Muscle synergies in neuroscience and robotics: from input-space to task-space perspectives

In this paper we review the works related to muscle synergies that have been carried-out in neuroscience and control engineering. In particular, we refer to the hypothesis that the central nervous system (CNS) generates desired muscle contractions by combining a small number of predefined modules, called muscle synergies. We provide an overview of the methods that have been employed to test the validity of this scheme, and we show how the concept of muscle synergy has been generalized for the control of artificial agents. The comparison between these two lines of research, in particular their different goals and approaches, is instrumental to explain the computational implications of the hypothesized modular organization. Moreover, it clarifies the importance of assessing the functional role of muscle synergies: although these basic modules are defined at the level of muscle activations (input-space), they should result in the effective accomplishment of the desired task. This requirement is not always explicitly considered in experimental neuroscience, as muscle synergies are often estimated solely by analyzing recorded muscle activities. We suggest that synergy extraction methods should explicitly take into account task execution variables, thus moving from a perspective purely based on input-space to one grounded on task-space as well

Functional Electrical Stimulation mediated by Iterative Learning Control and 3D robotics reduces motor impairment in chronic stroke

Background: Novel stroke rehabilitation techniques that employ electrical stimulation (ES) and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients’ voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL), a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. Methods: Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants’ arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC) algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl-Meyer, Action Research Arm Test) at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. Results: From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. Conclusions: The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this

A randomized controlled trial on the effects induced by robot-assisted and usual-care rehabilitation on upper limb muscle synergies in post-stroke subjects

Muscle synergies are hypothesized to reflect connections among motoneurons in the spinal cord activated by central commands and sensory feedback. Robotic rehabilitation of upper limb in post-stroke subjects has shown promising results in terms of improvement of arm function and motor control achieved by reassembling muscle synergies into a set more similar to that of healthy people. However, in stroke survivors the potentially neurophysiological changes induced by robot-mediated learning versus usual care have not yet been investigated. We quantified upper limb motor deficits and the changes induced by rehabilitation in 32 post-stroke subjects through the movement analysis of two virtual untrained tasks of object placing and pronation. The sample analyzed in this study is part of a larger bi-center study and included all subjects who underwent kinematic analysis and were randomized into robot and usual care groups. Post-stroke subjects who followed robotic rehabilitation showed larger improvements in axial-to-proximal muscle synergies with respect to those who underwent usual care. This was associated to a significant improvement of the proximal kinematics. Both treatments had negative effects in muscle synergies controlling the distal district. This study supports the definition of new rehabilitative treatments for improving the neurophysiological recovery after stroke

Coordination in adults with neurological impairment – a systematic review of uncontrolled manifold studies

Background: Analysis of sensorimotor synergies has been greatly advanced by the Uncontrolled Manifold (UCM) approach. The UCM method is based on partitioning inter-trial variance displayed by elemental variables into ‘good’ (VUCM) and ‘bad’ (VORT) variability that, respectively, indicate maintenance or loss of task stability. In clinical populations, these indices can be used to investigate the strength, flexibility, stereotypy and agility of synergistic control. Research question: How are synergies affected by neurological impairment in adults? Specifically, this study aimed to determine i) the impact of pathology on VUCM, VORT, and their ratio (synergy index); ii) the relationship between synergy indices and functional performance; iii) changes in anticipatory synergy adjustments (ASAs); and iv) the effects of interventions on synergies. Methods: Systematic review of UCM studies on adults with neurological impairment. Results: Most of the 17 studies had moderate to high quality scores in the adapted Critical Review Form and the UCM reporting quality checklist developed for this review. i) Most of the studies found reduced synergy indices for patients with Parkinson's disease (PD), olivo-ponto-cerebellar atrophy, multiple sclerosis and spinocerebellar degeneration, with variable levels of change in VUCM and VORT. Reduction in synergy indices was not as consistent for stroke, in three out of six studies it was unchanged. ii) Five of seven studies found no significant correlations between scores on motor function scales and UCM indices. iii) Seven studies consistently reported ASAs that are smaller in magnitude, delayed, or both, for patients compared to healthy controls. iv) Two studies reported increased synergy indices, either via increase in VUCM or decrease in VORT, after dopaminergic drugs for patients with PD. There were similar synergy indices but improved ASAs after deep brain stimulation for patients with PD. Significance: UCM can provide reliable and sensitive indicators of altered synergistic control in adults with neurological impairment

