Evaluating tactile feedback in addition to kinesthetic feedback for haptic shape rendering: a pilot study.

In current virtual reality settings for motor skill training, only visual information is usually provided regarding the virtual objects the trainee interacts with. However, information gathered through cutaneous (tactile feedback) and muscle mechanoreceptors (kinesthetic feedback) regarding, e.g., object shape, is crucial to successfully interact with those objects. To provide this essential information, previous haptic interfaces have targeted to render either tactile or kinesthetic feedback while the effectiveness of multimodal tactile and kinesthetic feedback on the perception of the characteristics of virtual objects still remains largely unexplored. Here, we present the results from an experiment we conducted with sixteen participants to evaluate the effectiveness of multimodal tactile and kinesthetic feedback on shape perception. Using a within-subject design, participants were asked to reproduce virtual shapes after exploring them without visual feedback and with either congruent tactile and kinesthetic feedback or with only kinesthetic feedback. Tactile feedback was provided with a cable-driven platform mounted on the fingertip, while kinesthetic feedback was provided using a haptic glove. To measure the participants' ability to perceive and reproduce the rendered shapes, we measured the time participants spent exploring and reproducing the shapes and the error between the rendered and reproduced shapes after exploration. Furthermore, we assessed the participants' workload and motivation using well-established questionnaires. We found that concurrent tactile and kinesthetic feedback during shape exploration resulted in lower reproduction errors and longer reproduction times. The longer reproduction times for the combined condition may indicate that participants could learn the shapes better and, thus, were more careful when reproducing them. We did not find differences between conditions in the time spent exploring the shapes or the participants' workload and motivation. The lack of differences in workload between conditions could be attributed to the reported minimal-to-intermediate workload levels, suggesting that there was little room to further reduce the workload. Our work highlights the potential advantages of multimodal congruent tactile and kinesthetic feedback when interacting with tangible virtual objects with applications in virtual simulators for hands-on training applications.

Designing for usability: development and evaluation of a portable minimally-actuated haptic hand and forearm trainer for unsupervised stroke rehabilitation.

In stroke rehabilitation, simple robotic devices hold the potential to increase the training dosage in group therapies and to enable continued therapy at home after hospital discharge. However, we identified a lack of portable and cost-effective devices that not only focus on improving motor functions but also address sensory deficits. Thus, we designed a minimally-actuated hand training device that incorporates active grasping movements and passive pronosupination, complemented by a rehabilitative game with meaningful haptic feedback. Following a human-centered design approach, we conducted a usability study with 13 healthy participants, including three therapists. In a simulated unsupervised environment, the naive participants had to set up and use the device based on written instructions. Our mixed-methods approach included quantitative data from performance metrics, standardized questionnaires, and eye tracking, alongside qualitative feedback from semi-structured interviews. The study results highlighted the device's overall ease of setup and use, as well as its realistic haptic feedback. The eye-tracking analysis further suggested that participants felt safe during usage. Moreover, the study provided crucial insights for future improvements such as a more intuitive and comfortable wrist fixation, more natural pronosupination movements, and easier-to-follow instructions. Our research underscores the importance of continuous testing in the development process and offers significant contributions to the design of user-friendly, unsupervised neurorehabilitation technologies to improve sensorimotor stroke rehabilitation.

Intraepithelial Lymphogram in the Diagnosis of Celiac Disease in Adult Patients: A Validation Cohort.

BACKGROUND: Celiac disease is a gluten-related pathology, highly prevalent and heterogeneous in its clinical presentation, which leads to delays in diagnosis and misdiagnosis. The analysis of duodenal intraepithelial lymphocytes (IELs) by flow cytometry (lymphogram) is emerging as a discriminative tool in the diagnosis of various forms of celiac disease (CD). AIMS: The aim of this study was to validate IEL lymphogram performance in the largest adult series to our knowledge, in support of its use as a diagnostic tool and as a biomarker of the dynamic celiac process. METHODS: This was a retrospective study including 768 adult patients (217 with active CD, 195 on a gluten-free diet, 15 potential CD patients, and 411 non-celiac controls). The IEL subset cut-off values were established to calculate the diagnostic accuracy of the lymphogram. RESULTS: A complete celiac lymphogram profile (≥14% increase in T cell receptor [TCR]γδ IELs and simultaneous ≤4% decrease in surface-negative CD3 [sCD3-] IELs) was strongly associated with active and potential forms in over 80% of the confirmed patients with CD, whereas the remaining patients with CD had partial lymphogram profiles (≥14% increase in TCRγδ or ≤4% decrease in sCD3- IELs), with lower diagnostic certainty. None of these patients had a non-celiac lymphogram. Quantifying the TCRγδ versus sCD3- imbalance as a ratio (≥5) is a discriminative index to discard or suspect CD at diagnosis. CONCLUSIONS: We have validated the IEL lymphogram's diagnostic efficiency (79% sensitivity, 98% specificity), with an LR+ accuracy of 36.2. As expected, the increase in TCRγδ IELs is a reliable marker for celiac enteropathy, while changes in sCD3- IEL levels throughout the dynamic CD process are useful biomarkers of mucosal lesions.

