Biology subjects

Moran, R.

Publications and source records attributed to Moran, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Reuse of learned subtask representations during human planning

The notion of a compositional reuse of previously learned problem solutions predicts that the human brain should reinstate such learned subtask representations during planning. Here, we test this in a value-ranking task implemented in an online and a magnetoencephalography (MEG) experiment, respectively. Participants first learned pairwise rankings and subsequently solved problems where these learned rankings could either be reused or required reordering. Behaviourally, in the online experiment, we show the availability of a reusable subtask structure improved accuracy, with computational modelling indicating a greater weighting of subtask-level value when participants could avail of this learnt structure. In MEG, during planning, we show enhanced reactivation of task-relevant subtask representations in the reusable condition, and particularly so early in the experiment. In a subsequent probe task, we show subtask-identity representations generalised to a novel context and that stimuli belonging to the same learned subtask manifest an increase in their neural similarity. Temporally delayed linear modelling (TDLM) revealed forward and backward sequential reactivation at a subtask level, alongside backward stimulus-level replay, with subtask sequenceness varying according to task context. The findings provide convergent behavioural, computational and neural evidence for reactivation and reuse of learnt relational structures for novel problem solving.

neuroscience↗

bioRxiv2026

Microvascular architecture and dynamics of the choroid plexus brain barrier

The choroid plexus is a specialized blood-cerebrospinal fluid barrier that supports cerebrospinal fluid production, immune surveillance, and molecular exchange between the circulation and the central nervous system, yet its vascular bed remains poorly understood. Here, we combine whole-tissue clearing and light-sheet imaging, single-nucleus transcriptomic reanalysis, and live calcium imaging of intact murine explants to define the structural and functional organization of choroid plexus endothelial networks across development. Three-dimensional imaging and reconstruction highlights a dense, epithelial-ensheathed vascular plexus that is continuous with the broader cerebrovasculature and organized into anatomically distinct inflow and ventricular margin regions. Transcriptomic analysis identified developmentally stratified endothelial subtypes, with embryonic populations enriched for proliferative, motor, and membrane remodeling programs and adult and aged populations enriched for adhesion, extracellular matrix, transport, and mechanosensory pathways. Endothelial subsets across stages expressed genes linked to flow sensing and calcium-dependent mechanotransduction, including Piezo1, Piezo2, and Trpv4. Consistent with these signatures, intact explants exhibited spontaneous, spatially graded calcium oscillations, and pharmacologic activation by Piezo1, triggered robust network-wide calcium responses in embryonic and adult tissue with distinct temporal dynamics. Piezo1 activation also promoted stabilization of PECAM1-associated endothelial adhesion under ex vivo flow conditions. Together, these findings establish the choroid plexus endothelium as a structurally specialized, developmentally dynamic, and mechanosensitive vascular network and provide a framework for investigating endothelial contributions to blood-cerebrospinal fluid barrier function in health and disease.

neuroscience↗

bioRxiv2025

Dopamine and serotonin transients predict depressive symptom relief following deep brain stimulation of human subcallosal cingulate cortex

Recent advances in deep brain stimulation (DBS) of the subcallosal cingulate (SCC) show promise in mitigating the symptoms of treatment-resistant depression (TRD) in humans1-3. Monoamines, such as dopamine and serotonin, mediate the effects of pharmacological treatments of depression. However, their roles in recovery following DBS remain elusive, largely due to technical limitations of measuring these neurotransmitters in the living human brain. Here, by leveraging machine learning-enhanced electrochemistry4-7, we show that dopamine and serotonin signaling following DBS to the SCC predicted later depressive symptom relief in humans with TRD. We found that both dopamine and serotonin levels increased following subtherapeutic intraoperative SCC stimulation, with each neurotransmitter showing selective responses to distinct decision-making tasks. Furthermore, acute dopamine increases predicted later mood improvements during a social decision-making task, while serotonin enhancement predicted faster responses during a non-social learning task longitudinally. Critically, changes in dopamine and serotonin levels during the social decision-making task jointly predicted depressive symptom remission at 6-month follow-up. These findings illustrate the contribution of both dopamine and serotonin signaling in predicting behavioral improvement and depressive symptom remission in humans with TRD. Such neurochemical plasticity may serve as potential mechanistic biomarkers for SCC DBS mechanism and TRD treatment response. Significance statementO_LIDopamine and serotonin levels increased following acute DBS to the SCC in humans. C_LIO_LIAcute dopamine and serotonin changes predicted later mood and response speed changes. C_LIO_LISustained TRD recovery was predicted by acute increases in both dopamine and serotonin estimates. C_LI

