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Electrophysiological Signatures of Intrinsic Functional Connectivity Related to rTMS Treatment for Mal de Debarquement Syndrome.

ABSTRACT: To determine intrinsic functional connectivity (IFC) related to symptom changes induced by rTMS in mal de debarquement syndrome (MdDS), a motion perceptual disorder induced by entrainment to oscillating motion. Twenty right-handed women (mean age: 52.9?±?12.6 years; mean duration illness: 35.2?±?24.2 months) with MdDS received five sessions of rTMS (1 Hz right DLPFC, 10 Hz left DLPFC) over consecutive days. High-density (128-channel) resting-state EEG were recorded prior to and following treatment sessions and analyzed using a group-level independent component (IC) analysis. IFC between 19 ICs was quantified by inter-IC phase coherence (ICPC) in six frequency bands (delta, theta, low alpha, high alpha, beta, gamma). Correlational analyses between IFCs and symptoms were performed. Symptom improvement after rTMS was significantly correlated with (1) an increase in low alpha band (8-10 Hz) IFC but a decrease of IFC in all other bands, and (2) high baseline IFC in the high alpha (11-13 Hz) and beta bands (14-30 Hz). Most treatment related IFC changes occurred between frontal and parietal regions with a linear association between the degree of symptom improvement and the number of coherent IFC changes. Frequency band and region specific IFC changes correlate with and can predict symptom changes induced by rTMS over DLPFC in MdDS. MdDS symptom response correlates with high baseline IFC in most frequency bands. Treatment induced increase in long-range low alpha IFC and decreases in IFC in other bands as well as the proportion of coherent IFC changes correlate with symptom reduction.

SUBMITTER: Cha YH

PROVIDER: S-EPMC6182441 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Electrophysiological Signatures of Intrinsic Functional Connectivity Related to rTMS Treatment for Mal de Debarquement Syndrome.

Cha Yoon-Hee YH Shou Guofa G Gleghorn Diamond D Doudican Benjamin C BC Yuan Han H Ding Lei L

Brain topography 20180811 6

To determine intrinsic functional connectivity (IFC) related to symptom changes induced by rTMS in mal de debarquement syndrome (MdDS), a motion perceptual disorder induced by entrainment to oscillating motion. Twenty right-handed women (mean age: 52.9 ± 12.6 years; mean duration illness: 35.2 ± 24.2 months) with MdDS received five sessions of rTMS (1 Hz right DLPFC, 10 Hz left DLPFC) over consecutive days. High-density (128-channel) resting-state EEG were recorded prior to and following treatme ...[more]

PMID: 30099627

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Project description:BackgroundIndividuals 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.MethodsTwenty 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.ResultsMdDS 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.ConclusionThese 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.

Project description:Introduction: Mal de Debarquement Syndrome (MdDS) is a poorly understood neurological disorder affecting mostly perimenopausal women. MdDS has been hypothesized to be a maladaptation of the vestibulo-ocular reflex, a neuroplasticity disorder, and a consequence of neurochemical imbalances and hormonal changes. Our hypothesis considers elements from these theories, but presents a novel approach based on the analysis of functional loops, according to Systems and Control Theory. Hypothesis: MdDS is characterized by a persistent sensation of self-motion, usually occurring after sea travels. We assume the existence of a neuronal mechanism acting as an oscillator, i.e., an adaptive internal model, that may be able to cancel a sinusoidal disturbance of posture experienced aboard, due to wave motion. Thereafter, we identify this mechanism as a multi-loop neural network that spans between vestibular nuclei and the flocculonodular lobe of the cerebellum. We demonstrate that this loop system has a tendency to oscillate, which increases with increasing strength of neuronal connections. Therefore, we hypothesize that synaptic plasticity, specifically long-term potentiation, may play a role in making these oscillations poorly damped. Finally, we assume that the neuromodulator Calcitonin Gene-Related Peptide, which is modulated in perimenopausal women, exacerbates this process thus rendering the transition irreversible and consequently leading to MdDS. Conclusion and Validation: The concept of an oscillator that becomes noxiously permanent can be used as a model for MdDS, given a high correlation between patients with MdDS and sea travels involving undulating passive motion, and an alleviation of symptoms when patients are re-exposed to similar passive motion. The mechanism could be further investigated utilizing posturography tests to evaluate if subjective perception of motion matches with objective postural instability. Neurochemical imbalances that would render individuals more susceptible to developing MdDS could be investigated through hormonal profile screening. Alterations in the connections between vestibular nuclei and cerebellum, notably GABAergic fibers, could be explored by neuroimaging techniques as well as transcranial magnetic stimulation. If our hypothesis were tested and verified, optimal targets for MdDS treatment could be found within both the neural networks and biochemical factors that are deemed to play a fundamental role in loop functioning and synaptic plasticity.

