Precision Connectivity in Arthritis Pain with Permutation and Network Analysis: A Key Step Toward Clinical Application

Abstract Objective This study seeks to identify brain regions with atypical neural connectivity in individuals suffering from arthritis-related chronic pain, compared to healthy controls, using resting-state functional magnetic resonance imaging (rs-fMRI). Methods A seed-based connectivity analysis was conducted between the known pain-related regions of interest (ROIs), derived from the MNI (n = 76) and the Automated Anatomical Labeling (AAL) whole brain atlas (n = 116). We examined the connectivity differences in a cohort of 56 osteoarthritis patients and 20 healthy controls. Connectivity matrices were compared using permutation tests corrected for multiple comparisons, identifying statistically significant differences (p < 0.05). Subsequent network analysis resulted in hub scores, identifying the most central and influential brain regions within the altered connectivity network in patients experiencing pain. Results The most significant atypical neural connections in osteoarthritis patients were identified in the cingulate gyrus, insula, inferior parietal lobe, and thalamus, with notable involvement of the occipital lobe, postcentral gyrus, inferior frontal gyrus, orbitofrontal cortex, temporal lobe, hippocampus, and basal ganglia. The thalamus, cingulate gyrus, and insula emerged as key hubs in the chronic pain network, reflecting disrupted sensory, emotional, and cognitive pain processing. No significant connectivity differences were found in the brainstem, cerebellum, superior parietal lobe, precentral gyrus, superior and middle frontal gyri, or amygdala. Conclusion Our data-driven approach reveals specific neural connectivity disruptions in OA, highlighting connections between the cingulate gyrus, temporal lobe, and thalamus. These findings identify specific network disruptions in OA-related pain, offering insight into altered brain connectivity and potential avenues for targeted interventions.