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Brain Connectivity and Corticospinal Excitability in Response to Moderate Hypoxia

Brain Connectivity and Corticospinal Excitability in Response to Moderate Hypoxia

Status
Not yet recruiting
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT07516028
Acronym
NEUROXIE
Enrollment
36
Registered
2026-04-07
Start date
2026-03-15
Completion date
2026-12-20
Last updated
2026-04-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Normoxia, Intermittent Moderate Hypoxia, Continuous Moderate Hypoxia

Keywords

hypoxia, eeg, fnirs, motor-evoked potentials, tms

Brief summary

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

DEVICEModerate 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 (SpO₂ = 85-90%).

DEVICENormoxia

Ambient air will be delivered through the same mask as that used during the hypoxia conditions.

DEVICETranscranial 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.

Sponsors

Universite du Littoral Cote d'Opale
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Electrical brain activityAssessed throughout the intervention, at Day 2, 3, and 4 of the protocol.Electroencephalography (EEG) data will be recorded using a SAGA system (TMSi, Einsteinweg, The Netherlands). This system includes 64 Ag/AgCl pin-type electrodes. An additional electrode will be positioned on either the left or right mastoid. The primary outcome will be the variation in spectral power within the alpha frequency band.
Haemodynamic activityAssessed throughout the intervention, at Day 2, 3, and 4 of the protocol.A Brite system (Artinis, Einsteinweg, The Netherlands) will be used to collect functional near-infrared spectroscopy (fNIRS) data. The equipment comprises four LED emitters and four photodiode receivers. A nine-channel montage will be designed to cover the regions of interest, namely the dorsolateral prefrontal cortex, the ventromedial prefrontal cortex, and the anterior prefrontal cortex. The primary outcome will be the variation in deoxyhaemoglobin (HbR).

Secondary

MeasureTime frameDescription
Corticospinal excitabilityAssessed at baseline and immediately post-intervention during each of the three experimental sessions (i.e., intermittent moderate hypoxia, continuous moderate hypoxia, normoxia).Corticospinal excitability will be assessed using transcranial magnetic stimulation (TMS) applied to the primary motor cortex. Motor evoked potentials (MEPs) are recorded using surface electromyography from the abductor pollicis brevis (APB) muscle of the dominant hand.The primary outcome will be the slope of the I/O curve.
EEG brain connectivityAssessed throughout the intervention, at Day 2, 3, and 4 of the protocol.Resting-state cortical connectivity will be examined using the EEG data, on which coherence analyses will be applied. The outcome measure will be the degree of functional connectivity between cortical regions, quantified through coherence values across specific frequency bands (e.g., alpha, beta), reflecting the synchronisation of neural activity between these regions.
fNIRS brain connectivityAssessed throughout the intervention, at Day 2, 3, and 4 of the protocol.Resting-state cortical connectivity will be examined using the fNIRS signals, through correlations of deoxyhaemoglobin (HbR) between the cortical regions of interest. The outcome measure will be the strength of functional connectivity between these regions, quantified by the correlation coefficients of haemodynamic fluctuations, reflecting the synchrony of cortical activity at rest.

Countries

France

Contacts

CONTACTSégolène M. R. Guérin, PhD
segolene.guerin@univ-littoral.fr+33 3 74 00 82 13

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Apr 8, 2026