Central Integration of Canal and Otolith Signals is Abnormal in Vestibular Migraine

Abstract

Vestibular migraine (VM), a common cause of vestibular symptoms within the general population, is a disabling and poorly understood form of dizziness. We sought to examine the underlying pathophysiology of VM with three studies, which involved the central synthesis of canal and otolith cues, and present preliminary results from each of these studies: (1) VM patients appear to have reduced motion perception thresholds when canal and otolith signals are modulated in a co-planar manner during roll tilt; (2) percepts of roll tilt appear to develop more slowly in VM patients than in control groups during a centrifugation paradigm that presents conflicting, orthogonal canal and otolith cues; and (3) eye movement responses appear to be different in VM patients when studied with a post-rotational tilt paradigm, which also presents a canal–otolith conflict, as the shift of the eye’s rotational axis was larger in VM and the relationship between the axis shift and tilt suppression of the vestibulo-ocular reflex differed in VM patients relative to control groups. Based on these preliminary perceptual and eye movement results obtained with three different motion paradigms, we present a hypothesis that the integration of canal and otolith signals by the brain is abnormal in VM and that this abnormality could be cerebellar in origin. We provide potential mechanisms that could underlie these observations, and speculate that one of more of these mechanisms contributes to the vestibular symptoms and motion intolerance that are characteristic of the VM syndrome.

Vestibular migraine pathophysiology: insights from structural and functional neuroimaging

“…In the past years, in addition to functional changes in patients with migraine, structural abnormalities have been demonstrated in brain areas involved in processing of pain perception and its cognitive-affective contents [18][19][20][21]. However, despite advances in neuroimaging techniques, it is not yet clear if migraine is associated with gray matter (GM) changes [22].…”

Comparison of linear motion perception thresholds in vestibular migraine and Menière’s disease

“…This finding supports the hypothesis that VM does not result from a general increased vestibular sensitivity. Instead, as previously suggested, increased vestibular sensitivity in VM could be a manifestation of abnormal central integration of canal and otolith signals, perhaps at the level of the caudal cerebellar vermis [33]. Other mechanisms such as increased excitability in thalamus [34] or alteration of brain regions characteristic for pain, multisensory vestibular processing and central vestibular compensation [35] in patients suffering VM may also play a role.…”

Correlation of 5‐HTR6 gene polymorphism with vestibular migraine

“…The present study compared the vestibular function test between the observation group and the control group and showed that the observation group had markedly higher abnormality rates in the caloric test, head‐shaking test, and vestibular autorotation test than the control group, indicating that VM can affect the vestibular peripheral and central functions. The central and peripheral vestibular regions participate in the pathogenic process of VM together, and when the integration of the vestibular and pain signaling pathways is abnormal, the migraine signal at the specific cortex will be integrated by the abnormal region and induces vestibular symptoms …”

“…16 All studies above have demonstrated that there is a correlation between 5-HT and the onset of VM, and the decrease in when the integration of the vestibular and pain signaling pathways is abnormal, the migraine signal at the specific cortex will be integrated by the abnormal region and induces vestibular symptoms. [18][19][20] The current studies have suggested that VM, a multigenic disease, is associated with the functional mutations of multiple ion channels and receptors in the vestibular and pain transmission pathways. 5-HRT6 is one of the 5-HT receptors, and its gene, located on chromosome 1p36-p35, can encode the proteins of the G protein-coupled receptor family and is expressed in tissues, such as the frontal cortex, caudate nucleus, and amygdala.…”