Peripheral direct current reduces naturally evoked nociceptive activity at the spinal cord in rodent models of pain.

Objective.Electrical neuromodulation is an established non-pharmacological treatment for chronic pain. However, existing devices using pulsatile stimulation typically inhibit pain pathways indirectly and are not suitable for all types of chronic pain. Direct current (DC) stimulation is a recently developed technology which affects small-diameter fibres more strongly than pulsatile stimulation. Since nociceptors are predominantly small-diameter Aδand C fibres, we investigated if this property could be applied to preferentially reduce nociceptive signalling.Approach.We applied a DC waveform to the sciatic nerve in rats of both sexes and recorded multi-unit spinal activity evoked at the hindpaw using various natural stimuli corresponding to different sensory modalities rather than broad-spectrum electrical stimulus. To determine if DC neuromodulation is effective across different types of chronic pain, tests were performed in models of neuropathic and inflammatory pain.Main results.We found that in both pain models tested, DC application reduced responses evoked by noxious stimuli, as well as tactile-evoked responses which we suggest may be involved in allodynia. Different spinal activity of different modalities were reduced in naïve animals compared to the pain models, indicating that physiological changes such as those mediated by disease states could play a larger role than previously thought in determining neuromodulation outcomes.Significance.Our findings support the continued development of DC neuromodulation as a method for reduction of nociceptive signalling, and suggests that it may be effective at treating a broader range of aberrant pain conditions than existing devices.

Galvanic vs. pulsatile effects on decision-making networks: reshaping the neural activation landscape.

Objective. Primarily due to safety concerns, biphasic pulsatile stimulation (PS) is the present standard for electrical excitation of neural tissue with a diverse set of applications. While pulses have been shown to be effective to achieve functional outcomes, they have well-known deficits. Due to recent technical advances, galvanic stimulation (GS), delivery of current for extended periods of time (>1 s), has re-emerged as an alternative to PS.Approach. In this paper, we use a winner-take-all decision-making cortical network model to investigate differences between pulsatile and GS in the context of a perceptual decision-making task.Main results. Based on previous work, we hypothesized that GS would produce more spatiotemporally distributed, network-sensitive neural responses, while PS would produce highly synchronized activation of a limited group of neurons. Our results in-silico support these hypotheses for low-amplitude GS but deviate when galvanic amplitudes are large enough to directly activate or block nearby neurons.Significance. We conclude that with careful parametrization, GS could overcome some limitations of PS to deliver more naturalistic firing patterns in the group of targeted neurons.

The Significance of Concentration-dependent Components in Computational Models of C-Fibers.

Computational models of neurons are valuable tools that allow researchers to form and evaluate hypotheses and minimize high-cost animal work. We soon plan to use computational modeling to explore the response of different sensory fiber types to long duration external stimulation to try to selectively block nociceptive C-fibers. In this work, we modified an existing C-fiber-specific axon model to additionally include concentration-dependent conductance changes, the contribution of longitudinal current flow to changes in local concentrations, and longitudinal currents generated by concentration gradients along the axon. Then, we examined the impact of these additional elements on the modeled action potential properties, activity-dependent latency increases, and concentration changes due to external stimulation. We found that these additional model elements did not significantly affect the action potential properties or activity-dependent behavior, but they did have a significant impact on the modeled response to external long duration stimulation.Clinical Relevance- This presents a computational model that can be used to help investigate and develop electrical stimulation therapies for pathological pain.

Low Cost, Ease-of-Access Fabrication of Microfluidic Devices Using Wet Paper Molds.

Rapid prototyping methods enable the widespread adoption of microfluidic technologies by empowering end-users from non-engineering disciplines to make devices using processes that are rapid, simple and inexpensive. In this work, we developed a liquid molding technique to create silicone/PDMS microfluidic devices by replica molding. To construct a liquid mold, we use inexpensive adhesive-backed paper, an acetate backing sheet, and an off-the-shelf digital cutter to create paper molds, which we then wet with predetermined amounts of water. Due to the immiscibility of water and PDMS, mold patterns can be effectively transferred onto PDMS similarly to solid molds. We demonstrate the feasibility of these wet paper molds for the fabrication of PDMS microfluidic devices and assess the influence of various process parameters on device yield and quality. This method possesses some distinct benefits compared to conventional techniques such as photolithography and 3D printing. First, we demonstrate that the shape of a channel's cross-section may be altered from rectangular to semicircular by merely modifying the wetting parameters. Second, we illustrate how electrical impedance can be utilized as a marker for inspecting mold quality and identifying defects in a non-invasive manner without using visual tools such as microscopes or cameras. As a proof-of-concept device, we created a microfluidic T-junction droplet generator to produce water droplets in mineral oil ranging in size from 1.2 µL to 75 µL. We feel that this technology is an excellent addition to the microfluidic rapid prototyping toolbox and will find several applications in biological research.

