Low-frequency local field potentials in primate motor cortex and their application to neural interfaces

PhD ThesisFor patients with spinal cord injury and paralysis, there are currently very limited options for clinical therapy. Brain-machine interfaces (BMIs) are neuroprosthetic devices that are being developed to record from the motor cortex in such patients, bypass the spinal lesion, and use decoded signals to control an effector, such as a prosthetic limb. The ideal BMI would be durable, reliable, totally predictable, fully-implantable, and have generous battery life. Current, state-of-the-art BMIs are limited in all of these domains; partly because the typical signals used—neuronal action potentials, or ‘spikes’—are very susceptible to micro-movement of recording electrodes. Recording spikes from the same neurons over many months is therefore difficult, and decoder behaviour may be unpredictable from day-today. Spikes also need to be digitized at high frequencies (~104 Hz) and heavily processed. As a result, devices are energy-hungry and difficult to miniaturise. Low-frequency local field potentials (lf-LFPs; < 5 Hz) are an alternative cortical signal. They are more stable and can be captured and processed at much lower frequencies (~101 Hz). Here we investigate rhythmical lf-LFP activity, related to the firing of local cortical neurons, during isometric wrist movements in Rhesus macaques. Multichannel spike-related slow potentials (SRSPs) can be used to accurately decode the firing rates of individual motor cortical neurons, and subjects can control a BMI task using this synthetic signal, as if they were controlling the actual firing rate. Lf-LFP–based firing rate estimates are stable over time – even once actual spike recordings have been lost. Furthermore, the dynamics of lf-LFPs are distinctive enough, that an unsupervised approach can be used to train a decoder to extract movement-related features for use in biofeedback BMIs. Novel electrode designs may help us optimise the recording of these signals, and facilitate progress towards a new generation of robust, implantable BMIs for patients.Research Studentship from the MRC, and Andy Jackson’s laboratory (hence this work) is supported by the Wellcome Trust

Modeling cerebrocerebellar control in horizontal planar arm movements of humans and the monkey

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2007.Includes bibliographical references (leaves 215-236).In daily life, animals including humans make a wide repertoire of limb movements effortlessly without consciously thinking about joint trajectories or muscle contractions. These movements are the outcome of a series of processes and computations carried out by multiple subsystems within the central nervous system. In particular, the cerebrocerebellar system is central to motor control and has been modeled by many investigators. The bulk of cerebrocerebellar control involves both forward command and sensory feedback information inextricably combined. However, it is not yet clear how these types of signals are reflected in spiking activity in cerebellar cells in vivo. Segmentation of apparently continuous movements was first observed more than a century ago. Since then, submovements, which have been identified by non-smooth speed profiles, have been described in many types of movements. However, physiological origins of submovement have not been well understood. This thesis demonstrates that a currently proposed recurrent integrator PID (RIPID) cerebellar limb control model (Massaquoi 2006a) is consistent with average neural activity recorded in a monkey by developing the Recurrent Integrator-based Cerebellar Simple Spike (RICSS) model.(cont.) The RICSS formulation is consistent with known or plausible cerebrocerebellar and spinocerebellar neurocircuitry, including hypothetical classification of mossy fiber signals. The RICSS model accounts well for variety of cerebellar simple spike activity recorded from the monkey and outperforms any other existing models. The RIPID model is extended to include a simplified cortico-basal ganglionic loop to capture statistical characterization of intermittency observed in individual trials of the monkey. In order to extend the capability of the RIPID model to a larger workspace and faster movements, the model needs to be gainscheduled based on the local state information. A linear parameter varying (LPV) formulation, which shares a similar structure to that suggested by the RICSS model, is performed and its applicability was tested on human subjects performing double step tasks which requires rapid change in movement directions.by Kazutaka Takahashi.Ph.D

