Hyperconnection and hyperperfusion of overlapping brain regions in patients with menstrual-related migraine: a multimodal neuroimaging study

DOI: https://doi.org/10.1007/s00234- 020- 02623- 5

Abstract-Summary Eigenvector centrality mapping (ECM) was performed on resting-state fMRI, and the relative cerebral blood flow (relCBF) was assessed using PASL-MRI.

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MRM patients showed a significantly increased eigenvector centrality in the

right medial frontal gyrus compared to healthy controls.

Seed-based ECM analysis revealed that increased centrality was associated with the right medial frontal gyrus’s hyperconnectivity with the left insula and the right supplementary motor area.

The perfusion MRI revealed significantly increased relCBF in the hypercon-

nected regions.

The results suggest that menstrual-related migraine is associated with cerebral

hyperconnection and hyperperfusion in critical pain-processing brain regions.

This elevated cerebral activity is correlated with different aspects of functional impairment in MRM patients suggesting that perfusion analysis, along with whole- brain connectivity analysis, can provide a comprehensive understanding of neural mechanisms of MRM.

Extended: Eigenvector centrality mapping (ECM) is a robust data-driven approach that has been previously utilized to investigate the reorganization of the functional brain network in various diseases, such as mild cognitive impairment [433], small vessel disease [434], and effects of acupuncture stimulation [435].

Introduction Gender-related functional connectivity differences in migraine have been reported in resting-state and task-based fMRI studies [436, 437].

Previous experiments mainly investigated the neural mechanism of migraine with/without aura, and very few studies have investigated the abnormal brain activ- ity in patients with MRM [438].

Since the BOLD fMRI signal is an indirect reflection of the neural activity and is sensitive to the changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) consumption [439], investigating the changes of both ECM and CBF would provide a comprehensive understanding of the neural mecha- nism of MRM.

The present study aims to evaluate the reorganization of the whole-brain network and changes in cerebral blood flow in MRM patients using the multimodal MRI technique.

The whole-brain network eigenvector centrality and the contributions of the whole-brain network on the altered centrality in MRM patients were investigated using resting-state BOLD fMRI.

We hypothesized that altered whole-brain functional connectivity and disrupted

perfusion contribute to the functional impairment in MRM patients.

Material and Methods For each participant, a high-resolution 3D anatomic image was first obtained using a T1-weighted sagittal magnetization-prepared rapid gradient echo (MPRAGE) sequence with the following parameters: repetition time (TR) = 2300 ms, echo time (TE) = 2.27 ms, flip angle = 9°, field of view (FOV) = 250 mm × 250 mm, data matrix = 256 × 256, slice thickness = 1 mm.

The perfusion-weighted image was further smoothed with a Gaussian kernel (FWHM  =  6  mm) and globally normalized by dividing the voxel-wise

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perfusion- weight image by the mean value of the whole brain to avoid individual hemodynamic variations and obtain the relative CBF (relCBF) image [440].

Results The results imply that the increased connectivity (both direct and indirect) between the medial frontal gyrus and the left insula and the right SMA would contribute to the hyperconnection in MRM patients.

The hyperconnection in the left insula showed a significantly positive correlation

with the attack frequency in MRM patients (r = 0.67, p = 0.009).

The results showed a significant positive correlation between the disease dura-

tion (years) and the averaged relCBF in the right SMA (r = 0.539, p = 0.047).

The relCBF in the left insula also showed a marginally positive correlation with

disease duration for MRM patients (r = 0.483, p = 0.080).

Discussion Another study exploring structural and functional changes associated with migraine reported a decreased gray matter volume in the left medial prefrontal cortex (MPFC) and increased functional connectivity of the left anterior cingulate cortex (ACC) with the prefrontal cortex [422].

These studies show a significant role of different regions of MPFC in migraine, and our results indicate that eigenvector centrality increases in the MPFC region which may be a neural marker in MRM patients.

A recent study exploring MRI perfusion abnormalities in female migraineurs without aura reported no significant CBF changes during migraine attacks as com- pared to headache-free status in the same group of patients [441].

These studies suggest that connectivity in pain-processing regions may indicate

functional impairment in headache disorders, including migraine.

Our results also suggest that the hyperconnection and hyperperfusion of pain-

processing regions are associated with functional impairment in MRM patients.

Acknowledgement A machine generated summary based on the work of Li, Xinyu; Khan, Ahsan; Li, Yingying; Chen, Diansen; Yang, Jing; Zhan, Haohui; Du, Ganqin; Xu, Jin; Lou, Wutao; Tong, Raymond Kai-yu. 2021 in Neuroradiology.

Cortical metabolic and structural differences in patients with chronic migraine. An exploratory 18FDG-PET and MRI study