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We present diagnostic criteria for mal de débarquement syndrome (MdDS) for inclusion into the International Classification of Vestibular Disorders. The criteria include the following: 1] Non-spinning vertigo characterized by an oscillatory perception (‘rocking,’ ‘bobbing,’ or ‘swaying’) present continuously or for most of the day; 2] Onset occurs within 48 hours after the end of exposure to passive motion, 3] Symptoms temporarily reduce with exposure to passive motion (e.g. driving), and 4] Symptoms persist for >48 hours. MdDS may be designated as “in evolution,” if symptoms are ongoing but the observation period has been less than 1 month; “transient,” if symptoms resolve at or before 1 month and the observation period extends at least to the resolution point; or “persistent” if symptoms last for more than 1 month. Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety. Features that distinguish MdDS from vestibular migraine, motion sickness, and persistent postural perceptual dizziness (PPPD) are reviewed. Motion-moderated oscillatory vertigo can also occur without a motion trigger, typically following another vestibular disorder, a medical illness, heightened psychological stress, or metabolic disturbance. Terminology for this non-motion triggered presentation has been varied as it has features of both MdDS and PPPD. Further research is needed into its phenomenological and biological relationship to MdDS, PPPD, and other vestibular disorders.

The virtual practice has made major advances in the way that we care for patients in the modern era. The culture of virtual practice, consulting, and telemedicine, which had started several years ago, took an accelerated leap as humankind was challenged by the novel coronavirus pandemic (COVID19). The social distancing measures and lockdowns imposed in many countries left medical care providers with limited options in evaluating ambulatory patients, pushing the rapid transition to assessments via virtual platforms. In this novel arena of medical practice, which may form new norms beyond the current pandemic crisis, we found it critical to define guidelines on the recommended practice in neurotology, including remote methods in examining the vestibular and eye movement function. The proposed remote examination methods aim to reliably diagnose acute and subacute diseases of the inner-ear, brainstem, and the cerebellum. A key aim was to triage patients into those requiring urgent emergency room assessment versus non-urgent but expedited outpatient management. Physicians who had expertise in managing patients with vestibular disorders were invited to participate in the taskforce. The focus was on two topics: (1) an adequate eye movement and vestibular examination strategy using virtual platforms and (2) a decision pathway providing guidance about which patient should seek urgent medical care and which patient should have non-urgent but expedited outpatient management. Electronic supplementary material The online version of this article (10.1007/s12311-020-01178-8) contains supplementary material, which is available to authorized users.

Background Electroencephalography (EEG) studies suggest that major depressive disorder (MDD) is associated with lower left than right frontal brain activity (asymmetry), a pattern appearing stronger in women than men, and when elicited during emotionally-relevant paradigms versus an uncontrolled resting state. However, it is unclear whether this asymmetry pattern generalizes to the common presentation of MDD with co-occurring anxiety. Moreover, asymmetry may differ for anxiety subtypes, wherein anxious apprehension (AnxApp: worry characteristic of generalized anxiety disorder) appears left-lateralized, but anxious arousal (AnxAro: panic characteristic of social anxiety, posttraumatic stress, and panic disorders) may be right-lateralized. Methods This analysis attempted to replicate frontal EEG asymmetry patterns using functional magnetic resonance imaging (fMRI). Participants completed clinical interviews and a monetary incentive delay (MID) task during fMRI recording. We compared five groups of right-handed women from the Tulsa 1000 study, MDD (n=40), MDD-AnxApp (n=26), MDD-AnxAro (n=34), MDD-Both (with AnxApp and AnxAro; n=26), and healthy controls (CTL; n=24), as a function of MID anticipation condition (no win/loss, win, loss) and hemisphere on frontal blood oxygen-level-dependent (BOLD) signal. Results CTL exhibited higher bilateral superior, middle, and inferior middle frontal gyrus BOLD signal than the four MDD groups for high arousal (win and loss) conditions. However, frontal attenuations were unrelated to current depression/anxiety symptoms, suggestive of a trait as opposed to a state marker. Limitations This was a cross-sectional analysis restricted to women. Conclusions Reduced prefrontal cortex recruitment during processing of both positively and negatively valenced stimuli is consistent with the emotion context insensitivity theory of MDD.