Difference in Network Effects of Pulsatile and Galvanic Stimulation.

Biphasic pulsatile stimulation is the present standard for neural prosthetic use, and it is used to understand connectivity and functionality of the brain in brain mapping studies. While pulses have been shown to drive behavioral changes, such as biasing decision making, they have deficits. For example, cochlear implants restore hearing but lack the ability to restore pitch perception. Recent work shows that pulses produce artificial synchrony in networks of neurons and non-linear changes in firing rate with pulse amplitude. Studies also show galvanic stimulation, delivery of current for extended periods of time, produces more naturalistic behavioral responses than pulses. In this paper, we use a winner-take-all decision-making network model to investigate differences between pulsatile and galvanic stimulation at the single neuron and network level while accurately modeling the effects of pulses on neurons for the first time. Results show pulses bias spike timing and make neurons more resistive to natural network inputs than galvanic stimulation at an equivalent current amplitude. Clinical Relevance- This establishes that pulsatile stimulation may disrupt natural spike timing and network-level interactions while certain parameterizations of galvanic stimulation avoid these effects and can drive network firing more naturally.

Ionic transistor using ion exchange membranes.

Ionic transistors can be used to modulate ionic current in a way that is analogous to their electronic counterparts. An ionic transistor can reversibly change its ionic conduction to control ionic current by injecting electrical charges. To facilitate its applications in biomedical devices (e.g., controlled drug delivery, rectification of ionic current, and signal processing), an ionic transistor should maintain high performance of ionic current control within physiological solutions (e.g., 0.9% NaCl) for long durations. Here, we introduce an ionic transistor using cation and anion exchange membranes (CEM and AEM). It could impose a 10× impedance change in a channel filled with 0.9% NaCl solution and we observed a stable modulation of ionic current throughout a test of 1000 cycles of on/off switching of the ionic transistor.

A Hydrogel-Based Microfluidic Nerve Cuff for Neuromodulation of Peripheral Nerves.

Implantable neuromodulation devices typically have metal in contact with soft, ion-conducting nerves. These neural interfaces excite neurons using short-duration electrical pulses. While this approach has been extremely successful for multiple clinical applications, it is limited in delivering long-duration pulses or direct current (DC), even for acute term studies. When the charge injection capacity of electrodes is exceeded, irreversible electrochemical processes occur, and toxic byproducts are discharged directly onto the nerve, causing biological damage. Hydrogel coatings on electrodes improve the overall charge injection limit and provide a mechanically pliable interface. To further extend this idea, we developed a silicone-based nerve cuff lead with a hydrogel microfluidic conduit. It serves as a thin, soft and flexible interconnection and provides a greater spatial separation between metal electrodes and the target nerve. In an in vivo rat model, we used this cuff to stimulate and record from sciatic nerves, with performance comparable to that of metal electrodes. Further, we delivered DC through the lead in an acute manner to induce nerve block that is reversible. In contrast to most metallic cuff electrodes, which need microfabrication equipment, we built this cuff using a consumer-grade digital cutter and a simplified molding process. Overall, the device will be beneficial to neuromodulation researchers as a general-purpose nerve cuff electrode for peripheral neuromodulation experiments.

A Machine Learning-based Neural Implant Front End for Inducing Naturalistic Firing.

Despite being able to restore speech perception with 99% success rate, cochlear implants cannot successfully restore pitch perception or music appreciation. Studies suggest that if auditory neurons were activated with fine timing closer to that of natural responses pitch would be restored. Predicting the timing of cochlear responses requires detailed biophysical models of sound transmission, inner hair cell responses, and outer hair cell responses. Performing these calculations is computationally costly for real time cochlear implant stimulation. Instead, implants typically modulate pulse amplitude of fixed pulse rate stimulation with the band-limited envelopes of incoming sound. This method is known to produce unrealistic responses, even to simple step inputs. Here we investigate using a machine learning algorithm to optimize the prediction of the desired firing patterns of the auditory afferents in response to sinusoidal and step modulation of pure tones. We conclude that a trained network that consists of 25 GRU nodes can reproduce fine timing with 4.4 percent error on a test set of sines and steps. This trained network can also transfer learn and capture features of natural sounds that are not captured by standard CI algorithms. Additionally, for 0.5 second test inputs, the ML algorithm completed the sound to spike rate conversion in 300x less time than the phenomenological model. This calculation occurs at a real-time compatible rate of 1 ms for 1 second of spike timing prediction on an i9 microprocessor. This suggests that this is a feasible approach to pursue for real-time CI implementation.

