Neural correlates of pain acceptance and the role of the cerebellum: Functional connectivity and anatomical differences in individuals with headaches versus matched controls

Background: Despite functional connectivity network dysfunction among indi-viduals with headaches, no studies have examined functional connectivity neuralcorrelates and anatomical differences in coping with headaches.Methods: This study investigated inter-individual variability in whole-brainfunctional connectivity and anatomical differences among 37 individuals withprimary headaches and 24 age- and gender-matched controls, and neural cor-relates of psychological flexibility (PF) that was previously found to contributeto headache adjustment. Participants (84% women; M headache severity = 4/10;M age = 43 years) underwent functional magnetic resonance imaging scans andcompleted questionnaires to examine global and subnetwork brain areas, andtheir relations with PF components, controlling for age, gender, education, andhead- motion.Results: Seed and voxel-based contrast analyses between groups showed atypicalfunctional connectivity of regions involved in pain matrix and core resting-statenetworks. Pain acceptance was the sole PF component that correlated with thecerebellum (x, y, z: 28, −72, −34, p-false discovery rate <0.001), where individualswith headaches showed higher grey matter density compared to controls.Conclusions: The cerebellum, recently implicated in modulating emotional andcognitive processes, was indicated to process information resembling what indi-viduals do when practicing pain acceptance. Our findings establish for the firsttime this connection of the cerebellum and its role in pain acceptance. We pro-pose that pain acceptance might be a behavioural biomarker target that couldmodulate problematic headache perceptions and brain networks abnormalities.