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.

BARD: A Structured Technique for Group Elicitation of Bayesian Networks to Support Analytic Reasoning.

In many complex, real-world situations, problem solving and decision making require effective reasoning about causation and uncertainty. However, human reasoning in these cases is prone to confusion and error. Bayesian networks (BNs) are an artificial intelligence technology that models uncertain situations, supporting better probabilistic and causal reasoning and decision making. However, to date, BN methodologies and software require (but do not include) substantial upfront training, do not provide much guidance on either the model building process or on using the model for reasoning and reporting, and provide no support for building BNs collaboratively. Here, we contribute a detailed description and motivation for our new methodology and application, Bayesian ARgumentation via Delphi (BARD). BARD utilizes BNs and addresses these shortcomings by integrating (1) short, high-quality e-courses, tips, and help on demand; (2) a stepwise, iterative, and incremental BN construction process; (3) report templates and an automated explanation tool; and (4) a multiuser web-based software platform and Delphi-style social processes. The result is an end-to-end online platform, with associated online training, for groups without prior BN expertise to understand and analyze a problem, build a model of its underlying probabilistic causal structure, validate and reason with the causal model, and (optionally) use it to produce a written analytic report. Initial experiments demonstrate that, for suitable problems, BARD aids in reasoning and reporting. Comparing their effect sizes also suggests BARD's BN-building and collaboration combine beneficially and cumulatively.

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.

Neural Correlates of Passive Position Finger Sense After Stroke.

Background. Proprioception of fingers is essential for motor control. Reduced proprioception is common after stroke and is associated with longer hospitalization and reduced quality of life. Neural correlates of proprioception deficits after stroke remain incompletely understood, partly because of weaknesses of clinical proprioception assessments. Objective. To examine the neural basis of finger proprioception deficits after stroke. We hypothesized that a model incorporating both neural injury and neural function of the somatosensory system is necessary for delineating proprioception deficits poststroke. Methods. Finger proprioception was measured using a robot in 27 individuals with chronic unilateral stroke; measures of neural injury (damage to gray and white matter, including corticospinal and thalamocortical sensory tracts), neural function (activation of and connectivity of cortical sensorimotor areas), and clinical status (demographics and behavioral measures) were also assessed. Results. Impairment in finger proprioception was present contralesionally in 67% and bilaterally in 56%. Robotic measures of proprioception deficits were more sensitive than standard scales and were specific to proprioception. Multivariable modeling found that contralesional proprioception deficits were best explained (r2 = 0.63; P = .0006) by a combination of neural function (connectivity between ipsilesional secondary somatosensory cortex and ipsilesional primary motor cortex) and neural injury (total sensory system injury). Conclusions. Impairment of finger proprioception occurs frequently after stroke and is best measured using a quantitative device such as a robot. A model containing a measure of neural function plus a measure of neural injury best explained proprioception performance. These measurements might be useful in the development of novel neurorehabilitation therapies.

In vitro elimination of gaseous microemboli utilizing hypobaric oxygenation in the Terumo® FX15 oxygenator.

BACKGROUND: This study examines the efficacy of hypobaric oxygenation as it relates to the elimination of gaseous microemboli (GME) at designated flow, pressure and temperature combinations. METHODS: Hypobaric oxygenation was employed for experimental trials (n=60), but not for control trials (n=60), while circuit design, data measurements and testing conditions were maintained for both settings. Hypobaric oxygenation conditions were created by applying 100% oxygen at sub-atmospheric sweep gas pressures of 0.67 atmospheres to the gas phase of an integrated hollow-fiber microporous membrane oxygenator. GME were quantified using an Emboli Detection and Classification system (EDAC), while a continuous air infusion, at a rate of 100 ml/min, was applied to the circuit. Trials were conducted at 37°C, 28°C, and 18°C and at two flow and line pressure combinations of: 3.5 L/min & 150 mmHg and 5 L/min & 200 mmHg. RESULTS: Sub-atmospheric sweep gas pressures allowed adequate oxygenation independent of carbon dioxide removal while significantly reducing the potential entrance of nitrogen into the blood. GME was reduced significantly across all temperatures and flows when compared to control trials; GME counts were reduced by 99.7% post-oxygenator and 99.99% at the arterial cannula. CONCLUSION: Correlation between the use of hypobaric oxygenation and GME counts suggests hypobaric oxygenation could play a significant role in the reduction of GME.

A multimodal approach to understanding motor impairment and disability after stroke.