Direct current effects on afferent and hair cell to elicit natural firing patterns.

In contrast to the conventional pulsatile neuromodulation that excites neurons, galvanic or direct current stimulation can excite, inhibit, or sensitize neurons. The vestibular system presents an excellent system for studying galvanic neural interface due to the spontaneously firing afferent activity that needs to be either suppressed or excited to convey head motion sensation. We determine the cellular mechanisms underlying the beneficial properties of galvanic vestibular stimulation (GVS) by creating a computational model of the vestibular end organ that elicits all experimentally observed response characteristics to GVS simultaneously. When GVS was modeled to affect the axon alone, the complete experimental data could not be replicated. We found that if GVS affects hair cell vesicle release and axonal excitability simultaneously, our modeling results matched all experimental observations. We conclude that contrary to the conventional belief that GVS affects only axons, the hair cells are likely also affected by this stimulation paradigm.

Predicting Response of Spontaneously Firing Afferents to Prosthetic Pulsatile Stimulation.

Pulsatile electrical stimulation is used in neural prostheses such as the vestibular prosthesis. In a healthy vestibular system, head motion is encoded by changes in the firing rates of afferents around their spontaneous baseline rate. For people suffering from bilateral vestibular disorder (BVD), head motion no longer modulates firing rate. Vestibular prostheses use a gyroscope to detect head motion and stimulate neurons directly in a way that mimics natural modulation. Proper restoration of vestibular function relies on the ability of stimulation to evoke the same firing patterns as the healthy system. For this reason, it is necessary to understand what firing rates are produced for different stimulation parameters. Two stimulation parameters commonly controlled in pulsatile neuromodulation are pulse rate and pulse amplitude. Previous neural recording experiments in the vestibular nerve contradict widely held assumptions about the relationship between pulse rates and evoked spike activity, and the relationship between pulse amplitude and neural activity has not been explored. Here we use a well-established computational model of the vestibular afferent to simulate responses to different pulse rates and amplitudes. We confirm that our simulated neural results agree with the existing experimental data. Finally, we developed the "Action Potential Collision" (APC) equation that defines induced firing as a function of spontaneous firing rate, pulse rate, and pulse amplitude. We show that this relationship can successfully predict simulated vestibular activity by accounting for interactions between pulses and spontaneous firing.

Ionic direct current modulation evokes spike-rate adaptation in the vestibular periphery.

Recent studies have shown that ionic direct current (iDC) can modulate the vestibular system in-vivo, with potential benefits over conventional pulsed stimulation. In this study, the effects of iDC stimulation on vestibular nerve fiber firing rate was investigated using loose-patch nerve fiber recordings in the acutely excised mouse crista ampullaris of the semicircular canals. Cathodic and anodic iDC steps instantaneously reduced and increased afferent spike rate, with the polarity of this effect dependent on the position of the stimulating electrode. A sustained constant anodic or cathodic current resulted in an adaptation to the stimulus and a return to spontaneous spike rate. Post-adaptation spike rate responses to iDC steps were similar to pre-adaptation controls. At high intensities spike rate response sensitivities were modified by the presence of an adaptation step. Benefits previously observed in behavioral responses to iDC steps delivered after sustained current may be due to post-adaptation changes in afferent sensitivity. These results contribute to an understanding of peripheral spike rate relationships for iDC vestibular stimulation and validate an ex-vivo model for future investigation of cellular mechanisms. In conjunction with previous in-vivo studies, these data help to characterize iDC stimulation as a potential therapy to restore vestibular function after bilateral vestibulopathy.

Continuous vestibular implant stimulation partially restores eye-stabilizing reflexes.

