Abstract
Oxygen is central to neural function, yet the precise mechanisms and effects by which varyingoxygen levels, whether through Hypoxia, Hyperoxia, or Hyperbaric Oxygen Therapy (HBOT),
shape cognition and brain activity remain incomplete. This thesis adopts a novel, multi-modal
framework that integrates normobaric gas manipulations, cognitive testing, Transcranial
Magnetic Stimulation (TMS), Electroencephalography (EEG), Functional Magnetic Resonance
Imaging (fMRI), and HBOT to examine how gas and pressure variability influences cognitive,
motor, and neural processes.
Chapter 3 presents the findings of a preliminary experiment investigating normobaric oxygen
manipulations on cognition. Standardised cognitive assessments revealed domain-general
impairments (i.e. memory and executive function) under Hypoxia, whereas Hyperoxia
produced smaller, and more inconsistent domain-specific changes. Notably, both conditions
increased movement time but left reaction time unaffected, implicating the motor system
rather than broad cognitive slowing. Chapter 4 extends this by probing the motor system with
TMS to measure Corticospinal Excitability (CSE). Hypoxia increased early motor neuron
recruitment at lower stimulation intensities yet lowered maximum excitability, while
Hyperoxia raised the saturation threshold for excitability, highlighting distinct motor
responsiveness under different levels of oxygen. Based on these motor findings, Chapter 5
explores neural oscillations and evoked responses with EEG. Hypoxia reduced Critical Flicker
Fusion (CFF) thresholds and altered Visual Evoked Potentials (VEPs), while Hyperoxia
generated smaller more transient changes in CFF and VEPs, with a specific reduced motor
Beta power, suggesting more localised oscillatory disruptions.
Chapter 6 then investigates HBOT using mobile EEG during a hyperbaric “dive,” to understand
the neural impacts of HBOT. The results showed Delta power decreased cumulatively
throughout the session, whereas Alpha, Beta, and Theta power increased during transitions
to a relatively lower partial pressure of oxygen, pointing to “relative Hypoxia” as a potential
driver of neuroplasticity. These results also showed heightened neural entropy during
transitions to higher oxygen levels, emphasising the importance of dynamic pressure changes
for neural adaptability. Chapter 7 examines CO₂-induced anxiety via a Carbon Dioxide
Challenge Model (CCM) and fMRI, revealing transient anxiogenic responses that increased
functional connectivity within networks involving the insula, amygdala, and frontal regions. A
correlation between subjective anxiety and connectivity between the brainstem and frontal
cortex was observed, highlighting the role of top-down emotional regulation and how
physiology interacts with anxiety.
Collectively, these findings demonstrate that oxygen variability significantly impacts cognition,
motor systems, and neural plasticity, with relative Hypoxia emerging as a particularly potent
stimulus for adaptive changes. By illustrating how normobaric manipulations, HBOT, and CO₂
induced anxiety each alter neural excitability and connectivity, this thesis offers an integrated
perspective on oxygen’s role in shaping brain function. It further establishes a framework for
potential novel therapeutic interventions, ranging from enhanced neurorehabilitation
protocols to strategies for managing anxiety and cognitive decline, that leverage controlled
oxygen variability for clinical and performance benefits.
| Date of Award | 2026 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Stephen Hall (Director of Studies (First Supervisor)), Gary Smerdon (Other Supervisor), Alastair Smith (Other Supervisor) & Jonathan Marsden (Other Supervisor) |
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