Neural Microstimulation Research Articles

Development and characterization of a fully flexible stimulation system based on embedded liquid metal channels.

Neuronal stimulation systems design is highly impacted by the overall resolution and adaptability of the device to the targeted application and area to stimulate. In this study is proposed a novel design for neural micro-stimulation electrode presenting high resolution and adaptability to any targeted area via a high flexibility. The use of liquid metal micro-channels encapsulated into a polymer allowed micro-stimulation pads at the tip of the channels. It presented a high degree of patternability to match different possible applications, as well as flexibility and interesting mechanic properties to make it insertable and adaptable in soft tissues. The design, fabrication process, and study of the electrical and mechanical behavior and stability of the device are discussed. Conductive U-shaped micro-channels down to a total diameter of 110 μm could be produced.

Development of a polymer based fully flexible electrode tip for neuronal micro-stimulation applications

Neural stimulation systems design is highly impacted by the overall resolution and adaptability of the device to the targeted application and area to stimulate. In this paper, we report a novel design for neural micro-stimulation electrode presenting high resolution and adaptability to any targeted area via a high flexibility. We propose the use of liquid metal micro-channels encapsulated into a polymer volume, achieving micro-stimulation pads at the tip of the channels. It presents a high degree of patternability to match different possible targeted applications, and good flexibility and mechanic properties to make it insertable and adaptable into soft tissues. A stable fabrication process, including insertion of the liquid alloy into 50 µm half-channels, the necessity of the U-shape to produce functional conductive micro-channels and the mechanical integrity of the device are discussed.

Improved Poly(3,4-Ethylenedioxythiophene) (PEDOT) for Neural Stimulation.

This study compares the stability of three variations of the conductive polymer poly(3,4-ethylenedioxythiophene) or PEDOT for neural micro-stimulation under both in vitro and in vivo conditions. We examined PEDOT films deposited with counter-ions tetrafluoroborate (TFB) and poly(styrenesulfonate) (PSS), and PSS combined with carbon nanotubes (CNTs). For the in vitro stability evaluation, implantable micro-wires were coated with the polymers, placed in a vial containing phosphate buffered saline (PBS) under accelerated aging conditions (60°C), and current pulses were applied. The resulting voltage profile was monitored over time. Following the same polymer deposition protocol, chronic neural micro-probes were modified and implanted in the motor cortex of two rats for the in vivo stability comparison. Similar stimulating current pulses were applied and the output voltage was examined. The electrochemical impedance spectroscopic (EIS) data were also recorded and fit to an equivalent circuit model that incorporates and quantifies the time-dependent polymer degradation and impedance associated with tissue surrounding each micro-electrode site. Both in vitro and in vivo voltage output profiles show relatively stable behavior for the TFB modified micro-electrodes compared to the PSS and CNT: PSS modified ones. EIS modeling demonstrates that the time-dependent increase in the polymeric resistance is roughly similar to the rise in the respective voltage output in vivo and indicates that the polymeric stability and conductivity, rather than the impedance due to the tissue response, is the primary factor determining the output voltage profile. It was also noted that the number of electrodes showing unit activity post-surgery did not decay for TFB as was the case for PSS and CNT: PSS. TFB may be an enabling material for achieving long lasting micro-stimulation and recording.

Microstimulation: Principles, Techniques, and Approaches to Somatosensory Neuroprosthesis.

The power of movement of electrically charged particles has been used to alleviate an array of illnesses and help control some human body parts. Microstimulation, the electrical current-driven excitation of neural elements, is now being aimed at brain-machine interfaces (BMIs), brain-controlled external devices that improve quality of life for people such as those who have lost the ability to use their limbs. This effort is motivated by behavioral experiments that indicate a direct link between microstimulation-induced sensory experience and behavior, pointing to the possibility of optimizing and controlling the outputs of BMIs. Several laboratories have focused on using electrical stimulation to return somatosensory feedback from prosthetic limbs directly to the user's central nervous system. However, the difficulty of the problem has led to limited success thus far, and there is a need for a better understanding of the basic principles of neural microstimulation. This article provides a review of the available literature and some recent work at Downstate Medical Center and Columbia University on microstimulation of the primate and rodent somatosensory (S1) cortex and the ventral posterolateral thalamus. It is aimed at contributing to the existing knowledge base to generate good behavioral responses and effective, BMI-appropriate somatosensory feedback. In general, the threshold for the particular brain tissue in response to current-amplitude has to be determined by rigorous experimentation. For consistently reproducible results, hardware and thresholds for microstimulation have to be specified. In addition, effects on motor functions, including unwanted side effects in response to the microstimulation of brain tissue, must be examined to take the field from bench to bedside.

