Severity-Dependent Interhemispheric White Matter Connectivity Predicts Poststroke Neglect Recovery.

Left-sided spatial neglect is a very common and challenging issue after right-hemispheric stroke, which strongly and negatively affects daily living behavior and recovery of stroke survivors. The mechanisms underlying recovery of spatial neglect remain controversial, particularly regarding the involvement of the intact, contralesional hemisphere, with potential contributions ranging from maladaptive to compensatory. In the present prospective, observational study, we assessed neglect severity in 54 right-hemispheric stroke patients (32 male; 22 female) at admission to and discharge from inpatient neurorehabilitation. We demonstrate that the interaction of initial neglect severity and spared white matter (dis)connectivity resulting from individual lesions (as assessed by diffusion tensor imaging, DTI) explains a significant portion of the variability of poststroke neglect recovery. In mildly impaired patients, spared structural connectivity within the lesioned hemisphere is sufficient to attain good recovery. Conversely, in patients with severe impairment, successful recovery critically depends on structural connectivity within the intact hemisphere and between hemispheres. These distinct patterns, mediated by their respective white matter connections, may help to reconcile the dichotomous perspectives regarding the role of the contralesional hemisphere as exclusively compensatory or not. Instead, they suggest a unified viewpoint wherein the contralesional hemisphere can - but must not necessarily - assume a compensatory role. This would depend on initial impairment severity and on the available, spared structural connectivity. In the future, our findings could serve as a prognostic biomarker for neglect recovery and guide patient-tailored therapeutic approaches.

Joint impact on attention, alertness and inhibition of lesions at a frontal white matter crossroad.

In everyday life, information from different cognitive domains-such as visuospatial attention, alertness and inhibition-needs to be integrated between different brain regions. Early models suggested that completely segregated brain networks control these three cognitive domains. However, more recent accounts, mainly based on neuroimaging data in healthy participants, indicate that different tasks lead to specific patterns of activation within the same, higher-order and 'multiple-demand' network. If so, then a lesion to critical substrates of this common network should determine a concomitant impairment in all three cognitive domains. The aim of the present study was to critically investigate this hypothesis, i.e. to identify focal stroke lesions within the network that can concomitantly affect visuospatial attention, alertness and inhibition. We studied an unselected sample of 60 first-ever right-hemispheric, subacute stroke patients using a data-driven, bottom-up approach. Patients performed 12 standardized neuropsychological and oculomotor tests, four per cognitive domain. A principal component analysis revealed a strong relationship between all three cognitive domains: 10 of 12 tests loaded on a first, common component. Analysis of the neuroanatomical lesion correlates using different approaches (i.e. voxel-based and tractwise lesion-symptom mapping, disconnectome maps) provided convergent evidence on the association between severe impairment of this common component and lesions at the intersection of superior longitudinal fasciculus II and III, frontal aslant tract and, to a lesser extent, the putamen and inferior fronto-occipital fasciculus. Moreover, patients with a lesion involving this region were significantly more impaired in daily living cognition, which provides an ecological validation of our results. A probabilistic functional atlas of the multiple-demand network was performed to confirm the potential relationship between patients' lesion substrates and observed cognitive impairments as a function of the multiple-demand network connectivity disruption. These findings show, for the first time, that a lesion to a specific white matter crossroad can determine a concurrent breakdown in all three considered cognitive domains. Our results support the multiple-demand network model, proposing that different cognitive operations depend on specific collaborators and their interaction, within the same underlying neural network. Our findings also extend this hypothesis by showing (i) the contribution of superior longitudinal fasciculus and frontal aslant tract to the multiple-demand network; and (ii) a critical neuroanatomical intersection, crossed by a vast amount of long-range white matter tracts, many of which interconnect cortical areas of the multiple-demand network. The vulnerability of this crossroad to stroke has specific cognitive and clinical consequences; this has the potential to influence future rehabilitative approaches.

Feasibility of a combined intermittent theta-burst stimulation and video game-based dexterity training in Parkinson's disease.

