CSMD3 Deficiency Leads to Motor Impairments and Autism-Like Behaviors via Dysfunction of Cerebellar Purkinje Cells in Mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with highly heritable heterogeneity. Mutations of CUB and sushi multiple domains 3 (CSMD3) gene have been reported in individuals with ASD. However, the underlying mechanisms of CSMD3 for the onset of ASD remain unexplored. Here, using male CSMD3 knock-out (CSMD3 -/-) mice, we found that genetic deletion of CSMD3 produced core autistic-like symptoms (social interaction deficits, restricted interests, and repetitive and stereotyped behaviors) and motor dysfunction in mice, indicating that the CSMD3 gene can be considered as a candidate for ASD. Moreover, we discovered that the ablation of CSMD3 in mice led to abnormal cerebellar Purkinje cell (PC) morphology in Crus I/II lobules, including aberrant developmental dendritogenesis and spinogenesis of PCs. Furthermore, combining in vivo fiber photometry calcium imaging and ex vivo electrophysiological recordings, we showed that the CSMD3 -/- mice exhibited an increased neuronal activity (calcium fluorescence signals) in PCs of Crus I/II lobules in response to movement activity, as well as an enhanced intrinsic excitability of PCs and an increase of excitatory rather than inhibitory synaptic input to the PCs, and an impaired long-term depression at the parallel fiber-PC synapse. These results suggest that CSMD3 plays an important role in the development of cerebellar PCs. Loss of CSMD3 causes abnormal PC morphology and dysfunction in the cerebellum, which may underlie the pathogenesis of motor deficits and core autistic-like symptoms in CSMD3 -/- mice. Our findings provide novel insight into the pathophysiological mechanisms by which CSMD3 mutations cause impairments in cerebellar function that may contribute to ASD.SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a neurodevelopmental disorder with highly heritable heterogeneity. Advances in genomic analysis have contributed to numerous candidate genes for the risk of ASD. Recently, a novel giant gene CSMD3 encoding a protein with CUB and sushi multiple domains (CSMDs) has been identified as a candidate gene for ASD. However, the underlying mechanisms of CSMD3 for the onset of ASD remain largely unknown. Here, we unravel that loss of CSMD3 results in abnormal morphology, increased intrinsic excitabilities, and impaired synaptic plasticity in cerebellar PCs, subsequently leading to motor deficits and ASD-like behaviors in mice. These results provide novel insight into the pathophysiological mechanisms by which CSMD3 mutations cause impairments in cerebellar function that may contribute to ASD.

System identification: a feasible, reliable and valid way to quantify upper limb motor impairments.

BACKGROUND: Upper limb impairments in a hemiparetic arm are clinically quantified by well-established clinical scales, known to suffer poor validity, reliability, and sensitivity. Alternatively, robotics can assess motor impairments by characterizing joint dynamics through system identification. In this study, we establish the merits of quantifying abnormal synergy, spasticity, and changes in joint viscoelasticity using system identification, evaluating (1) feasibility and quality of parametric estimates, (2) test-retest reliability, (3) differences between healthy controls and patients with upper limb impairments, and (4) construct validity. METHODS: Forty-five healthy controls, twenty-nine stroke patients, and twenty cerebral palsy patients participated. Participants were seated with the affected arm immobilized in the Shoulder-Elbow-Perturbator (SEP). The SEP is a one-degree-of-freedom perturbator that enables applying torque perturbations to the elbow while providing varying amounts of weight support to the human arm. Participants performed either a 'do not intervene' or a resist task. Elbow joint admittance was quantified and used to extract elbow viscosity and stiffness. Fifty-four of the participants performed two sessions to establish the test-retest reliability of the parameters. Construct validity was assessed by correlating system identification parameters to parameters extracted using a SEP protocol that objectifies current clinical scales (Re-Arm protocol). RESULTS: Feasibility was confirmed by all participants successfully completing the study protocol within ~ 25 min without reporting pain or burden. The parametric estimates were good with a variance-accounted-for of ~ 80%. A fair to excellent test-retest reliability was found ([Formula: see text]) for patients, except for elbow stiffness with full weight support ([Formula: see text]). Compared to healthy controls, patients had a higher elbow viscosity and stiffness during the 'do not intervene' task and lower viscosity and stiffness during the resist task. Construct validity was confirmed by a significant (all [Formula: see text]) but weak to moderate ([Formula: see text]) correlation with parameters from the Re-Arm protocol. CONCLUSIONS: This work demonstrates that system identification is feasible and reliable for quantifying upper limb motor impairments. Validity was confirmed by differences between patients and controls and correlations with other measurements, but further work is required to optimize the experimental protocol and establish clinical value.

