Chronic Motor Impairment Research Articles

Macrostructural Brain Abnormalities in Spinal Muscular Atrophy: A Case-Control Study.

Most individuals with spinal muscular atrophy (SMA) on disease-modifying therapies continue to have chronic motor impairment. Insights into brain involvement in SMA may open new pathways for adjunctive therapies to optimize outcomes. We aimed to characterize macrostructural brain abnormalities detected by MRI in individuals with SMA compared with peer controls. We conducted a cross-sectional case-control study of children and adults with a confirmed genetic diagnosis of 5q SMA, and peer controls matched by age and sex. Brain MRIs acquired on a 3T MRI scanner through a standardized research protocol were reviewed to qualitatively assess the presence of macrostructural changes. The primary outcome was the presence of any structural brain anomaly on MRI. In addition, the total volume of each participant's lateral ventricles was quantified by volumetry using MRIcron. Genetic and clinical variables, including SMN2 copy number and motor function (Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module scores), were then correlated with neuroimaging findings. A total of 42 participants completed the study (mean age 17.4, range 7-40; 67% male). Of the 21 individuals with 5q SMA, 9 (43%) had macrostructural brain abnormalities identified on MRI compared with 2 of 21 (10%) peer controls (odds ratio 7.1, 95% confidence interval 1.4-34.0). In patients with SMA, the most common structural changes were widening of the arachnoid spaces (n = 4) and ventriculomegaly (n = 4). Individuals with SMA had larger median lateral ventricular volume than their normally developing peers (9.3 mL, interquartile range [IQR] 5.5-13.1 vs 5.3 mL, IQR 3.8-9.8; p = 0.034). Structural brain abnormalities were more frequent in those with 2 SMN2 copies (3/5, 60%) compared with 3 or 4 SMN2 copies (4/10, 40% and 2/6, 33% respectively), not reaching significance. We found no association between structural changes and motor function scores. Individuals with SMA have higher rates of macrostructural brain abnormalities than their neurotypical peers, suggesting CNS involvement in SMA. Understanding changes in the brain architecture of the SMA population can inform the development of adjunct therapies targeting the CNS and potentially guide rehabilitation strategies.

Public Health Surveillance of Pediatric Polio in Pakistan: A Cohort Study.

Background and objective Polio continues to be endemic in Pakistan despite substantial international efforts to combat it, which presents a serious public health concern. Strategies for eradicating polio depend on understanding the dynamics of pediatric polio transmission and the efficacy of surveillance. This research study aimed to critically evaluate the public health surveillance system for pediatric polio in Pakistan and proposerecommendations for improvement. Methodology This study was conducted from June 2020 to July 2023 in three well-known hospitals in different areas of Pakistan and involved26 patients. Reviews of medical records, interviews, and surveillance report analysis were all part of the data collection process. Descriptive statistics, chi-square tests, and logistic regression analysis were performed using SPSS Statistics version 27.0 (IBM Corp., Armonk, NY) with the statistical significance set at p<0.05. Results The highest incidence of polio was observed in children aged 13-24 months (nine patients, 34.62%), with males accounting for 14 cases (53.85%) and urban residents16 cases (61.54%). Vaccination status significantly influences disease incidence (p<0.001), with two patients (7.69%) unvaccinated, 10 patients (38.46%) partially vaccinated, and 14 patients (53.85%) fully vaccinated. Paralysis was the predominant symptom in 16 patients (61.54%). Recovery outcomes varied, with eight patients (31%) fully recovering, 12 patients (46%) showing partial improvement, and six patients (23%) experiencing chronic motor impairments. Effective surveillance depends on timely reporting [odds ratio (OR): 2.15, p<0.001] and healthcare worker training (OR: 1.67, p<0.001), highlighting crucial aspects of polio management strategies. Conclusions Based on our findings, vaccination status significantly impacts polio occurrence, with a notable proportion found in partially vaccinated or unvaccinated children. Paralysis remains the primary symptom, with varied recovery outcomes, including chronic motor impairments in some cases. This study underscores Pakistan's ongoing challenges with pediatric polio, highlighting the crucial need for improved vaccination, surveillance, and rehabilitation efforts.

