Aberrant resting-state functional connectivity of the dorsolateral prefrontal cortex to the anterior insula and its association with fear avoidance belief in chronic neck pain patients

Abstract

Chronic neck pain (CNP), a global health problem, involves a large amount of psychological and socioeconomic burdens. Not only physical causes but also behavioral disorders such as a fear-avoidance belief (FAB) can associate with the chronicity of neck pain. However, functional brain mechanisms underlying CNP and its related behavioral disorders remain unknown. The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to explore how the functional brain networks differed between CNP patients and age- and sex-matched healthy, pain-free controls (HCs). We also investigated whether these possible brain network changes in CNP patients were associated with fear avoidance belief (FAB) and the intensity of pain. We analyzed the resting-state fMRI data of 20 CNP patients and 20 HCs. FAB and the intensity of pain were assessed by Tampa Scale for Kinesiophobia (TSK) and Visual Analog Scale (VAS) of pain. The whole brain analysis showed that CNP patients had significant different functional connectivity (FC) compared with HCs, and the right dorsolateral prefrontal cortex (DLPFC) was a core hub of these altered functional networks. Furthermore, general linear model analyses showed that, in CNP patients, the increased FC between the right DLPFC and the right anterior insular cortex (aIC) significantly associated with increased TSK (p = 0.01, statistical significance after Bonferroni correction: p<0.025), and the FC between the right DLPFC and dorsal posterior cingulate cortex had a trend of inverse association with VAS (p = 0.04). Our findings suggest that aberrant FCs between the right DLPFC and aIC associated with CNP and its related FAB.

Enhanced amygdala-frontal operculum functional connectivity during rest in women with chronic neck pain: Associations with impaired conditioned pain modulation

“…Guided by previous findings regarding brain alterations in patients with chronic neck pain, ROI-to-ROI ( Whitfield-Gabrieli and Nieto-Castanon, 2012 ) rsFC analyses were conducted with the following seed regions: precuneus, posterior cingulate cortex, left and right insula, left and right amygdala, anterior cingulate cortex, medial prefrontal cortex, left and right hippocampus, left and right thalamus, left and right pallidum, left and right temporal pole, left and right superior parietal cortex, left and right precentral gyrus, left and right superior temporal gyrus anterior and posterior division, left and right supramarginal gyrus anterior and posterior division, left and right frontal operculum, left and right middle frontal gyrus, left and right frontal orbital cortex, left and right postcentral gyrus, left and right superior frontal gyrus, and left and right frontal pole. These seeds (i.e., 22 seeds bilateral; 40 seeds when taking left and right separate) are observed to be structurally or functionally altered in previous studies in the chronic neck pain population of the present study ( Coppieters et al, 2017b , Coppieters et al, 2018 , De Pauw et al, 2019a , De Pauw et al, 2019b ) or in another chronic neck pain sample ( Ihara et al, 2019 ) compared to healthy controls. Also, seeds were selected based on our previously observed significant associations between structural or functional brain characteristics and pain-related measures in CINP and CWAD.…”

“…These finding are in line with previous studies. For instance, Ihara et al recently also revealed aberrant prefrontal rsFC in patients with chronic neck pain compared to healthy controls, albeit in coupling of the dorsolateral prefrontal cortex ( Ihara et al, 2019 ). Also in our previous graph analytical resting-state analysis, we found alterations in the amygdala ( De Pauw et al, 2019a ).…”

“…In addition, we have demonstrated changes in functional network properties during rest in the amygdala, posterior cingulate cortex, pallidum, and temporal pole in individuals with chronic neck pain compared to healthy controls using a graph theoretical approach ( De Pauw et al, 2019a ). Recently, another resting-state functional MRI (rs-fMRI) study observed multidirectional connectivity changes in the dorsolateral prefrontal cortex, hippocampus, dorsal posterior cingulate cortex, frontal pole, middle cingulate cortex, and anterior insula when comparing chronic neck pain patients with healthy pain-free persons ( Ihara et al, 2019 ). The dorsolateral prefrontal cortex was a core hub of these altered functional networks.…”

“…The second aim is to investigate associations between seed-to-seed rsFC across all selected regions and self-reported CS-related symptoms, and QST measures. Brain regions in which we previously identified structural brain alterations or altered network properties based on resting-state fMRI graph theoretical analyses in this chronic neck pain sample were selected as seeds ( Coppieters et al, 2017b , Coppieters et al, 2018 , De Pauw et al, 2019a , De Pauw et al, 2019b ), in addition to regions in which multidirectional rsFC changes were observed in another chronic neck pain sample ( Ihara et al, 2019 ), and regions showing associations between structural or functional brain characteristics and pain-related measures in patients with chronic neck pain. It is hypothesized that 1) rsFC across selected seeds differs between pain-free controls and both patient groups, with more pronounced differences in patients with CWAD, and that these rsFC group differences are associated with self-reported symptoms and QST measures (across both groups, in line with a hypothesized continuum of symptoms and rsFC alterations across the neck pain groups), and 2) rsFC investigated across predefined regions (n = 22) is associated with CS-related symptoms, and QST measures indicative of pain hypersensitivity (across the entire patient group, in line with a continuum).…”

Efficacy and central mechanism of acupuncture treatment in patients with neck pain: study protocol for a randomized controlled trial

“…Recently, significant alterations in the brain structure and function of NP patients have been reported by neuroimaging studies. Compared to healthy subjects, NP patients shown decreased functional activity in the left sensorimotor cortex and right temporoparietal junction [ 20 ], as well as increased functional connectivity between the right dorsolateral prefrontal cortex and the right anterior insula, which are associated with pain intensity [ 21 ]. Based on these findings, neuroimaging techniques appear to be useful tools for investigating the central mechanisms of acupuncture therapy for NP.…”