brain circuitry associated with bipolar disorder (BD) may offer a valuable approach to discover brain biomarkers for genetic and interventional studies of the disorder and related mental illnesses. Some diffusion MRI studies report evidence of microstructural abnormalities in white matter regions of interest, but we lack a fine-scale spatial mapping of brain microstructural differences along tracts in BD. We also lack large-scale studies that integrate tractometry data from multiple sites, as larger datasets can greatly enhance power to detect subtle effects and assess whether effects replicate across larger international datasets. In this multisite diffusion MRI study, we used BUndle ANalytics (BUAN, Chandio 2020), a recently developed analytic approach for tractography, to extract, map, and visualize profiles of microstructural abnormalities on 3D models of fiber tracts in 148 participants with BD and 259 healthy controls from 6 independent scan sites. Modeling site differences as random effects, we investigated along-tract white matter (WM) microstructural differences between diagnostic groups. QQ plots showed that group differences were gradually enhanced as more sites were added. Using the BUAN pipeline, BD was associated with lower mean fractional anisotropy (FA) in fronto-limbic, interhemispheric, and posterior pathways; higher FA was also noted in posterior bundles, relative to controls. By integrating tractography and anatomical information, BUAN effectively captures unique effects along white matter (WM) tracts, providing valuable insights into anatomical variations that may assist in the classification of diseases.

neuroscience↗

bioRxiv2021

Collaboration Between Host and Viral Factors Shape SARS-CoV-2 Evolution

SARS-CoV-2 continues to evolve, resulting in several variants of concern with novel properties. The factors driving SARS-CoV-2 fitness and evolution in the human respiratory tract remain poorly defined. Here, we provide evidence that both viral and host factors co-operate to shape SARS-CoV-2 genotypic and phenotypic change. Through viral whole-genome sequencing, we explored the evolution of two clinical isolates of SARS-CoV-2 during passage in unmodified Vero-derived cell lines and in parallel, in well-differentiated primary nasal epithelial cell (WD-PNEC) cultures. We identify a consistent, rich genetic diversity arising in vitro, variants of which could rapidly rise to near-fixation with 2 passages. Within isolates, SARS-CoV-2 evolution was dependent on host cells, with Vero-derived cells facilitating more profound genetic changes. However, most mutations were not shared between strains. Furthermore, comparison of both Vero-grown isolates on WD-PNECs disclosed marked growth attenuation mapping to the loss of the polybasic cleavage site (PBCS) in Spike while the strain with mutations in NSP12 (T293I), Spike (P812R) and a truncation of ORF7a remained viable in WD-PNECs. Our work highlights the significant genetic plasticity of SARS-CoV-2 while uncovering an influential role for collaboration between viral and host cell factors in shaping viral evolution and fitness in human respiratory epithelium.

microbiology↗

bioRxiv2021

Magnetic Field Mapping and Correction for Moving OP-MEG

BackgroundOptically pumped magnetometers (OPMs) have made moving, wearable magnetoencephalography (MEG) possible. The OPMs typically used for MEG require a low background magnetic field to operate, which is achieved using both passive and active magnetic shielding. However, the background magnetic field is never truly zero Tesla, and so the field at each of the OPMs changes as the participant moves. This leads to position and orientation dependent changes in the measurements, which manifest as low frequency artefacts in MEG data. ObjectiveWe modelled the spatial variation in the magnetic field and used the model to predict the movement artefact found in a dataset. MethodsWe demonstrate a method for modelling this field with a triaxial magnetometer, then showed that we can use the same technique to predict the movement artefact in a real OPM-based MEG (OP-MEG) dataset. ResultsUsing an 86-channel OP-MEG system, we found that this modelling method maximally reduced the power spectral density of the data by 26.2 {+/-} 0.6 dB at 0 Hz, when applied over 5 s non-overlapping windows. ConclusionThe magnetic field inside our state-of-the art magnetically shielded room can be well described by low-order spherical harmonic functions. We achieved a large reduction in movement noise when we applied this model to OP-MEG data. SignificanceReal-time implementation of this method could reduce passive shielding requirements for OP-MEG recording and allow the measurement of low-frequency brain activity during natural participant movement.

