Spatiotemporal modulation of a common set of muscle synergies during unpredictable and predictable gait perturbations in older adults.

Muscle synergies as functional low-dimensional building blocks of the neuromotor system regulate the activation patterns of muscle groups in a modular structure during locomotion. The purpose of the current study was to explore how older adults organize locomotor muscle synergies to counteract unpredictable and predictable gait perturbations during the perturbed steps and the recovery steps. Sixty-three healthy older adults (71.2±5.2 years) participated in the study. Mediolateral and anteroposterior unpredictable and predictable perturbations during walking were introduced using a treadmill. Muscle synergies were extracted from the electromyographic activity of 13 lower limb muscles using Gaussian non-negative matrix factorization. The four basic synergies responsible for unperturbed walking (weight acceptance, propulsion, early swing and late swing) were preserved in all applied gait perturbations, yet their temporal recruitment and muscle contribution in each synergy were modified (P<0.05). These modifications were observed for up to four recovery steps and were more pronounced (P<0.05) following unpredictable perturbations. The recruitment of the four basic walking synergies in the perturbed and recovery gait cycles indicates a robust neuromotor control of locomotion by using activation patterns of a few and well-known muscle synergies with specific adjustments within the synergies. The selection of pre-existing muscle synergies while adjusting the time of their recruitment during challenging locomotor conditions may improve the effectiveness to deal with perturbations and promote the transfer of adaptation between different kinds of perturbations.

Boys-men mean-power-frequency differences in progressive exercise to exhaustion, confounded by variability and adiposity.

BACKGROUND: Only scant research has compared children's mean power frequency (MPF) to adults', with a clear overview still lacking. A significant obstacle has been MPF's high variability, which this study aimed to overcome by elucidating the MPF characteristics distinguishing boys from men in progressive exhaustive exercise. METHODS: Electromyographic (EMG) data of 20 men (23.5 ± 2.5yrs) and 17 boys (10.2 ± 1.0 yrs), who performed progressively exhausting, intermittent isometric knee extensions, were subjected to secondary MPF analysis. Participants' vastus lateralis MPF data series were transformed to third-order polynomial regressions and expressed as percentages of the peak polynomial MPF values (%MPFpeak). The resulting curves were compared at 5-% time-to-exhaustion (TTE) intervals, using repeated-measures ANOVA. Raw MPFpeak values were adiposity corrected to 0% fat and used to convert the %MPFpeak data back to absolute MPF values (Hz) for estimating muscle-level MPF. RESULTS: No overall interaction or group effects could be shown between the %MPFpeak plots, but pairwise comparisons revealed significantly higher men's values at 50-70%TTE and lower at 100%TTE, i.e. boys' shallower MPF rise and decline. The adiposity-corrected boys' and men's composite MPF values peaked at 125.7 ± 2.5 and 166.0 ± 2.4 Hz, respectively (110.7 ± 1.7 and 122.5 ± 2.1 Hz, uncorrected), with a significant group effect (p < 0.05) and pairwise differences at all %TTE points. CONCLUSIONS: The boys were lower than the men in both the observed and, more so, in the adiposity-corrected MPF values that presumably estimate muscle-level MPF. The boys' shallower MPF rise and decline conform to children's claimed type-II motor-unit activation and/or compositional deficits and their related known advantage in muscular endurance.

Emerging methods for measuring physical activity using accelerometry in children and adolescents with neuromotor disorders: a narrative review.

