A Pilot Study of Individual Muscle Force Prediction during Elbow Flexion and Extension in the Neurorehabilitation Field

This paper proposes a neuromusculoskeletal (NMS) model to predict individual muscle force during elbow flexion and extension. Four male subjects were asked to do voluntary elbow flexion and extension. An inertial sensor and surface electromyography (sEMG) sensors were attached to subject's forearm. Joint angle calculated by fusion of acceleration and angular rate using an extended Kalman filter (EKF) and muscle activations obtained from the sEMG signals were taken as the inputs of the proposed NMS model to determine individual muscle force. The result shows that our NMS model can predict individual muscle force accurately, with the ability to reflect subject-specific joint dynamics and neural control solutions. Our method incorporates sEMG and motion data, making it possible to get a deeper understanding of neurological, physiological, and anatomical characteristics of human dynamic movement. We demonstrate the potential of the proposed NMS model for evaluating the function of upper limb movements in the field of neurorehabilitation

Computational neurorehabilitation: modeling plasticity and learning to predict recovery

Despite progress in using computational approaches to inform medicine and neuroscience in the last 30 years, there have been few attempts to model the mechanisms underlying sensorimotor rehabilitation. We argue that a fundamental understanding of neurologic recovery, and as a result accurate predictions at the individual level, will be facilitated by developing computational models of the salient neural processes, including plasticity and learning systems of the brain, and integrating them into a context specific to rehabilitation. Here, we therefore discuss Computational Neurorehabilitation, a newly emerging field aimed at modeling plasticity and motor learning to understand and improve movement recovery of individuals with neurologic impairment. We first explain how the emergence of robotics and wearable sensors for rehabilitation is providing data that make development and testing of such models increasingly feasible. We then review key aspects of plasticity and motor learning that such models will incorporate. We proceed by discussing how computational neurorehabilitation models relate to the current benchmark in rehabilitation modeling – regression-based, prognostic modeling. We then critically discuss the first computational neurorehabilitation models, which have primarily focused on modeling rehabilitation of the upper extremity after stroke, and show how even simple models have produced novel ideas for future investigation. Finally, we conclude with key directions for future research, anticipating that soon we will see the emergence of mechanistic models of motor recovery that are informed by clinical imaging results and driven by the actual movement content of rehabilitation therapy as well as wearable sensor-based records of daily activity

Flexible Virtual Reality System for Neurorehabilitation and Quality of Life Improvement

As life expectancy is mostly increasing, the incidence of many neurological disorders is also constantly growing. For improving the physical functions affected by a neurological disorder, rehabilitation procedures are mandatory, and they must be performed regularly. Unfortunately, neurorehabilitation procedures have disadvantages in terms of costs, accessibility and a lack of therapists. This paper presents Immersive Neurorehabilitation Exercises Using Virtual Reality (INREX-VR), our innovative immersive neurorehabilitation system using virtual reality. The system is based on a thorough research methodology and is able to capture real-time user movements and evaluate joint mobility for both upper and lower limbs, record training sessions and save electromyography data. The use of the first-person perspective increases immersion, and the joint range of motion is calculated with the help of both the HTC Vive system and inverse kinematics principles applied on skeleton rigs. Tutorial exercises are demonstrated by a virtual therapist, as they were recorded with real-life physicians, and sessions can be monitored and configured through tele-medicine. Complex movements are practiced in gamified settings, encouraging self-improvement and competition. Finally, we proposed a training plan and preliminary tests which show promising results in terms of accuracy and user feedback. As future developments, we plan to improve the system's accuracy and investigate a wireless alternative based on neural networks.Comment: 47 pages, 20 figures, 17 tables (including annexes), part of the MDPI Sesnsors "Special Issue Smart Sensors and Measurements Methods for Quality of Life and Ambient Assisted Living

Inverse kinematics of a 6 DoF human upper limb using ANFIS and ANN for anticipatory actuation in ADL-based physical Neurorehabilitation

Objective: This research is focused in the creation and validation of a solution to the inverse kinematics problem for a 6 degrees of freedom human upper limb. This system is intended to work within a realtime dysfunctional motion prediction system that allows anticipatory actuation in physical Neurorehabilitation under the assisted-as-needed paradigm. For this purpose, a multilayer perceptron-based and an ANFIS-based solution to the inverse kinematics problem are evaluated. Materials and methods: Both the multilayer perceptron-based and the ANFIS-based inverse kinematics methods have been trained with three-dimensional Cartesian positions corresponding to the end-effector of healthy human upper limbs that execute two different activities of the daily life: "serving water from a jar" and "picking up a bottle". Validation of the proposed methodologies has been performed by a 10 fold cross-validation procedure. Results: Once trained, the systems are able to map 3D positions of the end-effector to the corresponding healthy biomechanical configurations. A high mean correlation coefficient and a low root mean squared error have been found for both the multilayer perceptron and ANFIS-based methods. Conclusions: The obtained results indicate that both systems effectively solve the inverse kinematics problem, but, due to its low computational load, crucial in real-time applications, along with its high performance, a multilayer perceptron-based solution, consisting in 3 input neurons, 1 hidden layer with 3 neurons and 6 output neurons has been considered the most appropriated for the target application

