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  1. A key factor in the clinical translation of brain-machine interfaces (BMIs) for restoring hand motor function will be their robustness to changes in a task. With functional electrical stimulation (FES) for example, the patient’s own hand will be used to produce a wide range of forces in otherwise similar movements. To investigate the impact of task changes on BMI performance, we trained two rhesus macaques to control a virtual hand with their physical hand while we added springs to each finger group (index or middle-ring-small) or altered their wrist posture. Using simultaneously recorded intracortical neural activity, finger positions, and electromyography, we found that decoders trained in one context did not generalize well to other contexts, leading to significant increases in prediction error, especially for muscle activations. However, with respect to online BMI control of the virtual hand, changing either the decoder training task context or the hand’s physical context during online control had little effect on online performance. We explain this dichotomy by showing that the structure of neural population activity remained similar in new contexts, which could allow for fast adjustment online. Additionally, we found that neural activity shifted trajectories proportional to the required muscle activation in new contexts. This shift in neural activity possibly explains biases to off-context kinematic predictions and suggests a feature that could help predict different magnitude muscle activations while producing similar kinematics. 
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    Free, publicly-accessible full text available June 7, 2024
  2. Abstract

    Objective.While brain–machine interfaces (BMIs) are promising technologies that could provide direct pathways for controlling the external world and thus regaining motor capabilities, their effectiveness is hampered by decoding errors. Previous research has demonstrated the detection and correction of BMI outcome errors, which occur at the end of trials. Here we focus on continuous detection and correction of BMI execution errors, which occur during real-time movements.Approach.Two adult male rhesus macaques were implanted with Utah arrays in the motor cortex. The monkeys performed single or two-finger group BMI tasks where a Kalman filter decoded binned spiking-band power into intended finger kinematics. Neural activity was analyzed to determine how it depends not only on the kinematics of the fingers, but also on the distance of each finger-group to its target. We developed a method to detect erroneous movements, i.e. consistent movements away from the target, from the same neural activity used by the Kalman filter. Detected errors were corrected by a simple stopping strategy, and the effect on performance was evaluated.Mainresults.First we show that including distance to target explains significantly more variance of the recorded neural activity. Then, for the first time, we demonstrate that neural activity in motor cortex can be used to detect execution errors during BMI controlled movements. Keeping false positive rate below5%, it was possible to achieve mean true positive rate of28.1%online. Despite requiring 200 ms to detect and react to suspected errors, we were able to achieve a significant improvement in task performance via reduced orbiting time of one finger group.Significance.Neural activity recorded in motor cortex for BMI control can be used to detect and correct BMI errors and thus to improve performance. Further improvements may be obtained by enhancing classification and correction strategies.

     
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  3. Abstract Objective. Brain–machine interfaces (BMIs) have shown promise in extracting upper extremity movement intention from the thoughts of nonhuman primates and people with tetraplegia. Attempts to restore a user’s own hand and arm function have employed functional electrical stimulation (FES), but most work has restored discrete grasps. Little is known about how well FES can control continuous finger movements. Here, we use a low-power brain-controlled functional electrical stimulation (BCFES) system to restore continuous volitional control of finger positions to a monkey with a temporarily paralyzed hand. Approach. We delivered a nerve block to the median, radial, and ulnar nerves just proximal to the elbow to simulate finger paralysis, then used a closed-loop BMI to predict finger movements the monkey was attempting to make in two tasks. The BCFES task was one-dimensional in which all fingers moved together, and we used the BMI’s predictions to control FES of the monkey’s finger muscles. The virtual two-finger task was two-dimensional in which the index finger moved simultaneously and independently from the middle, ring, and small fingers, and we used the BMI’s predictions to control movements of virtual fingers, with no FES. Main results. In the BCFES task, the monkey improved his success rate to 83% (1.5 s median acquisition time) when using the BCFES system during temporary paralysis from 8.8% (9.5 s median acquisition time, equal to the trial timeout) when attempting to use his temporarily paralyzed hand. In one monkey performing the virtual two-finger task with no FES, we found BMI performance (task success rate and completion time) could be completely recovered following temporary paralysis by executing recalibrated feedback-intention training one time. Significance. These results suggest that BCFES can restore continuous finger function during temporary paralysis using existing low-power technologies and brain-control may not be the limiting factor in a BCFES neuroprosthesis. 
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    Free, publicly-accessible full text available May 9, 2024
  4. Abstract

