bioRxiv Science⌕ Search

Biology subjects

Tyrer, A.

Publications and source records attributed to Tyrer, A..

4 recordsLinked to original sources

Dissociable Microstructural Correlates of Learning Rate and Learning Noise in Gamified Reward-Based Decision-Making

Humans learn which actions yield the highest rewards through trial and error, gradually forming expectations about outcomes. Yet, people differ substantially in how quickly and precisely they learn. Such individual variability may partly be explained by differences in the brains microstructural organisation. In this large-scale study, 248 participants completed a gamified reward-learning task and underwent quantitative MRI to assess whole-brain microstructural indices of myelination (R1) and cortical iron (R2*). Using computational modelling, we quantified participants learning rates and learning noise, reflecting variability in how reward information is updated over time. Whole-brain voxel-based quantification analyses revealed that increased myelination in the cerebellum was associated with a higher learning rate, whereas learning noise was linked to increased myelination and iron concentration in the precentral gyrus. Together, these findings show that reward learning is not a unitary process but is instead shaped by distinct neurobiological pathways that support learning precision and noise. This work highlights how microstructural variation in sensorimotor and associative cortices contributes to stable versus variable reward learning behaviour across individuals. Significance StatementThis study deepens our understanding of the neural microstructures involved in reward-related decision-making by employing advanced quantitative imaging and computational modelling to investigate brain microstructures associated with individual differences in noisy reward learning and decision-making, using a gamified task. Our results reveal distinct brain microstructures for learning rate and learning noise, which have not been reported before, thereby providing a new understanding of what may be involved in reward-based decision-making. These results provide new potential target pathways for future clinical research in psychiatric disorders where reward processing is implicated, such as ADHD and OCD.

neuroscience↗

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↗

Peripheral Beta-Blockade Differentially Enhances Cardiac and Respiratory Interoception

Interoception, the perception of internal visceral states, arises from complex brain-body interactions across the central and peripheral nervous systems. Despite noradrenalines key role in these interactions, its specific contribution to interoceptive processes remains unclear. In a placebo-controlled, randomised, within-subject study, we employed computational modelling of interoceptive psychophysics to determine how pharmacological beta-adrenoceptor antagonism controls interoception across cardiac and respiratory domains. Both cardio-selective bisoprolol and non-selective propranolol improved cardiac perceptual sensitivity, with bisoprolol exerting an enhanced effect on cardiac metacognition. In contrast, both beta-blockers increased respiratory perceptual precision, with no corresponding changes in sensitivity or metacognition. These findings reveal a novel dissociation between central and peripheral beta-adrenergic mechanisms in interoception, highlighting the pivotal role of peripheral noradrenaline in regulating multi-organ brain-body interactions. Our results suggest that beta-blockers may provide promising routes for modulating distinct facets of interoception, potentially opening new avenues for intervention in conditions characterised by disrupted bodily self-awareness.

neuroscience↗

An efficient and scalable pipeline for epitope tagging in mammalian stem cells using Cas9 ribonucleoprotein

CRISPR/Cas9 can be used for precise genetic knock-in of epitope tags into endogenous genes, simplifying experimental analysis of protein function. However, Cas9-assisted epitope tagging in primary mammalian cell cultures is often inefficient and reliant on plasmid-based selection strategies. Here we demonstrate improved knock-in efficiencies of diverse tags (V5, 3XFLAG, Myc, HA) using co-delivery of Cas9 protein pre-complexed with two-part synthetic modified RNAs (annealed crRNA:tracrRNA) and single-stranded oligodeoxynucleotide (ssODN) repair templates. Knock-in efficiencies of ~5-30%, were achieved without selection in embryonic stem (ES) cells, neural stem (NS) cells, and brain tumour-derived stem cells. Biallelic-tagged clonal lines were readily derived and used to define Olig2 chromatin-bound interacting partners. Using our novel web-based design tool, we established a 96-well format pipeline that enabled V5-tagging of sixty different transcription factors. This efficient, selection-free and scalable epitope tagging pipeline enables systematic surveys of protein expression levels, subcellular localization, and interactors across diverse mammalian stem cells.

cell biology↗