NSF DARE-Transforming modeling in neurorehabilitation: Four threads for catalyzing progress.

We present an overview of the Conference on Transformative Opportunities for Modeling in Neurorehabilitation held in March 2023. It was supported by the Disability and Rehabilitation Engineering (DARE) program from the National Science Foundation's Engineering Biology and Health Cluster. The conference brought together experts and trainees from around the world to discuss critical questions, challenges, and opportunities at the intersection of computational modeling and neurorehabilitation to understand, optimize, and improve clinical translation of neurorehabilitation. We organized the conference around four key, relevant, and promising Focus Areas for modeling: Adaptation & Plasticity, Personalization, Human-Device Interactions, and Modeling 'In-the-Wild'. We identified four common threads across the Focus Areas that, if addressed, can catalyze progress in the short, medium, and long terms. These were: (i) the need to capture and curate appropriate and useful data necessary to develop, validate, and deploy useful computational models (ii) the need to create multi-scale models that span the personalization spectrum from individuals to populations, and from cellular to behavioral levels (iii) the need for algorithms that extract as much information from available data, while requiring as little data as possible from each client (iv) the insistence on leveraging readily available sensors and data systems to push model-driven treatments from the lab, and into the clinic, home, workplace, and community. The conference archive can be found at (dare2023.usc.edu). These topics are also extended by three perspective papers prepared by trainees and junior faculty, clinician researchers, and federal funding agency representatives who attended the conference.

Motor control complexity can be dynamically simplified during gait pattern exploration using motor control-based biofeedback.

Understanding how the central nervous system coordinates diverse motor outputs has been a topic of extensive investigation. Although it is generally accepted that a small set of synergies underlies many common activities, such as walking, whether synergies are equally robust across a broader array of gait patterns or can be flexibly modified remains unclear. Here, we evaluated the extent to which synergies changed as nondisabled adults (n = 14) explored gait patterns using custom biofeedback. Secondarily, we used Bayesian additive regression trees to identify factors that were associated with synergy modulation. Participants explored 41.1 ± 8.0 gait patterns using biofeedback, during which synergy recruitment changed depending on the type and magnitude of gait pattern modification. Specifically, a consistent set of synergies was recruited to accommodate small deviations from baseline, but additional synergies emerged for larger gait changes. Synergy complexity was similarly modulated; complexity decreased for 82.6% of the attempted gait patterns, but distal gait mechanics were strongly associated with these changes. In particular, greater ankle dorsiflexion moments and knee flexion through stance, as well as greater knee extension moments at initial contact, corresponded to a reduction in synergy complexity. Taken together, these results suggest that the central nervous system preferentially adopts a low-dimensional, largely invariant control strategy but can modify that strategy to produce diverse gait patterns. Beyond improving understanding of how synergies are recruited during gait, study outcomes may also help identify parameters that can be targeted with interventions to alter synergies and improve motor control after neurological injury.NEW & NOTEWORTHY We used a motor control-based biofeedback system and machine learning to characterize the extent to which nondisabled adults can modulate synergies during gait pattern exploration. Results revealed that a small library of synergies underlies an array of gait patterns but that recruitment from this library changes as a function of the imposed biomechanical constraints. Our findings enhance understanding of the neural control of gait and may inform biofeedback strategies to improve synergy recruitment after neurological injury.

Audiovisual biofeedback amplifies plantarflexor adaptation during walking among children with cerebral palsy.