BACKGROUND: Persons with Parkinson's disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL), inter alia due to dysfunctional supplementary motor area (SMA). Combined intermittent theta-burst stimulation (iTBS) over the SMA followed by video game-based training (VBT) may therefore improve dexterity related ADL. The VBT may induce high flow levels related to high performance during the training. The aim of this study is to evaluate the feasibility of a combined iTBS-VBT intervention in persons with PD. METHODS: A total of nine persons with PD (mean age 63.3 ± 8.76 years) with self-reported difficulties with dexterity related ADL were included in this pilot iTBS-VBT study. All participants received either iTBS or sham stimulation over the SMA followed by a 45-min VBT, three times a week for a total of three weeks. Feasibility was measured by means of the adherence rate and the system usability (System Usability Scale). Moreover, flow was measured after the last VBT session. RESULTS: Adherence rate was excellent with 100%. High system usability scores (i.e., mean 80%, range 55-97.5) and a significant Spearman's correlation with the Flow State Scale (r = .762, p = .017) further point to the high feasibility of the VBT. Neither demographic variables nor difficulties in dexterity related ADL affected the usability of the VBT. CONCLUSION: This study demonstrates the high feasibility of a combined iTBS-VBT intervention. Moreover, the level of self-reported usability was related to flow experience. Whether this kind of combined iTBS-VBT intervention improves dexterity will be evaluated in a randomized controlled trial. Trial registration clincaltrials.gov NCT04699149, date of registration 1. June 2021.

An Overview of Wearable Haptic Technologies and Their Performance in Virtual Object Exploration.

We often interact with our environment through manual handling of objects and exploration of their properties. Object properties (OP), such as texture, stiffness, size, shape, temperature, weight, and orientation provide necessary information to successfully perform interactions. The human haptic perception system plays a key role in this. As virtual reality (VR) has been a growing field of interest with many applications, adding haptic feedback to virtual experiences is another step towards more realistic virtual interactions. However, integrating haptics in a realistic manner, requires complex technological solutions and actual user-testing in virtual environments (VEs) for verification. This review provides a comprehensive overview of recent wearable haptic devices (HDs) categorized by the OP exploration for which they have been verified in a VE. We found 13 studies which specifically addressed user-testing of wearable HDs in healthy subjects. We map and discuss the different technological solutions for different OP exploration which are useful for the design of future haptic object interactions in VR, and provide future recommendations.

Signal Alteration of the Inner Ear on High-Resolution Three-Dimensional Constructive Interference in Steady State Sequence in Patients with Ménière's Disease and Labyrinthitis.

INTRODUCTION: The aim of this study is to evaluate signal alteration in the inner ear using three-dimensional (3D)-constructive interference in steady state (CISS) sequence in patients with Ménière's disease and labyrinthitis and its correlation with clinical and audiological parameters. METHODS: The medical records of the department of otorhinolaryngology were searched for patients with Ménière's disease or labyrinthitis who underwent MRI with 3D-CISS sequence. Blinded analysis of these patients and of MRI from control subjects without middle or inner ear symptoms was performed to detect any signal asymmetry of the inner ear structures. The results were correlated with clinical symptoms and results of audiological and vestibular tests. RESULTS: Fifty-eight patients with definite Ménière's disease and 5 patients with labyrinthitis as well as 41 control exams were included. A separate analysis was performed for patients with probable Ménière's disease (n = 68). A total of 172 3D-CISS sequences were analyzed by 2 blinded independent neuroradiologists. A CISS-hypointense signal of the inner ear structures was found in 3 patients with definite Ménière's disease (5.2%), in 4 patients with probable Ménière's disease (5.9%), and 2 patients with labyrinthitis (40%). No CISS hypointensity was found in the control group. Although no significant difference in symptoms or audiological test results was found between patients with and without this signal change, the side of hypointensity was frequently correlated with the symptomatic side and with hearing impairment. DISCUSSION/CONCLUSION: CISS hypointensity of the inner ear structures was evident in patients with clinical conditions other than vestibular schwannoma - more frequently in labyrinthitis than in Ménière's disease. This signal alteration was frequently encountered on the same symptomatic side as that of the pathological audiology tests, but it is not a predictor for hearing or vestibular impairment.

