Sex Differences in Dopamine Release in Nucleus Accumbens and Dorsal Striatum Determined by Chronic Fast Scan Cyclic Voltammetry: Effects of social housing and repeated stimulation.

We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation (ES; 60  Hz) induced DA release was recorded in the NAc of single or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than in males. Finally, DA release following ES of the medial forebrain bundle at 60  Hz was studied over four weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo.Significance Statement Dopamine release is not uniform or fixed. In the nucleus accumbens, pair housing, compared with individual housing, is shown to differentially affect dopamine responsiveness to stimulation in a sex-dependent and region-specific way. There are also sex differences in stimulated dopamine release in the dorsolateral striatum of intact rats, which are not seen in gonadectomized rats, indicating the hormone dependence of this sex difference. However, reuptake of dopamine was slower in females than in males, independent of gonadal hormones. Importantly, the electrical stimulation-induced dopamine release in the dorsolateral striatum of gonadectomized rats demonstrated sensitization of dopamine release in vivo within animals for the first time. Thus, stimulated dopamine release exhibits sex-specific neuroplasticity that is modified in females by the housing conditions.

Ultraflexible and Stretchable Intrafascicular Peripheral Nerve Recording Device with Axon-Dimension, Cuff-Less Microneedle Electrode Array.

Peripheral nerve mapping tools with higher spatial resolution are needed to advance systems neuroscience, and potentially provide a closed-loop biomarker in neuromodulation applications. Two critical challenges of microscale neural interfaces are 1) how to apply them to small peripheral nerves, and 2) how to minimize chronic reactivity. A flexible microneedle nerve array (MINA) is developed, which is the first high-density penetrating electrode array made with axon-sized silicon microneedles embedded in low-modulus thin silicone. The design, fabrication, acute recording, and chronic reactivity to an implanted MINA, are presented. Distinctive units are identified in the rat peroneal nerve. The authors also demonstrate a long-term, cuff-free, and suture-free fixation manner using rose bengal as a light-activated adhesive for two time-points. The tissue response is investigated at 1-week and 6-week time-points, including two sham groups and two MINA-implanted groups. These conditions are quantified in the left vagus nerve of rats using histomorphometry. Micro computed tomography (micro-CT) is added to visualize and quantify tissue encapsulation around the implant. MINA demonstrates a reduction in encapsulation thickness over previously quantified interfascicular methods. Future challenges include techniques for precise insertion of the microneedle electrodes and demonstrating long-term recording.

A Light-Tolerant Wireless Neural Recording IC for Motor Prediction With Near-Infrared-Based Power and Data Telemetry.

Miniaturized and wireless near-infrared (NIR) based neural recorders with optical powering and data telemetry have been introduced as a promising approach for safe long-term monitoring with the smallest physical dimension among state-of-the-art standalone recorders. However, a main challenge for the NIR based neural recording ICs is to maintain robust operation in the presence of light-induced parasitic short circuit current from junction diodes. This is especially true when the signal currents are kept small to reduce power consumption. In this work, we present a light-tolerant and low-power neural recording IC for motor prediction that can fully function in up to 300 µW/mm2 of light exposure. It achieves best-in-class power consumption of 0.57 µW at 38° C with a 4.1 NEF pseudo-resistorless amplifier, an on-chip neural feature extractor, and individual mote level gain control. Applying the 20-channel pre-recorded neural signals of a monkey, the IC predicts finger position and velocity with correlation coefficient up to 0.870 and 0.569, respectively, with individual mote level gain control enabled. In addition, wireless measurement is demonstrated through optical power and data telemetry using a custom PV/LED GaAs chip wire bonded to the proposed IC.

Surgically Implanted Electrodes Enable Real-Time Finger and Grasp Pattern Recognition for Prosthetic Hands.

Currently available prosthetic hands are capable of actuating anywhere from five to 30 degrees of freedom (DOF). However, grasp control of these devices remains unintuitive and cumbersome. To address this issue, we propose directly extracting finger commands from the neuromuscular system. Two persons with transradial amputations had bipolar electrodes implanted into regenerative peripheral nerve interfaces (RPNIs) and residual innervated muscles. The implanted electrodes recorded local electromyography with large signal amplitudes. In a series of single-day experiments, participants used a high speed movement classifier to control a virtual prosthetic hand in real-time. Both participants transitioned between 10 pseudo-randomly cued individual finger and wrist postures with an average success rate of 94.7% and trial latency of 255 ms. When the set was reduced to five grasp postures, metrics improved to 100% success and 135 ms trial latency. Performance remained stable across untrained static arm positions while supporting the weight of the prosthesis. Participants also used the high speed classifier to switch between robotic prosthetic grips and complete a functional performance assessment. These results demonstrate that pattern recognition systems can use intramuscular electrodes and RPNIs for fast and accurate prosthetic grasp control.

