Knee Angle Estimation from Surface EMG during Walking Using Attention-Based Deep Recurrent Neural Networks: Feasibility and Initial Demonstration in Cerebral Palsy.

Accurately estimating knee joint angle during walking from surface electromyography (sEMG) signals can enable more natural control of wearable robotics like exoskeletons. However, challenges exist due to variability across individuals and sessions. This study evaluates an attention-based deep recurrent neural network combining gated recurrent units (GRUs) and an attention mechanism (AM) for knee angle estimation. Three experiments were conducted. First, the GRU-AM model was tested on four healthy adolescents, demonstrating improved estimation compared to GRU alone. A sensitivity analysis revealed that the key contributing muscles were the knee flexor and extensors, highlighting the ability of the AM to focus on the most salient inputs. Second, transfer learning was shown by pretraining the model on an open source dataset before additional training and testing on the four adolescents. Third, the model was progressively adapted over three sessions for one child with cerebral palsy (CP). The GRU-AM model demonstrated robust knee angle estimation across participants with healthy participants (mean RMSE 7 degrees) and participants with CP (RMSE 37 degrees). Further, estimation accuracy improved by 14 degrees on average across successive sessions of walking in the child with CP. These results demonstrate the feasibility of using attention-based deep networks for joint angle estimation in adolescents and clinical populations and support their further development for deployment in wearable robotics.

A randomized cross-over study protocol to evaluate long-term gait training with a pediatric robotic exoskeleton outside the clinical setting in children with movement disorders.

Individuals with neuromuscular disorders display a combination of motor control deficits and lower limb weakness contributing to knee extension deficiency characterized by exaggerated stance phase knee flexion. There is a lack of evidence for long-term improvement of knee extension deficiency with currently available clinical treatment programs. Our previous work testing a wearable robotic exoskeleton with precisely timed assistive torque applied at the knee showed immediate increases in knee extension during walking for children with cerebral palsy, which continued to improve over an acute practice period. When we applied interleaved assistance and resistance to knee extension, we observed improvements in knee extension and increased muscle activation indicating the potential for muscle strengthening when used over time. There is a need for additional, high-quality trials to assess the impact of dosage, intensity and volume of training necessary to see persistent improvement in lower limb function for these patient populations. This randomized crossover study (ClinicalTrials.gov: NCT05726591) was designed to determine whether 12 weeks of overground gait training with a robotic exoskeleton outside of the clinical setting, following an initial in clinic accommodation period, has a beneficial effect on walking ability, muscle activity and overall motor function. Participants will be randomized to either complete the exoskeleton intervention or continue their standard therapy for 12 weeks first, followed by a crossover to the other study component. The primary outcome measure is change in peak knee extension angle during walking; secondary outcome measures include gait speed, strength, and validated clinical scales of motor function and mobility. Assessments will be completed before and after the intervention and at 6 weeks post-intervention, and safety and compliance will be monitored throughout. We hypothesize that the 12-week exoskeleton intervention outside the clinical setting will show greater improvements in study outcome measures than the standard therapy.

Functioning and activity outcomes of the Akwenda Intervention Program for children and young adults with cerebral palsy in Uganda: A cluster-randomized trial.

AIM: To evaluate the efficacy of the Akwenda Intervention Program on motor, self-care, and social function of children and young people with cerebral palsy (CP). METHOD: This was a cluster-randomized, controlled, single-blinded, intervention study of 100 participants with CP (2-23 years; 52 males) in rural eastern Uganda. Half were allocated to the intervention program, the remainder served as waitlist controls. Gross Motor Function Measure-66 (GMFM-66) and the Ugandan version of Pediatric Evaluation of Disability Inventory (PEDI-UG) were collected before group allocation and after intervention. General linear models and t-tests were used to compare changes within and between groups. Cohen's d estimated the effect size of group differences. Change scores were evaluated by age and mobility subgroups. RESULTS: Significant group by time interactions were found for GMFM-66 (p =0.003) and PEDI-UG outcomes (p <0.001), except mobility, with the intervention group demonstrating greater changes. Both groups increased their scores on the GMFM-66 and child PEDI-UG, while only the intervention group had significant increases in caregiver assistance scores and across all age and mobility subgroups. Cohen's d showed large effect sizes (d >0.8) of differences for PEDI-UG outcomes except mobility. INTERPRETATION: The Akwenda Intervention Program had a large positive impact on functioning and activity across age and mobility levels.

