Mesocorticolimbic system abnormalities in chronic cluster headache patients: A neural signature?

Abstract

Background: Converging evidence suggests that anatomical and functional mesocorticolimbic abnormalities support the chronicization of pain disorders. Methods: We mapped structural and functional alterations of the mesocorticolimbic system in a sample of chronic cluster headache patients (n = 28) in comparison to age and sex-matched healthy individuals (n = 28) employing structural MRI and resting-state functional MRI. Results: Univariate logistic regression models showed that several of the examined structures/areas (i.e., the bilateral nucleus accumbens, ventral diencephalon, hippocampus, and frontal pole, and the right amygdala) differentiated chronic cluster headache patients from healthy individuals (p < 0.05, uncorrected). Specifically, all the significant structures/areas had increased volumes in chronic cluster headache patients compared to healthy individuals. The examination of the groups suffering from left and right-sided cranial attacks showed a lateralization effect: ipsilateral to the pain ventral diencephalic regions and contralateral to the pain nucleus accumbens discriminated chronic cluster headache patients from healthy individuals. The resting-state functional MRI data analyses showed that chronic cluster headache patients compared to CTRL individuals present robust reduced functional connectivity in the right frontal pole-right amygdala pathway (p < 0.05, FDR-corrected) Conclusion: Our results showed that chronic cluster headache patients present anatomical and functional maladaptation of the mesocorticolimbic system, with functional data indicating a possible prefrontal areas' failure to modulate the mesolimbic structures. These results were opposite to what we hypothesized based on the previous literature on chronic pain conditions. Future studies should assess whether the observed mesocorticolimbic abnormalities are due to the neuroprotective effects of the assumed medications, or to the frequent comorbidity of CH with neuropsychiatric disorders or if they are a genuine neural signature of CH and/or chronic cluster headache condition.