Cellular-scale silicon probes for high-density, precisely localized neurophysiology.

Neural implants with large numbers of electrodes have become an important tool for examining brain functions. However, these devices typically displace a large intracranial volume compared with the neurons they record. This large size limits the density of implants, provokes tissue reactions that degrade chronic performance, and impedes the ability to accurately visualize recording sites within intact circuits. Here we report next-generation silicon-based neural probes at a cellular scale (5 × 10 µm cross section), with ultra-high-density packing (as little as 66 µm between shanks) and 64 or 256 closely spaced recording sites per probe. We show that these probes can be inserted into superficial or deep brain structures and record large spikes in freely behaving rats for many weeks. Finally, we demonstrate a slice-in-place approach for the precise registration of recording sites relative to nearby neurons and anatomical features, including striatal µ-opioid receptor patches. This scalable technology provides a valuable tool for examining information processing within neural circuits and potentially for human brain-machine interfaces.NEW & NOTEWORTHY Devices with many electrodes penetrating into the brain are an important tool for investigating neural information processing, but they are typically large compared with neurons. This results in substantial damage and makes it harder to reconstruct recording locations within brain circuits. This paper presents high-channel-count silicon probes with much smaller features and a method for slicing through probe, brain, and skull all together. This allows probe tips to be directly observed relative to immunohistochemical markers.

The future of upper extremity rehabilitation robotics: research and practice.

The loss of upper limb motor function can have a devastating effect on people's lives. To restore upper limb control and functionality, researchers and clinicians have developed interfaces to interact directly with the human body's motor system. In this invited review, we aim to provide details on the peripheral nerve interfaces and brain-machine interfaces that have been developed in the past 30 years for upper extremity control, and we highlight the challenges that still remain to transition the technology into the clinical market. The findings show that peripheral nerve interfaces and brain-machine interfaces have many similar characteristics that enable them to be concurrently developed. Decoding neural information from both interfaces may lead to novel physiological models that may one day fully restore upper limb motor function for a growing patient population.

Estimating Risk for Future Intracranial, Fully Implanted, Modular Neuroprosthetic Systems: A Systematic Review of Hardware Complications in Clinical Deep Brain Stimulation and Experimental Human Intracortical Arrays.

OBJECTIVE: A new age of neuromodulation is emerging: one of restorative neuroengineering and neuroprosthetics. As novel device systems move toward regulatory evaluation and clinical trials, a critical need arises for evidence-based identification of potential sources of hardware-related complications to assist in clinical trial design and mitigation of potential risk. MATERIALS AND METHODS: The objective of this systematic review is to provide a detailed safety analysis for future intracranial, fully implanted, modular neuroprosthetic systems. To achieve this aim, we conducted an evidence-based analysis of hardware complications for the most established clinical intracranial modular system, deep brain stimulation (DBS), as well as the most widely used intracranial human experimental system, the silicon-based (Utah) array. RESULTS: Of 2328 publications identified, 240 articles met the inclusion criteria and were reviewed for DBS hardware complications. The most reported adverse events were infection (4.57%), internal pulse generator malfunction (3.25%), hemorrhage (2.86%), lead migration (2.58%), lead fracture (2.56%), skin erosion (2.22%), and extension cable malfunction (1.63%). Of 433 publications identified, 76 articles met the inclusion criteria and were reviewed for Utah array complications. Of 48 human subjects implanted with the Utah array, 18 have chronic implants. Few specific complications are described in the literature; hence, implant duration served as a lower bound for complication-free operation. The longest reported duration of a person with a Utah array implant is 1975 days (~5.4 years). CONCLUSIONS: Through systematic review of the clinical and human-trial literature, our study provides the most comprehensive safety review to date of DBS hardware and human neuroprosthetic research using the Utah array. The evidence-based analysis serves as an important reference for investigators seeking to identify hardware-related safety data, a necessity to meet regulatory requirements and to design clinical trials for future intracranial, fully implanted, modular neuroprosthetic systems.

