Myoelectric control and virtual reality to enhance motor rehabilitation after stroke.

Effective upper-limb rehabilitation for severely impaired stroke survivors is still missing. Recent studies endorse novel motor rehabilitation approaches such as robotic exoskeletons and virtual reality systems to restore the function of the paretic limb of stroke survivors. However, the optimal way to promote the functional reorganization of the central nervous system after a stroke has yet to be uncovered. Electromyographic (EMG) signals have been employed for prosthetic control, but their application to rehabilitation has been limited. Here we propose a novel approach to promote the reorganization of pathological muscle activation patterns and enhance upper-limb motor recovery in stroke survivors by using an EMG-controlled interface to provide personalized assistance while performing movements in virtual reality (VR). We suggest that altering the visual feedback to improve motor performance in VR, thereby reducing the effect of deviations of the actual, dysfunctional muscle patterns from the functional ones, will actively engage patients in motor learning and facilitate the restoration of functional muscle patterns. An EMG-controlled VR interface may facilitate effective rehabilitation by targeting specific changes in the structure of muscle synergies and in their activations that emerged after a stroke-offering the possibility to provide rehabilitation therapies addressing specific individual impairments.

Exposure to an incompatible virtual surgery impacts the null space components of the muscle patterns after re-adaptation but not the task performance.

Under the synergy hypothesis, novel muscle synergies may be required for motor skill learning. We have developed a "virtual surgery" experimental paradigm that alters the mapping of muscle activations onto virtual cursor motion during an isometric reaching task using myoelectric control. By creating virtual surgeries that are "incompatible" with the original synergies, we can investigate learning new muscle synergies in controlled experimental conditions. We have previously shown that participants are able to improve their task performance after an incompatible virtual surgery, using novel muscle patterns to overcome the perturbation. In this work, we investigated whether the activation of novel muscle patterns, that are required after an incompatible virtual surgery, affects task performance or the muscle patterns after re-adaptation to the unperturbed baseline mapping. We found that experiencing an incompatible virtual surgery did not affect the task performance during the baseline mapping. However, the adaptation to the incompatible virtual surgery resulted in changes in the null space components of the muscle patterns used in the unperturbed task.

A novel force-constrained non-negative matrix factorization algorithm reveals the effectiveness of muscle synergies in the task space.

According to the synergy hypothesis, the motor system recruits a small number of synergies in a task-dependent manner. Existing synergy extraction algorithms typically only consider the muscle pattern and it remains unclear to which extent muscle synergies encode task-relevant variations of muscle activity. We propose a novel force-constrained non-negative matrix algorithm (FCNMF) based on a gradient descent update rule that considers also the task space by adding a term penalizing force reconstruction error in the cost function. We validated the FCNMF algorithm using simulated muscle data and corrupted them by noise. We compared task performances with reconstructed trajectories using synergies (RS) extracted from the FCNMF algorithm and from the standard multiplicative non-negative matrix factorization NMF algorithm. We found that FCNMF outperforms NMF for different types of noise. Finally, we demonstrated the effectiveness of FCNMF on EMG data collected during an isometric reaching task. The new algorithm accurately reconstructs the trajectories in all participants, even in those for which the NMF algorithm fails. These findings show the effectiveness of muscle synergies extracted considering the task space, possibly thanks to the robustness of FCNMF against non-isotropic noise present in muscle data, suggesting that they provide an effective strategy for motor coordination.

Persistent changes in motor adaptation strategies after perturbations that require exploration of novel muscle activation patterns.