Mal de debarquement syndrome (MdDS) is a disorder of persistent vertigo characterized by a feeling of oscillation such as rocking, bobbing, or swaying. It is triggered by passive motion, typically by exposure to water, air, or land transportation. This syndrome affects middle-aged individuals who are predominantly women. MdDS presents as a balance disorder that carries significant risk of morbidity due to both the direct effects of balance impairment and associated symptoms of fatigue, cognitive slowing, and visual motion intolerance. The Barany Society will be publishing criteria for diagnosing persistent MdDS. In addition, more insight has been gained into the pathophysiology of MdDS, with current hypotheses pointing to a cerebral and cerebellar basis. Treatments have expanded beyond medication trials, and now include the use of noninvasive brain stimulation and readaptation of the vestibulo-ocular reflex.

Determining the etiology of disorders that manifest with chronic dizziness can seem a daunting task, but extracting some basic elements of the patient's history can reduce the differential diagnosis significantly. This includes determining initial triggers, timing of symptoms, associated features, and exacerbating factors. This article covers distinct causes of chronic dizziness including persistent postural perceptual dizziness, mal de débarquement syndrome, motion sickness and visually induced motion sickness, bilateral vestibulopathy, and persistent dizziness after mild concussion.To date, none of the disorders above has a cure but are considered chronic syndromes with fluctuations that are both innate and driven by environmental stressors. As such, the mainstay of therapy for chronic disorders of dizziness involves managing factors that exacerbate symptoms and adding vestibular rehabilitation or cognitive-behavioral therapy alone or in combination, as appropriate. These therapies are supplemented by serotonergic antidepressants that modulate sensory gating and reduce anxiety. Besides expectation management, ruling out concurrent disorders and recognizing behavioral and lifestyle factors that affect symptom severity are critical issues in reducing morbidity for each disorder.Many syndromes of chronic dizziness can be diagnosed by recognition of key features, although many symptoms overlap between these groups. Symptoms may be manageable and improve with time, but they are often incompletely relieved.

Objective. Heterogeneous clinical responses to treatment with non-invasive brain stimulation are commonly observed, making it necessary to determine personally optimized stimulation parameters. We investigated neuroimaging markers of effective brain targets of treatment with continuous theta burst stimulation (cTBS) in mal de débarquement syndrome (MdDS), a balance disorder of persistent oscillating vertigo previously shown to exhibit abnormal intrinsic functional connectivity. Approach. Twenty-four right-handed, cTBS-naive individuals with MdDS received single administrations of cTBS over one of three stimulation targets in randomized order. The optimal target was determined based on the assessment of acute changes after the administration of cTBS over each target. Repetitive cTBS sessions were delivered on three consecutive days with the optimal target chosen by the participant. Electroencephalography (EEG) was recorded at single-administration test sessions of cTBS. Simultaneous EEG and functional MRI data were acquired at baseline and after completion of 10–12 sessions. Network connectivity changes after single and repetitive stimulations of cTBS were analyzed. Main results. Using electrophysiological source imaging and a data-driven method, we identified network-level connectivity changes in EEG that correlated with symptom responses after completion of multiple sessions of cTBS. We further determined that connectivity changes demonstrated by EEG during test sessions of single administrations of cTBS were signatures that could predict optimal targets. Significance. Our findings demonstrate the effect of cTBS on resting state brain networks and suggest an imaging-based, closed-loop stimulation paradigm that can identify optimal targets during short-term test sessions of stimulation. ClinicalTrials.gov Identifier: NCT02470377.

