Brain-wide neural co-activations in resting human.

Spontaneous neural activity in human as assessed with resting-state functional magnetic resonance imaging (fMRI) exhibits brain-wide coordinated patterns in the frequency of  < 0.1 Hz. However, understanding of fast brain-wide networks at the timescales of neuronal events (milliseconds to sub-seconds) and their spatial, spectral, and transitional characteristics remain limited due to the temporal constraints of hemodynamic signals. With milli-second resolution and whole-head coverage, scalp-based electroencephalography (EEG) provides a unique window into brain-wide networks with neuronal-timescale dynamics, shedding light on the organizing principles of brain functions. Using the state-of-the-art signal processing techniques, we reconstructed cortical neural tomography from resting-state EEG and extracted component-based co-activation patterns (cCAPs). These cCAPs revealed brain-wide intrinsic networks and their dynamics, indicating the configuration/reconfiguration of resting human brains into recurring and transitional functional states, which are featured with the prominent spatial phenomena of global patterns and anti-state pairs of co-(de)activations. Rich oscillational structures across a wide frequency band (i.e., 0.6 Hz, 5 Hz, and 10 Hz) were embedded in the nonstationary dynamics of these functional states. We further identified a superstructure that regulated between-state immediate and long-range transitions involving the entire set of identified cCAPs and governed a significant aspect of brain-wide network dynamics. These findings demonstrated how resting-state EEG data can be functionally decomposed using cCAPs to reveal rich dynamic structures of brain-wide human neural activations.

Transcranial direct current stimulation to modulate fMRI drug cue reactivity in methamphetamine users: A randomized clinical trial.

Transcranial direct current stimulation (tDCS) has been studied as a therapeutic option to alter maladaptive brain functions associated with chronic substance use. We present a randomized, triple-blind, sham-controlled, clinical trial to determine the neural substrates of tDCS effects on drug craving. Sixty participants with methamphetamine use disorder were assigned to two groups: active tDCS (5 x 7 cm2 , 2 mA, 20 min, anode/cathode over the F4/Fp1) and sham stimulation. Neuroimaging data of a methamphetamine cue reactivity task were collected immediately before and after stimulation. There was a significant reduction in self-reported craving after stimulation without any significant effect of time-by-group interaction. Our whole-brain analysis demonstrated that there was a global decrease in brain reactivity to cues following sham but not active tDCS. There were significant time-by-group interactions in five main clusters in middle and inferior frontal gyri, anterior insula, inferior parietal lobule, and precuneus with higher activations after active stimulation. There was a significant effect of stimulation type in the relationship between electrical current at the individual level and changes in task-modulated activation. Brain regions with the highest electric current in the prefrontal cortex showed a significant time-by-group interaction in task-modulated connectivity in the frontoparietal network. In this trial, there was no significant effect of the one session of active-F4/Fp1 tDCS on drug craving self-report compared to sham stimulation. However, activation and connectivity differences induced by active compared to sham stimulation suggested some potential mechanisms of tDCS to modulate neural response to drug cues.

Consensus on Virtual Management of Vestibular Disorders: Urgent Versus Expedited Care.

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.

Transcranial Alternating Current Stimulation Reduces Network Hypersynchrony and Persistent Vertigo.

OBJECTIVES: Persistent oscillating vertigo that occurs after entrainment to periodic motion is known as Mal de Débarquement 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 < 0.001). There was a significant decrease in the 40 Hz-ASSR response between responders compared to nonresponders to tACS (t-test, t15 = -2.26, p = 0.04). Both in-phase and anti-phase alpha tACS lead to symptom improvement but only antiphase alpha-tACS led to a significant decrease of 40 Hz-ASSR (t-test, t12 = -9.6, p < 0.001). CONCLUSIONS: Our findings suggest that tACS has the potential to reduce network-level hypersynchrony and pathological susceptibility to entrainment by sensory input. To the best of our knowledge, this is the first successful demonstration of desynchronization by noninvasive brain stimulation leading to reduced vertigo. Other disease states associated with pathological functional coupling of neuronal networks may similarly benefit from this novel approach.

Mal de Debarquement Syndrome.

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.

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

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.

Comparison of two different analysis approaches for DTI free-water corrected and uncorrected maps in the study of white matter microstructural integrity in individuals with depression.

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.

Episodic ataxia type 1: clinical characterization, quality of life and genotype-phenotype correlation.

