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1.
Nature ; 539(7628): 284-288, 2016 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-27830790

RESUMEN

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.


Asunto(s)
Interfaces Cerebro-Computador , Terapia por Estimulación Eléctrica/instrumentación , Trastornos Neurológicos de la Marcha/complicaciones , Trastornos Neurológicos de la Marcha/terapia , Marcha/fisiología , Prótesis Neurales , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/terapia , Animales , Modelos Animales de Enfermedad , Estimulación Eléctrica , Trastornos Neurológicos de la Marcha/fisiopatología , Pierna/fisiología , Locomoción/fisiología , Región Lumbosacra , Macaca mulatta , Masculino , Microelectrodos , Corteza Motora/fisiopatología , Parálisis/complicaciones , Parálisis/fisiopatología , Parálisis/terapia , Reproducibilidad de los Resultados , Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Tecnología Inalámbrica/instrumentación
2.
Science ; 347(6218): 159-63, 2015 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-25574019

RESUMEN

The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and elasticity of dura mater, the protective membrane of the brain and spinal cord. The electronic dura mater, which we call e-dura, embeds interconnects, electrodes, and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. The soft implants extracted cortical states in freely behaving animals for brain-machine interface and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Duramadre , Estimulación Eléctrica/métodos , Electroquimioterapia/métodos , Electrodos Implantados , Parálisis/terapia , Prótesis e Implantes , Traumatismos de la Médula Espinal/terapia , Animales , Materiales Biocompatibles/uso terapéutico , Interfaces Cerebro-Computador , Elasticidad , Locomoción , Ratones , Ratones Endogámicos , Corteza Motora/fisiopatología , Imagen Multimodal , Neuronas/fisiología , Parálisis/etiología , Parálisis/fisiopatología , Platino (Metal) , Silicio , Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/fisiopatología
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