Cerebellar Contributions to Motor Impairments in People with Multiple Sclerosis.

Although Charcot characterized classic cerebellar symptoms in people with multiple sclerosis (PwMS) in 1877, the impact of cerebellar dysfunction on MS symptoms has predominately been evaluated in the last two decades. Recent studies have clearly demonstrated the association between cerebellar pathology, including atrophy and reduced fractional anisotropy in the peduncles, and motor impairments, such as reduced gait velocity and time to complete walking tasks. However, future studies using novel imaging techniques are needed to elucidate all potential pathophysiology that is associated with disability in PwMS. Additionally, future studies are required to determine the most effective treatments for motor impairments in PwMS, including the specific type and duration of exercise interventions, and potential means to amplify their effects, such as transcranial direct current stimulation (tDCS). This mini-review critically discusses the distinct role of cerebellar dysfunction in motor impairments in PwMS, potential treatments, and directions for future studies.

Differential cholinergic systems' changes in progressive supranuclear palsy versus Parkinson's disease: an exploratory analysis.

Prior studies indicate more severe brainstem cholinergic deficits in Progressive Supranuclear Palsy (PSP) compared to Parkinson's disease (PD), but the extent and topography of subcortical deficits remains poorly understood. The objective of this study is to investigate differential cholinergic systems changes in progressive supranuclear palsy (PSP, n = 8) versus Parkinson's disease (PD, n = 107) and older controls (n = 19) using vesicular acetylcholine transporter [18F]-fluoroethoxybenzovesamicol (FEOBV) positron emission tomography (PET). A whole-brain voxel-based PET analysis using Statistical Parametric Mapping (SPM) software (SPM12) for inter-group comparisons using parametric [18F]-FEOBV DVR images. Voxel-based analyses showed lower FEOBV binding in the tectum, metathalamus, epithalamus, pulvinar, bilateral frontal opercula, anterior insulae, superior temporal pole, anterior cingulum, some striatal subregions, lower brainstem, and cerebellum in PSP versus PD (p < 0.05; false discovery rate-corrected). More severe and diffuse reductions were present in PSP vs controls. Higher frequency of midbrain cholinergic losses was seen in PSP compared to the PD participants using 5th percentile normative cut-off values (χ2 = 4.12, p < 0.05). When compared to PD, these findings suggested disease-specific cholinergic vulnerability in the tectum, striatal cholinergic interneurons, and projections from the pedunculopontine nucleus, medial vestibular nucleus, and the cholinergic forebrain in PSP.

In vitro and in vivo neuroprotective effect of novel mPGES-1 inhibitor in animal model of Parkinson's disease.

mPGES-1 is found to be up-regulated in the dopaminergic neurons of the substantia nigra pars compacta (SNpc) of postmortem brain tissue from Parkinson's disease (PD) patients and neurotoxin 6-hydroxydopamine (6-OHDA)-induced PD mice. Since the genetic deletion of mPGES-1 abolished 6-OHDA-induced PGE2 production and 6-OHDA-induced dopaminergic neurodegeneration in vitro and in vivo models, mPGES-1 enzyme has the potential to be an important target for PD therapy. In the present work, we investigated whether a small organic molecule as mPGES-1 inhibitor could exhibit the neuroprotective effects against 6-OHDA-induced neurotoxicity in in vitro and in vivo models. For this research goal, a new series of arylsulfonyl hydrazide derivatives was prepared and investigated whether these compounds may protect neurons against 6-OHDA-induced neurotoxicity in both in vitro and in vivo studies. Among them, compound 7s (MPO-0144) as a mPGES-1 inhibitor (PGE2 IC50 = 41.77 nM; mPGES-1 IC50 = 1.16 nM) exhibited a potent neuroprotection (ED50 = 3.0 nM) against 6-OHDA-induced in PC12 cells without its own neurotoxicity (IC50 = >10 µM). In a 6-OHDA-induced mouse model of PD, administration of compound 7s (1 mg/kg/day, for 7 days, i.p.) ameliorated motor impairments and dopaminergic neuronal damage. These significant biological effects of compound 7s provided the first pharmacological evidence that mPGES-1 inhibitor could be a promising therapeutic agent for PD patients.