Development and evaluation of a BCI-neurofeedback system with real-time EEG detection and electrical stimulation assistance during motor attempt for neurorehabilitation of children with cerebral palsy.

In the realm of motor rehabilitation, Brain-Computer Interface Neurofeedback Training (BCI-NFT) emerges as a promising strategy. This aims to utilize an individual's brain activity to stimulate or assist movement, thereby strengthening sensorimotor pathways and promoting motor recovery. Employing various methodologies, BCI-NFT has been shown to be effective for enhancing motor function primarily of the upper limb in stroke, with very few studies reported in cerebral palsy (CP). Our main objective was to develop an electroencephalography (EEG)-based BCI-NFT system, employing an associative learning paradigm, to improve selective control of ankle dorsiflexion in CP and potentially other neurological populations. First, in a cohort of eight healthy volunteers, we successfully implemented a BCI-NFT system based on detection of slow movement-related cortical potentials (MRCP) from EEG generated by attempted dorsiflexion to simultaneously activate Neuromuscular Electrical Stimulation which assisted movement and served to enhance sensory feedback to the sensorimotor cortex. Participants also viewed a computer display that provided real-time visual feedback of ankle range of motion with an individualized target region displayed to encourage maximal effort. After evaluating several potential strategies, we employed a Long short-term memory (LSTM) neural network, a deep learning algorithm, to detect the motor intent prior to movement onset. We then evaluated the system in a 10-session ankle dorsiflexion training protocol on a child with CP. By employing transfer learning across sessions, we could significantly reduce the number of calibration trials from 50 to 20 without compromising detection accuracy, which was 80.8% on average. The participant was able to complete the required calibration trials and the 100 training trials per session for all 10 sessions and post-training demonstrated increased ankle dorsiflexion velocity, walking speed and step length. Based on exceptional system performance, feasibility and preliminary effectiveness in a child with CP, we are now pursuing a clinical trial in a larger cohort of children with CP.

Attention-Based Deep Recurrent Neural Network to Estimate Knee Angle During Walking from Lower-Limb EMG.

Accurate prediction of joint angle during walking from surface electromyography (sEMG) offers the potential to infer movement intention and therefore represents a potentially useful approach for adaptive control of wearable robotics. Here, we present the use of a recurrent neural network (RNN) with gated recurrent units (GRUs) and an attention mechanism to estimate knee angle during overground walking from sEMG and its initial offline validation in healthy adolescents. Our results show that the attention mechanism improved estimation accuracy by focusing on the most relevant parts of the input dataset within each time window, particularly muscles active during knee excursion. Sensitivity analysis revealed knee extensor and flexor muscles to be most salient in accurately estimating joint angle. Additionally, we demonstrate the ability of the GRU-RNN approach to accurately estimate knee angle during overground walking in a child with cerebral palsy (CP) in the presence of exoskeleton knee extension assistance. Collectively, our findings establish the initial feasibility of using this approach to estimate user movement from sEMG, which is particularly important for developing robotic exoskeletons for children with neuromuscular disorders such as CP.

Associations between white matter integrity and postural control in adults with traumatic brain injury.

Abnormalities of postural sway have been extensively reported in traumatic brain injury (TBI). However, the underlying neural correlates of balance disturbances in TBI remain to be elucidated. Studies in children with TBI have reported associations between the Sensory Organization Test (SOT) and measures of white matter (WM) integrity with diffusion tensor imaging (DTI) in brain areas responsible for multisensory integration. This study seeks to replicate those associations in adults as well as explore relationships between DTI and the Limits of Stability (LOS) Test. Fifty-six participants (43±17 years old) with a history of TBI were tested 30 days to 5 years post-TBI. This study confirmed results in children for associations between the SOT and the medial lemniscus as well as middle cerebellar peduncle, and revealed additional associations with the posterior thalamic radiation. Additionally, this study found significant correlations between abnormal LOS scores and impaired WM integrity in the cingulum, corpus callosum, corticopontine and corticospinal tracts, fronto-occipital fasciculi, longitudinal fasciculi, medial lemniscus, optic tracts and thalamic radiations. Our findings indicate the involvement of a broad range of WM tracts in the control of posture, and demonstrate the impact of TBI on balance via disruptions to WM integrity.