Disruption of corticocortical information transfer during ketamine anesthesia in the primate brain.

The neural mechanisms of anesthetic-induced unconsciousness have yet to be fully elucidated, in part because of the diverse molecular targets of anesthetic agents. We demonstrate, using intracortical recordings in macaque monkeys, that information transfer between structurally connected cortical regions is disrupted during ketamine anesthesia, despite preserved primary sensory representation. Furthermore, transfer entropy, an information-theoretic measure of directed connectivity, decreases significantly between neuronal units in the anesthetized state. This is the first direct demonstration of a general anesthetic disrupting corticocortical information transfer in the primate brain. Given past studies showing that more commonly used GABAergic drugs inhibit surrogate measures of cortical communication, this finding suggests the potential for a common network-level mechanism of anesthetic-induced unconsciousness.

Surveying the interest of individuals with upper limb loss in novel prosthetic control techniques.

BACKGROUND: Novel techniques for the control of upper limb prostheses may allow users to operate more complex prostheses than those that are currently available. Because many of these techniques are surgically invasive, it is important to understand whether individuals with upper limb loss would accept the associated risks in order to use a prosthesis. METHODS: An online survey of individuals with upper limb loss was conducted. Participants read descriptions of four prosthetic control techniques. One technique was noninvasive (myoelectric) and three were invasive (targeted muscle reinnervation, peripheral nerve interfaces, cortical interfaces). Participants rated how likely they were to try each technique if it offered each of six different functional features. They also rated their general interest in each of the six features. A two-way repeated measures analysis of variance with Greenhouse-Geisser corrections was used to examine the effect of the technique type and feature on participants' interest in each technique. RESULTS: Responses from 104 individuals were analyzed. Many participants were interested in trying the techniques - 83 % responded positively toward myoelectric control, 63 % toward targeted muscle reinnervation, 68 % toward peripheral nerve interfaces, and 39 % toward cortical interfaces. Common concerns about myoelectric control were weight, cost, durability, and difficulty of use, while the most common concern about the invasive techniques was surgical risk. Participants expressed greatest interest in basic prosthesis features (e.g., opening and closing the hand slowly), as opposed to advanced features like fine motor control and touch sensation. CONCLUSIONS: The results of these investigations may be used to inform the development of future prosthetic technologies that are appealing to individuals with upper limb loss.

Intracellular neural control of an active feeding structure in Aplysia using a carbon fiber electrode array.

BACKGROUND: To study neural control of behavior, intracellular recording and stimulation of many neurons in freely moving animals would be ideal. However, current technologies limit the number of neurons that can be monitored and manipulated. A new technology has become available for intracellular recording and stimulation which we demonstrate in the tractable nervous system of Aplysia. NEW METHOD: Carbon fiber electrode arrays (whose tips are coated with platinum-iridium) were used with an in vitro feeding preparation to intracellularly record from and to control the activity of multiple neurons during feeding movements. RESULTS: In an in vitro feeding preparation, the carbon fiber electrode arrays recorded action potentials and subthreshold synaptic potentials during feeding movements. Depolarizing or hyperpolarizing currents activated or inhibited identified neurons (respectively), manipulating the movements of the feeding apparatus. COMPARISON WITH EXISTING METHOD(S): Standard glass microelectrodes that are commonly used for intracellular recording are stiff, liable to break in response to movement, and require many micromanipulators to be precisely positioned. In contrast, carbon fiber arrays are less sensitive to movement, but are capable of multiple channels of intracellular recording and stimulation. CONCLUSIONS: Carbon fiber arrays are a novel technology for intracellular recording that can be used in moving preparations. They can record both action potentials and synaptic activity in multiple neurons and can be used to stimulate multiple neurons in complex patterns.

Sex Differences in Dopamine Release in Nucleus Accumbens and Dorsal Striatum Determined by Chronic Fast Scan Cyclic Voltammetry: Effects of social housing and repeated stimulation.

We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation (ES; 60Hz) induced DA release was recorded in the NAc of single or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than in males. Finally, DA release following ES of the medial forebrain bundle at 60Hz was studied over four weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo.

Artificial neural network for brain-machine interface consistently produces more naturalistic finger movements than linear methods.

