A brain-spinal interface (BSI) system-on-chip (SoC) for closed-loop cortically-controlled intraspinal microstimulation

This paper reports on a fully miniaturized brain-spinal interface system for closed-loop cortically-controlled intraspinal microstimulation (ISMS). Fabricated in AMS 0.35 µm two-poly four-metal complementary metal–oxide–semiconductor technology, this system-on-chip measures ~ 3.46 mm × 3.46 mm and incorporates two identical 4-channel modules, each comprising a spike-recording front-end, embedded digital signal processing (DSP) unit, and programmable stimulating back-end. The DSP unit is capable of generating multichannel trigger signals for a wide array of ISMS triggering patterns based on real-time discrimination of a programmable number of intracortical neural spikes within a pre-specified time-bin duration via thresholding and user-adjustable time–amplitude windowing. The system is validated experimentally using an anesthetized rat model of a spinal cord contusion injury at the T8 level. Multichannel neural spikes are recorded from the cerebral cortex and converted in real time into electrical stimuli delivered to the lumbar spinal cord below the level of the injury, resulting in distinct patterns of hindlimb muscle activation

Inducing Neural Plasticity After Spinal Cord Injury To Recover Impaired Voluntary Movement

Spinal cord injury (SCI) is often an incapacitating neural injury most commonly caused by a traumatic blow to the spine. A SCI causes damage to the axons that carry sensory and motor signals between the brain and spinal cord, and in turn, the rest of the body. Depending on the severity and location of a SCI, many corticospinal axons and other descending motor pathways can remain intact. Moderate spontaneous functional recovery occurs in patients and animal models following incomplete SCI. This recovery is linked to changes occurring via the remaining pathways and throughout the entire nervous system, which is generally referred to as neuronal plasticity. It has been shown that plasticity can be induced via electrical stimulation of the brain and spinal cord targeting specific descending pathways, which can further improve impaired motor function. Most importantly, it has been shown that activity dependent stimulation (ADS), which is based on mechanisms of spike timing-dependent plasticity, can strengthen remaining pathways and promote functional recovery in various preclinical injury models of the central nervous system. The purpose of this dissertation was to determine if precisely-timed stimulation of the spinal cord triggered by the firing of neurons in the hindlimb motor cortex would result in potentiation of corticospinal connections as well as enhance hindlimb motor recovery after spinal cord contusion. In order to achieve this, we needed to determine the optimal neurophysiological conditions which would allow activity dependent stimulation (ADS) to facilitate enhanced communication between the cerebral cortex and spinal cord motor neurons. Thus, this dissertation project investigated three specific aims. The first study determined the effects of a contusive spinal cord injury on spinal motor neuron activity, corticospinal coupling, and conduction time in rats. It was discovered that spinal cord responses could still be evoked after spinal cord contusion, most likely via the cortico-reticulo-spinal pathway. The second study determined the optimal spike-stimulus delay for increasing synaptic efficacy in descending motor pathways using an ADS paradigm in an acute, anesthetized rat model of SCI. It was discovered that bouts of ADS conditioning can increase synaptic efficacy in intact descending motor pathways, as measured by cortically evoked activity in the spinal cord, after SCI. The third study determined whether spike-triggered intraspinal microstimulation (ISMS), using optimized spike-stimulus delays, results in improved motor performance in an ambulatory rat model of SCI. It was determined that ADS therapy can enhance the behavioral recovery of locomotor function after spinal cord injury. The results from this study indicate that activity-dependent stimulation is an effective treatment for behavioral recovery following a moderate spinal cord contusion in the rodent. The implications of these results have the potential to lead to a novel treatment for a variety of neurological disease and disorders

Cortical control of intraspinal microstimulation to restore motor function after paralysis

Phd ThesisSpinal cord injury (SCI) is a devastating condition affecting the quality of life of many otherwise healthy patients. To date, no cure or therapy is known to restore functional movements of the arm and hand, and despite considerable effort, stem cell based therapies have not been proven effective. As an alternative, nerves or muscles below the injury could be stimulated electrically. While there have been successful demonstrations of restoration of functional movement using muscle stimulation both in humans and non-human primates, intraspinal microstimulation (ISMS) could bear benets over peripheral stimulation. An extensive body of research on spinal stimulation has been accumulated – however, almost exclusively in non-primate species. Importantly, the primate motor system has evolved to be quite different from the frog’s or the cat’s – two commonly studied species –, reecting and enabling changes in how primates use their hands. Because of these functional and anatomical differences, it is fair to assume that also spinal cord stimulation will have different effects in primates. is question – what are the movements elicited by ISMS in the macaque – will be addressed in chapters and . Chronic intraspinal electrode implants so far have been difficult to realise. In chapter we describe a novel use of oating microelectrode arrays (FMAs) as chronic implants in the spinal cord. Compared to implanted microwires or other arrays, these FMAs have the benet of a high electrode density combined with different lengths of electrodes. We were able to maintain these arrays in the cord for months and could elicit movements at low thresholds throughout. If we could build a neural prosthesis stimulating the spinal cord, how would it be controlled? Remarkable progress has been recently achieved in the eld of brain-machine interfaces (BMIs), for example enabling patients to control robotic arms with neural signals recorded from chronically implanted electrodes. Chapter of this thesis examines an approach that combines ISMS with cortical control in a macaque model for upper limb paralysis for the rst time and shows that there is a behavioural improvement. We have devised an experiment in which a monkey trained to perform a grasp-and-pull task receives a temporary cortically induced paralysis of the hand reducing task performance. At the same time, cortical recordings from a different area allow us to control ISMS at sites evoking hand movements – thus partially restoring function. Finally, in appendix A we describe a system we developed in order to introduce automated positive reinforcement training (aPRT) both at the breeding facility and in our animal houses. is system potentially reduces time spent on training animals, adds enrichment to the monkeys’ home environment, and allows for suitability screening of monkeys for behavioural neuroscience experiments