Transcranial direct current stimulation (tDCS) has been studied as an adjunctive therapeutic option to alter maladaptive cortical excitability, activity, and connectivity associated with chronic substance use via the application of a weak direct current through the brain. The underlying mechanism of action remains ambiguous, however. We present a randomized, triple-blind, sham-controlled, clinical trial with two parallel arms conducted to determine the neural substrates of tDCS effects on drug craving using an fMRI drug cue reactivity paradigm. Sixty participants with methamphetamine use disorder were randomly assigned to two groups: 30 participants to active tDCS (5×7 cm2, 2 mA, for 20 minutes, anode/cathode over the F4/Fp1 in EEG 10-20 standard system) and 30 participants to the sham group. Neuroimaging data of a methamphetamine cue reactivity (MCR) task were collected immediately before and after stimulation with subjective craving assessed before, after, and during fMRI scans. There was a significant reduction in self-reported craving after stimulation (main effect of time) without any significant effect of group, time, or by group-time interaction. Our whole-brain analysis demonstrated that brain activation decreased in all parts of the brain in the second (post-stimulation) MCR imaging session after sham stimulation (habituation) but this uniform decrease did not occur throughout the brain in the active group. There were significant interactions between the group (active vs. sham) and time (after vs. before stimulation) in five main regions; medial frontal gyrus, anterior insula, inferior parietal lobule, precuneus, and inferior frontal gyrus with higher activations after active stimulation. We simulated computational head models for each individual. There was a significant effect of group in the relationship between level of current in the above-mentioned significant clusters and changes in task-modulated activation. We also found that brain regions with the highest electric fields in the prefrontal cortex showed a significant time by group interaction in task-modulated connectivity (psychophysiological interaction during MCR) in the frontoparietal network. In this two-parallel-arms triple-blind randomized control trial, we did not find any significant effect of the one session of active F4/Fp1 tDCS on drug craving self-report compared to sham stimulation. However, connectivity differences induced by active compared to sham stimulation suggested some potential mechanisms of tDCS to modulate neural response to drug cues among people with methamphetamine use disorder.HighlightsNo significant effect of active stimulation compared to sham was found in self-reported craving.Uniform habituation in response to drug cues happens only after the sham stimulation.MFG, IFG, insula, IPL, and precuneus show significantly higher responses to cues after active stimulation.Head models showed our stimulation montage (F4-Fp1) induces the highest level of current in rSFG.Cue reactivity modulated connectivity was significantly reduced by active stimulation between rSFG and rPPC.

OBJECTIVES Persistent oscillating vertigo that occurs after entrainment to periodic motion is known as Mal de Debarquement Syndrome (MdDS). Down-modulation of this oscillating vertigo is associated with reduction in long-range resting-state functional connectivity between fronto-parieto-occipital regions. In order to determine the association between this oscillating vertigo and hypersynchrony as measured by the auditory steady-state response (ASSR), we investigated the differences in ASSR between individuals with MdDS and healthy controls as well as the change in ASSR in individuals with MdDS before and after treatment with transcranial alternating current stimulation (tACS). MATERIALS AND METHODS Individuals with treatment refractory MdDS lasting at least six months received single administrations of fronto-parieto-occipital tACS in an "n-of-1" double-blind randomized design: alpha-frequency in-phase, alpha-frequency antiphase, and gamma frequency antiphase control. The treatment protocol that led to the most acute reduction in symptoms and improved balance was administered for 10-12 sessions given over three days (each session 20-min at 2-4 mA). RESULTS Twenty-four individuals with MdDS participated (mean age 53.0 ± 11.8 years [range: 22-66 years, median: 57.0 years]; mean duration of illness 38.6 ± 53.4 months [range: 6-240 months, median: 18.0 months]). Individuals with MdDS had elevated ASSR compared to healthy controls at baseline (t11 = 5.95, p

To report on the psychological, personality, and behavioral profiles of individuals with persistent Mal de Debarquement Syndrome (MdDS). Individuals with MdDS who participated in neuromodulation clinical trials between May 2013 and June 2019 completed a series of standardized psychological questionnaires and underwent the Structural Clinical Interview for DSM-IV-TR (SCID) for specific psychiatric diagnoses. All data reported are from baseline assessments prior to any study interventions. Scores were compared to population norms for adult women. Complete datasets were available for 55 women. Mean age of onset of MdDS was 49.0 ± 11.9 years (range 22–69 years) and median duration of illness of 22 months (6 months–20 years). SCID results were as follows: healthy (48.1%), any lifetime Major Depressive Disorder (35.2%, 7.4% current); any lifetime history of anxiety disorder (11.1%); any lifetime substance use disorders (18.5%, 0% current). Compared to population norms, the MdDS group scored significantly higher on the Patient Health Questionnaire-9 depression scale and the Generalized Anxiety Disorder 7 (GAD-7) anxiety scale, but only the GAD-7 correlated with symptom severity. The NEO-Five Factor Inventory for personality, Positive and Negative Affect Schedule, Behavioral Inhibition System/Behavioral Activation System Scale, and the Empathy Quotient metrics did not correlate with duration of illness. Disability assessed by the 12-item World Health Organization Disability Assessment Schedule 2.0 was 25.7 ± 6.7, comparable to reports for concussion. Disability correlated with severity of depression, anxiety, neuroticism, and affect but not to severity of MdDS. Psychological profiles of MdDS relate to disability but not to duration of illness.

