Biomechanical Loading as an Alternative Treatment for Tremor: A Review of Two Approaches

Background: Tremor is the most common movement disorder and strongly increases in incidence and prevalence with aging. Although not life threatening, upper-limb tremors hamper the independence of 65% of people suffering from them affected persons, greatly impacting their quality of life. Current treatments include pharmacotherapy and surgery (thalamotomy and deep brain stimulation). However, these options are not sufficient for approximately 25% of patients. Therefore, further research and new therapeutic options are required to effectively manage pathological tremor. Methods: This paper presents findings of two research projects in which two different wearable robots for tremor management were developed based on force loading and validated. The first consisted of a robotic exoskeleton that applied forces to tremulous limbs and consistently attenuated mild and severe tremors. The second was a neuroprosthesis based on transcutaneous neurostimulation. A total of 22 patients suffering from parkinsonian or essential tremor (ET) of different severities were recruited for experimental validation, and both systems were evaluated using standard tasks employed for neurological examination. The inclusion criterion was a postural and/or kinetic pathological upper-limb tremor resistant to medication. Results: The results demonstrate that both approaches effectively suppressed tremor in most patients, although further research is required. The work presented here is based on clinical evidence from a small number of patients (n = 10 for robotic exoskeleton and n = 12 for the neuroprosthesis), but most had a positive response to the approaches. In summary, biomechanical loading is non-invasive and painless. It may be effective in patients who are insufficiently responsive (or have adverse reactions) to drugs or in whom surgery is contraindicated. Discussion: This paper identifies and evaluates biomechanical loading approaches to tremor management and discusses their potential

