The posterior medial cortex in urologic chronic pelvic pain syndrome: detachment from default mode network-a resting-state study from the MAPP Research Network

Abstract

Altered resting-state (RS) brain activity, as a measure of functional connectivity (FC), is commonly observed in chronic pain. Identifying a reliable signature pattern of altered RS activity for chronic pain could provide strong mechanistic insights and serve as a highly beneficial neuroimaging-based diagnostic tool. We collected and analyzed RS functional magnetic resonance imaging data from female patients with urologic chronic pelvic pain syndrome (N = 45) and matched healthy participants (N = 45) as part of an NIDDK-funded multicenter project (www.mappnetwork.org). Using dual regression and seed-based analyses, we observed significantly decreased FC of the default mode network to 2 regions in the posterior medial cortex (PMC): the posterior cingulate cortex (PCC) and the left precuneus (threshold-free cluster enhancement, family-wise error corrected P < 0.05). Further investigation revealed that patients demonstrated increased FC between the PCC and several brain regions implicated in pain, sensory, motor, and emotion regulation processes (eg, insular cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus, putamen, amygdala, hippocampus). The left precuneus demonstrated decreased FC to several regions of pain processing, reward, and higher executive functioning within the prefrontal (orbitofrontal, anterior cingulate, ventromedial prefrontal) and parietal cortices (angular gyrus, superior and inferior parietal lobules). The altered PMC connectivity was associated with several phenotype measures, including pain and urologic symptom intensity, depression, anxiety, quality of relationships, and self-esteem levels in patients. Collectively, these findings indicate that in patients with urologic chronic pelvic pain syndrome, regions of the PMC are detached from the default mode network, whereas neurological processes of self-referential thought and introspection may be joined to pain and emotion regulatory processes.

Figure 1. Decreased regional functional connectivity (FC) of the posterior medial cortex (PMC) to the default mode network (DMN)

Dual regression analysis (masked for the DMN) demonstrated decreased FC within a region of the PCC (peak voxel, x = 4, y = −30, z = 36) (A) and left precuneus (peak voxel, x = −22, y = −74, z = 26) (B) to the DMN network in patients. DMN shown in green. Regions of decreased connectivity to the network in blue (TFCE, FWE corrected p<0.05).

Figure 2. Whole-brain, seed-based functional connectivity (FC) of the PCC seed region

Seed-based analysis revealed increased FC of the PCC seed region (peak voxel, x = 4, y = −30, z = 36) (A) in relation to several regions (B), including the bilateral insular cortex, bilateral globus pallidus, bilateral putamen, right thalamus, left amygdala, left hippocampus, and left dorsolateral prefrontal cortex (DLPFC) (Z > 2.3, cluster corrected p < 0.05).

Figure 3. Whole-brain, seed-based functional connectivity (FC) of the left precuneus seed region

Seed-based analysis revealed decreased FC of the left precuneus seed region (peak voxel, x = −22, y = −74, z = 26) (A) in relation to several regions (B), including the bilateral ventromedial prefrontal cortex (VMPFC), right anterior cingulate cortex (ACC), bilateral orbitofrontal cortex (OFC), bilateral precuneus cortex, left mid-cingulate cortex (MCC), right angular gyrus, and right superior and inferior parietal lobule (SPL, IPL respectively) (Z > 2.3, cluster corrected p < 0.05).