Negative mood influences default mode network functional connectivity in patients with chronic low back pain: implications for functional neuroimaging biomarkers

Abstract

The default mode network (DMN) has been proposed as a biomarker for several chronic pain conditions. DMN functional connectivity (fcMRI) is typically examined during resting-state fMRI, in which participants are instructed to let thoughts wander. However, factors at the time of data collection (e.g., negative mood) that might systematically impact pain perception and its brain activity, influencing the application of the DMN as a pain biomarker, are rarely reported. The present study measured whether positive and negative moods altered DMN fcMRI patterns in chronic low back pain (CLBP) patients, specifically focusing on negative mood due to its clinical-relevance. Thirty-three participants (CLBP = 17) underwent resting-state fMRI scanning before and after sad and happy mood inductions, and rated levels of mood and pain intensity at the time of scanning. Two-way repeated measures ANOVAs were conducted on resting-state functional connectivity data. Significant group (CLBP > HC) X condition (sadness > baseline) interaction effects were identified in clusters spanning parietal operculum/postcentral gyrus, insular cortices, anterior cingulate cortex, frontal pole, and a portion of the cerebellum (pFDR < .05). However, only one significant cluster covering a portion of the cerebellum was identified examining a two-way repeated measures ANOVA for happiness > baseline (pFDR < .05). Overall, these findings suggest that DMN fcMRI is affected by negative mood in individuals with and without CLBP. It is possible that DMN fcMRI seen in chronic pain patients is related to an affective dimension of pain, which is important to consider in future neuroimaging biomarker development and implementation.

Disentangling mood and pain: a commentary on 2 manuscripts

“…In this issue of PAIN, Letzen and Robinson [6] importantly extend our knowledge of mood’s influence on resting state functional connectivity (i.e., correlated oscillatory activity among brain regions), as demonstrated previously in healthy volunteers [3], by investigating mood’s effect in a chronic low back pain population. When mood was altered it changed functional connectivity between default mode network (DMN) hub seed regions (medial prefrontal cortex, mPFC and posterior cingulate cortex, PCC) with a different constellation of changes for patients as compared with healthy controls.…”

“…Some options are: A) to identify separate, specific pain and mood signatures by including patients without comorbid depression or anxiety, and directly manipulating mood states; B) to give up on such research concluding, “It’s too complicated!”, C) to identify each neurologic signature “as is” and then measure correlated effects of negative affect, mood, pain and other covariates and comorbidities. Letzen and Robinson [6] provide clear evidence that mood status influences resting state activity in persons with chronic low back pain. Hopefully, this work will be expanded upon to determine how activity between and within other brain networks and regions are affected by mood, and further, whether these effects differ among persons who vary with regard to type of chronic pain, sex, race, etc.…”

“…Additional experiments are therefore needed 1) that directly test for mood alterations (e.g. by mood induction) (as exemplified by Letzen and Robinson [7]), and 2) that rigorously measure correlations of differences in present mood, negative affect, medication status, and pain severity (as exemplified by López-Solà et al [6]). Together these efforts will move our understanding of mood, affect and pain in a positive direction.…”

<p>Brain Functional Alternations of the Pain-related Emotional and Cognitive Regions in Patients with Chronic Shoulder Pain</p>

“…9 The painrelated brain regions primarily included the thalamus, insula and anterior cingulate, while other brain regions were likely to be stimulus-specific. 10 In recent years, many studies have valuated the underlying neurophysiological mechanism of brain functional changes in low back pain, 11 trigeminal neuralgia, 12 chronic migraine, 13,14 fibromyalgia, 15 knee osteoarthritis, 16 visceral pain, 17 but literature focused on abnormal pattern of cerebral networks for pain processing in patients with shoulder pain is insufficient. In the brain, the functional interaction effects of pain, cognitive as well as negative affect have been widely reported 18,19 and multiple mechanisms are needed to fully explain the emotional and cognitive brain alternations associated with pain.…”

“…Overall, many neuroimaging studies have demonstrated that patients with pain-related symptoms have abnormal neuronal activity and structural function, [11][12][13][14][15][16][17] few have focused on chronic shoulder pain. Therefore, the main objective of our study is to investigate how chronic shoulder pain affects brain function.…”