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Abstract 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.

Abstract Practicing clinicians in neurorehabilitation continue to lack a systematic evidence base to personalize rehabilitation therapies to individual patients and thereby maximize outcomes. Computational modeling— collecting, analyzing, and modeling neurorehabilitation data— holds great promise. A key question is how can computational modeling contribute to the evidence base for personalized rehabilitation? As representatives of the clinicians and clinician-scientists who attended the 2023 NSF DARE conference at USC, here we offer our perspectives and discussion on this topic. Our overarching thesis is that clinical insight should inform all steps of modeling, from construction to output, in neurorehabilitation and that this process requires close collaboration between researchers and the clinical community. We start with two clinical case examples focused on motor rehabilitation after stroke which provide context to the heterogeneity of neurologic injury, the complexity of post-acute neurologic care, the neuroscience of recovery, and the current state of outcome assessment in rehabilitation clinical care. Do we provide different therapies to these two different patients to maximize outcomes? Asking this question leads to a corollary: how do we build the evidence base to support the use of different therapies for individual patients? We discuss seven points critical to clinical translation of computational modeling research in neurorehabilitation— (i) clinical endpoints, (ii) hypothesis- versus data-driven models, (iii) biological processes, (iv) contextualizing outcome measures, (v) clinical collaboration for device translation, (vi) modeling in the real world and (vii) clinical touchpoints across all stages of research. We conclude with our views on key avenues for future investment (clinical-research collaboration, new educational pathways, interdisciplinary engagement) to enable maximal translational value of computational modeling research in neurorehabilitation.

Control of foot placement is an essential strategy for maintaining balance during walking. During unperturbed, steady-state walking, foot placement can be accurately described as a linear function of the body’s centre of mass (CoM) state at midstance. However, it is uncertain if this mapping from CoM state to foot placement generalizes to larger perturbations that could potentially cause falls. Recovery from these perturbations may require reactive control strategies not observed during unperturbed walking. Here, we used unpredictable changes in treadmill belt speed to assess the generalizability of foot placement mappings identified during unperturbed walking. We found that foot placement mappings generalized poorly from unperturbed to perturbed walking and differed for forward perturbation versus backward perturbation. We also used the singular value decomposition of the mapping matrix to reveal that people were more sensitive to backward versus forward perturbations. Together, these results indicate that a single linear mapping cannot describe the foot placement control during both forward and backward losses of balance induced by treadmill belt speed perturbations. Better characterization of human balance control strategies could improve our understanding of why different neuromotor disorders result in heightened fall risk and inform the design of controllers for balance-assisting devices.

Animals must control numerous muscles to produce forces and movements with their limbs. Current theories of motor optimization and synergistic control are predicated on the assumption that there are multiple highly diverse feasible activations for any motor task (“muscle redundancy”). Here, we demonstrate that the dimensionality of the neuromuscular control problem is greatly reduced when adding the temporal constraints inherent to any sequence of motor commands: the physiological time constants for muscle activation-contraction dynamics. We used a seven-muscle model of a human finger to fully characterize the seven-dimensional polytope of all possible motor commands that can produce fingertip force vector in any direction in 3D, in alignment with the core models of Feasibility Theory. For a given sequence of seven force vectors lasting 300 ms, a novel single-step extended linear program finds the 49-dimensional polytope of all possible motor commands that can produce the sequence of forces. We find that muscle redundancy is severely reduced when the temporal limits on muscle activation-contraction dynamics are added. For example, allowing a generous ±12% change in muscle activation within 50 ms allows visiting only ∼7% of the feasible activation space in the next time step. By considering that every motor command conditions future commands, we find that the motor-control landscape is much more highly structured and spatially constrained than previously recognized. We discuss how this challenges traditional computational and conceptual theories of motor control and neurorehabilitation for which muscle redundancy is a foundational assumption.

Beta-band (15–30 Hz) synchronization between the EMG signals of active limb muscles can serve as a non-invasive assay of corticospinal tract integrity. Tasks engaging a single limb often primarily utilize one corticospinal pathway, although bilateral neural circuits can participate in goal-directed actions involving multi-muscle coordination and utilization of feedback. Suboptimal utilization of such circuits after CNS injury can result in unintended mirror movements and activation of pathological synergies. Accordingly, it is important to understand how the actions of one limb (e.g., a less-affected limb after strokes) influence the opposite corticospinal pathway for the rehabilitation target. Certain unimanual actions decrease the excitability of the “unengaged” corticospinal tract, presumably to prevent mirror movement, but there is no direct way to predict the extent to which this will occur. In this study, we tested the hypothesis that task-dependent changes in beta-band drives to muscles of one hand will inversely correlate with changes in the opposite corticospinal tract excitability. Ten participants completed spring pinching tasks known to induce differential 15–30 Hz drive to muscles. During compressions, transcranial magnetic stimulation single pulses to the ipsilateral M1 were delivered to generate motor-evoked potentials in the unengaged hand. The task-induced changes in ipsilateral corticospinal excitability were inversely correlated with associated changes in EMG-EMG coherence of the task hand. These results demonstrate a novel connection between intermuscular coherence and the excitability of the “unengaged” corticospinal tract and provide a springboard for further mechanistic studies of unimanual tasks of varying difficulty and their effects on neural pathways relevant to rehabilitation.