A study of motor control in healthy subjects and in Parkinson's disease patients

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008.Includes bibliographical references.Parkinson's disease (PD) is a primarily motor disorder which affects at least half a million people in the US alone. Deep brain stimulation (DBS) is a neurosurgical intervention by which neural structures are stimulated electrically by an implanted pacemaker. It has become the treatment of choice for PD, when not adequately controlled by drug therapy. We introduced a novel robotic platform for the study of the effects of DBS on motor control in PD. Subjects performed discrete wrist movements with and without a force field. We found preliminary indication that motor learning may be taking place with stimulation, and demonstrated how robotic testing can augment existing clinical tools in evaluation of the disease. To study the effect of stimulation on movement frequency, we employed a rhythmic task that required movements of the elbow to remain within a closed shape on a phase plane. Three closed shapes required varying frequency/amplitude combinations of elbow movement. The task was performed with and without visual feedback. Analysis of data from the healthy control subjects revealed a non-monotonic relation between accuracy on the phase plane and movement speed. Further kinematic analyses, including movement intermittency and harmonicity, number and type of submovements (movement primitives) fit per movement cycle, and the effects of vision on intermittency were used to support the model we propose, whereby there exist two subtypes of rhythmic movement; small-amplitude, high-frequency movements are nearly maximally harmonic, and harness the elastic properties of the limb to achieve smoothness and accuracy, and large-amplitude, low-frequency movements share characteristics with a string of discrete movements, and make use of visual feedback to achieve smoothness and accuracy.(cont.) Bradykinesia (slowness of movement) is one of the hallmarks of PD. We examined the effects of visual feedback on bradykinesia. PD patients off dopaminergic medication and healthy age-matched controls performed significantly faster movements when visual feedback was withdrawn. For the bradykinetic subjects, this increase in movement speed meant either a mitigation or an elimination of bradykinesia. Our results support a role of the basal ganglia in sensorimotor integration, and argue for the integration of nonvision exercises into patients' physical therapy regime.by Shelly Levy-Tzedek.Ph.D

On the structure of natural human movement

Understanding of human motor control is central to neuroscience with strong implications in the fields of medicine, robotics and evolution. It is thus surprising that the vast majority of motor control studies have focussed on human movement in the laboratory while neglecting behaviour in natural environments. We developed an experimental paradigm to quantify human behaviour in high resolution over extended periods of time in ecologically relevant environments. This allows us to discover novel insights and contradictory evidence to well-established findings obtained in controlled laboratory conditions. Using our data, we map the statistics of natural human movement and their variability between people. The variability and complexity of the data recorded in these settings required us to develop new tools to extract meaningful information in an objective, data-driven fashion. Moving from descriptive statistics to structure, we identify stable structures of movement coordination, particularly within the arm-hand area. Combining our data with numerous published findings, we argue that current hypotheses that the brain simplifies motor control problems by dimensionality reduction are too reductionist. We propose an alternative hypothesis derived from sparse coding theory, a concept which has been successfully applied to the sensory system. To investigate this idea, we develop an algorithm for unsupervised identification of sparse structures in natural movement data. Our method outperforms state-of-the-art algorithms for accuracy and data-efficiency. Applying this method to hand data reveals a dictionary of \emph{sparse eigenmotions} (SEMs) which are well preserved across multiple subjects. These are highly efficient and invariant representation of natural movement, and suggest a potential higher-order grammatical structure or ``movement language''. Our findings make a number of testable predictions about neural coding of movement in the cortex. This has direct consequences for advancing research on dextrous prosthetics and robotics, and has profound implications for our understanding of how the brain controls our body.Open Acces

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

Early, sustained and broadly-tuned discharge of fast-spiking interneurons in the premotor cortex during action planning