A neuroprothesis for tremor management

Tremor is the most common movement disorder, affecting ∼ 15 % of people over 50 years old according to some estimates. It appears due to a number of syndromes, being essential tremor and Parkinson's disease the most prevalent among them. None of these conditions is fully understood. Tremor is currently treated through drugs or neurosurgery, but unfortunately, it is not managed effectively in ∼25 % of the patients. Therefore, it constitutes a major cause of loss of independence and quality of life. Various alternative approaches for tremor management are reported in the literature. Among them, those devices that rely on the application of forces to the tremulous segments show a considerable potential. A number of prototypes that exploit this principle are available, spanning fixed devices and orthoses. However, none of them has fulfilled user's expectation for continuous use during daily living. This thesis presents the development and validation of a neuroprosthesis for tremor management. A neuroprosthesis is a system that restores or compensates for a neurological function that is lost. In this case, the neuroprosthesis aims at compensating the functional disability caused by the tremor. To this end, it applies forces to the tremulous limb through the control of muscle contraction, which is modulated according to the characteristics of the tremor. The concept design envisions the device as a textile that is worn on the affected limb, thus meeting the usability requirements defined by the patients. The development of the neuroprosthesis comprised the following tasks: 1. The development of a concept design of the neuroprosthesis, which incorporates state of the art knowledge on tremor, and user's needs. 2. The design and validation of a cognitive interface that parameterizes the tremor in functional contexts. This interface provides the information that the neuroprosthesis uses for tremor suppression. Two versions are developed: a multimodal interface that integrates the recordings of the whole neuromusculoskeletal system, and an interface incorporating only wearable movement sensors. The latter is intended for the functional validation of the neuroprosthesis, while the former is a proof of concept of an optimal interface for this type of applications. 3. The development of a novel approach for tremor suppression through transcutaneous neurostimulation. The approach relies on the modulation of muscle cocontraction as a means of attenuating the tremor without the need of conventional actuators. The experimental validation here provided demonstrates the feasibility and interest of the approach. In parallel with the validation of the neuroprosthesis, I performed a detailed study on the physiology of motoneurons in tremor, given the lack of a complete description of its behavior. The outcome of this study contributes to the interpretation of the results obtained with the neuroprosthesis, and opens new research lines, both related to alternative interventions and basic neuroscience. In summary, the results here presented demonstrate that tremor may be accurately parameterized while the patient performs functional activities, and that this information may be exploited to drive a neuroprosthesis for tremor management. Furthermore, the novel approach for tremor suppression presented in this dissertation constitutes a potential approach for treating upper limb tremor, either alone, or as a complement to pharmacotherapy. These results encourage the validation of the neuroprosthesis in a large cohort of patients, in order to enable its translation to the market. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------El temblor es el trastorno del movimiento más común, afectando, según algunas estimaciones, al ∼15 % de la población de más de 50 años. Existen diversos "síndromes" que causan temblor, siendo el temblor esencial y la enfermedad de Parkinson los que presentan mayor prevalencia. Además, cabe resaltar que no existe una descripción completa de ninguno de ellos. En la actualidad el temblor se trata mediante una serie de fármacos o neurocirugía. A pesar de ello, el ∼ 25 % de los pacientes sufren problemas funcionales debido a su condición. Por tanto, es evidente que el temblor constituye una de las principales causas de dependencia y pérdida de calidad de vida. Realizando una revisión de las publicaciones científicas sobre el temblor, se observa que se ha propuesto un considerable número de tratamientos alternativos. Entre ellos destacan los dispositivos que se fundamentan en la aplicación de fuerzas sobre los segmentos afectados por el temblor, de los que ya se ha evaluado una serie de prototipos. Estos abarcan desde dispositivos fijados a otras estructuras hasta ortesis. Sin embargo, ninguno de ellos satisface las expectativas de los usuarios para su uso durante el día a día. Esta tesis presenta el diseño y validación de una neruoprótesis para el tratamiento del temblor. Una neuroprótesis es un sistema que reemplaza o compensa una función neurológica perdida. En este caso, la neuroprótesis tiene como objetivo compensar la discapacidad motora causada por el temblor. Para ello aplica fuerzas al miembro afectado a través del control del nivel de contracción muscular, que se modula según las características del temblor. El diseño conceptual contempla al dispositivo como un textil que se viste en el brazo afectado, satisfaciendo los requisitos de usabilidad definidos por los pacientes. El desarrollo de la neuroprótesis abarcó las siguientes tareas: 1. El desarrollo del diseño conceptual de la neuroprótesis, que incorpora el conocimiento actual sobre el temblor, y las necesidades de los usuarios. 2. El diseño y validación de una interfaz cognitiva que parametriza el temblor durante tareas funcionales. La información obtenida con esta interfaz es usada por la neuroprótesis para modular la corriente aplicada mediante técnicas de neuroestimulación. Se desarrollan dos versiones de la interfaz cognitiva: una interfaz multimodal que integra información de todo el sistema neuromusculoesquelético, y una interfaz que implementa únicamente sensores vestibles de movimiento. La segunda interfaz fue la que se usó durante la validación funcional de la neuroprótesis, mientras que la primera es una prueba de concepto de una interfaz óptima para este tipo de aplicaciones. 3. El desarrollo de una nueva aproximación para la supresión del temblor mediante neuroestimulación transcutánea. Dicha aproximación se fundamenta en la modulación del grado de co-contracción de los músculos afectados como forma de atenuar el temblor, sin necesidad de usar actuadores convencionales. La evaluación experimental sirvió para demostrar la viabilidad e interés de la intervención. En paralelo a la validación de la neuroprótesis, llevé a cabo un estudio detallado de la fisiología de las motoneuronas en el caso del temblor, dado que no existe una descripción del funcionamiento de las mismas en el caso de este trastorno. Este estudio sirve para ayudar a la interpretación de los resultados de la neuroprótesis, y para abrir una serie de líneas futuras de investigación, tanto sobre nuevas intervenciones para el temblor, como sobre neurociencia básica. En resumen, los resultados que se presentan en esta tesis demuestran que es posible parametrizar de una forma precisa el temblor durante la realización de tareas funcionales, y que esta información sirve para controlar una neuroprótesis para el tratamiento del temblor. Además, la nueva aproximación para la compensación del temblor que se presenta tiene el potencial de convertirse en un tratamiento alternativo para el temblor de miembro superior, ya sea de forma independiente o como complemento a los fármacos. Estos resultados alientan la validación de la neuroprótesis en una cohorte grande de pacientes, con el objetivo de facilitar su transferencia al mercado

Development of EEG-based technologies for the characterization and treatment of neurological diseases affecting the motor function

