Abstract
Background: Chronic painful knee osteoarthritis (KOA) is a disabling physical health condition and ranked the 11th highest contributor to global disability. Persistent pain is a chief complaint associated with chronic KOA and does not always correlate with the structural changes in the knee joint. As an alternative pain generator, the sensitization and changes in the peripheral and central nervous systems have been linked to chronic pain. However, it remains unclear which brain regions and their activity (and connectivity) relate to the pain experience in KOA. Neurofeedback (NF) is a form of Brain-Computer Interface (BCI) training utilized to train brain regions associated with pain. Electroencephalography-based Infraslow fluctuation Neurofeedback (EEG-ISF-NF) is a recent development in neurofeedback training, focusing on modulating infra-slow and slow-wave activity (0–0.1 Hz) of the cortical regions linked to the pain experience.
Methods: This thesis consists of one systematic review and two studies/investigations (a feasibility clinical trial and a cross-sectional study) and is outlined in seven chapters with distinct objectives. The systematic review (chapter 3) synthesizes the available evidence on the EEG alteration associated with various musculoskeletal (MSK) pain states. The feasibility clinical trial (chapter 4) provides the feasibility, safety, and acceptability of the ISF-NF as a potential intervention for the management of pain in KOA. Chapter 5 is an exploratory analysis of the feasibility clinical trial sought to test if ISF-NF can produce changes in brain function. Chapter 6 is a cross-sectional study with a prospective component investigating the EEG changes in KOA against a matched healthy control group. This chapter also establishes the relationship between EEG changes and subjective and objective measures of pain and function in KOA. Finally, this chapter supports chapters 4 and 5 and provides the future directions informed by this thesis. Chapter 7 is a general discussion of the thesis findings and provides the implications for future research.
Results: The systematic review identified a 'very low' level of evidence for the changes in EEG and subjective outcome measures for both chronic and experimentally induced MSK pain. Overall, the findings of this review indicate a trend toward decreased alpha and beta EEG power in evoked chronic clinical pain conditions and increased theta and alpha power in resting-state EEG recorded from chronic MSK pain conditions. EEG characteristics are unclear under experimentally induced pain conditions. No studies demonstrated alterations in the slower EEG bands in people with chronic pain.
Study 1: The findings from the feasibility clinical trial indicated that the ISF-NF training is a feasible, safe, and acceptable intervention for pain management in people with KOA, with high levels of perceived effectiveness. Also, the ISF-NF training produced changes in cortical activity and functional connectivity between the chosen regions of interest. Furthermore, the EEG changes were correlated with differences in their clinical pain outcomes.
Study 2: Results from the cross-sectional study demonstrate increased brain activity in both lower and higher frequency bands in KOA compared to the healthy control cohort. Moreover, the EEG changes were associated with self-reported pain, psychological distress, and quantitative sensory testing measures.
Conclusions: The current thesis supports the potential of ISF-NF for the management of chronic pain experience in KOA. The primary study indicated that ratio ISF-NF training is a feasible and acceptable intervention for pain management. ISF-NF can potentially induce EEG-related changes in the ROI trained as well as the distant cortical regions linked to the pain experience. The cross-sectional investigation also supports these findings and provides additional cortical areas of target for ISF-NF training. Through this knowledge demonstrated in the primary studies, a full clinical trial is warranted to investigate the effect of ISF-NF on pain, including the 'a priori' regions and other cortical regions of interest.