neuroscience↗

bioRxiv2025

The Semantic Underpinnings of Speech Disorganization in Schizophrenia

Effective communication relies on shared semantic representations and their context-sensitive retrieval. Accordingly, difficulties in communicating coherently, as seen in some patients with schizophrenia, may reflect impairments at the level of semantic structure or the retrieval process operating on this structure. Disentangling these components is challenging. Here, we address this problem using a word association task and magnetoencephalography (MEG), allowing us to examine behavioral markers of semantic structure and retrieval as well as semantic representation in the brain. For the latter, we detail an approach that contrasts the brains encoding of concepts as predicted by generic versus personalized semantic models. In so doing, we provide converging evidence for semantic structure idiosyncrasy in patients with schizophrenia who also exhibit speech disorganization. The findings advance our understanding of the semantic underpinnings of speech disorganization in schizophrenia, while also revealing the potential of using personalized semantic models to explain neural representation and behavior.

neuroscience↗

bioRxiv2025

Pregnancy laboratory test dynamics resemble rejuvenation of some organs and aging of others

Aging and pregnancy both involve changes in many physiological systems. Some of these changes are similar, leading to suggestions that pregnancy may be a model for aging. Recent studies using DNA methylation clocks showed apparent aging during gestation which resolves postpartum. Since aging and pregnancy are complex, it is important to compare them in terms of many physiological parameters and at many time points. Here, we analyzed cross-sectional data on 62 lab tests at weekly resolution in 300,000 pregnancies and 1.4 million nonpregnant females aged 20-80. We trained a regression model to predict age from lab tests. Apparent age dropped by 8 years in early pregnancy, rose by 30 years towards delivery, and recovered postpartum. Certain systems exhibited rejuvenation, with opposite trends in pregnancy and aging, including renal, iron, and most liver tests. Others, such as coagulation, thyroid, muscle, and metabolic systems, showed apparent aging. Some systems displayed mixed trends. Notably, in the systems that showed apparent aging, the physiological mechanisms for the changes differed between pregnancy and aging. Pregnancy complications led to an additional apparent aging of 4-8 years. We conclude that pregnancy has features of rejuvenation for some systems, but its aging-like features involve different mechanisms than true aging. Gestational rejuvenation-like mechanisms may offer clues for slowing aspects of biological aging.

bioinformatics↗

bioRxiv2024

A neural mechanism for compositional generalization of structure in humans

A human ability to adapt to the dynamics of novel environments relies on abstracting and generalizing from past experiences. Previous research has focused on how humans generalize from isolated sequential processes, yet we know little about mechanisms that enable adaptation to more complex dynamics, including those that govern much everyday experience. Here, using a novel sequence learning task based on graph factorization, coupled with simultaneous magnetoencephalography (MEG) recordings, we ask whether reuse of experiential "building blocks" enable inference and generalization. Behavioral results were consistent with participants decomposing task experience into subprocesses, abstracting their dynamical structure away from their sensory specifics and transferring these to a new task environment. Neurally, this transfer was associated with a learning-induced, condition-specific, increase in neural similarity among stimuli conditional on their structural role in abstract subprocesses that were shared across task phases. Consistent with this, a complementary dynamical role decoding analysis revealed enhanced neural decodability for stimuli sharing identical structural transition types across experiential contexts, specifically when prior experience included the relevant graph structure. Decoding strength for these role representations was positively related to behavioral success in subprocess knowledge transfer, a relationship that will require future independent replication. These findings provide neural evidence consistent with the idea that a structural scaffolding mechanism supports generalization of experience to new contexts.