This thesis presents a set of studies applying signal processing and data mining techniques in real-time working systems to register, characterize and condition the movement-related cortical activity of healthy subjects and of patients with neurological disorders affecting the motor function. Patients with two of the most widespread neurological affections impairing the motor function are considered here: patients with essential tremor and patients who have suffered a cerebro-vascular accident. The different chapters in the presented thesis show results regarding the normal cortical activity associated with the planning and execution of motor actions with the upper-limb, and the pathological activity related to the patients' motor dysfunction (measurable with muscle electrodes or movement sensors). The initial chapters of the book present i) a revision of the basic concepts regarding the role of the cerebral cortex in the motor control and the way in which the electroencephalographic activity allows its analysis and conditioning, ii) a study on the cortico-muscular interaction at the tremor frequency in patients with essential tremor under the effects of a drug reducing their tremor, and finally iii) a study based on evolutionary algorithms that aims to identify cortical patterns related to the planning of a number of motor tasks performed with a single arm. In the second half of the thesis book, two brain-computer interface systems to be used in rehabilitation scenarios with essential tremor patients and with patients with a stroke are proposed. In the first system, the electroencephalographic activity is used to anticipate voluntary movement actions, and this information is integrated in a multimodal platform estimating and suppressing the pathological tremors. In the second case, a conditioning paradigm for stroke patients based on the identification of the motor intention with temporal precision is presented and tested with a cohort of four patients along a month during which the patients undergo eight intervention sessions. The presented thesis has yielded advances from both the technological and the scientific points of view in all studies proposed. The main contributions from the technological point of view are: ¿ The design of an integrated upper-limb platform working in real-time. The platform was designed to acquire information from different types of noninvasive sensors (EEG, EMG and gyroscopic sensors) characterizing the planning and execution of voluntary movements. The platform was also capable of processing online the acquired data and generating an electrical feedback. ¿ The development of signal processing and classifying techniques adapted to the kind of signal recorded in the two kinds of patients considered in this thesis (patients with essential tremor and patients with a stroke) and to the requirements of online processing and real-time single-trial function desired for BCI applications. Especially in this regard, an original methodology to detect onsets of voluntary movements using slow cortical potentials and cortical rhythms has been presented. ¿ The design and validation in real-time of asynchronous BCI systems using motor planning EEG segments to anticipate or detect when patients begin a voluntary movement with the upper-limb. ¿ The proof of concept of the advantages of an EEG system integrated in a multimodal human-robot interface architecture that constitutes the first multimodal interface using the combined acquisition of EEG, EMG and gyroscopic data, which allows the concurrent characterization of different parts of the body associated with the execution of a movement. The main scientific contributions of this thesis are: ¿ The study of the EEG-based anticipation of voluntary movements presented in Chapter 5 of the thesis was the first demonstration (to the author's knowledge) of the capacity of the EEG signal to provide reliable movement predictions based on single-trial classification of online data of healthy subjects and ET patients. This study also provides, for the first time, the results of a BCI system tested in ET patients and it represents an original approach to BCI applications for this group of patients. ¿ It has been presented the first neurophysiological study using EEG and EMG data to analyze the effects of a drug on cortical activity and tremors of patients with ET. In addition, the obtained results have shown for the first time that a significant correlation exists between the dynamics of specific cortical oscillations and pathological tremor manifestation as a consequence of the drug effects. ¿ It has been proposed for the first time an experiment to inspect whether the EEG signal carries enough information to classify up to seven different tasks performed with a single limb. Both the methodology applied and the validation procedure are also innovative in this sort of studies. ¿ It has been demonstrated for the first time the relevance of combining different cortical sources of information (such as BP and ERD) to estimate the initiation of voluntary movements with the upper-limb. In this line, special relevance may be given to the positive results achieved with stroke patients, improving the results presented by similar previous EEG-based studies by other research groups. It has also been proposed for the first time an upper-limb intervention protocol for stroke patients using BP and ERD patterns to provide proprioceptive feedback tightly associated with the patients' expectations of movement. The effects of the proposed intervention have been studied with a small group of patients

Entrenamiento y rehabilitación de la marcha en pacientes pediátricos a través de la plataforma robótica CPWalker