Motor skill learning requires the acquisition of novel muscle patterns and a new control policy-a process that requires time. In contrast, motor adaptation often requires only the adjustment of existing muscle patterns-a fast process. By altering the mapping of muscle activations onto cursor movements in a myoelectrically controlled virtual environment, we are able to create perturbations that require either the recombination of existing muscle synergies (compatible virtual surgery) or the learning of novel muscle patterns (incompatible virtual surgery). We investigated whether adaptation to a compatible surgery is affected by prior exposure to an incompatible surgery, i.e., a motor skill learning task. We found that adaptation to a compatible surgery was characterized by a decrease in the quality of muscle pattern reconstructions using the original synergies and an increase in reaction times only after exposure to an incompatible surgery. In contrast, prior exposure to a compatible surgery did not affect the learning process required to overcome an incompatible surgery. The fact that exposure to an incompatible surgery had a profound effect on the muscle patterns during the adaptation to a subsequent compatible surgery and not vice versa suggests that null space exploration, possibly combined with an explicit exploration strategy, is engaged during exposure to an incompatible surgery and remains enhanced during a new adaptation episode. We conclude that motor skill learning, requiring novel muscle activation patterns, leads to changes in the exploration strategy employed during a subsequent perturbation.NEW & NOTEWORTHY Motor skill learning requires the acquisition of novel muscle patterns, whereas motor adaptation requires adjusting existing ones. We wondered whether training a new motor skill affects motor adaptation strategies. We show that learning an incompatible perturbation, a complex skill requiring new muscle synergies, affects the muscle patterns observed during adaption to a compatible perturbation, which requires adjusting the existing synergies. Our results suggest that motor skill learning results in persistent changes in the exploration strategy.

Muscle synergy analysis yields an efficient and physiologically relevant method of assessing stroke.

The Fugl-Meyer Assessment is widely used to test motor function in stroke survivors. In the Fugl-Meyer Assessment, stroke survivors perform several movement tasks and clinicians subjectively rate the performance of each task item. The individual task items in the Fugl-Meyer Assessment are selected on the basis of clinical experience, and their physiological relevance has not yet been evaluated. In the present study, we aimed to objectively rate the performance of task items by measuring the muscle activity of 41 muscles from the upper body while stroke survivors and healthy participants performed 37 Fugl-Meyer Assessment upper extremity task items. We used muscle synergy analysis to compare muscle activity between subjects and found that 13 muscle synergies in the healthy participants (which we defined as standard synergies) were able to reconstruct all of the muscle activity in the Fugl-Meyer Assessment. Among the standard synergies, synergies involving the upper arms, forearms and fingers were activated to varying degrees during different task items. In contrast, synergies involving posterior trunk muscles were activated during all tasks, which suggests the importance of posterior trunk muscle synergies throughout all sequences. Furthermore, we noted the inactivation of posterior trunk muscle synergies in stroke survivors with severe but not mild impairments, suggesting that lower trunk stability and the underlying activity of posterior trunk muscle synergies may have a strong influence on stroke severity and recovery. By comparing the synergies of stroke survivors with standard synergies, we also revealed that some synergies in stroke survivors corresponded to merged standard synergies; the merging rate increased with the impairment of stroke survivors. Moreover, the degrees of severity-dependent changes in the merging rate (the merging rate-severity relationship) were different among different task items. This relationship was significant for 26 task items only and not for the other 11 task items. Because muscle synergy analysis evaluates coordinated muscle activities, this different dependency suggests that these 26 task items are appropriate for evaluating muscle coordination and the extent of its impairment in stroke survivors. Overall, we conclude that the Fugl-Meyer Assessment reflects physiological function and muscle coordination impairment and suggest that it could be performed using a subset of the 37 task items.

Task space exploration improves adaptation after incompatible virtual surgeries.

Humans have a remarkable capacity to learn new motor skills, a process that requires novel muscle activity patterns. Muscle synergies may simplify the generation of muscle patterns through the selection of a small number of synergy combinations. Learning of new motor skills may then be achieved by acquiring novel muscle synergies. In a previous study, we used myoelectric control to construct virtual surgeries that altered the mapping from muscle activity to cursor movements. After compatible virtual surgeries, which could be compensated by recombining subject-specific muscle synergies, participants adapted quickly. In contrast, after incompatible virtual surgeries, which could not be compensated by recombining existing synergies, participants explored new muscle patterns but failed to adapt. Here, we tested whether task space exploration can promote learning of novel muscle synergies required to overcome an incompatible surgery. Participants performed the same reaching task as in our previous study but with more time to complete each trial, thus allowing for exploration. We found an improvement in trial success after incompatible virtual surgeries. Remarkably, improvements in movement direction accuracy after incompatible surgeries occurred faster for corrective movements than for the initial movement, suggesting that learning of new synergies is more effective when used for feedback control. Moreover, reaction time was significantly higher after incompatible than compatible virtual surgeries, suggesting an increased use of an explicit adaptive strategy to overcome incompatible surgeries. Taken together, these results indicate that exploration is important for skill learning and suggest that human participants, with sufficient time, can learn new muscle synergies.NEW & NOTEWORTHY Motor skill learning requires the acquisition of novel muscle patterns, a slow adaptive process. Here we show that learning to control a cursor after an incompatible virtual surgery, a complex skill requiring new muscle synergies, is possible when enough time for task space exploration is provided. Our results suggest that learning new synergies is related to the exceptional human capacity to acquire a wide variety of novel motor skills with practice.