neuroscience↗

bioRxiv2024

The impact of heterogeneous spatial autocorrelation on comparisons of brain maps

It is increasingly common to statistically compare brain maps to assess how spatially similar they are. However, statistical inference can be challenging due to the presence of spatial autocorrelation. Therefore, random permutation approaches based on null models are widely used to address this concern. Here, we show how that the presence of heterogeneity in the spatial autocorrelation across brain maps impacts the validity of statistical inference in common approaches for spatially correlated maps. Furthermore, we illustrate how a Bayesian spatial regression approach can be applied to compare functional and structural cortical brain maps, yielding valid statistical inferences even in the presence of heterogeneity. Explicitly modelling spatial properties provides more valid inferences about whole brain spatial maps allowing a wider and more sophisticated range of neurobiological questions to be answered about the relationship between brain maps than are possible with current approaches.

neuroscience↗

bioRxiv2024

pQEB1: a hospital outbreak plasmid lineage carrying blaKPC-2

While conducting genomic surveillance of carbapenemase-producing Enterobacteriaceae (CPEs) from patient colonisation and clinical infections at Birminghams Queen Elizabeth Hospital (QE), we identified an N-type plasmid lineage, pQEB1, carrying several antibiotic resistance genes including the carbapenemase gene blaKPC-2. The pQEB1 lineage is concerning due to its conferral of multi-drug resistance, its host range and apparent transmissibility, and its potential for acquiring further resistance genes. Representatives of pQEB1 were found in three sequence types (STs) of Citrobacter freundii, two STs of Enterobacter cloacae, and three species of Klebsiella. Hosts of pQEB1 were isolated from 11 different patients who stayed in various wards throughout the hospital complex over a 13-month period from January 2023 to February 2024. At present, the only representatives of the pQEB1 lineage in GenBank were carried by an Enterobacter hormaechei isolated from a blood sample at the QE in 2016 and a Klebsiella pneumoniae isolated from a urine sample at University Hospitals Coventry and Warwickshire (UHCW) in May 2023. The UHCW patient had been treated at the QE. Long-read whole-genome sequencing was performed on Oxford Nanopore R10.4.1 flow cells, facilitating comparison of complete plasmid sequences. We identified structural variants of pQEB1 and defined the molecular events responsible for them. These have included IS26-mediated inversions and acquisitions of multiple insertion sequences and transposons, including carriers of mercury or arsenic resistance genes. We found that a particular inversion variant of pQEB1 was strongly associated with the QE Liver speciality after appearing in November 2023, but was found in different specialities and wards in January/February 2024. That variant has so far been seen in five different bacterial hosts from six patients, consistent with recent and ongoing inter-host and inter-patient transmission of pQEB1 in this hospital setting. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/597914v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@17cfa04org.highwire.dtl.DTLVardef@22fd6org.highwire.dtl.DTLVardef@192a339org.highwire.dtl.DTLVardef@1a2434_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Loss of type VI secretion systems in multi-drug resistant Escherichia coli clones