BACKGROUND: Children and adolescents with neuromotor disorders need regular physical activity to maintain optimal health and functional independence throughout their development. To this end, reliable measures of physical activity are integral to both assessing habitual physical activity and testing the efficacy of the many interventions designed to increase physical activity in these children. Wearable accelerometers have been used for children with neuromotor disorders for decades; however, studies most often use disorder-specific cut points to categorize physical activity intensity, which lack generalizability to a free-living environment. No reviews of accelerometer data processing methods have discussed the novel use of machine learning techniques for monitoring physical activity in children with neuromotor disorders. METHODS: In this narrative review, we discuss traditional measures of physical activity (including questionnaires and objective accelerometry measures), the limitations of standard analysis for accelerometry in this unique population, and the potential benefits of applying machine learning approaches. We also provide recommendations for using machine learning approaches to monitor physical activity. CONCLUSIONS: While wearable accelerometers provided a much-needed method to quantify physical activity, standard cut point analyses have limitations in children with neuromotor disorders. Machine learning models are a more robust method of analyzing accelerometer data in pediatric neuromotor disorders and using these methods over disorder-specific cut points is likely to improve accuracy of classifying both type and intensity of physical activity. Notably, there remains a critical need for further development of classifiers for children with more severe motor impairments, preschool aged children, and children in hospital settings.

Neurologic Status of Patients with Purine Nucleoside Phosphorylase Deficiency Before and After Hematopoetic Stem Cell Transplantation.

BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive combined immunodeficiency. The phenotype is profound T cell deficiency with variable B and NK cell functions and results in recurrent and persistent infections that typically begin in the first year of life. Neurologic findings occur in approximately two-thirds of patients. The mechanism of neurologic abnormalities is unclear. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for PNP deficiency. METHODS: We report here six patients from five unrelated families with PNP deficiency treated in two centers in Turkey. We evaluated the neurological status of patients and compared to post-transplantation period if available. Then, we performed PubMed, Google Scholar, and Researchgate searches using the terms "PNP" and "hematopoietic stem cell transplantation" to find all reported cases of PNP transplantation and compared to our cohort. RESULTS: Six patients were treated in two centers in Turkey. One patient died from post-transplant complications. The other four patients underwent successful HSCT with good immune reconstitution after transplantation (follow-up 21-48 months) and good neurological outcomes. The other patient with a new mutation is still waiting for a matching HLA donor. DISCUSSION: In PNP deficiency, clinical manifestations are variable, and this disease should be considered in the presence of many different clinical findings. Despite the comorbidities that occurred before transplantation, HSCT currently appears to be the only treatment option for this disease. HSCT not only cures immunologic disorders, but probably also improves or at least stabilizes the neurologic status of patients.

Long-term neurodevelopmental follow-up of children exposed to pravastatin in utero.

BACKGROUND: Preeclampsia, especially before term, increases the risk of child neurodevelopmental adverse outcomes. Biological plausibility, preclinical studies, and pilot clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Obstetric-Fetal Pharmacology Research Centers Network support the safety and use of pravastatin to prevent preeclampsia. OBJECTIVE: This study aimed to determine the effect of antenatal pravastatin treatment in high-risk pregnant individuals on their child's health, growth, and neurodevelopment. STUDY DESIGN: This was an ancillary follow-up cohort study of children born to mothers who participated in the Obstetric-Fetal Pharmacology Research Centers Network pilot trials of pravastatin vs placebo in individuals at high risk of preeclampsia (ClinicalTrials.gov; identifier NCT01717586). After obtaining written informed consent (and assent as appropriate), the parent was instructed to complete the Child Behavior Checklist. To assess the child's motor, cognitive, and developmental outcomes, a certified and blinded study psychologist completed child motor, cognitive, emotional, and behavioral assessments using validated tools. Given the small number of individuals in the studies, the 10- and 20-mg pravastatin groups were combined into 1 group, and the results of the pravastatin group were compared with that of the placebo group. RESULTS: Of 40 children born to mothers in the original trial, 30 (15 exposed in utero to pravastatin and 15 to placebo) were enrolled in this follow-up study. The time of follow-up, which was 4.7 years (interquartile range, 2.5-6.9), was not different between children in the pravastatin group and children in the placebo group. There was no difference in the child's body mass index percentiles per sex and corrected age, the rates of extremes of body mass index percentiles, or the report of any other medical or developmental complications between the 2 groups. No child born in the pravastatin group had any limitation in motor assessment compared with 2 children (13.3%) who walked with difficulty and 4 children (26.7%) who had reduced manual abilities in the placebo group. Moreover, children born to mothers who received pravastatin had a higher general mean conceptual ability score (98.2±16.7 vs 89.7±11.0; P=.13) and a lower frequency (15.4% vs 35.7%; P=.38) of having a score of <85 (ie, 1 standard deviation lower than the mean) compared with those in the placebo group. Finally, there was no difference in the parents' report on the Child Behavior Checklist between the 2 groups. CONCLUSION: This study reported on the long-term neuromotor, cognitive, and behavioral outcomes among children exposed to pravastatin in utero during the second and third trimesters of pregnancy. Although the data were limited by the original trial's sample size, no identifiable long-term neurodevelopmental safety signal was evident with the use of pravastatin during pregnancy. This favorable neonatal risk-benefit analysis justifies continued research using pravastatin in clinical trials.

