Rehabilitation of hand in subacute tetraplegic patients based on brain computer interface and functional electrical stimulation: a randomised pilot study

Objective. To compare neurological and functional outcomes between two groups of hospitalised patients with subacute tetraplegia. Approach. Seven patients received 20 sessions of brain computer interface (BCI) controlled functional electrical stimulation (FES) while five patients received the same number of sessions of passive FES for both hands. The neurological assessment measures were event related desynchronization (ERD) during movement attempt, Somatosensory evoked potential (SSEP) of the ulnar and median nerve; assessment of hand function involved the range of motion (ROM) of wrist and manual muscle test. Main results. Patients in both groups initially had intense ERD during movement attempt that was not restricted to the sensory-motor cortex. Following the treatment, ERD cortical activity restored towards the activity in able-bodied people in BCI-FES group only, remaining wide-spread in FES group. Likewise, SSEP returned in 3 patients in BCI-FES group, having no changes in FES group. The ROM of the wrist improved in both groups. Muscle strength significantly improved for both hands in BCI-FES group. For FES group, a significant improvement was noticed for right hand flexor muscles only. Significance. Combined BCI-FES therapy results in better neurological recovery and better improvement of muscle strength than FES alone. For spinal cord injured patients, BCI-FES should be considered as a therapeutic tool rather than solely a long-term assistive device for the restoration of a lost function

Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation.

After an initial period of recovery, human neurological injury has long been thought to be static. In order to improve quality of life for those suffering from stroke, spinal cord injury, or traumatic brain injury, researchers have been working to restore the nervous system and reduce neurological deficits through a number of mechanisms. For example, neurobiologists have been identifying and manipulating components of the intra- and extracellular milieu to alter the regenerative potential of neurons, neuro-engineers have been producing brain-machine and neural interfaces that circumvent lesions to restore functionality, and neurorehabilitation experts have been developing new ways to revitalize the nervous system even in chronic disease. While each of these areas holds promise, their individual paths to clinical relevance remain difficult. Nonetheless, these methods are now able to synergistically enhance recovery of native motor function to levels which were previously believed to be impossible. Furthermore, such recovery can even persist after training, and for the first time there is evidence of functional axonal regrowth and rewiring in the central nervous system of animal models. To attain this type of regeneration, rehabilitation paradigms that pair cortically-based intent with activation of affected circuits and positive neurofeedback appear to be required-a phenomenon which raises new and far reaching questions about the underlying relationship between conscious action and neural repair. For this reason, we argue that multi-modal therapy will be necessary to facilitate a truly robust recovery, and that the success of investigational microscopic techniques may depend on their integration into macroscopic frameworks that include task-based neurorehabilitation. We further identify critical components of future neural repair strategies and explore the most updated knowledge, progress, and challenges in the fields of cellular neuronal repair, neural interfacing, and neurorehabilitation, all with the goal of better understanding neurological injury and how to improve recovery