Many different measures have been found to be related to behavioral outcome after stroke. Preclinical studies emphasize the importance of brain injury and neural function. However, the measures most important to human outcomes remain uncertain, in part because studies often examine one measure at a time or enroll only mildly impaired patients. The current study addressed this by performing multimodal evaluation in a heterogeneous population. Patients (n = 36) with stable arm paresis 3-6 months post-stroke were assessed across 6 categories of measures related to stroke outcome: demographics/medical history, cognitive/mood status, genetics, neurophysiology, brain injury, and cortical function. Multivariate modeling identified measures independently related to an impairment-based outcome (arm Fugl-Meyer motor score). Analyses were repeated (1) identifying measures related to disability (modified Rankin Scale score), describing independence in daily functions and (2) using only patients with mild deficits. Across patients, greater impairment was related to measures of injury (reduced corticospinal tract integrity) and neurophysiology (absence of motor evoked potential). In contrast, (1) greater disability was related to greater injury and poorer cognitive status (MMSE score) and (2) among patients with mild deficits, greater impairment was related to cortical function (greater contralesional motor/premotor cortex activation). Impairment after stroke is most related to injury and neurophysiology, consistent with preclinical studies. These relationships vary according to the patient subgroup or the behavioral endpoint studied. One potential implication of these results is that choice of biomarker or stratifying variable in a clinical stroke study might vary according to patient characteristics.

Striatal hypertrophy and its cognitive effects in new-onset benign epilepsy with centrotemporal spikes.

PURPOSE: Benign epilepsy with centrotemporal spikes (BECTS), the most common childhood epilepsy syndrome, is a neurodevelopmental disorder with a genetic influence. Despite its signature electroencephalographic pattern and distinct focal motor seizure semiology, little is known about the underlying brain anatomic alteration and the corresponding cognitive consequences. Given the motor manifestations of seizures in BECTS, we hypothesize that anatomic networks in BECTS involve a distributed corticostriatal circuit. METHODS: We investigated volumetric differences and shape deformities of caudate, putamen, pallidum, and thalamus in a group of children with new- and recent-onset BECTS (N = 3) compared to healthy controls (N = 54). We correlated specific subcortical volumes in BECTS that were significantly different from those in healthy controls with performances in executive function. KEY FINDINGS: Children with BECTS demonstrated significantly hypertrophied putamen, which was selective among the subcortical regions examined. Shape analysis showed dorsoventral elongation of the left caudate and bilateral putamen, with subnuclei expansion in ventral and dorsal striatum. Larger putamen volumes were linked to better cognitive performances on two complementary executive function tests. SIGNIFICANCE: Children with BECTS showed aberrant volume and shape in subcortical regions that are critical for both motor processing and executive function. It is of importance to note that the hypertrophy appears to be cognitively adaptive, as enlargement was associated with improved cognitive performances. The anatomic abnormalities and their cognitive effects are evident in a group of children with new- and recent-onset epilepsy, suggesting that the structural brain anomalies occurred before the diagnosis of epilepsy.

Anatomy of stroke injury predicts gains from therapy.

BACKGROUND AND PURPOSE: Many therapies are emerging that aim to improve motor function in people with stroke. Identifying key biological substrates needed for treatment gains would help to predict treatment effects and to maximize treatment impact. The current study addressed the hypothesis that behavioral gains from therapy targeting distal upper extremity are predicted by the structural integrity of key motor system white matter tracts. METHODS: Twenty-three subjects with chronic left-sided stroke underwent robotic therapy targeting the distal right upper extremity. MRI was obtained at baseline and used to outline the infarct. For each subject, the degree to which stroke injured each of 4 descending white matter tracts (from the primary motor cortex, supplementary motor area, dorsal premotor cortex, and ventral premotor cortex, respectively) was determined. Correlations between tract-specific injury and behavioral gains from therapy were then examined. RESULTS: Numerous examples were found whereby tract-specific injury predicted treatment gains. The strongest correlations pertained to stroke injury to tracts descending from the primary motor cortex and dorsal premotor cortex. Infarct volume and baseline behavior were weak predictors of treatment gains. CONCLUSIONS: Extent of injury to specific motor tracts predicts behavioral gains from treatment in subjects with chronic stroke. This supports a role for these tracts in mediating treatment effects and reinforces the importance of lesion location in stroke. Tract-specific injury was stronger than infarct volume or baseline clinical status at predicting gains, identifies subjects with sufficient biological substrate to improve from therapy, and so might be useful as an entry criterion in repair-based trials.

Neuroplasticity and brain repair after stroke.

PURPOSE OF REVIEW: This review considers recent insights into the neurobiology of repair after stroke in animals and humans, the range of emerging therapies to promote repair and recovery after the acute phase of stroke, and issues related to optimizing trials of such therapies. RECENT FINDINGS: Animal studies continue to shed light on the molecular, vascular, glial, neuronal, behavioral, and environmental events that are important to the spontaneous behavioral recovery that is observed during the weeks after a stroke. Animal and human studies are examining a wide range of potential interventions that may favorably modify outcome, including small molecules, growth factors, cell-based approaches, electromagnetic stimulation, a range of devices and robots, and intense physiotherapy methods, including constraint-induced movement therapy. Optimal prescription of these restorative therapies in human patients with stroke requires further study, including defining potential roles for functional neuroimaging. SUMMARY: A wide range of therapies shows promise for improving poststroke brain repair. Insights into the neurobiology of brain repair after stroke in animals and in humans continue to accrue. This information might prove useful in designing and implementing clinical trials that aim to measure the clinical effects of restorative therapies after stroke.