    Objective.Extracting signals directly from the motor system poses challenges in obtaining both high amplitude and sustainable signals for upper-limb neuroprosthetic control. To translate neural interfaces into the clinical space, these interfaces must provide consistent signals and prosthetic performance.Approach.Previously, we have demonstrated that the Regenerative Peripheral Nerve Interface (RPNI) is a biologically stable, bioamplifier of efferent motor action potentials. Here, we assessed the signal reliability from electrodes surgically implanted in RPNIs and residual innervated muscles in humans for long-term prosthetic control.Main results.RPNI signal quality, measured as signal-to-noise ratio, remained greater than 15 for up to 276 and 1054 d in participant 1 (P1), and participant 2 (P2), respectively. Electromyography from both RPNIs and residual muscles was used to decode finger and grasp movements. Though signal amplitude varied between sessions, P2 maintained real-time prosthetic performance above 94% accuracy for 604 d without recalibration. Additionally, P2 completed a real-world multi-sequence coffee task with 99% accuracy for 611 d without recalibration.Significance.This study demonstrates the potential of RPNIs and implanted EMG electrodes as a long-term interface for enhanced prosthetic control.

     
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  5. Abstract Objective. The Utah array is widely used in both clinical studies and neuroscience. It has a strong track record of safety. However, it is also known that implanted electrodes promote the formation of scar tissue in the immediate vicinity of the electrodes, which may negatively impact the ability to record neural waveforms. This scarring response has been primarily studied in rodents, which may have a very different response than primate brain. Approach. Here, we present a rare nonhuman primate histological dataset ( n = 1 rhesus macaque) obtained 848 and 590 d after implantation in two brain hemispheres. For 2 of 4 arrays that remained within the cortex, NeuN was used to stain for neuron somata at three different depths along the shanks. Images were filtered and denoised, with neurons then counted in the vicinity of the arrays as well as a nearby section of control tissue. Additionally, 3 of 4 arrays were imaged with a scanning electrode microscope to evaluate any materials damage that might be present. Main results. Overall, we found a 63% percent reduction in the number of neurons surrounding the electrode shanks compared to control areas. In terms of materials, the arrays remained largely intact with metal and Parylene C present, though tip breakage and cracks were observed on many electrodes. Significance. Overall, these results suggest that the tissue response in the nonhuman primate brain shows similar neuron loss to previous studies using rodents. Electrode improvements, for example using smaller or softer probes, may therefore substantially improve the tissue response and potentially improve the neuronal recording yield in primate cortex. 
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  6. Abstract

    Objective.Characterizing the relationship between neuron spiking and the signals that electrodes record is vital to defining the neural circuits driving brain function and informing clinical brain-machine interface design. However, high electrode biocompatibility and precisely localizing neurons around the electrodes are critical to defining this relationship.Approach.Here, we demonstrate consistent localization of the recording site tips of subcellular-scale (6.8µm diameter) carbon fiber electrodes and the positions of surrounding neurons. We implanted male rats with carbon fiber electrode arrays for 6 or 12+ weeks targeting layer V motor cortex. After explanting the arrays, we immunostained the implant site and localized putative recording site tips with subcellular-cellular resolution. We then 3D segmented neuron somata within a 50µm radius from implanted tips to measure neuron positions and health and compare to healthy cortex with symmetric stereotaxic coordinates.Main results.Immunostaining of astrocyte, microglia, and neuron markers confirmed that overall tissue health was indicative of high biocompatibility near the tips. While neurons near implanted carbon fibers were stretched, their number and distribution were similar to hypothetical fibers placed in healthy contralateral brain. Such similar neuron distributions suggest that these minimally invasive electrodes demonstrate the potential to sample naturalistic neural populations. This motivated the prediction of spikes produced by nearby neurons using a simple point source model fit using recorded electrophysiology and the mean positions of the nearest neurons observed in histology. Comparing spike amplitudes suggests that the radius at which single units can be distinguished from others is near the fourth closest neuron (30.7 ± 4.6µm,Xˉ± S) in layer V motor cortex.Significance.Collectively, these data and simulations provide the first direct evidence that neuron placement in the immediate vicinity of the recording site influences how many spike clusters can be reliably identified by spike sorting.