neuroscience↗

bioRxiv2021

Sexual selection for rare beneficial mutations promotes the evolution of sexual reproduction and adaptation

Sexual selection is the process by which traits providing a mating advantage are favoured. Theoretical treatments of the evolution of sex by sexual selection propose that it operates by reducing the load of deleterious mutations. Here, we postulate instead that sexual selection primarily acts through females preferentially mating with males carrying beneficial mutations. We used simulation and analytical modelling to investigate the evolutionary dynamics of beneficial mutations in the presence of sexual selection. We found that female choice for males with beneficial mutations had a much greater impact on genetic quality than choice for males with low mutational load. We also relaxed the typical assumption of a fixed mutation rate. For deleterious mutations, mutation rate should always be minimized, but when rare beneficial mutations can occur, female choice for males with those rare beneficial mutations could overcome a decline in average fitness and allow an increase in mutation rate. We propose that sexual selection for beneficial mutations could overcome the two-fold cost of sex much more readily than choice for males with low mutational load and may therefore be a more powerful explanation for the prevalence of sexual reproduction than the existing theory. If sexual selection results in higher fitness at higher mutation rates and if the variability produced by mutation itself promotes sexual selection, then a feedback loop between these two factors could have had a decisive role in driving adaptation.

evolutionary biology↗

bioRxiv2021

Drift as a driver of language change: An artificial language experiment

Over half a century ago, George Zipf observed that more frequent words tend to be older. Corpus studies since then have confirmed this pattern, with more frequent words being replaced and regularized less often than less frequent words. Two main hypotheses have been proposed to explain this: that frequent words change less because selection against innovation is stronger at higher frequencies, or that they change less because stochastic drift is stronger at lower frequencies. Here, we report the first experimental test of these hypotheses. Participants were tasked with learning a miniature language consisting of two nouns and two plural markers. Nouns occurred at different frequencies and were subjected to treatments that varied drift and selection. Using a model that accounts for participant heterogeneity, we measured the rate of noun regularization, the strength of selection, and the strength of drift in participant responses. Results suggest that drift alone is sufficient to generate the elevated rate of regularization we observed in low-frequency nouns, adding to a growing body of evidence that drift may be a major driver of language change.

evolutionary biology↗

bioRxiv2020

HPF1 and nucleosomes mediate a dramatic switch in activity of PARP1 from polymerase to hydrolase

Poly(ADP-ribose) polymerase 1 (PARP1) is an important player in the response to DNA damage. Recently, histone PARylation factor (HPF1) was shown to be a critical modulator of the activity of PARP1 by facilitating PARylation of histones and redirecting the target amino acid specificity from acidic to serine residues. Here we investigate the mechanism and specific consequences of HPF1-mediated PARylation using nucleosomes as both activators and substrates for PARP1. HPF1 provides that catalytic base Glu284 to substantially redirect PARylation by PARP1 such that the histones in nucleosomes become the primary recipients of PAR chains. Surprisingly, HPF1 partitions most of the reaction product to free ADPR, resulting in much shorter PAR chains compared to reactions in the absence of HPF1. This HPF1-mediated switch from polymerase to hydrolase has important implications for the PARP1-mediated response to DNA damage and raises interesting new questions about the role of intracellular ADPR and depletion of NAD+.

biochemistry↗

bioRxiv2020

In vitro assessment of the virucidal activity of four mouthwashes containing Cetylpyridinium Chloride, ethanol, zinc and a mix of enzyme and proteins against a human coronavirus

