Vestibular migraine (VM) is among the leading causes of dizziness in general population. The VM pathophysiology is unknown with a major gap being lack of understanding neural mechanisms underlying symptoms related to spatial disorientation in these patients. While VM patients do not have peripheral vestibular dysfunction, their symptoms triggered by changes in the head position or visual surroundings indicate dysfunction at the high-level cortical mech- anisms or their interactions with the lower-level vestibular functions. We have studied spatial orientation in a novel context of Bayesian spatial model (BSM), which is built on decades of insights into neurophysiology of multisensory processing and integration for spatial orientation. Within this framework, sensory components that encode head and eye positions are taken into account to quantify spatial orientation. In prior work from our group, we showed that VM patients have altered spatial orientation with changes in the head tilt position as well as heightened sensi- tivity to visual motion. These findings suggest abnormal sensory integration for spatial orientation in VM patients. Using the effects of transcranial magnetic stimulation (TMS), we have shown that the multisensory vestibular cortex within the temporoparietal junction (TPJ) is involved in sensory integration for spatial orientation. We have also developed a novel neurophysiological technique that can probe modulating effect of TPJ on vestibulo-ocular func- tion, using transcranial direct current stimulation (tDCS). Through application of these methods, the overall objective of this proposal is to delineate mechanisms and neural correlates of VM spatial disorientation with links to clinical symptoms in patients. Our central hypothesis is that VM patients exhibit altered TPJ function within the vestibulo- cortical network associated with abnormal sensory integration for spatial orientation. To test this hypothesis, we (i) uncover distinct sensory mechanisms related to VM spatial disorientation, (ii) investigate whether such mechanisms are linked to clinical signs and symptoms (validated measures of visuospatial symptoms and postural instability), and (iii) delineate TPJ contributions to VM pathophysiology considering its role in both high and low level vestibular functions, and whether TPJ can be targeted using TMS to modulate spatial disorientation in these patients. These steps are crucial towards devising effective treatment strategies for debilitating dizziness and spatial disorientation in VM patients.
Vestibular migraine (VM) is among the leading causes of dizziness and spatial disorientation with an unknown pathophysiology. Here we apply a rigorous framework to (i) determine sensory contributions to spatial disorientation in VM patients, (ii) find the link between these measures and clinical sign and symptoms in VM patients, and 3) examine the role of neural networks that contribute to spatial disori- entation in VM pathophysiology. These are crucial steps towards devising effective treatment strategies for the debilitating symptoms in VM patients.