Preparatory neural activity in premotor areas is critical for planning and execution of voluntary movements. Previous studies in monkeys and mice have revealed how the discharges of pyramidal, excitatory neurons (PNs) encode a motor plan for an upcoming movement (Afshar et al., 2011; Chen et al., 2017; Li et al., 2015). However, the contribution of GABAergic interneurons, specifically fast-spiking interneurons (FSNs), to voluntary movements remains poorly understood. Putative premotor areas involved in action planning have been demonstrated in rodents. In particular, in mice, a premotor area controlling voluntary licking has been identified in the anterior-lateral motor cortex (ALM) (Komiyama et al., 2010). Also, ALM partially overlaps with the rostral forelimb area (RFA), the previously defined premotor region involved in the control of paw movement in rats and mice (Rouiller et al., 1993; Tennant et al., 2011). To understand the excitatory-inhibitory microcircuit involved in action planning, here I compare directly the response properties of PNs and FSNs during licking behaviour and forelimb retraction in the mouse. Recordings are carried out with both acute electrodes and chronic microelectrode arrays from both the two premotor areas, i.e. the ALM \u2013 responsible for licking \u2013, and RFA \u2013 involved in paw movement. Specifically, in a first set of experiments, I used head-restrained mice that spontaneously lick a reward delivered at random intervals from a drinking spout. Mice voluntary performed either single isolated or a burst of consecutive licks, which I categorized, a posteriori, in single (= 1 lick) and multiple licks ( 65 3 licks). During the task, I extracellularly recorded single units\u2019 activity from ALM, using acute in vivo electrophysiology. I identified putative PNs and FSNs, based on well-established features of their waveforms, and investigated their functional properties during the movement. Unexpectedly, I report that optogenetically-verified FSNs showed an earlier and more sustained activation than PNs. In particular, most of the neurons\u2019 activity anticipated the licking onset, consistently with an involvement of the ALM in movement planning. The majority of the neurons (~90%) increased their firing frequency in correspondence with the movement, but suppressive modulations were also observed in a subset of units. For both PNs and FSNs, I found significantly greater discharge during multiple than single licks and the peak discharge was significantly delayed for both subclasses during multiple licking events. However, FSNs modulated their activity about 100ms earlier than PNs. Furthermore, almost all FSNs showed a peak in their response before the beginning of the sequence of licks. Analysis of mean information content confirms that FSNs predict licking onset not only significantly better, but even earlier, than PNs. Chronic electrode arrays covering both the ALM and RFA were next used to simultaneously probe neural responses during (i) licking and (ii) forelimb pulling in a robotic device (Spalletti et al., 2017). I report that most of the FSNs respond with a stereotyped increase in their firing rates during both licking and pulling. In stark contrast, PNs show a variety of behaviours, dependent on movement type. At least for a minority of them, licking behaviour and forelimb retraction are represented as two different motor acts, reaching significant levels in the PNs. Accordingly, computational analysis shows that PNs carry more independent information than FSNs. Altogether, these data indicate that a global rise of GABAergic inhibition mediated by FSNs firing contributes to early action planning. Next, encouraged by the deeper understanding of the cortical microcircuits underlying movement planning in mice, I exploited this knowledge to explore more complex mechanisms, as action understanding. The neural circuits that integrate performed and observed actions have been found in the premotor cortex of monkeys and named as \u2018mirror neurons system\u2019 (di Pellegrino et al., 1992). Recently, the presence of mirror neurons have been demonstrated in rodents in the anterior cingulate cortex (Carrillo et al., 2019), but whether they could contribute to action understanding in the premotor cortex is still unclear. At behavioural level, the observation of actions can actually lead, in some cases, to the repetition of those same actions. This phenomenon has been named social facilitation, and the underlying motor program has been attributed to the mirror system (Ferrari et al., 2005). Here, I set up a behavioural task similar to the one exploited in monkeys to explore social facilitation in mice. I took advantage of licking behaviour to set up the social facilitation experiment. Therefore, head-restrained mice were allowed to lick water from a feeding needle. I found that mice can actually facilitated to lick more when another individual was engaged in the same action, supporting the hypothesis of a social facilitation in mouse. Altogether these results indicate that the observers\u2019 behaviour was actually influenced by the demonstrators\u2019 one, laying the groundwork for the study of mirror neurons in mice at cellular level

The effect of anodal transcranial direct current stimulation on spatial motor skill learning in healthy and spinal cord injured humans

