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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.

SUBMITTER: Liu J

PROVIDER: S-EPMC6867162 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Liu Jixin J Ma Shaohui S Mu Junya J Chen Tao T Xu Qing Q Dun Wanghuan W Tian Jie J Zhang Ming M

Human brain mapping 20170721 10

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 ...[more]

PMID: 28731567

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Project description:Introduction: Placebo and nocebo effects are positive and negative health outcomes that can be elicited by the psychosocial context. They can be mediated by expectations, and may emerge in somatic symptoms even when people are aware of these effects. Interindividual differences (e.g., in personality, affective states) could impact placebo and nocebo responding, but findings are inconsistent. Methods: The current work examined expectation as a mediator of the association between verbal placebo and nocebo suggestions (VSs) and histamine-induced itch across three experimental studies. Moreover, we examined whether interindividual differences (e.g., in optimism, neuroticism, behavioral activation system (BAS), body ignorance) modulated: (1) the direct association between VSs and itch (direct moderation), and (2) the indirect, expectation-mediated association between VSs and itch (moderated mediation). Positive VSs were compared to neutral instructions (Study 1; n = 92) or negative VSs (Studies 2+3; n = 203) in an open-label (i.e., explaining placebo and nocebo effects) or closed-label (concealed) context using PROCESS. First, mediation of VSs effects on itch by expectations was tested. Next, moderation by individual traits was explored using conditional process analyses. Results: The effects of VSs on itch were significantly mediated by expectation in Study 1 and in the open-label (but not closed-label) contexts of Studies 2 and 3. Ignorance of bodily signals marginally moderated the direct effects of VSs on itch when closed-label suggestions were given: at low levels of body ignorance, effects of positive and negative VSs were stronger. Moreover, moderated mediation was observed in the open-label groups of Studies 2 and 3: The expectation-mediated effects of VSs on itch were stronger when BAS drive was lower. Conclusion: Overall, the effects of VSs on itch were mediated by expectations in the open-label, but not the closed-label context. Moreover, the current work suggests that placebo and nocebo effects may be moderated by ignorance of bodily signals and the BAS. There was limited evidence that other interindividual differences modulated placebo and nocebo responding in itch.

Project description:The existence of "sex phenotype" in migraine is a long-standing scientific question. Fluctuations of female sex hormones contribute to migraine attacks, and women also have enhanced brain activity during emotional processing and their functional brain networks seem to be more vulnerable to migraine-induced disruption compared to men. Periaqueductal grey matter (PAG) is a core region of pain processing and modulation networks with possible sex-related implications in migraine. In our study, sex differences of PAG functional resting-state connectivity were investigated in the interictal state in 32 episodic migraines without aura patients (16 women and 16 men). A significant main effect of sex was detected in PAG connectivity with postcentral, precentral, and inferior parietal gyri, and further differences were found between right PAG and visual areas (superior occipital gyrus, calcarine, and cuneus), supplementary motor area, and mid-cingulum connectivity. In all cases, PAG functional connectivity was stronger in female migraineurs compared to males. However, higher average pain intensity of migraine attacks correlated with stronger connectivity of PAG and middle temporal, superior occipital, and parietal gyri in male migraineurs compared to females. Migraine-related disability is also associated with PAG connectivity but without sex differences. Our results indicate that sex differences in PAG connectivity with brain regions involved in sensory and emotional aspects of pain might contribute to the "sex-phenotype" in migraine. The stronger functional connectivity between PAG and pain processing areas may be a sign of increased excitability of pain pathways even in resting-state in females compared to male migraineurs, which could contribute to female vulnerability for migraine. However, pain intensity experienced by male migraineurs correlated with increased connectivity between PAG and regions involved in the subjective experience of pain and pain-related unpleasantness. The demonstrated sex differences of PAG functional connectivity may support the notion that the female and male brain is differently affected by migraine.

Project description:Background: In attempts to understand the migraine patients' overall brain functional architecture, blood oxygenation level-dependent (BOLD) signals in the white matter (WM) and gray matter (GM) were considered in the current study. Migraine, a severe and multiphasic brain condition, is characterized by recurrent attacks of headaches. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both WM and GM. It is feasible to explore the functional interactions between WM tracts and GM regions in migraine. Methods: Forty-eight migraineurs without aura (MWoA) and 48 healthy controls underwent resting-state functional magnetic resonance imaging. Pearson's correlations between the mean time courses of 48 white matter (WM) bundles and 82 gray matter (GM) regions were computed for each subject. Two-sample t-tests were performed on the Pearson's correlation coefficients (CC) to compare the differences between the MWoA and healthy controls in the GM-averaged CC of each bundle and the WM-averaged CC of each GM region. Results: The MWoAs exhibited an overall decreased average temporal CC between BOLD signals in 82 GM regions and 48 WM bundles compared with healthy controls, while little was increased. In particular, WM bundles such as left anterior corona radiata, left external capsule and bilateral superior longitudinal fasciculus had significantly decreased mean CCs with GM in MWoA. On the other hand, 16 GM regions had significantly decreased mean CCs with WM in MWoA, including some areas that are parts of the somatosensory regions, auditory cortex, temporal areas, frontal areas, cingulate cortex, and parietal cortex. Conclusion: Decreased functional connections between WM bundles and GM regions might contribute to disrupted functional connectivity between the parts of the pain processing pathway in MWoAs, which indicated that functional and connectivity abnormalities in cortical regions may not be limited to GM regions but are instead associated with functional abnormalities in WM tracts.

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

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

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