Influence of head orientation and implantation site of a novel transcutaneous bone conduction implant on MRI metal artifact reduction sequence.

PURPOSE: The use of magnetic resonance imaging (MRI) is often limited in patients with auditory implants because of the presence of metallic components and magnets. The aim of this study was to evaluate the clinical usefulness of a customized MRI sequence for metal artifact suppression in patients with BONEBRIDGETM BCI 602 implants (MED-EL, Innsbruck, Austria), the successor of the BCI 601 model. METHODS: Using our in-house developed and customized metal artifact reduction sequence (SEMAC-VAT WARP), MRI artifacts were evaluated qualitatively and quantitatively. MRI sequences were performed with and without artifact reduction on two whole head specimens with and without the BCI 602 implant. In addition, the influence of two different implantation sites (mastoid versus retrosigmoid) and head orientation on artifact presence was investigated. RESULTS: Artifact volume was reduced by more than the 50%. Results were comparable with those obtained with the BCI 601, showing no significant differences in the dimensions of artifacts caused by the implant. CONCLUSION: SEMAC-VAT WARP was once more proved to be efficient at reducing metal artifacts on MR images. The dimensions of artifacts associated with the BCI 602 are not smaller than those caused by the BCI 601.

Usability of Two New Interactive Game Sensor-Based Hand Training Devices in Parkinson's Disease.

This pilot cross-sectional study aimed to evaluate the usability of two new interactive game sensor-based hand devices (GripAble and Smart Sensor Egg) in both healthy adults as well as in persons with Parkinson's Disease (PD). Eight healthy adults and eight persons with PD participated in this study. Besides a standardised usability measure, the state of flow after one training session and the effect of cognitive abilities on flow were evaluated. High system usability scores (SUS) were obtained both in healthy participants (72.5, IQR = 64.375-90, GripAble) as well as persons with PD (77.5, IQR = 70-80.625, GripAble; 77.5, IQR = 75-82.5, Smart Sensor Egg). Similarly, high FSSOT scores were achieved after one training session (42.5, IQR = 39.75-50, GripAble; 50, IQR = 47-50, Smart Sensor Egg; maximum score 55). Across both groups, FSSOT scores correlated significantly with SUS scores (r = 0.52, p = 0.039). Finally, MoCA did not correlate significantly with FSSOT scores (r = 0.02, p = 0.9). The present study shows high usability for both interactive game sensor-based hand training devices, for persons with PD and healthy participants.

Sensing form - finger gaiting as key to tactile object exploration - a data glove analysis of a prototypical daily task.

BACKGROUND: Motor hand skill and associated dexterity is important for meeting the challenges of daily activity and an important resource post-stroke. In this context, the present study investigated the finger movements of right-handed subjects during tactile manipulation of a cuboid, a prototypical task underlying tactile exploration. During one motor act, the thumb and fingers of one hand surround the cuboid in a continuous and regular manner. While the object is moved by the guiding thumb, the opposed supporting fingers are replaced once they reach their joint limits by free fingers, a mechanism termed finger gaiting. METHODS: For both hands of 22 subjects, we acquired the time series of consecutive manipulations of a cuboid at a frequency of 1 Hz, using a digital data glove consisting of 29 sensors. Using principle component analysis, we decomposed the short action into motor patterns related to successive manipulations of the cuboid. The components purport to represent changing grasp configurations involving the stabilizing fingers and guiding thumb. The temporal features of the components permits testing whether the distinct configurations occur at the frequency of 1 Hz, i.e. within the time window of 1 s, and, thus, taxonomic classification of the manipulation as finger gaiting. RESULTS: The fraction of variance described by the principal components indicated that three components described the salient features of the single motor acts for each hand. Striking in the finger patterns was the prominent and varying roles of the MCP and PIP joints of the fingers, and the CMC joint of the thumb. An important aspect of the three components was their representation of distinct finger configurations within the same motor act. Principal component and graph theory analysis confirmed modular, functionally synchronous action of the involved joints. The computation of finger trajectories in one subject illustrated the workspace of the task, which differed for the right and left hands. CONCLUSION: In this task one complex motor act of 1 s duration could be described by three elementary and hierarchically ordered grasp configurations occurring at the prescribed frequency of 1 Hz. Therefore, these configurations represent finger gaiting, described until now only in artificial systems, as the principal mechanism underlying this prototypical task. TRIAL REGISTRATION: clinicaltrials.gov, NCT02865642 , registered 12 August 2016.