The repeated emergence of multi-drug resistant (MDR) Escherichia coli clones is a threat to public health globally. In recent work, drug resistant E. coli were shown to be capable of displacing commensal E. coli in the human gut. Given the rapid colonisation observed in travel studies, it is possible that the presence of a type VI secretion system (T6SS) may be responsible for the rapid competitive advantage of drug resistant E. coli clones. We employed large scale genomic approaches to investigate this hypothesis. First, we searched for T6SS genes across a curated dataset of over 20,000 genomes representing the full phylogenetic diversity of E. coli. This revealed large, non-phylogenetic variation in the presence of T6SS genes. No association was found between T6SS gene carriage and MDR lineages. However, multiple clades containing MDR clones have lost essential structural T6SS genes. We characterised the T6SS loci of ST410 and ST131 and identified specific recombination and insertion events responsible for the parallel loss of essential T6SS genes in two MDR clones. Data SummaryThe genome sequence data generated in this study is publicly available from NCBI under BioProject PRJNA943186, alongside a complete assembly in GenBank under accessions CP120633-CP120634. All other sequence data used in this paper has been taken from ENA with the appropriate accession numbers listed within the methods section. The E. coli genome data sets used in this work are from a previous publication, the details of which can be found in the corresponding supplementary data files 10.6084/m9.figshare.21360108 [1]. Impact StatementEscherichia coli is a globally significant pathogen that causes the majority of urinary tract infections. Treatment of these infections is exacerbated by increasing levels of drug resistance. Pandemic multi-drug resistant (MDR) clones, such as ST131-C2/H30Rx, contribute significantly to global disease burden. MDR E. coli clones are able to colonise the human gut and displace the resident commensal E. coli. It is important to understand how this process occurs to better understand why these pathogens are so successful. Type VI secretion systems may be one of the antagonistic systems employed by E. coli in this process. Our findings provide the first detailed characterisation of the T6SS loci in ST410 and ST131 and shed light on events in the evolutionary pathways of the prominent MDR pathogens ST410-B4/H42RxC and ST131-C2/H30Rx.

microbiology↗

bioRxiv2022

Genetic mapping of craniofacial traits in the Mexican tetra reveals loci associated with bite differences between cave and surface fish

The Mexican tetra, Astyanax mexicanus, includes interfertile surface-dwelling and cave-dwelling morphs, enabling powerful studies aimed at uncovering genes involved in the evolution of cave-associated traits. Compared to surface fish, cavefish harbor several extreme traits within their skull, such as a protruding lower jaw, a wider gape, and an increase in tooth number. These features are highly variable between individual cavefish and even across different cavefish populations. To investigate these traits, we created a novel feeding behavior assay wherein bite impressions could be obtained. We determined that fish with an underbite leave larger bite impressions with an increase in the number of tooth marks. Capitalizing on the ability to produce hybrids from surface and cavefish crosses, we investigated genes underlying these segregating orofacial traits by performing Quantitative Trait Loci (QTL) analysis with F2 hybrids. We discovered significant QTL for bite (underbite vs. overbite) that mapped to a single region of the Astyanax genome. This work highlights cavefish as a valuable genetic model for orofacial patterning and will provide insight into the genetic regulators of jaw and tooth development.

evolutionary biology↗

bioRxiv2021

Neurocomputational mechanisms of confidence in self and others

Computing confidence in ones own and others decisions is crucial for success in many social situations. While there has been substantial progress in our understanding of confidence in oneself, little is known about how we form confidence about others. Here, we address this question by asking subjects undergoing fMRI to place bets on perceptual decisions made by themselves or one of three other players of varying ability. We show that subjects compute confidence in another players decisions by combining distinct estimates of player ability and decision difficulty - allowing them to predict that a good player may get a difficult decision wrong and that a bad player may get an easy decision right. We find that this computation is supported by an interaction between brain systems traditionally implicated in decision-making (LIP) and theory of mind (TPJ, dmPFC). These results reveal a neurocomputational interplay between self- and other-related processes during social cognition.

neuroscience↗

bioRxiv2021

Dopamine enhances model-free credit assignment through boosting of retrospective model-based inference

