Brain Connectivity and Corticospinal Excitability in Response to Moderate Hypoxia

Overview

Hypoxia, defined as a reduction in the availability of oxygen, induces significant physiological adaptations. While the deleterious effects of severe and chronic hypoxia are well documented, several studies indicate that moderate hypoxia - particularly when administered intermittently - may produce beneficial effects on cardiometabolic health (e.g., improved regulation of blood pressure and better glycaemic control). However, its impact on the dynamics of brain circuits in humans remains relatively underexplored. The present project aims to characterise the effects of continuous and intermittent moderate hypoxia on resting-state brain dynamics in healthy adults. To this end, simultaneous electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) recordings will be conducted in order to extract functional and haemodynamic markers of brain activity. This project will contribute to a better understanding of the neurophysiological mechanisms associated with hypoxic conditioning and to the assessment of its potential application in innovative therapeutic approaches.

Hypoxia refers to a condition in which the availability of oxygen (O₂) is reduced relative to normal conditions. While severe hypoxia is well known for its deleterious effects, moderate hypoxia - particularly when administered intermittently - may produce potentially beneficial effects on cardiometabolic health, such as improved regulation of blood pressure and enhanced energy metabolism. Animal models indicate that hypoxia can promote the expression of neurotrophic factors, stimulate neuroplasticity, and enhance cerebrovascular function. In humans, several studies suggest that intermittent hypoxia induces more pronounced cardiometabolic adaptations than continuous hypoxia and may improve certain cognitive functions in older adults. Recent findings also indicate that moderate hypoxia alters spontaneous brain activity at rest, particularly in the alpha frequency band, suggesting a possible influence on functional brain networks. However, the effects of moderate hypoxia on resting-state brain dynamics remain poorly documented in humans. A detailed characterisation of both the electrical and haemodynamic responses of the brain is therefore required in order to better understand the potential adaptive processes involved and to evaluate the relevance of intermittent hypoxia as a non-pharmacological intervention for optimising brain health. The primary objective of this project is to evaluate the effects of continuous and intermittent moderate hypoxia on resting-state brain dynamics in healthy individuals. To this end, simultaneous EEG and fNIRS recordings will be collected in order to extract functional markers of resting brain activity. A secondary objective is to investigate the impact of moderate hypoxia on brain connectivity and corticospinal excitability. This is a single-centre exploratory descriptive study. Each participant will be assessed during three experimental sessions (i.e. intermittent hypoxia, continuous hypoxia, and normoxia) separated by at least one week and presented in a pseudo-randomised order. During the hypoxic periods, a peripheral oxygen saturation (SpO₂) between 85% and 90% will be targeted. * Session A: exposure to continuous moderate hypoxia (30 minutes) * Session B: exposure to intermittent moderate hypoxia (six cycles of 5 minutes of hypoxia followed by 5 minutes of normoxia) * Session C: exposure to normoxia for 30 minutes Participants will be fitted with a cap enabling the simultaneous recording of EEG activity and haemodynamic signals (via measurements of oxyhaemoglobin \[HbO₂\] and deoxyhaemoglobin \[HbR\] concentrations) using fNIRS. The activity of the first dorsal interosseous muscle of the dominant hand will be recorded using surface electromyography. During the recordings (i.e., hypoxia or normoxia exposure), participants will remain at rest, without any motor activity or specific cognitive stimulation. Corticospinal excitability will be assessed using TMS before and after each hypoxic exposure period. For this purpose, we will measure the amplitude of motor-evoked potentials in the first dorsal interosseous muscle of the dominant hand following stimulation of the contralateral motor cortex using TMS at 120% of the resting motor threshold. This measure will be complemented by the assessment of the efficiency of three intracortical mechanisms that contribute to changes in the excitability of the primary motor cortex: short- and long-interval intracortical inhibition (SICI and LICI, respectively), as well as intracortical facilitation (ICF). These measures will be obtained using paired-pulse TMS protocols.