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

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

Evaluating Neuromuscular Function of the Biceps Brachii after Spinal Cord Injury: Assessment of Voluntary Activation and Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) or peripherally (VAPNS) to reveal what levels of the nervous system are disrupting the innervation of muscle fibers. Voluntary activation measured with TMS (VATMS) can indicate deficits in voluntary cortical drive to innervate muscle. However, measurement of VATMS is limited by technical challenges, including the difficulty in preferential stimulation of cortical neurons projecting to the target muscle and minimal stimulation of antagonists. Thus, the motor evoked potential (MEP) response to TMS in the target muscle compared to its antagonist (i.e. MEP ratio) may be an important parameter in the assessment of VATMS. Using current methodology, VATMS cannot be reliably assessed in patient populations including individuals with tetraplegia. The overall purpose of this work was to investigate novel TMS-based methods to evaluate neuromuscular function after spinal cord injury. First, we developed and evaluated new methodology to assess VATMS in individuals with tetraplegia. The objective of the first study was to optimize the biceps/triceps MEP ratio using modulation of isometric elbow flexion angle in nonimpaired participants and participants with tetraplegia following cervical SCI (C5-C6). We hypothesized that the more flexed elbow angle would increase the MEP ratio. The MEP ratio was only modulated in the nonimpaired group but not across the entire range of voluntary efforts used to estimate VATMS. However, we established that VATMS and VAPNS in individuals with tetraplegia were repeatable across days. In a second study, we aimed to optimize MEPs during the assessment of VATMS using paired pulse TMS to elicit intracortical facilitation and short-interval intracortical inhibition. We hypothesized that intracortical facilitation would lead to an increased MEP ratio compared to single pulse and that short-interval intracortical inhibition would lead to a lower MEP ratio. The MEP ratio was modulated in both groups but not across the entire range of voluntary efforts, and did not affect VATMS estimation compared to single pulse TMS. Paired pulse TMS outcomes revealed abnormal patterns of intracortical inhibition in individuals with tetraplegia. Further, VATMS was sensitive to the linearity of the voluntary moment and superimposed twitch relationship. Linearity was lower in SCI relative to nonimpaired participants. We discuss the limitations of VATMS in assessing neuromuscular impairments in tetraplegia. In a third study, we aimed to collect MEP input-output curves of the biceps in SCI and nonimpaired and evaluate curve-fitting methodology as well as their repeatability across sessions. We hypothesized that slopes would be greater in the SCI group compared to nonimpaired. Slopes obtained with linear regression were greater in tetraplegia compared to nonimpaired participants, suggesting compensatory reorganization of corticomotor pathways after SCI. Linear regression accurately represented the slope of the modeled data compared to sigmoidal function curve-fitting method. Slopes were also found to be repeatable across days in both groups. In a fourth study, we aimed to implement a low-cost navigated TMS system (\u3c $3000) that uses motion tracking, 3D printed parts and open-source software to monitor coil placement during stimulation. We hypothesized that using this system would improve coil position and orientation consistency and decrease MEP variability compared to the conventional method when targeting the biceps at rest and during voluntary contractions across two sessions in nonimpaired participants. Coil orientation error was reduced but the improvement did not translate to lower MEP variability. This low-cost approach is an alternative to expensive systems in tracking the motor hotspot between sessions and quantifying the error in coil placement when delivering TMS. Finally, we conclude and recommend future research directions to address the challenges that we identified during this work to improve our ability to monitor neuromuscular impairments and contribute to the development of more effective neurorehabilitation strategies

Robotic exoskeletons: A perspective for the rehabilitation of arm coordination in stroke patients

Upper-limb impairment after stroke is caused by weakness, loss of individual joint control, spasticity, and abnormal synergies. Upper-limb movement frequently involves abnormal, stereotyped, and fixed synergies, likely related to the increased use of sub-cortical networks following the stroke. The flexible coordination of the shoulder and elbow joints is also disrupted. New methods for motor learning, based on the stimulation of activity- dependent neural plasticity have been developed. These include robots that can adaptively assist active movements and generate many movement repetitions. However, most of these robots only control the movement of the hand in space. The aim of the present text is to analyze the potential of robotic exoskeletons to specifically rehabilitate joint motion and particularly inter-joint coordination. First, a review of studies on upper-limb coordination in stroke patients is presented and the potential for recovery of coordination is examined. Second, issues relating to the mechanical design of exoskeletons and the transmission of constraints between the robotic and human limbs are discussed. The third section considers the development of different methods to control exoskeletons: existing rehabilitation devices and approaches to the control and rehabilitation of joint coordinations are then reviewed, along with preliminary clinical results available. Finally, perspectives and future strategies for the design of control mechanisms for rehabilitation exoskeletons are discussed