Association between residential exposure to road traffic noise and cognitive and motor function outcomes in children and preadolescents.

BACKGROUND: Exposure to environmental noise is increasing in recent years but most of the previous literature in children has evaluated the effect of aircraft noise exposure at schools on cognition. OBJECTIVE: To assess whether residential exposure to road traffic noise during pregnancy and childhood is associated with cognitive and motor function in children and preadolescents. METHODS: The study involved 619 participants from the Spanish INMA-Sabadell cohort and 7,115 from the Dutch Generation R Study. We used noise maps to estimate the average day-evening-night road traffic noise levels at each participant's residential address during pregnancy and childhood periods. Validated tests were administered throughout childhood in both cohorts to assess non-verbal and verbal intelligence, memory, processing speed, attentional function, working memory, cognitive flexibility, risky decision-making, and fine and gross motor function. Linear models, linear mixed models, and negative binomial models were run depending on the outcome in cohort-specific analysis and combined with a random-effects meta-analysis. All models were adjusted for several socioeconomic and lifestyle variables and results corrected for multiple testing. RESULTS: Average road traffic noise exposure levels during pregnancy and childhood were 61.3 (SD 6.0) and 61.5 (SD 5.4) dB for the INMA-Sabadell cohort and 54.6 (SD 7.9) and 53.5 (SD 6.5) dB for the Generation R Study, respectively. Road traffic noise exposure during pregnancy and childhood was not related to any of the cognitive and motor function outcomes examined in this study (e.g. -0.92 (95 % CI -2.08; 0.24) and 0.20 (95 % CI -0.96; 1.35) in overall estimates of memory and fine motor function, respectively, when road traffic noise increases by 10 dB during childhood). CONCLUSIONS: These findings suggest that child's cognitive or motor functions are not affected by residential exposure to road traffic noise. However, more studies evaluating this association at school and home settings as well as noise events are needed.

Improving the Diagnosis of Dermatitis Herpetiformis Using the Intraepithelial Lymphogram.

Dermatitis herpetiformis is a cutaneous manifestation of celiac disease. Phenotyping of intraepithelial lymphocytes in the small bowel mucosa can strengthen the diagnosis of celiac disease when it is not clear-cut. We aim to evaluate the usefulness of the intraepithelial lymphogram to confirm dermatitis herpetiformis in equivocal cases. We performed a retrospective multicenter study on patients diagnosed with dermatitis herpetiformis and collected data from the intraepithelial lymphogram assessed by flow cytometry. A total of 36 patients were analyzed in relation to the severity of intestinal damage (18 had non-atrophic mucosa) at baseline (N = 28) and/or after the adoption of a gluten-free diet (median follow-up of three years, N = 16). We observed that patients with atrophy more often had positive celiac serology (p = 0.019), celiac clinical symptoms (p = 0.018), and iron-deficiency anemia (p = 0.018), but the severity of skin damage was similar in both groups (p = 0.79). At baseline, increased TCRγδ+ cells were present in 94% of patients with atrophy and 67% with non-atrophic lesions (p = 0.13). After a gluten-free diet, increased TCRγδ+ cells persisted in 100% and 63% of cases, respectively (p = 0.21). We concluded that increased TCRγδ+ cells may be helpful in confirming the diagnosis of dermatitis herpetiformis in equivocal cases, even in patients who were started on a gluten-free diet.

Quantitative and Qualitative Evaluation of Exoskeleton Transparency Controllers for Upper-Limb Neurorehabilitation.

High transparency is a fundamental requirement for upper-limb exoskeletons to promote active patient participation. Although various control strategies have been suggested to improve the transparency of these robots, there are still some limitations, such as the need for precise dynamic models and potential safety issues when external forces are applied to the robot. This study presents a novel hybrid controller designed to tackle these limitations by combining a traditional zero-torque controller with an interaction torque observer that compensates for residual undesired disturbances. The transparency of the proposed controller was evaluated using both quantitative-e.g., residual joint torques and movement smoothness-and qualitative measures-e.g., comfort, agency, and perceived resistance-in a pilot study with six healthy participants. The performance of the new controller was compared to that of two conventional controllers: a zero-torque closed-loop controller and a velocity-based disturbance observer. Our preliminary results show that the proposed hybrid controller may be a good alternative to state-of-the-art controllers as it allows participants to perform precise and smooth movements with low interaction joint torques. Importantly, participants rated the new controller higher in comfort and agency, and lower in perceived resistance. This study highlights the importance of incorporating both quantitative and qualitative assessments in evaluating control strategies developed to enhance the transparency of rehabilitation robots.