BACKGROUND: Biofeedback is a promising noninvasive strategy to enhance gait training among individuals with cerebral palsy (CP). Commonly, biofeedback systems are designed to guide movement correction using audio, visual, or sensorimotor (i.e., tactile or proprioceptive) cues, each of which has demonstrated measurable success in CP. However, it is currently unclear how the modality of biofeedback may influence user response which has significant implications if systems are to be consistently adopted into clinical care. METHODS: In this study, we evaluated the extent to which adolescents with CP (7M/1F; 14 [12.5,15.5] years) adapted their gait patterns during treadmill walking (6 min/modality) with audiovisual (AV), sensorimotor (SM), and combined AV + SM biofeedback before and after four acclimation sessions (20 min/session) and at a two-week follow-up. Both biofeedback systems were designed to target plantarflexor activity on the more-affected limb, as these muscles are commonly impaired in CP and impact walking function. SM biofeedback was administered using a resistive ankle exoskeleton and AV biofeedback displayed soleus activity from electromyography recordings during gait. At every visit, we measured the time-course response to each biofeedback modality to understand how the rate and magnitude of gait adaptation differed between modalities and following acclimation. RESULTS: Participants significantly increased soleus activity from baseline using AV + SM (42.8% [15.1, 59.6]), AV (28.5% [19.2, 58.5]), and SM (10.3% [3.2, 15.2]) biofeedback, but the rate of soleus adaptation was faster using AV + SM biofeedback than either modality alone. Further, SM-only biofeedback produced small initial increases in plantarflexor activity, but these responses were transient within and across sessions (p > 0.11). Following multi-session acclimation and at the two-week follow-up, responses to AV and AV + SM biofeedback were maintained. CONCLUSIONS: This study demonstrated that AV biofeedback was critical to increase plantarflexor engagement during walking, but that combining AV and SM modalities further amplified the rate of gait adaptation. Beyond improving our understanding of how individuals may differentially prioritize distinct forms of afferent information, outcomes from this study may inform the design and selection of biofeedback systems for use in clinical care.

Soleus H-reflex modulation in cerebral palsy and its relationship with neural control complexity: a pilot study.

Individuals with cerebral palsy (CP) display motor control patterns that suggest decreased supraspinal input, but it remains unknown if they are able to modulate lower-limb reflexes in response to more complex tasks, or whether global motor control patterns relate to reflex modulation capacity in this population. Eight ambulatory individuals with CP (12-18 years old) were recruited to complete a task complexity protocol, where soleus H-reflex excitability was compared between bilateral (baseline) and unilateral (complex) standing. We also investigated the relationship between each participant's ability to modulate soleus H-reflex excitability and the complexity of their walking neural control pattern determined from muscle synergy analysis. Finally, six of the eight participants completed an exoskeleton walking protocol, where soleus H-reflexes were collected during the stance phase of walking with and without stance-phase plantar flexor resistance. Participants displayed a significant reduction in soleus H-reflex excitability (- 26 ± 25%, p = 0.04) with unilateral standing, and a strong positive relationship was observed between more refined neural control during walking and an increased ability to modulate reflex excitability (R = 0.79, p = 0.04). There was no difference in neuromuscular outcome measures with and without the ankle exoskeleton (p values all > 0.05), with variable reflex responses to walking with ankle exoskeleton resistance. These findings provide evidence that ambulatory individuals with CP retain some capacity to modulate lower-limb reflexes in response to increased task complexity, and that less refined neural control during walking appears to be related to deficits in reflex modulation.

Muscle synergy structure and gait patterns in children with spastic cerebral palsy.

AIM: To determine if muscle synergy structure (activations and weights) differs between gait patterns in children with spastic cerebral palsy (CP). METHOD: In this cross-sectional study, we classified 188 children with unilateral (n=82) or bilateral (n=106) spastic CP (mean age: 9y 5mo, SD: 4y 3mo, range: 3y 9mo-17y 7mo; 75 females; Gross Motor Function Classification System [GMFCS] level I: 106, GMFCS level II: 55, GMFCS level III: 27) into a minor deviations (n=34), drop foot (n=16), genu recurvatum (n=26), apparent equinus (n=53), crouch (n=39), and jump gait pattern (n=20). Surface electromyography recordings from eight lower limb muscles of the most affected side were used to calculate synergies with weighted non-negative matrix factorization. We compared synergy activations and weights between the patterns. RESULTS: Synergy structure was similar between gait patterns, although weights differed in the more impaired children (crouch and jump gait) when compared to the other patterns. Variability in synergy structure between participants was high. INTERPRETATION: The similarity in synergy structure between gait patterns suggests a generic motor control strategy to compensate for the brain lesion. However, the differences in weights and high variability between participants indicate that this generic motor control strategy might be individualized and dependent on impairment level.

Energy consumption does not change after selective dorsal rhizotomy in children with spastic cerebral palsy.

