3.1 Structural network analysis
We found no significant difference (p > 0.05) in age and sex between the groups : EM - HC, CM - HC and EM - CM. Comparing networks obtained using graph theoretical framework between EM and HC, we found significantly (p < 0.05, FDR corrected) higher transitivity and assortativity in EM (Fig. 2). We further obtained the centrality measures, namely mean node and edge-betweenness to be higher in EM. For the contrast ‘CM – HC’, we found significantly higher modularity (and assortativity in CM. We further obtained higher centrality measures (mean node and edge-betweenness) in CM. For the comparison of the networks between two patient groups, we found significantly higher modularity but lower clustering coefficient and transitivity in CM compared to EM.
When comparing similar networks obtained using values of subcortical volumes between EM and HC, we found higher transitivity and assortativity significantly in EM. The comparison CM and HC revealed significantly higher modularity, transitivity and assortativity in CM. All sub-cortical network results are shown in Fig. 3.
Among the regions showing significant regional network difference in terms of clustering, degree and nodal edge-betweenness, NBS further revealed distinct networks with lower interregional connectivity for EM and CM when compared to HC (Fig. 4). For EM, all 20 nodes (regions) showing the graph theory differences formed a network of significantly (p < 0.05, corrected) reduced connectivity in comparison to HC. However, for CM, out of 22 nodes (regions) only 19 formed a network of significantly (p < 0.05, corrected) reduced connectivity when compared to HC.
Finally, the network measures (assortativity, transitivity and modularity) showing a significant difference between the groups, additionally yielded a significant interrelation for MIDAS and attacks per month for the migraineurs (Fig. 5). Considering all network measures together, the SVR yield MIDAS (across EM and CM) with a regression coefficient of 0.779 and attacks with 0.798. Using only assortativity as network measure, the association for MIDAS and attacks was with a regression coefficient of 0.779 and 0.812, respectively. Similarly, for transitivity – MIDAS it was 0.655 and for transitivity – attacks it was 0.649. Modularity alone could reveal the interrelation to the MIDAS and attacks with regression coefficient of 0.655 and 0.649 respectively.
3.2. CT analysis
All reported CT group-differences and correlations were observed with age and sex as nuisance variables (p < 0.001, uncorrected as none of them survived multiple comparison (FDR) correction). Comparing EM to HC (supp. Figure 1), average CT was significantly increased in EM in left lateral occipital cortex, supramarginal gyrus as well as in the right insula, lingual gyrus and precuneus. Additionally, the correlation of the average CT with HADS-A was significantly different in right precentral and inferior parietal cortex between EM and HC. Similarly, the correlation of the average CT with HADS-D was significantly different in left lingual gyrus and right supramarginal gyrus as well as the correlation of the average CT with hours of sleep in left superior parietal and right supramarginal gyrus and caudal middle frontal cortex between EM and HC.
The average CT was significantly increased in CM compared to HC in the left insula and posterior cingulate cortex (PCC) and significantly decreased in the bilateral inferior parietal and right lateral occipital cortex (supp. Figure 2). Additionally, the correlation of the average CT with HADS-A was significantly different in right caudal anterior cingulate and precentral cortex between CM and HC. Similarly, the correlation of the average CT with HADS-D was significantly different in left lingual and PCC as well as the right supramarginal gyrus and precuneus between CM and HC. The correlation of the average CT with the hours of sleep differ significantly in left pars opercularis, superior parietal, insula and right lateral occipital and supramarginal gyrus.
The contrast ‘EM – CM’ (supp. Figure 3) revealed significantly decreased average CT in EM in the left insula and significantly increased in right insula-, supramarginal- and postcentral gyrus. Additionally, the correlation of the average CT with HADS-A was significantly different in the bilateral inferior parietal and left superior parietal lobule. Similarly, the correlation of the average CT with HADS-D was significantly dissimilar in left insula between EM and CM. The correlation of the average CT with hours of sleep varied significantly in left superior parietal, insula and right supramarginal, postcentral and insula between EM and CM. Moreover, the correlation of the average CT with headache attacks per month was significantly different in left insula between these groups.