Episodic ataxia type 1 is considered a rare neuronal ion channel disorder characterized by brief attacks of unsteadiness and dizziness with persistent myokymia. To characterize the natural history, develop outcome measures for future clinical trials, and correlate genotype with phenotype, we undertook an international, prospective, cross-sectional study. Thirty-nine individuals (51% male) were enrolled: median age 37 years (range 15-65 years). We identified 10 different pathogenic point mutations in KCNA1 that accounted for the genetic basis of 85% of the cohort. Participants with KCNA1 mutations were more likely to have a positive family history. Analysis of the total cohort showed that the first episode of ataxia occurred before age 20 in all but one patient, with an average age of onset of 7.9 years. Physical exertion, emotional stress and environmental temperature were the most common triggers for attacks. Attack frequency ranged from daily to monthly, even with the same KCNA1 genotype. Average attack duration was in the order of minutes. Ten participants (26%) developed permanent cerebellar signs, which were related to disease duration. The average Scale for the Assessment and Rating of Ataxia score (SARA, a standardized measure of cerebellar dysfunction on clinical examination, scores range from 0-40) was an average of 3.15 for all participants (range 0-14), but was only 2 in those with isolated episodic ataxia compared with 7.7 in those with progressive cerebellar ataxia in addition to episodic ataxia. Thirty-seven participants completed the SF-36, a quality of life survey; all eight domain norm-based average scores (mean=50) were below normal with mental health being the lowest (41.3) in those with mutation positive episodic ataxia type 1. Scores on SF-36 correlated negatively with attack frequency. Of the 39 participants in the study, 33 harboured mutations in KCNA1 whereas the remaining six had no mutation identified. Episodic ataxia type 1 phenocopies have not been described previously and we report their clinical features, which appear to be different to those with a KCNA1 mutation. This large prospective study of both genetically confirmed episodic ataxia type 1 and episodic ataxia type 1 phenocopies provides detailed baseline characteristics of these disorders and their impact on participants. We found that attacks had a significant effect on quality of life. Unlike previous studies, we found that a significant number of individuals with genetically confirmed episodic ataxia type 1 (21%) had accumulated persistent cerebellar symptoms and signs. These data will enable the development of outcome measures for clinical trials of treatment.

Rocking dizziness and headache: a two-way street.

BACKGROUND: Chronic rocking dizziness, often described as the feeling of being on a boat, is classically triggered by prolonged exposure to passive motion. Patients with this motion-triggered sensation of rocking, which is also known as MAL DE DEBARQUEMENT SYNDROME , often develop new onset headaches along with the dizziness. Chronic rocking dizziness has also been noted in vestibular migraine, occurring without a motion trigger. We sought to clarify the association between both motion-triggered (MT) and non-motion-triggered (non-MT) chronic rocking dizziness and headache history. METHODS: Our methods included questionnaire and interview study of subjects with either MT or non-MT chronic rocking dizziness. RESULTS: Onset of headaches was earlier in patients with non-MT rocking dizziness (median 26 years: MT; 16 years: non-MT). In MT subjects, there was a bimodal peak of age of onset of headache (20-29 years and 40-49 years). Most headache met criteria for migraine in both groups. By the time that chronic dizziness occurred, both groups had a comparable prevalence of migraine headache (41%: MT; 46%: non-MT). Pre-existing headache usually worsened after the onset of dizziness. DISCUSSION: Though rocking dizziness does not meet current criteria for vestibular migraine, migraine physiology may predispose to, develop in, or worsen with the onset of chronic rocking dizziness.

Spinning Through History: Evolution of the Concept of Vestibular Migraine.

Vestibular migraine represents a growing public health problem, imposing enormous societal burdens in the form of patient suffering, loss of productivity, and direct healthcare costs. This raises the question of how we developed our ideas about vestibular migraine and how these ideas shape how we treat it. This review walks through the history of how our conceptualization of migraine and vestibular symptoms evolved, starting with clinical observations in ancient times, inclusion under the umbrella of Meniere's disease, and then separation from Meniere's disease with its own identity. Tradition, clinical observations, and diagnostic criteria developed by professional societies have played prominent roles in building our current concept of vestibular migraine. A review of the ideas that have shaped our current conception of vestibular migraine may help us to see which ones have stood the test of time and which ones should continue to evolve. As in other disciplines, we study history in medicine to be inspired, warned, and sometimes, to be freed.

Double-blind randomized N-of-1 trial of transcranial alternating current stimulation for mal de débarquement syndrome.

BACKGROUND: Mal 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 METHODS: Individuals 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). RESULTS: Of 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. CONCLUSION: Fronto-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].

Psychological assessment of individuals with Mal de Débarquement Syndrome.

OBJECTIVE: To report on the psychological, personality, and behavioral profiles of individuals with persistent Mal de Débarquement Syndrome (MdDS). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Psychological profiles of MdDS relate to disability but not to duration of illness.