Decoding of unimanual and bimanual reach-and-grasp actions from EMG and IMU signals in persons with cervical spinal cord injury.

Objective. Chronic motor impairments of arms and hands as the consequence of a cervical spinal cord injury (SCI) have a tremendous impact on activities of daily life. A considerable number of people however retain minimal voluntary motor control in the paralyzed parts of the upper limbs that are measurable by electromyography (EMG) and inertial measurement units (IMUs). An integration into human-machine interfaces (HMIs) holds promise for reliable grasp intent detection and intuitive assistive device control.Approach. We used a multimodal HMI incorporating EMG and IMU data to decode reach-and-grasp movements of groups of persons with cervical SCI (n = 4) and without (control, n = 13). A post-hoc evaluation of control group data aimed to identify optimal parameters for online, co-adaptive closed-loop HMI sessions with persons with cervical SCI. We compared the performance of real-time, Random Forest-based movement versus rest (2 classes) and grasp type predictors (3 classes) with respect to their co-adaptation and evaluated the underlying feature importance maps.Main results. Our multimodal approach enabled grasp decoding significantly better than EMG or IMU data alone (p<0.05). We found the 0.25 s directly prior to the first touch of an object to hold the most discriminative information. Our HMIs correctly predicted 79.3 ± STD 7.4 (102.7 ± STD 2.3 control group) out of 105 trials with grand average movement vs. rest prediction accuracies above 99.64% (100% sensitivity) and grasp prediction accuracies of 75.39 ± STD 13.77% (97.66 ± STD 5.48% control group). Co-adaption led to higher prediction accuracies with time, and we could identify adaptions in feature importances unique to each participant with cervical SCI.Significance. Our findings foster the development of multimodal and adaptive HMIs to allow persons with cervical SCI the intuitive control of assistive devices to improve personal independence.

Data-driven biomarkers better associate with stroke motor outcomes than theory-based biomarkers.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have associated motor outcomes with the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to model chronic motor outcomes after stroke and compares the accuracy of these associations to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients from the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) Stroke Recovery Working Group. Using the explained variance metric to measure the strength of the association between chronic motor outcomes and imaging biomarkers, we compared theory-based biomarkers, like lesion load to known motor tracts, to three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had stronger associations with chronic motor outcomes accuracy than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R 2 = 0.210, P < 0.001), performing significantly better than the theory-based biomarkers of lesion load of the corticospinal tract (R 2 = 0.132, P < 0.001) and of multiple descending motor tracts (R 2 = 0.180, P < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R 2 = 0.200, P < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R 2 = 0.167, P < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved the strength of associations for theory-based and data-driven biomarkers. Combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R 2 = 0.241, P < 0.001. Overall, these results demonstrate that out-of-sample associations between chronic motor outcomes and data-driven imaging features, particularly when lesion data is represented in terms of structural disconnection, are stronger than associations between chronic motor outcomes and theory-based biomarkers. However, combining both theory-based and data-driven models provides the most robust associations.

Chronic motor performance following different traumatic brain injury severity-A systematic review.