Simultaneous control of natural and extra degrees of freedom by isometric force and electromyographic activity in the muscle-to-force null space.

Objective.Muscle activation patterns in the muscle-to-force null space, i.e. patterns that do not generate task-relevant forces, may provide an opportunity for motor augmentation by allowing to control additional end-effectors simultaneously to natural limbs. Here we tested the feasibility of muscular null space control for augmentation by assessing simultaneous control of natural and extra degrees of freedom.Approach.We instructed eight participants to control translation and rotation of a virtual 3D end-effector by simultaneous generation of isometric force at the hand and null space activity extracted in real-time from the electromyographic signals recorded from 15 shoulder and arm muscles. First, we identified the null space components that each participant could control more naturally by voluntary co-contraction. Then, participants performed several blocks of a reaching and holding task. They displaced an ellipsoidal cursor to reach one of nine targets by generating force, and simultaneously rotated the cursor to match the target orientation by activating null space components. We developed an information-theoretic metric, an index of difficulty defined as the sum of a spatial and a temporal term, to assess individual null space control ability for both reaching and holding.Main results.On average, participants could reach the targets in most trials already in the first block (72%) and they improved with practice (maximum 93%) but holding performance remained lower (maximum 43%). As there was a high inter-individual variability in performance, we performed a simulation with different spatial and temporal task conditions to estimate those for which each individual participants would have performed best.Significance.Muscular null space control is feasible and may be used to control additional virtual or robotics end-effectors. However, decoding of motor commands must be optimized according to individual null space control ability.

Can spatial filtering separate voluntary and involuntary components in children with dyskinetic cerebral palsy?

The design of myocontrolled devices faces particular challenges in children with dyskinetic cerebral palsy because the electromyographic signal for control contains both voluntary and involuntary components. We hypothesized that voluntary and involuntary components of movements would be uncorrelated and thus detectable as different synergistic patterns of muscle activity, and that removal of the involuntary components would improve online EMG-based control. Therefore, we performed a synergy-based decomposition of EMG-guided movements, and evaluated which components were most controllable using a Fitts' Law task. Similarly, we also tested which muscles were most controllable. We then tested whether removing the uncontrollable components or muscles improved overall function in terms of movement time, success rate, and throughput. We found that removal of less controllable components or muscles did not improve EMG control performance, and in many cases worsened performance. These results suggest that abnormal movement in dyskinetic CP is consistent with a pervasive distortion of voluntary movement rather than a superposition of separable voluntary and involuntary components of movement.

Does the cerebellum shape the spatiotemporal organization of muscle patterns? Insights from subjects with cerebellar ataxias.

The role of the cerebellum in motor control has been investigated extensively, but its contribution to the muscle pattern organization underlying goal-directed movements is still not fully understood. Muscle synergies may be used to characterize multimuscle pattern organization irrespective of time (spatial synergies), in time irrespective of the muscles (temporal synergies), and both across muscles and in time (spatiotemporal synergies). The decomposition of muscle patterns as combinations of different types of muscle synergies offers the possibility to identify specific changes due to neurological lesions. In this study, we recorded electromyographic activity from 13 shoulder and arm muscles in subjects with cerebellar ataxias (CA) and in age-matched healthy subjects (HS) while they performed reaching movements in multiple directions. We assessed whether cerebellar damage affects the organization of muscle patterns by extracting different types of muscle synergies from the muscle patterns of each HS and using these synergies to reconstruct the muscle patterns of all other participants. We found that CA muscle patterns could be accurately captured only by spatial muscle synergies of HS. In contrast, there were significant differences in the reconstruction R2 values for both spatiotemporal and temporal synergies, with an interaction between the two synergy types indicating a larger difference for spatiotemporal synergies. Moreover, the reconstruction quality using spatiotemporal synergies correlated with the severity of impairment. These results indicate that cerebellar damage affects the temporal and spatiotemporal organization, but not the spatial organization, of the muscle patterns, suggesting that the cerebellum plays a key role in shaping their spatiotemporal organization.NEW & NOTEWORTHY In recent studies, the decomposition of muscle activity patterns has revealed a modular organization of the motor commands. We show, for the first time, that muscle patterns of subjects with cerebellar damage share with healthy controls spatial, but not temporal and spatiotemporal, modules. Moreover, changes in spatiotemporal organization characterize the severity of the subject's impairment. These results suggest that the cerebellum has a specific role in shaping the spatiotemporal organization of the muscle patterns.

