Home Use of a Percutaneous Wireless Intracortical Brain-Computer Interface by Individuals With Tetraplegia.

OBJECTIVE: Individuals with neurological disease or injury such as amyotrophic lateral sclerosis, spinal cord injury or stroke may become tetraplegic, unable to speak or even locked-in. For people with these conditions, current assistive technologies are often ineffective. Brain-computer interfaces are being developed to enhance independence and restore communication in the absence of physical movement. Over the past decade, individuals with tetraplegia have achieved rapid on-screen typing and point-and-click control of tablet apps using intracortical brain-computer interfaces (iBCIs) that decode intended arm and hand movements from neural signals recorded by implanted microelectrode arrays. However, cables used to convey neural signals from the brain tether participants to amplifiers and decoding computers and require expert oversight, severely limiting when and where iBCIs could be available for use. Here, we demonstrate the first human use of a wireless broadband iBCI. METHODS: Based on a prototype system previously used in pre-clinical research, we replaced the external cables of a 192-electrode iBCI with wireless transmitters and achieved high-resolution recording and decoding of broadband field potentials and spiking activity from people with paralysis. Two participants in an ongoing pilot clinical trial completed on-screen item selection tasks to assess iBCI-enabled cursor control. RESULTS: Communication bitrates were equivalent between cabled and wireless configurations. Participants also used the wireless iBCI to control a standard commercial tablet computer to browse the web and use several mobile applications. Within-day comparison of cabled and wireless interfaces evaluated bit error rate, packet loss, and the recovery of spike rates and spike waveforms from the recorded neural signals. In a representative use case, the wireless system recorded intracortical signals from two arrays in one participant continuously through a 24-hour period at home. SIGNIFICANCE: Wireless multi-electrode recording of broadband neural signals over extended periods introduces a valuable tool for human neuroscience research and is an important step toward practical deployment of iBCI technology for independent use by individuals with paralysis. On-demand access to high-performance iBCI technology in the home promises to enhance independence and restore communication and mobility for individuals with severe motor impairment.

Auditory cues reveal intended movement information in middle frontal gyrus neuronal ensemble activity of a person with tetraplegia.

Intracortical brain-computer interfaces (iBCIs) allow people with paralysis to directly control assistive devices using neural activity associated with the intent to move. Realizing the full potential of iBCIs critically depends on continued progress in understanding how different cortical areas contribute to movement control. Here we present the first comparison between neuronal ensemble recordings from the left middle frontal gyrus (MFG) and precentral gyrus (PCG) of a person with tetraplegia using an iBCI. As expected, PCG was more engaged in selecting and generating intended movements than in earlier perceptual stages of action planning. By contrast, MFG displayed movement-related information during the sensorimotor processing steps preceding the appearance of the action plan in PCG, but only when the actions were instructed using auditory cues. These results describe a previously unreported function for neurons in the human left MFG in auditory processing contributing to motor control.

Replay of Learned Neural Firing Sequences during Rest in Human Motor Cortex.

The offline "replay" of neural firing patterns underlying waking experience, previously observed in non-human animals, is thought to be a mechanism for memory consolidation. Here, we test for replay in the human brain by recording spiking activity from the motor cortex of two participants who had intracortical microelectrode arrays placed chronically as part of a brain-computer interface pilot clinical trial. Participants took a nap before and after playing a neurally controlled sequence-copying game that consists of many repetitions of one "repeated" sequence sparsely interleaved with varying "control" sequences. Both participants performed repeated sequences more accurately than control sequences, consistent with learning. We compare the firing rate patterns that caused the cursor movements when performing each sequence to firing rate patterns throughout both rest periods. Correlations with repeated sequences increase more from pre- to post-task rest than do correlations with control sequences, providing direct evidence of learning-related replay in the human brain.

The Discriminative Kalman Filter for Bayesian Filtering with Nonlinear and Nongaussian Observation Models.

The Kalman filter provides a simple and efficient algorithm to compute the posterior distribution for state-space models where both the latent state and measurement models are linear and gaussian. Extensions to the Kalman filter, including the extended and unscented Kalman filters, incorporate linearizations for models where the observation model p(observation|state) is nonlinear. We argue that in many cases, a model for p(state|observation) proves both easier to learn and more accurate for latent state estimation. Approximating p(state|observation) as gaussian leads to a new filtering algorithm, the discriminative Kalman filter (DKF), which can perform well even when p(observation|state) is highly nonlinear and/or nongaussian. The approximation, motivated by the Bernstein-von Mises theorem, improves as the dimensionality of the observations increases. The DKF has computational complexity similar to the Kalman filter, allowing it in some cases to perform much faster than particle filters with similar precision, while better accounting for nonlinear and nongaussian observation models than Kalman-based extensions. When the observation model must be learned from training data prior to filtering, off-the-shelf nonlinear and nonparametric regression techniques can provide a gaussian model for p(observation|state) that cleanly integrates with the DKF. As part of the BrainGate2 clinical trial, we successfully implemented gaussian process regression with the DKF framework in a brain-computer interface to provide real-time, closed-loop cursor control to a person with a complete spinal cord injury. In this letter, we explore the theory underlying the DKF, exhibit some illustrative examples, and outline potential extensions.

