Mal de Debarquement Syndrome explained by a vestibulo–cerebellar oscillator

Abstract

Mal de Debarquement Syndrome (MdDS) is a puzzling central vestibular disorder characterized by a long-lasting perception of oscillatory postural instability that may occur after sea travels or flights. We have postulated that MdDS originates from the post-disembarking persistence of an adaptive internal oscillator consisting of a loop system, involving the right and left vestibular nuclei, and the Purkinje cells of the right and left flocculonodular cerebellar cortex, connected by GABAergic and glutamatergic fibers. We have formulated here a mathematical model of the vestibulo–cerebellar loop system and carried out a computational analysis based on a set of differential equations describing the interactions among the loop elements and containing Hill functions that model input–output firing rates relationships among neurons. The analysis indicates that the system acquires a spontaneous and permanent oscillatory behavior for a decrease of threshold and an increase of sensitivity in neuronal input–output responses. These results suggest a role for synaptic plasticity in MdDS pathophysiology, thus reinforcing our previous hypothesis that MdDS may be the result of excessive synaptic plasticity acting on the vestibulo–cerebellar network during its entraining to an oscillatory environment. Hence, our study points to neuroendocrine pathways that lead to increased synaptic response as possible new therapeutic targets for the clinical treatment of the disorder.

Assessing the synergistic effectiveness of intermittent theta burst stimulation and the vestibular ocular reflex rehabilitation protocol in the treatment of Mal de Debarquement Syndrome: a randomised controlled trial

“…immunoendocrine condition or disruption). A computational analysis of this proposed loop was investigated by Burlando et al [ 97 ] and showed that parameter changes, typically induced by synaptic plasticity, increased the system’s tendency to oscillate. The results of this study may suggest that iTBS over the left DLPFC is not effective in disrupting the system of loops that are theorised to exist between the vestibular nuclei and the cerebellum, whereas cTBS over the cerebellum may be able to affect the noxious oscillator as evidenced by the positive effects of this approach observed in previous research [ 50 ].…”