Backgroundsaliva is established to contain high counts SARS-CoV-2 virus and contact with saliva droplets, contaminated surfaces or airborne particles are sources of viral transmission. The generation of infective aerosols during clinical procedures is of particular concern. Therefore, a fuller understanding of the potential of mouthwash to reduce viral counts and modulate the risk of transmission in medical professional and public context is an important research topic. Methodwe determined the virucidal activity of four anti-bacterial mouthwashes against a surrogate for SARS-CoV-2, Human CoV-SARS 229E, using a standard ASTM suspension test, with dilution and contact times applicable to recommended mouthwash use. Resultsthe mouthwash formulated with 0.07% Cetylpyridinium Chloride exhibited virucidal effects providing a [≥]3.0 log reduction HCoV-229E viral count. Mouthwashes containing 15.7% ethanol, 0.2% zinc sulphate heptahydrate and a mix of enzymes and proteins did not demonstrate substantive virucidal activity in this test. Conclusionmouthwash containing 0.07% Cetylpyridinium Chloride warrants further laboratory and clinical assessment to determine their potential benefit in reducing the risk of SARS-CoV-2. HighlightsSARS-CoV-2 can be transmitted through contact with infective saliva. Studies are needed to understand if mouthwash can lower SARS-CoV-2 transmission risk. 0.07% Cetylpyridinium Chloride (CPC) mouthwash exhibited virucidal effects against HCoV-SARS 229E. Further studies on potential of 0.07% CPC mouthwash against SARS-CoV-2 are warranted.

microbiology↗

bioRxiv2020

What we talk about when we talk about color

Names for colors vary widely across languages, but color categories are remarkably consistent (Berlin & Kay, 1969). Shared mechanisms of color perception help explain consistent partitions of visible light into discrete color vocabularies (Regier et al., 2007). But the mappings from colors to words are not identical across languages, which may reflect communicative needs - how often speakers must refer to objects of different color (Gibson et al., 2017). Here we quantify the communicative needs of colors in 130 different languages by means of a novel inference algorithm. We find that communicative needs are not uniform: some regions of color space exhibit 30-fold greater demand for communication than other regions. The regions of greatest demand correlate with the colors of salient objects, including ripe fruits in primate diets. Our analysis also reveals a hidden diversity in the communicative needs of colors across different languages, which is partly explained by differences in geographic location and the local biogeography of linguistic communities. Accounting for language-specific, non-uniform communicative needs improves predictions for how a language maps colors to words, and how these mappings vary across languages. Our account closes an important gap in the compression theory of color naming, while opening new directions to study cross-cultural variation in the need to communicate different colors and its impact on the cultural evolution of color categories.

animal behavior and cognition↗

bioRxiv2020

Mouth magnetoencephalography: A unique perspective on the human hippocampus

Traditional magnetoencephalographic (MEG) brain imaging scanners consist of a rigid sensor array surrounding the head; this means that they are maximally sensitive to superficial brain structures. New technology based on optical pumping means that we can now consider more flexible and creative sensor placement. Here we explored the magnetic fields generated by a model of the human hippocampus not only across scalp but also at the roof of the mouth. We found that simulated hippocampal sources gave rise to dipolar field patterns with one scalp surface field extremum at the temporal lobe and a corresponding maximum or minimum at the roof of the mouth. We then constructed a fitted dental mould to accommodate an Optically Pumped Magnetometer (OPM). We collected data using a previously validated hippocampal-dependent task to test the empirical utility of a mouth-based sensor, with an accompanying array of left and right temporal lobe OPMs. We found that the mouth sensor showed the greatest task-related theta power change. We also found that, as predicted by the simulations, the mouth sensor was anti-correlated with those on over the temporal lobes. We found that this sensor had a mild effect on the reconstructed power in the hippocampus (~10% change) but that coherence images between the mouth sensor and reconstructed source images showed a global maximum in the right hippocampus. We conclude that augmenting a scalp-based MEG array with sensors in the mouth shows unique promise for both basic scientists and clinicians interested in interrogating the hippocampus.

neuroscience↗

bioRxiv2020

Comparative primary paediatric nasal epithelial cell culture differentiation and RSV-induced cytopathogenesis following culture in two commercial media.