AIM: To determine whether energy consumption changes after selective dorsal rhizotomy (SDR) among children with cerebral palsy (CP). METHOD: We retrospectively evaluated net nondimensional energy consumption during walking among 101 children with bilateral spastic CP who underwent SDR (59 males, 42 females; median age [5th centile, 95th centile] 5y 8mo [4y 2mo, 9y 4mo]) compared to a control group of children with CP who did not undergo SDR. The control group was matched by baseline age, spasticity, and energy consumption (56 males, 45 females; median age [5th centile, 95th centile] 5y 8mo [4y 1mo, 9y 6mo]). Outcomes were compared at baseline and follow-up (SDR: mean [SD] 1y 7mo [6mo], control: 1y 8mo [8mo]). RESULTS: The SDR group had significantly greater decreases in spasticity compared to matched controls (-42% SDR vs -20% control, p<0.001). While both groups had a modest reduction in energy consumption between visits (-12% SDR, -7% control), there was no difference in change in energy consumption (p=0.11) or walking speed (p=0.56) between groups. INTERPRETATION: The SDR group did not exhibit greater reductions in energy consumption compared to controls. The SDR group had significantly greater spasticity reduction, suggesting that spasticity had minimal impact on energy consumption during walking in CP. These results support prior findings that spasticity and energy consumption decrease with age in CP. Identifying matched control groups is critical for outcomes research involving children with CP to account for developmental changes.

Feasibility of using acceleration-derived jerk to quantify bimanual arm use.

BACKGROUND: Accelerometers have become common for evaluating the efficacy of rehabilitation for patients with neurologic disorders. For example, metrics like use ratio (UR) and magnitude ratio (MR) have been shown to differentiate movement patterns of children with cerebral palsy (CP) compared to typically-developing (TD) peers. However, these metrics are calculated from "activity counts" - a measure based on proprietary algorithms that approximate movement duration and intensity from raw accelerometer data. Algorithms used to calculate activity counts vary between devices, limiting comparisons of clinical and research results. The goal of this research was to develop complementary metrics based on raw accelerometer data to analyze arm movement after neurologic injury. METHOD: We calculated jerk, the derivative of acceleration, to evaluate arm movement from accelerometer data. To complement current measures, we calculated jerk ratio (JR) as the relative jerk magnitude of the dominant (non-paretic) and non-dominant (paretic) arms. We evaluated the JR distribution between arms and calculated the 50th percentile of the JR distribution (JR50). To evaluate these metrics, we analyzed bimanual accelerometry data for five children with hemiplegic CP who underwent Constraint-Induced Movement Therapy (CIMT) and five typically developing (TD) children. We compared JR between the CP and TD cohorts, and to activity count metrics. RESULTS: The JR50 differentiated between the CP and TD cohorts (CP = 0.578 ± 0.041 before CIMT, TD = 0.506 ± 0.026), demonstrating increased reliance on the dominant arm for the CP cohort. Jerk metrics also quantified changes in arm use during and after therapy (e.g., JR50 = 0.378 ± 0.125 during CIMT, 0.591 ± 0.057 after CIMT). The JR was strongly correlated with UR and MR (r = - 0.92, 0.89) for the CP cohort. For the TD cohort, JR50 was repeatable across three data collection periods with an average similarity of 0.945 ± 0.015. CONCLUSIONS: Acceleration-derived jerk captured differences in motion between TD and CP cohorts and correlated with activity count metrics. The code for calculating and plotting JR is open-source and available for others to use and build upon. By identifying device-independent metrics that can quantify arm movement in daily life, we hope to facilitate collaboration for rehabilitation research using wearable technologies.

Accelerometer Measurements Indicate That Arm Movements of Children With Cerebral Palsy Do Not Increase After Constraint-Induced Movement Therapy (CIMT).