Multiple proprioceptive signals, like those from muscle spindles, are thought to enable robust estimates of body configuration. Yet, it remains unknown whether spindle signals suffice to discriminate limb movements. Here, a simulated 4-musculotendon, 2-joint planar limb model produced repeated cycles of five end-point trajectories in forward and reverse directions, which generated spindle Ia and II afferent signals (proprioceptors for velocity and length, respectively) from each musculotendon. We find that cross-correlation of the 8D time series of raw firing rates (four Ia, four II) cannot discriminate among most movement pairs (∼ 29% accuracy). However, projecting these signals onto their 1st and 2nd principal components greatly improves discriminability of movement pairs (82% accuracy). We conclude that high-dimensional ensembles of muscle proprioceptors can discriminate among limb movements—but only after dimensionality reduction. This may explain the pre-processing of some afferent signals before arriving at the somatosensory cortex, such as processing of cutaneous signals at the cat’s cuneate nucleus.

Synergy analysis via dimensionality reduction is a standard approach in biomechanics to capture the dominant features of limb kinematics or muscle activation signals, which can be called “coarse synergies.” Here we demonstrate that the less dominant features of these signals, which are often explicitly disregarded or considered noise, can nevertheless exhibit “fine synergies” that reveal subtle, yet functionally important, adaptations. To find the coarse synergies, we applied non-negative matrix factorization (NMF) to unilateral EMG data from eight muscles of the involved leg in ten people with drop-foot (DF), and of the right leg of 16 unimpaired (control) participants. We then extracted the fine synergies for each group by removing the coarse synergies (i.e., first two factors explaining ≥85% of variance) from the data and applying Principal Component Analysis (PCA) to those residuals. Surprisingly, the time histories and structure of the coarse EMG synergies showed few differences between DF and controls—even though the kinematics of drop-foot gait is evidently different from unimpaired gait. In contrast, the structure of the fine EMG synergies (as per their PCA loadings) showed significant differences between groups. In particular, loadings for Tibialis Anterior, Peroneus Longus, Gastrocnemius Lateralis, Biceps and Rectus Femoris, Vastus Medialis and Lateralis muscles differed between groups (p

Quantifying the dynamical features of discrete tasks is essential to understanding athletic performance for many sports that are not repetitive or cyclical. We compared three dynamical features of the (i) bow hand, (ii) drawing hand, and (iii) center of mass during a single bow-draw movement between professional and neophyte archers: dispersion (convex hull volume of their phase portraits), persistence (tendency to continue a trend as per Hurst exponents), and regularity (sample entropy). Although differences in the two groups are expected due to their differences in skill, our results demonstrate we can quantify these differences. The center of mass of professional athletes exhibits tighter movements compared to neophyte archers (6.3 < 11.2 convex hull volume), which are nevertheless less persistent (0.82 < 0.86 Hurst exponent) and less regular (0.035 > 0.025 sample entropy). In particular, the movements of the bow hand and center of mass differed more between groups in Hurst exponent analysis, and the drawing hand and center of mass were more different in sample entropy analysis. This suggests tighter neuromuscular control over the more fluid dynamics of the movement that exhibits more active corrections that are more individualized. Our work, therefore, provides proof of principle of how well-established dynamical analysis techniques can be used to quantify the nature and features of neuromuscular expertise for discrete movements in elite athletes.

Tendon transfer surgery is often used to restore hand grasp function following high median-ulnar nerve palsy. This surgery typically reroutes and sutures the tendon of the extensor carpi radialis longus (ECRL) muscle to all four flexor digitorum profundus (FDP) tendons of the hand, coupling them together. This makes it difficult to grasp irregularly shaped objects. We propose inserting a novel implantable passive device between the FDP tendons to surgically construct a differential mechanism, enabling the fingers to individually adapt to the irregular contours during grasping. These passive implants with no moving parts are fabricated from biocompatible materials. We tested the implants’ ability to create differential flexion between the index and middle fingers when actuated by a single muscle in two human cadaver hands using a computerized closed-loop control paradigm. In these cadaveric models, the implants enabled significantly more differential flexion between the index and middle fingers for a wide range of donor tendon tensions. The implants also redistributed fingertip forces between fingers. When grasping uneven objects, the difference in contact forces between fingers reduced by nearly 23% compared to the current suture-based surgery. These results suggest that self-adaptive grasp is possible in tendon transfers that drive multiple distal flexor tendons.

The importance of the image in the communicative process is not questionable. The goal of this study is to consider the implications that derive from the translation of a text that combines the visual with the verbal code; we refer to the comic or comic strip. In academic circles, this iconic-verbal object has not enjoyed excessive attention, even sometimes it has been called an uncomfortable object. However, there is no lack of studies that in their time underlined its academic interest and currently there are different works that focus on this mode of expression underlining its importance. Therefore, the Italian translation of El Eternauta will be the object of our research.