A flexible user-interface for audiovisual presentation and interactive control in neurobehavioral experiments

A major problem facing behavioral neuroscientists is a lack of unified, vendor-distributed data acquisition systems that allow stimulus presentation and behavioral monitoring while recording neural activity. Numerous systems perform one of these tasks well independently, but to our knowledge, a useful package with a straightforward user interface does not exist. Here we describe the development of a flexible, script-based user interface that enables customization for real-time stimulus presentation, behavioral monitoring and data acquisition. The experimental design can also incorporate neural microstimulation paradigms. We used this interface to deliver multimodal, auditory and visual (images or video) stimuli to a nonhuman primate and acquire single-unit data. Our design is cost-effective and works well with commercially available hardware and software. Our design incorporates a script, providing high-level control of data acquisition via a sequencer running on a digital signal processor to enable behaviorally triggered control of the presentation of visual and auditory stimuli. Our experiments were conducted in combination with eye-tracking hardware. The script, however, is designed to be broadly useful to neuroscientists who may want to deliver stimuli of different modalities using any animal model.

Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2–15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets for sensory neuroprostheses with potential to achieve recruitment of a range of sensory fiber types over multiple months after implantation.

Current approaches to model extracellular electrical neural microstimulation

Nowadays, high-density microelectrode arrays provide unprecedented possibilities to precisely activate spatially well-controlled central nervous system (CNS) areas. However, this requires optimizing stimulating devices, which in turn requires a good understanding of the effects of microstimulation on cells and tissues. In this context, modeling approaches provide flexible ways to predict the outcome of electrical stimulation in terms of CNS activation. In this paper, we present state-of-the-art modeling methods with sufficient details to allow the reader to rapidly build numerical models of neuronal extracellular microstimulation. These include (1) the computation of the electrical potential field created by the stimulation in the tissue, and (2) the response of a target neuron to this field. Two main approaches are described: First we describe the classical hybrid approach that combines the finite element modeling of the potential field with the calculation of the neuron's response in a cable equation framework (compartmentalized neuron models). Then, we present a “whole finite element” approach allowing the simultaneous calculation of the extracellular and intracellular potentials, by representing the neuronal membrane with a thin-film approximation. This approach was previously introduced in the frame of neural recording, but has never been implemented to determine the effect of extracellular stimulation on the neural response at a sub-compartment level. Here, we show on an example that the latter modeling scheme can reveal important sub-compartment behavior of the neural membrane that cannot be resolved using the hybrid approach. The goal of this paper is also to describe in detail the practical implementation of these methods to allow the reader to easily build new models using standard software packages. These modeling paradigms, depending on the situation, should help build more efficient high-density neural prostheses for CNS rehabilitation.

A flexible user-interface for audiovisual presentation and interactive control in neurobehavioral experiments

A major problem facing behavioral neuroscientists is a lack of unified, vendor-distributed data acquisition systems that allow stimulus presentation and behavioral monitoring while recording neural activity. Numerous systems perform one of these tasks well independently, but to our knowledge, a useful package with a straightforward user interface does not exist. Here we describe the development of a flexible, script-based user interface that enables customization for real-time stimulus presentation, behavioral monitoring and data acquisition. The experimental design can also incorporate neural microstimulation paradigms. We used this interface to deliver multimodal, auditory and visual (images or video) stimuli to a nonhuman primate and acquire single-unit data. Our design is cost-effective and works well with commercially available hardware and software. Our design incorporates a script, providing high-level control of data acquisition via a sequencer running on a digital signal processor to enable behaviorally triggered control of the presentation of visual and auditory stimuli. Our experiments were conducted in combination with eye-tracking hardware. The script, however, is designed to be broadly useful to neuroscientists who may want to deliver stimuli of different modalities using any animal model.

A flexible user-interface for audiovisual presentation and interactive control in neurobehavioral experiments

A major problem facing behavioral neuroscientists is a lack of unified, vendor-distributed data acquisition systems that allow stimulus presentation and behavioral monitoring while recording neural activity. Numerous systems perform one of these tasks well independently, but to our knowledge, a useful package with a straightforward user interface does not exist. Here we describe the development of a flexible, script-based user interface that enables customization for real-time stimulus presentation, behavioral monitoring and data acquisition. The experimental design can also incorporate neural microstimulation paradigms. We used this interface to deliver multimodal, auditory and visual (images or video) stimuli to a nonhuman primate and acquire single-unit data. Our design is cost-effective and works well with commercially available hardware and software. Our design incorporates a script, providing high-level control of data acquisition via a sequencer running on a digital signal processor to enable behaviorally triggered control of the presentation of visual and auditory stimuli. Our experiments were conducted in combination with eye-tracking hardware. The script, however, is designed to be broadly useful to neuroscientists who may want to deliver stimuli of different modalities using any animal model.

