Advanced visual network and cerebellar hyperresponsiveness to trigeminal nociception in migraine with aura

Abstract

BackgroundDespite the growing body of advanced studies investigating the neuronal correlates of pain processing in patients with migraine without aura (MwoA), only few similar studies have been conducted in patients with migraine with aura (MwA). Therefore, we aimed to explore the functional brain response to trigeminal noxious heat stimulation in patients with MwA.MethodsSeventeen patients with MwA and 15 age- and sex-matched healthy controls (HC) underwent whole-brain blood oxygen level–dependent (BOLD) fMRI during trigeminal noxious heat stimulation. To examine the specificity of any observed differences between patients with MwA and HC, the functional response of neural pathways to trigeminal noxious heat stimulation in patients with MwA was compared with 18 patients with MwoA. Secondary analyses investigated the correlations between BOLD signal changes and clinical parameters of migraine severity.ResultsWe observed a robust cortical and subcortical pattern of BOLD response to trigeminal noxious heat stimulation across all participants. Patients with MwA showed a significantly increased activity in higher cortical areas known to be part of a distributed network involved in advanced visual processing, including lingual gyrus, inferior parietal lobule, inferior frontal gyrus and medial frontal gyrus. Moreover, a significantly greater cerebellar activation was observed in patients with MwA when compared with both patients with MwA and HC. Interestingly, no correlations were found between migraine severity parameters and magnitude of BOLD response in patients with MwA.ConclusionOur findings, characterized by abnormal visual pathway response to trigeminal noxious heat stimulation, support the role of a functional integration between visual and trigeminal pain networks in the pathophysiological mechanisms underlying migraine with aura. Moreover, they expand the concept of “neurolimbic-pain network” as a model of MwoA including both limbic dysfunction and cortical dys-excitability. Indeed, we suggest a model of “neurolimbic-visual-pain network” in MwA patients, characterized by dysfunctional correlations between pain-modulating circuits not only with the cortical limbic areas but with advanced visual areas as well. Furthermore, the abnormal cerebellar response to trigeminal noxious heat stimulation may suggest a dysfunctional cerebellar inhibitory control on thalamic sensory gating, impinging on the advanced visual processing cortical areas in patients with MwA.Electronic supplementary materialThe online version of this article (10.1186/s10194-019-1002-3) contains supplementary material, which is available to authorized users.

Imaging the Visual Network in the Migraine Spectrum

“…The same group has also recently demonstrated an abnormal response to trigeminal nociceptive stimulation in the lingual gyrus, inferior parietal lobule and cerebellum of MwA patients. This confirms the involvement of areas of higher visual processing in MwA, and possibly shows that functional integration between visual and trigeminal pain networks could represent a key pathophysiological mechanisms underlying migraine with aura (43).…”

Altered lateral geniculate nucleus functional connectivity in migraine without aura: a resting-state functional MRI study

“…Not only the FC of the lingual gyrus in MWA patients has changed, but also the abnormal FC of the lingual gyrus in MwoA patients has been recently discovered. Compared with HC, BOLDresponse of lingual gyrus in MwoA is significantly greater during moderate painful trigeminal nerve thermal stimulation [31]. This finding increases the likelihood of "silent" lingual gyrus hyperactivity in MwoA.…”

“…The surface area of the left inferior frontal gyrus increased significantly in the MwoA group compared to that in the normal control group [30]. Compared with HC, the BOLD response of the left inferior frontal gyrus in MwoA was significantly greater when moderately painful trigeminal nerves are thermally stimulated [31]. Some research results showed that spectrum of different colors can selectively regulate the perception of headache intensity.…”

“…In order to clarify the role of the cerebellum in migraine, some structural and functional studies have also been conducted. Antonio Russoa's results showed a significant increase in cerebellar activation both in MWA and MwoA patients compared to HC patients under thermal stimulation of the trigeminal nerve [31]. The cerebellum of migraine patients (a mix group with MWA and MwoA) and controls was functionally and structurally different.…”

“…The cerebral cortex and subcortex have extensive connections with the cerebellum, including descending afferent and ascending efferent. The structures involved include dorsolateral prefrontal cortex, inferior parietal lobule, primary motor cortex, periaqueductal gray (PAG), parahippocampal gyrus (PHG), primary somatosensory cortex (S1), the thalamus and the hypothalamus, which are considered to be involved in sensorimotor, cognitive, pain, and emotional information processing, as well as in the pathophysiology of migraine [31,33,36]. Enhanced functional connectivity between left LGN and left cerebellum may demonstrated interactions between visual pathway and the pain perception regulatory network.…”