High occurrence of perinatal risk factors and more severe impairments in children with postneonatal cerebral palsy in Norway.

AIM: To describe causal events, perinatal risk factors and clinical characteristics in children with postneonatal cerebral palsy (PNCP). METHODS: Population-based registry study of Norwegian children born 1999-2013. Prevalence, causal events and clinical characteristics of PNCP were described. The occurrence of perinatal risk factors for CP was compared with the general population. RESULTS: Among 1710 children with CP, 67 had PNCP (3.9%; 0.75 per 10,000 livebirths [95%CI: 0.59-0.96]). The prevalence of PNCP decreased during the study period. Leading causal events were cerebrovascular events (32.8%), head injuries/other accidents (22.4%), infections (19.4%) and hypoxic events (14.9%). Spastic hemiplegic (53.7%) or spastic quadriplegic/dyskinetic CP (31.3%) was more common in children with PNCP than non-PNCP (42.3% and 20.1%, respectively; p < 0.001). Children with PNCP had more severe motor and associated impairments. Perinatal risk factors for CP were more common in children with PNCP than in the general population. CONCLUSION: The prevalence of PNCP among Norwegian children was low and decreasing. The main causes were cerebrovascular events and head injuries/other accidents. Although spastic hemiplegic CP was the dominating subtype, children with PNCP had more severe motor and associated impairments than children with non-PNCP, as well as a higher occurrence of perinatal risk factors than in the general population.

Personalised Gait Recognition for People with Neurological Conditions.

There is growing interest in monitoring gait patterns in people with neurological conditions. The democratisation of wearable inertial sensors has enabled the study of gait in free living environments. One pivotal aspect of gait assessment in uncontrolled environments is the ability to accurately recognise gait instances. Previous work has focused on wavelet transform methods or general machine learning models to detect gait; the former assume a comparable gait pattern between people and the latter assume training datasets that represent a diverse population. In this paper, we argue that these approaches are unsuitable for people with severe motor impairments and their distinct gait patterns, and make the case for a lightweight personalised alternative. We propose an approach that builds on top of a general model, fine-tuning it with personalised data. A comparative proof-of-concept evaluation with general machine learning (NN and CNN) approaches and personalised counterparts showed that the latter improved the overall accuracy in 3.5% for the NN and 5.3% for the CNN. More importantly, participants that were ill-represented by the general model (the most extreme cases) had the recognition of gait instances improved by up to 16.9% for NN and 20.5% for CNN with the personalised approaches. It is common to say that people with neurological conditions, such as Parkinson's disease, present very individual motor patterns, and that in a sense they are all outliers; we expect that our results will motivate researchers to explore alternative approaches that value personalisation rather than harvesting datasets that are may be able to represent these differences.

Haloperidol-induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies.

Several useful animal models for parkinsonism have been developed so far. Haloperidol-induced catalepsy is often used as a rodent model for the study of motor impairments observed in Parkinson's disease and related disorders and for the screening of potential antiparkinsonian compounds. The objective of this systematic review is to identify publications that used the haloperidol-induced catalepsy model for parkinsonism and to explore the methodological characteristics and the main questions addressed in these studies. A careful systematic search of the literature was carried out by accessing articles in three different databases: Web of Science, PubMed and SCOPUS. The selection and inclusion of studies were performed based on the abstract and, subsequently, on full-text analysis. Data extraction included the objective of the study, study design and outcome of interest. Two hundred and fifty-five articles were included in the review. Publication years ranged from 1981 to 2020. Most studies used the model to explore the effects of potential treatments for parkinsonism. Although the methodological characteristics used are quite varied, most studies used Wistar rats as experimental subjects. The most frequent dose of haloperidol used was 1.0 mg/kg, and the horizontal bar test was the most used to assess catalepsy. The data presented here provide a framework for an evidence-based approach to the design of preclinical research on parkinsonism using the haloperidol-induced catalepsy model. This model has been used routinely and successfully and is likely to continue to play a critical role in the ongoing search for the next generation of therapeutic interventions for parkinsonism.

