Atypical resting-state functional connectivity of affective pain regions in chronic migraine

Abstract

Objective: Chronic migraineurs (CM) have painful intolerances to somatosensory, visual, olfactory, and auditory stimuli during and between migraine attacks. These intolerances are suggestive of atypical affective responses to potentially noxious stimuli. We hypothesized that atypical resting-state functional connectivity (rs-fc) of affective pain-processing brain regions may associate with these intolerances. This study compared rs-fc of affective pain-processing regions in CM with controls.

Methods: Twelve minutes of resting-state blood oxygenation level-dependent data were collected from 20 interictal adult CM and 20 controls. Rs-fc between 5 affective regions (anterior cingulate cortex, right/left anterior insula, and right/left amygdala) with the rest of the brain was determined. Functional connections consistently differing between CM and controls were identified using summary analyses. Correlations between number of migraine years and the strengths of functional connections that consistently differed between CM and controls were calculated.

Results: Functional connections with affective pain regions that differed in CM and controls included regions in anterior insula, amygdala, pulvinar, mediodorsal thalamus, middle temporal cortex, and periaqueductal gray. There were significant correlations between the number of years with CM and functional connectivity strength between the anterior insula with mediodorsal thalamus and anterior insula with periaqueductal gray.

Conclusion: CM is associated with interictal atypical rs-fc of affective pain regions with pain-facilitating and pain-inhibiting regions that participate in sensory-discriminative, cognitive, and integrative domains of the pain experience. Atypical rs-fc with affective pain regions may relate to aberrant affective pain processing and atypical affective responses to painful stimuli characteristic of CM.

Figure 1. Flow-Diagram Summarizing the Methods Used to Analyze Resting State Data

Rs-fc = resting state functional connectivity; ROI = region of interest; CM = chronic migraine

Figure 2. Resting State Functional Connectivity with the 5 Pain ROIs – Summary Analyses

Voxels with significant rs-fc with at least 2 of 5 a priori selected pain ROIs are illustrated. Axial slices are shown with the left hemisphere on the left side. Green = voxel has rs-fc with 2 of 5 a priori ROIs; Blue = voxel has rs-fc with 3 of 5 a priori ROIs. Red = voxel has rs-fc with 4 of 5 a priori ROIs. Yellow = voxel has rs-fc with 5 of 5 a priori ROIs. PCC = posterior cingulate cortex/precuneus; LPC = lateral parietal cortex; ACC = anterior cingulate cortex; SSC = somatosensory cortex; Inf Frontal = inferior frontal; Sup Frontal = superior frontal; Ang Gyrus = angular gyrus.

Figure 3. Resting State Functional Connectivity with Pain Regions Differs in Chronic Migraineurs Compared to Controls

Summary analyses of 2-sample t-tests for each of the 5 pain ROIs identified voxels with rs-fc that differed between chronic migraineurs and controls. Axial slices are shown with the left hemisphere on the left side. Green = the rs-fc of that voxel with 2 of 5 a priori pain ROIs differs between chronic migraineurs and controls; Blue = the rs-fc of that voxel with 3 of 5 a priori pain ROIs differs between groups; Red = the rs-fc of that voxel with 4 of 5 a priori pain ROIs differs between groups; Yellow = the rs-fc of that voxel with 5 of 5 a priori pain ROIs differs between groups. ACC = anterior cingulate cortex; VLPFC = ventrolateral prefrontal cortex; Mid Temp = middle temporal cortex; MD Thal = medial dorsal thalamus; PAG = periaqueductal gray; SSC = somatosensory cortex.

Figure 4. Resting State Functional Connections to Affective Pain Regions that Significantly Differ Between Chronic Migraineurs and Controls

After correction for multiple comparisons, the strengths of 16 functional connections significantly differ between chronic migraine and control subjects. The scatterplot illustrates the BOLD time series correlations (functional connectivity strength) on the Y-axis for individual chronic migraine and control subjects. The locations of the regions involved in the functional connections that differed between chronic migraine and control subjects are shown on the axial brain slices (all slices are shown with the left hemisphere on the left side). Rt = right; Lt = left; Ant = anterior; Mid = middle; Temp = temporal; MD = mediodorsal; Thal = thalamus; PAG = periaqueductal gray; Sup = superior; Inf = inferior; ROIs = regions of interest.