Neurorehabilitation of hand functions using brain computer interface

Introduction: Brain computer interface (BCI) is a promising new technology with possible application in neurorehabilitation after spinal cord injury. Movement imagination or attempted movement-based BCI coupled with functional electrical stimulation (FES) enables the simultaneous activation of the motor cortices and the muscles they control. When using the BCI- coupled with FES (known as BCI-FES), the subject activates the motor cortex using attempted movement or movement imagination of a limb. The BCI system detects the motor cortex activation and activates the FES attached to the muscles of the limb the subject is attempting or imaging to move. In this way the afferent and the efferent pathways of the nervous system are simultaneously activated. This simultaneous activation encourages Hebbian type learning which could be beneficial in functional rehabilitation after spinal cord injury (SCI). The FES is already in use in several SCI rehabilitation units but there is currently not enough clinical evidence to support the use of BCI-FES for rehabilitation. Aims: The main aim of this thesis is to assess outcomes in sub-acute tetraplegic patients using BCI-FES for functional hand rehabilitation. In addition, the thesis explores different methods for assessing neurological rehabilitation especially after BCI-FES therapy. The thesis also investigated mental rotation as a possible rehabilitation method in SCI. Methods: Following investigation into applicable methods that can be used to implement rehabilitative BCI, a BCI based on attempted movement was built. Further, the BCI was used to build a BCI-FES system. The BCI-FES system was used to deliver therapy to seven sub-acute tetraplegic patients who were scheduled to receive the therapy over a total period of 20 working days. These seven patients are in a 'BCI-FES' group. Five more patients were also recruited and offered equivalent FES quantity without the BCI. These further five patients are in a 'FES-only' group. Neurological and functional measures were investigated and used to assess both patient groups before and after therapy. Results: The results of the two groups of patients were compared. The patients in the BCI-FES group had better improvements. These improvements were found with outcome measures assessing neurological changes. The neurological changes following the use of the BCI-FES showed that during movement attempt, the activation of the motor cortex areas of the SCI patients became closer to the activation found in healthy individuals. The intensity of the activation and its spatial localisation both improved suggesting desirable cortical reorganisation. Furthermore, the responses of the somatosensory cortex during sensory stimulation were of clear evidence of better improvement in patients who used the BCI-FES. Missing somatosensory evoked potential peaks returned more for the BCI-FES group while there was no overall change in the FES-only group. Although the BCI-FES group had better neurological improvement, they did not show better functional improvement than the FES-only group. This was attributed mainly to the short duration of the study where therapies were only delivered for 20 working days. Conclusions: The results obtained from this study have shown that BCI-FES may induce cortical changes in the desired direction at least faster than FES alone. The observation of better improvement in the patients who used the BCI-FES is a good result in neurorehabilitation and it shows the potential of thought-controlled FES as a neurorehabilitation tool. These results back other studies that have shown the potential of BCI-FES in rehabilitation following neurological injuries that lead to movement impairment. Although the results are promising, further studies are necessary given the small number of subjects in the current study

Brain-machine interfaces for rehabilitation in stroke: A review

BACKGROUND: Motor paralysis after stroke has devastating consequences for the patients, families and caregivers. Although therapies have improved in the recent years, traditional rehabilitation still fails in patients with severe paralysis. Brain-machine interfaces (BMI) have emerged as a promising tool to guide motor rehabilitation interventions as they can be applied to patients with no residual movement. OBJECTIVE: This paper reviews the efficiency of BMI technologies to facilitate neuroplasticity and motor recovery after stroke. METHODS: We provide an overview of the existing rehabilitation therapies for stroke, the rationale behind the use of BMIs for motor rehabilitation, the current state of the art and the results achieved so far with BMI-based interventions, as well as the future perspectives of neural-machine interfaces. RESULTS: Since the first pilot study by Buch and colleagues in 2008, several controlled clinical studies have been conducted, demonstrating the efficacy of BMIs to facilitate functional recovery in completely paralyzed stroke patients with noninvasive technologies such as the electroencephalogram (EEG). CONCLUSIONS: Despite encouraging results, motor rehabilitation based on BMIs is still in a preliminary stage, and further improvements are required to boost its efficacy. Invasive and hybrid approaches are promising and might set the stage for the next generation of stroke rehabilitation therapies.This study was funded by the Bundesministerium für Bildung und Forschung BMBF MOTORBIC (FKZ13GW0053)andAMORSA(FKZ16SV7754), the Deutsche Forschungsgemeinschaft (DFG), the fortüne-Program of the University of Tübingen (2422-0-0 and 2452-0-0), and the Basque GovernmentScienceProgram(EXOTEK:KK2016/00083). NIL was supported by the Basque Government’s scholarship for predoctoral students

Brain-computer interface technology and neuroelectrical imaging to improve motor recovery after stroke