Traumatic brain injury (TBI) is now known to be a chronic disease, causing ongoing neurodegeneration and linked to increased risk of neurodegenerative motor diseases, such as Parkinson's disease and amyotrophic lateral sclerosis. While the presentation of motor deficits acutely following traumatic brain injury is well-documented, however, less is known about how these evolve in the long-term post-injury, or how the initial severity of injury affects these outcomes. The purpose of this review, therefore, was to examine objective assessment of chronic motor impairment across the spectrum of TBI in both preclinical and clinical models. PubMed, Embase, Scopus, and PsycINFO databases were searched with a search strategy containing key search terms for TBI and motor function. Original research articles reporting chronic motor outcomes with a clearly defined TBI severity (mild, repeated mild, moderate, moderate-severe, and severe) in an adult population were included. A total of 97 studies met the inclusion criteria, incorporating 62 preclinical and 35 clinical studies. Motor domains examined included neuroscore, gait, fine-motor, balance, and locomotion for preclinical studies and neuroscore, fine-motor, posture, and gait for clinical studies. There was little consensus among the articles presented, with extensive differences both in assessment methodology of the tests and parameters reported. In general, an effect of severity was seen, with more severe injury leading to persistent motor deficits, although subtle fine motor deficits were also seen clinically following repeated injury. Only six clinical studies investigated motor outcomes beyond 10 years post-injury and two preclinical studies to 18-24 months post-injury, and, as such, the interaction between a previous TBI and aging on motor performance is yet to be comprehensively examined. Further research is required to establish standardized motor assessment procedures to fully characterize chronic motor impairment across the spectrum of TBI with comprehensive outcomes and consistent protocols. Longitudinal studies investigating the same cohort over time are also a key for understanding the interaction between TBI and aging. This is particularly critical, given the risk of neurodegenerative motor disease development following TBI.

The Finer Aspects of Grid-Walking and Cylinder Tests for Experimental Stroke Recovery Studies in Mice.

The choice of behavioral tests and their proper execution is critically important for experimental and preclinical therapeutic stroke recovery studies, where improvement of impaired neurological function(s) is the main outcome measure. Two tests that focus on spontaneous motor behaviors of the forelimb during gait and exploratory rearing and are expert recommended for stroke recovery studies in mice are grid-walking and cylinder tasks. Both tests have been widely used in various experimental stroke studies to evaluate acute and chronic motor impairment. To facilitate adoption of these tests and consistency of use between different research laboratories, this chapter describes a simple and rigorous protocol and our schemes to successfully perform both tasks in mice and evaluate motor dysfunction and recovery after stroke. In addition, we provide practical tips to minimize experimental bias and acquire data for analyses.

Body Structural Description Impairment in Complex Regional Pain Syndrome Type I.

BackgroundComplex Regional Pain Syndrome (CRPS) is a clinical syndrome composed of chronic pain, motor impairment, and autonomic dysfunction, usually affecting a limb. Although CRPS seems to be a peripheral disorder, it is accompanied by parietal alterations leading to body schema impairments (the online representations of the body). Impairments to body structural description (the topographical bodily map) were not assessed systematically in CRPS. A patient we encountered with severe disruption to her bodily structural description led us to study this domain further.AimsTo document aberrant body structural description in subjects with CRPS using an object assembly task.MethodsBody Schema Study: 6 subjects with CRPS-I and six age and sex-matched healthy controls completed visual puzzles taken from WAIS-III and WAIS-R. The puzzles were either related to the human body or non-human body objects. Mann–Whitney U-tests were performed to compare groups’ performances.ResultsThe CRPS group received relatively lower scores compared to controls for human body objects (u = 3, p < 0.05), whereas the non-human object scoring did not reveal significant differences between groups (u = 9, p > 0.05).ConclusionCRPS subjects suffer from impaired body structural description, taking the form of body parts disassembly and body parts discontinuity. This impairment can serve as a nidus for aberrant psychological representation of the body.

A comparison of lesion-overlap approaches to quantify corticospinal tract involvement in chronic stroke

• Corticospinal tract involvement with a stroke lesion is a biomarker of motor outcome. • Four approaches quantifying corticospinal tract involvement were compared. • All approaches explained 20–30% of variance in chronic stroke motor impairment. • Maximum overlap and percent subsections injured approaches explained most variance.

Effects of Repetitive Peripheral Sensory Stimulation in the Subacute and Chronic Phases After Stroke: Study Protocol for a Pilot Randomized Trial.

