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.

New Daily Persistent Headache in the Pediatric and Adolescent Population: An Updated Review

“…Interestingly, a 2023 study used structural MRI to distinguish between adolescents with long COVID headache and those with primary headache disorders, including NDPH, revealing potential biomarkers for conditions that, so far, have only clinical criteria [ 32 ]. While a 2022 adult study did not show any gray matter differences in NDPH compared to healthy controls [ 33 ], a 2023 study investigating patients aged 14–70 showed changes in brain morphology such as cortical surface area, cortical thickness, and GM volume, accompanied by abnormal cortical neural activity [ 34 ]. A 2023 brain mapping study in adults showed abnormal functional connectivity in multiple brain regions involved in the perception and regulation of emotion and pain [ 35 ].…”

“…Within the CDH population at tertiary centers, the prevalence of NDPH in children and adolescents ranges from 0.9 to 35%, compared to 1.7 to 10.8% in adults [19]. It maintains a female predominance throughout life, with a 2.5:1 female/male ratio in adults and a 1.8:1 female/male ratio in children and adolescents, and has an earlier age at onset in females (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) than in males (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) [2].…”

A state-of-the-art review of functional magnetic resonance imaging technique integrated with advanced statistical modeling and machine learning for primary headache diagnosis

“…Research has analyzed a subtype of headache within this category known as new daily persistent headache (NDPH) ( Robbins et al, 2010 ), characterized by the sudden onset of daily headaches lasting for 3 months or longer, with secondary causes excluded. A study ( Qiu et al, 2023 ) using structural magnetic resonance imaging combined with multimodal brain imaging analysis of magnetoencephalography found that NDPH patients had abnormal brain morphology such as cortical area, cortical thickness, and gray matter volume, accompanied by abnormal cortical neural activity. Another study ( Wang et al, 2023 ) using fMRI to map abnormal FC in NDPH patients showed abnormal FC in multiple brain regions involved in emotion and pain perception and regulation, but these abnormalities did not correlate with clinical features.…”

Altered functional connectivity of brainstem nuclei in new daily persistent headache: Evidence from resting‐state functional magnetic resonance imaging

“…6 Our previous studies showed that adult patients with NDPH have unique alterations in hemodynamics, regional homogeneity, multiple frequency amplitudes of low-frequency fluctuation, cortical activity, and brain functional connectivity (FC) in certain brain regions. [7][8][9][10] FC is defined as the temporal coincidence of spatially distant neurophysiological events. Over the last decade, an increasing number of studies have applied magnetic resonance imaging (MRI) to explore FC in headache disorders.…”

“…Some evidence suggested that there were abnormalities in brain function and structure in adolescents with NDPH 6 . Our previous studies showed that adult patients with NDPH have unique alterations in hemodynamics, regional homogeneity, multiple frequency amplitudes of low‐frequency fluctuation, cortical activity, and brain functional connectivity (FC) in certain brain regions 7–10 . FC is defined as the temporal coincidence of spatially distant neurophysiological events.…”