Integration of white matter network is associated with interindividual differences in psychologically mediated placebo response in migraine patients

Abstract

Individual differences of brain changes of neural communication and integration in the modular architecture of the human brain network exist for the repeated migraine attack and physical or psychological stressors. However, whether the interindividual variability in the migraine brain connectome predicts placebo response to placebo treatment is still unclear. Using DTI and graph theory approaches, we systematically investigated the topological organization of white matter networks in 71 patients with migraine without aura (MO) and 50 matched healthy controls at three levels: global network measure, nodal efficiency, and nodal intramodule/intermodule efficiency. All patients participated in an 8-week sham acupuncture treatment to induce analgesia. In our results, 30% (n = 21) of patients had 50% change in migraine days from baseline after placebo treatment. At baseline, abnormal increased network integration was found in MO patients as compared with the HC group, and the increased global efficiency before starting clinical treatment was associated with their following placebo response. For nodal efficiency, significantly increased within-subnetwork nodal efficiency and intersubnetwork connectivity of the hippocampus and middle frontal gyrus in patients' white matter network were correlated with the responses of follow-up placebo treatment. Our findings suggested that the trait-like individual differences in pain-related maladaptive stress interfered with and diminished the capacity of chronic pain modulation differently, and the placebo response for treatment could be predicted from a prior white matter network modular structure in migraineurs. Hum Brain Mapp 38:5250-5259, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: acupuncture; brain connectome; migraine.

Figure 1

The intermediate modular structure. Six modules were identified for the group‐level network of healthy controls including the anterior default mode network (aDMN, red) and posterior default mode network (pDMN, light green). Two contralaterally matched modules were localized to the dorsolateral prefrontal cortices, insula, and striatum of a single hemisphere (M1_left and M1_right, dark blue and red). The two remaining modules included contralateral regions of temporo‐parietal areas and occipital cortices of a single hemisphere (M2_left and M2_right, yellow and light blue). The results are represented by using the BrainNet viewer [Xia et al., 2013]. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Disrupted intramodule and intermodule structural connectivity between HC and patient groups. The red and blue lines indicate significant between group differences (a. HC vs. MO; b. MOr vs. MOp). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Nodal efficiency was significantly increased in the middle frontal gyrus (MFG), precentral gyrus, hippocampus, insula, olfactory cortex, and inferior occipital gyrus in the patient group as compared with the controls (a). No significant decreased nodal efficiency was found in the patient group. Significant association was found between the changes in migraine days and the nodal efficiency of the hippocampus and MFG (b), within‐module nodal efficiency of the hippocampus (c), and the participation coefficient of the hippocampus and MFG (d). The results are represented by using the BrainNet viewer [Xia et al., 2013]. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Between group differences of the nodal efficiency between MOr and MOp patients (a. within‐module nodal efficiency; b. participation coefficient). [Color figure can be viewed at http://wileyonlinelibrary.com]