Development and Validation of a Kinematically Accurate Upper-Limb Exoskeleton Digital Twin for Stroke Rehabilitation.

Rehabilitation robotics combined with virtual reality using head-mounted displays enable naturalistic, immersive, and motivating therapy for people after stroke. There is growing interest in employing digital twins in robotic neurore-habilitation, e.g., in telerehabilitation for virtual coaching and monitoring, as well as in immersive virtual reality applications. However, the kinematic matching of the robot's visualization with the real robot movements is hardly validated, potentially affecting the users' experience while immersed in the virtual environment due to a visual-proprioceptive mismatch. The kinematic mismatch may also limit the validity of assessment measures recorded with the digital twin. We present the development and low-cost kinematic validation of a digital twin of a seven active degrees-of-freedom exoskeleton for stroke rehabilitation. We validated the kinematic accuracy of the digital twin end-effector by performing two tasks-a planar reaching task and a 3D functional task-performed by a single healthy participant. We computed the end-effector position and rotation from the forward kinematics of the robot, the digital twin, and data recorded from the real robot using a low-cost tracking system based on HTC VIVE trackers and compared them pair-wise. We found that the digital twin closely matches the forward kinematics and tracked movement of the real robot and thus provides a reliable platform for future research on digital twins for stroke rehabilitation.

Outdoor residential noise exposure and sleep in preadolescents from two European birth cohorts.

OBJECTIVE: To examine whether outdoor residential exposure to annual average road traffic and multiple (i.e., road traffic, railway, aircraft, industry) noise levels is related with preadolescents' sleep using maternal-reported and wrist-actigraphy data in two European birth cohorts. METHODS: This cross-sectional study used data of 1245 preadolescents from the Dutch Generation R Study and 232 from the Spanish INMA-Sabadell cohort with a mean age of 12.3 years old. We used noise maps to assess average outdoor road traffic and multiple noise levels (day-evening-night noise indicator, LDEN) at each child's residential address for the year before the sleep assessment. Sleep disturbances were reported by mothers through the Sleep Disturbance Scale for Children and objectively recorded using GeneActiv wrist-actigraphy during seven subsequent days. Linear and Poisson regression models adjusted for several potential confounding variables were performed. RESULTS: The mean (SD) exposure to road traffic noise was 53.2 dB (7.3) in the Generation R Study and 61.3 dB (5.9) in the INMA-Sabadell cohort. Exposure to road traffic was related with reduced total sleep time and longer wake after sleep onset (e.g. -3.62 min (95%CI -6.87; -0.37) and 6.88 min (95%CI 1.15; 12.61) per an increase of 10 dB in road traffic noise, respectively) collected by wrist-actigraphy. We observed no association between road traffic exposure and maternal-reported sleep disturbances. Results were similar for multiple noise exposure. CONCLUSIONS: These findings indicate that sleep may be compromised for preadolescents living in areas highly exposed to outdoor residential noise. Future studies using longitudinal designs to further explore these associations during the different stages of sleep development across childhood and adolescence are warranted. Also, wrist-actigraphy measurements which provide more accurate information and may be complementary to the parental- and self-reported data should be considered.

Control strategies used in lower limb exoskeletons for gait rehabilitation after brain injury: a systematic review and analysis of clinical effectiveness.

