Diffusion MRI analysis of TMS effects on cognitive pain processing and descending pain modulation in chronic knee osteoarthritis
It is increasingly recognized that chronic pain is characterized by abnormalities in the neural circuits that process the pain signal. The anterior insula (AI) and anterior cingulate cortex (ACC) are two key hubs of high-level attentional processing that have been observed to be altered in chronic p...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
2025
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| Online Access: | https://eprints.nottingham.ac.uk/81001/ |
| Summary: | It is increasingly recognized that chronic pain is characterized by abnormalities in the neural circuits that process the pain signal. The anterior insula (AI) and anterior cingulate cortex (ACC) are two key hubs of high-level attentional processing that have been observed to be altered in chronic pain. Furthermore, the descending pain modulation system (DPMS) that exerts top-down control over afferent nociceptive signals can exhibit maladaptive dynamics in chronic pain. Transcranial magnetic stimulation (TMS) has been proposed as a non-invasive therapy for inducing normalization of aberrant brain circuits. A randomized sham-controlled clinical trial (BoostCPM) was conducted to evaluate the efficacy of an accelerated TMS protocol for treating chronic pain in a cohort of patients with knee osteoarthritis. Diffusion MRI (dMRI) was collected at baseline and after TMS treatment to assess for neuroplastic changes in key pain processing centers.
This thesis presents an analysis of the dMRI data from the BoostCPM trial. The details of this image analysis were defined a priori in a documented plan uploaded to the University of Nottingham’s Research Data Repository (http://doi.org/10.17639/nott.7388). The dMRI data was processed through an extensive pipeline and closely inspected for quality control at every step. Minor errors in data processing were noted and discussed alongside final results. Grey matter hubs of cognitive pain processing and the DPMS were chosen as regions of interest. Three advanced dMRI models were applied, generating five quantitative indices of neural microstructure. Statistical tests were performed for comparisons within-group (pre- vs. post-TMS) and between-group (active vs. sham intervention). Six significant results were obtained out of 135 tests; none of these survived p-value correction for multiple tests. Interpretation the results within the context of the analysis methods used and plausible neurobiological mechanisms tends to suggest that the six significant test results are spurious. It is most reasonably concluded that accelerated TMS does not induce structural neuroplasticity in grey matter pain centers within this cohort of knee osteoarthritis patients. |
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