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

Neuromuscular Control Strategy during Object Transport while Walking: Adaptive Integration of Upper and Lower Limb Movements

When carrying an object while walking, a significant challenge for the central nervous system (CNS) is to preserve the object’s stability against the inter-segmental interaction torques and ground reaction forces. Studies documented several strategies used by the CNS: modulation of grip force (GF), alterations in upper limb kinematics, and gait adaptations. However, the question of how the CNS organizes the multi-segmental joint and muscle coordination patterns to deal with gait-induced perturbations remains poorly understood. This dissertation aimed to explore the neuromuscular control strategy utilized by the CNS to transport an object during walking successfully. Study 1 examined the inter-limb coordination patterns of the upper limbs when carrying a cylinder-shaped object while walking on a treadmill. It was predicted that transporting an object in one hand would affect the movement pattern of the contralateral arm to maintain the overall angular momentum. The results showed that transporting an object caused a decreased anti-phase coordination, but it did not induce significant kinematic and muscle activation changes in the unconstrained arm. Study 2 examined muscle synergy patterns for upper limb damping behavior by using non-negative matrix factorization (NNMF) method. Four synergies were identified, showing a proximal-to-distal pattern of activation preceding heel contacts. Study 3 examined the effect of different precision demands (carrying a cup with or without a ball) and altered visual information (looking forward vs. looking at an object) on the upper limb damping behavior and muscle synergies. Increasing precision demand induced stronger damping behavior and increased the electromyography (EMG) activation of wrist/hand flexors and extensors. The NNMF results replicated Study 2 in that the stabilization of proximal joints occurred before the distal joints. The results indicated that the damping incorporates tonic and phasic muscle activation to ensure object stabilization. Overall, three experiments showed that the CNS adopts a similar synergy pattern regardless of task constraint or altered gaze direction while modulating the amount of muscle activation for object stabilization. Kinematic changes can differ depending on the different levels of constraint, as shown in the smaller movement amplitude of the shoulder joint in the transverse plane during the task with higher precision demand

Physical demand but not dexterity is associated with motor flexibility during rapid reaching in healthy young adults

Healthy humans are able to place light and heavy objects in small and large target locations with remarkable accuracy. Here we examine how dexterity demand and physical demand affect flexibility in joint coordination and end-effector kinematics when healthy young adults perform an upper extremity reaching task. We manipulated dexterity demand by changing target size and physical demand by increasing external resistance to reaching. Uncontrolled manifold analysis was used to decompose variability in joint coordination patterns into variability stabilizing the end-effector and variability de-stabilizing the end-effector during reaching. Our results demonstrate a proportional increase in stabilizing and de-stabilizing variability without a change in the ratio of the two variability components as physical demands increase. We interpret this finding in the context of previous studies showing that sensorimotor noise increases with increasing physical demands. We propose that the larger de-stabilizing variability as a function of physical demand originated from larger sensorimotor noise in the neuromuscular system. The larger stabilizing variability with larger physical demands is a strategy employed by the neuromuscular system to counter the de-stabilizing variability so that performance stability is maintained. Our findings have practical implications for improving the effectiveness of movement therapy in a wide range of patient groups, maintaining upper extremity function in old adults, and for maximizing athletic performance

Upper limb movement control after stroke and in healthy ageing: does intensive upper limb neurorehabilitation improve motor control and reduce motor impairment in the chronic phase of stroke?

Stroke affects people of all ages, but many are in the elderly population. 75% of stroke survivors have residual upper limb motor impairment and resultant disability. This thesis firstly examines upper limb motor control in chronic stroke. Evidence is emerging that high dose, high intensity complex neurorehabilitation interventions in chronic stroke patients produce unprecedented gains on clinical outcome scores of motor impairment, function and activity. But whether these clinical improvements represent behavioural repair or merely behavioural compensation remains undetermined. To address this question, upper limb movement kinematics, strength and joint range and clinical scores were measured in 52 chronic stroke patients before and after an intensive three-week treatment intervention. 29 chronic stroke patients who had not undergone treatment were similarly assessed, three-weeks apart. Significant improvements in motor control, arm strength and joint range in addition to gains on clinical scores were observed in the impaired arm of the intervention group. Crucially, changes in motor control occurred independently of changes in strength and joint range. Improvements in motor control were retained in a cohort of 28 patients in the intervention group, also assessed 6-weeks and 6-months after treatment had ended, demonstrating persistent changes in motor behaviour. These results suggest that behavioural restitution has occurred. Secondly, knowledge of the effects of normal healthy ageing on upper limb motor control is essential to informing research and delivery of clinical services. To this end, movement kinematics were measured in both arms of 57 healthy adults aged 22 to 82 years. A decline in motor control was observed as age increased, particularly in the non-dominant arm. However, motor control in healthy adults of all ages remained significantly better than in chronic stroke patients pre- and post-intervention. This thesis provides new evidence that treatment-driven improvements in motor control are achievable in the chronic post-stroke upper limb, which strongly suggests that motor control should remain a therapeutic target well beyond the current three to six-month post-stroke window. It will inform the continued development and delivery of high dose, high intensity upper limb neurorehabilitation treatment interventions for stroke patients of all ages