BACKGROUND: In the past decade, there has been substantial progress in the development of robotic controllers that specify how lower-limb exoskeletons should interact with brain-injured patients. However, it is still an open question which exoskeleton control strategies can more effectively stimulate motor function recovery. In this review, we aim to complement previous literature surveys on the topic of exoskeleton control for gait rehabilitation by: (1) providing an updated structured framework of current control strategies, (2) analyzing the methodology of clinical validations used in the robotic interventions, and (3) reporting the potential relation between control strategies and clinical outcomes. METHODS: Four databases were searched using database-specific search terms from January 2000 to September 2020. We identified 1648 articles, of which 159 were included and evaluated in full-text. We included studies that clinically evaluated the effectiveness of the exoskeleton on impaired participants, and which clearly explained or referenced the implemented control strategy. RESULTS: (1) We found that assistive control (100% of exoskeletons) that followed rule-based algorithms (72%) based on ground reaction force thresholds (63%) in conjunction with trajectory-tracking control (97%) were the most implemented control strategies. Only 14% of the exoskeletons implemented adaptive control strategies. (2) Regarding the clinical validations used in the robotic interventions, we found high variability on the experimental protocols and outcome metrics selected. (3) With high grade of evidence and a moderate number of participants (N = 19), assistive control strategies that implemented a combination of trajectory-tracking and compliant control showed the highest clinical effectiveness for acute stroke. However, they also required the longest training time. With high grade of evidence and low number of participants (N = 8), assistive control strategies that followed a threshold-based algorithm with EMG as gait detection metric and control signal provided the highest improvements with the lowest training intensities for subacute stroke. Finally, with high grade of evidence and a moderate number of participants (N = 19), assistive control strategies that implemented adaptive oscillator algorithms together with trajectory-tracking control resulted in the highest improvements with reduced training intensities for individuals with chronic stroke. CONCLUSIONS: Despite the efforts to develop novel and more effective controllers for exoskeleton-based gait neurorehabilitation, the current level of evidence on the effectiveness of the different control strategies on clinical outcomes is still low. There is a clear lack of standardization in the experimental protocols leading to high levels of heterogeneity. Standardized comparisons among control strategies analyzing the relation between control parameters and biomechanical metrics will fill this gap to better guide future technical developments. It is still an open question whether controllers that provide an on-line adaptation of the control parameters based on key biomechanical descriptors associated to the patients' specific pathology outperform current control strategies.

Effects of 10-kHz Subthreshold Stimulation on Human Peripheral Nerve Activation.

OBJECTIVE: The mechanisms of action of high-frequency stimulation (HFS) are unknown. We investigated the possible mechanism of subthreshold superexcitability of HFS on the excitability of the peripheral nerve. MATERIALS AND METHODS: The ulnar nerve was stimulated at the wrist in six healthy participants with a single (control) stimulus, and the responses were compared with the responses to a continuous train of 5 seconds at frequencies of 500 Hz, 2.5 kHz, 5 kHz, and 10 kHz. Threshold intensity for compound muscle action potential (CMAP) was defined as intensity producing a 100-µV amplitude in ten sequential trials and "subthreshold" as 10% below the CMAP threshold. HFS threshold was defined as stimulation intensity eliciting visible tetanic contraction. RESULTS: Comparing the threshold of single pulse stimulation for eliciting CMAP vs threshold for HFS response and pooling data at different frequencies (500 Hz-10 kHz) revealed a significant difference (p = 0.00015). This difference was most obvious at 10 kHz, with a mean value for threshold reduction of 42.2%. CONCLUSIONS: HFS with a stimulation intensity below the threshold for a single pulse induces axonal superexcitability if applied in a train. It can activate the peripheral nerve and produce a tetanic muscle response. Subthreshold superexcitability may allow new insights into the mechanism of HFS.

Lifetime prevalence and temporal trends of incidence of child's mental disorder diagnoses in Catalonia, Spain.

INTRODUCTION: Most mental disorders have its onset during childhood, but less than one third of affected children seek professional help. The aim of this study is to (1) estimate the lifetime prevalence of mood, anxiety, conduct, and eating disorder diagnoses in 18-year-olds in 2017 and (2) the temporal trends of incidence diagnosis rates in 2009-2017 in children aged 2-18 in Catalonia, Spain. MATERIAL AND METHODS: We used a registry-based cohort including all children aged 2-18 living in Catalonia in 2009-2017, from the Catalan Health Service. Cases were identified with ICD-9 codes. Lifetime prevalence was calculated for 2017, and annual incidence for 2009-2017. Temporal trends were analyzed with multivariate negative binomial regression models. RESULTS: Lifetime prevalence of diagnoses was highest for conduct disorders (5.05%), followed by anxiety (4.37%), mood (3.07%), and eating disorders (2.11%). Median age of diagnosis was 16 years for mood, anxiety and eating disorders, and 15 years for conduct disorders. Comorbidity was present in 20.74% of those diagnosed with a mental disorder. Annual incidence rates for all disorders increased in 2011-2013/2014, and then stabilized. However, incidence rate of anxiety diagnoses in 13-18-year-old children doubled between 2016 and 2017. CONCLUSIONS: Lifetime prevalence of diagnoses are lower than the expected rates of mental disorders based on interview/survey European studies. Further research is needed into the factors underlying (1) the underdiagnoses of mental disorders in children and (2) the increasing trend of anxiety disorder diagnoses in older children.