We present diagnostic criteria for motion sickness, visually induced motion sickness (VIMS), motion sickness disorder (MSD), and VIMS disorder (VIMSD) to be included in the International Classification of Vestibular Disorders. Motion sickness and VIMS are normal physiological responses that can be elicited in almost all people, but susceptibility and severity can be high enough for the response to be considered a disorder in some cases. This report provides guidelines for evaluating signs and symptoms caused by physical motion or visual motion and for diagnosing an individual as having a response that is severe enough to constitute a disorder. The diagnostic criteria for motion sickness and VIMS include adverse reactions elicited during exposure to physical motion or visual motion leading to observable signs or symptoms of greater than minimal severity in the following domains: nausea and/or gastrointestinal disturbance, thermoregulatory disruption, alterations in arousal, dizziness and/or vertigo, headache and/or ocular strain. These signs and/or symptoms occur during the motion exposure, build as the exposure is prolonged, and eventually stop after the motion ends. Motion sickness disorder and VIMSD are diagnosed when recurrent episodes of motion sickness or VIMS are reliably triggered by the same or similar stimuli, severity does not significantly decrease after repeated exposure, and signs/symptoms lead to activity modification, avoidance behavior, or aversive emotional responses. Motion sickness/MSD and VIMS/VIMSD can occur separately or together. Severity of symptoms in reaction to physical motion or visual motion stimuli varies widely and can change within an individual due to aging, adaptation, and comorbid disorders. We discuss the main methods for measuring motion sickness symptoms, the situations conducive to motion sickness and VIMS, and the individual traits associated with increased susceptibility. These additional considerations will improve diagnosis by fostering accurate measurement and understanding of the situational and personal factors associated with MSD and VIMSD.

The combination of non-invasive brain stimulation interventions with human brain mapping methods have supported research beyond correlational associations between brain activity and behavior. Functional MRI (fMRI) partnered with transcranial electrical stimulation (tES) methods, i.e., transcranial direct current (tDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation, explore the neuromodulatory effects of tES in the targeted brain regions and their interconnected networks and provide opportunities for individualized interventions. Advances in the field of tES-fMRI can be hampered by the methodological variability between studies that confounds comparability/replicability. In order to explore variability in the tES-fMRI methodological parameter space (MPS), we conducted a systematic review of 222 tES-fMRI experiments (181 tDCS, 39 tACS and 2 tRNS) published before February 1, 2019, and suggested a framework to systematically report main elements of MPS across studies. Publications dedicated to tRNS-fMRI were not considered in this systematic review. We have organized main findings in terms of fMRI modulation by tES. tES modulates activation and connectivity beyond the stimulated areas particularly with prefrontal stimulation. There were no two studies with the same MPS to replicate findings. We discuss how to harmonize the MPS to promote replication in future studies.