Project description:BackgroundIndividuals with Mal de Debarquement syndrome (MdDS) experience persistent oscillating vertigo lasting for months or years. Transcranial magnetic stimulation (TMS) can modulate the motion perception of MdDS.Materials and methodsTwenty-six TMS naive individuals received single administrations of continuous theta burst stimulation (cTBS) over the occipital cortex, cerebellar vermis, and lateral cerebellar hemisphere, in randomized order. A 0-100 point Visual Analogue Scale was used to assess acute changes in oscillating vertigo severity after each session. Repeated treatments were given over the target that led to the most acute reduction in symptoms. All treatments were performed with neuronavigation using the participant's own brain MRI. The Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS) were assessed weekly at four pretreatment and six posttreatment time points.ResultsTwenty participants chose either the occipital cortex (11) or cerebellar vermis (9) targets as most effective in reducing the oscillating vertigo; one chose lateral cerebellar hemisphere; five chose none. After 10 to 12 sessions of 1,200 pulses over the target of choice, 19 of 25 treatment completers noted ≥ 25% reduction, 12 of 25 ≥50% reduction, and 8 of 25 ≥75% reduction in oscillating vertigo intensity. A one-way repeated measures ANOVA of DHI, MBRS, and HADS scores before and after treatment showed significant reductions in DHI, MBRS, and the HADS Anxiety subscore immediately after treatment with most improvement lasting through posttreatment week 6. There were no significant Depression subscore changes. Participants who had chosen vermis stimulation had comparatively worse balance at baseline than those who had chosen occipital cortex stimulation.ConclusioncTBS over either the occipital cortex or cerebellar vermis is effective in reducing the oscillating vertigo of MdDS acutely and may confer long-term benefits. Sustained improvement requires more frequent treatments.

Project description:Introduction: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a perception of self-motion in the absence of a stimulus, with two onset types: Motion-Triggered and Spontaneous. Currently, the pathophysiology is unknown and consequently, the therapeutic options are limited. One proposed treatment protocol, developed by Dai and colleagues is based on optokinetic stimulation, which aims to re-adapt the vestibular ocular reflex. This study aimed to reproduce the treatment protocol developed by Dai and colleagues and to assess if a placebo effect is present in the treatment protocol and lastly, aimed to further investigate the treatment on MdDS patient outcomes. Method: Twenty-five MdDS patients (13 Motion-Triggered and 12 Spontaneous) were exposed to 5 consecutive days of optokinetic treatment (consisting of exposure to optokinetic stimuli with head movements). Eleven of these 25 patients were also exposed to 2 days of a sham treatment prior to the OKN treatment. Posturography measurements and reported symptoms [e.g., using the visual analog scale (VAS)] of patients were assessed throughout the treatment. Posturography data of the patients was compared with the data of 20 healthy controls. Results: No placebo effect was recorded with any changes in postural data and VAS scale. After the optokinetic treatment, a significant improvement in postural control was observed in 48% of patients, of whom 70% were of the Motion-Triggered subtype (p-values: Area under the Curve-Anterior Posterior < 0.001; Area under the Curve-Medio Lateral p < 0.001, Confidence Ellipse Area (CEA) < 0.001, Velocity < 0.001). Conclusion: The protocol was effective in approximately half of the MdDS patients that took part in the study, with no placebo effect recorded. The Motion-Triggered group responded better to treatment than the Spontaneous group. In addition to this, this study indicates that the greatest postural changes occur within the first 3 days of treatment, suggesting that a shorter protocol is possible. Overall, these findings support what was previously observed in Dai's studies, that optokinetic stimulation can reduce and ease self-motion perception in those with MdDS. Thus, validating the reproducibility of this protocol, suggesting that a consistent and uncomplicated implementation across treatment centers is possible.