Asociación entre obesidad y embarazo cronológicamente prolongado: estudio retrospectivo observacional / Association between obesity and chronologically prolonged pregnancy: a retrospective observational study

Objetivos: Determinar si la obesidad, definida como índice de masa corporal (IMC) ≥30 kg/m2 al inicio del embarazo, es más frecuente en las gestaciones cronológicamente prolongadas (GCP), consideradas aquellas de 41 semanas o más, frente a los embarazos a término, y averiguar si existe relación entre las GCP y otras variables estudiadas. Material y métodos: Estudio retrospectivo observacional sobre una muestra seleccionada aleatoriamente de pacientes que dieron a luz en el Complejo Hospitalario de Pontevedra durante 2019. Resultados: N= 196 (98 GCP y 98 gestaciones a término). La prevalencia de obesidad en la primera consulta de embarazo fue del 23,5 % en las GCP y del 10,2 % en los embarazos a término (p= 0,013). El IMC promedio en las GCP estaba en el rango de sobrepeso y en las gestaciones a término en normopeso (p= 0,001). El porcentaje de partos instrumentales y cesáreas en las GCP fue del 20,4 y 22,4 %, respectivamente, estando en las gestaciones a término en un 15,3 y 4,1 % (p <0,001). La primiparidad (p <0,001) y la ganancia de peso por encima de las recomendaciones (p= 0,004) mostraron una asociación significativa con las GCP, mientras que la edad materna, el sexo fetal, el peso del recién nacido y el sobrepeso materno no. El análisis multivariante halló como factores de riesgo independientes de GCP: la primiparidad, el IMC ≥30 kg/m2 y la ganancia de peso por encima de las recomendaciones. Conclusiones: La obesidad al inicio del embarazo es un factor de riesgo de GCP, al igual que la primiparidad y la ganancia de peso mayor a la recomendada. Existe asociación entre las GCP y el parto instrumental y la cesárea. (AU)

Objectives: To determine whether obesity, defined as body mass index (BMI) ≥30 kg/m2 at the beginning of pregnancy, is more frequent in chronologically prolonged gestations (CPG), considered those of 41 weeks or more, versus term pregnancies, and to find out if there is a relationship between CPG and other variables studied. Material and methods: Retrospective observational study on a randomly selected sample of patients who gave birth at the Complejo Hospitalario de Pontevedra during 2019. Results: N=196 (98 CPG and 98 term gestations). The frequency of obesity at the first pregnancy visit was 23.5% in CPGs and 10.2% in term pregnancies (p=0.013). The average BMI in CPGs was in the overweight range and in term pregnancies in the normal weight range (p=0.001). The percentage of instrumental deliveries and cesarean sections in the CPGs was 20.4% and 22.4%, while in the term gestations it was 15.3% and 4.1% (p<0.001). Primiparity (p<0.001) and weight gain above recommendations (p=0.004) showed a significant association with CPG, while maternal age, fetal sex, newborn weight and maternal overweight did not. Multivariate analysis found as independent risk factors for CPG: primiparity, BMI ≥30 kg/m2 and weight gain above recommendations. Conclusions: Obesity in early pregnancy is a risk factor for CPG, as is primiparity and weight gain greater than recommended. There is an association between CPG and instrumental delivery and cesarean section. (AU)

Resting-State Functional Networks Correlate with Motor Performance in a Complex Visuomotor Task: An EEG Microstate Pilot Study on Healthy Individuals.

Developing motor and cognitive skills is needed to achieve expert (motor) performance or functional recovery from a neurological condition, e.g., after stroke. While extensive practice plays an essential role in the acquisition of good motor performance, it is still unknown whether certain person-specific traits may predetermine the rate of motor learning. In particular, learners' functional brain organisation might play an important role in appropriately performing motor tasks. In this paper, we aimed to study how two critical cognitive brain networks-the Attention Network (AN) and the Default Mode Network (DMN)-affect the posterior motor performance in a complex visuomotor task: virtual surfing. We hypothesised that the preactivation of the AN would affect how participants divert their attention towards external stimuli, resulting in robust motor performance. Conversely, the excessive involvement of the DMN-linked to internally diverted attention and mind-wandering-would be detrimental for posterior motor performance. We extracted seven widely accepted microstates-representing participants mind states at rest-out of the Electroencephalography (EEG) resting-state recordings of 36 healthy volunteers, prior to execution of the virtual surfing task. By correlating neural biomarkers (microstates) and motor behavioural metrics, we confirmed that the preactivation of the posterior DMN was correlated with poor posterior performance in the motor task. However, we only found a non-significant association between AN preactivation and the posterior motor performance. In this EEG study, we propose the preactivation of the posterior DMN-imaged using EEG microstates-as a neural trait related to poor posterior motor performance. Our findings suggest that the role of the executive control system is to preserve an homeostasis between the AN and the DMN. Therefore, neurofeedback-based downregulation of DMN preactivation could help optimise motor training.