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Anodal transcranial direct current stimulation (tDCS) is an intervention which is thought to enhance motor learning in healthy and stroke-injured states, when applied adjunctively during skill learning. We set out to investigate whether anodal tDCS might enhance functional rehabilitation from incomplete tetraplegic SCI. To address current limitations in the measurement of task-dependent skill, a novel integrated skill training and measurement task, the Motor Skill Rehabilitation Task (MSRT) was designed and developed. Measures of performance from this task delivered the functional measure of spatial motor skill learning, Task Productivity Rate (TPR). TPR was analysed and validated as a univariate dependent outcome, which is of potential importance to the future development of clinical measures measuring goal-directed motor skills. The MSRT was included alongside conventional behavioural measures in a repeated-measures RCT pilot study, the first to investigate the effect of anodal tDCS on rehabilitation of motor skill from chronic spinal cord injury. Adjunctive application of anodal tDCS had a statistically significant benefit upon retention of skill in the incomplete spinal cord injured population, but only when the independent factor of sensory acuity was included in the analysis. Differences between the development of task-dependent skill and generic dexterity over time suggested that spatial skill development was subject to an interaction of short-term and lasting effects. A larger study in healthy persons further investigated these phenomena, also applying Transcranial Magnetic Stimulation (TMS)–evoked measurements to investigate intervention-dependent effects upon the excitability of projections between the primary motor cortex and muscles involved in the prehension task. The findings revealed that active tDCS did not enhance skill learning at 7 days beyond the training period, but did significantly alter the development of motor skill following a period of learning and subsequent skill consolidation which was associated with underlying perturbation of motor control strategy. Significant and divergent patterns of cortical plasticity were evoked in projections to muscles necessary for reaching and grasping. The main findings of this thesis do not support anodal tDCS as an effective adjunctive means of enhancing spatial motor skill in rehabilitation from incomplete tetraplegic SCI. If applied in patient populations, the clinical benefits of anodal tDCS may be contingent both on the nature of the sensorimotor deficit affecting upper limb function and the spatial demands of the behavioural task. The findings of this project serve to inform further research in relation to the effect of anodal tDCS on the brain and behavioural outcomes, the potential for efficacy in target patient groups and the sensitivity of outcome measures to spatial and temporal dimensions of practical motor skills.This study was partly supported by The Brunel University Isambard Research Scholarship, and The Orthotist Education and Training Trust

Modeling middle cerebral artery stroke in rats : an examination of the skilled reaching impairments

xiii, 345 leaves : ill. ; 29 cm. + 1 CD-ROMMiddle cerebral artery (MCA) stroke can produce chronic incapacitating motor impairments. Understanding the neural basis of the motor syndromes is complicated by the diversity of neural structures damaged but the problem can be addressed in laboratory rats by inducing selective infarcts. Nevertheless, the motor syndromes that ensue from stroke in rats remain poorly understood and undermine its potential as a model for clinical stroke. The objective of the present thesis was to document the skilled reaching impairments from neocortical and subcortical MCA infarcts in rats. In addition, the integrity of the motor system components spared by the infarct was assessed neurophysiologically and neuroanatomically. Characteristic reaching impairments emerged from each infarct but there were also some overlapping features that might be explained by neural dysfunction extending beyond the boundaries of the infarct. The present studies showed that the laboratory rat is an ideal animal model for studying stroke, which should be of interest to both clinical and research scientists studying stroke

Functional network analyses and dynamical modeling of proprioceptive updating of the body schema

Proprioception is an ability to perceive the position and speed of body parts that is important for construction of the body schema in the brain. Proper updating of the body schema is necessary for appropriate voluntary movement. However, the mechanisms mediating such an updating are not well understood. To study these mechanisms when the body part was at rest, electroencephalography (EEG) and evoked potentials studies were employed, and when the body was in motion, kinematic studies were performed. An experimental approach to elicit proprioceptive P300 evoked potentials was developed providing evidence that processing of novel passive movements is similar to processing of novel visual and auditory stimuli. The latencies of the proprioceptive P300 potentials were found to be greater than those elicited by auditory, but not different from those elicited by the visual stimuli. The features of the functional networks that generated the P300s were analyzed for each modality. Cross-correlation networks showed both common features, e.g. connections between frontal and parietal areas, and the stimulus-specific features, e.g. increases of the connectivity for temporal electrodes in the visual and auditory networks, but not in the proprioceptive ones. The magnitude of coherency networks showed a reduction in alpha band connectivity for most of the electrodes groupings for all stimuli modalities, but did not demonstrate modality-specific features. Kinematic study compared performances of 19 models previously proposed in the literature for movements at the shoulder and elbow joints in terms of their ability to reconstruct the speed profiles of the wrist pointing movements. It was found that lognormal and beta function models are most suitable for wrist speed profile modeling. In addition, an investigation of the blinking rates during the P300 potentials recordings revealed significantly lower rates in left-handed participants, compared to the right-handed ones. Future work will include expanding the experimental and analytical methodologies to different kinds of proprioceptive stimuli (displacements and speeds) and experimental paradigms (error-related negativity potentials), and comparing the models of the speed profiles produced by the feet to those of the wrists, as well as replicating the observations made on the blinking rates in a larger scale study

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