Executive function in children with and without developmental coordination disorder: A comparative study.

BACKGROUND: Children with motor impairments also show poor performance in some executive functions' components. However, there is no consensus on which specific executive subdomain is more impacted. AIM: The objective of this study was to compare executive functions in children with developmental coordination disorder (DCD), at risk for DCD (r-DCD), and in typically developing (TD) children. METHODS AND PROCEDURES: A sample of 397 children was assessed using the MABC-2. Two groups of children were identified; DCD (n = 63) and at r-DCD (n = 31). A third matched group of children with TD (n = 63) was formed. The MABC-2 checklist and the WASI tests were used as screening tools. Measures of executive function including verbal and nonverbal tasks for working memory, inhibitory control, and cognitive flexibility were tested. Multivariate analysis of variance followed by analyses of variance and Bonferroni tests were used to verify group effects on executive functions. RESULTS: A significant group effects were found for Working Memory, Λ = .78, F(4, 360) = 10.12, p ≤ .001, ηp2 = .12; Inhibitory Control, Λ = .59, F(16, 294) = 5.48, p ≤ .001, ηp2 = .23; and Cognitive Flexibility and Inhibitory Control, Λ = .60, F(22, 288) = 3.74, p ≤ .001, ηp2 = .22, with moderate effect sizes. The DCD group showed lower scores compared with the TD group on the visuospatial and verbal working memory; inhibitory control and in tasks of cognitive flexibility; the r-DCD group showed lower scores compared with the TD group for visuospatial working memory and for cognitive flexibility. CONCLUSIONS AND IMPLICATIONS: Poor performance in several measures of executive functions in children with DCD emphasized the need of motor/executive task-specific interventions. Furthermore, children at r-DCD showed low scores in several executive functions; therefore, preventive services should also be provided for this subclinical group.

Assessing support needs in children with intellectual disability and motor impairments: measurement invariance and group differences.

BACKGROUND: This study assessed the equivalence of the measurement of support needs between children with intellectual disability (ID) and children with intellectual and motor disabilities (IMD) and compared both groups in the different domains of support. METHOD: The Supports Intensity Scale-Children's Version was used to assess the support needs of 713 children with ID and 286 children with IMD, mainly associated with cerebral palsy. RESULTS: The results supported measurement invariance between the group of ID and IMD, which allowed to conduct comparison between them. Children with IMD scored higher on support needs than did children without IMD, suggesting that children with IMD needed more support than their peers without motor impairments. Furthermore, the ID levels interacted with motor impairments: at the highest levels of ID, groups tended to be similar in support needs, with high scores and low variability. The greatest differences were found in the domains of Home and Community activities. CONCLUSIONS: This study points to the across-condition of the construct of support needs in populations with intellectual and developmental disabilities. However, additional mobility impairments should be considered during the evaluation and planning of systems of support. In this regard, the Supports Intensity Scale-Children's Version might have limitations when discriminating between samples with high support needs.

Motor and cognitive impairments in spinocerebellar ataxia type 7 and its correlations with cortical volumes.

Spinocerebellar Ataxia Type 7 (SCA7) is a neurodegenerative disorder caused by cytosine-adenine-guanine (CAG) repeat expansion. It is clinically characterized by ataxia and visual loss. To date, little is known about SCA7 cognitive impairments and its relationship with grey matter volume (GMV) changes. The aim of this study was to explore SCA7 patients' performance in specific components of auditory-verbal neuropsychological tests and to correlate their scores with genetic mutation, severity of ataxia and GMV. We assessed verbal memory and verbal fluency proficiencies in 31 genetically confirmed SCA7 patients, and compared their results with 32 healthy matched volunteers; we also correlated CAG repeats and severity of motor symptoms with performance in the auditory-verbal tests. SCA7 patients exhibited deficiencies in several components of these cognitive tasks, which were independent of motor impairments and showed no relation to CAG repeats. Based on Resonance Images performed in 27 patients we found association between ataxia severity and GMV in "sensoriomotor" cerebellum, as well as correlations of impaired verbal memory and semantic fluency scores with GMV in association cortices, including the right parahippocampal gyrus. To our knowledge, this is the first report of deficits in the organization of semantic information and in the evocation of verbal material, as well as greater susceptibility to proactive interference in SCA7 patients. These findings bring novel information about specific cognitive abilities in SCA7 patients, particularly verbal memory and fluency, and their relation with GMV variations in circumscribed brain regions, including association cortices known to have functional relationships with the cerebellum.