[Resumen] La Parálisis Cerebral (PC) está relacionada con un trastorno de la postura y el movimiento debido a una lesión ocasionada en el cerebro cuando éste no se ha desarrollado completamente. Al ser una de las discapacidades más prevalentes a edades tempranas, la investigación y el desarrollo de dispositivos robóticos para la rehabilitación de la marcha en estos pacientes ha incrementado en los últimos tiempos. Sin embargo, los dispositivos actuales están enfocados sólo en controlar trayectorias de movimiento, olvidando el control postural del usuario y la adaptación de la terapia a las necesidades específicas de cada paciente. Este documento presenta los resultados preliminares de la aplicación de una nueva plataforma robótica (CPWalker) en la rehabilitación de la marcha de niños con diplejía espástica, durante una validación de cinco semanas. CPWalker está formado por un andador inteligente con sistema de control de peso y locomoción autónoma y un exoesqueleto robótico que realiza el movimiento guiado de las articulaciones. Además, el dispositivo incluye la posibilidad de mejorar el control postural del paciente durante la marcha, adaptando la terapia a las necesidades demandadas por el usuario.El trabajo presentado en este documento ha sido financiado por el Ministerio de Economía y Competitividad español, a través del contrato DPI2012-39133-C03-01https://doi.org/10.17979/spudc.978849749808

Myoelectric Control Architectures to Drive Upper Limb Exoskeletons

Myoelectric interfaces are sensing devices based on electromyography (EMG) able to read the electrical activity of motoneurons and muscles. These interfaces can be used to infer movement volition and to control assistive devices. Currently, these interfaces are widely used to control robotic prostheses for amputees, but their use could be beneficial even for people suffering from motor disabilities where the peripheral nervous system is intact and the impairment is only due to the muscles, e.g. muscular dystrophy, myopathies, or ageing. In combination with recent robotic orthoses and exoskeletons, myoelectric interfaces could dramatically improve these patients’ quality of life. Unfortunately, despite a wide plethora of methodologies has been proposed so far, a natural, intuitive, and reliable interface able to follow impaired subjects’ volition is still missing. The first contribution of this work is to provide a review of existing approaches. In this work we found that existing EMG-based control interfaces can be viewed as specific cases of a generic myoelectric control architecture composed by three distinct functional modules: a decoder to extract the movement intention from EMG signals, a controller to accomplish the desired motion through an actual command given to the actuators, and an adapter to connect them. The latter is responsible for translating the signal from decoder’s output to controller’s input domain and for modulating the level of provided assistance. We used this concept to analyse the case of study of linear regression decoders and an elbow exoskeleton. This thesis has the scientific objective to determine how these modules affect performance of EMG-driven exoskeletons and wearer’s fatigue. To experimentally test and compare myoelectric interfaces this work proposes: (1) a procedure to automatically tune the decoder module in order to equally compare or to normalize the decoder output among different sessions and subjects; (2) a procedure to automatically tune gravity compensation even for subjects suffering from severe disabilities, allowing them to perform the experimental tests; (3) a methodology to guide the impaired patients through the experimental session; (4) an evaluation procedure and metrics allowing statistically significant and unbiased comparison of different myoelectric interfaces. A further contribution of this work is the design of an experimental test bed composed by an elbow exoskeleton and by a software framework able to collect EMG signals and make them available to the exoskeleton’s actuators with minimal latency. Using this test bed, we were able to test different myoelectric interfaces based on our architecture, with different modules choices and tunings. We used linear regression decoders calibrated to predict the muscular torque, low-level controllers having torque or velocity as reference, and adapters consisting of a properly dimensioned gain or simple dynamic systems, such as an integrator or a mass-damping system. The results we obtained allow to conclude that EMG-based control is a viable technology to assist muscular weakness patients. Moreover, all the components of the myoelectric control architecture – decoder, adapter, controller, and their tuning – significantly affect the task-based performance measures we collect. Further investigations should be devoted to a methodology to automatically tune all the components, not the decoders only, and to the quantitative study of the effect the adapter has on the regulation of the assistance level and of the tradeoff between speed and accuracy

Closed-loop approaches for innovative neuroprostheses

The goal of this thesis is to study new ways to interact with the nervous system in case of damage or pathology. In particular, I focused my effort towards the development of innovative, closed-loop stimulation protocols in various scenarios: in vitro, ex vivo, in vivo

