Altered attentional control over the salience network in complex regional pain syndrome

Abstract

The degree and salience of pain have been known to be constantly monitored and modulated by the brain. In the case of maladaptive neural responses as reported in centralized pain conditions such as complex regional pain syndrome (CRPS), the perception of pain is amplified and remains elevated even without sustained peripheral pain inputs. Given that the attentional state of the brain greatly influences the perception and interpretation of pain, we investigated the role of the attention network and its dynamic interactions with other pain-related networks of the brain in CRPS. We examined alterations in the intra- and inter-network functional connectivities in 21 individuals with CRPS and 49 controls. CRPS-related reduction in intra-network functional connectivity was found in the attention network. Individuals with CRPS had greater inter-network connectivities between the attention and salience networks as compared with healthy controls. Furthermore, individuals within the CRPS group with high levels of pain catastrophizing showed greater inter-network connectivities between the attention and salience networks. Taken together, the current findings suggest that these altered connectivities may be potentially associated with the maladaptive pain coping as found in CRPS patients.

Figure 1

Statistical parametric map of the t-statistic images of significant clusters indicating the group differences in functional connectivity and group-averaged functional connectivity maps for each group (control vs. CRPS). For clusters in the attention network, there were reduced functional connectivity in individuals with CRPS relative to the control group. For the pain-related RSNs, individuals with CRPS showed enhanced functional connectivity in the salience network as compared with the control group. In contrast, reduced functional connectivity was observed in the clusters of the sensorimotor and default mode networks in the CRPS group, as compared with the control group. BrainNet Viewer was used to visualize three-dimensional rendering of the clusters and the RSNs in the MNI space. CON, control; CRPS, complex regional pain syndrome; RSN, resting state network; MNI, Montreal Neurological Institute.

Figure 2

Inter-network correlations between brain networks in the CRPS and control groups. Functional coupling of the attention and salience networks was greater in the CRPS group relative to the control group. Enhanced inter-network connectivity between the attention and sensorimotor networks was also observed in the CRPS group, as compared with the control group. However, there were no significant group differences in the inter-network connectivity between the attention and default mode networks. *Permutation-adjusted P < 0.05; **Permutation-adjusted P < 0.01; DMN, default mode network; NS, non-significant; CON, control; CRPS, complex regional pain syndrome; ant, anterior; post, posterior.

Figure 3

Correlations between the total scores on the Pain Catastrophizing Scale (PCS) in individuals with CRPS and functional connectivity in brain networks. (a) Scatter plots and regression lines between PCS scores and intra-network functional connectivity in the salience and attention networks. A significant positive correlation between PCS scores and enhanced intra-network functional connectivity in the salience, while a significant negative correlation between PCS scores and functional connectivity in the attention network were observed in individuals with CRPS. (b) Scatter plot and regression line between PCS scores and inter-network functional connectivity. A significant positive correlation was observed between PCS scores and enhanced functional coupling between the attention and salience networks in individuals with CRPS. CRPS, complex regional pain syndrome.