Neuromechanical Biomarkers for Robotic Neurorehabilitation

: One of the current challenges for translational rehabilitation research is to develop the strategies to deliver accurate evaluation, prediction, patient selection, and decision-making in the clinical practice. In this regard, the robot-assisted interventions have gained popularity as they can provide the objective and quantifiable assessment of the motor performance by taking the kinematics parameters into the account. Neurophysiological parameters have also been proposed for this purpose due to the novel advances in the non-invasive signal processing techniques. In addition, other parameters linked to the motor learning and brain plasticity occurring during the rehabilitation have been explored, looking for a more holistic rehabilitation approach. However, the majority of the research done in this area is still exploratory. These parameters have shown the capability to become the "biomarkers" that are defined as the quantifiable indicators of the physiological/pathological processes and the responses to the therapeutical interventions. In this view, they could be finally used for enhancing the robot-assisted treatments. While the research on the biomarkers has been growing in the last years, there is a current need for a better comprehension and quantification of the neuromechanical processes involved in the rehabilitation. In particular, there is a lack of operationalization of the potential neuromechanical biomarkers into the clinical algorithms. In this scenario, a new framework called the "Rehabilomics" has been proposed to account for the rehabilitation research that exploits the biomarkers in its design. This study provides an overview of the state-of-the-art of the biomarkers related to the robotic neurorehabilitation, focusing on the translational studies, and underlying the need to create the comprehensive approaches that have the potential to take the research on the biomarkers into the clinical practice. We then summarize some promising biomarkers that are being under investigation in the current literature and provide some examples of their current and/or potential applications in the neurorehabilitation. Finally, we outline the main challenges and future directions in the field, briefly discussing their potential evolution and prospective

Augmentation of Brain Function: Facts, Fiction and Controversy. Volume III: From Clinical Applications to Ethical Issues and Futuristic Ideas

The final volume in this tripartite series on Brain Augmentation is entitled “From Clinical Applications to Ethical Issues and Futuristic Ideas”. Many of the articles within this volume deal with translational efforts taking the results of experiments on laboratory animals and applying them to humans. In many cases, these interventions are intended to help people with disabilities in such a way so as to either restore or extend brain function. Traditionally, therapies in brain augmentation have included electrical and pharmacological techniques. In contrast, some of the techniques discussed in this volume add specificity by targeting select neural populations. This approach opens the door to where and how to promote the best interventions. Along the way, results have empowered the medical profession by expanding their understanding of brain function. Articles in this volume relate novel clinical solutions for a host of neurological and psychiatric conditions such as stroke, Parkinson’s disease, Huntington’s disease, epilepsy, dementia, Alzheimer’s disease, autism spectrum disorders (ASD), traumatic brain injury, and disorders of consciousness. In disease, symptoms and signs denote a departure from normal function. Brain augmentation has now been used to target both the core symptoms that provide specificity in the diagnosis of a disease, as well as other constitutional symptoms that may greatly handicap the individual. The volume provides a report on the use of repetitive transcranial magnetic stimulation (rTMS) in ASD with reported improvements of core deficits (i.e., executive functions). TMS in this regard departs from the present-day trend towards symptomatic treatment that leaves unaltered the root cause of the condition. In diseases, such as schizophrenia, brain augmentation approaches hold promise to avoid lengthy pharmacological interventions that are usually riddled with side effects or those with limiting returns as in the case of Parkinson’s disease. Brain stimulation can also be used to treat auditory verbal hallucination, visuospatial (hemispatial) neglect, and pain in patients suffering from multiple sclerosis. The brain acts as a telecommunication transceiver wherein different bandwidth of frequencies (brainwave oscillations) transmit information. Their baseline levels correlate with certain behavioral states. The proper integration of brain oscillations provides for the phenomenon of binding and central coherence. Brain augmentation may foster the normalization of brain oscillations in nervous system disorders. These techniques hold the promise of being applied remotely (under the supervision of medical personnel), thus overcoming the obstacle of travel in order to obtain healthcare. At present, traditional thinking would argue the possibility of synergism among different modalities of brain augmentation as a way of increasing their overall effectiveness and improving therapeutic selectivity. Thinking outside of the box would also provide for the implementation of brain-to-brain interfaces where techniques, proper to artificial intelligence, could allow us to surpass the limits of natural selection or enable communications between several individual brains sharing memories, or even a global brain capable of self-organization. Not all brains are created equal. Brain stimulation studies suggest large individual variability in response that may affect overall recovery/treatment, or modify desired effects of a given intervention. The subject’s age, gender, hormonal levels may affect an individual’s cortical excitability. In addition, this volume discusses the role of social interactions in the operations of augmenting technologies. Finally, augmenting methods could be applied to modulate consciousness, even though its neural mechanisms are poorly understood. Finally, this volume should be taken as a debate on social, moral and ethical issues on neurotechnologies. Brain enhancement may transform the individual into someone or something else. These techniques bypass the usual routes of accommodation to environmental exigencies that exalted our personal fortitude: learning, exercising, and diet. This will allow humans to preselect desired characteristics and realize consequent rewards without having to overcome adversity through more laborious means. The concern is that humans may be playing God, and the possibility of an expanding gap in social equity where brain enhancements may be selectively available to the wealthier individuals. These issues are discussed by a number of articles in this volume. Also discussed are the relationship between the diminishment and enhancement following the application of brain-augmenting technologies, the problem of “mind control” with BMI technologies, free will the duty to use cognitive enhancers in high-responsibility professions, determining the population of people in need of brain enhancement, informed public policy, cognitive biases, and the hype caused by the development of brain- augmenting approaches