Age-related changes of whole-brain dynamics in spontaneous neuronal coactivations.

Human brains experience whole-brain anatomic and functional changes throughout the lifespan. Age-related whole-brain network changes have been studied with functional magnetic resonance imaging (fMRI) to determine their low-frequency spatial and temporal characteristics. However, little is known about age-related changes in whole-brain fast dynamics at the scale of neuronal events. The present study investigated age-related whole-brain dynamics in resting-state electroencephalography (EEG) signals from 73 healthy participants from 6 to 65 years old via characterizing transient neuronal coactivations at a resolution of tens of milliseconds. These uncovered transient patterns suggest fluctuating brain states at different energy levels of global activations. Our results indicate that with increasing age, shorter lifetimes and more occurrences were observed in the brain states that show the global high activations and more consecutive visits to the global highest-activation brain state. There were also reduced transitional steps during consecutive visits to the global lowest-activation brain state. These age-related effects suggest reduced stability and increased fluctuations when visiting high-energy brain states and with a bias toward staying low-energy brain states. These age-related whole-brain dynamics changes are further supported by changes observed in classic alpha and beta power, suggesting its promising applications in examining the effect of normal healthy brain aging, brain development, and brain disease.

Chronic Dizziness.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Neuroimaging Markers of Mal de Débarquement Syndrome.

Mal de débarquement syndrome (MdDS) is a motion-induced disorder of oscillating vertigo that persists after the motion has ceased. The neuroimaging characteristics of the MdDS brain state have been investigated with studies on brain metabolism, structure, functional connectivity, and measurements of synchronicity. Baseline metabolism and resting-state functional connectivity studies indicate that a limbic focus in the left entorhinal cortex and amygdala may be important in the pathology of MdDS, as these structures are hypermetabolic in MdDS and exhibit increased functional connectivity to posterior sensory processing areas and reduced connectivity to the frontal and temporal cortices. Both structures are tunable with periodic stimulation, with neurons in the entorhinal cortex required for spatial navigation, acting as a critical efferent pathway to the hippocampus, and sending and receiving projections from much of the neocortex. Voxel-based morphometry measurements have revealed volume differences between MdDS and healthy controls in hubs of multiple resting-state networks including the default mode, salience, and executive control networks. In particular, volume in the bilateral anterior cingulate cortices decreases and volume in the bilateral inferior frontal gyri/anterior insulas increases with longer duration of illness. Paired with noninvasive neuromodulation interventions, functional neuroimaging with functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and simultaneous fMRI-EEG have shown changes in resting-state functional connectivity that correlate with symptom modulation, particularly in the posterior default mode network. Reduced parieto-occipital connectivity with the entorhinal cortex and reduced long-range fronto-parieto-occipital connectivity correlate with symptom improvement. Though there is a general theme of desynchronization correlating with reduced MdDS symptoms, the prediction of optimal stimulation parameters for noninvasive brain stimulation in individuals with MdDS remains a challenge due to the large parameter space. However, the pairing of functional neuroimaging and noninvasive brain stimulation can serve as a probe into the biological underpinnings of MdDS and iteratively lead to optimal parameter space identification.

Remotely Monitored Home-Based Neuromodulation With Transcranial Alternating Current Stimulation (tACS) for Mal de Débarquement Syndrome.

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.

Brain network effects by continuous theta burst stimulation in mal de débarquement syndrome: simultaneous EEG and fMRI study.

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.

Motion sickness diagnostic criteria: Consensus Document of the Classification Committee of the Bárány Society.

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.

fMRI and transcranial electrical stimulation (tES): A systematic review of parameter space and outcomes.

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.

Migraine-associated vertigo: diagnosis and treatment.

Migraine-associated vertigo has become a well-recognized disease entity diagnosed based on a clinical history of recurrent vertigo attacks unexplained by other central or peripheral otologic abnormalities, which occurs in the patient with a history of migraine headaches. There is no international agreement on what spectrum of symptoms should be covered under this diagnosis, or what terminology should be used. The headaches and vestibular symptoms of migraine-associated vertigo may not be temporally associated, which often obscures the association. Diagnostic tests usually show nonspecific abnormalities that are also seen in patients with migraine who do not experience vestibular symptoms. Management generally follows the recommended treatment of migraine headaches, and includes dietary and lifestyle modifications and medical treatment with beta blockers, calcium channel blockers, and tricyclic amines. Small case series show that acetazolamide and lamotrigine appear to be more effective for the vertigo attacks than headaches. Vestibular rehabilitation has also been shown to be helpful in several studies. In this review, the epidemiologic and clinical features of the disorder, as well as the current state of knowledge on pathophysiology, diagnostic testing, and treatment are described.