BACKGROUNDBilateral loss of vestibular (inner ear inertial) sensation causes chronically blurred vision during head movement, postural instability, and increased fall risk. Individuals who fail to compensate despite rehabilitation therapy have no adequate treatment options. Analogous to hearing restoration via cochlear implants, prosthetic electrical stimulation of vestibular nerve branches to encode head motion has garnered interest as a potential treatment, but prior studies in humans have not included continuous long-term stimulation or 3D binocular vestibulo-ocular reflex (VOR) oculography, without which one cannot determine whether an implant selectively stimulates the implanted ear's 3 semicircular canals.METHODSWe report binocular 3D VOR responses of 4 human subjects with ototoxic bilateral vestibular loss unilaterally implanted with a Labyrinth Devices Multichannel Vestibular Implant System vestibular implant, which provides continuous, long-term, motion-modulated prosthetic stimulation via electrodes in 3 semicircular canals.RESULTSInitiation of prosthetic stimulation evoked nystagmus that decayed within 30 minutes. Stimulation targeting 1 canal produced 3D VOR responses approximately aligned with that canal's anatomic axis. Targeting multiple canals yielded responses aligned with a vector sum of individual responses. Over 350-812 days of continuous 24 h/d use, modulated electrical stimulation produced stable VOR responses that grew with stimulus intensity and aligned approximately with any specified 3D head rotation axis.CONCLUSIONThese results demonstrate that a vestibular implant can selectively, continuously, and chronically provide artificial sensory input to all 3 implanted semicircular canals in individuals disabled by bilateral vestibular loss, driving reflexive VOR eye movements that approximately align in 3D with the head motion axis encoded by the implant.TRIAL REGISTRATIONClinicalTrials.gov: NCT02725463.FUNDINGNIH/National Institute on Deafness and Other Communication Disorders: R01DC013536 and 2T32DC000023; Labyrinth Devices, LLC; and Med-El GmbH.

Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy.

Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.

Ionic Direct Current Modulation for Combined Inhibition/Excitation of the Vestibular System.

OBJECTIVE: Prosthetic electrical stimulation delivered to the vestibular nerve could provide therapy for people suffering from bilateral vestibular dysfunction. Common encoding methods use pulse-frequency modulation (PFM) to stimulate the semicircular canals of the vestibular system. We previously showed that delivery of ionic direct current (iDC) can also modulate the vestibular system. In this study, we compare the dynamic range of head velocity encoding from iDC modulation to that of PFM controls. METHODS: Gentamicin-treated wild-type chinchillas were implanted with microcatheter tubes that delivered ionic current to the left ear vestibular canals and stimulated with steps of anodic/cathodic iDC or PFM. Evoked vestibulo-ocular reflex eye velocity was used to compare PFM and iDC vestibular modulation. RESULTS: Cathodic iDC steps effectively elicited eye rotations consistent with an increased firing rate of the implanted semicircular canal afferents. Anodic iDC current steps elicited eye rotations in the opposite direction that, when paired with an adapted cathodic offset, increased the dynamic range of eye rotation velocities in comparison to PFM controls. CONCLUSION: Our results suggest that iDC modulation can effectively modulate the vestibular system across a functional range of rotation vectors and velocities, with a potential benefit over a PFM stimulation paradigm. SIGNIFICANCE: In conjunction with a safe dc delivery system, iDC modulation could potentially increase the range of simulated head rotation velocities available to neuroelectric vestibular prostheses.

Wireless control of cellular function by activation of a novel protein responsive to electromagnetic fields.

The Kryptopterus bicirrhis (glass catfish) is known to respond to electromagnetic fields (EMF). Here we tested its avoidance behavior in response to static and alternating magnetic fields stimulation. Using expression cloning we identified an electromagnetic perceptive gene (EPG) from the K. bicirrhis encoding a protein that responds to EMF. This EPG gene was cloned and expressed in mammalian cells, neuronal cultures and in rat's brain. Immunohistochemistry showed that the expression of EPG is confined to the mammalian cell membrane. Calcium imaging in mammalian cells and cultured neurons expressing EPG demonstrated that remote activation by EMF significantly increases intracellular calcium concentrations, indicative of cellular excitability. Moreover, wireless magnetic activation of EPG in rat motor cortex induced motor evoked responses of the contralateral forelimb in vivo. Here we report on the development of a new technology for remote, non-invasive modulation of cell function.

Usefulness of a Noninvasive Device to Identify Elevated Left Ventricular Filling Pressure Using Finger Photoplethysmography During a Valsalva Maneuver.

The high rate of re-hospitalization for heart failure might be reduced by improving noninvasive techniques for identifying elevated left ventricular (LV) filling pressure. We previously showed that changes in a finger photoplethysmography (PPG) waveform during the Valsalva maneuver (VM) reflect invasively measured LV end-diastolic pressure (LVEDP). We have since developed a hand-held device that analyzes PPG while guiding the expiratory effort of a VM. Here we assessed the sensitivity and specificity of this device for identifying elevated LVEDP in patients. We tested 82 participants (28 women), aged 40 to 85 years, before a clinically indicated left heart catheterization. Each performed a VM between 18 and 25 mm Hg for 10 seconds into a pressure transducer. PPG was recorded continuously before and during the VM. LVEDP was measured during the catheterization. An equation for calculating LVEDP was derived using (1) ratio of signal amplitudes: minimum during VM to average at baseline, (2) ratio of peak-to-peak time intervals: minimum during VM to average at baseline, and (3) mean blood pressure. Calculated and measured LVEDP were compared. The range of measured LVEDP was 4 to 35 mm Hg. Calculated LVEDP correlated with measured LVEDP (p <0.0001, r = 0.56). A calculated LVEDP >20 mm Hg had a 70% sensitivity and 86% specificity for identifying measured LVEDP >20 mm Hg (area under receiver-operating characteristic curve 0.83). In conclusion, a hand-held device for assessing LV filling pressure had high specificity and good sensitivity for identifying LVEDP >20 mm Hg, a clinically meaningful threshold in heart failure.