Neural Representation of Observed, Imagined, and Attempted Grasping Force in Motor Cortex of Individuals with Chronic Tetraplegia.

Hybrid kinetic and kinematic intracortical brain-computer interfaces (iBCIs) have the potential to restore functional grasping and object interaction capabilities in individuals with tetraplegia. This requires an understanding of how kinetic information is represented in neural activity, and how this representation is affected by non-motor parameters such as volitional state (VoS), namely, whether one observes, imagines, or attempts an action. To this end, this work investigates how motor cortical neural activity changes when three human participants with tetraplegia observe, imagine, and attempt to produce three discrete hand grasping forces with the dominant hand. We show that force representation follows the same VoS-related trends as previously shown for directional arm movements; namely, that attempted force production recruits more neural activity compared to observed or imagined force production. Additionally, VoS-modulated neural activity to a greater extent than grasping force. Neural representation of forces was lower than expected, possibly due to compromised somatosensory pathways in individuals with tetraplegia, which have been shown to influence motor cortical activity. Nevertheless, attempted forces (but not always observed or imagined forces) could be decoded significantly above chance, thereby potentially providing relevant information towards the development of a hybrid kinetic and kinematic iBCI.

Cortical control of a tablet computer by people with paralysis.

General-purpose computers have become ubiquitous and important for everyday life, but they are difficult for people with paralysis to use. Specialized software and personalized input devices can improve access, but often provide only limited functionality. In this study, three research participants with tetraplegia who had multielectrode arrays implanted in motor cortex as part of the BrainGate2 clinical trial used an intracortical brain-computer interface (iBCI) to control an unmodified commercial tablet computer. Neural activity was decoded in real time as a point-and-click wireless Bluetooth mouse, allowing participants to use common and recreational applications (web browsing, email, chatting, playing music on a piano application, sending text messages, etc.). Two of the participants also used the iBCI to "chat" with each other in real time. This study demonstrates, for the first time, high-performance iBCI control of an unmodified, commercially available, general-purpose mobile computing device by people with tetraplegia.

Robust Closed-Loop Control of a Cursor in a Person with Tetraplegia using Gaussian Process Regression.

Intracortical brain computer interfaces can enable individuals with paralysis to control external devices through voluntarily modulated brain activity. Decoding quality has been previously shown to degrade with signal nonstationarities-specifically, the changes in the statistics of the data between training and testing data sets. This includes changes to the neural tuning profiles and baseline shifts in firing rates of recorded neurons, as well as nonphysiological noise. While progress has been made toward providing long-term user control via decoder recalibration, relatively little work has been dedicated to making the decoding algorithm more resilient to signal nonstationarities. Here, we describe how principled kernel selection with gaussian process regression can be used within a Bayesian filtering framework to mitigate the effects of commonly encountered nonstationarities. Given a supervised training set of (neural features, intention to move in a direction)-pairs, we use gaussian process regression to predict the intention given the neural data. We apply kernel embedding for each neural feature with the standard radial basis function. The multiple kernels are then summed together across each neural dimension, which allows the kernel to effectively ignore large differences that occur only in a single feature. The summed kernel is used for real-time predictions of the posterior mean and variance under a gaussian process framework. The predictions are then filtered using the discriminative Kalman filter to produce an estimate of the neural intention given the history of neural data. We refer to the multiple kernel approach combined with the discriminative Kalman filter as the MK-DKF. We found that the MK-DKF decoder was more resilient to nonstationarities frequently encountered in-real world settings yet provided similar performance to the currently used Kalman decoder. These results demonstrate a method by which neural decoding can be made more resistant to nonstationarities.

A Comparison of Intention Estimation Methods for Decoder Calibration in Intracortical Brain-Computer Interfaces.