MRI Metal Artifact Reduction Sequence for Auditory Implants: First Results with a Transcutaneous Bone Conduction Implant.

OBJECTIVE: Magnetic resonance imaging (MRI) is often limited in patients with auditory implants because of the presence of metallic components and magnets. The aim of this study was to evaluate the clinical usefulness of a customized MRI sequence for metal artifact suppression for patients with implants in the temporal bone region, specifically patients with a transcutaneous bone conduction implant. METHODS: Two whole head specimens were unilaterally implanted with a transcutaneous bone conduction implant. MRI examinations with and without a primarily self-build sequence (SEMAC-VAT WARP) for metal artifact suppression were performed. The diagnostic usefulness of the acquired MRI scans was rated independently by two neuroradiologists. The sequence was also used to acquire postimplantation follow-up MRI in a patient with a transcutaneous bone conduction implant. RESULTS: The customized SEMAC-VAT WARP sequence significantly improved the diagnostic usefulness of the postimplantation MRIs. The image acquisition time was 12 min and 20 s for the T1-weighted and 12 min and 12 s for the T2-weighted MRI. There was good agreement between the two blinded raters (Cohen's κ = 0.61, p < 0.001). CONCLUSION: The sequence for metal artifact reduction optimized in Bern enables MRI at 1.5 T in patients with active transcutaneous bone conduction implants without sacrificing diagnostic imaging quality. Particularly on the implanted side, imaging of intracranial and supra- and infratentorial brain pathologies is clinically more valuable than standard diagnostic MRI without any artifact reduction sequences.

The Brainfit study: efficacy of cognitive training and exergaming in pediatric cancer survivors - a randomized controlled trial.

BACKGROUND: Cancer survival comes at a price: pediatric cancer survivors bear a high risk for a wide range of cognitive difficulties. Therefore, interventions targeting these difficulties are required. The aim of the present clinical trial is to extend empirical evidence about efficacy of cognitive and physical training in pediatric cancer survivors. It is hypothesized that early cognitive and physical interventions affect the remediation of pediatric cancer survivors in terms of improved executive functions (primary outcome). Additional positive effects of cognitive and physical intervention to other areas such as memory and attention are expected (secondary outcome). Changes in cognitive performance are expected to be associated with structural and functional changes in the brain. METHODS: Overall, 150 pediatric cancer survivors and 50 matched controls will be included in this trial. The cancer survivors will be randomly assigned to either a computerized cognitive training, a physical training (exergaming) or a waiting control group. They will be assessed with neuropsychological tests, tests of sport motor performance and physical fitness before and after 8 weeks of training and again at a 3-months follow-up. Moreover, neuroimaging will be performed at each of the three time points to investigate the training impact on brain structure and function. DISCUSSION: With increasing cancer survival rates, evidence-based interventions are of particular importance. New insights into training-related plasticity in the developing brain will further help to develop tailored rehabilitation programs for pediatric cancer survivors. TRIAL REGISTRATION: KEK BE 196/15; KEK ZH 2015-0397; ICTRP NCT02749877 ; date of registration: 30.11.2016; date of first participant enrolment: .18.01.2017.

