White matter tract microstructure of the mPFC-amygdala predicts interindividual differences in placebo response related to treatment in migraine patients.

To investigate whether interindividual variability of white matter (WM) tract microstructure of the medial prefrontal cortex (mPFC)-amygdala circuit could predict 8-week placebo treatment outcomes in patients with migraine without aura (MO) using diffusion tensor imaging (DTI) with a tractography atlas-based analysis algorithm and a linear support vector machine algorithm. This study received institutional review board approval, and all subjects gave informed consent. One hundred and twenty-four MO had an 8-week sham acupuncture treatment. Patients were subdivided into recovering (MOr, >50% improvement in migraine attack frequency after treatment) and persisting (MOp, <50% reduction in number of migraine days). Neuroimaging was collected via magnetic resonance imaging (MRI) in all subjects. Patients were imaged during the interictal phase of migraine (at least 72 hr after, and not within 24 hr of a migraine) before the treatment. WM microstructures were quantified along the selected fiber pathway and were used to evaluate the discrimination performance for classifying MOr and MOp. The combined features of diffusion measures from vertices along the pathways of the mPFC-amygdala accurately discriminated MOr from MOp migraineurs with an accuracy of 84.0% (p < .005, permutation test). The most discriminative WM features that contributed to the classification were located in the external capsule and ACC/mPFC. Our findings suggested that the variability of placebo treatment outcomes in migraineurs could be predicted from priori diffusion measures along the fiber pathways of the mPFC-amygdala, which may demonstrate a potential of WM neuroimaging features as imaging markers for identifying placebo responders in migraine patients.

Altered thalamic connectivity during spontaneous attacks of migraine without aura: A resting-state fMRI study.

Background Functional connectivity of brain networks may be altered in migraine without aura patients. Functional magnetic resonance imaging (fMRI) studies have demonstrated changed activity in the thalamus, pons and cerebellum in migraineurs. Here, we investigated the thalamic, pontine and cerebellar network connectivity during spontaneous migraine attacks. Methods Seventeen patients with episodic migraine without aura underwent resting-state fMRI scan during and outside of a spontaneous migraine attack. Primary endpoint was a difference in functional connectivity between the attack and the headache-free days. Functional connectivity was assessed in four different networks using seed-based analysis. The chosen seeds were in the thalamus (MNI coordinates x,y,z: right, 22,-24,0 and left, -22,-28,6), pons (right, 8,-24,-32 and left, -8,-24,-32), cerebellum crus I (right, 46,-58,-30 and left, -46,-58,-30) and cerebellum lobule VI (right, 34,-42,-36 and left, -32,-42,-36). Results We found increased functional connectivity between the right thalamus and several contralateral brain regions (superior parietal lobule, insular cortex, primary motor cortex, supplementary motor area and orbitofrontal cortex). There was decreased functional connectivity between the right thalamus and three ipsilateral brain areas (primary somatosensory cortex and premotor cortex). We found no change in functional connectivity in the pontine or the cerebellar networks. Conclusions The study indicates that network connectivity between thalamus and pain modulating as well as pain encoding cortical areas are affected during spontaneous migraine attacks.

Brain structural properties predict psychologically mediated hypoalgesia in an 8-week sham acupuncture treatment for migraine.

Neuroimaging studies described brain structural changes that comprise the mechanisms underlying individual differences in migraine development and maintenance. However, whether such interindividual variability in migraine was observed in a pretreatment scan is a predisposition for subsequent hypoalgesia to placebo treatment that remains largely unclear. Using T1-weighted imaging, we investigated this issue in 50 healthy controls (HC) and 196 patients with migraine without aura (MO). An 8-week double-blinded, randomized, placebo-controlled acupuncture was used, and we only focused on the data from the sham acupuncture group. Eighty patients participated in an 8-weeks sham acupuncture treatment, and were subdivided (50% change in migraine days from baseline) into recovering (MOr) and persisting (MOp) patients. Optimized voxel-based morphometry (VBM) and functional connectivity analysis were performed to evaluate brain structural and functional changes. At baseline, MOp and MOr had similar migraine activity, anxiety and depression; reduced migraine days were accompanied by decreased anxiety in MOr. In our findings, the MOr group showed a smaller volume in the left medial prefrontal cortex (mPFC), and decreased mPFC-related functional connectivity was found in the default mode network. Additionally, the reduction in migraine days after placebo treatment was significantly associated with the baseline gray matter volume of the mPFC which could also predict post-treatment groups with high accuracy. It indicated that individual differences for the brain structure in the pain modulatory system at baseline served as a substrate on how an individual facilitated or diminished hypoalgesia responses to placebo treatment in migraineurs. Hum Brain Mapp 38:4386-4397, 2017. © 2017 Wiley Periodicals, Inc.

Structural abnormalities in the thalamus of migraineurs with aura: a multiparametric study at 3 T.

BACKGROUND AND OBJECTIVES: The thalamus exerts a pivotal role in pain processing and cortical excitability control, and migraine is characterized by repeated pain attacks and abnormal cortical habituation to excitatory stimuli. This work aimed at studying the microstructure of the thalamus in migraine patients using an innovative multiparametric approach at high-field magnetic resonance imaging (MRI). DESIGN: We examined 37 migraineurs (22 without aura, MWoA, and 15 with aura, MWA) as well as 20 healthy controls (HC) in a 3-T MRI equipped with a 32-channel coil. We acquired whole-brain T1 relaxation maps and computed magnetization transfer ratio (MTR), generalized fractional anisotropy, and T2* maps to probe microstructural and connectivity integrity and to assess iron deposition. We also correlated the obtained parametric values with the average monthly frequency of migraine attacks and disease duration. RESULTS: T1 relaxation time was significantly shorter in the thalamus of MWA patients compared with MWoA (P < 0.001) and HC (P ≤ 0.01); in addition, MTR was higher and T2* relaxation time was shorter in MWA than in MWoA patients (P < 0.05, respectively). These data reveal broad microstructural alterations in the thalamus of MWA patients compared with MWoA and HC, suggesting increased iron deposition and myelin content/cellularity. However, MWA and MWoA patients did not show any differences in the thalamic nucleus involved in pain processing in migraine. CONCLUSIONS: There are broad microstructural alterations in the thalamus of MWA patients that may underlie abnormal cortical excitability control leading to cortical spreading depression and visual aura.

[Effect of ear point combined therapy on plasma substance P in patients of no-aura migraine at different stages].

OBJECTIVE: To evaluate the therapeutic effect of ear point combined therapy on no-aura migraine at different stages and the mechanism. METHODS: Thirty cases of no-aura migraine at different stages were treated with ear point combined therapy, including blood-letting at the ear back, injection of auto-blood into Fengchi (GB 20), Yanglingquan (GB 34), and pricking at ear points Nie (AT2), Yidan (CO11), Shenmen (TF4), etc. Their clinical therapeutic effects were evaluated at the end of one therapeutic course, and substance P (SP) contents were detected before and after treatment. RESULTS: The clinical effective rate was 86.7%, and the effective rate was 87.5% at the attack stage and 86.4% at the remission stage with no significant difference between the attack stage and the remission stage (P>0.05); after treatment, SP content had significant change as compared with that before treatment (P<0.05, P<0.01), and there was very significant difference in SP content between the attack stage before treatment and the remission stage (P<0.01). CONCLUSION: The ear point combined therapy can relieve pain possibly through decreasing plasma SP content, and the SP con tent possibly is one of main factors inducing migraine attack.