Lateral Symmetry of Synergies in Lower Limb Muscles of Acute Post-stroke Patients After Robotic Intervention

Gait disturbance is commonly associated with stroke, which is a serious neurological disease. With current technology, various exoskeletons have been developed to provide therapy, leading to many studies evaluating the use of such exoskeletons as an intervention tool. Although these studies report improvements in patients who had undergone robotic intervention, they are usually reported with clinical assessment, which are unable to characterize how muscle activations change in patients after robotic intervention. We believe that muscle activations can provide an objective view on gait performance of patients. To quantify improvement of lateral symmetry before and after robotic intervention, muscle synergy analysis with Non-Negative Matrix Factorization was used to evaluate patients\u27 EMG data. Eight stroke patients in their acute phase were evaluated before and after a course of robotic intervention with the Hybrid Assistive Limb (HAL), lasting over 3 weeks. We found a significant increase in similarity between lateral synergies of patients after robotic intervention. This is associated with significant improvements in gait measures like walking speed, step cadence, stance duration percentage of gait cycle. Clinical assessments [Functional Independence Measure-Locomotion (FIM-Locomotion), FIM-Motor (General), and Fugl-Meyer Assessment-Lower Extremity (FMA-LE)] showed significant improvements as well. Our study shows that muscle synergy analysis can be a good tool to quantify the change in neuromuscular coordination of lateral symmetry during walking in stroke patients

Functional synergy recruitment index as a reliable biomarker of motor function and recovery in chronic stroke patients

Objective. Stroke affects the expression of muscle synergies underlying motor control, most notably in patients with poorer motor function. The majority of studies on muscle synergies have conventionally approached this analysis by assuming alterations in the inner structures of synergies after stroke. Although different synergy-based features based on this assumption have to some extent described pathological mechanisms in post-stroke neuromuscular control, a biomarker that reliably reflects motor function and recovery is still missing. Approach. Based on the theory of muscle synergies, we alternatively hypothesize that functional synergy structures are physically preserved and measure the temporal correlation between the recruitment profiles of healthy modules by paretic and healthy muscles, a feature hereafter reported as the FSRI. We measured clinical scores and extracted the muscle synergies of both ULs of 18 chronic stroke survivors from the electromyographic activity of 8 muscles during bilateral movements before and after 4 weeks of non-invasive BMI controlled robot therapy and physiotherapy. We computed the FSRI as well as features quantifying inter-limb structural differences and evaluated the correlation of these synergy-based measures with clinical scores. Main results. Correlation analysis revealed weak relationships between conventional features describing inter-limb synergy structural differences and motor function. In contrast, FSRI values during specific or combined movement data significantly correlated with UL motor function and recovery scores. Additionally, we observed that BMI-based training with contingent positive proprioceptive feedback led to improved FSRI values during the specific trained finger extension movement. Significance. We demonstrated that FSRI can be used as a reliable physiological biomarker of motor function and recovery in stroke, which can be targeted via BMI-based proprioceptive therapies and adjuvant physiotherapy to boost effective rehabilitation.This study was funded by the Fortüne-Program of the University of Tübingen (2452-0-0/2), the Bundesministerium für Bildung und Forschung (AMORSA (FKZ-16SV7754), REHOME (V5GR2001M1007-01)), EUROSTARS (SubliminalHomeRehab (FKZ: 01QE2023C E! 113928)) and the Basque Government Science Program (SINICTUS (2018222036), MODULA (KK-2019/00018), Elkartek-EXOTEK (KK-2016/00083)). N Irastorza-Landa's work was funded by the Basque Government's scholarship for predoctoral students