Psychological theories of suicide suggest that certain traits may reduce aversion to physical threat and increase the probability of transitioning from suicidal ideation to action. Here, we investigated whether blunted sensitivity to bodily signals is associated with suicidal action by comparing individuals with a history of attempted suicide to a matched psychiatric reference sample without suicide attempts. We examined interoceptive processing across a panel of tasks: breath-hold challenge, cold-pressor challenge, and heartbeat perception during and outside of functional magnetic resonance imaging. Suicide attempters tolerated the breath-hold and cold-pressor challenges for significantly longer and displayed lower heartbeat perception accuracy than non-attempters. These differences were mirrored by reduced activation of the mid/posterior insula during attention to heartbeat sensations. Our findings suggest that suicide attempters exhibit an ‘interoceptive numbing’ characterized by increased tolerance for aversive sensations and decreased awareness of non-aversive sensations. We conclude that blunted interoception may be implicated in suicidal behavior., eLife digest The human brain closely monitors body signals essential for our survival, including our heartbeat, our breathing and even the temperature of our skin. This mostly unconscious process is called interoception. It helps people perceive potential or actual threats and helps them to respond appropriately. For example, a person charged by a wild animal will act instinctively to run, fight or freeze. Unlike most creatures, humans show an ability to counteract these survival instincts, and are capable of intentionally engaging in behaviors that result in physical harm. Recent increases in the rate of suicide have made it more urgent to try to understand what leads to this behavior in humans. Now, DeVille et al. show that people with psychiatric disorders who have survived a suicide attempt have blunted interoception. In four experiments, people with a history of suicide attempts were compared to another group of individuals without a history of suicide attempts. The groups were carefully matched such that there were no significant differences in the demographic and clinical characteristics of the two groups, including in terms of their age, sex, body mass index and psychiatric symptoms. Both groups completed uncomfortable tasks like holding their breath or keeping their hand in icy cold water. The participants also completed two tasks that required them to focus on their own heartbeat, one of which was paired with functional magnetic resonance imaging. Those with a history of suicide attempts held their breath and kept their hand in cold water for longer, and also were less in tune with their heart rate. This “interoceptive numbing” was associated with less activity in part of the brain called the insular cortex. These differences could not be explained by the individuals having a psychiatric disorder or a history of considering suicide, or by them taking psychiatric medications. Instead, the interoceptive numbing was most often seen in individuals who made an attempt on their own life. The experiments identify physical characteristics that may differentiate people who attempt suicide from those who do not. This lays the groundwork for future research aimed at identifying biological indicators of suicide risk. More studies are needed to verify the results. If the results are verified, the next step would be prospective studies to determine whether measuring interoception can help clinicians predict who is at risk of a suicide attempt. If it does, it might give clinicians a new tool to try to prevent suicide by ensuring those at greatest risk receive appropriate care.

The phenomena of migraine headache and vertigo share many epidemiological, anatomical, and clinical characteristics. The historically parallel development of the neuroscience of each field has formally intersected in the development of consensus criteria for vestibular migraine and the inclusion of vestibular migraine in the International Classification of Headache Disorders. Differences exist in the temporal profile of head pain and vertigo as manifestations of migraine, which can obscure the association. However, the growing body of evidence on the common demographic, neurochemical signature, and treatment responses of pain and vestibular symptoms indicate that they exist as symptoms of a common syndrome, one which can only be fully understood by recognizing the significance of each kind of manifestation.

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.

Biological Psychiatry, 3 (6), ISSN:0006-3223, ISSN:1873-2402

Repetitive transcranial magnetic stimulation (rTMS) has been used in experimental protocols to treat mal de debarquement syndrome (MdDS), a neurological condition that represents a maladaptive brain state resulting from entrainment to external oscillating motion. Medical treatments and biomarkers for MdDS remain limited but neuromodulation with rTMS has shown evidence for therapeutic effects. This study took a neuroimaging approach to examine the neuromodulatory effect of rTMS on MdDS. Twenty individuals with MdDS underwent five daily treatments of rTMS over bilateral dorsolateral prefrontal cortex (DLPFC). Participants received 1 Hz over right DLPFC (1200 pulses) followed by 10 Hz over left DLPFC (2000 pulses). Resting state functional magnetic resonance imaging was acquired before and after treatments to determine functional connectivity changes associated with a positive treatment effect. A single-subject-based analysis protocol was developed to capture the degree of resting state functional connectivity (RSFC) between the rTMS target and the entorhinal cortex (EC), an area previously shown to be hypermetabolic in MdDS. Our results showed that rocking motion perception in subjects was modulated by rTMS over the DLPFC. Improvements in symptoms correlated most strongly with a post-rTMS reduction in functional connectivity between the left EC and the precuneus, right inferior parietal lobule, and the contralateral EC, which are part of the posterior default mode network. Positive response to rTMS correlated with higher baseline RSFC between the DLPFC and the EC. Our findings suggest that baseline prefrontal-limbic functional connectivity may serve as a predictor of treatment response to prefrontal stimulation in MdDS and that RSFC may serve as a dynamic biomarker of symptom status.