OBJECTIVE: Recent reports indicate that making better assumptions about the user's intended movement can improve the accuracy of decoder calibration for intracortical brain-computer interfaces. Several methods now exist for estimating user intent, including an optimal feedback control model, a piecewise-linear feedback control model, ReFIT, and other heuristics. Which of these methods yields the best decoding performance? METHODS: Using data from the BrainGate2 pilot clinical trial, we measured how a steady-state velocity Kalman filter decoder was affected by the choice of intention estimation method. We examined three separate components of the Kalman filter: dimensionality reduction, temporal smoothing, and output gain (speed scaling). RESULTS: The decoder's dimensionality reduction properties were largely unaffected by the intention estimation method. Decoded velocity vectors differed by <5% in terms of angular error and speed vs. target distance curves across methods. In contrast, the smoothing and gain properties of the decoder were greatly affected (> 50% difference in average values). Since the optimal gain and smoothing properties are task-specific (e.g. lower gains are better for smaller targets but worse for larger targets), no one method was better for all tasks. CONCLUSION: Our results show that, when gain and smoothing differences are accounted for, current intention estimation methods yield nearly equivalent decoders and that simple models of user intent, such as a position error vector (target position minus cursor position), perform comparably to more elaborate models. Our results also highlight that simple differences in gain and smoothing properties have a large effect on online performance and can confound decoder comparisons.

Rapid calibration of an intracortical brain-computer interface for people with tetraplegia.

OBJECTIVE: Brain-computer interfaces (BCIs) can enable individuals with tetraplegia to communicate and control external devices. Though much progress has been made in improving the speed and robustness of neural control provided by intracortical BCIs, little research has been devoted to minimizing the amount of time spent on decoder calibration. APPROACH: We investigated the amount of time users needed to calibrate decoders and achieve performance saturation using two markedly different decoding algorithms: the steady-state Kalman filter, and a novel technique using Gaussian process regression (GP-DKF). MAIN RESULTS: Three people with tetraplegia gained rapid closed-loop neural cursor control and peak, plateaued decoder performance within 3 min of initializing calibration. We also show that a BCI-naïve user (T5) was able to rapidly attain closed-loop neural cursor control with the GP-DKF using self-selected movement imagery on his first-ever day of closed-loop BCI use, acquiring a target 37 s after initiating calibration. SIGNIFICANCE: These results demonstrate the potential for an intracortical BCI to be used immediately after deployment by people with paralysis, without the need for user learning or extensive system calibration.

Spatial Control of Functional Response in 4D-Printed Active Metallic Structures.

We demonstrate a method to achieve local control of 3-dimensional thermal history in a metallic alloy, which resulted in designed spatial variations in its functional response. A nickel-titanium shape memory alloy part was created with multiple shape-recovery stages activated at different temperatures using the selective laser melting technique. The multi-stage transformation originates from differences in thermal history, and thus the precipitate structure, at various locations created from controlled variations in the hatch distance within the same part. This is a first example of precision location-dependent control of thermal history in alloys beyond the surface, and utilizes additive manufacturing techniques as a tool to create materials with novel functional response that is difficult to achieve through conventional methods.

Retrospectively supervised click decoder calibration for self-calibrating point-and-click brain-computer interfaces.

Brain-computer interfaces (BCIs) aim to restore independence to people with severe motor disabilities by allowing control of acursor on a computer screen or other effectors with neural activity. However, physiological and/or recording-related nonstationarities in neural signals can limit long-term decoding stability, and it would be tedious for users to pause use of the BCI whenever neural control degrades to perform decoder recalibration routines. We recently demonstrated that a kinematic decoder (i.e. a decoder that controls cursor movement) can be recalibrated using data acquired during practical point-and-click control of the BCI by retrospectively inferring users' intended movement directions based on their subsequent selections. Here, we extend these methods to allow the click decoder to also be recalibrated using data acquired during practical BCI use. We retrospectively labeled neural data patterns as corresponding to "click" during all time bins in which the click log-likelihood (decoded using linear discriminant analysis, or LDA) had been above the click threshold that was used during real-time neural control. We labeled as "non-click" those periods that the kinematic decoder's retrospective target inference (RTI) heuristics determined to be consistent with intended cursor movement. Once these neural activity patterns were labeled, the click decoder was calibrated using standard supervised classifier training methods. Combined with real-time bias correction and baseline firing rate tracking, this set of "retrospectively labeled" decoder calibration methods enabled a BrainGate participant with amyotrophic lateral sclerosis (T9) to type freely across 11 research sessions spanning 29days, maintaining high-performance neural control over cursor movement and click without needing to interrupt virtual keyboard use for explicit calibration tasks. By eliminating the need for tedious calibration tasks with prescribed targets and pre-specified click times, this approach advances the potential clinical utility of intracortical BCIs for individuals with severe motor disability.