Research Topic

Functional and Structural Brain Alterations in Headache: A Trait or a State?

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Over the last decades, our knowledge of the biology of primary and secondary headaches has improved considerably. Functional imaging studies have shed light on the mechanisms responsible for initiation and propagation of migraine attacks, and has disclosed the activity of cortical, subcortical and brainstem ...

Over the last decades, our knowledge of the biology of primary and secondary headaches has improved considerably. Functional imaging studies have shed light on the mechanisms responsible for initiation and propagation of migraine attacks, and has disclosed the activity of cortical, subcortical and brainstem regions during the various migraine phases. A specific hypothalamic activation has been demonstrated during the pain phase in “in-bout” cluster headache patients. In association with functional imaging abnormalities, modern morphometric techniques have shown widespread structural abnormalities in migraine and cluster headache patients, both in the course of an acute attack and during the interictal phase. Whether such alterations represent a predisposing trait or are the consequence of the recurrence of headache attacks is still a matter of debate. Many studies demonstrated that brain regions, like the brainstem, thalamus and hypothalamus, have a pivotal role in triggering the migraine and cluster headache attacks. Other studies have shown that Magnetic Resonance Imaging (MRI) changes in brain regions involved in multisensory processing, including pain, are dynamic and can be remodelled over time. Structural and functional abnormalities in nociceptive brain areas have also been revealed in patients with medication overuse and post-traumatic headache. Thus, raising the question whether it is possible to identify a specific MRI pattern for each different headache phenotype. There is evidence demonstrating that patients with medication overuse headache can experience brain changes not only in regions that are part of the pain network but also in areas implicated in addiction. Some of these abnormalities normalized following discontinuation of the overused medication, while others persisted. These findings suggest that some brain alterations are secondary to the frequent intake of acute treatments and associated headache, whereas others might represent a brain trait that predispose to development of medication overuse. Recent imaging studies demonstrated distinct patterns of structural brain abnormalities in patients with persistent post-traumatic headache compared to patients with migraine. Interestingly, previous data has showed that brain structural alterations of nociceptive areas were not present in patients with post-traumatic headache in the acute phase but developed after three months. These changes completely reverted after one year together with the headache resolution.

The scope of this Research Topic is to outline the current state of the art on functional and structural brain abnormalities in primary and secondary headaches and highlight different opinions and perspectives about whether these brain alterations might represent headache brain traits, states or a combination of both. New evidence demonstrating that distinct imaging patterns can predispose to different headache phenotypes or that brain alterations are secondary to disease activity are welcomed. This Research Topic aims also to discuss how a better understanding of functional and structural brain alterations will help to develop new anti-migraine treatments.


Keywords: Headaches, migraine, cluster headache, neuroimaging, functional MRI, structural MRI


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