Interaction with a Hand Rehabilitation Exoskeleton in EMG-Driven Bilateral Therapy: Influence of Visual Biofeedback on the Users' Performance.

The effectiveness of EMG biofeedback with neurorehabilitation robotic platforms has not been previously addressed. The present work evaluates the influence of an EMG-based visual biofeedback on the user performance when performing EMG-driven bilateral exercises with a robotic hand exoskeleton. Eighteen healthy subjects were asked to perform 1-min randomly generated sequences of hand gestures (rest, open and close) in four different conditions resulting from the combination of using or not (1) EMG-based visual biofeedback and (2) kinesthetic feedback from the exoskeleton movement. The user performance in each test was measured by computing similarity between the target gestures and the recognized user gestures using the L2 distance. Statistically significant differences in the subject performance were found in the type of provided feedback (p-value 0.0124). Pairwise comparisons showed that the L2 distance was statistically significantly lower when only EMG-based visual feedback was present (2.89 ± 0.71) than with the presence of the kinesthetic feedback alone (3.43 ± 0.75, p-value = 0.0412) or the combination of both (3.39 ± 0.70, p-value = 0.0497). Hence, EMG-based visual feedback enables subjects to increase their control over the movement of the robotic platform by assessing their muscle activation in real time. This type of feedback could benefit patients in learning more quickly how to activate robot functions, increasing their motivation towards rehabilitation.

A Dynamical Systems Approach to Characterizing Brain-Body Interactions during Movement: Challenges, Interpretations, and Recommendations.

Brain-body interactions (BBIs) have been the focus of intense scrutiny since the inception of the scientific method, playing a foundational role in the earliest debates over the philosophy of science. Contemporary investigations of BBIs to elucidate the neural principles of motor control have benefited from advances in neuroimaging, device engineering, and signal processing. However, these studies generally suffer from two major limitations. First, they rely on interpretations of 'brain' activity that are behavioral in nature, rather than neuroanatomical or biophysical. Second, they employ methodological approaches that are inconsistent with a dynamical systems approach to neuromotor control. These limitations represent a fundamental challenge to the use of BBIs for answering basic and applied research questions in neuroimaging and neurorehabilitation. Thus, this review is written as a tutorial to address both limitations for those interested in studying BBIs through a dynamical systems lens. First, we outline current best practices for acquiring, interpreting, and cleaning scalp-measured electroencephalography (EEG) acquired during whole-body movement. Second, we discuss historical and current theories for modeling EEG and kinematic data as dynamical systems. Third, we provide worked examples from both canonical model systems and from empirical EEG and kinematic data collected from two subjects during an overground walking task.

A longitudinal perspective of hormone replacement therapies (HRTs) on neuromotor capabilities in males with 47,XXY (Klinefelter syndrome).

