EVALUATION COMMITTEE

The Faculty Council has appointed the following adjudication committee to evaluate the thesis and the associated lecture: 

• Dr. Ali Mazaheri, Centre for Human Brain Health, School of Psychol-ogy, University of Birmingham, UK
• Dr. Giulia Liberati, Institute of Neuroscience (IoNS), Université catholique de Louvain, Belgium
• Dr. Sabata Gervasio, associate professor, Health Science and Technology, Aalborg University, Denmark (Chairman).

Moderator:
Prof. Thomas Graven-Nielsen, HST, Aalborg University

ABSTRACT

The neuroplastic mechanisms underlying the transition to persistent pain are still unclear. The default mode network (DMN) is a major network in the dynamic pain connectome, whose resting-state functional connectivity (rsFC) is altered during both acute and chronic pain, suggesting that alterations in this network may be a part of the neuroplastic mechanisms underlying this transition. Experimental prolonged pain models, albeit unable to capture the complexity of chronic pain conditions, can provide a unique reversible manifestation of pain-driven changes providing better insights into persistent pain conditions. Unfortunately, most experimental pain studies rely on short-term models (seconds to minutes), which can uncover pain effects in the very early stages but fall short in modeling chronic pain.

 

This work aimed to understand the neuroplastic mechanisms underlying the transition from tonic (one hour) to prolonged (24 hours) pain as reflected in changes in electroencephalographic (EEG)-based DMN rsFC. Pain was evoked using a capsaicin patch applied to the right forearm. Unlike other connections within the DMN, the angular gyrus (AG) connections during pain are largely understudied; hence Paper I established the effect of tonic pain on AG connections within the DMN during eyes closed (EC) and eyes open (EO) in two groups of participants (EC-EO, EO-EC groups) divided based on the eye sequence during EEG acquisition. Paper II examined changes in DMN connectivity between one hour and 24 hours of pain and whether these changes are resistant to changes in pain intensity. Paper III determined whether pain-free DMN connectivity could contribute to individual differences in subjective pain intensity.

Paper I demonstrated that one hour of capsaicin-induced pain decreased AG connectivity at lower alpha but exclusively during EC in EC-EO group. At beta, the results showed decreased left AG and right AG connectivity in EC-EO group and increased left AG connectivity in EO-EC group. No significant change in connectivity was observed during EO for both groups at both lower alpha and beta oscillations. Paper II showed the same decrease following one hour of pain among the right AG connections as well as mPFC connections that persisted 24 hours later, despite the reduction in pain intensity between one and 24 hours. This decrease was bidirectional spanning mPFC and right AG at lower alpha and beta oscillations as well as PCC and right AG at beta oscillations. Cooling or heating the capsaicin patch did not significantly change the decreased connectivity following 24 hours. Paper III revealed that pain-free DMN connectivity, especially mPFC-left AG, can predict the variation in subjective pain intensity beyond the contribution of emotional and pain-specific psychological factors.

These findings indicate that tonic and prolonged pain are associated with robust decreased DMN connectivity occurring in continuous loops between regions linked to attentional and emotional processing. As pain progresses, these loops grow resistant to pain relief or exacerbation, which may signify a shift to emotional/attentional processing, possibly contributing to more persistent pain conditions. Additionally, pain-free DMN connectivity can identify individuals susceptible to enhanced pain perception. Further, when assessing the effect of pain on DMN connectivity using EEG, the eyes-closed state may be a more appropriate baseline than the eyes-open state. Finally, the order of eye-states recording is crucial when both eye-states are examined.  

This work has elucidated the role of the DMN in pain processing, highlighting possible emotional/attentional processes encoded in the DMN that may be involved in the transition to more persistent pain states. Identifying these processes at the early stages of pain may help design therapeutic approaches that can address these processes before they contribute to this transition. This work has also established pain-free DMN connectivity (at lower alpha) based on EEG measures as a potential screening tool for pain-related vulnerability, which can be efficiently utilized in clinical settings.