Robotics Rehabilitation for Training and Assessment of Upper Extremities

Robotic Rehabilitation is a prominent rehabilitation tool that provides comprehensive repetitive tasks, diversity and feedback for cost efficiency with quantitative measurement of human motor performances substituting the conventional physiotherapy. However, the current literature has a paucity of robotic devices assessment on the human motor performances with different handedness. Therefore, this study aims to investigate both hands kinematic abilities to accomplish a reaching task which is the virtual supermarket game (picking up the food) with their effect of handedness is conducted by using rehabilitation robotic, Armeo®Spring along with the surface electromyography (sEMG) to evaluate the ability of individual muscle activation when performing an upper extremities reaching task. Moreover, a Robotics Rehabilitation Management Tool is developed as a user-friendly clinical management tool for physiotherapist and patients. Fifteen (15) subjects, 9 males, and 6 females are divided into different groups; males right-handed, males left-handed, female right-handed, female left-handed and males both-handed. From the study, the range of motion (ROM) and muscle activation (sEMG signal) of the subject were significantly dependent on the handedness. On the contrary, the game scoring and hand position/opening reach were not affected by handedness

Self-Powered Robots to Reduce Motor Slacking During Upper-Extremity Rehabilitation: A Proof of Concept Study

Background: Robotic rehabilitation is a highly promising approach to recover lost functions after stroke or other neurological disorders. Unfortunately, robotic rehabilitation currently suffers from motor slacking , a phenomenon in which the human motor system reduces muscle activation levels and movement excursions, ostensibly to minimize metabolic- and movement-related costs. Consequently, the patient remains passive and is not fully engaged during therapy. To overcome this limitation, we envision a new class of body-powered robots and hypothesize that motor slacking could be reduced if individuals must provide the power to move their impaired limbs via their own body (i.e., through the motion of a healthy limb). Objective: To test whether a body-powered exoskeleton (i.e. robot) could reduce motor slacking during robotic training. Methods: We developed a body-powered robot that mechanically coupled the motions of the user\u27s elbow joints. We tested this passive robot in two groups of subjects (stroke and able-bodied) during four exercise conditions in which we controlled whether the robotic device was powered by the subject or by the experimenter, and whether the subject\u27s driven arm was engaged or at rest. Motor slacking was quantified by computing the muscle activation changes of the elbow flexor and extensor muscles using surface electromyography. Results: Subjects had higher levels of muscle activation in their driven arm during self-powered conditions compared to externally-powered conditions. Most notably, subjects unintentionally activated their driven arm even when explicitly told to relax when the device was self-powered. This behavior was persistent throughout the trial and did not wane after the initiation of the trial. Conclusions: Our findings provide novel evidence indicating that motor slacking can be reduced by self-powered robots; thus demonstrating promise for rehabilitation of impaired subjects using this new class of wearable system. The results also serve as a foundation to develop more sophisticated body-powered robots (e.g., with controllable transmissions) for rehabilitation purposes

Bimanual coordination and motor learning in children with unilateral motor disorders

Introduction Appropriate bimanual coordination is essential for many tasks in daily life. Children with unilateral cerebral palsy (uCP) however struggle with the execution of such tasks. Extensive research has been done investigating motor impairments on a functional level using standardized procedures. There is a lack of studies however looking at the specific problem of coordination of a bimanual task, especially with respect to the different underlying neuropathologies. Aims & Methods Within this thesis, kinematics of bimanual hand movement during a role differentiated bimanual box opening task in children with uCP, as well as in typically developing children (TDC) of similar ages, were investigated. The aims were: i) to identify behavioural changes in peak periods of development of the corpus callosum and areas of the prefrontal cortex, both of which are related to bimanual function in typically developing children; ii) to explore the relation between motor impairments of children with uCP and their bimanual coordination and iii) to investigate the impact of various underlying neuropathologies on bimanual coordination in children with uCP. Results For the first study, a total of 37 TDC between 5 and 16 years were included and allocated to their respective age-group: Young Children (YC: 5-6 years), Old Children (OC: 7-9 years) and Adolescents (AD: 10-16 years). The two older groups performed the task significantly faster than YC. Likewise, a trend (yet without reaching significance) towards a more ideal temporal sequencing was shown between YC and the two older groups. In contrast, spatial accuracy as expressed by the path length increased only in the AD group. For the second study, a total of 37 children with uCP between 7 and 17 years were included. Children presented manual impairments between levels I and III (according to the Manual Ability Classification System). It could be shown that task duration increased and spatial accuracy decreased with increasing levels of impairment, especially in children with higher levels of impairment (level III). Furthermore it could be shown that a subgroup of children experienced an involuntary interference when moving their affected hand, limiting the use of their less affected hand. The third study utilised a multiple case study involving nine children diagnosed with uCP with neuroimaging and neurophysiological data. The children were found to have various neuropathological patterns resulting in different forms and severities of motor impairments. It could be shown that grey-matter lesions had the most severe impact on manual abilities. Conclusion In TDC, performance of bimanual hand movements was temporally related to peak developmental periods of the corpus callosum, emphasizing the importance of interhemispheric exchange of information for bimanual coordination. In children with uCP, bimanual performance was related to the level of impairment of the affected hand. In addition it was found however that some children show excessive bimanual interference when using their affected hand in a bimanual task which limits the functionality of the less affected hand, possibly related to i) ipsilateral corticomotor projection patterns from the less affected hemisphere to the affected hand or ii) lack of suppression of interhemispheric crosstalk. It could also be shown that the various neuropathologies can affect bimanual motor control differently. Detailed diagnosis of the neuropathology and motor impairment are thus essential for the planning of tailored therapy interventions