Volume of Hypothalamus as a Diagnostic Biomarker of Chronic Migraine

Abstract

It is believed than hypothalamus (HTH) might be involved in generation of migraine, and evidence from high resolution fMRI reported that the more anterior part of HTH seemed to play an important role in migraine chronification. The current study was aimed to identify the alteration of morphology and resting-state functional connectivity (FC) of the hypothalamus (HTH) in interictal episodic migraine (EM) and chronic migraine (CM). High-resolution structural and resting-state functional magnetic resonance images were acquired in 18 EM patients, 16 CM patients, and 21 normal controls (NC). The volume of HTH was calculated and voxel-based morphometry (VBM) was performed over the whole HTH. Receiver operating characteristics (ROC) curve analysis was applied to evaluate the diagnostic efficacy of HTH volume. Correlation analyses with clinical variables were performed and FC maps were generated for positive HTH regions according to VBM comparison. The volume of the HTH significantly decreased in both EM and CM patients compared with NC. The cut-off volume of HTH as 1.429 ml had a good diagnostic accuracy for CM with sensitivity of 81.25% and specificity of 100%. VBM analyses identified volume reduction of posterior HTH in EM vs. NC which was negatively correlated with headache frequency. The posterior HTH presented decreased FC with the left inferior temporal gyrus (Brodmann area 20) in EM. Decreased volume of anterior HTH was identified in CM vs. NC and CM vs. EM which was positively correlated with headache frequency in CM. The anterior HTH presented increased FC with the right anterior orbital gyrus (AOrG) (Brodmann area 11) in CM compared with NC and increased FC with the right medial orbital gyrus (MOrG) (Brodmann area 11) in CM compared with EM. Our study provided evidence of structural plasticity and FC changes of HTH in the pathogensis of migraine generation and chronification, supporting potential therapeutic target toward the HTH and its peptide.

Keywords: chronic migraine; chronicification; episodic migraine; functional connectivity; hypothalamus; volume; voxel-based morphomethy.

Figure 1

Individual HTH segment. Top line: high resolution probabilistic in vivo HTH template was resliced into MNI space; Bottom line: Individual T1 images were segmented, and generated deformation field, which would be used to generate individual HTH using pull-back strategy. Red and purple represent 3D visualization of HTH template and individual HTH.

Figure 2

The individual anterior and posterior HTH segment. CM, chronic migraine; EM, episodic migraine; HTH, hypothalamus; NC, normal control; VBM, voxel-based morphometry.

Figure 3

HTH volume distribution plot of NC, EM and CM patients.

Figure 4

Pairwise comparison of ROC curve for NC vs. EM and NC vs. CM. The AUC for NC vs. CM was 0.90 ± 0.06, and for NC vs. EM was 0.77 ± 0.08.

Figure 5

The decreased HTH volume of EM located in the posterior HTH (top line), while the decreased HTH volume of CM located in the anterior HTH (middleline) compared with NC. Compared with EM, the decreased HTH region located in the anterior HTH (bottom line).

Figure 6

The altered functional connectivity of positive HTH region among EM, CM and NC. The top line presented the decreased functional connectivity of posterior HTH located in the left inferior temporal gyrus in EM compared with that in NC. The middle line presented the increased functional connectivity of anterior HTH of CM located in the right anterior orbital gyrus compared with NC. Bottom line showed that the increased functional connectivity of anterior HTH of CM located in the right medial orbital gyrus compared with EM.

Figure 7

Contrast estimates and 90% CI for the significant voxels.