Dopamine is implicated in signalling model-free (MF) reward prediction errors and various aspects of model-based (MB) credit assignment and choice. Recently, we showed that cooperative interactions between MB and MF systems include guidance of MF credit assignment by MB inference. Here, we used a double-blind, placebo-controlled, within-subjects design to test the hypothesis that enhancing dopamine levels, using levodopa, boosts the guidance of MF credit assignment by MB inference. We found that levodopa enhanced retrospective guidance of MF credit assignment by MB inference, without impacting on MF and MB influences per se. This drug effect positively correlated with working memory, but only in a context where reward needed to be recalled for MF credit assignment. The dopaminergic enhancement in MB-MF interactions correlated negatively with a dopamine-dependent change in MB credit assignment, possibly reflecting a potential trade-off between these two components of behavioural control. Thus, our findings demonstrate that dopamine boosts MB inference during guidance of MF learning, supported in part by working memory, but trading-off with a dopaminergic enhancement of MB credit assignment. The findings highlight a novel role for a DA influence on MB-MF interactions.

neuroscience↗

bioRxiv2020

Evidence integration and decision-confidence are modulated by stimulus consistency

Evidence-integration is a normative algorithm for choosing between alternatives with noisy evidence, which has been successful in accounting for a vast amount of behavioral and neural data. However, this mechanism has been challenged as tracking integration boundaries sub-serving choice has proven elusive. Here we first show that the decision boundary can be monitored using a novel, model-free behavioral method, termed Decision-Classification Boundary. This method allowed us to both provide direct support for evidence-integration contributions and to identify a novel integration-bias, whereby incoming evidence is modulated based on its consistency with evidence from preceding time-frames. This consistency bias was supported in three cross-domain experiments, involving decisions with perceptual and numerical evidence, which showed that choice-accuracy and decision confidence are modulated by stimulus consistency. Strikingly, despite its seeming sub-optimality, this bias fosters performance by enhancing robustness to integration noise. We argue this bias constitutes a new form of micro-level, within-trial, confirmation bias and discuss implications to broad aspects of decision making.

neuroscience↗

bioRxiv2020

Pleiotropic function of the oca2 gene underlies the evolution of sleep loss and albinism in cavefish

Adaptation to novel environments often involves the evolution of multiple morphological, physiological and behavioral traits. One striking example of multi-trait evolution is the suite of traits that has evolved repeatedly in cave animals, including regression of eyes, loss of pigmentation, and enhancement of non-visual sensory systems [1,3]. The Mexican tetra, Astyanax mexicanus, consists of fish that inhabit at least 30 caves in Northeast Mexico and ancestral-like surface fish which inhabit the rivers of Mexico and Southern Texas [6]. Cave A. mexicanus are interfertile with surface fish and have evolved a number of traits that are common to cave animals throughout the world, including albinism, eye loss, and alterations to behavior [8-10]. To define relationships between different cave-evolved traits, we phenotyped 208 surface-cave F2 hybrid fish for numerous morphological and behavioral traits. We found significant differences in sleep between pigmented and albino hybrid fish, raising the possibility that these traits share a genetic basis. In cavefish and many other species, mutations in oculocutaneous albinism 2 (oca2) cause albinism [11-15]. Surface fish with CRISPR-induced mutations in oca2 displayed both albinism and reduced sleep. Further, this mutation in oca2 fails to complement sleep loss when surface fish harboring this engineered mutation are crossed to different, independently evolved populations of albino cavefish with naturally occurring mutations in oca2, confirming that oca2 contributes to sleep loss. Finally, analysis of the oca2 locus in wild caught cave and surface fish suggests that oca2 is under positive selection in at least three cave populations. Taken together, these findings identify oca2 as a novel regulator of sleep and suggest that a pleiotropic function of oca2 underlies the adaptive evolution of both of albinism and sleep loss.

