Brain functional connectivity and morphology changes in medication-overuse headache: Clue for dependence-related processes?

Background: Several imaging studies have identified localized anatomical and functional brain changes in medication-overuse headache (MOH). Objective: The objective of this article is to evaluate whole-brain functional connectivity at rest together with voxel-based morphometry in MOH patients, in comparison with episodic migraine (EM) patients and healthy controls (HCs). Methods: Anatomical MRI and resting-state functional MRI scans were obtained in MOH patients (n = 17 and 9, respectively),= EM patients (n = 18 and 15, respectively) and HCs (n = 17 and 17). SPM8 was used to analyze voxel-based morphometry and seed (left precuneus) to voxel connectivity data in the whole brain. Results: Functional connectivity at rest was altered in MOH patients. Connectivity was decreased between precuneus and regions of the default-mode network (frontal and parietal cortices), but increased between precuneus and hippocampal/temporal areas. These functional modifications were not accompanied by significant gross morphological changes. Furthermore, connectivity between precuneus and frontal areas in MOH was negatively correlated with migraine duration and positively correlated with self-evaluation of medication dependence. Gray matter volumes of frontal regions, precuneus and hippocampus were also negatively related to migraine duration. Functional connectivity within the defaultmode network appeared to predict anxiety scores of MOH patients while gray matter volumes in this network predicted their depression scores. Conclusions: Our data suggest that MOH is associated with functional alterations within intrinsic brain networks rather than with macrostructural changes. They also support the view that dependence-related processes might play a prominent role in its development and maintenance.