Influence of regional iron on the motor impairments of Parkinson's disease: A quantitative susceptibility mapping study.

PURPOSE: Because the roles of striatal-thalamo-cortical and cerebello-thalamo-cortical circuits in the heterogeneous motor impairments of Parkinson's disease (PD) are becoming recognized, this study was designed to investigate the relationships between regional iron in the cardinal subcortical nuclei in these circuits and the different motor impairments. MATERIALS AND METHODS: Sixty-two PD patients and 40 normal subjects were included and accepted for Enhanced T2 -Star Weighted Angiography Scanning (3.0T). According to the Unified Parkinson's Disease Rating Scale, patients were divided into tremor-dominant (PD-TD) and akinetic/rigid-dominant groups (PD-AR). The intergroup differences of magnetic susceptibility in those cardinal nuclei were measured. Correlation analyses between magnetic susceptibility and motor impairments were performed in all patients. RESULTS: Nigral magnetic susceptibility significantly increased for each PD group compared with controls (P < 0.001 for PD-TD; P = 0.001 for PD-AR). Magnetic susceptibility in the dentate nucleus (DN) and red nucleus (RN) for the PD-TD patients were significantly increased compared with controls (P < 0.001 and P = 0.004, respectively). Magnetic susceptibility in these regions was also significantly correlated with tremor severity (r = 0.444, P = 0.001 for DN; r = 0.418, P = 0.001 for RN). Significant correlation between caudate magnetic susceptibility and akinetic/rigid severity were observed (r = -0.322, P = 0.015). CONCLUSION: This study provides evidence that nigral iron accumulation is a common characteristic in PD, while iron accumulation in the DN and RN is correlated with tremor symptoms. Our data also indicate that caudate iron content may be a potential marker for akinetic/rigid progression. LEVEL OF EVIDENCE: 3 J. MAGN. RESON. IMAGING 2017;45:1335-1342.

The Association Between Parkinson's Disease Motor Impairments and Pain.

OBJECTIVE: This study aimed to: 1) examine the severity and frequency of pain and the extent to which pain interferes with work and 2) explore the contributions of motor impairments to pain in people with Parkinson's disease (PD). METHOD: Pain severity, frequency and the impact of pain on work were determined using subscores from the SF-36TM, Parkinson's Disease Questionnaire and SF-12v2TM, respectively, in 231 people with Parkinson's disease. Motor impairments were measured using the Unified Parkinson's Disease Rating Scale. Freezing of gait was determined as its presence or absence in the last month. Associations between impairments and pain were examined using logistic regression. RESULTS: Pain was reported by 187 (81%) participants, with 91 (39%) reporting pain of moderate severity or worse. Pain interfered with work to some extent in 158 (68%) participants. After adjusting for age and gender, increased rigidity was associated with higher pain frequency and more pain that interfered with work (for both models, Odds Ratio = 1.14, 95% confidence interval 1.0-1.3). Tremor was not associated with any measures of pain and motor impairments were not associated with pain severity. CONCLUSIONS: Most people with PD experience pain at least monthly and pain interferes with daily activities. PD impairments are associated with more frequent pain and pain that interferes with work, with rigidity having the strongest association. Development of Parkinson's disease-specific pain assessments and further investigation into the association between PD impairments and pain is warranted.

Bottom-up or top-down in dream neuroscience? A top-down critique of two bottom-up studies.

Recent neuroscientific studies of dreaming, specifically those in relation to waking sensory-motor impairments, but also more generally, betray a faulty understanding of the sort of process that dreaming is. They adhere to the belief that dreaming is a bottom-up phenomenon, whose form and content is dictated by sensory-motor brain stem activity, rather than a top-down process initiated and controlled by higher-level cognitive systems. But empirical data strongly support the latter alternative, and refute the conceptualization and interpretation of recent studies of dreaming in sensory-motor impairment in particular and of recent dream neuroscience in general.

