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A wireless brain–spine interface is presented that enables macaques with a spinal cord injury to regain locomotor movements of a paralysed leg. Locomotion restored after spinal cord injury in a primate Grégoire Courtine and colleagues show that a fully implantable, wireless brain–spine interface can be used to improve locomotion after a unilateral spinal lesion in monkeys without training. The authors implanted monkeys with an electrode array in the leg area of the motor cortex and a stimulator in the lumbar spinal cord, enabling real-time decoding and stimulation. Decoded activity from the motor cortex was used to stimulate 'hotspot' locations in the lumbar spinal cord that control hindlimb flexion and extension during locomotion. Stimulating these hotspots enhanced flexion and extension of the target muscles during locomotion in intact monkeys and restored weight-bearing locomotion of the paralysed leg in monkeys with a unilateral spinal cord lesion six days after the injury. This proof-of-principle study shows that a similar system may improve or restore locomotion in people with spinal cord injury. Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces 1 , 2 , 3 have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis 1 , 4 . Theoretically, this strategy could also restore control over leg muscle activity for walking 5 . However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges 6 , 7 . 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 8 , 9 , 10 . 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.

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival 1 – 3 , impairs neurological recovery 4 , 5 , increases the risk of cardiovascular disease 6 , 7 , and reduces quality of life 8 , 9 . Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord 10 , which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury 11 , and restored walking after paralysis 12 . Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This ‘neuroprosthetic baroreflex’ controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI. An epidural spinal cord stimulation system regulates blood pressure in the acute and chronic phases of spinal cord injury.

Professor Denison holds a joint appointment in Engineering Science and Clinical Neurosciences at Oxford, where he explores the fundamentals of physiologic closed-loop systems. Prior to that, Tim was a Technical Fellow at Medtronic PLC and Vice President of Research & Core Technology for the Restorative Therapies Group, where he helped oversee the design of next generation neural interface and algorithm technologies for the treatment of chronic neurological disease. In 2012, he was awarded membership to the Bakken Society, Medtronic’s highest technical and scientific honor, and in 2014 he was awarded the Wallin leadership award, becoming only the second person in Medtronic history to receive both awards. In 2015, he was elected to the College of Fellows for the American Institute of Medical and Biological Engineering (AIMBE). Tim received an A.B. in Physics from The University of Chicago, and an M.S. and Ph.D. in Electrical Engineering from MIT. He recently completed his MBA and was named a Wallman Scholar at Booth, The University of Chicago.The total economic cost of neurological disorders exceeds £100B per annum in the UK alone, yet pharmaceutical companies continue to cut investment due to failed clinical studies and risk. An alternative to solely pharmacological treatments is therefore warranted. The emerging field of ‘bioelectronics’ suggests a novel alternative to pharmaceutical intervention, by using electronic hardware to directly stimulate the nervous system with physiologically-inspired electrical signals. Given the processing capability of electronics and precise targeting of electrodes, the potential advantages of bioelectronics include specificity in time, method, and location of treatment, with the ability to iteratively refine and update therapy algorithms in software. The primary disadvantage of current systems is invasiveness, as hardware placement can often require surgery.This paper will discuss the efforts to address the current shortcomings limiting bioelectronics as a common treatment modality for disorders of the nervous system. While the first generation of bioelectronic systems achieved measured success, such as deep brain stimulation (DBS) for Parkinson’s disease, the technology is still falling far short of its potential. To improve the translation of this technology, several fundamental issues must be resolved: 1) Most existing therapies do not take advantage of the capability of bioelectronics to dynamically adjust stimulation parameters in response to the patient’s needs. With the absence of adaptive capability, the devices are essentially running ‘open loop’ between periodic clinical visits using a compromise setting for treatment. 2) The lack of device responsivity is compounded by the absence of an objective physiologic state estimate in many diseases. Likewise, there is an incomplete understanding of the optimal stimulation parameters to use to achieve a more ‘neurotypical’ state. 3) While the effectiveness of DBS for Parkinson’s is established, it is still an intervention that requires invasive surgery, and fear of complications frightens many patients; clearly there is a desire to lower the invasiveness of therapeutic systems. 4) Finally, the economic incentives of personalized medicine that bioelectronics might enable still needs alignment across healthcare stakeholders.We will first summarize the challenges and opportunities of bioelectronic medicines face when bridging basic science, advanced technology, and health care economics. We will then propose a self-reinforcing innovation framework -- from designing bespoke, instrumented implantable platforms that enable novel clinical neuroscience, to applying these platforms and the resulting science to prototype new therapies – which can help catalyse new treatments for disease. To provide specific context for the platform, we will describe problematic clinical needs are currently being explored in translational studies, including postural instability in Parkinson’s disease, seizure prevention in paediatric epilepsy, and modifications of sensory processing to treat centralized chronic pain. The breadth of these examples reflects the diversity of challenges created by neurological disorders, but also the hope that bioelectronic systems can help address them.

A spinal cord injury interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis 1 , 2 . Here, we restored this communication with a digital bridge between the brain and spinal cord that enabled an individual with chronic tetraplegia to stand and walk naturally in community settings. This brain–spine interface (BSI) consists of fully implanted recording and stimulation systems that establish a direct link between cortical signals 3 and the analogue modulation of epidural electrical stimulation targeting the spinal cord regions involved in the production of walking 4 – 6 . A highly reliable BSI is calibrated within a few minutes. This reliability has remained stable over one year, including during independent use at home. The participant reports that the BSI enables natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains. Moreover, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis. A reliable digital bridge restored communication between the brain and spinal cord and enabled natural walking in a participant with spinal cord injury.

Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury. Spatially selective and temporally controlled stimulation of the spinal cord, together with rehabilitation, results in substantial restoration of locomotor function in humans with spinal cord injury.

Conference proceedings. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI. Implantation of a multielectrode paddle that allows personalized electrical stimulation to all regions of the spinal cord involved in leg and trunk movements rapidly restores motor function in patients with spinal cord injury with complete paralysis.

Neurotechnologies combine engineering methods and neuroscientific knowledge to design devices that interface the brain with the outside world. Since the early 2000s, inspiring and encouraging neurotechnology examples have been the subject of high-profile scientific articles and made headlines in popular media. However, although neurotechnologies have the potential to improve people’s lives in ways that cannot be achieved by other solutions such as pharmaceuticals, only a few of them have established themselves as clinical solutions. In this Review, we provide a systematic, state-of-the-art assessment of the opportunities and shortcomings of neurotechnology’s engineering and scientific components, and highlight the requirements to overcome translational barriers. Finally, we present a comprehensive framework to aid the clinical and commercial translation of neurotechnologies.Despite inspiring proof-of-concepts that are often widely covered by the media, only a few neurotechnologies have firmly established themselves as clinical solutions. In this Review, we discuss opportunities and shortcomings of this technology, and provide a framework to facilitate clinical and commercial translation.

Presents empirical evidence in the context of grocery shopping to challenge the assumption that routine shopping is considered invariably to be a low-involvement activity. Argues that certain situational factors may give rise to routine purchases becoming more involving than others and studies the case of stock-out situations. Finds that there is some evidence to suggest that routine food shopping for many consumers can be highly involving at times.