Brain structure and cortical activity changes of new daily persistent headache: multimodal evidence from MEG/sMRI

Abstract

Background: New daily persistent headache (NDPH) is a rare but debilitating primary headache disorder that poses a significant burden on individuals and society. Despite its clinical importance, the underlying pathophysiological mechanisms of NDPH remain unclear. In this study, we aimed to investigate the brain structural changes and neural activity patterns in patients with NDPH using multimodal brain imaging analysis of structural magnetic resonance imaging (sMRI) combined with magnetoencephalography (MEG).

Methods: Twenty-eight patients with NDPH and 37 healthy controls (HCs) were recruited for this study, and their structural and resting-state data were collected by 3.0 Tesla MRI and MEG. We analyzed the brain morphology using voxel-based morphometry and source-based morphometry. In each brain region, MEG sensor signals from 1 to 200 Hz were analyzed using an adapted version of Welch's method. MEG source localization was conducted using the dynamic statistical parametric mapping, and the difference of source distribution between patients with NDPH and HCs was examined.

Results: Our results revealed significant differences in the regional grey matter volume, cortical thickness, and cortical surface area between the two groups. Specifically, compared with HCs, patients with NDPH showed a significant decrease in cortical thickness of the left rostral cortex in the middle frontal gyrus, decreased cortical surface area of the left fusiform gyrus, decreased grey matter volume of the left superior frontal gyrus and the left middle frontal gyrus, and increased grey matter volume of the left calcarine. Furthermore, the power of the whole brain, bilateral frontal lobes, and right temporal lobe in the NDPH group were higher than that in HCs in the ripple frequency band (80-200 Hz). Functional and structural analysis suggested that there were structural changes and abnormal high frequency cortical activity in both frontal and temporal lobes in patients with NDPH.

Conclusion: Our findings indicated that patients with NDPH have abnormalities in brain morphology, such as cortical area, cortical thickness, and grey matter volume, accompanied by abnormal cortical neural activity. Brain structural changes in the frontotemporal cortex and abnormalities in cortical ripple activity may be involved in the pathogenesis of NDPH.

Keywords: Magnetoencephalography; Multimodal; New daily persistent headache; Structural magnetic resonance imaging.

Fig. 1

The pipeline of resting-state magnetoencephalographic spectral and source analysis

Fig. 2

The abnormal cortical thickness and surface area in NDPH. A The NDPH group showed significantly decreased cortical thickness in the left rostral middle frontal gyrus compared with HCs. B The NDPH group showed significantly decreased cortical surface area in the left fusiform gyrus compared with HCs. HCs, healthy controls; NDPH, new daily persistent headache;  L Left; R Right

Fig. 3

The abnormal grey matter volume in NDPH. A The NDPH group showed decreased grey matter volume in the left superior frontal and middle frontal gyrus compared with HCs. B The NDPH group showed increased grey matter volume in the calcarine compared with HCs. HCs, healthy controls; NDPH, new daily persistent headache;  L Left; R Right

Fig. 4

The distribution of neuromagnetic activity in the ripple band. The distribution of the neuromagnetic activity was significantly different between the HC and NDPH groups. HC, healthy control; NDPH, new daily persistent headache. L_F, left frontal lobe; R_F, right frontal lobe; L_P, left parietal lobe; R_P, right parietal lobe; L_O, left occipital lobe; R_O, right occipital lobe; L_T, left temporal lobe; R_T, right temporal lobe