Gender-related differences in the dysfunctional resting networks of migraine suffers

Abstract

Background: Migraine shows gender-specific incidence and has a higher prevalence in females. However, little is known about gender-related differences in dysfunctional brain organization, which may account for gender-specific vulnerability and characteristics of migraine. In this study, we considered gender-related differences in the topological property of resting functional networks.

Methodology/principal findings: Data was obtained from 38 migraine patients (18 males and 20 females) and 38 healthy subjects (18 males and 20 females). We used the graph theory analysis, which becomes a powerful tool in investigating complex brain networks on a whole brain scale and could describe functional interactions between brain regions. Using this approach, we compared the brain functional networks between these two groups, and several network properties were investigated, such as small-worldness, network resilience, nodal centrality, and interregional connections. In our findings, these network characters were all disrupted in patients suffering from chronic migraine. More importantly, these functional damages in the migraine-affected brain had a skewed balance between males and females. In female patients, brain functional networks showed worse resilience, more regions exhibited decreased nodal centrality, and more functional connections revealed abnormalities than in male patients.

Conclusions: These results indicated that migraine may have an additional influence on females and lead to more dysfunctional organization in their resting functional networks.

Figure 1. The mean and standard deviation of small-worldness from the resting networks at different sparsity values.

The colored lines show small-worldness differences among (A) male PM, (B) female PM and matched controls. The horizontal stars indicate the significant difference of the small-worldness between HC and PM (p<0.05, FDR corrected).

Figure 2. Correlation between the small-worldness of female PM resting networks and the migraine duration while controlling for patients' age at threshold S = 15%.

Figure 3. Network robustness analysis for targeted attacks.

Graph presents the mean size of the largest connected component versus the proportion of total nodes eliminated by targeted attacks among (A) male PM, (B) female PM and matched controls. The horizontal dotted line indicates the significant difference between HC and PM (p<0.05).

Figure 4. Significant interactions (nodal centrality differences) between gender (male vs. female) and disease state (patients vs. controls) effects.

A two-way ANOVA was performed (p<0.05, corrected). This figure was visualized with the BrainNet viewer.

Figure 5. Significant differences in the intensity of the functional connection in male PM resting networks.

Ten connections (red lines) showed increased intensity in the male PM resting networks (migraine > HC, p<0.05, FDR corrected). This figure was visualized with the BrainNet viewer.

Figure 6. Significant differences in the intensity of the functional connections in the female PM resting networks.

Ten connections (red lines) showed increased intensity in the female PM resting networks (migraine > HC, p<0.05, FDR corrected). This figure was visualized with the BrainNet viewer.