Biology subjects

Allen, M. G.

Publications and source records attributed to Allen, M. G..

8 recordsLinked to original sources

bioRxiv2026

Genomic history and selection in Roman and early medieval Britain

Leading biomedical resources rely on genome variation in Britain1-3, but the historical processes that shaped present-day fine-scale diversity remain debated4-13. Here we sequenced 1039 ancient shotgun genomes from Britain (median 1.4-fold coverage), primarily dating to the first millennium CE. We imputed [~]660 million variants in the UK Biobank14-16 and employed genealogy-based ancestry reconstruction. We found an association between Iron Age consanguinity and matrilineal burial practices17, later disrupted following the Roman Conquest. Despite this societal impact, only 20% of Roman-period individuals carried detectable ancestry from outside Britain. In contrast, from the 6th century CE we detect widespread influx of ancestry in over 70% of individuals in southernAnglo-Saxon Britain, with limited local admixture. We find previously underappreciated heterogeneity, with ancestries associated with Central and Southern Europe rising in prevalence from the 7th century CE. We demonstrate distinct Scandinavian-related ancestry in many Viking-associated contexts, but show that the population-level impact of the Viking Age in Britain was limited. Finally, we detect pre-medieval selection on variants linked with key immunity genes TLR10-TLR1 and IRF8. These results identify population-level and selective processes that shape variation and disease risk in Britain today.

genomics↗

bioRxiv2025

Prevalence, distribution, and mechanisms of genetic dominance in the yeast mating pathway

The proportion of mutations that are dominant is a fundamental genetic parameter affecting the rate of adaptation, the efficacy of selection, and the maintenance of variation in populations. Yet, estimates for this parameter vary greatly. Here we directly quantify the rates and genetic targets of dominant and recessive mutations in the yeast mating pathway by performing parallel genetic screens in haploid (MATa) and diploid (MATa/a) yeast. We find that [~]1% of alpha-factor resistant mutations are dominant. We sequenced 95 alpha-factor resistant mutants to determine the genetic architecture of dominant and recessive mutations. We find recessive mutations throughout the mating pathway; however, dominant mutations are concentrated in three genes: STE4, GPA1, and CLN3. Finally, we investigate the mechanism of genetic dominance in each of these genes. This work sheds light on the prevalence and molecular basis of genetic dominance in a model eukaryotic signal transduction pathway.

genetics↗

bioRxiv2025

Cortical Microstructural Variations Explain Individual Differences in Gamified Exploration-Exploitation Behaviours

The exploration-exploitation trade-off is ubiquitous in our everyday lives, and individuals display considerable variability in their preferred decision-making strategies. Most previous work pertaining to neural signatures of exploration is restricted to functional pathways. However, the specific contributions of cortical microarchitectures to high-level cognitive processes such as decision-making are as yet unknown. Here, we investigated the neuroanatomical foundations of inter-individual variability in decision-making strategies. To this end, 122 healthy participants completed a gamified multi-armed bandit paradigm aimed at teasing apart distinct exploration-exploitation decision strategies. We also collected whole-brain quantitative MRI maps indexing microstructural features of cortical myelination and iron content. Through computational modelling, we disentangled individual-specific exploration strategies, including value-free random exploration. Whole-brain regression analyses identified significant associations between value-free exploration and increased cortical myelination in right frontal brain areas with reported links to impulsivity. By elucidating the brain microstructural correlates of distinct exploration-exploitation strategies, we aimed to further our understanding of why individuals differ in their decision-making capabilities, and how decision-making may become aberrant in mental health conditions.

neuroscience↗

bioRxiv2024

Body-wandering reveals an embodied dimension of thought with distinct affective and neural signatures

When at rest, the mind becomes preoccupied with self-generated thoughts, commonly known as mind-wandering. While the social, autobiographical, and temporal features of these thoughts have been extensively studied, little is known about how frequently the wandering mind turns towards the interoceptive and somatic body. To map this under-explored component of "body-wandering," we conducted a large-scale neuroimaging study in 536 healthy participants, expanding a retrospective multidimensional experience sampling approach to include probes targeting visceral and somatomotor thoughts. Our findings reveal a robust inter-individual dimension of body-wandering characterized by negative affect, high autonomic arousal, and a reduction in socially oriented thoughts. Despite this negative tone, individual differences in the propensity for body-wandering were associated with lower self-reported symptoms of ADHD and depression. Multivariate functional connectivity analyses further revealed that affective, body-oriented thoughts are related to a pattern of thalamocortical connectivity interlinking somatomotor and interoceptive-allostatic cortical networks. Collectively, these results demonstrate that self-generated thoughts exhibit core embodied features which are linked to the ongoing physical and emotional milieu of the visceral body. Significance statementNeuroimaging studies often treat the resting state as a purely cognitive baseline, overlooking the participants embodied experience within the scanner. Here we show that individuals robustly vary in their degree of body-wandering, such that a more somatically focused stream of thought is associated with negative affect, higher arousal, and increased thalamocortical-somatomotor connectivity. Paradoxically, while this state is experienced negatively in the moment, the propensity for embodied mind-wandering correlates with reduced trait level symptoms of depression and ADHD. Collectively, these findings indicate that we must account for the embodied nature of the resting mind to fully understand the neural and clinical mechanisms of self-generated thought.