Diffusion tensor imaging (DTI) has often been used to examine white matter (WM) tract abnormalities in depressed subjects, but these studies have yielded inconsistent results, probably, due to gender composition or small sample size. In this study, we applied different analysis pipelines to a relatively large sample of individuals with depression to determine whether previous findings in depression can be replicated with these pipelines. We used a "standard" DTI algorithm and maps computed through a free-water (FW) corrected DTI. This latter algorithm is able to identify and separate the effects of extracellular FW on DTI metrics. Additionally, skeletonized and WM voxel-based analysis (VBA) methods were used. Using the skeletonized method, DTI maps showed lower fractional anisotropy (FA) in depressed subjects in the left brain hemisphere, including the anterior thalamic radiation (ATR L), cortical spinal tract (CST L), inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus (SLF L). Differences in radial diffusivity (RD) were also found. For the VBA using RD, we found different results when we used FW uncorrected and corrected DTI metrics. Relative to the VBA approach, the skeletonized analysis was able to identify more clusters where WM integrity was altered in depressed individuals. Different significant correlations were found between RD and the Patient Health Questionnaire in the CST L, and SLF L. In conclusion, the skeletonized method revealed more clusters than the VBA and individuals with depression showed multiple WM abnormalities, some of which were correlated with disease severity Hum Brain Mapp 38:4690-4702, 2017. © 2017 Wiley Periodicals, Inc.

Background Individuals 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 methods Twenty-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. Results Twenty 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. Conclusion cTBS 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.

Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used to treat many neurological and neuropsychiatric disorders. However, the clinical response is heterogeneous mainly due to our inability to predict the effect of rTMS on the human brain. Our previous investigation based on functional magnetic resonance imaging (fMRI) suggested that neuroimaging-guided navigation for rTMS could be informed by understanding connectivity patterns that correlate with treatment response. In this study, 20 individuals with a balance disorder called Mal de Debarquement Syndrome completed high-density resting-state electroencephalogram (EEG) and fMRI recordings before and after 5 days of rTMS stimulation over both dorsolateral prefrontal cortices. Based on temporal independent component analysis of source-level EEG data, large-scale electrophysiological resting-state networks were reconstructed and connectivity values in each individual were quantified both before and after treatment. Our results show that high-density, resting-state EEG can reveal connectivity changes in brain networks after rTMS that correlate with symptom changes. The connectivity changes measured by EEG were primarily superficial cortical areas that correlate with previously shown default mode network changes revealed by fMRI. Further, higher baseline EEG connectivity values in the primary visual cortex were predictive of symptom reduction after rTMS. Our findings suggest that multimodal EEG and fMRI measures of brain networks can be biomarkers that correlate with the treatment effect of rTMS. Since EEG is compatible with rTMS, real-time navigation based on an EEG neuroimaging marker may augment rTMS optimization.

International audience; There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data - emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

Background Mal de debarquement syndrome is a medically refractory disorder characterized by chronic rocking dizziness that occurs after exposure to passive motion. Repetitive transcranial magnetic stimulation (rTMS) can acutely suppress the rocking dizziness but treatment options that extend the benefit of rTMS are needed. Objectives 1) To determine whether transcranial direct current stimulation (tDCS) added after rTMS can extend the benefit of rTMS; 2) to determine whether participants can safely perform tDCS at home. Methods Participants were given five days of rTMS (1 Hz right DLPFC/10 Hz left DLPFC in right-handers, vice versa in left-handers), according to a previously piloted protocol. They received three days of training on tDCS self-administration and were then randomized to either real or sham tDCS for four-weeks (anode left DLPFC/cathode right DLPFC for right-handers, vice versa for left-handers). Results Twenty-three participants completed the study. Those who received real tDCS after rTMS showed significant improvements in the degree of rocking perception as measured by the MdDS Balance Rating Scale and anxiety ratings by Week 4 of tDCS and a trend for improvement on the Dizziness Handicap Inventory. Two rTMS non-responders responded well to subsequent open-label tDCS. Side effects were mild and not different between real and sham tDCS. There were no episodes of skin burns in a group total of 556 sessions of tDCS. Satisfaction was rated high. Conclusions Home-based tDCS can be performed safely and may be beneficial in selected individuals. Adequate teaching, automatic device safety features, and a good communications infrastructure are components of successful home therapy.