PURPOSE: The purpose of this study was to delineate the effects of variable hormone replacement therapies on neuromotor function in a large cohort of males with 47,XXY from birth to adulthood. METHODS: A total of 270 participants aged 16 days to 17 years 11 months prenatally diagnosed with 47,XXY were assessed by their pediatric endocrinologist and were administered hormone replacement therapies accordingly. Infants and school-aged children with 47,XXY were administered neuromotor assessments during routine neurodevelopmental evaluations. For statistical analysis, participants were segregated on the basis of treatment status. Two-tailed t tests, 1-way analysis of variance, and post hoc analysis determined significant group differences on each assessment. RESULTS: In infants, the early hormonal treatment (EHT) group performed significantly better than the untreated group on fine motor and motor composite domains. In school-aged children, we observed significantly improved scores on fine motor control, coordination, agility, and strength domains among males treated with EHT (or any combination thereof) compared with those who did not receive early treatment. CONCLUSION: The highest treated combination group was associated with the highest neuromotor function, although the EHT group also often performed better than the other groups. This suggests EHT may be essential in promoting long-term optimal neuromotor outcome in males with an additional X.

Pathogenic convergence of CNVs in genes functionally associated to a severe neuromotor developmental delay syndrome.

BACKGROUND: Complex developmental encephalopathy syndromes might be the consequence of unknown genetic alterations that are likely to contribute to the full neurological phenotype as a consequence of pathogenic gene combinations. METHODS: To identify the additional genetic contribution to the neurological phenotype, we studied as a test case a boy, with a KCNQ2 exon-7 partial duplication, by single-nucleotide polymorphism (SNP) microarray to detect copy-number variations (CNVs). RESULTS: The proband presented a cerebral palsy like syndrome with a severe motor and developmental encephalopathy. The SNP array analysis detected in the proband several de novo CNVs, nine partial gene losses (LRRC55, PCDH9, NALCN, RYR3, ELAVL2, CDH13, ATP1A2, SLC17A5, ANO3), and two partial gene duplications (PCDH19, EFNA5). The biological functions of these genes are associated with ion channels such as calcium, chloride, sodium, and potassium with several membrane proteins implicated in neural cell-cell interactions, synaptic transmission, and axon guidance. Pathogenically, these functions can be associated to cerebral palsy, seizures, dystonia, epileptic crisis, and motor neuron dysfunction, all present in the patient. CONCLUSIONS: Severe motor and developmental encephalopathy syndromes of unknown origin can be the result of a phenotypic convergence by combination of several genetic alterations in genes whose physiological function contributes to the neurological pathogenic mechanism.

Motor and visuomotor function in 10-year-old children with congenital heart disease: association with behaviour.

BACKGROUND: Children with CHD are at increased risk for neurodevelopmental impairments. There is little information on long-term motor function and its association with behaviour. AIMS: To assess motor function and behaviour in a cohort of 10-year-old children with CHD after cardiopulmonary bypass surgery. METHODS: Motor performance and movement quality were examined in 129 children with CHD using the Zurich Neuromotor Assessment providing four timed and one qualitative component, and a total timed motor score was created based on the four timed components. The Beery Test of Visual-Motor Integration and the Strengths and Difficulties Questionnaire were administered. RESULTS: All Zurich Neuromotor Assessment motor tasks were below normative values (all p ≤ 0.001), and the prevalence of poor motor performance (≤10th percentile) ranged from 22.2% to 61.3% in the different components. Visuomotor integration and motor coordination were poorer compared to norms (all p ≤ 0.001). 14% of all analysed children had motor therapy at the age of 10 years. Children with a total motor score ≤10th percentile showed more internalising (p = 0.002) and externalising (p = 0.028) behavioural problems. CONCLUSIONS: School-aged children with CHD show impairments in a variety of motor domains which are related to behavioural problems. Our findings emphasise that motor problems can persist into school-age and require detailed assessment and support.

Effect of the START-Play Physical Therapy Intervention on Cognitive Skills Depends on Caregiver-Provided Learning Opportunities.