A flexible user-interface for audiovisual presentation and interactive control in neurobehavioral experiments

A major problem facing behavioral neuroscientists is a lack of unified, vendor-distributed data acquisition systems that allow stimulus presentation and behavioral monitoring while recording neural activity. Numerous systems perform one of these tasks well independently, but to our knowledge, a useful package with a straightforward user interface does not exist. Here we describe the development of a flexible, script-based user interface that enables customization for real-time stimulus presentation, behavioral monitoring and data acquisition. The experimental design can also incorporate neural microstimulation paradigms. We used this interface to deliver multimodal, auditory and visual (images or video) stimuli to a nonhuman primate and acquire single-unit data. Our design is cost-effective and works well with commercially available hardware and software. Our design incorporates a script, providing high-level control of data acquisition via a sequencer running on a digital signal processor to enable behaviorally triggered control of the presentation of visual and auditory stimuli. Our experiments were conducted in combination with eye-tracking hardware. The script, however, is designed to be broadly useful to neuroscientists who may want to deliver stimuli of different modalities using any animal model.

Extracellular Neural Microstimulation May Activate Much Larger Regions than Expected by Simulations: A Combined Experimental and Modeling Study

Electrical stimulation of the central nervous system has been widely used for decades for either fundamental research purposes or clinical treatment applications. Yet, very little is known regarding the spatial extent of an electrical stimulation. If pioneering experimental studies reported that activation threshold currents (TCs) increase with the square of the neuron-to-electrode distance over a few hundreds of microns, there is no evidence that this quadratic law remains valid for larger distances. Moreover, nowadays, numerical simulation approaches have supplanted experimental studies for estimating TCs. However, model predictions have not yet been validated directly with experiments within a common paradigm. Here, we present a direct comparison between experimental determination and modeling prediction of TCs up to distances of several millimeters. First, we combined patch-clamp recording and microelectrode array stimulation in whole embryonic mouse spinal cords to determine TCs. Experimental thresholds did not follow a quadratic law beyond 1 millimeter, but rather tended to remain constant for distances larger than 1 millimeter. We next built a combined finite element – compartment model of the same experimental paradigm to predict TCs. While theoretical TCs closely matched experimental TCs for distances <250 microns, they were highly overestimated for larger distances. This discrepancy remained even after modifications of the finite element model of the potential field, taking into account anisotropic, heterogeneous or dielectric properties of the tissue. In conclusion, these results show that quadratic evolution of TCs does not always hold for large distances between the electrode and the neuron and that classical models may underestimate volumes of tissue activated by electrical stimulation.

Focalizing electrical neural stimulation with penetrating microelectrode arrays: A modeling study

Penetrating neural probes are considered for neuroprosthetic devices to restore sensory or motor functions of the CNS using electrical neural microstimulation. These multielectrode systems require optimal electrode configurations to allow precise and focused tissue activation. Combining a finite element model of the spinal cord and compartmentalized models of both simple and complex neuron morphologies, we evaluated the use of the “ground surface” configuration, which consists in the integration of a conductive layer on the front side of electrode shanks, for the return of the stimulation current. Compared to the classical monopolar and bipolar configurations, this strategy resulted in a focalization of both the potential field and the threshold–distance curves. The improvement in focalization was highest for lowest impedance of the ground surface. Moreover, the gain in focality was highest on the side of the shank opposite to the electrode, so that only the neurons located in front of stimulation electrode were activated. This focalizing strategy will allow the design of new microstimulation paradigms aiming at precisely targeting the CNS with complex spatio-temporal stimulation patterns, which could benefit to future stimulation-based neuroprosthesis.