Brain-machine interfaces (BMI) aim to restore function to persons living with spinal cord injuries by 'decoding' neural signals into behavior. Recently, nonlinear BMI decoders have outperformed previous state-of-the-art linear decoders, but few studies have investigated what specific improvements these nonlinear approaches provide. In this study, we compare how temporally convolved feedforward neural networks (tcFNNs) and linear approaches predict individuated finger movements in open and closed-loop settings. We show that nonlinear decoders generate more naturalistic movements, producing distributions of velocities 85.3% closer to true hand control than linear decoders. Addressing concerns that neural networks may come to inconsistent solutions, we find that regularization techniques improve the consistency of tcFNN convergence by 194.6%, along with improving average performance, and training speed. Finally, we show that tcFNN can leverage training data from multiple task variations to improve generalization. The results of this study show that nonlinear methods produce more naturalistic movements and show potential for generalizing over less constrained tasks. Teaser: A neural network decoder produces consistent naturalistic movements and shows potential for real-world generalization through task variations.

Fabrication and Validation of Sub-Cellular Carbon Fiber Electrodes.

Multielectrode arrays for interfacing with neurons are of great interest for a wide range of medical applications. However, current electrodes cause damage over time. Ultra small carbon fibers help to address issues but controlling the electrode site geometry is difficult. Here we propose a methodology to create small, pointed fiber electrodes (SPFe). We compare the SPFe to previously made blowtorched fibers in characterization. The SPFe result in small site sizes [Formula: see text] with consistently sharp points (20.8 ± 7.64°). Additionally, these electrodes were able to record and/or stimulate neurons multiple animal models including rat cortex, mouse retina, Aplysia ganglia and octopus axial cord. In rat cortex, these electrodes recorded significantly higher peak amplitudes than the traditional blowtorched fibers. These SPFe may be applicable to a wide range of applications requiring a highly specific interface with individual neurons.

Electrical Stimulation of Regenerative Peripheral Nerve Interfaces (RPNIs) Induces Referred Sensations in People With Upper Limb Loss.

Individuals with upper limb loss lack sensation of the missing hand, which can negatively impact their daily function. Several groups have attempted to restore this sensation through electrical stimulation of residual nerves. The purpose of this study was to explore the utility of regenerative peripheral nerve interfaces (RPNIs) in eliciting referred sensation. In four participants with upper limb loss, we characterized the quality and location of sensation elicited through electrical stimulation of RPNIs over time. We also measured functional stimulation ranges (sensory perception and discomfort thresholds), sensitivity to changes in stimulation amplitude, and ability to differentiate objects of different stiffness and sizes. Over a period of up to 54 months, stimulation of RPNIs elicited sensations that were consistent in quality (e.g. tingling, kinesthesia) and were perceived in the missing hand and forearm. The location of elicited sensation was partially-stable to stable in 13 of 14 RPNIs. For 5 of 7 RPNIs tested, participants demonstrated a sensitivity to changes in stimulation amplitude, with an average just noticeable difference of 45 nC. In a case study, one participant was provided RPNI stimulation proportional to prosthetic grip force. She identified four objects of different sizes and stiffness with 56% accuracy with stimulation alone and 100% accuracy when stimulation was combined with visual feedback of hand position. Collectively, these experiments suggest that RPNIs have the potential to be used in future bi-directional prosthetic systems.

Realizing Upper Extremity Bionic Limbs: Leveraging Neuroprosthetic Control Strategies.

SUMMARY: Innovations in the fields of prosthetic devices and neuroprosthetic control strategies have opened new frontiers for the treatment and rehabilitation of individuals undergoing amputation. Commercial prosthetic devices are now available with sophisticated electrical and mechanical components that can closely replicate the functions of the human musculoskeletal system. However, to truly recognize the potential of such prosthetic devices and develop the next generation of bionic limbs, a highly reliable prosthetic device control strategy is required. In the past few years, refined surgical techniques have enabled neuroprosthetic control strategies to record efferent motor and stimulate afferent sensory action potentials from a residual limb with extraordinary specificity, signal quality, and long-term stability. As a result, such control strategies are now capable of facilitating intuitive, real-time, and naturalistic prosthetic experiences for patients with amputations. This article summarizes the current state of upper extremity neuroprosthetic devices and discusses the leading control strategies that are critical to the ongoing advancement of prosthetic development and implementation.

Automated assembly of high-density carbon fiber electrode arrays for single unit electrophysiological recordings.