Naturalistic visualization of reaching movements using head-mounted displays improves movement quality compared to conventional computer screens and proves high usability.

BACKGROUND: The relearning of movements after brain injury can be optimized by providing intensive, meaningful, and motivating training using virtual reality (VR). However, most current solutions use two-dimensional (2D) screens, where patients interact via symbolic representations of their limbs (e.g., a cursor). These 2D screens lack depth cues, potentially deteriorating movement quality and increasing cognitive load. Head-mounted displays (HMDs) have great potential to provide naturalistic movement visualization by incorporating improved depth cues, reduce visuospatial transformations by rendering movements in the space where they are performed, and preserve eye-hand coordination by showing an avatar-with immersive VR (IVR)-or the user's real body-with augmented reality (AR). However, elderly populations might not find these novel technologies usable, hampering potential motor and cognitive benefits. METHODS: We compared movement quality, cognitive load, motivation, and system usability in twenty elderly participants (>59 years old) while performing a dual motor-cognitive task with different visualization technologies: IVR HMD, AR HMD, and a 2D screen. We evaluated participants' self-reported cognitive load, motivation, and usability using questionnaires. We also conducted a pilot study with five brain-injured patients comparing the visualization technologies while using an assistive device. RESULTS: Elderly participants performed straighter, shorter duration, and smoother movements when the task was visualized with the HMDs than screen. The IVR HMD led to shorter duration movements than AR. Movement onsets were shorter with IVR than AR, and shorter for both HMDs than the screen, potentially indicating facilitated reaction times due to reduced cognitive load. No differences were found in the questionnaires regarding cognitive load, motivation, or usability between technologies in elderly participants. Both HMDs proved high usability in our small sample of patients. CONCLUSIONS: HMDs are a promising technology to be incorporated into neurorehabilitation, as their more naturalistic movement visualization improves movement quality compared to conventional screens. HMDs demonstrate high usability, without decreasing participants' motivation, and might potentially lower cognitive load. Our preliminary clinical results suggest that brain-injured patients may especially benefit from more immersive technologies. However, larger patient samples are needed to draw stronger conclusions.*.

Enhancing touch sensibility by sensory retraining in a sensory discrimination task via haptic rendering.

Stroke survivors are commonly affected by somatosensory impairment, hampering their ability to interpret somatosensory information. Somatosensory information has been shown to critically support movement execution in healthy individuals and stroke survivors. Despite the detrimental effect of somatosensory impairments on performing activities of daily living, somatosensory training-in stark contrast to motor training-does not represent standard care in neurorehabilitation. Reasons for the neglected somatosensory treatment are the lack of high-quality research demonstrating the benefits of somatosensory interventions on stroke recovery, the unavailability of reliable quantitative assessments of sensorimotor deficits, and the labor-intensive nature of somatosensory training that relies on therapists guiding the hands of patients with motor impairments. To address this clinical need, we developed a virtual reality-based robotic texture discrimination task to assess and train touch sensibility. Our system incorporates the possibility to robotically guide the participants' hands during texture exploration (i.e., passive touch) and no-guided free texture exploration (i.e., active touch). We ran a 3-day experiment with thirty-six healthy participants who were asked to discriminate the odd texture among three visually identical textures -haptically rendered with the robotic device- following the method of constant stimuli. All participants trained with the passive and active conditions in randomized order on different days. We investigated the reliability of our system using the Intraclass Correlation Coefficient (ICC). We also evaluated the enhancement of participants' touch sensibility via somatosensory retraining and compared whether this enhancement differed between training with active vs. passive conditions. Our results showed that participants significantly improved their task performance after training. Moreover, we found that training effects were not significantly different between active and passive conditions, yet, passive exploration seemed to increase participants' perceived competence. The reliability of our system ranged from poor (in active condition) to moderate and good (in passive condition), probably due to the dependence of the ICC on the between-subject variability, which in a healthy population is usually small. Together, our virtual reality-based robotic haptic system may be a key asset for evaluating and retraining sensory loss with minimal supervision, especially for brain-injured patients who require guidance to move their hands.

Design of a Haptic Palmar Device with Thumb Flexion and Circumduction Movements for Sensorimotor Stroke Rehabilitation.