Project description:Introduction: Mal de Debarquement Syndrome (MdDS) is a neurological disorder which affects the vestibular system pathways, manifesting as a constant sensation of movement in the form of rocking, bobbing, or swaying. The mechanism of MdDS is poorly understood and there is a lack of awareness amongst medical professionals about the condition. This study aimed to examine treatments and symptom management strategies used by MdDS patients and evaluate their self-reported effectiveness. Method: Motion-Triggered and Spontaneous/Other onset MdDS patients responded to a set of comprehensive questions as a retrospective survey regarding epidemiological details, diagnostic procedures, onset, and symptom triggers, hormonal influences as well as treatments and symptom management strategies used to reduce symptoms. The Motion-Triggered questionnaire was made available through Survey Monkey and the Spontaneous/Other Onset questionnaire through Qualtrics. The link for each questionnaire was made available on online MdDS support groups and on various research websites. Descriptive statistics were used for epidemiological data and Pearson's Chi Square tests were used for comparisons between and within both subtype groups. Results: A total of 370 patients participated in the surveys, with 287 valid responses collected for the section regarding treatment and symptom management strategies. The success of the treatments and symptom management strategies did not vary between subtypes Benzodiazepines/Antidepressants were reported as being most beneficial in reducing symptoms in both groups. Conclusion: This was the first attempt to evaluate the reported success of treatments and symptom management strategies in MdDS patients by assessing the patients' perceived helpfulness. The treatments and symptom management strategies reported to be the most helpful in managing and/or reducing symptoms are proposed to be effective due to their stress-reducing capacities. We hope this study will broaden MdDS awareness and that this study will increase patient knowledge regarding treatments and symptom management strategies that other patients found helpful.

Project description:Objective: To determine whether remotely-monitored transcranial alternating current stimulation (tACS) may be a viable and safe treatment option for Mal de Débarquement Syndrome (MdDS). Background: Mal de Débarquement Syndrome is a neurotological disorder characterized by persistent oscillating vertigo that is triggered by entrainment to passive oscillatory motion such as occurs during water-based travel. Treatment options for MdDS are limited, variably effective, and can be undone by further travel. Design and Methods: This was a remotely-monitored open-label optional extension phase of a double-blind randomized onsite study of tACS for medically refractory MdDS. The primary goal was to determine safety, feasibility, and blinded participant feedback. The secondary goal was to determine efficacy. Thirteen participants (all women), aged 22-67 years, experiencing a duration of illness of 11-72 months, were a subset of 24 individuals who participated in an on-site study of tACS. They had either not responded to the on-site protocol or had relapsed after travel home. Treatment accessories and a tablet controlled tACS stimulator (Pulvinar XCSITE-100) were mailed to participants. Three teaching sessions were performed via webcam followed by on-going remote monitoring of treatment logs and participants' reports through a daily on-line diary and weekly questionnaires. Treatment continued until an effective protocol was administered for 4 weeks and then tapered over 4 weeks. Participants completed a blinded feedback survey and a debriefing interview at the completion of the entire study. Results: Treatment duration ranged from 4 to 31 weeks followed by a 4-week taper accounting for 578 verified sessions. Of the 13 total participants, seven agreed or agreed strongly in the blinded survey that tACS treatment was beneficial; 2) Twelve were comfortable utilizing tACS on their own; 3) Eleven preferred stimulation above their individual alpha frequency; 4) Side effects were generally mild and typical of tACS. In the debriefing interview completed 2-9 months after the last stimulation, five participants reported doing "great," with no to minimal symptoms, four reported doing "good," with moderate symptoms, and four reported no change compared to pre-study baseline. Conclusion: Remotely-monitored tACS may be a safe treatment option for MdDS with the potential for lasting outcomes, increased accessibility, and reduction in travel-related treatment reversal.

Dataset Information

Electrophysiological Signatures of Intrinsic Functional Connectivity Related to rTMS Treatment for Mal de Debarquement Syndrome.

Publications

Electrophysiological Signatures of Intrinsic Functional Connectivity Related to rTMS Treatment for Mal de Debarquement Syndrome.

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