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BackgroundMal de Débarquement Syndrome (MdDS) is a medically refractory neurotological disorder characterized by persistent oscillating vertigo that follows a period of entrainment to oscillating motion such as experienced during sea or air travel. Fronto-occipital hypersynchrony may correlate with MdDS symptom severity.Materials and methodsIndividuals with treatment refractory MdDS lasting at least 6 months received single administrations of three fronto-occipital transcranial alternating current stimulation (tACS) protocols in an "n-of-1" double-blind randomized design: alpha frequency anti-phase, alpha-frequency in-phase, and gamma frequency control. Baseline assessments were made on Day 1. The treatment protocol that led to the most acute reduction in symptoms during a test session on Day 2 was administered for 10-12 stacked sessions given on Days 3 through 5 (20-minutes at 2-4mA). Pre to post symptom changes were assessed on Day 1 and Day 5. Participants who could clearly choose a preferred protocol on Day 2 did better on Day 5 than those who could not make a short-term determination on Day 2 and either chose a protocol based on minimized side effects or were randomized to one of the three protocols. In addition, weekly symptom assessments were made for four baseline and seven post stimulation points for the Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS).ResultsOf 24 participants, 13 chose anti-phase, 7 chose in-phase, and 4 chose control stimulation. Compared to baseline, 10/24 completers noted ≥ 25% reduction, 5/24 ≥50% reduction, and 2/24 ≥75% reduction in oscillating vertigo intensity from Day 1 to Day 5. Stimulating at a frequency slightly higher than the individual alpha frequency (IAF) was better than stimulating at exactly the IAF, and slightly better than stimulating with a strategy of standardized stimulation at 10Hz. A one-way repeated measures ANOVA of weekly DHI, MBRS, and HADS measurements showed significant reductions immediately after treatment with improvement increasing through post-treatment week 6.ConclusionFronto-occipital tACS may be effective in reducing the oscillating vertigo of MdDS and serve as a portable neuromodulation alternative for longer-term treatment. Stimulation frequency relative to the IAF may be important in determining the optimum treatment protocol [ClinicalTrials.gov study NCT02540616. https://clinicaltrials.gov/ct2/show/NCT02540616].

Mal de debarquement syndrome (MdDS) is a disorder of chronic self-motion perception that occurs though entrainment to rhythmic background motion, such as from sea voyage, and involves the perception of low-frequency rocking that can last for months or years. The neural basis of this persistent sensory perception abnormality is not well understood.We investigated grey matter volume differences underlying persistent MdDS by performing voxel-based morphometry on whole brain and pre-specified ROIs in 28 individuals with MdDS and comparing them to 18 age, sex, and handedness matched controls.MdDS participants exhibited greater grey matter volume in the left inferior parietal lobule, right inferior occipital gyrus (area V3v), right temporal pole, bilateral cerebellar hemispheric lobules VIII/IX and left lobule VIIa/VIIb. Grey matter volumes were lower in bilateral inferior frontal, orbitofrontal, pregenual anterior cingulate cortex (pgACC) and left superior medial gyri (t = 3.0, p

Individuals with mal de debarquement syndrome (MdDS) experience a chronic illusion of self-motion triggered by prolonged exposure to passive motion, such as from sea or air travel. The experience is one of rocking dizziness similar to when the individual was originally on the motion trigger such as a boat or airplane. MdDS represents a prolonged version of a normal phenomenon familiar to most individuals but which persists for months or years in others. It represents a natural example of the neuroplasticity of motion adaptation. However, the localization of where that motion adaptation occurs is unknown. Our goal was to localize metabolic and functional connectivity changes associated with persistent MdDS.Twenty subjects with MdDS lasting a median duration of 17.5 months were compared to 20 normal controls with (18)F FDG PET and resting state fMRI. Resting state metabolism and functional connectivity were calculated using age, grey matter volume, and mood and anxiety scores as nuisance covariates.MdDS subjects showed increased metabolism in the left entorhinal cortex and amygdala (z>3.3). Areas of relative hypometabolism included the left superior medial gyrus, left middle frontal gyrus, right amygdala, right insula, and clusters in the left superior, middle, and inferior temporal gyri. MdDS subjects showed increased connectivity between the entorhinal cortex/amygdala cluster and posterior visual and vestibular processing areas including middle temporal gyrus, motion sensitive area MT/V5, superior parietal lobule, and primary visual cortex, while showing decreased connectivity to multiple prefrontal areas.These data show an association between resting state metabolic activity and functional connectivity between the entorhinal cortex and amygdala in a human disorder of abnormal motion perception. We propose a model for how these biological substrates can allow a limited period of motion exposure to lead to chronic perceptions of self-motion.