Children With Bilateral Cerebral Palsy Exhibit Bimanual Asymmetric Motor Deficits and EEG Evidence of Dominant Sensorimotor Hemisphere Overreliance During Reaching.

BACKGROUND: Reaching is a fundamental motor skill often impaired in cerebral palsy (CP). Studies on manual function, intervention, and underlying brain mechanisms largely focus on unilateral CP. This first electroencephalography (EEG) evaluation of reaching exclusively in bilateral CP aims to quantify and relate brain activation patterns to bimanual deficits in this population. METHODS: A total of 15 children with bilateral CP (13.4 ± 2.9 years) and 13 with typical development (TD: 14.3 ± 2.4 years) performed 45 reaches per hand while recording motion capture and EEG data. The Box and Blocks test was administered bilaterally. Cortical sources were identified using independent component analysis and clustered using k-means. Alpha (8-12 Hz) and beta (13-30 Hz) band event-related desynchronization (ERD) values were compared across groups and hands within clusters, between dominant and non-dominant sensorimotor clusters, and related to reach kinematics and the Box and Block test. RESULTS: The group with CP demonstrated bimanual motor deficits with slower reaches, lower Box and Blocks scores, and stronger hand preference than in TD. Beta ERD, representing motor execution, was notably higher in the dominant sensorimotor cluster in CP compared to TD. Both groups demonstrated more contralateral than ipsilateral activity in both hands and clusters, with CP showing a less lateralized (more bilateral) alpha response. Higher brain activation was generally related to better function. CONCLUSION: Bimanual deficits in bilateral CP and related EEG differences warrant more clinical and research attention particularly earlier in life when greater potential for neural and functional recovery exists.

Investigation of brain mechanisms underlying upper limb function in bilateral cerebral palsy using EEG.

OBJECTIVE: Few studies focus on upper limbs in bilateral cerebral palsy (CP) despite potential bimanual deficits. Electroencephalography (EEG) was utilized to investigate brain mechanisms underlying upper limb tasks in bilateral CP and typical development (TD) and relationships to function. METHODS: 26 (14 CP; 12 TD) completed the Box and Blocks Test and transport task with paper, sponge or mixed blocks, while recording EEG and motion data. RESULTS: Group effects for path time, path length and Box and Blocks Test revealed bimanual deficits. Four sensorimotor-related EEG clusters were identified. Group effects were found in premotor and dominant motor clusters with greater beta event-related desynchronization (ERD) in CP. Hand and hand by group effects were found in the dominant motor cluster, showing greater ERD with the more affected hand in CP. Condition effects were prominent in the posterior parietal cluster with higher ERD reflecting greater difficulty in force modulation. CONCLUSIONS: Higher brain activation associated with greater bimanual deficits is similar to our lower limb findings but contrasts studies in TD or unilateral CP linking higher ERD to greater proficiency. SIGNIFICANCE: Bilateral CP shows overreliance on the dominant hemisphere with the less functional hand and higher brain activity presumably related to excessive intracortical connectivity.

Implementation of Early Detection and Intervention for Cerebral Palsy in High-Risk Infant Follow-Up Programs: U.S. and Global Considerations.

Early detection and intervention for cerebral palsy is best practice for all high-risk infants according to international guidelines, consensus statements and research-supported evidence. It allows support for families and optimization of developmental trajectories into adulthood. All phases of implementation of CP early detection can be found across the world in high-risk infant follow-up programs, demonstrating feasibility and acceptability through standardized implementation science. The largest clinical network for CP early detection and intervention in the world has now sustained an average age at detection less than 12 months corrected age for more than 5 years. Targeted referrals and interventions for CP can now be offered to patients in optimal periods of neuroplasticity, and new therapies researched as the age of detection decreases. Implementation of guidelines and incorporation of rigorous CP research studies both allow high-risk infant follow-up programs to fulfill their mission of improving outcomes of those with the most vulnerable developmental trajectories from birth.

The effects of power exercises on body structure and function, activity and participation in children with cerebral palsy: an ICF-based systematic review.

