Abstract

Oxygen is central to neural function, yet the precise mechanisms and effects by which varying oxygen 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 CO₂induced 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.

Awarding Institution(s)

University of Plymouth

Supervisor

Stephen Hall, Gary Smerdon, Alastair Smith, Jonathan Marsden

Document Type

Thesis

Publication Date

2026

Embargo Period

2026-02-11

Deposit Date

February 2026

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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