While recent advances in intracortical brain-computer interfaces (iBCI) have demonstrated the ability to restore motor and communication functions, such demonstrations have generally been confined to controlled experimental settings and have required bulky laboratory hardware. Here, we developed and evaluated a self-contained portable iBCI that enabled the user to interact with various computer programs. The iBCI, which weighs 1.5 kg, consists of digital headstages, a small signal processing hub, and a tablet PC. A human participant tested the portable iBCI in laboratory and home settings under an FDA Investigational Device Exemption (NCT01894802). The participant successfully completed 96% of trials in a 2D cursor center-out task with the portable iBCI, a rate indistinguishable from that achieved with the standard laboratory iBCI. The participant also completed a variety of free-form tasks, including drawing, gaming, and typing.

Objective: Individuals with paralysis often have mobility and dexterity impairments that limit their ability to operate motor vehicle controls. Integrating brain-machine interface (BMI) neurotechnology with vehicle control systems (VCS) provides a novel solution to this problem. In this proof-of-concept study, we show that an intracortical BMI developed to restore voluntary grasp can be repurposed to decode motor intention for vehicle velocity and steering control. Methods: The BMI-VCS consists of four components: 1) implanted motor cortex microelectrode array and NeuroPort data acquisition system, 2) machine learning workstation, 3) Python interface to generate control signals, and 4) vehicle control system. Results: Direct cortical steering and velocity control were achieved through accurate decoding of movement intention (supination, pronation, hand open, hand close) from the participant's motor cortex, translating intention into vehicle commands (turn right, turn left, accelerate, decelerate, respectively), and dynamically switching between commands to turn corners, start and stop, shift from forward to reverse, and parallel park. Conclusion: By translating BMI decoder outputs into high-level vehicle commands, a participant with tetraparesis from C5 ASIA A spinal cord injury successfully navigated CARLA driving simulator courses in real time. These decoder outputs could also be used offline for shared control of a scale model car. Significance: High-level, shared vehicle control with BMI-VCS offers an innovative way to return independent driving abilities to those with disability. BMI systems that can control multiple end-effectors may be particularly useful to those with paralysis.

The Utah electrode array (UEA) and its many derivatives have become a gold standard for high-channel count bi-directional neural interfaces, in particular in human subject applications. The chapter provides a brief overview of leading electrode concepts and the context in which the UEA has to be understood. It goes on to discuss the key advances and developments of the UEA platform in the past 15 years, as well as novel wireless and system integration technologies that will merge into future generations of fully integrated devices. Aspects covered include novel device architectures that allow scaling of channel count and density of electrode contacts, material improvements to substrate, electrode contacts, and encapsulation. Further subjects are adaptations of the UEA platform to support IR and optogenetic simulation as well as an improved understanding of failure modes and methods to test and accelerate degradation in vitro such as to better predict device failure and lifetime in vivo.

Objective. Intracortical microstimulation has shown promise as a means of evoking somatosensory percepts as part of a bidirectional brain-computer interface (BCD. However, microstimulation generates large electrical artifacts that dominate the recordings necessary for BCI control. These artifacts must be eliminated from the signal in real-time to allow for uninterrupted BCI decoding. Approach. We present a simple, robust modification to an existing clinical BCI system to allow for simultaneous recording and stimulation using a combination of signal blanking and digital filtering, without needing to explicitly account for varying parameters such as electrode locations or amplitudes. We validated our artifact rejection scheme by recording from microelectrodes in primary motor cortex (M1) while stimulating in somatosensory cortex of a person with a spinal cord injury. Main results. M1 recordings were digitally blanked using a sample-and-hold circuit triggered just prior to stimulus onset and a first-order 750 Hz high-pass Butterworth filter was used to reduce distortion of the remaining artifact. This scheme enabled spike detection in M1 to resume as soon as 740 mu s after each stimulus pulse. We demonstrated the effectiveness of the complete bidirectional BCI system by comparing functional performance during a 5 degree of freedom robotic arm control task, with and without stimulation. When stimulation was delivered without this artifact rejection scheme, the number of objects the subject was able to move across a table in 2 min under BCI control declined significantly compared to trials without stimulation (p < 0.01). When artifact rejection was implemented, performance was no different than in trials that did not include stimulation (p = 0.621). Significance. The proposed technique uses simple changes in filtering and digital signal blanking with FDA-cleared hardware and enables artifact-free recordings during bidirectional BCI control.

