Biology subjects

Caeyenberghs, K.

Publications and source records attributed to Caeyenberghs, K..

6 recordsLinked to original sources

bioRxiv2026

Endocrine-metabolic decoupling drives stress vulnerability in dystrophin deficiency

Skeletal muscle orchestrates systemic metabolism, dynamically coordinating glucose uptake and fuel use to match energy demand. In Duchenne muscular dystrophy, loss of dystrophin is associated with altered metabolic regulation. In the mdx mouse, we show that physiological stress reveals impaired coordination between insulin and stress responses: glucocorticoid signalling increases without a proportional rise in insulin secretion, resulting in systemic hyperglycaemia despite preserved capacity for muscle glucose uptake. These data support a multi-tissue dystrophinopathy associated with altered endocrine-metabolic coordination. Skeletal muscle glycogen is elevated and incompletely mobilised under stress. The heart maintains high glucose uptake, whereas the brain exhibits reduced uptake, highlighting tissue specific differences in metabolic response. Acute insulin supplementation improves systemic glucose control and restores stress-induced behavioural deficits. Likewise, empagliflozin-mediated glucose offloading reduces stress-associated blood glucose spikes and is associated with improved muscle function to levels comparable with standard care prednisolone. These findings identify impaired coordination of endocrine and metabolic responses during stress as a contributor to metabolic vulnerability in DMD and suggest that modulating insulin availability or glucose flux can improve systemic metabolic control.

systems biology↗

bioRxiv2024

Working Memory Bridges Cognition, Emotion, and Brain Structure: A Multilayer Network Analysis of the Human Connectome Project-Young Adult

Multilayer network analyses allow for the exploration of complex relationships across different modalities. Specifically, this study employed a novel method that integrates psychometric networks with structural covariance networks to explore the relationships between cognition, emotion and the brain. Psychological (NIH Toolbox Cognition Battery and NIH Toolbox Emotion Battery) and anatomical MRI (cortical volume) data were extracted from the Human Connectome Project Young Adult dataset (n = 1109). Partial correlation networks with graphical lasso regularisation and extended Bayesian information criterion tuning were used to model a psychometric bi-layer network consisting of seven cognitive nodes and four emotion nodes, as well as a neuro-psychometric tri-layer network consisting of these same nodes in addition to 24 brain nodes from the central executive and salience networks. Bridge strength centrality was used to identify nodes that bridged between layers. For the bi-layer network, it was found that stress was the only bridge node. For the tri-layer network, six bridge nodes were identified, with the left insula emerging as the most central. These findings demonstrate the utility of multilayer networks in integrating psychological and neurobiological data for the potential identification of targets to improve psychological wellbeing.

neuroscience↗

bioRxiv2023

Accelerated Aging after Traumatic Brain Injury: an ENIGMA Multi-Cohort Mega-Analysis

ObjectiveThe long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. In light of current evidence that even a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using MRI data. Complicated mild, moderate and severe TBI (cmsTBI) is associated with a higher predicted (brain) age difference (PAD), but the progression of PAD over time remains unclear. Here we sought to examine whether PAD increases as a function of time since injury (TSI). MethodsAs part of the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n=343), along with controls, for a total sample size of 540, to reproduce and extend prior findings in the study of TBI brain age. T1w-MRI data were aggregated across 7 cohorts and brain age was established using a similar brain age algorithm to prior work in TBI. ResultsFindings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find evidence supporting a link between PAD and cognitive performance. InterpretationThis work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability, eventually leading to further changes in the decades after a single cmsTBI.

neuroscience↗

bioRxiv2023

Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium

Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 individuals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each individuals latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our conversion tool is freely available online. This demonstrates that large-scale data sharing and harmonization initiatives can address reproducibility and integration challenges across the behavioral sciences. TeaserWe present a global effort to devise harmonization procedures necessary to meaningfully leverage big data.

neuroscience↗

bioRxiv2020

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric msTBI

Annually, approximately 3 million children around the world experience traumatic brain injuries (TBIs), of which up to 20% are characterized as moderate to severe (msTBI) and/or have abnormal imaging findings. Affected children are vulnerable to long-term cognitive and behavioral dysfunction, as injury can disrupt or alter ongoing brain maturation. Post-injury outcomes are highly variable, and there is only limited understanding of how inter-individual differences in outcomes arise. Small sample sizes have also complicated efforts to better understand factors influencing the impact of TBI on the developing brain. White matter (WM) disruption is a critical aspect of TBI neuropathology and diffusion MRI (dMRI) is particularly sensitive to microstructural abnormalities. Here we present the results of a coordinated analysis of dMRI data across ten cohorts from three countries. We had three primary aims: (1) to characterize the nature and extent of WM disruption across key post-injury intervals (acute/subacute - within 2 months, post-acute - 2-6 months, chronic - 6+ months); (2) evaluate the impact of age and sex on WM in the context of injury; and (3) to examine associations between WM and neurobehavioral outcomes. Based on data from 507 children and adolescents (244 with complicated mild to severe TBI and 263 control children), we report widespread WM disruption across all post-injury intervals. As expected, injury severity was a significant contributor to the pattern and extent of WM degradation, but explained less variance in dMRI measures with increasing time since injury, supporting other research indicating that other factors contribute increasingly to outcomes over time. The corpus callosum appears to be particularly vulnerable to injury, an effect that persists years post-TBI. We also report sex differences in the effect of TBI on the uncinate fasciculus (UNC), a structure with a key role in emotion regulation. Females with a TBI had significantly lower fractional anisotropy (FA) in the UNC than those with no TBI, and this phenomenon was further associated with more frequent parent-reported behavioral problems as measured by the Child Behavior Checklist (CBCL). These effects were not detected in males. With future harmonization of imaging and neurocognitive data, more complex modeling of factors influencing outcomes will be possible and help to identify clinically-meaningful patient subtypes.

neuroscience↗

bioRxiv2020

Sleeping While Awake: The Intrusion of Neural Activity Associated with Sleep Onset in the Awake Human Brain

Sleep can intrude into the awake human brain when sleep deprived or fatigued, even while performing cognitive tasks. However, how the brain activity associated with sleep onset can co-exist with the activity associated with cognition in the awake humans remains unexplored. Here, we used simultaneous fMRI and EEG to generate fMRI activity maps associated with EEG theta (4-7 Hz) activity associated with sleep onset. We implemented a method to track these fMRI activity maps in individuals performing a cognitive task after well-rested and sleep-deprived nights. We found frequent intrusions of the fMRI maps associated with sleep-onset in the task-related fMRI data. These sleep events elicited a pattern of transient fMRI activity, which was spatially distinct from the task-related activity in the frontal and parietal areas of the brain. They were concomitant with reduced arousal as indicated by decreased pupil size and increased response time. Graph theoretical modelling showed that the activity associated with sleep onset emerges from the basal forebrain and spreads anterior-posteriorly via the brains structural connectome. We replicated the key findings in an independent dataset, which suggests that the approach can be reliably used in understanding the neuro-behavioural consequences of sleep and circadian disturbances in humans.

neuroscience↗