Gray matter cortical changes in patients with persistent headache after COVID-19 infection: an exploratory study

Objective: To evaluate gray matter alterations in patients with persistent headache after COVID-19 resolution.
Methods: Exploratory case-control study. Highresolution 3D brain T1-weighted Magnetic Resonance Imaging data were acquired in patients with persistent
headache after COVID-19 infection and healthy controls (HC). FreeSurfer (version 6.0) was employed to segment the T1-weighted images and extract the mean values of the cortical curvature (CC) and thickness (CT), surface area (SA) and gray matter volume (GMV) of 68 cortical regions. GMV comparisons were adjusted for intracranial volume. Significant results were considered with p < 0.05 (False Discovery Rate corrected).
Results: Ten patients with persistent headache after COVID-19 (mean age: 53.8 +- 7.8 years; nine women) and 10 HC balanced for age and sex (mean age: 53.1 +- 7.0 years; nine women) were included in the study. Significant higher mean SA and GMV values were found in patients with persistent headache compared to HC in the bilateral medial orbitofrontal cortex, left rostral middle frontal gyrus, and right pars opercularis and superior frontal gyrus. In the patients, significant higher GMV in the right caudal anterior cingulate gyrus and SA values in five temporal, frontal and parietal regions were observed. No CC or CT changes were found.
Conclusions: Persistent headache after COVID-19 infection is related to gray matter cortical changes defined by higher GMV and SA values mainly localized in frontal regions.