In recent years, chemical sensing microsystems have become the de facto standard for many day-to-day tests performed both in laboratory settings and in the field. A few examples of how these types of microsystems are used today are the monitoring of biological fluids for illicit drugs in the workplace, point of care clinical testing, and the monitoring of toxic substance levels in industrial effluents. This chapter describes the principles of action and fabrication techniques for electrochemical sensors designed to monitor liquid-phase chemicals. The chapter begins with an introduction to electrochemical theory that describes the foundational electrochemical equations, the methods of electrochemical transduction, and the principal components of an electrochemical cell. The chapter next describes two electrochemical transduction techniques, potentiometry, and voltammetry. Descriptions of the most common measurement methods for sensors based on these two techniques and sample fabrication flows for each type of sensor are presented, as well as a comparison of the two techniques. The remainder of the chapter describes the integration of chemical sensors and electronics, and packaging considerations for liquid-phase chemical sensors.

Objective. Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications. Approach. To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency-shift key-modulated signal at 5.7-5.8 GHz to a receiver up to 10m away. The system is powered by two CR123A, 3 V batteries for 2 h of operation. Main results. We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely moving animals can capture phenomena that are absent in the traditional head-fixed paradigm. Significance. We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates, which can potentially move systems neuroscience to a new direction by allowing one to record neural signals while animals interact with their environment.

We have designed, fabricated, and tested an advanced neural interface based on the Utah Electrode Array (UEA) integrated with a custom ASIC that is currently able to acquire 200 channels of neural recordings. The Active Arrays are designed to acquire more neural data with the goal of controlling advanced prosthetic devices with as many as 17 degrees of freedom (DoF). The system is comprised of two modified UEAs, a custom ASIC, SMD capacitors, a Neu- roport™ (Blackrock Microsystems) percutaneous connector, 44 wires, and encapsulation materials. A photograph of the final device is presented in Fig. 1. The device has been tested in-vitro through soak testing in 0.15M PBS with synthetic neural signals applied to measure lifetime and recording fidelity. In-vivo measurements were collected using non-human primate (NHP) models.

Several methods for the manufacturing of Iridium Oxide (IrOx) electrodes have been discussed in the literature. Two commonly used fabrication methods are Sputtered Iridium Oxide Films (SIROF) and Activated Iridium Oxide Films (AIROF). Most of the studies for in vivo electrodes have reported optimizations to these methods in the context of stimulation of and recording from neural tissue. In this work we characterize three fabrication methods of IrOx films for use as reference electrodes during in vivo neurochemical recordings, and we conclude that AIROF electrodes are preferable as reference electrodes due to their superior open circuit potential (OCP) stability.

Implantable microfabricated microelectrode arrays represent a versatile and powerful tool to record electrophysiological activity across multiple spatial locations in the brain. Spikes and field potentials, however, correspond to only a fraction of the physiological information available at the neural interface. In urethane-anesthetized rats, microfabricated microelectrode arrays were implanted acutely for simultaneous recording of striatal local field potentials, spikes, and electrically evoked dopamine overflow on the same spatiotemporal scale. During these multi-modal recordings we observed (1) that the amperometric method used to detect dopamine did not significantly influence electrophysiological activity, (2) that electrical stimulation in the medial forebrain bundle (MFB) region resulted in electrochemically transduced dopamine transients in the striatum that were spatially heterogeneous within at least 200μm, and (3) following MFB stimulation, dopamine levels and electrophysiological activity within the striatum exhibited similar temporal profiles. These neural probes are capable of incorporating customized microelectrode geometries and configurations, which may be useful for examining specific spatiotemporal relationships between electrical and chemical signaling in the brain.

We report for the first time a micromachined, silicon neural probe with an integrated iridium oxide (IrO) quasi reference electrode for neurochemical recordings. The probes have a 1.5 times 103 mum2 IrO reference electrode, a 1.5 times 103 mum2 Pt counter electrode, three circular Pt working electrodes, and three circular IrO electrodes for electrical recording. Several different electrode sizes (4 to 50 mum radius) were fabricated in order to study the effects of electrode size. In vitro evaluation of the probes demonstrated close correlation between results obtained using a Ag/AgCl reference electrode and the on-chip IrOx reference electrode

Electrochemical sensing with microelectrode arrays provides a means for monitoring neurotransmitter dynamics across multiple locations within a micro-scale region of brain tissue. Here we present a multi-modal neural probe design for concurrent recording of neurochemical and electrophysiological signals in vivo. Prior to implantation, platinum sites on each array underwent platinum-black electroplating and Nafion electropolymerization, which increased sensitivity to dopamine by 74% and decreased sensitivity to common interferents by at least 89%. In a series of three rats, we applied various electrochemical waveforms to platinum sites and monitored neural activity on adjacent iridium sites. We found that chronoamperometry and constant-potential amperometry did not alter firing rates at +0.25, +0.50, and +0.75 V. In addition, we have demonstrated multi-modal recordings of striatal neurons in response to medial forebrain bundle stimulation