PURPOSE: To systematically review the literature for evidence of effectiveness of power exercises on physical, physiological, and functional outcomes in children and adolescents with cerebral palsy (CP). MATERIALS AND METHODS: Methodological quality and evidence synthesis were assessed with using the Cochrane Risk of Bias (RoB) Tools and Modified Bakker Scale. Using the International Classification of Functioning (ICF), outcome measures for muscle agriculture, gait, balance, motor function, aerobic/anaerobic fitness, daily living, mobility, and school participation were categorised. RESULTS: The overall RoB of four randomised clinical trials was low, one had some concerns and two were rated as high. Moderate evidence was found that power exercises increased walking speed, activities of daily living, muscle strength, and enhanced gross motor function more than a routine physical therapy program. CONCLUSIONS: The lack of stronger evidence for power training interventions to improve muscle architecture, muscle function, walking capacity, and mobility in children with CP might be explained by the differences in training protocols and degree to which these meet the physiological definition of power, different methods of measuring power, limited durations of training, and the relative effectiveness of control interventions. Future studies should include a stronger focus on child and family-centred participation goals.Implications For RehabilitationPower training can improve gross motor function, walking speed, muscle strength, and activities of daily living more than routine physical therapy.Results comparing power training versus traditional strength training were less pronounced likely because both are intensive and may have positive effects.More research is needed to investigate effects of power training on participation.

External walking environment differentially affects muscle synergies in children with cerebral palsy and typical development.

Despite external environmental changes in walking, such as manipulating gait speed, previous studies have shown that the underlying muscle synergy structures (synergy weights or vectors) rarely vary. The purpose of this study is to examine if external environmental changes to the walking task influence muscle synergies in children with cerebral palsy (CP) and/or typical development (TD). To identify muscle synergies, we extracted muscle synergies from eight children with CP and eight age-matched TD in three treadmill walking conditions, e.g., baseline (adjusted to individual comfortable walking speed), variable speed (VS), or restricted foot width (RW). Then, we grouped similar muscle synergies using k-mean clustering and discriminant analyses from all datasets of individual synergy structures. Proportion tests exhibited six clusters of muscle synergies predominantly arising from children with CP and four clusters from children with TD. Also, the proportion of muscle synergies was significantly different in four of the CP-preferred clusters across conditions. Specifically, the proportion of the baseline condition was significantly different from VS and RW conditions in one and two clusters, respectively. The proportion was significantly different between VS and RW conditions in four clusters. Cadence and step lengths differed across conditions but not groups which makes the group differences in proportion even more notable. In contrast, step width, while significantly lower in CP, did not differ across conditions. Our findings demonstrate that muscle synergies in children with CP are more sensitive to changes in the external walking environment than in typically developing children.

Functional and Structural Brain Connectivity in Children With Bilateral Cerebral Palsy Compared to Age-Related Controls and in Response to Intensive Rapid-Reciprocal Leg Training.

Background: Compared to unilateral cerebral palsy (CP), less is known about brain reorganization and plasticity in bilateral CP especially in relation or response to motor training. The few trials that reported brain imaging results alongside functional outcomes include a handful of studies in unilateral CP, and one pilot trial of three children with bilateral CP. This study is the first locomotor training randomized controlled trial (RCT) in bilateral CP to our knowledge reporting brain imaging outcomes. Methods: Objective was to compare MRI brain volumes, resting state connectivity and white matter integrity using DTI in children with bilateral CP with PVL and preterm birth history (<34 weeks), to age-related controls, and from an RCT of intensive 12 week rapid-reciprocal locomotor training using an elliptical or motor-assisted cycle. We hypothesized that connectivity in CP compared to controls would be greater across sensorimotor-related brain regions and that functional (resting state) and structural (fractional anisotropy) connectivity would improve post intervention. We further anticipated that baseline and post-intervention imaging and functional measures would correlate. Results: Images were acquired with a 3T MRI scanner for 16/27 children with CP in the trial, and 18 controls. No conclusive evidence of training-induced neuroplastic effects were seen. However, analysis of shared variance revealed that greater increases in precentral gyrus connectivity with the thalamus and pons may be associated with larger improvements in the trained device speed. Exploratory analyses also revealed interesting potential relationships between brain integrity and multiple functional outcomes in CP, with functional connectivity between the motor cortex and midbrain showing the strongest potential relationship with mobility. Decreased posterior white matter, corpus callosum and thalamic volumes, and FA in the posterior thalamic radiation were the most prominent group differences with corticospinal tract differences notably not found. Conclusions: Results reinforce the involvement of sensory-related brain areas in bilateral CP. Given the wide individual variability in imaging results and clinical responses to training, a greater focus on neural and other mechanisms related to better or worse outcomes is recommended to enhance rehabilitation results on a patient vs. group level.