Clinical Recovery from CNS Damage

After decades of focusing on how to alleviate and prevent recurrence of acute CNS injuries, the emphasis has finally shifted towards repairing such devastating events and rehabilitation. This development has been made possible by substantial progress in understanding the scientific underpinnings of recovery as well as by novel diagnostic tools, and most importantly, by emerging therapies awaiting clinical trials. In this publication, several international experts introduce novel areas of neurological reorganization and repair following CNS damage. Principles and methods to monitor and augment neuroplasticity are explored in depth and supplemented by a critical appraisal of neurological repair mechanisms and possibilities to curtail disability using computer or robotic interfaces. Rather than providing a textbook approach of CNS restoration, the editors selected topics where progress is most imminent in this labyrinthine domain of medicine

Effectiveness of intensive physiotherapy for gait improvement in stroke: systematic review

Introduction: Stroke is one of the leading causes of functional disability worldwide. Approximately 80% of post-stroke subjects have motor changes. Improvement of gait pattern is one of the main objectives of physiotherapists intervention in these cases. The real challenge in the recovery of gait after stroke is to understand how the remaining neural networks can be modified, to be able to provide response strategies that compensate for the function of the affected structures. There is evidence that intensive training, including physiotherapy, positively influences neuroplasticity, improving mobility, pattern and gait velocity in post-stroke recovery. Objectives: Review and analyze in a systematic way the experimental studies (RCT) that evaluate the effects of Intensive Physiotherapy on gait improvement in poststroke subjects. Methodology: Were only included all RCT performed in humans, without any specific age, that had a clinical diagnosis of stroke at any stage of evolution, with sensorimotor deficits and functional gait changes. The databases used were: Pubmed, PEDro (Physiotherapy Evidence Database) and CENTRAL (Cochrane Center Register of Controlled Trials). Results: After the application of the criteria, there were 4 final studies that were included in the systematic review. 3 of the studies obtained a score of 8 on the PEDro scale and 1 obtained a score of 4. The fact that there is clinical and methodological heterogeneity in the studies evaluated, supports the realization of the current systematic narrative review, without meta-analysis. Discussion: Although the results obtained in the 4 studies are promising, it is important to note that the significant improvements that have been found, should be carefully considered since pilot studies with small samples, such as these, are not designed to test differences between groups, in terms of the effectiveness of the intervention applied. Conclusion: Intensive Physiotherapy seems to be safe and applicable in post-stroke subjects and there are indications that it is effective in improving gait, namely speed, travelled distance and spatiotemporal parameters. However, there is a need to develop more RCTs with larger samples and that evaluate the longterm resultsN/

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function161CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP465686/2014-1Não tem2014/50909-8; 13/10187–0; 14/10134–7The authors thank the Ministry of Education (MEC), FAPESP - São Paulo Research Foundation, Universidade Estadual de Londrina, Universidade Federal do Rio Grande do Norte and Universidade Federal do ABC for its support. Postdoctoral scholarships to DGSM from the Coordination for the Improvement of Higher Education Personnel (CAPES). Source(s) of financial support: This study was partially funded by grants to MB from NIH (NIH-NIMH 1R01MH111896, NIH-NINDS 1R01NS101362, NIH-NCI U54CA137788/U54CA132378, R03 NS054783) and New York State Department of Health (NYS DOH, DOH01-C31291GG), CEPID/BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology (Process: 13/07559–3) to LML, Brazilian National Research Council (CNPq, Grant # 465686/2014-1) and the São Paulo Research Foundation (Grant # 2014/50909-8) to MSC, and Postdoctoral scholarships to AHO from FAPESP - Sao Paulo Research Foundation (Process: 13/10187–0 and 14/10134–7

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function