Diverging lesion and connectivity patterns influence early and late swallowing recovery after hemispheric stroke.

Knowledge about the recovery of oral intake after hemispheric stroke is important to guide therapeutic decisions, including the administration of enteral tube feeding and the choice of the appropriate feeding route. They aimed to determine the localization and connectivity of lesions in impaired recovery versus recovered swallowing after initially dysphagic stroke. Sixty-two acute ischemic hemispheric stroke patients with impaired oral intake were included in a prospective observational cohort study. Voxel-based lesion-symptom mapping and probabilistic tractography were used to determine the association of lesion location and connectivity with impaired recovery of oral intake ≥7 days (indication for early tube feeding) and ≥4 weeks (indication for percutaneous endoscopic gastrostomy feeding) after stroke. Two distinct patterns influencing recovery of swallowing were recognized. Firstly, impaired recovery of oral intake after ≥7 days was significantly associated with lesions of the superior corona radiata (65% of statistical map, P < 0.05). The affected fibers were connected with the thalamus, primary motor, and supplemental motor areas and the basal ganglia. Secondly, impaired recovery of oral intake after ≥4 weeks significantly correlated with lesions of the anterior insula (54% of statistical map, P < 0.05), which was connected to adjacent operculo-insular areas of deglutition. These findings indicate that early swallowing recovery is influenced by white matter lesions disrupting thalamic and corticobulbar projection fibers. Late recovery is determined by specific cortical lesions affecting association fibers. This knowledge may help clinicians to identify patients at risk of prolonged swallowing problems that would benefit from enteral tube feeding. Hum Brain Mapp 38:2165-2176, 2017. © 2017 Wiley Periodicals, Inc.

Graded peak cycle ergometer test for cognitively impaired patients with Parkinson's disease: a pilot study.

BACKGROUND: Cognitive decline affects up to 50% of patients with Parkinson's disease (PD) in the course of the disease and may be amenable to exercise interventions. To accurately set adequate training intensities, standardized exercise testing is required but such testing takes considerable time and effort. The aim of this pilot study was to investigate the feasibility of a graded peak cycle ergometer exercise test in cognitively impaired patients with Parkinson's Disease (PD), and to define whether age-predicted maximal heart rate (HRmax) matched measured HRmax. METHODS: A convenience sample of seven patients with PD (Hoehn and Yahr: 2-4, and cognitive impairment (Montreal Cognitive Assessment (MoCA) ≤ 26) completed a graded peak cycle ergometer test to voluntary exhaustion. Borg Rating of Perceived Exertion was used to record the individual's perception of exertion. Pre-defined age-predicted HRmax (calculated as 208-(0.7 × age) was compared with the measured HRmax using Bland-Altman plot and a two-one-sided test. RESULTS: All PD patients completed the graded exercise test between 8-12 minutes, showing therefore 100% compliance to the test protocol. No adverse events occurred. Predicted HRmax and measured HRmax did not differ. CONCLUSION: We demonstrate feasibility of graded peak cycle ergometer testing in PD patients with cognitive impairment. The good correspondence of age-predicted HRmax equation with measured HRmax, in this small sample, may in the future provide clinicians with a tool to define training intensities in cognitively impaired PD, without cardiac disease. However, further research is needed to confirm these results.

Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurologic Impairment in Neonates With Stroke.