IMPORTANCE: Constraint-induced movement therapy (CIMT) is a common treatment for children with unilateral cerebral palsy (CP). Although clinic-based assessments have demonstrated improvements in arm function after CIMT, whether these changes are translated and sustained outside of a clinic setting remains unclear. OBJECTIVE: Accelerometers were used to quantify arm movement for children with CP 1 wk before, during, and 4 wk or more after CIMT; measurements were compared with those from typically developing (TD) peers. DESIGN: Observational. SETTING: Tertiary hospital and community. PARTICIPANTS: Seven children with CP (5 boys, 2 girls; average [AVE] age ± standard deviation [SD] = 7.4 ± 1.2 yr) and 7 TD peers (2 boys, 5 girls; AVE age ± SD = 7.0 ± 2.3 yr). INTERVENTION: 30-hr CIMT protocol. OUTCOMES AND MEASURES: Use ratio, magnitude ratio, and bilateral magnitude were calculated from the accelerometer data. Clinical measures were administered before and after CIMT, and parent surveys assessed parent and child perceptions of wearing accelerometers. RESULTS: During CIMT, the frequency and magnitude of paretic arm use among children with CP increased in the clinic and in daily life. After CIMT, although clinical scores showed sustained improvement, the children's accelerometry data reverted to baseline values. Children and parents in both cohorts had positive perceptions of accelerometer use. CONCLUSIONS AND RELEVANCE: The lack of sustained improvement in accelerometry metrics after CIMT suggests that therapy gains did not translate to increased movement outside the clinic. Additional therapy may be needed to help transfer gains outside the clinic. WHAT THIS ARTICLE ADDS: Accelerometer measurements were effective at monitoring arm movement outside of the clinic during CIMT and suggested that additional interventions may be needed after CIMT to sustain benefits.

"Look, Your Muscles Are Firing!": A Qualitative Study of Clinician Perspectives on the Use of Surface Electromyography in Neurorehabilitation.

OBJECTIVE: To examine the perceived value, benefits, drawbacks, and ideas for technology development and implementation of surface electromyography recordings in neurologic rehabilitation practice from clinical stakeholder perspectives. DESIGN: A qualitative, phenomenological study was conducted. In-depth, semistructured interviews and focus groups were completed. Sessions included questions about clinician perspectives and demonstrations of surface electromyography systems to garner perceptions of specific system features. SETTING: The study was conducted at hospital systems in a large metropolitan area. PARTICIPANTS: Adult and pediatric physical therapists, occupational therapists, and physiatrists from inpatient, outpatient, and research settings (N=22) took part in the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Interviews and focus groups were audio-recorded, transcribed verbatim, then coded for analysis into themes. RESULTS: Four major themes emerged: (1) low-tech clinical practice and future directions for rehabilitation; (2) barriers to surface electromyography uptake and potential solutions; (3) benefits of surface electromyography for targeted populations; and (4) essential features of surface electromyography systems. CONCLUSIONS: Surface electromyography systems were not routinely utilized for assessment or intervention following neurologic injury. Despite recognition of potential clinical benefits of surface electromyography use, clinicians identified limited time and resources as key barriers to implementation. Perspectives on design and surface electromyography system features indicated the need for streamlined, intuitive, and clinically effective applications. Further research is needed to determine feasibility and clinical relevance of surface electromyography in rehabilitation intervention.

Muscle synergies demonstrate only minimal changes after treatment in cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP) have altered synergies compared to typically-developing peers, reflecting different neuromuscular control strategies used to move. While these children receive a variety of treatments to improve gait, whether synergies change after treatment, or are associated with treatment outcomes, remains unknown. METHODS: We evaluated synergies for 147 children with CP before and after three common treatments: botulinum toxin type-A injection (n = 52), selective dorsal rhizotomy (n = 38), and multi-level orthopaedic surgery (n = 57). Changes in synergy complexity were measured by the number of synergies required to explain > 90% of the total variance in electromyography data and total variance accounted for by one synergy. Synergy weights and activations before and after treatment were compared using the cosine similarity relative to average synergies of 31 typically-developing (TD) peers. RESULTS: There were minimal changes in synergies after treatment despite changes in walking patterns. Number of synergies did not change significantly for any treatment group. Total variance accounted for by one synergy increased (i.e., moved further from TD peers) after botulinum toxin type-A injection (1.3%) and selective dorsal rhizotomy (1.9%), but the change was small. Synergy weights did not change for any treatment group (average 0.001 ± 0.10), but synergy activations after selective dorsal rhizotomy did change and were less similar to TD peers (- 0.03 ± 0.07). Only changes in synergy activations were associated with changes in gait kinematics or walking speed after treatment. Children with synergy activations more similar to TD peers after treatment had greater improvements in gait. CONCLUSIONS: While many of these children received significant surgical procedures and prolonged rehabilitation, the minimal changes in synergies after treatment highlight the challenges in altering neuromuscular control in CP. Development of treatment strategies that directly target impaired control or are optimized to an individual's unique control may be required to improve walking function.