Stroke is defined as a focal lesion in the brain caused by acute ischemia or hemorrhage. The events that characterize acute stroke as well as the spontaneous recovery process occurring in the subacute phase, demonstrate that the focal damage affects remote interconnected areas. On the other hand, interconnected areas largely contribute to reorganization of the central nervous system (CNS) along the recovery process (plasticity) throughout compensatory or restorative mechanisms which can also lead to unwanted effects (maladaptive plasticity). Such post-stroke brain reorganization occurring spontaneously or within a rehabilitation program, is the object of wide literature in the fields of neuroimaging and neurophysiology. Brain-Computer Interfaces (BCIs) allow recognition, monitoring and reinforcement of specific brain activities as recorded eg. via electroencephalogram (EEG) and use such brain activity to control external devices via a computer. Sensorimotor rhythm (SMR) based BCIs exploit the modulation occurring in the EEG in response to motor imagery (MI) tasks: the subject is asked to perform MI of eg. left or right hand in order to control a cursor on a screen. In the context of post-stroke motor rehabilitation, such recruitment of brain activity within the motor system through MI can be used to harness brain reorganization towards a better functional outcome. Since 2009 my research activity has been focused mainly on BCI applications for upper limb motor rehabilitation after stroke within national (Ministry of Health) and international (EU) projects. I conducted (or participated to) several basic and clinical studies involving both healthy subjects and stroke patients and employing a combination of neurophysiological techniques (EEG, transcranial magnetic stimulation – TMS) and BCI technology (De Vico Fallani et al., 2013; Kaiser et al., 2012; Morone et al., 2015; Pichiorri et al., 2011). Such studies culminated in a randomized controlled trial (RCT) conducted on subacute stroke patients in which we demonstrated that a one-month training with a BCI system, which was specifically designed to support upper limb rehabilitation after stroke, significantly improved functional outcome (upper limb motor function) in the target population. Moreover, we observed changes in brain activity and connectivity (from high-density EEG recordings) occurring in motor related frequency ranges that significantly correlated to the functional outcome in the target group (Pichiorri et al., 2015). Following these promising results, my activity proceeded along two main pathways during the PhD course. On one hand, efforts were made ameliorate the prototypal BCI system used in (Pichiorri et al., 2015); the current system (called Promotœr) is an all-in-one BCI training station with several improvements in usability for both the patient and the therapist (it is easier to use, employs wireless EEG system with reduced number of electrodes) (Colamarino et al., 2017a,b). The Promotœr system is currently employed in add-on to standard rehabilitation therapy in patients admitted at Fondazione Santa Lucia. Preliminary results are available on chronic stroke patients, partially retracing those obtained in the subacute phase (Pichiorri et al., 2015) as well as explorative reports on patients with upper limb motor deficit of central origin other than stroke (eg. spinal cord injury at the cervical level). In the last year, I submitted research projects related to the Promotœr system to private and public institutions. These projects foresee i) the addition of a proprioceptive feedback to the current visual one by means of Functional Electrical Stimulation (FES) ii) online evaluation of residual voluntary movement as recorded via electromyography (EMG), and iii) improvements in the BCI control features to integrate concepts derived from recent advancements in brain connectivity. On these themes, I recently obtained a grant from a private Swedish foundation. On the other hand, I conducted further analyses of data collected in the RCT (Pichiorri et al., 2015) to identify possible neurophysiological markers of good motor recovery. Specifically, I focused on interhemispheric connectivity (EEG derived) and its correlation with the integrity of the corticospinal tract (as assessed by TMS) and upper limb function (measured with clinical scales) in subacute stroke patients. The results of these analyses were recently published on an international peer-reviewed journal (Pichiorri et al., 2018). In the first chapter of this thesis, I will provide an updated overview on BCI application in neurorehabilitation (according to the current state-of-the-art). The content of this chapter is part of a wider book chapter, currently in press in Handbook of Clinical Neurology (Pichiorri and Mattia, in press). In the second chapter, I will report on the status of BCI applications for motor rehabilitation of the upper limb according to the approach I developed along my research activity, including ongoing projects and prliminary findings. In the third chapter I will present the results of a neurophysiological study on subacute stroke patients, exploring EEG derived interhemispheric connectivity as a possible neurophysiological correlate of corticospinal tract integrity and functional impairment of the upper limb. Overall this work aims to outline the current and potential role of BCI technology and EEG based neuroimaging in post-stroke rehabilitation mainly in relation to upper limb motor function, nonetheless touching upon possible different applications and contexts in neighboring research fields

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

RiceWrist Robotic Device for Upper Limb Training: Feasibility Study and Case Report of Two Tetraplegic Persons with Spinal Cord Injury