Determining optimal mobile neurofeedback methods for motor neurorehabilitation in children and adults with non-progressive neurological disorders: a scoping review.

BACKGROUND: Brain-computer interfaces (BCI), initially designed to bypass the peripheral motor system to externally control movement using brain signals, are additionally being utilized for motor rehabilitation in stroke and other neurological disorders. Also called neurofeedback training, multiple approaches have been developed to link motor-related cortical signals to assistive robotic or electrical stimulation devices during active motor training with variable, but mostly positive, functional outcomes reported. Our specific research question for this scoping review was: for persons with non-progressive neurological injuries who have the potential to improve voluntary motor control, which mobile BCI-based neurofeedback methods demonstrate or are associated with improved motor outcomes for Neurorehabilitation applications? METHODS: We searched PubMed, Web of Science, and Scopus databases with all steps from study selection to data extraction performed independently by at least 2 individuals. Search terms included: brain machine or computer interfaces, neurofeedback and motor; however, only studies requiring a motor attempt, versus motor imagery, were retained. Data extraction included participant characteristics, study design details and motor outcomes. RESULTS: From 5109 papers, 139 full texts were reviewed with 23 unique studies identified. All utilized EEG and, except for one, were on the stroke population. The most commonly reported functional outcomes were the Fugl-Meyer Assessment (FMA; n = 13) and the Action Research Arm Test (ARAT; n = 6) which were then utilized to assess effectiveness, evaluate design features, and correlate with training doses. Statistically and functionally significant pre-to post training changes were seen in FMA, but not ARAT. Results did not differ between robotic and electrical stimulation feedback paradigms. Notably, FMA outcomes were positively correlated with training dose. CONCLUSION: This review on BCI-based neurofeedback training confirms previous findings of effectiveness in improving motor outcomes with some evidence of enhanced neuroplasticity in adults with stroke. Associative learning paradigms have emerged more recently which may be particularly feasible and effective methods for Neurorehabilitation. More clinical trials in pediatric and adult neurorehabilitation to refine methods and doses and to compare to other evidence-based training strategies are warranted.

Evaluation of Multi-layer Perceptron Neural Networks in Predicting Ankle Dorsiflexion in Healthy Adults using Movement-related Cortical Potentials for BCI-Neurofeedback Applications.

Brain computer interface (BCI) systems were initially developed to replace lost function; however, they are being increasingly utilized in rehabilitation to restore motor functioning after brain injury. In such BCI-mediated neurofeedback training (BCI-NFT), the brain-state associated with movement attempt or intention is used to activate an external device which assists the movement while providing sensory feedback to enhance neuroplasticity. A critical element in the success of BCI-NFT is accurate timing of the feedback within the active period of the brain state. The overarching goal of this work was to develop a reliable deep learning model that can predict motion before its onset, and thereby deliver the sensory stimuli in a timely manner for BCI-NFT applications. To this end, the main objective of the current study was to design and evaluate a Multi-layer Perceptron Neural Network (MLP-NN). Movement-related cortical potentials (MRCP) during planning and execution of ankle dorsiflexion was used to train the model to classify dorsiflexion planning vs. rest. The accuracy and reliability of the model was evaluated offline using data from eight healthy individuals (age: 26.3 ± 7.6 years). First, we evaluated three different epoching strategies for defining our 2 classes, to identify the one which best discriminated rest from dorsiflexion. The best model accuracy for predicting ankle dorsiflexion from EEG before movement execution was 84.7%. Second, the effect of various spatial filters on the model accuracy was evaluated, demonstrating that the spatial filtering had minimal effect on model accuracy and reliability.

Early intervention for very young children with or at high likelihood for autism spectrum disorder: An overview of reviews.