A CMOS Neural Interface for a Multichannel Vestibular Prosthesis.

We present a high-voltage CMOS neural-interface chip for a multichannel vestibular prosthesis (MVP) that measures head motion and modulates vestibular nerve activity to restore vision- and posture-stabilizing reflexes. This application specific integrated circuit neural interface (ASIC-NI) chip was designed to work with a commercially available microcontroller, which controls the ASIC-NI via a fast parallel interface to deliver biphasic stimulation pulses with 9-bit programmable current amplitude via 16 stimulation channels. The chip was fabricated in the ONSemi C5 0.5 micron, high-voltage CMOS process and can accommodate compliance voltages up to 12 V, stimulating vestibular nerve branches using biphasic current pulses up to 1.45±0.06 mA with durations as short as 10 µs/phase. The ASIC-NI includes a dedicated digital-to-analog converter for each channel, enabling it to perform complex multipolar stimulation. The ASIC-NI replaces discrete components that cover nearly half of the 2nd generation MVP (MVP2) printed circuit board, reducing the MVP system size by 48% and power consumption by 17%. Physiological tests of the ASIC-based MVP system (MVP2A) in a rhesus monkey produced reflexive eye movement responses to prosthetic stimulation similar to those observed when using the MVP2. Sinusoidal modulation of stimulus pulse rate from 68-130 pulses per second at frequencies from 0.1 to 5 Hz elicited appropriately-directed slow phase eye velocities ranging in amplitude from 1.9-16.7 °/s for the MVP2 and 2.0-14.2 °/s for the MVP2A. The eye velocities evoked by MVP2 and MVP2A showed no significant difference ( t-test, p=0.34), suggesting that the MVP2A achieves performance at least as good as the larger MVP2.

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models.

Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp2(-/y) and Shank3B(-/-) lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive self-grooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques.

MouthLab: A Tricorder Concept Optimized for Rapid Medical Assessment.

The goal of rapid medical assessment (RMA) is to estimate the general health of a patient during an emergency room or a doctor's office visit, or even while the patient is at home. Currently the devices used during RMA are typically "all-in-one" vital signs monitors. They require time, effort and expertise to attach various sensors to the body. A device optimized for RMA should instead require little effort or expertise to operate and be able to rapidly obtain and consolidate as much information as possible. MouthLab is a battery powered hand-held device intended to acquire and evaluate many measurements such as non-invasive blood sugar, saliva and respiratory biochemistry. Our initial prototype acquires standard vital signs: pulse rate (PR), breathing rate (BR), temperature (T), blood oxygen saturation (SpO2), blood pressure (BP), and a three-lead electrocardiogram. In our clinical study we tested the device performance against the measurements obtained with a standard patient monitor. 52 people participated in the study. The measurement errors were as follows: PR: -1.7 ± 3.5 BPM, BR: 0.4 ± 2.4 BPM, T: -0.4 ± 1.24 °F, SpO2: -0.6 ± 1.7%. BP systolic: -1.8 ± 12 mmHg, BP diastolic: 0.6 ± 8 mmHg. We have shown that RMA can be easily performed non-invasively by patients with no prior training.

Safe direct current stimulator 2: concept and design.

Essentially all neuroprostheses use alternating biphasic current pulses to stimulate neural tissue. While this method can effectively excite neurons, it is not very effective for inhibiting them. In contrast, direct current (DC) can excite, inhibit, and modulate sensitivity of neurons. However, DC stimulation is biologically unsafe because it violates safe charge injection criteria. We have previously described the concept of a safe direct current stimulator (SDCS) that overcomes this constraint. The SDCS drives DC ionic current into the tissue by switching fluid valves in phase with biphasic current pulses delivered to the metal electrodes within the device. The original prototype of this device, SDCS1, could both suppress and excite the vestibular nerve with DC stimulation delivered by the device. In the process of building the SDCS1 we identified several problems that must be addressed to further develop this technology. Consequently, we designed the SDCS2, which eliminates periodic interruptions in stimulation current flow observed in the original SDCS1 design and is small enough for head-mounted use in chronic animal studies.