To address the clinical need for high-intensity, repetitive sensorimotor hand training after stroke, we developed in a first step a novel haptic device for practicing finger movements. Because the thumb plays a fundamental role in the loss of autonomy and prehensile functions after stroke, we present here the development of a thumb module that complements our previous design. The novelties of our device are that it reduces the complexity to a minimum from a user perspective while still allowing anatomical thumb flexion/extension and circumduction movements with a highly functional range of motion. Moreover, it enables sensorimotor training thanks to its backlash-free and backdrivable actuation that allows for high-quality haptic rendering. Our device was co-created together with clinicians to incorporate clinical and anatomical requirements, and therefore, maximize its clinical relevance.

Associations of Air Pollution on the Brain in Children: A Brain Imaging Study.

Introduction: Epidemiological studies are highlighting the negative effects of the exposure to air pollution on children's neurodevelopment. However, most studies assessed children's neurodevelopment using neuropsychological tests or questionnaires. Using magnetic resonance imaging (MRI) to precisely measure global and region-specific brain development would provide details of brain morphology and connectivity. This would help us understand the observed cognitive and behavioral changes related to air pollution exposure. Moreover, most studies assessed only a few air pollutants. This project investigates whether air pollution exposure to many pollutants during pregnancy and childhood is associated with the morphology and connectivity of the brain in school-age children and pre-adolescents. Methods: We used data from the Generation R Study, a population-based birth cohort set up in Rotterdam, the Netherlands in 2002-2006 (n = 9,610). We used land-use regression (LUR) models to estimate the levels of 14 air pollutants at participant's homes during pregnancy and childhood: nitrogen oxides (NOx), nitrogen dioxide (NO2), particulate matter with aerodynamic diameter ≤10 µm (PM10) or ≤2.5 µm (PM2.5), PM between 10 µm and 2.5 µm (PMCOARSE), absorbance of the PM2.5 fraction - a measure of soot (PM2.5absorbance), the composition of PM2.5 such as polycyclic aromatic hydrocarbons (PAHs), organic carbon (OC), copper (Cu), iron (Fe), silicon (Si), zinc (Zn), and the oxidative potential of PM2.5 evaluated using two acellular methods: dithiothreitol (OPDTT) and electron spin resonance (OPESR). We performed MRI measurements of structural morphology (i.e., brain volumes, cortical thickness, and cortical surface area) using T1-weighted images in 6- to 10-year-old school-age children and 9- to 12-year-old pre-adolescents, structural connectivity (i.e., white matter microstructure) using diffusion tensor imaging (DTI) in pre-adolescents, and functional connectivity (i.e., connectivity score between brain areas) using resting-state functional MRI (rs-fMRI) in pre-adolescents. We assessed cognitive function using the Developmental Neuropsychological Assessment test (NEPSY-II) in school-age children. For each outcome, we ran regression analysis adjusted for several socioeconomic and lifestyle characteristics. We performed single-pollutant analyses followed by multipollutant analyses using the deletion/substitution/addition (DSA) approach. Results: The project has air pollution and brain MRI data for 783 school-age children and 3,857 pre-adolescents. First, exposure to air pollution during pregnancy or childhood was not associated with global brain volumes (e.g., total brain, cortical gray matter, and cortical white matter) in school-age children or pre-adolescents. However, higher pregnancy or childhood exposure to several air pollutants was associated with a smaller corpus callosum and hippocampus, and a larger amygdala, nucleus accumbens, and cerebellum in pre-adolescents, but not in school-age children. Second, higher exposure to several air pollutants during pregnancy was associated with a thinner cortex in various regions of the brain in both school-age children and pre-adolescents. Higher exposure to air pollution during childhood was also associated with a thinner cortex in a single region in pre-adolescents. A thinner cortex in two regions mediated the association between higher exposure to air pollution during pregnancy and an impaired inhibitory control in school-age children. Third, higher exposure to air pollution during childhood was associated with smaller cortical surface areas in various regions of the brain except in a region where we observed a larger cortical surface area in pre-adolescents. In relation to brain structural connectivity, higher exposure to air pollution during pregnancy and childhood was associated with an alteration in white matter microstructure in pre-adolescents. In relation to brain functional connectivity, a higher exposure to air pollution, mainly during pregnancy and early childhood, was associated with a higher brain functional connectivity among several brain regions in pre-adolescents. Overall, we identified several air pollutants associated with brain structural morphology, structural connectivity, and functional connectivity, such as NOx, NO2, PM of various size fractions (i.e., PM10, PMCOARSE, and PM2.5), PM2.5absorbance, PAHs, OC, three elemental components of PM2.5 (i.e., Cu, Si, Zn), and the oxidative potential of PM2.5. Conclusions: The results of this project suggest that exposure to air pollution during pregnancy and childhood play an adverse role in brain development. We observed this relationship even at levels of exposure that were below the European Union legislations. We acknowledge that identifying the independent effects of specific pollutants was particularly challenging. Most of our conclusions generally refer to traffic-related air pollutants. However, we did identify pollutants specifically originating from brake linings, tire wear, and tailpipe emissions from diesel combustion. The current direction toward innovative solutions for cleaner energy vehicles is a step in the right direction. However, our findings indicate that these measures might not be completely adequate to mitigate health problems attributable to traffic-related air pollution, as we also observed associations with markers of brake linings and tire wear.