BACKGROUND AND OBJECTIVES: Research investigating neonatal arterial ischemic stroke (NAIS) outcomes have shown that combined cortical and basal ganglia infarction or involvement of the corticospinal tract predict cerebral palsy (CP). The research question was whether voxel-based lesion-symptom mapping (VLSM) on acute MRI can identify brain regions associated with CP and neurodevelopmental impairments in NAIS. METHODS: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language and cognitive-behavioral impairments were assessed using the Pediatric Stroke Outcome Measure, dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using diffusion-weighted imaging, registered to a neonatal-specific brain template. VLSM was conducted using MATLAB SPM12 toolbox. A general linear model was used to correlate lesion masks with motor, language, and cognitive-behavioral outcomes. Voxel-wise t-statistics were calculated, correcting for multiple comparisons using family-wise error (FWE) rate. RESULTS: Eighty-five newborns met the inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%), and bilateral (30%). At a median age of 2.1 years (interquartile range 1.9-2.6), 33% developed CP and 42% had neurologic impairments. Fifty-four grey and white matter regions correlated with CP (t > 4.33; FWE < 0.05), including primary motor pathway regions, such as the precentral gyrus, and cerebral peduncle, and regions functionally connected to the primary motor pathway, such as the pallidum, and corpus callosum motor segment. No significant correlations were found for language or cognitive-behavioral outcomes. DISCUSSION: CP after NAIS correlates with infarct regions directly involved in motor control and in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear.

Distinguishing transient from persistent tactile agnosia after partial anterior circulation infarcts - Behavioral and neuroimaging evidence for white matter disconnection.

From a cohort of 36 patients presenting apperceptive tactile agnosia after first cortical ischemic stroke, 14 showed temporary impairment at admission. A previous multi-voxel analysis of the cortical lesions, using as explanatory variable the course of tactile object recognition performance over the recovery period of 9 months, partitioned the cohort into three subgroups. Of the 14 patients constituting two of the subgroups, 7 recovered from their impairment whereas 7 did not. These two subgroups could not be distinguished at admission. The primary aim of the present study is to present two assessments that can do so. The first assessment comprises a pattern of behavioral measures, determined via principal component analysis, encoded in three tests: picking small objects, macrogeometrical discrimination and tactile object recognition. The receiver operating characteristic curve derived from permutation of the behavioral test scores yielded an 80% probability of correct identification of the patient subgroup and an 8% probability for false identification. As done with the permuted scores, the pattern could predict the persistence of affliction of new stroke patients with tactile agnosia. The second predictive assessment extends our previous evaluation of cortical MRI lesion maps to include subcortical regions. Confirming our previous study, the lesions of the persistently impaired subgroup disrupted significantly the anterior arcuatus fasciculus and associated superior longitudinal fasciculus III in the ipsilesional hemisphere, impeding reciprocal information transfer between supramarginal gyrus and both the ventral premotor cortex and Brodmann area 44. Due to the importance of interhemispheric information transfer in tactile agnosia, we performed a supplementary analysis of tactile object recognition scores. It showed that haptic information transfer from the non-affected to the affected hands in the persistent cases partly restored function during the nine months, possibly following restoration of functional interhemispheric haptic information transfer at the border of posterior corpus callosum and splenium. In conclusion, the combined findings of the cortical lesion at subarea PFt of the inferior parietal lobule and the associated subcortical tract lesions permit almost perfect prediction of persistent impairment of tactile object recognition. The study substantiates the need for combined analysis of both cortical lesions and white matter tract disconnections.

Improved gesturing in left-hemispheric stroke by right inferior parietal theta burst stimulation.

Objectives: Apraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation. Materials and methods: Nineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model. Results: Pairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 - 18.13, p < 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI -0.20 - 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI -0.49 - 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R. Conclusion: One single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia.

Tablet app-based dexterity training in multiple sclerosis (TAD-MS): a randomized controlled trial.