BackgroundRepetitive peripheral nerve sensory stimulation (RPSS) is a potential add-on intervention to motor training for rehabilitation of upper limb paresis after stroke. Benefits of RPSS were reported in subjects in the chronic phase after stroke, but there is limited information about the effects of this intervention within the 1st weeks or months. The primary goal of this study is to compare, in a head-to-head proof-of-principle study, the impact of a single session of suprasensory vs. subsensory RPSS on the upper limb motor performance and learning in subjects at different phases after stroke subacute and chronic phases and mild upper limb motor impairments after stroke. In addition, we examine the effects of RPSS on brain perfusion, functional imaging activation, and γ-aminobutyric acid (GABA) levels. Subjects with mild upper limb motor impairments will be tested with MRI and clinical assessment either at an early (7 days to 3 months post-stroke) or at a chronic (>6 months) stage after stroke.MethodsIn this multicenter, randomized, parallel-group, proof-of-principle clinical trial with blinded assessment of outcomes, we compare the effects of one session of suprasensory or subsensory RPSS in patients with ischemic or hemorrhagic stroke and upper limb paresis. Clinical assessment and MRI will be performed only once in each subject (either at an early or at a chronic stage). The primary outcome is the change in performance in the Jebsen–Taylor test. Secondary outcomes: hand strength, cerebral blood flow assessed with arterial spin labeling, changes in the blood oxygenation level-dependent (BOLD) effect in ipsilesional and contralesional primary motor cortex (M1) on the left and the right hemispheres assessed with functional MRI (fMRI) during a finger-tapping task performed with the paretic hand, and changes in GABA levels in ipsilesional and contralesional M1 evaluated with spectroscopy. The changes in outcomes will be compared in four groups: suprasensory, early; subsensory, early; suprasensory, chronic; and subsensory, chronic.DiscussionThe results of this study are relevant to inform future clinical trials to tailor RPSS to patients more likely to benefit from this intervention.Trial RegistrationNCT03956407.

Altered biomechanical strategies of the paretic hip and knee joints during a step-up task

ABSTRACT Background Stroke often leads to chronic motor impairments in the paretic lower limb that can constrain lower extremity movement and negatively impact the ability to navigate stairs or curbs. This cross-sectional study investigated the differences in hip and knee biomechanical strategies during a step-up task between five adults with hemiparetic stroke and five age-matched adults without stroke. Methods Participants were instructed to step up onto a 10.2 cm platform, where joint biomechanics were quantified for the hip in the frontal plane and the hip and knee in the sagittal plane. Peak joint kinematics were identified during the leading limb swing phase, and peak joint moments and power were identified during the leading limb pull-up phase of stance. Mixed effects regression models estimated fixed effects of limb (three levels: control dominant, stroke non-paretic, and stroke paretic) on biomechanical outcomes, while a random effect of participant controlled for within-participant correlations. Results Repeated assessments within participants (approximately 60 trials per lower limb) increased the effective sample size to between 12.0 and 19.6. Altered biomechanical strategies of the paretic lower limb included reduced flexion angles and increased pelvic obliquity angles during swing, decreased power generation in the hip frontal plane during stance, and decreased moment and power generation in the knee sagittal plane during stance. A strategy of substantial interest was the elevated hip sagittal plane moment and power generation in both stroke limbs. Conclusions Our findings suggest that chronic motor impairments following stroke can lead to inefficient biomechanical strategies when stepping up.