Objective.Carbon fiber (CF) is good for chronic neural recording due to the small diameter (7µm), high Young's modulus, and low electrical resistance, but most high-density carbon fiber (HDCF) arrays are manually assembled with labor-intensive procedures and limited by the accuracy and repeatability of the operator handling. A machine to automate the assembly is desired.Approach.The HDCF array assembly machine contains: (1) a roller-based CF extruder, (2) a motion system with three linear and one rotary stages, (3) an imaging system with two digital microscope cameras, and (4) a laser cutter. The roller-based extruder automatically feeds single CF as raw material. The motion system aligns the CF with the array backend then places it. The imaging system observes the relative position between the CF and the backend. The laser cutter cuts off the CF. Two image processing algorithms are implemented to align the CF with the support shanks and circuit connection pads.Main results.The machine was capable of precisely handling 6.8µm carbon fiber electrodes (CFEs). Each electrode was placed into a 12µm wide trenches in a silicon support shank. Two HDCF arrays with 16 CFEs populated on 3 mm shanks (with 80µm pitch) were fully assembled. Impedance measurements were found to be in good agreement with manual assembled arrays. One HDCF array was implanted in the motor cortex in an anesthetized rat and was able to detect single unit activity.Significance.This machine can eliminate the manual labor-intensive handling, alignment and placement of single CF during assembly, providing a proof-of-concepts towards fully automated HDCF array assembly and batch production.

Combining voltage-sensitive dye, carbon fiber array, and extracellular nerve electrodes using a 3-D printed recording chamber and manipulators.

BACKGROUND: The analyses of neuronal circuits require high-throughput technologies for stimulating and recording many neurons simultaneously with single-neuron precision. Voltage-sensitive dyes (VSDs) have enabled the monitoring of membrane potentials of many (10-100 s) neurons simultaneously. Carbon fiber electrode (CFE) arrays allow for stimulation and recording of many neurons simultaneously, including intracellularly. NEW METHOD: Combining CFE with VSD leverages the advantages of both technologies, allowing for stimulation of single neurons while recording the activity of the entire network. 3-D printing technology was used to develop a chamber to simultaneously perform VSD imaging, CFE array recording, and extracellular recording from individual glass electrodes. RESULTS: Aplysia buccal ganglia were stained with VSD and imaged while also recording using a CFE array and extracellular nerve electrodes. Coincident spiking activity was recorded by VSD, CFE, and extracellular nerve electrodes. Current injection with CFE electrodes could activate and inhibit individual neurons as detected by VSD and nerve recordings. COMPARISON TO EXISTING METHODS: The large size of traditional manipulators limits the number of electrodes used and the number of neurons recorded during an experiment. Here we present a method to build a 3-D printed recording chamber that includes a 3-axis micromanipulator to position a CFE array and eight 2-axis manipulators to position eight extracellular electrodes. CONCLUSIONS: 3-D printing technology can be used to build a custom recording chamber and micromanipulators. Combining these technologies allows for the direct modulation of the activity of neurons while recording the activity of 100 s of neurons simultaneously.

Balancing Memorization and Generalization in RNNs for High Performance Brain-Machine Interfaces.

Brain-machine interfaces (BMIs) can restore motor function to people with paralysis but are currently limited by the accuracy of real-time decoding algorithms. Recurrent neural networks (RNNs) using modern training techniques have shown promise in accurately predicting movements from neural signals but have yet to be rigorously evaluated against other decoding algorithms in a closed-loop setting. Here we compared RNNs to other neural network architectures in real-time, continuous decoding of finger movements using intracortical signals from nonhuman primates. Across one and two finger online tasks, LSTMs (a type of RNN) outperformed convolutional and transformer-based neural networks, averaging 18% higher throughput than the convolution network. On simplified tasks with a reduced movement set, RNN decoders were allowed to memorize movement patterns and matched able-bodied control. Performance gradually dropped as the number of distinct movements increased but did not go below fully continuous decoder performance. Finally, in a two-finger task where one degree-of-freedom had poor input signals, we recovered functional control using RNNs trained to act both like a movement classifier and continuous decoder. Our results suggest that RNNs can enable functional real-time BMI control by learning and generating accurate movement patterns.

Post-explant profiling of subcellular-scale carbon fiber intracortical electrodes and surrounding neurons enables modeling of recorded electrophysiology.

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,X-± 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.

Error detection and correction in intracortical brain-machine interfaces controlling two finger groups.

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.