AIMS: This study evaluated whether caregiver-provided learning opportunities moderated the effect of START-Play physical therapy intervention on the cognitive skills of young children with neuromotor delays, and whether START-Play impacted caregiver-provided learning opportunities over time. METHODS: One hundred and twelve children with neuromotor delays (7-16 months) participated in a multisite randomized clinical trial evaluating the efficacy of START-Play. Children were assessed at baseline and 3 (post intervention), 6, and 12 months post baseline. Cognition was scored from the Bayley Scales of Infant & Toddler Development, Third Edition, cognitive scale. The proportion of time caregivers spent providing learning opportunities was coded from a 5-minute caregiver-child free play interaction. RESULTS: Baseline caregiver-provided learning opportunities moderated the 3- and 12-month effects of START-Play on cognition. Cognitive gains due to START-Play were more pronounced for children whose caregivers provided more learning opportunities. START-Play did not impact caregiver-provided learning opportunities over time. CONCLUSIONS: START-Play may have a lasting effect on children's cognition, but this effect is contingent on caregivers providing their child with ample opportunities to practice cognitive skills. Strategies for improving caregivers' uptake and transfer of START-Play principles to their daily routines should be evaluated. TRIAL REGISTRATION: ClinicalTrials.gov NCT02593825.

The Outcomes of Robotic Rehabilitation Assisted Devices Following Spinal Cord Injury and the Prevention of Secondary Associated Complications.

Spinal cord injuries (SCIs) have major consequences on the patient's health and life. Voluntary muscle paralysis caused by spinal cord damage affects the patient's independence. Following SCI, an irreversible motor and sensory deficit occurs (spasticity, muscle paralysis, atrophy, pain, gait disorders, pain). This pathology has implications on the whole organism: on the osteoarticular, muscular, cardiovascular, respiratory, gastrointestinal, genito-urinary, skin, metabolic disorders, and neuro-psychic systems. The rehabilitation process for a subject having SCIs can be considered complex, since the pathophysiological mechanism and biochemical modifications occurring at the level of spinal cord are not yet fully elucidated. This review aims at evaluating the impact of robotic-assisted rehabilitation in subjects who have suffered SCI, both in terms of regaining mobility as a major dysfunction in patients with SCI, but also in terms of improving overall fitness and cardiovascular function, respiratory function, as well as the gastrointestinal system, bone density and finally the psychosocial issues, based on multiple clinical trials, and pilot studies. The researched literature in the topic revealed that in order to increase the chances of neuro-motor recovery and to obtain satisfactory results, the combination of robotic therapy, a complex recovery treatment and specific medication is one of the best decisions. Furthermore, the use of these exoskeletons facilitates better/greater autonomy for patients, as well as optimal social integration.

The Effects of Concussions on Batting Performance in Major League Baseball Players: A Critically Appraised Topic.

Clinical Scenario: The impact of concussion in baseball athletes is far reaching although typically less studied than collision sports. The neuromotor sequelae of these injuries can have lasting effects on the high level of coordination needed in baseball skills. In professional athletes, the long-term effects of concussion combined with the high demands for performance can potentially shorten athletes' careers. Clinical Question: Do Major League Baseball players who have had a concussion compared with those with no history of concussions have decreased batting performance after they return to full participation? Summary of Key Findings: Seven articles meeting criteria for level 2 evidence were identified in this critically appraised topic. Four of 7 studies found deficits in batting performance following concussion. However, the 3 studies that did not identify differences lacked a comparative control group. Clinical Bottom Line: Evidence supports a relationship between concussion and decreased batting performance. This suggests there is a demand for screening and rehabilitation strategies aimed at improving sport-specific neuromotor and coordination skills in these individuals. Strength of Recommendation: Collectively, the body of evidence included to answer the clinical question aligns with the strength of recommendation of B.

49,XXXXY syndrome: A study of neurological function in this uncommon X and Y chromosomal disorder.