Animal model of repeated low-level blast traumatic brain injury displays acute and chronic neurobehavioral and neuropathological changes

Blast-induced neurotrauma (BINT) is not only a signature injury to soldiers in combat field and training facilities but may also a growing concern in civilian population due to recent increases in the use of improvised explosives by insurgent groups. Unlike moderate or severe BINT, repeated low-level blast (rLLB) is different in its etiology as well as pathology. Due to the constant use of heavy weaponry as part of combat readiness, rLLB usually occurs in service members undergoing training as part of combat readiness. rLLB does not display overt pathological symptoms; however, earlier studies report chronic neurocognitive changes such as altered mood, irritability, and aggressive behavior, all of which may be caused by subtle neuropathological manifestations. Current animal models of rLLB for investigation of neurobehavioral and neuropathological alterations have not been adequate and do not sufficiently represent rLLB conditions. Here, we developed a rat model of rLLB by applying controlled low-level blast pressures (<10 psi) repeated successively five times to mimic the pressures experienced by service members. Using this model, we assessed anxiety-like symptoms, motor coordination, and short-term memory as a function of time. We also examined levels of superoxide-producing enzyme NADPH oxidase, microglial activation, and reactive astrocytosis as factors likely contributing to these neurobehavioral changes. Animals exposed to rLLB displayed acute and chronic anxiety-like symptoms, motor and short-term memory impairments. These changes were paralleled by increased microglial activation and reactive astrocytosis. Conversely, animals exposed to a single low-level blast did not display significant changes. Collectively, this study demonstrates that, unlike a single low-level blast, rLLB exerts a cumulative impact on different brain regions and produces chronic neuropathological changes in so doing, may be responsible for neurobehavioral alterations.

Very preterm birth and trajectories of domain-specific self-concept from childhood into adulthood.

Self-concept refers to individuals' perceptions of themselves in specific domains and is closely related with their overall self-esteem. Lower self-esteem has been reported in those born preterm (<37 weeks gestation), but the development of self-concept has not been studied in this population. This study investigates whether differences in trajectories of domain-specific self-concepts are explained by premature birth or other risk factors, using the Bavarian Longitudinal Study (N = 460), a population-based study of very preterm (VP; <32 weeks gestation)/very low birth weight (VLBW; <1500 g) cohort and term-born controls. Trajectories of body and social self-concept from 6 to 26 years of age were estimated using latent class growth analysis. Regression models examined the effects of VP/VLBW and other individual, social, and family factors. Two trajectories - one stable and one decreasing - were identified for both self-concepts. VP/VLBW birth was associated with decreasing self-concept in both domains, although the effect of VP/VLBW on social self-concept was weakened in the adjusted analysis. Furthermore, mediated pathways were found from VP/VLBW to decreasing social self-concept via chronic bullying (β = 0.05, 95% CI [0.002, 0.12]) and motor impairments (β = 0.04, 95% CI [0.01, 0.07]), suggesting that negative self-concept in the VP/VLBW population is partially modifiable through improving peer relationships and motor impairments in childhood.

Chronic musculoskeletal impairment is associated with alterations in brain regions responsible for the production and perception of movement.

Key points Massive irreparable rotator cuff tear was used as a model to study the impact of chronic pain and motor impairment on the motor systems of the human brain using magnetic resonance imaging.Patients show markers of lower grey/white matter integrity and lower functional connectivity compared with control participants in regions responsible for movement and the perception of visual movement and body shape.An independent cohort of patients showed relative deficits in the perception of visual motion and hand laterality compared with an age‐matched control group.These data support the hypothesis that the structure and function of the motor control system differs in patients who have experienced chronic motor impairment.This work also raises a new hypothesis, supported by neuroimaging and behaviour, that a loss of motor function could also be associated with off‐target effects, namely a reduced ability to perceive motion and body form. Changes in the way we move can induce changes in the brain, yet we know little of such plasticity in relation to musculoskeletal diseases. Here we use massive irreparable rotator cuff tear as a model to study the impact of chronic motor impairment and pain on the human brain. Cuff tear destabilises the shoulder, impairing upper‐limb function in overhead and load‐bearing tasks. We used neuroimaging and behavioural testing to investigate how brain structure and function differed in cuff tear patients and controls (imaging: 21 patients, age 76.3 ± 7.68; 18 controls, age 74.9 ± 6.59; behaviour: 13 patients, age 75.5 ± 10.2; 11 controls, age 73.4 ± 5.01). We observed lower grey matter density and cortical thickness in cuff tear patients in the postcentral gyrus, inferior parietal lobule, temporal‐parietal junction and the pulvinar – areas implicated in somatosensation, reach/grasp and body form perception. In patients we also observed lower functional connectivity between the motor network and the middle temporal visual cortex (MT), a region involved in visual motion perception. Lower white matter integrity was observed in patients in the inferior fronto‐occipital/longitudinal fasciculi. We investigated the cognitive domains associated with the brain regions identified. Patients exhibited relative impairment in visual body judgements and the perception of biological/global motion. These data support our initial hypothesis that cuff tear is associated with differences in the brain's motor control regions in comparison with unaffected individuals. Moreover, our combination of neuroimaging and behavioural data raises a new hypothesis that chronic motor impairment is associated with an altered perception of visual motion and body form.

