Biology subjects

Shephard, E.

Publications and source records attributed to Shephard, E..

3 recordsLinked to original sources

bioRxiv2025

Growth charts of infant visual neurodevelopment generalize across global contexts

Normative brain growth charts in early life hold great promise for furthering basic and clinical science. We leverage the rapid, substantial development of visual cortex function that is indexed by visual-evoked potentials (VEP) in electroencephalography to create longitudinal normative growth curves of task-related brain function with 1374 observations contributed by 802 infants (57 to 579 days old) from South Africa, Brazil, and the United States. Site-specific models were cross-validated and showed excellent fits to other sites samples, demonstrating functional growth curves generalize across contexts robustly. Deviations from the normative growth models associated with early environmental and behavioral measures such as prenatal exposures and postnatal cognition. These findings demonstrate the utility of using functional growth charts to understand and potentially act on individual neurodevelopmental trajectories. VEP brain function growth charts represent a new direction for EEG research to support healthy brain development globally.

neuroscience↗

bioRxiv2024

Spatiotemporal dynamics of EEG microstate networks over the first two years of life: A multi-cohort longitudinal study

The first two years of life are marked by rapid development of large-scale brain networks that support emerging cognition and behavior. Magnetic-resonance approaches have revealed much about largescale networks in sleep, but very little is known about functional network dynamics in awake, behaving infants during this period of substantial development. Microstates are brief instances of distinct spatial topographies of largescale neural activity measured with electroencephalography (EEG) that offer a novel approach to studying whole-brain network dynamics at sub-second scale in awake infants by capturing their temporally coherent brain activity. While emerging literature is leveraging microstate dynamics in adults to understand mature largescale network function, developmental trajectories during networks rapid construction in infancy remain uncharacterized. In this study, we leveraged longitudinal resting-state EEG data from 854 infants across two geoculturally diverse cohorts to explore largescale network development through EEG microstates over the first two years of life. We provide evidence for conserved emergence of various network configurations (microstate classes A-G) through infancy across cohorts using data-driven clustering analyses. We also demonstrate significant longitudinal changes in microstate dynamics during this period, characterized by more numerous and more rapid transitions between largescale configurations, especially over early infancy. While patterns of sensory microstate development were largely consistent between cohorts, higher-order cognitive microstates showed context-specific developmental trends. Together these results provide novel insights into how large-scale brain networks functionally develop and organize across the first two years of life.

neuroscience↗

bioRxiv2023

Metabolomic and transcriptomic analyses of Fmo5-/- mice reveal roles for flavin-containing monooxygenase 5 (FMO5) in NRF2-mediated oxidative stress, the unfolded protein response, lipid homeostasis, and carbohydrate and one-carbon metabolism

Flavin-containing monooxygenase 5 (FMO5) is a member of the FMO family of proteins best known for their roles in the detoxification of foreign chemicals and more recently in endogenous metabolism. We have previously shown that Fmo5-/- mice display an age-related lean phenotype, with much reduced weight gain from 20 weeks of age. The phenotype is characterized by decreased fat deposition, lower plasma concentrations of glucose and cholesterol, higher glucose tolerance and insulin sensitivity, and resistance to diet-induced obesity. In the present study we report the use of metabolomic and transcriptomic analyses of livers of Fmo5-/- and wild-type mice to identify factors underlying the lean phenotype of Fmo5-/- mice and gain insights into the function of FMO5. Disruption of the Fmo5 gene has wide-ranging effects on the abundance of metabolites and expression of genes in the liver. The results reveal that FMO5 is involved in upregulating the NRF2-mediated oxidative stress response, the unfolded protein response and response to hypoxia and cellular stress, indicating a role for the enzyme in adaptation to oxidative and metabolic stress. FMO5 also plays a role in stimulating a wide range of metabolic pathways and processes, particularly ones involved in the regulation of lipid homeostasis, the uptake and metabolism of glucose, the generation of cytosolic NADPH, and in one-carbon metabolism. The results predict that FMO5 acts by stimulating the NRF2, XBP1, PPARA and PPARG regulatory pathways, while inhibiting STAT1 and IRF7 pathways.

biochemistry↗