49,XXXXY is a rare chromosomal variation characterized by deficits in motor, language, and cognitive domains. This study reports on the neurological function and dysmorphic features in the largest cohort to date. Seventy-two boys with 49,XXXXY were evaluated on a variety of domains including a neurological examination and neuromotor assessments including the Beery Buktenica Developmental Test of Visual-Motor Integration, Sixth Edition, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), and the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Results supported previous literature by describing high occurrences of truncal and extremity hypotonia, which significantly impacts on motor milestones and ambulation in this population. The boys presented with dysmorphic features including epicanthal folds, frontal bossing, and synophrys. Visual perception skills were mildly impaired and cranial nerves were typically intact, however capabilities in motor coordination and fine motor precision were greatly delayed, supporting deficits in refined and controlled hand movements versus widespread visual deficits. Preschool boys treated with testosterone replacement had significantly increased scores when compared to the untreated group on the BSID-III Psychomotor Development Index, further supporting previous research indicating that testosterone replacement may have a positive impact on neurodevelopmental outcomes in males with additional X chromosomes. Boys with 49,XXXXY may benefit from hormonal treatment in conjunction with early intervention services to address their significant motor deficits.

Fully percutaneous fetoscopic repair of myelomeningocele: 30-month follow-up data.

OBJECTIVE: This observational study reports on the postnatal mortality and 30-month outcome of children who underwent fully percutaneous fetoscopic repair of myelomeningocele (MMC) at a single center in Giessen, Germany. METHODS: Between October 2010 and August 2014, a total of 72 patients underwent fully percutaneous fetoscopic MMC closure at 21 + 0 to 29 + 1 (mean, 23 + 5) weeks' gestation. Of these, 52 (72%) participated in this study; however, 30-month mortality data are available for all 72 children. Children were examined at four timepoints: shortly after birth and at 3 months, 12 months and 30 months of corrected age. The patients underwent age-specific standardized neurological examinations and assessment of leg movements and ambulation at all timepoints. Cognitive and motor development were assessed using the Bayley Scales of Infant Development, second edition (BSID-II), at 30 months. RESULTS: All 72 children survived the intrauterine procedure, however, four (5.6%) infants died postnatally (including two of the 52 comprising the study cohort). Of the 52 patients included in the study, 11.5% were delivered before the 30th week of gestation (mean, 33 + 1 weeks) and, of the survivors, 48.1% had ventriculoperitoneal shunt placement. Of the 50 infants that were alive at 30 months, independent ambulation, without orthosis, was feasible for 46%. At 30 months of follow-up, 46% of children presented with a functional level that was at least two segments better than the anatomical level of the lesion. At 30 months, 70% of the children presented with BSID-II psychomotor development index score of ≥ 70 and 80% with BSID-II mental development index score of ≥ 70. CONCLUSION: Intrauterine repair of MMC by percutaneous fetoscopy shows largely similar outcomes to those reported for open repair, with respect to mortality, prematurity, shunt-placement rates, motor and mental development and free ambulation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Learning to walk with a wearable robot in 880 simple steps: a pilot study on motor adaptation.

BACKGROUND: Wearable robots have been shown to improve the efficiency of walking in diverse scenarios. However, it is unclear how much practice is needed to fully adapt to robotic assistance, and which neuromotor processes underly this adaptation. Familiarization strategies for novice users, robotic optimization techniques (e.g. human-in-the-loop), and meaningful comparative assessments depend on this understanding. METHODS: To better understand the process of motor adaptation to robotic assistance, we analyzed the energy expenditure, gait kinematics, stride times, and muscle activities of eight naïve unimpaired participants across three 20-min sessions of robot-assisted walking. Experimental outcomes were analyzed with linear mixed effect models and statistical parametric mapping techniques. RESULTS: Most of the participants' kinematic and muscular adaptation occurred within the first minute of assisted walking. After ten minutes, or 880 steps, the energetic benefits of assistance were realized (an average of 5.1% (SD 2.4%) reduction in energy expenditure compared to unassisted walking). Motor adaptation was likely driven by the formation of an internal model for feedforward motor control as evidenced by the reduction of burst-like muscle activity at the cyclic end of robotic assistance and an increase in arm-swing asymmetry previously associated with increased cognitive load. CONCLUSION: Humans appear to adapt to walking assistance from a wearable robot over 880 steps by forming an internal model for feedforward control. The observed adaptation to the wearable robot is well-described by existing three-stage models that start from a cognitive stage, continue with an associative stage, and end in autonomous task execution. Trial registration Not applicable.

