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The delivery of brain-controlled neuromodulation therapies during motor rehabilitation may augment recovery from neurological disorders. To test this hypothesis, we conceived a brain-controlled neuromodulation therapy that combines the technical and practical features necessary to be deployed daily during gait rehabilitation. Rats received a severe spinal cord contusion that led to leg paralysis. We engineered a proportional brain–spine interface whereby cortical ensemble activity constantly determines the amplitude of spinal cord stimulation protocols promoting leg flexion during swing. After minimal calibration time and without prior training, this neural bypass enables paralyzed rats to walk overground and adjust foot clearance in order to climb a staircase. Compared to continuous spinal cord stimulation, brain-controlled stimulation accelerates and enhances the long-term recovery of locomotion. These results demonstrate the relevance of brain-controlled neuromodulation therapies to augment recovery from motor disorders, establishing important proofs-of-concept that warrant clinical studies. Brain–spine interfaces have been used to enable leg movement following spinal cord injury, but movement is either involuntary or not adjustable. Here, the authors show in rats that a proportional stimulation interface permits voluntary movement and augments recovery in conjunction with rehabilitation.

Half of human spinal cord injuries lead to chronic paralysis. Here, we introduce an electrochemical neuroprosthesis and a robotic postural interface designed to encourage supraspinally mediated movements in rats with paralyzing lesions. Despite the interruption of direct supraspinal pathways, the cortex regained the capacity to transform contextual information into task-specific commands to execute refined locomotion. This recovery relied on the extensive remodeling of cortical projections, including the formation of brainstem and intraspinal relays that restored qualitative control over electrochemically enabled lumbosacral circuitries. Automated treadmill-restricted training, which did not engage cortical neurons, failed to promote translesional plasticity and recovery. By encouraging active participation under functional states, our training paradigm triggered a cortex-dependent recovery that may improve function after similar injuries in humans.

Analysis of synergistic muscle activations during locomotion and anatomical tracing of muscle synergy representations in the rodent spinal cord guide the development of a new spinal implant for neuromodulation therapy. In multiple rodent models of spinal cord injury, spatiotemporal stimulation that mimics naturalistic muscle activation patterns promotes improved functional recovery over previously described continuous stimulation protocols. Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans.

A spinal cord injury usually spares some components of the locomotor circuitry. Deep brain stimulation (DBS) of the midbrain locomotor region and epidural electrical stimulation of the lumbar spinal cord (EES) are being used to tap into this spared circuitry to enable locomotion in humans with spinal cord injury. While appealing, the potential synergy between DBS and EES remains unknown. Here, we report the synergistic facilitation of locomotion when DBS is combined with EES in a rat model of severe contusion spinal cord injury leading to leg paralysis. However, this synergy requires high amplitudes of DBS, which triggers forced locomotion associated with stress responses. To suppress these undesired responses, we link DBS to the intention to walk, decoded from cortical activity using a robust, rapidly calibrated unsupervised learning algorithm. This contingency amplifies the supraspinal descending command while empowering the rats into volitional walking. However, the resulting improvements may not outweigh the complex technological framework necessary to establish viable therapeutic conditions. Deep brain stimulation and epidural electrical stimulation of the spinal cord enable locomotion in humans with spinal cord injury (SCI) but the potential synergy between both approaches is unclear. The authors show that a complex technological approach is required to enable volitional walking in rats with SCI.

[...]the decoded movement was conveyed to a shared controller that merged the participant's intent, robotic position feedback, and constraining task-dependent features to guide the optimum execution of robot movements.9 The resulting control architecture strikingly resembles the organisation of the CNS in mammals.

Vestibular prosthetics transmit angular velocities to the nervous system via electrical stimulation. Head-fixed gyroscopes measure angular motion, but the gyroscope coordinate system will not be coincident with the sensory organs the prosthetic replaces. Here we show a simple calibration method to align gyroscope measurements with the anatomical coordinate system. We benchmarked the method with simulated movements and obtain proof-of-concept with one healthy subject. The method was robust to misalignment, required little data, and minimal processing.

After spinal cord injury (SCI), sensory feedback circuits critically contribute to leg motor execution. Compelled by the importance to engage these circuits during gait rehabilitation, assistive robotics and training protocols have primarily focused on guiding leg movements to reinforce sensory feedback. Despite the importance of trunk postural dynamics on gait and balance, trunk assistance has comparatively received little attention. Typically, trunk movements are either constrained within bodyweight support systems, or manually adjusted by therapists. Here, we show that real-time control of trunk posture re-established dynamic balance amongst bilateral proprioceptive feedback circuits, and thereby restored left-right symmetry, loading and stepping consistency in rats with severe SCI. We developed a robotic system that adjusts mediolateral trunk posture during locomotion. This system uncovered robust relationships between trunk orientation and the modulation of bilateral leg kinematics and muscle activity. Computer simulations suggested that these modulations emerged from corrections in the balance between flexor- and extensor-related proprioceptive feedback. We leveraged this knowledge to engineer control policies that regulate trunk orientation and postural sway in real-time. This dynamical postural interface immediately improved stepping quality in all rats regardless of broad differences in deficits. These results emphasize the importance of trunk regulation to optimize performance during rehabilitation.

The National Institute of Allergy and Infectious Diseases (NIAID) Data Ecosystem Discovery Portal (https://data.niaid.nih.gov) provides a unified search interface for over 4 million data sets relevant to infectious and immune-mediated disease (IID) research. Integrating metadata from domain-specific and generalist repositories, the Portal enables researchers to identify and access data sets using user-friendly filters or advanced queries, without requiring technical expertise. The Portal supports discovery of a wide range of resources, including epidemiological, clinical, and multi-omic data sets and is designed to accommodate exploratory browsing and precise searches. The Portal provides filters, prebuilt queries, and data set collections to simplify the discovery process for users. The Portal additionally provides documentation and an API for programmatic access to harmonized metadata. By easing access barriers to important biomedical data sets, the NIAID Data Ecosystem Discovery Portal serves as an entry point for researchers working to understand, diagnose, or treat IID.IMPORTANCEValuable data sets are often overlooked because they are difficult to locate. The NIAID Data Ecosystem Discovery Portal fills this gap by providing a centralized, searchable interface that empowers users with varying levels of technical expertise to find and reuse data. By standardizing key metadata fields and harmonizing heterogeneous formats, the Portal improves data findability, accessibility, and reusability. This resource supports hypothesis generation, comparative analysis, and secondary use of public data by the IID research community, including those funded by NIAID. The Portal supports data sharing by standardizing metadata and linking to source repositories and maximizes the impact of public investment in research data by supporting scientific advancement via secondary use.

Many neuroprosthetic applications require the use of very small, flexible multi-channel microelectrodes (e.g. polyimide-based film-like electrodes) to fit anatomical constraints. By arranging the electrode contacts on both sides of the polyimide film, selectivity can be further increased without increasing size. In this work, two approaches to create such double-sided electrodes are described and compared: sandwich electrodes prepared by precisely gluing two single-sided structures together, and monolithic electrodes created using a new double-sided photolithography process. Both methods were successfully applied to manufacture double-sided electrodes for stimulation of the vestibular system. In a case study, the electrodes were implanted in the semicircular canals of three guinea pigs and proven to provide electrical stimulation of the vestibular nerve. For both the monolithic electrodes and the sandwich electrodes , long-term stability and functionality was observed over a period of more than 12 months. Comparing the two types of electrodes with respect to the manufacturing process, it can be concluded that monolithic electrodes are the preferred solution for very thin electrodes (<20 μm), while sandwich electrode technology is especially suitable for thicker electrodes (40–50 μm).