Human papillomavirus vaccine to prevent cervical intraepithelial neoplasia in Japan: A nationwide case-control study.

Cervical cancer remains among the most common cancers in women worldwide and can be prevented by vaccination. The Ministry of Health, Labour and Welfare of Japan suspended active recommendation of regular human papillomavirus (HPV) vaccines in 2013 because of various symptoms including chronic pain and motor impairment. This nationwide case‐control study from April 2013 to March 2017 targeted women aged 20‐24 years old at cervical screening. We compared HPV vaccination exposure between those with abnormal and normal cytology. Abnormal cytology was classified based on the results of histological test and we calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 – OR) × 100. A total of 2483 cases and 12 296 controls (one‐to‐five matching) were eligible in 31 municipalities in Japan. The distribution of histological abnormalities among cases was 797 CIN1 (including dysplasia) (32.1%), 165 CIN2 (6.7%), 44 CIN3 (1.8%), and eight squamous cell carcinoma (SCC) (0.3%). The OR of HPV vaccination compared with no vaccination for abnormal cytology, CIN1+, CIN2+, and CIN3+ versus controls was 0.42 (95% CI, 0.34‐0.50), 0.42 (95% CI, 0.31‐0.58), 0.25 (95% CI, 0.12‐0.54), and 0.19 (95% CI, 0.03‐1.15), respectively, equating to a vaccine effectiveness of 58.5%, 57.9%, 74.8%, and 80.9%, respectively. Eight patients had SCC, none was vaccinated. This nationwide case‐control study in Japan demonstrated a substantial risk reduction in abnormal cytology and CIN among women who did versus those who did not receive HPV vaccination.

Reorganization of functional brain network architecture in chronic osteoarthritis pain.

Osteoarthritis (OA) manifests with chronic pain, motor impairment, and proprioceptive changes. However, the role of the brain in the disease is largely unknown. Here, we studied brain networks using the mathematical properties of graphs in a large sample of knee and hip OA (KOA, n = 91; HOA, n = 23) patients. We used a robust validation strategy by subdividing the KOA data into discovery and testing groups and tested the generalizability of our findings in HOA. Despite brain global topological properties being conserved in OA, we show there is a network wide pattern of reorganization that can be captured at the subject‐level by a single measure, the hub disruption index. We localized reorganization patterns and uncovered a shift in the hierarchy of network hubs in OA: primary sensory and motor regions and parahippocampal gyrus behave as hubs and insular cortex loses its central placement. At an intermediate level of network structure, frontoparietal and cingulo‐opercular modules showed preferential reorganization. We examined the association between network properties and clinical correlates: global disruption indices and isolated degree properties did not reflect clinical parameters; however, by modeling whole brain nodal degree properties, we identified a distributed set of regions that reliably predicted pain intensity in KOA and generalized to hip OA. Together, our findings reveal that while conserving global topological properties, brain network architecture reorganizes in OA, at both global and local scale. Network connectivity related to OA pain intensity is dissociated from the major hub disruptions, challenging the extent of dependence of OA pain on nociceptive signaling.