Regaining upper extremity function is the primary concern of persons with tetraplegia caused by spinal cord injury (SCI). Robotic rehabilitation has been inadequately tested and underutilized in rehabilitation of the upper extremity in the SCI population. Given the acceptance of robotic training in stroke rehabilitation and SCI gait training, coupled with recent evidence that the spinal cord, like the brain, demonstrates plasticity that can be enhanced by repetitive movement training such as that available with robotic devices, it is probable that robotic upper extremity training of persons with SCI could be clinically beneficial. The primary goal of this pilot study was to test the feasibility of using a novel robotic device –the RiceWrist Exoskeleton- for rehabilitation of the upper limbs (UL) of two tetraplegic persons with incomplete SCI. Two pilot experiments were conducted. Experiment 1was the first novel attempt to administer treatment with the RiceWrist. The left UL of a tetraplegic subject was treated during seven therapy sessions. The subject’s feedback and the investigator’s obser-vations were used to enhance the robotic device and the corresponding graphical-interface. In Experiment 2, a second tetra-plegic subject underwent 10 three-hour training sessions administered by a physical therapist. Smoothness factor (FS) –a new measure developed in Experiment 1- was used as the primary outcome to test the subject’s performance before and after the training. The RiceWrist was modified according to the feedback obtained in Experiment 1. Thereafter, the device was suc-cessfully administered for upper limb training of the tetraplegic individual. Noticeable improvements in FS were observed for the stronger arm of the subject who completed 10 sessions of training. Improvements were also observed in the subject’s hand according to the Jebsen-Taylor Hand Function Test. Results from this study suggest a potential application of the RiceWrist for rehabilitation of SCI individuals and offer valuable information regarding development of UL robotic devices for this population

Boosting brain–computer interfaces with functional electrical stimulation: potential applications in people with locked-in syndrome

Individuals with a locked-in state live with severe whole-body paralysis that limits their ability to communicate with family and loved ones. Recent advances in brain–computer interface (BCI) technology have presented a potential alternative for these people to communicate by detecting neural activity associated with attempted hand or speech movements and translating the decoded intended movements to a control signal for a computer. A technique that could potentially enrich the communication capacity of BCIs is functional electrical stimulation (FES) of paralyzed limbs and face to restore body and facial movements of paralyzed individuals, allowing to add body language and facial expression to communication BCI utterances. Here, we review the current state of the art of existing BCI and FES work in people with paralysis of body and face and propose that a combined BCI-FES approach, which has already proved successful in several applications in stroke and spinal cord injury, can provide a novel promising mode of communication for locked-in individuals

Fusion of virtual reality and brain-machine interfaces for the assessment and rehabilitation of patients with spinal cord injury

La presente tesis está centrada en la utilización de nuevas tecnologías (Interfaces Cerebro-Máquina y Realidad Virtual). En la primera parte de la tesis se describe la definición y la aplicación de un conjunto de métricas para evaluar el estado funcional de los pacientes con lesión medular en el contexto de un sistema de realidad virtual para la rehabilitación de los miembros superiores. El objetivo de este primer estudio es demostrar que la realidad virtual puede utilizarse, en combinación con sensores inerciales para rehabilitar y evaluar simultáneamente. 15 pacientes con lesión medular llevaron a cabo 3 sesiones con el sistema de realidad virtual Toyra y se aplicó el conjunto definido de métricas a las grabaciones obtenidas con los sensores inerciales. Se encontraron correlaciones entre algunas de las métricas definidas y algunas de las escalas clínicas utilizadas con frecuencia en el contexto de la rehabilitación. En la segunda parte de la tesis se ha combinado una retroalimentación virtual con un estimulador eléctrico funcional (en adelante FES, por sus siglas en inglés Functional Electrical Stimulator), ambos controlados por un Interfaz Cerebro-Máquina (BMI por sus siglas en inglés Brain-Machine Interface), para desarrollar un nuevo tipo de enfoque terapéutico para los pacientes. El sistema ha sido utilizado por 4 pacientes con lesión medular que intentaron mover sus manos. Esta intención desencadenó simultáneamente el FES y la retroalimentación virtual, cerrando la mano de los pacientes y mostrándoles una fuente adicional de retroalimentación para complementar la terapia. Este trabajo es, de acuerdo al estado del arte revisado, el primero que integra BMI, FES y realidad virtual como terapia para pacientes con lesión medular. Se han obtenido resultados clínicos prometedores por 4 pacientes con lesión medular después de realizar 5 sesiones de terapia con el sistema, mostrando buenos niveles de precisión en las diferentes sesiones (79,13% en promedio). En la tercera parte de la tesis se ha definido una nueva métrica para estudiar los cambios de conectividad cerebral en los pacientes con lesión medular, que incluye información de las interacciones neuronales entre diferentes áreas. El objetivo de este estudio ha sido extraer información clínicamente relevante de la actividad del EEG cuando se realizan terapias basadas en BMI

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