Feasibility of Muscle Synergy Outcomes in Clinics, Robotics, and Sports: A Systematic Review

In the last years, several studies have been focused on understanding how the central nervous system controls muscles to perform a specific motor task. Although it still remains an open question, muscle synergies have come to be an appealing theory to explain the modular organization of the central nervous system. Even though the neural encoding of muscle synergies remains controversial, a large number of papers demonstrated that muscle synergies are robust across different tested conditions, which are within a day, between days, within a single subject and between subjects that have similar demographic characteristics. Thus, muscle synergy theory has been largely used in several research fields, such as clinics, robotics and sports. The present systematical review aims at providing an overview on the applications of muscle synergy theory in clinics, robotics and sports; in particular, the review is focused on the papers that provide tangible information for: (i) diagnosis or pathology assessment in clinics; (ii) robot-control design in robotics; and (iii) athletes’ performance assessment or training guidelines in sports

Analysis of the Interlimb similarity of motor patterns for improving stroke assessment and neurorehabilitation

Stroke is the leading cause of adult disability, with upper limb hemiparesis being one of the most common consequences. Regaining voluntary arm movement is one of the major goals of rehabilitation. However, even with intensive rehabilitation, approximately 30% of patients remain permanently disabled and only 5 to 20% of them recover full independence. Hence, there is an increasing interest in incorporating the latest advances in neuroscience, medicine and engineering to improve the efficacy of conventional therapies. In the last years, a variety of promising targets have been identified to improve rehabilitation. However, there is no consensus on which measure should be applied as a gold standard to study functional recovery. This fact dramatically hinders the development of new interventions since it turns difficult to compare different clinical trials and draw consistent conclusions about therapeutic efficiency. In addition, available scales are subjective, qualitative and often lead to incongruent outcomes. Indeed, there is increasing suspicion that the lack of optimal assessment measures hampers the detection of benefits of new therapies. Moreover, existing scales totally ignore the neuromuscular state of the patient masking the ongoing recovery processes. In consequence, making appropriate clinical decisions in such environment is almost impossible. In light of all these facts, the need for new objective biomarkers to develop effective therapies is undeniable. To give response to these demands we have organized this thesis into two main branches. On the one hand, we have developed an innovative physiological scale that reveals the neuromuscular state of the patient and is able to discriminate between motor impairment levels. The innovation here resides in the concept of interlimb similarity (ILS). Based on the latest findings about the modular organization of the motor system and taking into account that stroke provokes unilateral motor damage, we propose comparing the control structure of the unaffected arm with the control structure of the paretic arm to quantify motor impairment. We have defined the control structure as the set of muscle synergies and activation coefficients needed to complete a task. The advantage of this approach is not only its capacity to provide neuromuscular information about the patient, but also that the ILS is personalized to each patient and can purposely guide rehabilitation based on the patient¿s own physiological patterns. This supposes a huge advance taking into account the heterogeneity of stroke pathogenesis. On other hand, we have characterized the therapeutic potential of Visual Feedback (VF) as a tool to purposely induce neuroplastic changes. We have chosen VF among the various interventions proven to improve motor performance, because VF is a cheap strategy that can be implemented in almost any rehabilitation center. We demonstrate that VF is able to modulate the human control structure. In healthy subjects, it seems that VF makes accessible the refined dominant motor programs for the nondominant hemisphere giving rise to an increased interlimb similarity of the control structure. Interestingly, in stroke patients VF is able to manipulate the ILS of upper-limb kinematics in favor of finer