Combined Use of EMG and EEG Techniques for Neuromotor Assessment in Rehabilitative Applications: A Systematic Review.

Electroencephalography (EEG) and electromyography (EMG) are widespread and well-known quantitative techniques used for gathering biological signals at cortical and muscular levels, respectively. Indeed, they provide relevant insights for increasing knowledge in different domains, such as physical and cognitive, and research fields, including neuromotor rehabilitation. So far, EEG and EMG techniques have been independently exploited to guide or assess the outcome of the rehabilitation, preferring one technique over the other according to the aim of the investigation. More recently, the combination of EEG and EMG started to be considered as a potential breakthrough approach to improve rehabilitation effectiveness. However, since it is a relatively recent research field, we observed that no comprehensive reviews available nor standard procedures and setups for simultaneous acquisitions and processing have been identified. Consequently, this paper presents a systematic review of EEG and EMG applications specifically aimed at evaluating and assessing neuromotor performance, focusing on cortico-muscular interactions in the rehabilitation field. A total of 213 articles were identified from scientific databases, and, following rigorous scrutiny, 55 were analyzed in detail in this review. Most of the applications are focused on the study of stroke patients, and the rehabilitation target is usually on the upper or lower limbs. Regarding the methodological approaches used to acquire and process data, our results show that a simultaneous EEG and EMG acquisition is quite common in the field, but it is mostly performed with EMG as a support technique for more specific EEG approaches. Non-specific processing methods such as EEG-EMG coherence are used to provide combined EEG/EMG signal analysis, but rarely both signals are analyzed using state-of-the-art techniques that are gold-standard in each of the two domains. Future directions may be oriented toward multi-domain approaches able to exploit the full potential of combined EEG and EMG, for example targeting a wider range of pathologies and implementing more structured clinical trials to confirm the results of the current pilot studies.

Disproportionate loss of excitatory inputs to smaller phrenic motor neurons following cervical spinal hemisection.

KEY POINTS: Motor units, comprising a motor neuron and the muscle fibre it innervates, are activated in an orderly fashion to provide varying amounts of force. A unilateral C2 spinal hemisection (C2SH) disrupts predominant excitatory input from medulla, causing cessation of inspiratory-related diaphragm muscle activity, whereas higher force, non-ventilatory diaphragm activity persists. In this study, we show a disproportionately larger loss of excitatory glutamatergic innervation to small phrenic motor neurons (PhMNs) following C2SH, as compared with large PhMNs ipsilateral to injury. Our data suggest that there is a dichotomy in the distribution of inspiratory-related descending excitatory glutamatergic input to small vs. large PhMNs that reflects their differential recruitment. ABSTRACT: Excitatory glutamatergic input mediating inspiratory drive to phrenic motor neurons (PhMNs) emanates primarily from the ipsilateral ventrolateral medulla. Unilateral C2 hemisection (C2SH) disrupts this excitatory input, resulting in cessation of inspiratory-related diaphragm muscle (DIAm) activity. In contrast, after C2SH, higher force, non-ventilatory DIAm activity persists. Inspiratory behaviours require recruitment of only smaller PhMNs, whereas with more forceful expulsive/straining behaviours, larger PhMNs are recruited. Accordingly, we hypothesize that C2SH primarily disrupts glutamatergic synaptic inputs to smaller PhMNs, whereas glutamatergic synaptic inputs to larger PhMNs are preserved. We examined changes in glutamatergic presynaptic input onto retrogradely labelled PhMNs using immunohistochemistry for VGLUT1 and VGLUT2. We found that 7 days after C2SH there was an ∼60% reduction in glutamatergic inputs to smaller PhMNs compared with an ∼35% reduction at larger PhMNs. These results are consistent with a more pronounced impact of C2SH on inspiratory behaviours of the DIAm, and the preservation of higher force behaviours after C2SH. These results indicate that the source of glutamatergic synaptic input to PhMNs varies depending on motor neuron size and reflects different functional control - perhaps separate central pattern generator and premotor circuits. For smaller PhMNs, the central pattern generator for inspiration is located in the pre-Bötzinger complex and premotor neurons in the ventrolateral medulla, sending predominantly ipsilateral projections via the dorsolateral funiculus. C2SH disrupts this glutamatergic input. For larger PhMNs, a large proportion of excitatory inputs appear to exist below the C2 level or from contralateral regions of the brainstem and spinal cord.