     
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  7. Abstract

    Despite the rapid progress and interest in brain-machine interfaces that restore motor function, the performance of prosthetic fingers and limbs has yet to mimic native function. The algorithm that converts brain signals to a control signal for the prosthetic device is one of the limitations in achieving rapid and realistic finger movements. To achieve more realistic finger movements, we developed a shallow feed-forward neural network to decode real-time two-degree-of-freedom finger movements in two adult male rhesus macaques. Using a two-step training method, a recalibrated feedback intention–trained (ReFIT) neural network is introduced to further improve performance. In 7 days of testing across two animals, neural network decoders, with higher-velocity and more natural appearing finger movements, achieved a 36% increase in throughput over the ReFIT Kalman filter, which represents the current standard. The neural network decoders introduced herein demonstrate real-time decoding of continuous movements at a level superior to the current state-of-the-art and could provide a starting point to using neural networks for the development of more naturalistic brain-controlled prostheses.

     
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  8. Abstract Objective . Brain–machine interfaces (BMIs) have the potential to restore motor function but are currently limited by electrode count and long-term recording stability. These challenges may be solved through the use of free-floating ‘motes’ which wirelessly transmit recorded neural signals, if power consumption can be kept within safe levels when scaling to thousands of motes. Here, we evaluated a pulse-interval modulation (PIM) communication scheme for infrared (IR)-based motes that aims to reduce the wireless data rate and system power consumption. Approach . To test PIM’s ability to efficiently communicate neural information, we simulated the communication scheme in a real-time closed-loop BMI with non-human primates. Additionally, we performed circuit simulations of an IR-based 1000-mote system to calculate communication accuracy and total power consumption. Main results . We found that PIM at 1 kb/s per channel maintained strong correlations with true firing rate and matched online BMI performance of a traditional wired system. Closed-loop BMI tests suggest that lags as small as 30 ms can have significant performance effects. Finally, unlike other IR communication schemes, PIM is feasible in terms of power, and neural data can accurately be recovered on a receiver using 3 mW for 1000 channels. Significance. These results suggest that PIM-based communication could significantly reduce power usage of wireless motes to enable higher channel-counts for high-performance BMIs. 
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  9. Abstract Objective. To understand neural circuit dynamics, it is critical to manipulate and record many individual neurons. Traditional recording methods, such as glass microelectrodes, can only control a small number of neurons. More recently, devices with high electrode density have been developed, but few of them can be used for intracellular recording or stimulation in intact nervous systems. Carbon fiber electrodes (CFEs) are 8 µ m-diameter electrodes that can be assembled into dense arrays (pitches ⩾ 80 µ m). They have good signal-to-noise ratios (SNRs) and provide stable extracellular recordings both acutely and chronically in neural tissue in vivo (e.g. rat motor cortex). The small fiber size suggests that arrays could be used for intracellular stimulation. Approach. We tested CFEs for intracellular stimulation using the large identified and electrically compact neurons of the marine mollusk Aplysia californica . Neuron cell bodies in Aplysia range from 30 µ m to over 250 µ m. We compared the efficacy of CFEs to glass microelectrodes by impaling the same neuron’s cell body with both electrodes and connecting them to a DC coupled amplifier. Main results. We observed that intracellular waveforms were essentially identical, but the amplitude and SNR in the CFE were lower than in the glass microelectrode. CFE arrays could record from 3 to 8 neurons simultaneously for many hours, and many of these recordings were intracellular, as shown by simultaneous glass microelectrode recordings. CFEs coated with platinum-iridium could stimulate and had stable impedances over many hours. CFEs not within neurons could record local extracellular activity. Despite the lower SNR, the CFEs could record synaptic potentials. CFEs were less sensitive to mechanical perturbations than glass microelectrodes. Significance. The ability to do stable multi-channel recording while stimulating and recording intracellularly make CFEs a powerful new technology for studying neural circuit dynamics. 
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