Is Cortical Theta-Gamma Phase-Amplitude Coupling Memory-Specific?

One of the proposed neural mechanisms involved in working memory is coupling between the theta phase and gamma amplitude. For example, evidence from intracranial recordings shows that coupling between hippocampal theta and cortical gamma oscillations increases selectively during working memory tasks. Theta-gamma phase-amplitude coupling can also be measured non-invasively through scalp EEG; however, EEG can only assess coupling within cortical areas, and it is not yet clear if this cortical-only coupling is truly memory-specific, or a more general phenomenon. We tested this directly by measuring cortical coupling during three different conditions: a working memory task, an attention task, and a passive perception condition. We find similar levels of theta-gamma coupling in all three conditions, suggesting that cortical theta-gamma phase-amplitude coupling is not a memory-specific signal, but instead reflects some other attentional or perceptual processes. Implications for understanding the brain dynamics of visual working memory are discussed.

Towards Unsupervised Rehabilitation: Development of a Portable Compliant Device for Sensorimotor Hand Rehabilitation.

Sensorimotor impairments of the hand after stroke can drastically reduce the ability to perform activities of daily living. Recently, there has been an increased interest in minimally supervised and unsupervised rehabilitation to increase therapy dosage and to complement conventional therapy. Several devices have been developed that are simple to use and portable. Yet, they do not incorporate diversified somatosensory feedback, which has been suggested to promote sensorimotor recovery. Here we present the prototype of a portable one-degree-of-freedom hand trainer based on a novel compliant shell mechanism. Our solution is safe, intuitive, and can be used for various hand sizes. Importantly, it also provides rich sensory feedback through haptic rendering. We complement our device with a rehabilitation game, where we leverage interactive tangible game elements with diverse haptic characteristics to provide somatosensory training and foster recovery.

Exposure to traffic-related air pollution and noise during pregnancy and childhood, and functional brain connectivity in preadolescents.

BACKGROUND: The amount of people affected by traffic-related air pollution and noise is continuously increasing, but limited research has been conducted on the association between these environmental exposures and functional brain connectivity in children. OBJECTIVE: This exploratory study aimed to analyze the associations between the exposure to traffic-related air pollution and noise during pregnancy and childhood, and functional brain connectivity amongst a wide-swath of brain areas in preadolescents from 9 to 12 years of age. METHODS: We used data of 2,197 children from the Generation R Study. Land use regression models were applied to estimate nitrogen oxides and particulate matter levels at participant's homes for several time periods: pregnancy, birth to 3 years, 3 to 6 years, and 6 years of age to the age at magnetic resonance imaging (MRI) assessment. Existing noise maps were used to estimate road traffic noise exposure at participant's homes for the same time periods. Resting-state functional MRI was obtained at 9-12 years of age. Pair-wise correlation coefficients of the blood-oxygen-level-dependent signals between 380 brain areas were calculated. Linear regressions were run and corrected for multiple testing. RESULTS: Preadolescents exposed to higher levels of NO2, NOx, and PM2.5 absorbance, from birth to 3 years, and from 3 to 6 years of age showed higher correlation coefficients among several brain regions (e.g. from 0.16 to 0.19 higher correlation coefficient related to PM2.5 absorbance exposure, depending on the brain connection). Overall, most identified associations were between brain regions of the task positive and task negative networks, and were mainly inter-network (20 of 26). Slightly more than half of the connections were intra-hemispheric (14 of 26), predominantly in the right hemisphere. Road traffic noise was not associated with functional brain connectivity. CONCLUSIONS: This exploratory study found that exposure to traffic-related air pollution during the first years of life was related to higher functional brain connectivity predominantly in brain areas located in the task positive and task negative networks, in preadolescents from 9 to 12 years of age. These results could be an indicator of differential functional connectivity in children exposed to higher levels of air pollution.