Impaired neuromuscular transmission of the tibialis anterior in a rodent model of hypertonia.

Early-onset hypertonia is characteristic of developmental neuromotor disorders, including cerebral palsy (CP). The spa transgenic mouse displays early-onset spasticity, abnormal gait, and motor impairments that are remarkably similar to symptoms of human CP. Previously, we showed that spa mice have fewer motor neurons innervating the tibialis anterior (TA). An expanded innervation ratio may result in increased susceptibility to neuromuscular transmission failure (NMTF). We assessed NMTF in an ex vivo TA muscle nerve preparation from spa and wild-type (WT) mice by comparing forces elicited by nerve versus muscle stimulation. TA muscle innervation ratio was assessed by counting the number of muscle fibers and dividing by the number of TA motor neurons. Muscle fiber cross-sectional areas were also assessed in the TA muscle. We observed that NMTF was immediately present in spa mice, increased with repetitive stimulation, and associated with increased innervation ratio. These changes were concomitant with reduced TA muscle fiber cross-sectional area in spa mice compared with WT. Early-onset hypertonia is associated with increased innervation ratio and impaired neuromuscular transmission. These disturbances may exacerbate the underlying gait abnormalities present in individuals with hypertonia.NEW & NOTEWORTHY Nerve-muscle interaction is poorly understood in the context of early-onset spasticity and hypertonia. In an animal model of early-onset spasticity, spa mice, we found a marked impairment of tibialis anterior neuromuscular transmission. This impairment is associated with an increased innervation ratio (mean number of muscle fibers innervated by a single motor neuron). These disturbances may underlie weakness and gait disturbances observed in individual with developmental hypertonia and spasticity.

Heterogeneous glutamatergic receptor mRNA expression across phrenic motor neurons in rats.

The diaphragm muscle comprises various types of motor units that are recruited in an orderly fashion governed by the intrinsic electrophysiological properties (membrane capacitance as a function of somal surface area) of phrenic motor neurons (PhMNs). Glutamate is the main excitatory neurotransmitter at PhMNs and acts primarily via fast acting AMPA and N-methyl-D-aspartic acid (NMDA) receptors. Differences in receptor expression may also contribute to motor unit recruitment order. We used single cell, multiplex fluorescence in situ hybridization to determine glutamatergic receptor mRNA expression across PhMNs based on their somal surface area. In adult male and female rats (n = 9) PhMNs were retrogradely labeled for analyses (n = 453 neurons). Differences in the total number and density of mRNA transcripts were evident across PhMNs grouped into tertiles according to somal surface area. A ~ 25% higher density of AMPA (Gria2) and NMDA (Grin1) mRNA expression was evident in PhMNs in the lower tertile compared to the upper tertile. These smaller PhMNs likely comprise type S motor units that are recruited first to accomplish lower force, ventilatory behaviors. In contrast, larger PhMNs with lower volume densities of AMPA and NMDA mRNA expression presumably comprise type FInt and FF motor units that are recruited during higher force, expulsive behaviors. Furthermore, there was a significantly higher cytosolic NMDA mRNA expression in small PhMNs suggesting a more important role for NMDA-mediated glutamatergic neurotransmission at smaller PhMNs. These results are consistent with the observed order of motor unit recruitment and suggest a role for glutamatergic receptors in support of this orderly recruitment. Cover Image for this issue: doi: 10.1111/jnc.14747.