Regional and Cross-Network Brain Dynamics in Acute and Chronic Pain

Chronic pain is a major societal burden, affecting nearly 1 in 5 Canadians. Chronic pain patients demonstrate a great degree of variability in the way they perceive and cope with pain, experience symptoms, and respond to treatment. These individual differences may in part be due to the brain dynamics associated with the processing and modulation of nociceptive signals. Thus, the overall goal of this thesis was to understand the role of regional brain dynamics in acute and chronic pain. Towards this goal, I first established a link between regional BOLD signal variability and pain sensitivity and the effect of pain on cognitive performance in healthy individuals. I then examined frequency-specific regional BOLD signal variability abnormalities in chronic pain patients with ankylosing spondylitis (AS) and related these abnormalities to pain intensity. Finally, I investigated the brain plasticity in regional and cross-network brain dynamics that subserve successful response to ketamine therapy in patients with refractory chronic neuropathic pain (NP). Healthy individuals and chronic pain patients (AS and NP) underwent a resting-state fMRI scan and completed a psychophysical session and a battery of questionnaires (e.g., assessing pain intensity etc.). The main findings of this thesis are: 1) Regional BOLD signal variability within the ascending nociceptive pathway and networks of the dynamic pain connectome are increased in healthy individuals who are less pain sensitive and have good cognitive performance during a pain-interference task; 2) Patients with AS exhibit elevated regional frequency-specific BOLD signal variability in the ascending nociceptive pathway and networks of the dynamic pain connectome; these abnormalities are related to chronic pain intensity; 3) Ketamine reduces regional BOLD signal variability within the default mode network (DMN); and 4) Effective ketamine-treatment outcome is associated with decreased static functional connectivity of the DMN with the salience network and with the sensorimotor network. Therefore, this thesis demonstrates that regional BOLD signal variability serves as a functional metric that underlies individual differences in acute pain, and the clinical symptoms and treatment outcomes in chronic pain. These findings provide novel insight into chronic pain etiology that serve to advance the knowledge base needed to develop new treatment options.Ph.D