Central nervous system microstimulation: Towards selective micro-neuromodulation

Electrical stimulation technologies capable of modulating neural activity are well established for neuroscientific research and neurotherapeutics. Recent micro-neuromodulation experimental results continue to explain neural processing complexity and suggest the potential for assistive technologies capable of restoring or repairing of basic function. Nonetheless, performance is dependent upon the specificity of the stimulation. Increasingly specific stimulation is hypothesized to be achieved by progressively smaller interfaces. Miniaturization is a current focus of neural implants due to improvements in mitigation of the body's foreign body response. It is likely that these exciting technologies will offer the promise to provide large-scale micro-neuromodulation in the future. Here, we highlight recent successes of assistive technologies through bidirectional neuroprostheses currently being used to repair or restore basic brain functionality. Furthermore, we introduce recent neuromodulation technologies that might improve the effectiveness of these neuroprosthetic interfaces by increasing their chronic stability and microstimulation specificity. We suggest a vision where the natural progression of innovative technologies and scientific knowledge enables the ability to selectively micro-neuromodulate every neuron in the brain

SISTEMA ROBÓTICO HÍBRIDO PARA REABILITAÇÃO DE MEMBRO SUPERIOR DE INDIVÍDUOS PÓS- ACIDENTE VASCULAR ENCEFÁLICO:Design Centrado no Usuário

Post-stroke individuals have upper limb motor limitations that interfere with their ability to independently perform activities of daily living, compromising functionality, affecting social participation and quality of life. Innovative rehabilitation alternatives consist of Robot- Assisted Therapy (RT) and Hybrid Robotic Rehabilitation Systems (HRRS), an approach that combines repetitive muscle practice provided by robotic therapy with muscle activation provided by Functional Electrical Stimulation (FES). Despite the proven benefits of these technologies, a lack of uptake and limited implementation in clinical practice is still observed. This is because most hybrid devices are only in the early stages of development and the robotic equipment available today, presents several disadvantages related to the difficulty of control, little functionality, aesthetics and high cost, compromising their results and applicability. The objective of this study was to develop a hybrid robotic system for use in individuals with upper limb motor impairment due to stroke with advantages over the ones currently available. The competitive differentials concern its aesthetics, structure, drive and control system, portability, joint concomitance, and low cost. An exploratory study was conducted in two stages. The first stage consisted of developing the robotic orthosis prototype and validating the biomechanical functioning through a pilot study with four participants. The second stage consisted in improving the structure and control system, adding FES to the drive, transforming it into a hybrid robotic system. A multicenter pilot study was conducted with 10 participants in order to identify the needs and preferences of users to increase the acceptance and implementation of this technology. The correct functioning of the device was verified through standardized bench tests, resulting in the acquisition of a new and promising equipment for upper limb rehabilitation, capable of aiding in the recovery of functional abilities of individuals with loss of upper limb motor function.Les personnes ayant subi un AVC présentent des limitations motrices dans le membre supérieur qui interfèrent avec la capacité d'effectuer de manière autonome les activités de la vie quotidienne, compromettant la fonctionnalité, affectant la participation sociale et la qualité de vie. Les alternatives innovantes en matière de réadaptation sont la thérapie assistée par robot (RT) et les systèmes de réadaptation hybrides robotiques (SRHR), une approche qui combine la pratique musculaire répétitive fournie par la thérapie robotique avec l'activation musculaire fournie par la stimulation électrique fonctionnelle (FES). Malgré les avantages avérés de ces technologies, on observe encore un manque d'adhésion et une mise en œuvre limitée dans la pratique clinique. En effet, la plupart des dispositifs hybrides n'en sont qu'aux premiers stades de développement et les équipements robotiques disponibles aujourd'hui présentent plusieurs inconvénients liés à la difficulté du contrôle, au peu de fonctionnalité, à l'esthétique et au coût élevé, ce qui compromet leurs résultats et leur applicabilité. L'objectif de cette étude était de développer un système robotique hybride pour les personnes souffrant d'une déficience motrice des membres supérieurs due à une AVC, avec des avantages par rapport aux systèmes actuellement disponibles. Les différentiels concurrentiels concernent son esthétique, sa structure, son système d'entraînement et de contrôle, sa portabilité et la concomitance de ses articulations. Une étude exploratoire a été réalisée en deux étapes. La première étape a consisté à développer le prototype d'orthèse robotique et à valider le fonctionnement de la partie biomécanique par une étude pilote avec quatre participants. La deuxième étape a consisté à améliorer la structure et le système de contrôle, en ajoutant le FES à l'entraînement, le transformant en un système robotique hybride. Une étude pilote multicentrique a été menée auprès de 10 participants afin d'identifier les besoins et les préférences des utilisateurs de manière à accroître l'acceptation et la mise en œuvre de cette technologie. Le bon fonctionnement de l'appareil a été vérifié au moyen d'essais au banc standardisés, ce qui a permis d'acquérir un nouvel équipement prometteur pour la rééducation des membres supérieurs, capable de contribuer à la récupération des capacités fonctionnelles des personnes ayant perdu la fonction motrice des membres supérieurs.Indivíduos pós-acidente vascular encefálico (AVE) apresentam limitações motoras no membro superior que interferem na capacidade de realizar de forma independente as atividades de vida diária, comprometendo a funcionalidade, afetando a participação social e qualidade de vida. Alternativas inovadoras de reabilitação consistem na Terapia Assistida por Robô (RT) e nos Sistemas Robóticos Híbridos de Reabilitação (SRHR), abordagem que combina a prática muscular repetitiva fornecida pela terapia robótica com a ativação muscular proporcionada pela Estimulação Elétrica Funcional (FES). Apesar dos benefícios comprovados dessas tecnologias, observa-se ainda uma falta de adesão e implementação limitada na prática clínica. Isso porque a maioria dos dispositivos híbridos estão apenas nos estágios iniciais de desenvolvimento e os equipamentos robóticos hoje disponíveis, apresentam diversas desvantagens relacionadas à dificuldade de controle, pouca funcionalidade, estética e custo elevado, comprometendo seus resultados e aplicabilidade. O objetivo deste estudo foi desenvolver um sistema robótico híbrido para uso em pessoas com comprometimento motor de membro superior decorrente de AVE com vantagens em relação aos disponíveis atualmente. Os diferenciais competitivos dizem respeito a sua estética, estrutura, sistema de acionamento e de controle, portabilidade e concomitância de articulação. Foi realizado um estudo exploratório em duas etapas. A primeira etapa consistiu no desenvolvimento do protótipo de órtese robótica e validação do funcionamento da parte biomecânica por meio de estudo piloto com quatro participantes. A segunda etapa consistiu no aprimoramento da estrutura e sistema de controle, acrescentando a FES ao acionamento, transformando-o em um sistema robótico híbrido. Foi realizado um estudo piloto multicêntrico com 10 participantes a fim de identificar as necessidades e preferências dos usuários de forma a aumentar a aceitação e implementação dessa tecnologia. Foi verificado correto funcionamento do dispositivo por meio de testes padronizados de bancada, resultando na aquisição de um novo e promissor equipamento para reabilitação de membro superior, capaz de auxiliar na recuperação das habilidades funcionais de pessoas com perda da função motora de membro superior

