From Pain to Brain: Exploring Functional Connectivity in Chronic Pain Patients with Magnetoencephalography

Abstract

Introduction:
Chronic Pain (CP) presents a complex and prevalent issue that significantly affects individuals and society. Exploring the complexities of CP involves analyzing Functional Connectivity (FC), a process that identifies how different brain regions communicate across distances. Magnetoencephalography (MEG) is particularly effective for FC analysis, offering advantages over Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) due to its superior temporal resolution. Most studies on FC in CP have focused on resting-state analyses, leaving a gap in research on connectivity responses to noxious stimuli in CP.

Study aim:
The overarching goal of my exploring study is to investigate FC differences in response to noxious stimuli between individuals with CP and Healthy Controls (HCs) across different frequency bands, using MEG. This encompasses the comparison of FC patterns within pain-related brain regions between these two groups, the analysis of their response to a noxious stimulus, and the synthesis of these findings to identify potential differences in how the two groups respond to noxious stimuli.

Methods:
The study involved 17 individuals with CP and 17 HCs, each undergoing MEG sessions within a conditioned pain modulation (CPM) paradigm. During each CPM block, 22 noxious stimuli were applied to the right tibial nerve. FC was computed between pain-processing regions using phase and amplitude-based metrics in different frequency bands. Connectivity patterns were compared between the groups using a non-parametric permutation test. Connectivity was also evaluated on a time-scale to observe potential changes in the FC in response to the stimulus. These results were taken together to observe potential differences in the groups in response to the stimulus.

Results:
In comparing FC patterns across the entire epoch between the HC and CP groups, there is a predominant observation of increased FC in the CP group relative to the HC group. The insula and Dorsolateral Prefrontal Cortex (DLPFC) emerged as central hubs, and these alterations were most prominent in the beta (13-29 Hz) and gamma-low bands (30-45 Hz). An increase in FC in the mean response over all scout pairs and both groups was observed immediately following the stimulus, particularly in the theta band (5-7 Hz). Additionally, in investigating the specific hypothesis that there may be distinct FC responses to noxious stimuli between the HC and CP group, the findings indicate subtle differences rather than clear, pronounced patterns, with findings in the theta, alpha and gamma-low bands.

Conclusion:
My study explored FC differences in response to noxious stimuli between individuals with CP and HCs across different frequency bands, using MEG. Higher FC was predominantly observed in the CP group, suggesting more interconnected pain-processing networks. Key regions demonstrating this increased FC included the insula and the DLPFC, suggesting an altered insula-DLPFC network potentially influenced by underlying physiological factors of the CP group. Specifically examining differences in FC response to the noxious stimulus between the HC and the CP group yielded in subtle differences rather than clear, distinct patterns. This study stands out as the first using MEG to identify FC in CP in response to noxious stimuli. Future research should focus on refining connectivity as a biomarker for treatment follow-up and potential outcome predictor.