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.

Detailed description

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.

Interventions

• Device Moderate hypoxia
  Altitude conditions (normobaric hypoxia) will be reproduced using the OnePlus VA device (GO2Altitude, Biomedtech, Melbourne, Australia). This device modulates the fraction of inspired oxygen (FiO₂) through a patented semi-permeable membrane system developed by the company. It thereby produces a gas mixture that is inhaled by the participant through a mask. This device included an oxygen-reduction algorithm, that adjusts the FiO₂ in real time according to a target peripheral oxygen saturation (Sp
• Device Normoxia
  Ambient air will be delivered through the same mask as that used during the hypoxia conditions.
• Device Transcranial Magnetic Stimulation
  Single- and paired-pulse TMS will be applied over the primary motor cortex (M1) to assess corticospinal excitability, along with intracortical inhibitory and facilitatory mechanisms. Motor-evoked potentials will be recorded from the abductor pollicis brevis (APB) muscle of the dominant hand.

Primary outcome measures

• Electrical brain activity [Time frame: Assessed throughout the intervention, at Day 2, 3, and 4 of the protocol.]
• Haemodynamic activity [Time frame: Assessed throughout the intervention, at Day 2, 3, and 4 of the protocol.]

Secondary outcome measures (3)

• Corticospinal excitability [Time frame: Assessed at baseline and immediately post-intervention during each of the three experimental sessions (i.e., intermittent moderate hypoxia, continuous moderate hypoxia, normoxia).]
• EEG brain connectivity [Time frame: Assessed throughout the intervention, at Day 2, 3, and 4 of the protocol.]
• fNIRS brain connectivity [Time frame: Assessed throughout the intervention, at Day 2, 3, and 4 of the protocol.]

Eligibility criteria

Inclusion criteria

• Male or female aged 18 to 65 years
• Healthy right- or left-handed individuals with no self-reported neurological disorders or history of neurological conditions (e.g., epilepsy, stroke, brain or spinal surgery, or neurological diseases affecting motor or sensory function such as multiple sclerosis, or neurodegenerative diseases such as Parkinson's or Alzheimer's)
• Individuals who have provided informed consent and have sufficient proficiency in French
• Participants affiliated with, or beneficiaries of, a social security scheme

Exclusion criteria

• Body mass index (BMI) greater than 30 kg/m²
• Diagnosed and untreated obstructive sleep apnoea syndrome
• Inability to provide informed consent
• History of cardiac (e.g., ischaemic heart disease, heart failure) and/or respiratory disorders (e.g., COPD, chronic respiratory insufficiency, persistent or uncontrolled asthma)
• Current smokers
• Contraindications to TMS (e.g., uncontrolled epilepsy, intracranial metallic foreign body, hearing aid or cochlear implant, implanted stimulator or pump, scalp lesions, elevated intracranial pressure, cerebrospinal fluid shunt)
• Use of psychotropic medication
• Individuals under legal guardianship or curatorship
• Pregnant or breastfeeding women
• Participants who have flown by air or travelled to terrestrial altitudes above 1500 metres within the seven days prior to inclusion

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Basic science

Study locations

France · 1 center

• Eurasport — Loos

Identifiers

NCT: NCT07516028 · 2025-A02509-40

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