Muscle patterns underlying voluntary modulation of co-contraction.

Manipulative actions involving unstable interactions with the environment require controlling mechanical impedance through muscle co-contraction. While much research has focused on how the central nervous system (CNS) selects the muscle patterns underlying a desired movement or end-point force, the coordination strategies used to achieve a desired end-point impedance have received considerably less attention. We recorded isometric forces at the hand and electromyographic (EMG) signals in subjects performing a reaching task with an external disturbance. In a virtual environment, subjects displaced a cursor by applying isometric forces and were instructed to reach targets in 20 spatial locations. The motion of the cursor was then perturbed by disturbances whose effects could be attenuated by increasing co-contraction. All subjects could voluntarily modulate co-contraction when disturbances of different magnitudes were applied. For most muscles, activation was modulated by target direction according to a cosine tuning function with an offset and an amplitude increasing with disturbance magnitude. Co-contraction was characterized by projecting the muscle activation vector onto the null space of the EMG-to-force mapping. Even in the baseline the magnitude of the null space projection was larger than the minimum magnitude required for non-negative muscle activations. Moreover, the increase in co-contraction was not obtained by scaling the baseline null space projection, scaling the difference between the null space projections in any block and the projection of the non-negative minimum-norm muscle vector, or scaling the difference between the null space projections in the perturbed blocks and the baseline null space projection. However, the null space projections in the perturbed blocks were obtained by linear combination of the baseline null space projection and the muscle activation used to increase co-contraction without generating any force. The failure of scaling rules in explaining voluntary modulation of arm co-contraction suggests that muscle pattern generation may be constrained by muscle synergies.

Effective force control by muscle synergies.

Muscle synergies have been proposed as a way for the central nervous system (CNS) to simplify the generation of motor commands and they have been shown to explain a large fraction of the variation in the muscle patterns across a variety of conditions. However, whether human subjects are able to control forces and movements effectively with a small set of synergies has not been tested directly. Here we show that muscle synergies can be used to generate target forces in multiple directions with the same accuracy achieved using individual muscles. We recorded electromyographic (EMG) activity from 13 arm muscles and isometric hand forces during a force reaching task in a virtual environment. From these data we estimated the force associated to each muscle by linear regression and we identified muscle synergies by non-negative matrix factorization. We compared trajectories of a virtual mass displaced by the force estimated using the entire set of recorded EMGs to trajectories obtained using 4-5 muscle synergies. While trajectories were similar, when feedback was provided according to force estimated from recorded EMGs (EMG-control) on average trajectories generated with the synergies were less accurate. However, when feedback was provided according to recorded force (force-control) we did not find significant differences in initial angle error and endpoint error. We then tested whether synergies could be used as effectively as individual muscles to control cursor movement in the force reaching task by providing feedback according to force estimated from the projection of the recorded EMGs into synergy space (synergy-control). Human subjects were able to perform the task immediately after switching from force-control to EMG-control and synergy-control and we found no differences between initial movement direction errors and endpoint errors in all control modes. These results indicate that muscle synergies provide an effective strategy for motor coordination.

Differences in adaptation rates after virtual surgeries provide direct evidence for modularity.