The culture of differentiated human airway epithelial cells allows the study of pathogen-host interactions and innate immune responses in a physiologically relevant in vitro model. As the use of primary cell culture has gained popularity the availability of the reagents needed to generate these cultures has increased. In this study we assessed two different media, Promocell and PneumaCult, during the differentiation and maintenance of well-differentiated primary nasal epithelial cell cultures (WD-PNECs). We compared and contrasted the consequences of these media on WD-PNEC morphological and physiological characteristics and their responses to respiratory syncytial virus (RSV) infection. We found that cultures generated using PneumaCult resulted in greater total numbers of smaller, tightly packed, pseudostratified cells. However, cultures from both media resulted in similar proportions of ciliated and goblet cells. There were no differences in RSV growth kinetics, although more ciliated cells were infected in the PneumaCult cultures. There was also significantly more IL-29/IFN{lambda}1 secreted from PneumaCult compared to Promocell cultures. In conclusion, the type of medium used for the differentiation of primary human airway epithelial cells impacts experimental results.

cell biology↗

bioRxiv2019

Pragmatic spatial sampling for wearable MEG arrays

Several new technologies have recently emerged promising new MEG systems in which the sensors can be placed close to the scalp. One such technology, Optically Pumped Magnetometry MEG (OP-MEG) allows for a scalp mounted flexible system that provides field measurements within mm of the scalp surface. A question that arises in developing on-scalp systems, such as OP-MEG scanners, is: how many sensors are necessary to achieve adequate performance/spatial discrimination? There are many factors to consider in answering this question such as the signal to noise ratio (SNR), the locations and depths of the sources of interest, the density of spatial sampling, sensor gain errors (due to interference, subject movement, cross-talk, etc.) and, of course, the desired spatial discrimination. In this paper, we provide simulations which show the impact these factors have on designing sensor arrays for wearable MEG. While OP-MEG has the potential to provide high information content at dense spatial samplings, we find that adequate spatial discrimination of sources (<1cm) can be achieved with relatively few sensors (<100) at coarse spatial samplings (~30mm) at high SNR. Comparable discrimination for traditional cryogenic systems require far more channels by these same metrics. Finally we show that sensor gain errors have the greatest impact on discrimination between deep sources at high SNR.

neuroscience↗

bioRxiv2019

Kin selection, not indirect reciprocity, explains helping those who help others in image scoring

Helping those who help others appears to be a widespread phenomenon. It is typically framed as indirect reciprocity in which individuals who are seen to help later receive returns from third parties. However, indirect reciprocity only works when individuals condition their help not just on how their recipient has behaved in the past but also on whether their recipient was justified in behaving that way. It also requires sufficient repeated interactions of this type among other individuals for a benefit to be reciprocated. These factors limit the scope of indirect reciprocity to explain cases where people do help those who help others. Here, I propose instead that helping can be explained by the indirect fitness benefits (or relatedness) that result from helping other helpers in groups. This means that when individuals help other helpers, they may not make any returns via indirect reciprocity, but rather they may be helping a strategy of helping those who help. In this way, the helping strategy can spread even when helping has no net benefit to the individual helper. This is a form of relatedness in which individuals help their kin that are recognized by their helping behaviour. As such, conditional helping is likely to be found where population structure promotes relatedness through non-random association. The analysis suggests indirect reciprocity may not have played the decisive role in the evolution of human cooperation that is often thought, but paradoxically that the use of image scores deserves renewed attention as a strategy of helping those with the same behaviour.

evolutionary biology↗

bioRxiv2019

Honest signalling of trustworthiness

Trust can transform conflicting interests into cooperation. But how can individuals know when to trust others? Here, I develop the theory that reputation building may signal cooperative intent, or trustworthiness. I model a simple representation of this theory in which individuals (1) optionally invest in a reputation by performing costly helpful behaviour ( signalling); (2) optionally use others reputations when choosing a partner; and (3) optionally cooperate with that partner. In evolutionary simulations, high levels of reputation building; of choosing partners based on reputation; and of cooperation within partnerships emerged. Costly helping behaviour evolved into an honest signal of trustworthiness when it was adaptive for cooperators, relative to defectors, to invest in the long-term benefits of a reputation for helping. I show using game theory that this occurs when cooperators gain larger marginal benefits from investing in signalling than do defectors. This happens without the usual costly signalling assumption that individuals are of two types which differ in quality. Signalling of trustworthiness may help explain phenomena such as philanthropy, pro-sociality, collective action, punishment, and advertising in humans and may be particularly applicable to courtship in other animals.

animal behavior and cognition↗