Functional magnetic resonance imaging in migraine: A systematic review

Abstract

Background Migraine is a highly prevalent primary headache disorder. Despite a high burden of disease, key disease mechanisms are not entirely understood. Functional magnetic resonance imaging is an imaging method using the blood-oxygen-level-dependent signal, which has been increasingly used in migraine research over recent years. This systematic review summarizes recent findings employing functional magnetic resonance imaging for the investigation of migraine. Methods We conducted a systematic search and selection of functional magnetic resonance imaging applications in migraine from April 2014 to December 2021 (PubMed and references of identified articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines). Methodological details and main findings were extracted and synthesized. Results Out of 224 articles identified, 114 were included after selection. Repeatedly emerging structures of interest included the insula, brainstem, limbic system, hypothalamus, thalamus, and functional networks. Assessment of functional brain changes in response to treatment is emerging, and machine learning has been used to investigate potential functional magnetic resonance imaging-based markers of migraine. Conclusions A wide variety of functional magnetic resonance imaging-based metrics were found altered across the brain for heterogeneous migraine cohorts, partially correlating with clinical parameters and supporting the concept to conceive migraine as a brain state. However, a majority of findings from previous studies have not been replicated, and studies varied considerably regarding image acquisition and analyses techniques. Thus, while functional magnetic resonance imaging appears to have the potential to advance our understanding of migraine pathophysiology, replication of findings in large representative datasets and precise, standardized reporting of clinical data would likely benefit the field and further increase the value of observations.

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

“…MRI studies have reported inconsistent differences between individuals with migraine and healthy controls [ 7 ]. Structural MRI studies have reported abnormalities such as white matter hyperintensities and volumetric changes in individuals with migraine [ 54 ], while fMRI studies have suggested changes in pain-processing and visual networks [ 55 – 57 ]. Reasons for the failure to consistently replicate these findings may include insufficient sample sizes, heterogeneous populations, and differences in analytical approaches [ 54 , 55 , 57 ].…”

“…Structural MRI studies have reported abnormalities such as white matter hyperintensities and volumetric changes in individuals with migraine [ 54 ], while fMRI studies have suggested changes in pain-processing and visual networks [ 55 – 57 ]. Reasons for the failure to consistently replicate these findings may include insufficient sample sizes, heterogeneous populations, and differences in analytical approaches [ 54 , 55 , 57 ]. Few fMRI studies have explored the efficacy predictors of mAbs against CGRP signaling, or erenumab-induced biomarker changes.…”

Galcanezumab treatment changes visual related EEG connectivity patterns in migraine patients

“…Accordingly, patients with less frequent use of symptomatics after galcanezumab therapy improved more evidently in global efficiency. These correlations, although not exhaustive regarding a direct effect of CGRP inhibition in normalizing cortical networking, could support the hypothesis that an efficient and specific antinociception, whenever wielded in the periphery, could potentially act on the complex brain dysfunctions predisposing to attack onset (4,31).…”

Pathophysiology of Migraine

“…14 A dural inflammatory theory poses that the vasoactive neurotransmitters released by dural stimulation cause neurogenic inflammation and secondary vasodilatation, 15 but this mechanism is not supported by the fact that nonvasoconstricting inhibitors of neurogenic inflammation have not been effective in the treatment of migraine 16 and that longitudinal structural imaging has never detected the consequences of repeated dural inflammation. 17 In recent years, a primarily neural theory has been supported by functional imaging studies during migraine, which have consistently demonstrated activation of central brain areas, including the brainstem in both spontaneous and triggered migraine, 18 as well as early functional imaging changes before pain onset, suggesting that attack initiation must occur centrally. 6 An intact blood-brain barrier has been suggested on imaging during migraine attacks, 19 so dural changes that could be the source of headache are unlikely to be the first process in the migraine attack.…”

“…In recent years, a primarily neural theory has been supported by functional imaging studies during migraine, which have consistently demonstrated activation of central brain areas, including the brainstem in both spontaneous and triggered migraine, 18 as well as early functional imaging changes before pain onset, suggesting that attack initiation must occur centrally 6 . An intact blood-brain barrier has been suggested on imaging during migraine attacks, 19 so dural changes that could be the source of headache are unlikely to be the first process in the migraine attack.…”