Background Childhood trauma is a significant risk factor for adult psychopathology. Previous investigations have implicated childhood trauma–related structural changes in anterior cingulate, dorsolateral prefrontal and orbitofrontal cortex, and hippocampus. Using a large transdiagnostic community sample, the goal of this investigation was to differentially associate regional gray matter (GM) volume with childhood trauma severity specifically, distinct from adult psychopathology. Methods A total of 577 non–treatment-seeking adults (n = 207 men) completed diagnostic, childhood trauma, and structural magnetic resonance imaging assessments with regional GM volume estimated using FreeSurfer. Elastic net analysis was conducted in a nested cross-validation framework, with GM volumes, adult psychopathology, age, education, sex, and magnetic resonance imaging coil type as potential predictors for childhood trauma severity. Results Elastic net identified age, education, sex, medical condition, adult psychopathology, and 13 GM regions as predictors of childhood trauma severity. GM regions identified included right caudate; left pallidum; bilateral insula and cingulate sulcus; left superior, inferior, and orbital frontal regions; and regions within temporal and parietal lobes and cerebellum. Conclusions Results from this large, transdiagnostic sample implicate GM volume in regions central to current neurobiological theories of trauma (e.g., prefrontal cortex) as well as additional regions involved in reward, interoceptive, attentional, and sensory processing (e.g., striatal, insula, and parietal/occipital cortices). Future longitudinal studies examining the functional impact of structural changes in this broader network of regions are needed to clarify the role each may play in longer-term outcomes following trauma.

Multimodal neuroimaging, such as combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), are being increasingly used to investigate the human brain in healthy and diseased conditions. However, certain neuroimaging data are typically acquired in different body positions, e.g., supine fMRI and upright EEG, overlooking the effect of body position on signal characteristics. In the current study we examined EEG signals in three different positions, i.e., supine, standing and sitting, in patients with a balance disorder called mal de debarquement syndrome (MdDS). Individuals with MdDS experience a chronic illusion of self-motion triggered by prolonged exposure to passive motion, such as from sea or air travel. The degree of perception of rocking dizziness is modulated by body position, suggesting a physiological effect related to body positions. In the present study, EEG features were quantified as peak frequency, peak amplitude, and average amplitude of the alpha band due to its strongest signal characteristics compared to other frequencies. The effect of body position was examined in EEG features from data acquired before and after the individuals received treatment with repetitive transcranial magnetic stimulation. Our results indicate a significant effect of body positions on the EEG signals in MdDS.

Mal de debarquement syndrome (MdDS) is a neurological condition typically characterized by a sensation of motion, which in most cases manifests after disembarking from a vehicle (e.g., boat, plane, and car). However, the same symptoms can also occur spontaneously. Two main theories of the pathophysiology of MdDS are briefly summarized here. In this perspective, we aimed to report the most recent findings on neuroimaging studies related to MdDS, as well as to suggest further potential research questions that could be addressed with the use of neuroimaging techniques. A detailed analysis of previous work on MdDS has led to five main research questions that could be addressed in new neuroimaging studies. Furthermore, in this perspective, we propose new stepping-stones to addressing critical research questions related to MdDS and its pathophysiology. We propose considerations for new studies, as well as a detailed analysis of the current limitations and challenges present when studying MdDS patients. We hope that our examination of the nuances of MdDS as a neurological disorder will contribute to more directed research on this topic.

