Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration

Rehabilitative devices for a top-down approach

In recent years, neurorehabilitation has moved from a "bottom-up" to a "top down" approach. This change has also involved the technological devices developed for motor and cognitive rehabilitation. It implies that during a task or during therapeutic exercises, new "top-down" approaches are being used to stimulate the brain in a more direct way to elicit plasticity-mediated motor re-learning. This is opposed to "Bottom up" approaches, which act at the physical level and attempt to bring about changes at the level of the central neural system. Areas covered: In the present unsystematic review, we present the most promising innovative technological devices that can effectively support rehabilitation based on a top-down approach, according to the most recent neuroscientific and neurocognitive findings. In particular, we explore if and how the use of new technological devices comprising serious exergames, virtual reality, robots, brain computer interfaces, rhythmic music and biofeedback devices might provide a top-down based approach. Expert commentary: Motor and cognitive systems are strongly harnessed in humans and thus cannot be separated in neurorehabilitation. Recently developed technologies in motor-cognitive rehabilitation might have a greater positive effect than conventional therapies

Computational neurorehabilitation: modeling plasticity and learning to predict recovery

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

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

A robot hand testbed designed for enhancing embodiment and functional neurorehabilitation of body schema in subjects with upper limb impairment or loss.

Many upper limb amputees experience an incessant, post-amputation "phantom limb pain" and report that their missing limbs feel paralyzed in an uncomfortable posture. One hypothesis is that efferent commands no longer generate expected afferent signals, such as proprioceptive feedback from changes in limb configuration, and that the mismatch of motor commands and visual feedback is interpreted as pain. Non-invasive therapeutic techniques for treating phantom limb pain, such as mirror visual feedback (MVF), rely on visualizations of postural changes. Advances in neural interfaces for artificial sensory feedback now make it possible to combine MVF with a high-tech "rubber hand" illusion, in which subjects develop a sense of embodiment with a fake hand when subjected to congruent visual and somatosensory feedback. We discuss clinical benefits that could arise from the confluence of known concepts such as MVF and the rubber hand illusion, and new technologies such as neural interfaces for sensory feedback and highly sensorized robot hand testbeds, such as the "BairClaw" presented here. Our multi-articulating, anthropomorphic robot testbed can be used to study proprioceptive and tactile sensory stimuli during physical finger-object interactions. Conceived for artificial grasp, manipulation, and haptic exploration, the BairClaw could also be used for future studies on the neurorehabilitation of somatosensory disorders due to upper limb impairment or loss. A remote actuation system enables the modular control of tendon-driven hands. The artificial proprioception system enables direct measurement of joint angles and tendon tensions while temperature, vibration, and skin deformation are provided by a multimodal tactile sensor. The provision of multimodal sensory feedback that is spatiotemporally consistent with commanded actions could lead to benefits such as reduced phantom limb pain, and increased prosthesis use due to improved functionality and reduced cognitive burden

Robotic and clinical evaluation of upper limb motor performance in patients with Friedreich's Ataxia: an observational study

Background: Friedreich’s ataxia (FRDA) is the most common hereditary autosomal recessive form of ataxia. In this disease there is early manifestation of gait ataxia, and dysmetria of the arms and legs which causes impairment in daily activities that require fine manual dexterity. To date there is no cure for this disease. Some novel therapeutic approaches are ongoing in different steps of clinical trial. Development of sensitive outcome measures is crucial to prove therapeutic effectiveness. The aim of the study was to assess the reliability and sensitivity of quantitative and objective assessment of upper limb performance computed by means of the robotic device and to evaluate the correlation with clinical and functional markers of the disease severity. Methods: Here we assess upper limb performances by means of the InMotion Arm Robot, a robot designed for clinical neurological applications, in a cohort of 14 children and young adults affected by FRDA, matched for age and gender with 18 healthy subjects. We focused on the analysis of kinematics, accuracy, smoothness, and submovements of the upper limb while reaching movements were performed. The robotic evaluation of upper limb performance consisted of planar reaching movements performed with the robotic system. The motors of the robot were turned off, so that the device worked as a measurement tool. The status of the disease was scored using the Scale for the Assessment and Rating of Ataxia (SARA). Relationships between robotic indices and a range of clinical and disease characteristics were examined. Results: All our robotic indices were significantly different between the two cohorts except for two, and were highly and reliably discriminative between healthy and subjects with FRDA. In particular, subjects with FRDA exhibited slower movements as well as loss of accuracy and smoothness, which are typical of the disease. Duration of Movement, Normalized Jerk, and Number of Submovements were the best discriminative indices, as they were directly and easily measurable and correlated with the status of the disease, as measured by SARA. Conclusions: Our results suggest that outcome measures obtained by means of robotic devices can improve the sensitivity of clinical evaluations of patients’ dexterity and can accurately and efficiently quantify changes over time in clinical trials, particularly when functional scales appear to be no longer sensitive

Effects on mobility training and de-adaptations in subjects with Spinal Cord Injury due to a Wearable Robot: A preliminary report

open7noopenSale, Patrizio; Russo, Emanuele Francesco; Russo, Michele; Masiero, Stefano; Piccione, Francesco; Calabrò, Rocco Salvatore; Filoni, SerenaSale, Patrizio; Russo, Emanuele Francesco; Russo, Michele; Masiero, Stefano; Piccione, Francesco; Calabrò, Rocco Salvatore; Filoni, Seren

Visual Error Augmentation for Enhancing Motor Learning and Rehabilitative Relearning

We developed a real-time controller for a 2 degree-of-freedom robotic system using xPC Target. This system was used to investigate how different methods of performance error feedback can lead to faster and more complete motor learning in individuals asked to compensate for a novel visuo-motor transformation (a 30 degree rotation). Four groups of normal human subjects were asked to reach with their unseen arm to visual targets surrounding a central starting location. A cursor tracking hand motion was provided during each reach. For one group of subjects, deviations from the ideal compensatory hand movement (i.e. trajectory errors) were amplified with a gain of 2 whereas another group was provided visual feedback with a gain of 3.1. Yet another group was provided cursor feedback wherein the cursor was rotated by an additional (constant) offset angle. We compared the rates at which the hand paths converged to the steady-state trajectories. Our results demonstrate that error-augmentation can improve the rate and extent of motor learning of visuomotor rotations in healthy subjects. We also tested this method on straightening the movements of stroke subjects, and our early results suggest that error amplification can facilitate neurorehabilitation strategies in brain injuries such as stroke