A review : a comprehensive review of soft and rigid wearable rehabilitation and assistive devices with a focus on the shoulder joint

The importance of the human upper limb role in performing daily life and personal activities is significant. Improper functioning of this organ due to neurological disorders or surgeries can greatly affect the daily activities performed by patients. This paper aims to comprehensively review soft and rigid wearable robotic devices provided for rehabilitation and assistance focusing on the shoulder joint. In the last two decades, many devices have been proposed in this regard, however, there have been a few groups whose devices have had effective therapeutic capability with acceptable clinical evidence. Also, there were not many portable, lightweight and user-friendly devices. Therefore, this comprehensive study could pave the way for achieving optimal future devices, given the growing need for these devices. According to the results, the most commonly used plan was Exoskeleton, the most commonly used actuators were electrical, and most devices were considered to be stationary and rigid. By doing these studies, the advantages and disadvantages of each method are also presented. The presented devices each have a new idea and attitude in a specific field to solve the problems of movement disorders and rehabilitation, which were in the form of prototypes, initial clinical studies and sometimes comprehensive clinical and commercial studies. These plans need more comprehensive clinical trials to become a complete and efficient plan. This article could be used by researchers to identify and evaluate the important features and strengths and weaknesses of the plans to lead to the presentation of more optimal plans in the future