Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI

Abstract

Background: Previous studies have defined low-frequency, spatially consistent intrinsic connectivity networks (ICN) in resting functional magnetic resonance imaging (fMRI) data which reflect functional interactions among distinct brain areas. We sought to explore whether and how repeated migraine attacks influence intrinsic brain connectivity, as well as how activity in these networks correlates with clinical indicators of migraine.

Methods/principal findings: Resting-state fMRI data in twenty-three patients with migraines without aura (MwoA) and 23 age- and gender-matched healthy controls (HC) were analyzed using independent component analysis (ICA), in combination with a "dual-regression" technique to identify the group differences of three important pain-related networks [default mode network (DMN), bilateral central executive network (CEN), salience network (SN)] between the MwoA patients and HC. Compared with the HC, MwoA patients showed aberrant intrinsic connectivity within the bilateral CEN and SN, and greater connectivity between both the DMN and right CEN (rCEN) and the insula cortex - a critical region involving in pain processing. Furthermore, greater connectivity between both the DMN and rCEN and the insula correlated with duration of migraine.

Conclusions: Our findings may provide new insights into the characterization of migraine as a condition affecting brain activity in intrinsic connectivity networks. Moreover, the abnormalities may be the consequence of a persistent central neural system dysfunction, reflecting cumulative brain insults due to frequent ongoing migraine attacks.

Figure 1. ICN group and difference maps.

A. Spatial group maps of three important pain-related ICNs (DMN, CEN and SN) covering all participants (including the HC and MwoA patients), with the CEN split into a right and left lateralized network (P<0.05, FWE corrected); B. Group comparison maps of the DMN, CEN, and SN contrasting MwoA versus HC (MwoA>HC, P<0.05, FWE corrected). Of the ICNs evaluated, intrinsic connectivity demonstrated significant differences between MwoA patients and HC. MwoA patients showed greater intra-network connectivity within the right middle frontal gyrus (rMFG) for the rCEN and left inferior frontal gyrus (lIFG) for the lCEN, and decreased intra-network connectivity within the right supplementary motor area (rSMA) for the SN. MwoA patients also demonstrated greater intrinsic DMN connectivity to the rAI and lAI, and greater intrinsic rCEN connectivity to the rAI. ICN = intrinsic connectivity network; DMN = default mode network; rCEN = right central executive network; lCEN = left central executive network; SN = salience network; rAI = right anterior insula; lAI = left anterior insula; rMFG = right middle frontal gyrus; lIFG = left inferior frontal gyrus; rSMA = right supplementary motor area; MwoA = migraines without aura; HC = healthy control; FWE = family-wise error.

Figure 2. Correlation analysis between intrinsic connectivity abnormalities and clinical indicators of migraine.

Correlation analysis results of the greater intrinsic connectivity between both the DMN and rCEN and the rAI to duration of migraine attacks (P<0.05). The relationship between these resting-state abnormalities and the average pain intensity and attack frequency were also checked. No results exceeded the threshold. DMN = default mode network; rCEN = right central executive network; rAI = right anterior insula;