Personalized neuroprosthetics

Decades of technological developments have populated the field of neuroprosthetics with myriad replacement strategies, neuromodulation therapies, and rehabilitation procedures to improve the quality of life for individuals with neuromotor disorders. Despite the few but impressive clinical successes, and multiple breakthroughs in animal models, neuroprosthetic technologies remain mainly confined to sophisticated laboratory environments. We summarize the core principles and latest achievements in neuroprosthetics, but also address the challenges that lie along the path toward clinical fruition. We propose a pragmatic framework to personalise neurotechnologies and rehabilitation for patient-specific impairments to achieve the timely dissemination of neuroprosthetic medicine

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

De animais a máquinas : humanos tecnicamente melhores nos imaginários de futuro da convergência tecnológica

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Sociais, Departamento de Sociologia, 2020.O tema desta investigação é discutir os imaginários sociais de ciência e tecnologia que emergem a partir da área da neuroengenharia, em sua relação com a Convergência Tecnológica de quatro disciplinas: Nanotecnologia, Biotecnologia, tecnologias da Informação e tecnologias Cognitivas - neurociências- (CT-NBIC). Estas áreas desenvolvem-se e são articuladas por meio de discursos que ressaltam o aprimoramento das capacidades físicas e cognitivas dos seres humanos, com o intuito de construir uma sociedade melhor por meio do progresso científico e tecnológico, nos limites das agendas de pesquisa e desenvolvimento (P&D). Objetivos: Os objetivos nesse cenário, são discutir as implicações éticas, econômicas, políticas e sociais deste modelo de sistema sociotécnico. Nos referimos, tanto as aplicações tecnológicas, quanto as consequências das mesmas na formação dos imaginários sociais, que tipo de relações se estabelecem e como são criadas dentro desse contexto. Conclusão: Concluímos na busca por refletir criticamente sobre as propostas de aprimoramento humano mediado pela tecnologia, que surgem enquanto parte da agenda da Convergência Tecnológica NBIC. No entanto, as propostas de melhoramento humano vão muito além de uma agenda de investigação. Há todo um quadro de referências filosóficas e políticas que defendem o aprimoramento da espécie, vertentes estas que se aliam a movimentos trans-humanistas e pós- humanistas, posições que são ao mesmo tempo éticas, políticas e econômicas. A partir de nossa análise, entendemos que ciência, tecnologia e política estão articuladas, em coprodução, em relação às expectativas de futuros que são esperados ou desejados. Ainda assim, acreditamos que há um espaço de diálogo possível, a partir do qual buscamos abrir propostas para o debate público sobre questões de ciência e tecnologia relacionadas ao aprimoramento da espécie humana.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The subject of this research is to discuss the social imaginaries of science and technology that emerge from the area of neuroengineering in relation with the Technological Convergence of four disciplines: Nanotechnology, Biotechnology, Information technologies and Cognitive technologies -neurosciences- (CT-NBIC). These areas are developed and articulated through discourses that emphasize the enhancement of human physical and cognitive capacities, the intuition it is to build a better society, through the scientific and technological progress, at the limits of the research and development (R&D) agendas. Objectives: The objective in this scenery, is to discuss the ethic, economic, politic and social implications of this model of sociotechnical system. We refer about the technological applications and the consequences of them in the formation of social imaginaries as well as the kind of social relations that are created and established in this context. Conclusion: We conclude looking for critical reflections about the proposals of human enhancement mediated by the technology. That appear as a part of the NBIC technologies agenda. Even so, the proposals of human enhancement go beyond boundaries that an investigation agenda. There is a frame of philosophical and political references that defend the enhancement of the human beings. These currents that ally to the transhumanism and posthumanism movements, positions that are ethic, politic and economic at the same time. From our analysis, we understand that science, technology and politics are articulated, are in co-production, regarding the expected and desired futures. Even so, we believe that there is a space of possible dialog, from which we look to open proposals for the public discussion on questions of science and technology related to enhancement of human beings