Functional connectivity of the default mode network and its association with pain networks in irritable bowel patients assessed via lidocaine treatment

Abstract

The default mode network (DMN), a group of brain regions implicated in passive thought processes, has been proposed as a potentially informative neural marker to aid in novel treatment development. However, the DMN's internal connectivity and its temporal relationship (ie, functional network connectivity) with pain-related neural networks in chronic pain conditions is poorly understood, as is the DMN's sensitivity to analgesic effects. The current study assessed how DMN functional connectivity and its temporal association with 3 pain-related networks changed after rectal lidocaine treatment in irritable bowel syndrome patients. Eleven females with irritable bowel syndrome underwent a rectal balloon distension paradigm during functional magnetic resonance imaging in 2 conditions: natural history (ie, baseline) and lidocaine. Results showed increased DMN connectivity with pain-related regions during natural history and increased within-network connectivity of DMN structures under lidocaine. Further, there was a significantly greater lag time between 2 of the pain networks, those involved in cognitive and in affective pain processes, comparing lidocaine to natural history. These findings suggest that 1) DMN plasticity is sensitive to analgesic effects, and 2) reduced pain ratings via analgesia reflect DMN connectivity more similar to pain-free individuals. Findings show potential implications of this network as an approach for understanding clinical pain management techniques.

Perspective: This study shows that lidocaine, a peripheral analgesic, significantly altered DMN connectivity and affected its relationship with pain-related networks. These findings suggest that the DMN, which is hypothesized to represent non-goal-oriented activity, is sensitive to analgesic effects and could be useful to understand pain treatment mechanisms.

Keywords: Default mode network; fMRI; functional network connectivity; irritable bowel syndrome; lidocaine.

Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

The functional magnetic resonance imaging scanning session consisted of seven 44-s runs, with 24 s of rest and 20 s of rectal balloon distension. Pain ratings were collected at the end of each run, and participants were given 20 s before the start of the subsequent run. An example of the first 2 runs is portrayed above.

Figure 2

Significant differences (P ≤ .05, FDR ≤ .05) between the NH and RL conditions emerged in the regions functionally connected with the DMN. Regions identified as significantly more connected with the DMN in NH include the insula and precentral gyrus (orange, pictured left), whereas the superior and middle temporal gyri, angular gyrus, and inferior parietal lobule were significantly more connected with the DMN in RL (blue, pictured left). Abbreviation: FDR, false discovery rate.

Figure 3

Lag times reported in the FNC analyses were calculated based on the time courses of the DMN and 3 pain-processing networks (SMN, ISN, and CCN). The waveforms represent each IC’s time course, or pattern of activation, over the period of the fMRI task. Time courses from the ICs in the NH condition are shown on the left, and time courses from the ICs in the RL condition are shown on the right.

Figure 4

The temporal relationships between the DMN and pain-related neural networks (ie, ICs) are represented above. Arrows represent the presence of a correlation between network pairs, and lag times are denoted by arrow color, with longer lag times displayed in darker arrow colors. The direction of the arrow indicates that one network precedes another network by a certain amount of time. For example, ISN → CCN shows that the ISN precedes the CCN. Significant correlations were present among all network pairs in both the NH and RL conditions (left and right, respectively). The only significant condition-level differences were found for the ISN → CCN relationship (center). In the RL condition, the CCN lagged the ISN significantly more than in the NH condition (P ≤ .05, FDR ≤ .05). All images are in radiologic convention, and Z-plane coordinates for each network are located at SMN = 32, CCN = 38; ISN = 7, DMN = 18. Abbreviation: FDR, false discovery rate.