The Chronic Migraine Brain: What Have We Learned From Neuroimaging?

Abstract

Chronic migraine is a highly disabling disease with a great impact on socioeconomic functioning and quality of life of migraine patients. Chronic migraine usually evolves from episodic migraine that gradually increases in attack frequency, supporting the view of migraine as a spectrum disorder. Pathophysiological mechanisms responsible for migraine chronification are not fully understood. Likewise episodic migraine, chronic migraine patients show widespread functional and structural alterations of cortical and subcortical pain-related brain areas. However, chronic migraine patients experience a more pronounced dysfunction of the pain inhibitory network and an increased sensitization of the central pain pathways, which might explain the higher susceptibility to migraine attacks. Imaging studies have highlighted that brain regions with a key role in migraine attack generation, like the pons and hypothalamus, might also be involved in migraine chronification. Whether brain alterations are biomarkers that predispose migraine patients to chronification or reflect adaptive or maladaptive responses to the increasing headache frequency is still a matter of debate. The central mechanisms of action of chronic migraine preventive treatments and imaging biomarkers that could predict patients' treatment response have also been explored. In this new era of migraine treatments, a better understanding of chronic migraine pathophysiology will pave the way for the development of new improved treatments specifically designed for chronic migraine patients.

Altered local and distant functional connectivity density relate to headache frequency in migraine without aura

“…Previous studies have found an increased prevalence of ischemic lesions in the cerebellar posterior lobe [25]. In addition, relatively consistent findings of reduced gray matter volume were reported in the cerebellum in EM and CM [26][27][28]. Collectively, increased lFCD in the cerebellum in our study may indicate common ineffective inhibition of pain perception in EM and CM.…”

Response inhibition alterations in migraine: evidence from event-related potentials and evoked oscillations

“…Migraineurs display a lack of physiological habituation to repeated sensory stimulation especially during the intervals between attacks [10,14,15]. Despite ongoing debates about the nature of the mechanisms giving rise to these abnormalities [8,16], the presence of deficient inhibitory cortical processes has been argued to be one possible mechanism underlying the pathogenesis of these conditions [16][17][18][19][20]. Available evidence supporting this claim is mainly based on previous studies on the cortical response to external sensory stimuli in migraineurs [10,14,21,22].…”

Response inhibition alterations in migraine: Evidence from event-related potentials and evoked oscillations

“…Although the arguments above focus on the maladaptive inhibitory circuit in patients with MwoA, this does not rule out alternative accounts for pathophysiological features of dysfunctional response inhibition in migraineurs. Given that response inhibition is an important component of the executive system (70,71) and weaker functional connectivity within regions of the pre-frontal executive network (middle frontal gyrus and dorsal anterior cingulate cortex) has been well documented (18,20,72), there is a high probability that weaker network activity within the pre-frontal executive regions may lead to dysfunctional response inhibition in patients with MwoA. In addition, sensory and motor networks in the centro-parietal regions have been found to show altered long-range functional connections to higher order networks (18,73).…”

“…Migraineurs display a lack of physiological habituation to repeated sensory stimulation especially during the intervals between attacks (10,14,15). Despite ongoing debates about the nature of the mechanisms giving rise to these abnormalities (8,16), the presence of de cient inhibitory cortical processes has been argued to be one possible mechanism underlying the pathogenesis of these conditions (16)(17)(18)(19)(20). Available evidence supporting this claim is mainly based on previous studies on the cortical response to external sensory stimuli in migraineurs (10,14,21,22).…”