Feasibility of Neural Stimulation With Floating-Light-Activated Microelectrical Stimulators

Neural microstimulation is becoming a powerful tool for the restoration of impaired functions in the central nervous system. Microelectrode arrays with fine wire interconnects have traditionally been used in the development of these neural prosthetic devices. However, these interconnects are usually the most vulnerable part of the neuroprosthetic implant that can eventually cause the device to fail. In this paper, we investigate the feasibility of floating-light-activated microelectrical stimulators (FLAMES) for wireless neural stimulation. A computer model was developed to simulate the micro stimulators for typical requirements of neural activation in the human white and gray matters. First, the photon densities due to a circular laser beam were simulated in the neural tissue at near-infrared (NIR) wavelengths. Temperature elevation in the tissue was calculated and the laser power was retrospectively adjusted to 325 and 250 mW/cm(2) in the gray and white matters, respectively, to limit ΔT to 0.5 °C. Total device area of the FLAMES increased with all parameters considered but decreased with the output voltage. We conclude that the number of series photodiodes in the device can be used as a free parameter to minimize the device size. The results suggest that floating, optically activated stimulators are feasible at submillimeter sizes for the activation of the brain cortex or the spinal cord.

Microfabrication of new microelectrode arrays equipped with a ground surface configuration for focal neural microstimulation

Extracellular electrical stimulation of the central nervous system has been used empirically for decades, with both fundamental and clinical goals. Currently, microelectrode arrays (MEAs) offer new possibilities for CNS microstimulation, allowing in principle to activate only neurons located in the vicinity of the stimulation sites. To overcome the lack of focality of monopolar stimulations, multipolar approaches are commonly used, multiplying therefore the number of electrodes of the arrays and the complexity of the connection system behind. To overcome these limitations, we developed a ground surface configuration consisting in surrounding all the electrodes with a conductive surface laying over the MEA substrate, and using it for the stimulation current return. We first report the microfabrication of a prototype of MEA equipped with this configuration. We also perform experimental recordings of the potential field induced by microstimulations and confirm the expected increased focality with the ground surface configuration. This will open the way to focal ‘pixel-like’ microstimulation of neural networks using MEAs.

Anodically electrodeposited iridium oxide films microelectrodes for neural microstimulation and recording

An efficient and reliable electrochemical method for preparing electrodeposited iridium oxide film (EIROF) microelectrodes by an anodic electrochemical process is reported. The EIROF microelectrodes exhibited remarkably high safe charge injection ( Q inj) limits of ∼2.6 mC/cm 2 for anodic-first pulses and ∼1.4 mC/cm 2 for cathodic-first pulses, and the electrode impedance at 1 kHz was significantly reduced by ∼92%. The EIROF microelectrodes also exhibited good mechanical and electrochemical stability, as well as an excellent super-Nernstian slope in a broad pH range (1–13). All of these characteristics are greatly desired for neural sensor applications including electrical neural microstimulation, neural signal recording as well as pH monitoring in vivo. Moreover, the electrodepositing method can be facilely incorporated into thin-film technology and Microelectromechanical Systems (MEMS).

Activated iridium oxide films fabricated by asymmetric pulses for electrical neural microstimulation and recording

An efficient and reliable electrochemical method for preparation of activated iridium oxide films (AIROFs) microelectrodes by applying an asymmetric pulse train in Na 2HPO 4 solution was reported. The AIROFs microelectrodes exhibited a very high safe charge injection ( Q inj) limit (∼4.1 mC/cm 2), as well as excellent mechanical and electrochemical stability. Electrode impedance at 1 kHz has been significantly reduced by ∼92%. All of these characteristics are greatly desired for electrical neural microstimulation and recording applications. In addition, the activation method can be easily incorporated into other fabrication processes such as micro electrical mechanical system (MEMS).

A Wideband Frequency-Shift Keying Wireless Link for Inductively Powered Biomedical Implants

A high data-rate frequency-shift keying (FSK) modulation protocol, a wideband inductive link, and three demodulator circuits have been developed with a data-rate-to-carrier-frequency ratio of up to 67%. The primary application of this novel FSK modulation/demodulation technique is to send data to inductively powered wireless biomedical implants at data rates in excess of 1 Mbps, using comparable carrier frequencies. This method can also be used in other applications such as radio-frequency identification tags and contactless smartcards by adding a back telemetry link. The inductive link utilizes a series-parallel inductive-capacitance tank combination on the transmitter side to provide more than 5 MHz of bandwidth. The demodulator circuits detect data bits by directly measuring the duration of each received FSK carrier cycle, as well as derive a constant frequency clock, which is used to sample the data bits. One of the demodulator circuits, digital FSK, occupies 0.29 mm/sup 2/ in the AMI 1.5-/spl mu/m, 2M/2P, standard CMOS process, and consumes 0.38 mW at 5 V. This circuit is simulated up to 4 Mbps, and experimentally tested up to 2.5 Mbps with a bit error rate of 10/sup -5/, while receiving a 5/10-MHz FSK carrier signal. It is also used in a wireless implantable neural microstimulation system.