Feasibility of Two Different EMG-Based Pattern Recognition Control Paradigms to Control a Robot After Stroke - Case Study.

Stroke often results in chronic motor impairment of the upper-extremity yet neither traditional- nor robotics-based therapy has been able to affect this in a profound way. Supporting the weak affected shoulder against gravity improves reaching distance and minimizes abnormal co-contraction of the elbow, wrist, and fingers after stroke. However, it is necessary to assess the feasibility and efficacy of real-time controllers for this population as technology advances and a wearable shoulder device comes closer to reality. The aim of this study is to test two EMG-based controllers in this regard. A linear discriminant analysis based classifier was trained using extracted time domain and auto-regressive features from electromyographic data acquired during muscle effort required to move a load equivalent to 50 and 100% limb weight (abduction) and 150 and 200% limb weight (adduction). While rigidly connected to a custom lab-based robot, the participant was required to complete a series of lift and reach tasks under two different control paradigms: position-based control and force-based control. The participant successfully controlled the robot under both paradigms as indicated by first moving the robot arm into the proper vertical window and then reaching out as far as possible while remaining within the vertical window. This case study begins to assess the feasibility of using electromyographic data to classify the intended shoulder movement of a participant with stroke during a functional lift and reach type task. Next steps will assess how this type of support affects reaching function.

Playback of 50-kHz ultrasonic vocalizations overcomes psychomotor deficits induced by sub-chronic haloperidol treatment in rats

RationaleIn rodents, acute haloperidol treatment induces psychomotor impairments known as catalepsy, which models akinesia in humans and is characterized as an animal model of acute Parkinsonism, whereas sub-chronic haloperidol reduces exploratory behavior, which resembles bradykinesia. Haloperidol-induced catalepsy in rats can be ameliorated by playback of 50-kHz ultrasonic vocalizations (USV), an emotionally and motivationally relevant appetitive auditory stimulus, representing an animal model of paradoxical kinesia. In a condition like PD where patients suffer from chronic motor impairments, it is paramount to assess the long-term symptom relief in an animal model of Parkinsonism.ObjectivesWe investigated whether 50-kHz USV playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen.MethodsIn phase 1, distance traveled and number of rearing behavior were assessed in an activity chamber in order to investigate whether sub-chronic haloperidol treatment induced psychomotor impairments. In phase 2, we investigated whether 50-kHz USV playback could overcome these impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50-kHz USV radial maze playback paradigm.ResultsSub-chronic haloperidol treatment led to psychomotor deficits since the distance traveled and number of rearing behavior were reduced as compared to saline control group or baseline. These psychomotor impairments were ameliorated during playback of 50-kHz USV, with haloperidol treated rats showing a clear social approach behavior towards the sound source exclusively during playback.ConclusionsThis study provides evidence that 50-kHz USV playback induces paradoxical kinesia in rats exhibiting motor deficits after sub-chronic haloperidol, as we previously showed after acute haloperidol treatment.

Specific vagus nerve stimulation parameters alter serum cytokine levels in the absence of inflammation

