Neuroprosthetic system to restore locomotion after neuromotor disorder

Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with Spinal Cord Injury (SCI) and Parkinson disease. Stimulation parameters are tuned manually and remain constant during motor execution which is suboptimal to mediate maximum therapeutic effects. Here, I present a novel neuroprosthetic system that enabled adaptive changes of neuromodulation parameters during locomotion and allowed to restore high-fidelity control over leg movements in paralyzed rats. Beyond the therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders. Several limitations have restricted the development of neuroprosthetic systems for closed loop neuromodulation. (1) First, it required a mechanistic understanding of the relationships between stimulation features and the recruitment of specific sensorimotor circuits. I found that electrical neuromodulation primarily recruits afferent reflex pathways that lead to coordinated activity of leg muscles during stepping. Moreover, the specific electrode location on the spinal cord could activate distinct reflex pathways and activate specific leg muscle groups of paralyzed rats. These results have been leveraged for the design of flexible and stretchable multi-electrode arrays for electrical and chemical spinal cord stimulation. (2) Second, it was necessary to perform comprehensive mapping experiments to characterize the effect of neuromodulation parameters on hind limb kinematics in order to establish stable and robust feedback signals for real time control. Step height and ground reaction forces emerged as the primary targets for the control of closed loop neuromodulation after spinal cord injury. (3) Third, implementation and optimization of closed-loop neuromodulation strategies necessitated the development of an advanced technological platform that combined feedback and feed-forward loops that match the natural flow of information in the modulated neural systems. These integrated developments allowed animals with complete spinal cord injury to perform over 1000 successive steps without failure, and to climb staircases of various heights and lengths with precision and fluidity. Moreover, the neuroprosthetic system was able to alleviate locomotor deficits in an alpha-synuclein rodent model of Parkinsonâs disease. Current knowledge of human spinal cord properties in response to electrical neuromodulation suggests that the developed control policies can translate into clinical applications to improve neurorehabilitation therapies. Moreover, the developed neuroprosthetic system can readily be interfaced with control signals from the brain to establish cortico-spinal neuroprostheses that are intended to promote activity-dependent plasticity during recovery from spinal cord injury

Evaluating the impact of intracortical microstimulation on distant cortical brain regions for neuroprosthetic applications

Enhancing functional motor recovery after localized brain injury is a widely recognized priority in healthcare as disorders of the nervous system that cause motor impairment, such as stroke, are among the most common causes of adult-onset disability. Restoring physiological function in a dysfunctional brain to improve quality of life is a primary challenge in scientific and clinical research and could be driven by innovative therapeutic approaches. Recently, techniques using brain stimulation methodologies have been employed to promote post-injury neuroplasticity for the restitution of motor function. One type of closed-loop stimulation, i.e., activity-dependent stimulation (ADS), has been shown to modify existing functional connectivity within either healthy or injured cerebral cortices and used to increase behavioral recovery following cortical injury. The aim of this PhD thesis is to characterize the electrophysiological correlates of such behavioral recovery in both healthy and injured cortical networks using in vivo animal models. We tested the ability of two different intracortical micro-stimulation protocols, i.e., ADS and its randomized open-loop version (RS), to potentiate cortico-cortical connections between two distant cortical locations in both anaesthetized and awake behaving rats. Thus, this dissertation has the following three main goals: 1) to investigate the ability of ADS to induce changes in intra-cortical activity in healthy anesthetized rats, 2) to characterize the electrophysiological signs of brain injury and evaluate the capability of ADS to promote electrophysiological changes in the damaged network, and 3) to investigate the long-term effects of stimulation by repeating the treatment for 21 consecutive days in healthy awake behaving animals. The results of this study indicate that closed-loop activity-dependent stimulation induced greater changes than open-loop random stimulation, further strengthening the idea that Hebbian-inspired protocols might potentiate cortico-cortical connections between distant brain areas. The implications of these results have the potential to lead to novel treatments for various neurological diseases and disorders and inspire new neurorehabilitation therapies

European governance challenges in bio-engineering : making perfect life : bio-engineering (in) the 21st century : final report

In the STOA project Making Perfect Life four fields were studied of 21st century bio-engineering: engineering of living artefacts, engineering of the body, engineering of the brain, and engineering of intelligent artefacts. This report describes the main results of the project. It shows how developments in the four fields of bio-engineering are shaped by two megatrends: "biology becoming technology" and "technology becoming biology". These developments result in a broadening of the bio-engineering debate in our society. The report addresses the long term views that are inspiring this debate and discusses a multitude of ethical, legal and social issues that arise from bio-engineering developments in the fields described. Against this background four specific developments are studied in more detail: the rise of human genome sequencing, the market introduction of neurodevices, the capturing by information technology of the psychological and physiological states of users, and the pursuit of standardisation in synthetic biology. These developments are taken in this report as a starting point for an analysis of some of the main European governance challenges in 21st century bio-engineering

European governance challenges in bio-engineering : making perfect life : bio-engineering (in) the 21st century : final report

