Biology subjects

Elwell, C. E.

Publications and source records attributed to Elwell, C. E..

3 recordsLinked to original sources

bioRxiv2024

Growth in early infancy drives optimal brain functional connectivity which predicts cognitive flexibility in later childhood

Functional brain network organization, measured by functional connectivity (FC), reflects key neurodevelopmental processes for healthy development. Early exposure to adversity, e.g. undernutrition, affects neurodevelopment, observable via disrupted FC, and leads to poorer outcomes from preschool age onward. We assessed longitudinally the impact of early growth trajectories on developmental FC in a rural Gambian population from age 5 to 24 months. To investigate how these early trajectories relate to later childhood outcomes, we assessed cognitive flexibility at 3-5 years. We observed that early physical growth before the fifth month of life drove optimal developmental trajectories of FC that in turn predicted cognitive flexibility at pre-school age. In contrast to previously studied developmental populations, this Gambian sample exhibited long-range interhemispheric FC that decreased with age. Our results highlight the measurable effects that poor growth in early infancy has on brain development and the possible subsequent impact on pre-school age cognitive development, underscoring the need for early life interventions throughout global settings of adversity.

neuroscience↗

bioRxiv2023

The influence of carbon dioxide on cerebral metabolism and oxygen consumption: combining multimodal monitoring with dynamic systems modelling

Hypercapnia increases cerebral blood flow, but the effect on cerebral metabolism in humans remains incompletely understood. Either increased or reduced oxygen consumption has been predicted from Fick models incorporating cerebral oxygen extraction fraction and cerebral blood flow. Hypercapnia also results in oxidation of cytochrome c oxidase, complex IV of the mitochondrial respiratory chain, implicating a change in cellular metabolism. The aim of this study was to combine systems modelling with non-invasive measurements of cerebral tissue oxygenation, cerebral blood flow, and cytochrome c oxidase redox state to evaluate any metabolic effects of hypercapnia. Cerebral tissue oxygen saturation and cytochrome oxidase redox state were measured with broadband near infrared spectroscopy and cerebral blood flow velocity using transcranial Doppler ultrasound. Data collected during 5-minutes hypercapnia in human volunteers were analyzed using a Fick model to determine changes in brain oxygen consumption and a mathematical model of cerebral hemodynamics and metabolism (BrainSignals) to inform on the potential mechanisms of any observed changes. Systemic physiology - blood pressure, arterial oxygen saturations and end-tidal carbon dioxide - served as model inputs. The extent of the hypercapnic oxidation of cytochrome oxidase required modifications of the BrainSignals model; simulations compared two possible modifications that could cause this oxidation - a decrease in metabolic substrate supply or an increase in metabolic demand. Only the decrease in substrate supply was able to explain both the enzyme redox state changes and the Fick calculated drop in brain oxygen consumption. These modelled outputs are consistent with, but do not prove, previous reports of CO2 inhibition of succinate dehydrogenase, complex II of the mitochondrial respiratory chain. These findings suggest that hypercapnia may have physiologically significant effects suppressing oxidative metabolism in humans and perturbing mitochondrial signaling pathways in health and disease.

physiology↗

bioRxiv2022

Mapping human social brain specialisation beyond the neuron using multimodal imaging in human infants

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of this process is based on evidence from unitary imaging modalities and has thus focused on isolated changes in spatial or temporal precision of neural or haemodynamic activation alone, giving an incomplete picture of the process. We speculate that neural specialisation of function will be underpinned by better coordinated haemodynamic and metabolic changes in a broader orchestrated physiological response. Thus, we present a harmonised framework in which specialisation is indexed by the emergence of coupling between neuronal activity and vascular supply of oxygen and energy. Here, we combine simultaneous measures of coordinated neural activity (EEG), metabolic rate and oxygenated blood supply (broadband near-infrared spectroscopy) to measure emerging specialisation in the infant brain. In 4-to-7-month-old infants, we show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high frequency brain activity. We conclude that functional specialisation of the brain is a coordinated activity across neural, haemodynamic, and metabolic changes, and our ability to measure these simultaneously opens new vistas in understanding how the brain is shaped by its environment.

developmental biology↗