neuroscience↗

bioRxiv2024

Uncertainty in Thermosensory Expectations Enhances an Illusion of Pain

The human brain has a remarkable ability to learn and update its beliefs about the world. Here, we investigate how thermosensory learning shapes our subjective experience of temperature and the misperception of pain in response to harmless thermal stimuli. Through computational modeling, we demonstrate that the brain uses a probabilistic predictive coding scheme to update beliefs about temperature changes based on their uncertainty. We find that these expectations directly modulate the perception of pain in the thermal grill illusion. Quantitative microstructural brain imaging revealed that the myeloarchitecture and iron content of the somatosensory cortex, the posterior insula and the amygdala reflect inter-individual variability in computational parameters related to learning and the degree to which uncertainty modulates illusory pain perception. Our findings offer a new framework to explain how the brain infers pain from innocuous thermal inputs. Our model has important implications for understanding the etiology of thermosensory symptoms in chronic pain conditions.

neuroscience↗

bioRxiv2024

Assessing Individual Sensitivity to the Thermal Grill Illusion: A Two-Dimensional Adaptive Psychophysical Approach

In the thermal grill illusion (TGI), the spatial alternation of non-noxious warm and cold temperatures elicits burning sensations that resemble the presence of noxious stimuli. Previous research has largely relied on the use of specific temperature values (i.e., 20{degrees}C and 40{degrees}C) to study this phenomenon in both healthy individuals and patient populations. However, this methodology fails to account for inter-individual differences in thermal sensitivity, limiting the precision with which TGI responses can be evaluated across diverse populations. To address this gap, we created a Two-Dimensional Thermal Grill Calibration (2D-TGC) protocol, enabling an efficient and precise estimation of the combinations of warm and cold temperatures needed to elicit burning sensations tailored to each individual. By applying the 2D-TGC protocol in 43 healthy participants, we demonstrated key findings: (1) The TGI can be thresholded using an adaptive psychophysical method. (2) Multiple combinations of warm and cold temperatures can elicit this phenomenon. (3) The protocol facilitated the identification of temperature combinations that elicit TGI with varying levels of probability, intensity, and perceived quality ranging from freezing cold to burning hot. (4) TGI responsivity can be quantified as a continuous variable, moving beyond the conventional classification of individuals as responders vs. non-responders based on arbitrary temperature values. The 2D-TGC offers a comprehensive approach to investigate the TGI across populations with altered thermal sensitivity, and can be integrated with other methods (e.g., neuroimaging) to elucidate the mechanisms responsible for perceptual illusions in the thermo-nociceptive system.

neuroscience↗

bioRxiv2023

Temporal Contrast Enhancement in Thermosensation: A Framework for Understanding Paradoxical Heat Sensation

Paradoxical Heat Sensation (PHS) is the remarkable feeling of warmth or heat pain while the skin is cooling. Despite its initial documentation over 100 years ago, a unified explanation for this perplexing experience remains elusive. Here we apply contrast enhancement principles, known for their instrumental role in understanding visual illusions, to the domain of thermosensation. Contrast enhancement describes the amplification of two contrasting visual features, such as the enhanced perception of an edge between a light and dark bar. In thermosensation, this encompasses an enhancement of the difference between sequential warming and cooling of the skin, and is defined as the normalised difference between successive temporal warm and cold temperatures. Remarkably, thermal contrast predicts the occurrence of PHS. Our findings reveal compelling evidence supporting the role of thermal contrast in the generation of PHS, shedding light on its underlying mechanism and offering a framework for broader encoding principles in thermosensation and pain.

neuroscience↗

bioRxiv2017

Wireless Implantable Sensor For Non-Invasive, Longitudinal Quantification Of Axial Strain Across Rodent Long Bone Defects

Bone development, maintenance, and regeneration are remarkably sensitive to mechanical cues. Consequently, mechanical stimulation has long been sought as a putative target to promote endogenous healing after fracture. Given the transient nature of bone repair, tissue-level mechanical cues evolve rapidly over time after injury and are challenging to measure non-invasively. The objective of this work was to develop and characterize an implantable strain sensor for non-invasive monitoring of axial strain across a rodent femoral defect during functional activity. Herein, we present the design, characterization, and in vivo demonstration of the devices capabilities for quantitatively interrogating physiological dynamic strains during bone regeneration. Ex vivo experimental characterization of the device showed that it exceeded the technical requirements for sensitivity, signal resolution, and electromechanical stability. The digital telemetry minimized power consumption, enabling long-term intermittent data collection. Devices were implanted in a rat 6 mm femoral segmental defect model and after three days, data were acquired wirelessly during ambulation and synchronized to corresponding radiographic videos, validating the ability of the sensor to non-invasively measure strain in real-time. Lastly, in vivo strain measurements were utilized in a finite element model to estimate the strain distribution within the defect region. Together, these data indicate the sensor is a promising technology to quantify local tissue mechanics in a specimen specific manner, facilitating more detailed investigations into the role of the mechanical environment in dynamic skeletal healing and remodeling.

bioengineering↗