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 to controls. Methods Twelve minutes of resting 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 number of years with CM and functional connectivity strength between the anterior insula with mediodorsal thalamus and anterior insula with periaqueductal gray. Conclusions 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.

Migraine and its psychiatric comorbidities

“…Resting-state functional connectivity studies have shown that compared with healthy controls, people with migraine have stronger connectivity between affective-motivational brain regions and those responsible for sensory-discriminative processing. For example, studies demonstrate that people with migraine have stronger connectivity between anterior insula with primary visual cortex, primary auditory cortex and thalamus, and between amygdala with visceroceptive insular cortex, auditory cortex, thalamus and somatosensory cortex 89 91 93. Stronger functional connectivity could predispose the person with migraine to greater emotional responses to noxious sensory stimuli during the migraine attack.…”

The anterior insula shows heightened interictal intrinsic connectivity in migraine without aura

“…5,6 Other studies used region-of-interest (ROI) analysis, focusing on pain-related regions such as the periaqueductal gray or amygdala and found increased connectivity in these networks. [7][8][9] Still others have used differences identified with voxel-based morphometry to seed ROI-based connectivity studies. [10][11][12][13] This approach has identified differences between females and males in cortical thickness and connectivity of the posterior insula and precuneus.…”

Diagnosis, pathophysiology and management of chronic migraine: a proposal of the Belgian Headache Society

“…responsivity to sensory stimuli [26,43,44] % cortical thickness and activation S1, temporal lobe ! insula, cingulate [26] % rs connectivity limbic areas (Am, Ins, ACC)-thalamus, PAG, midtemporal, entorhinal, S1 [131] ! rs connectivity caudate-insula; % putamen-insula [132] % activation dorsolateral pons [47] %% iron content PAG and globus pallidus (T2) [29,31] !…”