PURPOSE: Mobile health applications (mHealth apps) may lead to health benefits. In recent years, the use of apps in multiple sclerosis (MS) has increased. Apps to train and improve dexterity in MS are scarce. This study investigated the effectiveness of a tablet app-based home-based training to improve dexterity in individuals with MS. MATERIALS AND METHODS: In a randomized controlled trial, two standardized 4-week home-based interventions focussing on different aspects of dexterity and upper limb function were compared. Assessments were done at baseline, post-intervention and 12-week follow-up. The primary endpoint was the Arm Function in Multiple Sclerosis Questionnaire, a dexterity-related measure of patient-reported activities of daily living. Secondary endpoints were dexterous function, grip strength and health-related quality of life. RESULTS: Forty-eight individuals were randomly assigned to a tablet app-based program (n = 26) or a control strengthening exercise program (n = 22). No significant differences were found for the primary endpoint (p = 0.35). Some significant differences in favour of the app-group were found in fine coordinated finger movements and strength. No significant differences were found at the 12-week follow-up for all endpoints. Adherence in both groups was above 90%. CONCLUSIONS: App-based training was not superior compared to a control strengthening exercise program concerning the arm- and hand function from the participant's perspective. However, app-based training was found to be effective in improving specific dimensions (finger movements and strength), and can easily be applied at home. Therefore, individuals living with MS with impaired dexterity should consider app-based training. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT03369470.

This study provides initial evidence for the effectiveness of a home-based app-based program for improving dexterous function in individuals living with multiple sclerosis through the implementation of a tablet app-based dexterity training.App-based training was not superior compared to a control strengthening exercise program concerning the arm- and hand function from the participant's perspective.Patients attending the app-based dexterity program showed some statistically significant improvements in fine coordinated finger movements and strength.

Distended Seminal Vesicles Are Involved in Specific Cerebral Sexual Arousal: A Pilot Study Using Functional Brain Imaging in Young Healthy Men.

Background: Whether seminal vesicles play a role in sexual activity in men is unknown. No study so far has compared the neural processing of visual sexual stimuli in men depending on the filling state of the seminal vesicles. Objective: To evaluate potential specific cortical activation by visual sexual stimuli with distended and empty seminal vesicles. Design setting and participants: A prospective case-control trial was conducted. Six male individuals underwent two visits on 2 consecutive days for hormone analyses; Derogatis Interview for Sexual Functioning (DISF) questionnaire; functional magnetic resonance imaging (fMRI) with passively viewing sexual, neutral, positive, and negative emotional pictures; and structural pelvic MRI. After the first visit, the participants had to empty seminal vesicles by masturbation. During fMRI, every participant viewed alternating blocks of sexual, neutral, positive, and negative emotional pictures. Outcome measurements and statistical analysis: Comparisons between days 1 and 2 were evaluated using paired t tests. Results and limitations: No significant differences were observed regarding hormone analyses, DISF questionnaire score, and arousal scoring between days 1 and 2. Seminal vesicle volume was significantly lower on day 2 (p = 0.003). Significantly higher activation was observed in the right precentral gyrus, middle frontal gyrus, and right superior temporal sulcus when contrasted for sexual over neutral (p < 0.05). Conclusions: In response to pictures with sexual emotional content, significantly higher activation was detected in brain areas involved in motor preparation (arousal) and coding of desirability of visual sexual stimuli in men with distended seminal vesicles than in the same men with emptied seminal vesicles. This suggests that the filling state of the seminal vesicles may influence sexual desire in men. Patient summary: We compared brain activity of men with filled and emptied seminal vesicles by functional magnetic resonance imaging. We found that men with filled seminal vesicles had higher activation of brain areas involved in arousal and sexual desire.

Combining Repetitive Transcranial Magnetic Stimulation and Video Game-Based Training to Improve Dexterity in Parkinson's Disease: Study Protocol of a Randomized Controlled Trial.

