• Vasilis S Vasiliou, Nikos Konstantinou, Yiolanda Christou, Savvas Papacostas, Fofi Constantinidou, Eleni Heracleous, Ioannis Seimenis, and Maria Karekla.
• Department of Psychology, Royal Holloway, University of London, Egham, UK.
• Eur J Pain. 2024 Oct 1.

BackgroundDespite functional connectivity network dysfunction among individuals with headaches, no studies have examined functional connectivity neural correlates and anatomical differences in coping with headaches.MethodsThis study investigated inter-individual variability in whole-brain functional connectivity and anatomical differences among 37 individuals with primary headaches and 24 age- and gender-matched controls, and neural correlates of psychological flexibility (PF) that was previously found to contribute to headache adjustment. Participants (84% women; M headache severity = 4/10; M age = 43 years) underwent functional magnetic resonance imaging scans and completed questionnaires to examine global and subnetwork brain areas, and their relations with PF components, controlling for age, gender, education, and head-motion.ResultsSeed and voxel-based contrast analyses between groups showed atypical functional connectivity of regions involved in pain matrix and core resting-state networks. Pain acceptance was the sole PF component that correlated with the cerebellum (x, y, z: 28, -72, -34, p-false discovery rate <0.001), where individuals with headaches showed higher grey matter density compared to controls.ConclusionsThe cerebellum, recently implicated in modulating emotional and cognitive processes, was indicated to process information resembling what individuals do when practicing pain acceptance. Our findings establish for the first time this connection of the cerebellum and its role in pain acceptance. We propose that pain acceptance might be a behavioural biomarker target that could modulate problematic headache perceptions and brain networks abnormalities.SignificanceThis study highlights the potential use of emerging behavioural biomarkers in headache management, such as pain acceptance, and their role in modifying the headache experience. Notably, grey matter reorganization in the cerebellum and other known brain pain networks, could indicate brain networks that can be modified from targeted behavioural interventions to help decode the nociplastic mechanisms that predominates in headaches.© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.

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