In the STOA project Making Perfect Life four fields were studied of 21st century bio-engineering: engineering of living artefacts, engineering of the body, engineering of the brain, and engineering of intelligent artefacts. This report describes the main results of the project. It shows how developments in the four fields of bio-engineering are shaped by two megatrends: "biology becoming technology" and "technology becoming biology". These developments result in a broadening of the bio-engineering debate in our society. The report addresses the long term views that are inspiring this debate and discusses a multitude of ethical, legal and social issues that arise from bio-engineering developments in the fields described. Against this background four specific developments are studied in more detail: the rise of human genome sequencing, the market introduction of neurodevices, the capturing by information technology of the psychological and physiological states of users, and the pursuit of standardisation in synthetic biology. These developments are taken in this report as a starting point for an analysis of some of the main European governance challenges in 21st century bio-engineering

Topics in Neuromodulation Treatment

"Topics in Neuromodulation Treatment" is a book that invites to the reader to make an update in this important and well-defined area involved in the Neuroscience world. The book pays attention in some aspects of the electrical therapy and also in the drug delivery management of several neurological illnesses including the classic ones like epilepsy, Parkinson's disease, pain, and other indications more recently incorporated to this important tool like bladder incontinency, heart ischemia and stroke. The manuscript is dedicated not only to the expert, but also to the scientist that begins in this amazing field. The authors are physicians of different specialties and they guarantee the clinical expertise to provide to the reader the best guide to treat the patient

Intelligent technologies for the aging brain: opportunities and challenges

Intelligent computing is rapidly reshaping healthcare. In light of the global burden of population aging and neurological disorders, dementia and elderly care are among the healthcare sectors that are most likely to benefit from this technological revolution. Trends in artificial intelligence, robotics, ubiquitous computing, neurotechnology and other branches of biomedical engineering are progressively enabling novel opportunities for technology-enhanced care. These Intelligent Assistive Technologies (IATs) open the prospects of supporting older adults with neurocognitive disabilities, maintain their independence, reduce the burden on caregivers and delay the need for long-term care (1, 2). While technology develops fast, yet little knowledge is available to patients and health professionals about the current availability, applicability, and capability of existing IATs. This thesis proposes a state-of-the-art analysis of IATs in dementia and elderly care. Our findings indicate that advances in intelligent technology are resulting in a rapidly expanding number and variety of assistive solutions for older adults and people with neurocognitive disabilities. However, our analysis identifies a number of challenges that negatively affect the optimal deployment and uptake of IATs among target users and care institutions. These include design issues, sub-optimal approaches to product development, translational barriers between lab and clinics, lack of adequate validation and implementation, as well as data security and cyber-risk weaknesses. Additionally, in virtue of their technological novelty, intelligent technologies raise a number of Ethical, Legal and Social Implications (ELSI). Therefore, a significant portion of this thesis is devoted to providing an early ethical Technology Assessment (eTA) of intelligent technology, hence contributing to preparing the terrain for its safe and ethically responsible adoption. This assessment is primarily focused on intelligent technologies at the human-machine interface, as these applications enable an unprecedented exposure of the intimate dimension of individuals to the digital infosphere. Issues of privacy, integrity, equality, and dual-use were addressed at the level of stakeholder analysis, normative ethics and human-rights law. Finally, this thesis is aimed at providing evidence-based recommendations for guiding participatory and responsible development in intelligent technology, and delineating governance strategies that maximize the clinical benefits of IATs for the aging world, while minimizing unintended risks

Deep Brain Stimulation (DBS) Applications

The issue is dedicated to applications of Deep Brain Stimulation and, in this issue, we would like to highlight the new developments that are taking place in the field. These include the application of new technology to existing indications, as well as ‘new’ indications. We would also like to highlight the most recent clinical evidence from international multicentre trials. The issue will include articles relating to movement disorders, pain, psychiatric indications, as well as emerging indications that are not yet accompanied by clinical evidence. We look forward to your expert contribution to this exciting issue

Sleep homeostasis in the European jackdaw (<i>Coloeus monedula</i>):Sleep deprivation increases NREM sleep time and EEG power while reducing hemispheric asymmetry

Introduction: Sleep is a wide-spread phenomenon that is thought to occur in all animals. Yet, the function of it remains an enigma. Conducting sleep experiments in different species may shed light on the evolution and functions of sleep. Therefore, we studied sleep architecture and sleep homeostatic responses to sleep deprivation in the European jackdaw (Coloeus monedula).Methods: A total of nine young adult birds were implanted with epidural electrodes and equipped with miniature data loggers for recording movement activity (accelerometery) and electroencephalogram (EEG). Individually-housed jackdaws were recorded under controlled conditions with a 12:12-h light-dark cycle.Results: During baseline, the birds spent on average 48.5% of the time asleep (39.8% non-rapid eye movement (NREM) sleep and 8.7% rapid eye movement (REM) sleep). Most of the sleep occurred during the dark phase (dark phase: 75.3% NREM sleep and 17.2% REM sleep; light phase 4.3% NREM sleep and 0.1% REM sleep). After sleep deprivation of 4 and 8 h starting at lights off, the birds showed a dose-dependent increase in NREM sleep time. Also, NREM sleep EEG power in the 1.5–3 Hz frequency range, which is considered to be a marker of sleep homeostasis in mammals, was significantly increased for 1-2 h after both 4SD and 8SD. While there was little true unihemispheric sleep in the Jackdaws, there was a certain degree of hemispheric asymmetry in NREM sleep EEG power during baseline, which reduced after sleep deprivation in a dose-dependent manner.Conclusion: In conclusion, jackdaws display homeostatic regulation of NREM sleep and sleep pressure promotes coherence in EEG power