BackgroundElectrical stimulation of peripheral nerves is a widely used technique to treat a variety of conditions including chronic pain, motor impairment, headaches, and epilepsy. Nerve stimulation to achieve efficacious symptomatic relief depends on the proper selection of electrical stimulation parameters to recruit the appropriate fibers within a nerve. Recently, electrical stimulation of the vagus nerve has shown promise for controlling inflammation and clinical trials have demonstrated efficacy for the treatment of inflammatory disorders. This application of vagus nerve stimulation activates the inflammatory reflex, reducing levels of inflammatory cytokines during inflammation.MethodsHere, we wanted to test whether altering the parameters of electrical vagus nerve stimulation would change circulating cytokine levels of normal healthy animals in the absence of increased inflammation. To examine this, we systematically tested a set of electrical stimulation parameters and measured serum cytokine levels in healthy mice.ResultsSurprisingly, we found that specific combinations of pulse width, pulse amplitude, and frequency produced significant increases of the pro-inflammatory cytokine tumor necrosis factor (TNF), while other parameters selectively lowered serum TNF levels, as compared to sham-stimulated mice. In addition, serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) were significantly increased by select parameters of electrical stimulation but remained unchanged with others.ConclusionsThese results indicate that electrical stimulation parameter selection is critically important for the modulation of cytokines via the cervical vagus nerve and that specific cytokines can be increased by electrical stimulation in the absence of inflammation. As the next generation of bioelectronic therapies and devices are developed to capitalize on the neural regulation of inflammation, the selection of nerve stimulation parameters will be a critically important variable for achieving cytokine-specific changes.

Self-efficacy and Reach Performance in Individuals With Mild Motor Impairment Due to Stroke

Background: Persistent deficits in arm function are common after stroke. An improved understanding of the factors that contribute to the performance of skilled arm movements is needed. One such factor may be self-efficacy (SE). Objective: To determine the level of SE for skilled, goal-directed reach actions in individuals with mild motor impairment after stroke and whether SE for reach performance correlated with actual reach performance. Methods: A total of 20 individuals with chronic stroke (months poststroke: mean 58.1 ± 38.8) and mild motor impairment (upper-extremity Fugl-Meyer [FM] motor score: mean 53.2, range 39 to 66) and 6 age-matched controls reached to targets presented in 2 directions (ipsilateral, contralateral). Prior to each block (24 reach trials), individuals rated their confidence on reaching to targets accurately and quickly on a scale that ranged from 0 (not very confident) to 10 (very confident). Results: Overall reach performance was slower and less accurate in the more-affected arm compared with both the less-affected arm and controls. SE for both reach speed and reach accuracy was lower for the more-affected arm compared with the less-affected arm. For reaches with the more-affected arm, SE for reach speed and age significantly predicted movement time to ipsilateral targets (R2 = 0.352), whereas SE for reach accuracy and FM motor score significantly predicted end point error to contralateral targets (R2 = 0.291). Conclusions: SE relates to measures of reach control and may serve as a target for interventions to improve proximal arm control after stroke.

Combinatorial Prg4 and Il-1ra Gene Therapy Protects Against Hyperalgesia and Cartilage Degeneration in Post-Traumatic Osteoarthritis.

Osteoarthritis (OA) is a degenerative disease of synovial joints characterized by progressive loss of articular cartilage, subchondral bone remodeling, and intra-articular inflammation with synovitis that results in chronic pain and motor impairment. Despite the economic and health impacts, current medical therapies are targeted at symptomatic relief of OA and fail to alter its progression. Given the complexity of OA pathogenesis, we hypothesized that a combinatorial gene therapy approach, designed to inhibit inflammation with interleukin-1 receptor antagonist (IL-1Ra) while promoting chondroprotection using lubricin (PRG4), would improve preservation of the joint compared to monotherapy alone. Employing two surgical techniques to model mild, moderate and severe posttraumatic OA, we found that combined delivery of helper-dependent adenoviruses (HDVs), expressing IL-1Ra and PRG4, preserved articular cartilage better than either monotherapy in both models as demonstrated by preservation of articular cartilage volume and surface area. This improved protection was associated with increased expression of proanabolic and cartilage matrix genes together with decreased expression of catabolic genes and inflammatory mediators. In addition to improvements in joint tissues, this combinatorial gene therapy prolonged protection against thermal hyperalgesia compared to either monotherapy. Taken together, our results show that a combinatorial strategy is superior to monotherapeutic approaches for treatment of posttraumatic OA.