Biology subjects

Corbett, J.

Publications and source records attributed to Corbett, J..

4 recordsLinked to original sources

bioRxiv2025

Effective connectivity reveals dual-route mechanism of visual prediction precision via insula and pulvinar

The brains ability to weight predictions by their precision is a central mechanism in predictive processing, enabling optimal integration of prior expectations with incoming sensory input. Despite its theoretical significance, the neural circuitry that implements precision-weighted prediction remains unclear. Using 7-Tesla fMRI and dynamic causal modelling (DCM), this study investigated how the brain encodes the precision of predictions during a visual cueing task with high- and low-precision conditions. We focused on the key regions implicated in predictive processing: the insular cortex, the pulvinar nucleus of the thalamus, and primary visual cortex (V1). Behaviourally, participants showed significantly greater accuracy in the high-precision condition (p < .001), confirming effective task manipulation. DCM analyses revealed that high-precision predictions elicited excitatory modulation of connectivity from the insula to V1 (Pp = .95), alongside inhibitory influences from the insula to the pulvinar (Pp = .99) and from the pulvinar to V1 (Pp = .89). Furthermore, leave-one-out cross validation revealed that individual differences in behavioural sensitivity to precision were positively predicted by pulvinar-to-insula connectivity (r = .36, p = .026) and negatively predicted by the connectivity between pulvinar and V1 (pulvinar to V1: r = .35, p = .033; V1 to pulvinar: r = .37, p = .026), highlighting the behavioural relevance of these pathways. Together, these findings suggest a dual-route mechanism whereby the insula directly enhances top-down predictions in V1 while indirectly dampening bottom-up sensory input via the pulvinar. This mechanism may facilitate Bayesian integration under uncertainty and offers new hypotheses into how precision weighting may be disrupted in neuropsychiatric conditions.

neuroscience↗

bioRxiv2025

Non-invasive assessment of integrated cardiorespiratory network dynamics after physiological stress in humans

BackgroundPhysiological variables provide critical insights into the integrated control of the cardiorespiratory system, reflecting the bodys real-time responses to internal and external perturbations. Visualizing the exchange of information between different components of the cardiorespiratory system is beneficial for monitoring individuals in various clinical settings and extreme environments. This study aimed to develop a non-invasive method, using principles of information theory, to visualize the flow of information between physiological variables, with a focus on the integrated cardiorespiratory responses to different physiological stressors. MethodsHeart rate, respiratory rate, minute ventilation, respiratory frequency, tidal volume, capillary oxygen saturation (SpO2), end-tidal oxygen, and end-tidal carbon dioxide concentrations were recorded from 22 healthy participants. Transfer entropy, which reflects measures of causal relationships between parallel time-series, was used to compute the flow of information between cardiorespiratory signals into network maps. Network mapping was performed after rest in a control condition and following exposure to the isolated and combined effects of normobaric hypoxia (FIO2: 0.12), moderate intensity cycling exercise (100W), and overnight sleep deprivation. For each intervention, 10-minute segments of physiological signals (from minutes 5 to 15 after the commencement of hypoxia and/or exercise) were used for analysis. ResultsEach physiological stressor was associated with a distinctive pattern of information flow between physiological variables. Hypoxia led to the engagement of SpO2 a hub in the network, facilitating the exchange of information with end-tidal oxygen concentration and heart rate. Sleep deprivation was associated with a shift in the flow of information from SpO2 to other nodes, such as respiratory rate, during hypoxia. During exercise, heart rate emerged as the central node for receiving information, while SpO2 acted as the primary node disseminating information to other nodes. Increased connectivity within the networks was observed during exercise alone or when combined with other stressors. ConclusionThis non-invasive network mapping technique visualizes the interaction of various cardiorespiratory variables following exposure to physiological stressors. By mapping normative responses, this approach may help identify outliers associated with various disease states.

physiology↗

bioRxiv2024

Connexin 43 mediated mitochondrial transfer prevents cisplatin induced sensory neurodegeneration.

Platinum based chemotherapeutics including cisplatin are front-line treatments for paediatric and adult cancer. Despite advancements in medical interventions, chemotherapy-induced peripheral sensory neuropathy is a common adverse health related complication that can persist for the long-term and impacts upon an individuals quality of life. Recently, the causes of chemotherapy induced sensory neurodegeneration has been linked to sensory neuronal mitochondrial dysfunction. Here this study investigated how monocytic mitochondria donation to recipient cisplatin damaged dorsal root ganglia (DRG) sensory neurons prevented platinum-based chemotherapy-induced sensory neurotoxicity. Neuronal cell line, SH-SY5Y, or mouse DRG sensory neurons were treated with either vehicle or cisplatin, and co-cultured with mitotracker-labelled THP1 monocytes. Cisplatin induced dysmorphic mitochondria and diminished oxidative phosphorylation dependent energy production in cisplatin treated dorsal root ganglia sensory neurons. DRG sensory neurons exposed to cisplatin were recipients of monocyte mitochondria indicated by increased intracellular mitotracker fluorescent labelling. Mitochondrial transfer to sensory neurons was neuroprotective, preventing neurite loss and sensory neuronal apoptosis. Vehicle treated DRG sensory neurons did not demonstrate significant mitochondrial uptake. Furthermore, cisplatin induced mitochondrial transfer was prevented by pharmacological inhibition of gap junction protein, connexin 43. Connexin 43 inhibition led to reduced neuroprotective capacity via mitochondrial transfer. These findings demonstrate that monocytic mitochondria transfer to DRG sensory neurons damaged by cisplatin, is dependent upon gap junction intercellular communication to promote sensory neuronal survival. This novel process in sensory neuronal protection is a potential novel therapeutic intervention for alleviating neuropathic pain in individuals treated for cancer.

neuroscience↗

bioRxiv2019

SurfaceGenie: A web-based application for integrating predictive and experimental data for rational candidate surface marker prioritization

MotivationCell-type specific surface proteins can be exploited as valuable markers for a range of applications including immunophenotyping live cells, targeted drug delivery, and in vivo imaging. Despite their utility and relevance, the unique combination of molecules present at the cell surface are not yet described for most cell types. A significant challenge in analyzing omic discovery datasets is the selection of candidate markers that are most applicable for downstream applications. ResultsHere, we developed GenieScore, a prioritization metric that integrates a consensus-based prediction of cell surface localization with user-input data to rank-order candidate cell-type specific surface markers. In this report, we demonstrate the utility of GenieScore for analyzing human and rodent data from proteomic and transcriptomic experiments in the areas of cancer, stem cell, and islet biology. We also demonstrate that permutations of GenieScore, termed IsoGenieScore and OmniGenieScore, can efficiently prioritize co-expressed and intracellular cell-type specific markers, respectively. Availability and ImplementationCalculation of GenieScores and lookup of SPC scores is made freely accessible via the SurfaceGenie web-application: www.cellsurfer.net/surfacegenie.

systems biology↗