AIM: To identify which interventions are supported by evidence and the quality of that evidence in very young children with or at high likelihood for autism spectrum disorder (ASD) to improve child outcomes. METHOD: We conducted an overview of reviews to synthesize early intervention literature for very young children with or at high likelihood for ASD. Cochrane guidance on how to perform overviews of reviews was followed. Comprehensive searches of databases were conducted for systematic reviews and meta-analyses between January 2009 and December 2020. Review data were extracted and summarized and methodological quality was assessed. Primary randomized controlled trial evidence was summarized and risk of bias assessed. This overview of reviews was not registered. RESULTS: From 762 records, 78 full texts were reviewed and seven systematic reviews and meta-analyses with 63 unique studies were identified. Several interventional approaches (naturalistic developmental behavioral intervention, and developmental and behavioral interventions) improved child developmental outcomes. Heterogeneity in design, intervention and control group, dose, delivery agent, and measurement approach was noted. Inconsistent methodological quality and potential biases were identified. INTERPRETATION: While many early interventional approaches have an impact on child outcomes, study heterogeneity and quality had an impact on our ability to draw firm conclusions regarding which treatments are most effective. Advances in trial methodology and design, and increasing attention to mitigating measurement bias, will advance the quality of the ASD early intervention evidence base. WHAT THIS PAPER ADDS: Naturalistic developmental behavioral interventions, as well as developmental and behavioral interventions, improve child outcomes in autism spectrum disorder (ASD). If only randomized controlled trials are considered, guidelines for early intensive behavioral intervention in younger children should be revisited. The greatest intervention impacts were on proximal, intervention-specific outcomes. Inadequacies in the quality of the early ASD intervention evidence base were observed.

Interleaved Assistance and Resistance for Exoskeleton Mediated Gait Training: Validation, Feasibility and Effects.

Strength and selective motor control are primary determinants of pathological gait in children with cerebral palsy (CP) and other neuromotor disorders. Emerging evidence suggests robotic application of task-specific resistance to functional movements may provide the opportunity to strengthen muscles and improve neuromuscular function during walking in children with CP. Such a strategy could be most beneficial to children who are more severely affected by the pathology but their ability to overcome such resistance and maintain functional ambulation remains unclear. The goal of this study was to design, validate and evaluate initial feasibility and effects of a novel exoskeleton strategy that provides interleaved assistance and resistance to knee extension during overground walking. One participant with CP (GMFCS III) was recruited and completed ten total visits, nine walking with the exoskeleton. Our results validated the controller's ability to parse the gait cycle into five discrete phases (mean accuracy 91%) and provide knee extension assistance during stance and resistance during swing. Following acclimation to the interleaved strategy, peak knee extension was significantly improved in both the left (mean 7.9 deg) and right (15.2 deg) limbs when walking with the exoskeleton. Knee extensor EMG during late swing phase increased to 2.7 (left leg) and 1.7 (right leg) times the activation level during baseline exoskeleton walking without resistance. These results indicate that this interleaved strategy warrants further investigation in a longitudinal intervention study, particularly in individuals who may be more severely affected such that they are unable to ambulate overground using an exoskeleton training strategy that only deploys targeted resistance to limb motion.

Effect of muscle strength training in children and adolescents with spastic cerebral palsy: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis investigates the effects of strength training program in children and adolescents with cerebral palsy to improve function, activity, and participation. DATA SOURCES: Five electronic databases (MEDLINE-Pubmed, Cochrane Library, PEDro, CINAHL, and SPORTDiscus) were systematically searched for full-text articles published from inception to 30 June 2021. REVIEW METHODS: Randomized controlled trials were included, who compared: (i) child population with spastic cerebral palsy population between 0 and 22 years; (ii) studies in which a muscle strength training program was performed and included dosing information; (iii) studies comparing strength training with other physical therapy technique(s) or untreated control group. Studies with similar outcomes were pooled by calculating standardized mean differences. Risk of bias was assessed with Cochrane Collaboration's tool for assessing the risk of bias and PROSPERO's registration number ID: CRD42020193535. RESULTS: Twenty-seven studies, comprising 847 participants with spastic cerebral palsy. The meta-analyses demonstrated significant standardized mean differences in favor of strength training program compared to other physical therapy technique(s) or untreated control group(s) for muscle strength at the knee flexors, at the knee extensor, at the plantarflexors, maximum resistance, balance, gait speed, GMFM (global, D and E dimension) and spasticity. CONCLUSION: A strength training program has positive functional and activity effects on muscle strength, balance, gait speed, or gross motor function without increasing spasticity for children and adolescents with cerebral palsy in Gross Motor Function Classification System levels I, II, and III when adequate dosage and specific principles are utilized.