Introduction: Patients with Parkinson's disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL) due to dysfunctional supplementary motor area (SMA). The aim of this clinical trial protocol work is to describe how the effectiveness of a combined repetitive transcranial magnetic stimulation (rTMS) over SMA and video-game-based skill training (VBT) in PD will be evaluated. The short and long-term benefits are assessed. Methods and analysis: A single-blind (patients) stratified (based on Hoehn & Yahr) parallel randomized sham-controlled rTMS-VBT study with a baseline and two follow-up measurements (3 and 12 weeks) is being conducted. These measurements include the dexterity questionnaire 24 (DextQ-24) as a primary outcome, and nine hole peg test and coin rotation task as main secondary dexterity outcomes. Further secondary outcomes will be the subscale II of the movement disorders society unified PD rating scale (MDS-UPDRS) to assess improvements on overall ADL and the Parkinson's Disease Questionnaire-39 to assess quality of life. Thirty-six outpatients (from one neurorehabilitation center) with PD (diagnosis based on brain bank criteria) will be recruited who report difficulties with dexterity in performing ADL. All PD patients will receive a 45-min VBT three times a week for 3 weeks. The PD patients randomized in the experimental group will receive VBT preceded by real rTMS, being intermittent theta burst (iTBS) stimulation sessions. The PD patients randomized to the control group receive a VBT with sham rTMS. Discussion: The study will provide evidence to determine whether a combined iTBS and VBT skill intervention is more effective than a VBT intervention alone to improve dexterity in PD. Ethics and dissemination: The study was approved by the Ethics Committee for Northwest and Central Switzerland (EKNZ), Switzerland 2019-00433. The study will be conducted in accordance with the Helsinki Declaration and the Guidelines of Good Clinical Practice. Informed consent will be signed prior to subject enrolment. Dissemination will include submission to international peer-reviewed professional journals and presentation at international congresses. The study protocol has been registered in the clinicaltrials.gov registry with the identification code: NCT04699149.

Non-invasive brain stimulation in limb praxis and apraxia: A scoping review in healthy subjects and patients with stroke.

Non-invasive brain stimulation (NIBS) techniques are widely used in research settings to investigate brain mechanisms and increasingly being used for treatment purposes. The aim of this study was to systematically identify and review the current literature on NIBS studies of limb praxis and apraxia in healthy subjects and stroke patients with a scoping review using PRISMA-ScR guidelines. MEDLINE-PubMed, EMBASE and PsycINFO were searched. Inclusion criteria were English peer-reviewed studies focusing on the investigation of limb praxis/apraxia using repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS). Fourteen out of 139 records met the inclusion criteria, including thirteen studies with healthy subjects and one with stroke patients. The results of our systematic review suggest that in healthy subjects NIBS over left inferior parietal lobe (IPL) mainly interfered with gesture processing, by either affecting reaction times in judgment tasks or real gesturing. First promising results suggest that inhibitory continuous theta burst stimulation (cTBS) over right IPL may enhance gesturing in healthy subjects, explained by transcallosal facilitation of left IPL. In stroke patients, excitatory anodal tDCS over left IPL may improve limb apraxia. However, larger well powered and sham-controlled clinical trials are needed to expand on these proof-of-concept results, before NIBS could be a treatment option to improve limb apraxia in stroke patients.

The Working Memory Network and Its Association with Working Memory Performance in Survivors of non-CNS Childhood Cancer.

Childhood cancer and its treatment puts survivors at risk of low working memory capacity. Working memory represents a core cognitive function, which is crucial in daily life and academic tasks. The aim of this functional MRI (fMRI) study was to examine the working memory network of survivors of childhood cancer without central nervous system (CNS) involvement and its relation to cognitive performance. Thirty survivors (aged 7-16 years, ≥ 1 year after cancer treatment) and 30 healthy controls performed a visuospatial working memory task during MRI, including a low- and a high-demand condition. Working memory performance was assessed using standardized tests outside the scanner. When cognitive demands increased, survivors performed worse than controls and showed evidence for slightly atypical working memory-related activation. The survivor group exhibited hyperactivation in the right-hemispheric superior parietal lobe (SPL) in the high- compared to the low-demand working memory condition, while maintaining their performance levels. Hyperactivation in the right SPL coincided with poorer working memory performance outside the scanner in survivors. Even in survivors of childhood cancer without CNS involvement, we find neural markers pointing toward late effects in the cerebral working memory network.AbbreviationsfMRI: Functional magnetic resonance imaging; CNS: Central nervous system; MNI: Montreal Neurological Institute; SES: Socioeconomic status; SPL: Superior parietal lobe.