Motor Impairment Referrals to an International Child Development Clinic: It is Not Always Cerebral Palsy.

BACKGROUND: The majority of the estimated 50 to 100 million children living with disability worldwide reside in low- or middle-income countries. As families migrate to avoid humanitarian crises, children with developmental disability and delay warrant particular attention in refugee and international health settings. During transitions, medical documentation may be lost and diagnoses may not be fully understood, contributing to the challenges of determining etiologies of motor impairment. METHODS: Of the first 100 refugee children who were referred to the Child Development Clinic, we identified a subset of children referred for motor impairment or cerebral palsy. Data on their presentation, diagnoses following evaluation, and therapeutic services required was collected by retrospective chart review. RESULTS: Twenty children were referred for motor impairment and cerebral palsy. Average age was 8.9 years; 45% were female. Eight children were eventually diagnosed with cerebral palsy, and 12 had alternate or inconclusive diagnoses. Microcephaly was more common in children diagnosed with cerebral palsy. CONCLUSIONS: The frequent differences between referral and final diagnoses in refugee children referred for cerebral palsy highlights the need for pediatricians' careful examination and diagnostic reasoning upon initial presentation.

Poor Motor Competence Affects Functional Capacities and Healthcare in Children and Adolescents with Obesity.

BACKGROUND: From a young age, children learn different motor skills known as fundamental motor skills. The acquisition of these skills is crucial for the future development of context-tailored actions that could improve adherence to physical activity (PA) practice. Motor competence and function deficits have been associated with pediatric obesity. We reviewed the literature data regarding motor competence in pediatrics and impaired motor performance in children and adolescents with obesity. METHODS: We assessed the abstracts of the available literature (n = 110) and reviewed the full texts of potentially relevant articles (n = 65) that were analyzed to provide a critical discussion. RESULTS: Children and adolescents with obesity show impaired motor performance, executive functions, postural control, and motor coordination. Children's age represents a crucial point in the development of motor skills. Early interventions are crucial to preventing declines in motor proficiency and impacting children's PA and overall fitness levels. CONCLUSIONS: To involve children, the PA protocol must be fun and tailored in consideration of several aspects, such as clinical picture, level of physical fitness, and motor skills. A supervised adapted exercise program is useful to personalized PA programs from an early pediatric age.

Children with bilateral cerebral palsy use their hip joint to complete a step-up task.

Performance in stair-climbing is largely associated with disruptions to mobility and community participation in children with cerebral palsy (CP). It is important to understand the nature of motor impairments responsible for making stairs a challenge in children with bilateral CP to clarify underlying causes of impaired mobility. In pediatric clinical populations, sensitive measurements of movement quality can be captured during the initial step of stair ascent. Thus, the purpose of this study was to quantify the lower limb joint moments of children with bilateral CP during the stance phases of a step-up task. Participants performed multiple stepping trials in a university gait laboratory. Outcome measures included extensor support moments (the sum of hip, knee, and ankle sagittal plane moments), hip abduction moments, and their timing. We recruited seven participants per group. We found that peak support and hip abduction moments were similar in the bilateral CP group compared to the typical development (TD) group. We also found that children with bilateral CP timed their peak moments closer together and increasingly depended on the hip joint to complete the task, especially in their more affected (MA) lower limb. Our investigation highlights some underlying causes that may make stair climbing a challenge for the CP population, including a loss of selective voluntary motor control (SVMC), and provides a possible treatment approach to strengthen lower limb muscles.

How Do People with Limited Movement Personalize Upper-Body Gestures? Considerations for the Design of Personalized and Accessible Gesture Interfaces.

