Neuroplasticity may play a critical role in developing robust, naturally controlled neuroprostheses. This learning, however, is sensitive to system changes such as the neural activity used for control. The ultimate utility of neuroplasticity in real-world neuroprostheses is thus unclear. Adaptive decoding methods hold promise for improving neuroprosthetic performance in nonstationary systems. Here, we explore the use of decoder adaptation to shape neuroplasticity in two scenarios relevant for real-world neuroprostheses: nonstationary recordings of neural activity and changes in control context. Nonhuman primates learned to control a cursor to perform a reaching task using semistationary neural activity in two contexts: with and without simultaneous arm movements. Decoder adaptation was used to improve initial performance and compensate for changes in neural recordings. We show that beneficial neuroplasticity can occur alongside decoder adaptation, yielding performance improvements, skill retention, and resistance to interference from native motor networks. These results highlight the utility of neuroplasticity for real-world neuroprostheses.

Closed-loop decoder adaptation (CLDA) shows great promise to improve closed-loop brain-machine interface (BMI) performance. Developing adaptation algorithms capable of rapidly improving performance, independent of initial performance, may be crucial for clinical applications where patients have limited movement and sensory abilities due to motor deficits. Given the subject-decoder interactions inherent in closed-loop BMIs, the decoder adaptation time-scale may be of particular importance when initial performance is limited. Here, we present SmoothBatch, a CLDA algorithm which updates decoder parameters on a 1-2 min time-scale using an exponentially weighted sliding average. The algorithm was experimentally tested with one nonhuman primate performing a center-out reaching BMI task. SmoothBatch was seeded four ways with varying offline decoding power: 1) visual observation of a cursor ( n = 20), 2) ipsilateral arm movements ( n = 8), 3) baseline neural activity ( n = 17), and 4) arbitrary weights ( n = 11). SmoothBatch rapidly improved performance regardless of seeding, with performance improvements from 0.018 ±0.133 successes/min to > 8 successes/min within 13.1 ±5.5 min ( n = 56). After decoder adaptation ceased, the subject maintained high performance. Moreover, performance improvements were paralleled by SmoothBatch convergence, suggesting that CLDA involves a co-adaptation process between the subject and the decoder.

Much progress has been made in brain-machine interfaces (BMI) using decoders such as Kalman filters and finding their parameters with closed-loop decoder adaptation (CLDA). However, current decoders do not model the spikes directly, and hence may limit the processing time-scale of BMI control and adaptation. Moreover, while specialized CLDA techniques for intention estimation and assisted training exist, a unified and systematic CLDA framework that generalizes across different setups is lacking. Here we develop a novel closed-loop BMI training architecture that allows for processing, control, and adaptation using spike events, enables robust control and extends to various tasks. Moreover, we develop a unified control-theoretic CLDA framework within which intention estimation, assisted training, and adaptation are performed. The architecture incorporates an infinite-horizon optimal feedback-control (OFC) model of the brain’s behavior in closed-loop BMI control, and a point process model of spikes. The OFC model infers the user’s motor intention during CLDA—a process termed intention estimation. OFC is also used to design an autonomous and dynamic assisted training technique. The point process model allows for neural processing, control and decoder adaptation with every spike event and at a faster time-scale than current decoders; it also enables dynamic spike-event-based parameter adaptation unlike current CLDA methods that use batch-based adaptation on much slower adaptation time-scales. We conducted closed-loop experiments in a non-human primate over tens of days to dissociate the effects of these novel CLDA components. The OFC intention estimation improved BMI performance compared with current intention estimation techniques. OFC assisted training allowed the subject to consistently achieve proficient control. Spike-event-based adaptation resulted in faster and more consistent performance convergence compared with batch-based methods, and was robust to parameter initialization. Finally, the architecture extended control to tasks beyond those used for CLDA training. These results have significant implications towards the development of clinically-viable neuroprosthetics.

Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called “Neural Matrix,” that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.

A fundamental organizational principle of the primate motor system is cortical control of contralateral limb movements. Motor areas also appear to play a role in the control of ipsilateral limb movements. Several studies in monkeys have shown that individual neurons in primary motor cortex (M1) may represent, on average, the direction of movements of the ipsilateral arm. Given the increasing body of evidence demonstrating that neural ensembles can reliably represent information with a high temporal resolution, here we characterize the distributed neural representation of ipsilateral upper limb kinematics in both monkey and man. In two macaque monkeys trained to perform center-out reaching movements, we found that the ensemble spiking activity in M1 could continuously represent ipsilateral limb position. Interestingly, this representation was more correlated with joint angles than hand position. Using bilateral electromyography recordings, we excluded the possibility that postural or mirror movements could exclusively account for these findings. In addition, linear methods could decode limb position from cortical field potentials in both monkeys. We also found that M1 spiking activity could control a biomimetic brain-machine interface reflecting ipsilateral kinematics. Finally, we recorded cortical field potentials from three human subjects and also consistently found evidence of a neural representation for ipsilateral movement parameters. Together, our results demonstrate the presence of a high-fidelity neural representation for ipsilateral movement and illustrates that it can be successfully incorporated into a brain-machine interface.

Brain-machine interfaces (BMI) create novel sensorimotor pathways for action. Much as the sensorimotor apparatus shapes natural motor control, the BMI pathway characteristics may also influence neuroprosthetic control. Here, we explore the influence of control and feedback rates, where control rate indicates how often motor commands are sent from the brain to the prosthetic, and feedback rate indicates how often visual feedback of the prosthetic is provided to the subject. We developed a new BMI that allows arbitrarily fast control and feedback rates, and used it to dissociate the effects of each rate in two monkeys. Increasing the control rate significantly improved control even when feedback rate was unchanged. Increasing the feedback rate further facilitated control. We also show that our high-rate BMI significantly outperformed state-of-the-art methods due to higher control and feedback rates, combined with a different point process mathematical encoding model. Our BMI paradigm can dissect the contribution of different elements in the sensorimotor pathway, providing a unique tool for studying neuroprosthetic control mechanisms.

Overall, our results demonstrate proficient, continuous BMI control using LFPs and provide insight into the subject-specific spectral patterns of LFP activity modulated during control.

Closed-loop decoder adaptation (CLDA) is an emerging paradigm for achieving rapid performance improvements in online brain-machine interface (BMI) operation. Designing an effective CLDA algorithm requires making multiple important decisions, including choosing the timescale of adaptation, selecting which decoder parameters to adapt, crafting the corresponding update rules, and designing CLDA parameters. These design choices, combined with the specific settings of CLDA parameters, will directly affect the algorithm's ability to make decoder parameters converge to values that optimize performance. In this article, we present a general framework for the design and analysis of CLDA algorithms and support our results with experimental data of two monkeys performing a BMI task. First, we analyze and compare existing CLDA algorithms to highlight the importance of four critical design elements: the adaptation timescale, selective parameter adaptation, smooth decoder updates, and intuitive CLDA parameters. Second, we introduce mathematical convergence analysis using measures such as mean-squared error and KL divergence as a useful paradigm for evaluating the convergence properties of a prototype CLDA algorithm before experimental testing. By applying these measures to an existing CLDA algorithm, we demonstrate that our convergence analysis is an effective analytical tool that can ultimately inform and improve the design of CLDA algorithms.