Oxygen Concentration Modulates Cortical Excitability in Humans

Background and objectivesCortical excitability is fundamental to neuroplasticity, particularly relevant in conditions like stroke and neurodegeneration. Despite the well-known role of oxygen in brain metabolism, the effects of hyperoxia on cortical excitability are relatively unknown, representing a fundamental gap in neuromodulation research. Understanding how oxygen levels modulate excitability is critical to improving therapeutic approaches aimed at enhancing recovery in neurological disorders. This study is the first to directly examine the effects of both hypoxia and hyperoxia on corticospinal excitability (CSE) in humans, utilising non-linear modelling of transcranial magnetic stimulation (TMS) recruitment curves to accurately characterise changes in excitability.MethodsIn a single-blinded, randomised, within-subjects experiment, 37 participants were exposed to three oxygen conditions: hypoxia (10.5% O2), normoxia (21% O2), and hyperoxia (100% O2). TMS was applied at varying intensities to generate motor-evoked potentials (MEPs), using a Boltzman Sigmoid Curve approach to optimise estimation of CES from recruitment curves.ResultsHypoxia significantly enhanced CSE sensitivity at lower intensities but plateaued at higher levels, likely due to metabolic constraints. Hyperoxia increased CSE at higher intensities without reaching a ceiling, indicating enhanced metabolic efficiency and excitability. Recruitment curves demonstrated distinct mechanisms, with hypoxia lowering the half-maximal intensity and hyperoxia increasing maximum excitability and slope steepness.ConclusionsThis is the first study to reveal hyperoxia’s capacity to elevate CSE in humans, highlighting the critical role of oxygen in modulating excitability. These findings suggest oxygen-based therapies could be strategically used to enhance neuroplasticity, offering novel avenues for clinical interventions in rehabilitation of neurological disorders.