Always-on, upper-body input from sensors like accelerometers, infrared cameras, and electromyography hold promise to enable accessible gesture input for people with upper-body motor impairments. When these sensors are distributed across the person's body, they can enable the use of varied body parts and gestures for device interaction. Personalized upper-body gestures that enable input from diverse body parts including the head, neck, shoulders, arms, hands and fingers and match the abilities of each user, could be useful for ensuring that gesture systems are accessible. In this work, we characterize the personalized gesture sets designed by 25 participants with upper-body motor impairments and develop design recommendations for upper-body personalized gesture interfaces. We found that the personalized gesture sets that participants designed were highly ability-specific. Even within a specific type of disability, there were significant differences in what muscles participants used to perform upper-body gestures, with some pre-dominantly using shoulder and upper-arm muscles, and others solely using their finger muscles. Eight percent of gestures that participants designed were with their head, neck, and shoulders, rather than their hands and fingers, demonstrating the importance of tracking the whole upper-body. To combat fatigue, participants performed 51% of gestures with their hands resting on or barely coming off of their armrest, highlighting the importance of using sensing mechanisms that are agnostic to the location and orientation of the body. Lastly, participants activated their muscles but did not visibly move during 10% of the gestures, demonstrating the need for using sensors that can sense muscle activations without movement. Both inertial measurement unit (IMU) and electromyography (EMG) wearable sensors proved to be promising sensors to differentiate between personalized gestures. Personalized upper-body gesture interfaces that take advantage of each person's abilities are critical for enabling accessible upper-body gestures for people with upper-body motor impairments.

Biochemical and behavioral effects of rosmarinic acid treatment in an animal model of Parkinson's disease induced by MPTP.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The main therapeutic approach available nowadays relieves motor symptoms but does not prevent or stop neurodegeneration. Rosmarinic acid (RA), an ester of caffeic and 3,4-dihydroxyphenylacetic acids, is obtained from numerous plant species such as Salvia officinalis L. (sage) and Rosmarinus officinalis (rosemary). This compound has a wide spectrum of biological activities, such as antioxidant and anti-inflammatory, and could be an additional therapy for neurodegenerative disorders. Here we evaluated the potential neuroprotective effects of RA treatment in a murine model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were separated into four groups: CN, Control/saline; RA, Rosmarinic acid/vehicle; MPTP, MPTP/saline; MPTP+RA, MPTP/RA. RA (20 mg/kg, or vehicle) was administered orally by intra-gastric gavage for 14 days, one hour before MPTP or saline injection. MPTP groups received the drug (30 mg/kg, intraperitoneally) once a day for five days (fourth to the eighth day of the experiment). MPTP-treated animals displayed hyperlocomotion behavior, which was significantly prevented by RA treatment. In addition, RA treatment increased dopaminergic signaling in the parkinsonian mice and improved the monoaminergic system in healthy animals. Analysis of alterations in the striatal mRNA expression of dopaminergic system components showed that MAO-A expression was increased in the MPTP+AR group. Overall, this study brings new evidence of the potential neuroprotective properties of RA not only in preventing behavioral features observed in PD, but also by improving neurotransmission in the healthy brain.

Effect of Neural Tissue Mobilization on Sensory-Motor Impairments in Breast Cancer Survivors with Lymphedema: An Experimental Study.

BACKGROUND: Breast surgery, Axillary Lymph Node Dissection (ALND), radiation and chemotherapy may develop several complications such as axillary web syndrome, frozen shoulder, numbness, shoulder pain and range of motion restriction, lymphostasis, and lymphedema. Up to 77% report sensory disturbance in the breast or arm after breast surgery. These short- and long-term consequences have dramatic impact on physical function and quality of life in this population. AIMS: The aim of the study was to determine the effect of neural tissue mobilization on sensory-motor impairments in breast cancer survivors with lymphedema. SUBJECTS AND METHODS: This study was carried out by analyzing total 100 breast cancer survivor women, with lymphedema aged between 30-65 years of age who had undergone breast surgery mostly lumpectomy along with chemotherapy or radiation therapy. Participants were divided into two groups by random allocation. One group underwent neurodynamic mobilization and the other group conventional physiotherapy.The treatment protocol was given for 6 weeks. Parameters such ROM, pain, lymphedema and sensory-motor impairments were assessed at the baseline before the treatment and 6 weeks after the treatment. RESULT: The result from this study shows that there is significant improvement (p<0.0001, t-value 4.69) in mTNS of patients undergoing neural tissue mobilization,whereas there was no significant improvement (p=0.05, t-value 1.951) seen in patients undergoing conventional physiotherapy. CONCLUSION: This study concludes that effect of neural tissue mobilization has significant impact on sensory motor impairments as compared to conventional treatment protocol in breast cancer survivors with lymphedema.Pain and ROM showed similar difference with both the treatment protocols. It was also observed that patients with mild and moderate lymphedema showed significant improvement as compared to patients with severe lymphedema.