Whether the nervous system relies on modularity to simplify acquisition and control of complex motor skills remains controversial. To date, evidence for modularity has been indirect, based on statistical regularities in the motor commands captured by muscle synergies. Here we provide direct evidence by testing the prediction that in a truly modular controller it must be harder to adapt to perturbations that are incompatible with the modules. We investigated a reaching task in which human subjects used myoelectric control to move a mass in a virtual environment. In this environment we could perturb the normal muscle-to-force mapping, as in a complex surgical rearrangement of the tendons, by altering the mapping between recorded muscle activity and simulated force applied on the mass. After identifying muscle synergies, we performed two types of virtual surgeries. After compatible virtual surgeries, a full range of movements could still be achieved recombining the synergies, whereas after incompatible virtual surgeries, new or modified synergies would be required. Adaptation rates after the two types of surgery were compared. If synergies were only a parsimonious description of the regularities in the muscle patterns generated by a nonmodular controller, we would expect adaptation rates to be similar, as both types of surgeries could be compensated with similar changes in the muscle patterns. In contrast, as predicted by modularity, we found strikingly faster adaptation after compatible surgeries than after incompatible ones. These results indicate that muscle synergies are key elements of a modular architecture underlying motor control and adaptation.

Finding neural assemblies with frequent item set mining.

Cell assemblies, defined as groups of neurons exhibiting precise spike coordination, were proposed as a model of network processing in the cortex. Fortunately, in recent years considerable progress has been made in multi-electrode recordings, which enable recording massively parallel spike trains of hundred(s) of neurons simultaneously. However, due to the challenges inherent in multivariate approaches, most studies in favor of cortical cell assemblies still resorted to analyzing pairwise interactions. However, to recover the underlying correlation structures, higher-order correlations need to be identified directly. Inspired by the Accretion method proposed by Gerstein et al. (1978) we propose a new assembly detection method based on frequent item set mining (FIM). In contrast to Accretion, FIM searches effectively and without redundancy for individual spike patterns that exceed a given support threshold. We study different search methods, with which the space of potential cell assemblies may be explored, as well as different test statistics and subset conditions with which candidate assemblies may be assessed and filtered. It turns out that a core challenge of cell assembly detection is the problem of multiple testing, which causes a large number of false discoveries. Unfortunately, criteria that address individual candidate assemblies and try to assess them with statistical tests and/or subset conditions do not help much to tackle this problem. The core idea of our new method is that in order to cope with the multiple testing problem one has to shift the focus of statistical testing from specific assemblies (consisting of a specific set of neurons) to spike patterns of a certain size (i.e., with a certain number of neurons). This significantly reduces the number of necessary tests, thus alleviating the multiple testing problem. We demonstrate that our method is able to reliably suppress false discoveries, while it is still very sensitive in discovering synchronous activity. Since we exploit high-speed computational techniques from FIM for the tests, our method is also computationally efficient.

Effort minimization and synergistic muscle recruitment for three-dimensional force generation.

To generate a force at the hand in a given spatial direction and with a given magnitude the central nervous system (CNS) has to coordinate the recruitment of many muscles. Because of the redundancy in the musculoskeletal system, the CNS can choose one of infinitely many possible muscle activation patterns which generate the same force. What strategies and constraints underlie such selection is an open issue. The CNS might optimize a performance criterion, such as accuracy or effort. Moreover, the CNS might simplify the solution by constraining it to be a combination of a few muscle synergies, coordinated recruitment of groups of muscles. We tested whether the CNS generates forces by minimum effort recruitment of either individual muscles or muscle synergies. We compared the activation of arm muscles observed during the generation of isometric forces at the hand across multiple three-dimensional force targets with the activation predicted by either minimizing the sum of squared muscle activations or the sum of squared synergy activations. Muscle synergies were identified from the recorded muscle pattern using non-negative matrix factorization. To perform both optimizations we assumed a linear relationship between rectified and filtered electromyographic (EMG) signal which we estimated using multiple linear regressions. We found that the minimum effort recruitment of synergies predicted the observed muscle patterns better than the minimum effort recruitment of individual muscles. However, both predictions had errors much larger than the reconstruction error obtained by the synergies, suggesting that the CNS generates three-dimensional forces by sub-optimal recruitment of muscle synergies.

Viewing strategy of Cebus monkeys during free exploration of natural images.