motor control but a single training session seems not to be enough to fix those changes in the neuromuscular system of a damaged brain. Overall, these findings offer a new promising framework to develop and assess an effective intervention to guide the restoration of the original neuromuscular patterns and avoid unwanted maladaptive neuroplasticity. In conclusion, this thesis seeks moving forward in the understanding of human motor recovery processes and their relationship with neuroplasticity. In this sense, it provides important advances in the design of a new biomarker of motor impairment and tests the power of VF to modulate the neuromuscular control of patients with stroke.L'ictus és la principal causa de discapacitat en adults, essent l'hemiparèsia del membre superior una de les conseqüències més comunes. Els programes de rehabilitació tenen com a objectiu fonamental restituir la mobilitat del braç afectat. No obstant això, es calcula que només entre el 5 i el 20% dels pacients aconsegueixen recuperar la seva independència mentre que el 30% queden incapacitats permanentment. En front d'aquest escenari es fa necessari incorporar els últims avenços de la neurociència, la medicina i l'enginyeria en aquesta àrea. En els darrers anys s'han identificat diversos aspectes clau per intentar millorar la rehabilitació. El problema, però, és que no hi ha consens per definir una mesura com a "gold estàndard" per avaluar la recuperació funcional, motiu pel qual, el desenvolupament de noves teràpies queda profundament afectat, ja que esdevé impossible poder comparar diferents assajos clínics i extreure conclusions consistents sobre la seva eficiència terapèutica. A més, les diverses mesures que s'utilitzen són subjectives, qualitatives i sovint donen resultats incongruents. De fet, se sospita que la manca de mesures d'avaluació òptimes dificulta la detecció dels beneficis de noves teràpies. A tot això se li ha d'afegir que les mesures actuals no consideren l'estat neuromuscular del pacient, emmascarant els processos reparadors subjacents. Així doncs, prendre les decisions clíniques adequades sota aquestes condicions esdevé pràcticament impossible. En aquestes circumstàncies, no es pot ignorar el requeriment de nous biomarcadors que proporcionin dades objectives per catalitzar el disseny de teràpies efectives. Per donar resposta a aquesta situació, la tesi s'ha estructurat en dues parts. Per una banda, s'ha desenvolupat una innovadora escala fisiològica que revela l'estat neuromuscular del pacient i és capaç de discriminar entre diferents nivells d'incapacitat motora. La innovació rau en el concepte de similitud entre membres (ILS, en anglès). Així, basant-nos en els darrers descobriments sobre l'organització modular del sistema motor, i en el fet que l'ictus provoca dany unilateral, proposem comparar l'estructura de control del braç no-afectat amb l'estructura de control del braç parètic per quantificar la incapacitat motora. L'estructura de control l'hem definida com el conjunt de sinergies musculars i coeficients d'activació que es necessiten per a dur a terme una tasca. L'avantatge d'aquesta proposta és doble, ja que proporciona informació sobre l'estat neuromuscular del pacient i en ser personalitzable, pot guiar la rehabilitació d'acord amb els patrons fisiològics propis de cada pacient. Això suposa un enorme avenç en aquesta àrea, donada la immensa heterogeneïtat de la patogènesi d'aquest trastorn. D'altra banda, s'ha caracteritzat el potencial terapèutic del feedback visual (VF) per induir canvis neuroplàstics. Aquesta és una eina molt interessant perquè a més de millorar el control motor, és assequible per gairebé qualsevol centre de rehabilitació. S'ha demostrat que el VF és capaç de modular l'estructura de control. Concretament, el VF sembla transferir els programes motors de l'hemisferi dominant al costat no dominant augmentant així el ILS dels subjectes sans. En pacients amb ictus, el VF és capaç d'augmentar el ILS cinemàtic afavorint patrons de control més fins. En conclusió, l'objectiu d'aquesta tesi és aprofundir en la comprensió dels processos de recuperació motora i la seva relació amb la neuroplasticitat. La tesi ofereix un nou i prometedor marc per desenvolupar i avaluar procediments efectius per guiar la restauració dels patrons neuromusculars originals i evitar que el cervell pateixi canvis neuroplàstics indesitjables. Així, la tesi proporciona avanços importants en el disseny d'un biomarcador per quantificar la incapacitat motora i avaluar el potencial del VF per modular el control neuromuscular de pacients amb ictus.Postprint (published version