Mal de Debarquement Syndrome (MdDS) is an enigmatic neurotological disorder with high morbidity, psychosocial burden, and few treatment options. Fortunately, there has been recent growth in scientific interest in understanding the biological basis of and in treating MdDS. Recent studies using functional neuroimaging have shown increased glucose metabolism in the left entorhinal cortex (EC) and amygdala in the setting of decreased prefrontal and temporal cortex metabolism in subjects with persistent MdDS. The EC is a key player in processing and gating spatial information to be stored in the hippocampus and is a major driver of brain oscillations. A limbic focus may also be key to spontaneous MdDS-like symptoms occurring in individuals with a history of anxiety or chronic stress. Treatment with repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex can decrease the rocking dizziness of MdDS, with successful responses associated with decreases in the coherence between brain networks with nodes in the parietal and occipital lobes. A new theory of MdDS is proposed as pathology secondary to entrainment of intrinsic brain networks driven by oscillatory motion exposure coupled with an inability to subsequently desynchronize the activity of these nodes. Future treatment strategies may be directed toward unyoking these networks.

Repetitive transcranial magnetic stimulation (rTMS) has been increasingly explored for many neurological and neuropsychiatric conditions. However, the response rate is variable depending on baseline conditions. Optimizing rTMS protocols to improve treatment effects and response rates will depend on reliably assessing brain state conditions. In this regard, neural activity guided optimization has shown potential in several neuroimaging studies. In this paper, we present our ongoing work on optimizing rTMS treatment of a balance disorder called Mal de Debarquement Syndrome (MdDS), a motion perception disorder caused by entrainment to background motion. Our previous work has revealed that a neuroimaging marker of resting state functional connectivity may help predict therapeutic effect. Motivated by our previous pilot study with fMRI, the present study aims to extend the investigation to EEG data that were simultaneously acquired with fMRI, with the aim of transferring the fMRI imaging marker to a more accessible neural recording technology. Our current findings demonstrate that integrating EEG with fMRI measures of neural synchrony and functional connectivity may hold promise in optimizing rTMS protocols.

Functional intrinsic brain networks (IBNs) has been widely studied due to its close relationship to different brain functions and diseases. In these studies, linear metrics, e.g., correlation, have been commonly used in identifying brain networks, especially on functional magnetic resonance imaging (fMRI) data. However, nonlinear mechanism is believed to exist in forming brain networks. In the present study, we investigated the performance of a nonlinear metric, i.e., phase coherence, in probing brain networks, as compared with a linear metric, i.e., power correlation. Specifically, individual IBNs were firstly obtained by a time-frequency independent component analysis (tfICA), and then the interaction among them were probed using either phase coherence (inter-component phase coherence, ICPC) or power correlation coefficient (PCC). We examined them using high-density resting-state electroencephalography (EEG) data from a group of patients with a balance disorder who received repetitive transcranial magnetic stimulation (rTMS) treatments. The results indicated that the use of ICPC indicated more detections of significant connectivity crossing multiple brain regions in various frequency bands than PCC. Moreover, consistent treatment-related network changes, as compared with previous neuroimaging findings, in this brain disorder were more successfully detected with ICPC. Therefore, it is important to use nonlinear metric in characterizing interactions between different brain regions and IBNs.

Diffusion tensor imaging (DTI) has often been used to examine white matter (WM) tract abnormalities in depressed subjects, but these studies have yielded inconsistent results, probably, due to gender composition or small sample size. In this study, we applied different analysis pipelines to a relatively large sample of individuals with depression to determine whether previous findings in depression can be replicated with these pipelines. We used a “standard” DTI algorithm and maps computed through a free‐water (FW) corrected DTI. This latter algorithm is able to identify and separate the effects of extracellular FW on DTI metrics. Additionally, skeletonized and WM voxel‐based analysis (VBA) methods were used. Using the skeletonized method, DTI maps showed lower fractional anisotropy (FA) in depressed subjects in the left brain hemisphere, including the anterior thalamic radiation (ATR L), cortical spinal tract (CST L), inferior fronto‐occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus (SLF L). Differences in radial diffusivity (RD) were also found. For the VBA using RD, we found different results when we used FW uncorrected and corrected DTI metrics. Relative to the VBA approach, the skeletonized analysis was able to identify more clusters where WM integrity was altered in depressed individuals. Different significant correlations were found between RD and the Patient Health Questionnaire in the CST L, and SLF L. In conclusion, the skeletonized method revealed more clusters than the VBA and individuals with depression showed multiple WM abnormalities, some of which were correlated with disease severity Hum Brain Mapp 38:4690–4702, 2017. © 2017 Wiley Periodicals, Inc.