Humans and other primates move their eyes several times per second to foveate at different locations of a visual scene. What features of a scene guide eye movements in natural vision? We recorded eye movements of three monkeys during free exploration of natural scenes and propose a simple model to explain their dynamics. We use the spatial clustering of fixation positions to define the monkeys' subjective regions-of-interest (ROI) in natural scenes. For most images the subjective ROIs match significantly the computed saliency of the natural scene, except when the image contains human or primate faces. We also investigated the temporal sequence of eye movements by computing the probability that a fixation will be made inside or outside of the ROI, given the current fixation position. We fitted a Markov chain model to the sequence of fixation positions, and find that fixations made inside a ROI are more likely to be followed by another fixation in the same ROI. This is true, independent of the image saliency in the area of the ROI. Our results show that certain regions in a natural scene are explored locally before directing the focus to another local region. This strategy could allow for quick integration of the visual features that constitute an object, and efficient segmentation of objects from other objects and the background during free viewing of natural scenes.

Efficient identification of assembly neurons within massively parallel spike trains.

The chance of detecting assembly activity is expected to increase if the spiking activities of large numbers of neurons are recorded simultaneously. Although such massively parallel recordings are now becoming available, methods able to analyze such data for spike correlation are still rare, as a combinatorial explosion often makes it infeasible to extend methods developed for smaller data sets. By evaluating pattern complexity distributions the existence of correlated groups can be detected, but their member neurons cannot be identified. In this contribution, we present approaches to actually identify the individual neurons involved in assemblies. Our results may complement other methods and also provide a way to reduce data sets to the "relevant" neurons, thus allowing us to carry out a refined analysis of the detailed correlation structure due to reduced computation time.

Synchronization of neuronal responses in primary visual cortex of monkeys viewing natural images.

When inspecting visual scenes, primates perform on average four saccadic eye movements per second, which implies that scene segmentation, feature binding, and identification of image components is accomplished in <200 ms. Thus individual neurons can contribute only a small number of discharges for these complex computations, suggesting that information is encoded not only in the discharge rate but also in the timing of action potentials. While monkeys inspected natural scenes we registered, with multielectrodes from primary visual cortex, the discharges of simultaneously recorded neurons. Relating these signals to eye movements revealed that discharge rates peaked around 90 ms after fixation onset and then decreased to near baseline levels within 200 ms. Unitary event analysis revealed that preceding this increase in firing there was an episode of enhanced response synchronization during which discharges of spatially distributed cells coincided within 5-ms windows significantly more often than predicted by the discharge rates. This episode started 30 ms after fixation onset and ended by the time discharge rates had reached their maximum. When the animals scanned a blank screen a small change in firing rate, but no excess synchronization, was observed. The short latency of the stimulation-related synchronization phenomena suggests a fast-acting mechanism for the coordination of spike timing that may contribute to the basic operations of scene segmentation.

Applications, complications, and outcomes of transvenous pacemaker implantation in 105 dogs (1997-2002).

We reviewed the indications for age and breeds of dogs who received transvenous endocardial artificial pacemaker (AP) implantation (n = 105) and complications and survival thereafter at a single institution over a 6-year period. A third-degree atrioventricular (AV) block (59%) and sick sinus syndrome (SSS; 27%) were the most common indications, along with a high-grade second-degree AV block (9%) and atrial standstill (5%). The most common breeds identified were Labrador Retriever (n = 16; 11 with a third-degree AV block), American Cocker Spaniel (n = 14; 10 with SSS), and Miniature Schnauzer (n = 13; all with SSS). Common presenting complaints were syncope (n = 66) and exercise intolerance or lethargy (n = 25). Half of the dogs (n = 52) had a history of acute onset of clinical signs (<2 weeks). Mean survival time for the 60 dogs who died during the study period was 2.2 years (range, 0.1-5.8 years). Major complications occurred in 13% of dogs and included lead displacement (n = 7), sensing problems that led to syncope (n = 3), infection at the pacemaker site (n = 1), bleeding (n = 1), and ventricular fibrillation during implantation (n = 1; successfully defibrillated). Minor complications occurred in 11 dogs (11%). The success rate of transvenous AP implantation was comparatively high (all dogs survived the first 48 hours), and the complication rate was comparatively low when compared with a previous multicenter study, most likely because of how commonly the procedure was performed and supervisory experience.