evolutionary biology↗

bioRxiv2020

Parallel cortical-brainstem pathways to attentional analgesia

Pain perception is diminished when attention is diverted. Our previous human fMRI study, using a 2x2 factorial design with thermal stimuli and concurrent visual attention task, linked the brainstem triad of locus coeruleus (LC), rostroventromedial medulla (RVM) and periaqueductal grey (PAG) to attentional analgesia. This study was repeated with a larger cohort, replicating our earlier findings. Pain intensity was encoded by the RVM, whilst activity in the contralateral LC correlated with the magnitude of attentional analgesia. Psycho-Physiological Interaction analysis informed subsequent Dynamic Causal Modelling and identified two parallel paths between forebrain and the brainstem regions involved in analgesia. These cortico-brainstem connections were modulated by attentional demand: a bidirectional anterior cingulate cortex (ACC) - right-LC loop, and a top-down influence of task on ACC-PAG-RVM. Under conditions of competing attentional demands the ACC recruits discrete brainstem circuits to modulate nociceptive input.

neuroscience↗

bioRxiv2020

Noradrenaline modulates tabula-rasa exploration

An exploration-exploitation trade-off, the arbitration between sampling a lesser-known against a known rich option, is thought to be solved using computationally demanding exploration algorithms. Given known limitations in human cognitive resources, we hypothesised the presence of additional cheaper strategies. We examined for such heuristics in choice behaviour where we show this involves a value-free random exploration, that ignores all prior knowledge, and a novelty exploration that targets novel options alone. In a double-blind, placebo-controlled drug study, assessing contributions of dopamine (400mg amisulpride) and noradrenaline (40mg propranolol), we show that value-free random exploration is attenuated under the influence of propranolol, but not under amisulpride. Our findings demonstrate that humans deploy distinct computationally cheap exploration strategies and where value-free random exploration is under noradrenergic control. Data and materials availabilityData and code will be provided upon acceptance.

neuroscience↗

bioRxiv2020

Phylogenomic resolution of sea spider diversification through integration of multiple data classes

Despite significant advances in invertebrate phylogenomics over the past decade, the higher-level phylogeny of Pycnogonida (sea spiders) remains elusive. Due to the inaccessibility of some small-bodied lineages, few phylogenetic studies have sampled all sea spider families. Previous efforts based on a handful of genes have yielded unstable tree topologies. Here, we inferred the relationships of 89 sea spider species using targeted capture of the mitochondrial genome, 56 conserved exons, 101 ultraconserved elements, and three nuclear ribosomal genes. We inferred molecular divergence times by integrating morphological data for fossil species to calibrate 15 nodes in the arthropod tree of life. This integration of data classes resolved the basal topology of sea spiders with high support. The enigmatic family Austrodecidae was resolved as the sister group to the remaining Pycnogonida and the small-bodied family Rhynchothoracidae as the sister group of the robust-bodied family Pycnogonidae. Molecular divergence time estimation recovered a basal divergence of crown group sea spiders in the Ordovician. Comparison of diversification dynamics with other marine invertebrate taxa that originated in the Paleozoic suggests that sea spiders and some crustacean groups exhibit resilience to mass extinction episodes, relative to mollusk and echinoderm lineages.

evolutionary biology↗

bioRxiv2019

Transferring structural knowledge across cognitive maps in humans and models

Relations between task elements often follow hidden underlying structural forms such as periodicities or hierarchies, whose inferences fosters performance. However, transferring structural knowledge to novel environments requires flexible representations that are generalizable over particularities of the current environment, such as its stimuli and size. We suggest that humans represent structural forms as abstract basis sets and that in novel tasks, the structural form is inferred and the relevant basis set is transferred. Using a computational model, we show that such representation allows inference of the underlying structural form, important task states, effective behavioural policies and the existence of unobserved state-trajectories. In two experiments, participants learned three abstract graphs during two successive days. We tested how structural knowledge acquired on Day-1 affected Day-2 performance. In line with our model, participants who had a correct structural prior were able to infer the existence of unobserved state-trajectories and appropriate behavioural policies.

neuroscience↗