Programmable Stimulator Research Articles

An innovative electrical neurostimulation approach to mimic reflexive urination control in spinal cord injury models

Neurogenic lower urinary tract dysfunction (NLUTD) is a frequent consequence of spinal cord injury (SCI), leading to symptoms that significantly impact quality of life. Although many life-saving techniques are available, current treatment strategies for managing NLUTD still exhibit limitations and drawbacks. Here, we introduce a new electrical neuromodulation strategy involving electrical stimulation of the major pelvic ganglion (MPG) to initiate bladder contraction, in conjunction with innovative programmable (IPG) electrical stimulation on the pudendal nerve (PN) to induce external urethral sphincter (EUS) relaxation in freely moving or anesthetized SCI mice. Furthermore, we conducted the void spot assay, and cystometry coupled with EUS electromyography (EMG) recordings to evaluate voiding function, and monitor bladder pressure and EUS activity. Our findings demonstrate that our novel electrical neuromodulation approach effectively triggers coordinated bladder muscle contraction and EUS relaxation, effectively counteracting SCI-induced NLUTD. Additionally, this electrical neuromodulation method enhances voiding efficiency, closely resembling natural reflexive urination in SCI mice. Thus, our study offers a promising electrical neurostimulation approach aimed at restoring physiological coordination and potentially offering personalized treatment for improving voiding efficiency in individuals with SCI-associated NLUTD.

Magnetoelectrics for Implantable Bioelectronics: Progress to Date.

ConspectusThe coupling of magnetic and electric properties manifested in magnetoelectric (ME) materials has unlocked numerous possibilities for advancing technologies like energy harvesting, memory devices, and medical technologies. Due to this unique coupling, the magnetic properties of these materials can be tuned by an electric field; conversely, their electric polarization can be manipulated through a magnetic field.Over the past seven years, our lab work has focused on leveraging these materials to engineer implantable bioelectronics for various neuromodulation applications. One of the main challenges for bioelectronics is to design miniaturized solutions that can be delivered with minimally invasive procedures and yet can receive sufficient power to directly stimulate tissue or power electronics to perform functions like communication and sensing.Magnetoelectric coupling in ME materials is strongest when the driving field matches a mechanical resonant mode. However, miniaturized ME transducers typically have resonance frequencies >100 kHz, which is too high for direct neuromodulation as neurons only respond to low frequencies (typically <1 kHz). We discuss two approaches that have been proposed to overcome this frequency mismatch: operating off-resonance and rectification. The off-resonance approach is most common for magnetoelectric nanoparticles (MENPs) that typically have resonance frequencies in the gigahertz range. In vivo experiments on rat models have shown that MENPs could induce changes in neural activity upon excitation with <200 Hz magnetic fields. However, the neural response has latencies of several seconds due to the weak coupling in the off-resonance regime.To stimulate neural responses with millisecond precision, we developed methods to rectify the ME response so that we could drive the materials at their resonant frequency but still produce the slowly varying voltages needed for direct neural stimulation. The first version of the stimulator combined a ME transducer and analog electronics for rectification. To create even smaller solutions, we introduced the first magnetoelectric metamaterial (MNM) that exhibits self-rectification. Both designs have effectively induced neural modulation in rat models with less than 5 ms latency.Based on our experience with in vivo testing of the rectified ME stimulators, we found it challenging to deliver the precisely controlled therapy required for clinical applications, given the ME transducer's sensitivity to the external transmitter alignment. To overcome this challenge, we developed the ME-BIT (MagnetoElectric BioImplanT), a digitally programmable stimulator that receives wireless power and data through the ME link.We further expanded the utility of this technology to neuromodulation applications that require high stimulation thresholds by introducing the DOT (Digitally programmable Overbrain Therapeutic). The DOT has voltage compliance up to 14.5 V. We have demonstrated the efficacy of these designs through various in vivo studies for applications like peripheral nerve stimulation and epidural cortical stimulation.To further improve these systems to be adaptive and enable a network of coordinated devices, we developed a bidirectional communication system to transmit data to and from the implant. To enable even greater miniaturization, we developed a way to use the same ME transducer for wireless power and data communication by developing the first ME backscatter communication protocol.

Selective activation of photoactivatable fluorescent protein based on binary holography

The ability to deliver laser doses to different target locations with high spatial and temporal resolution has been a long-sought goal in photo-stimulation and optogenetics research via, for example, photoactivatable proteins. These light-sensitive proteins undergo conformational changes upon photoactivation, serving functions such as triggering fluorescence, modulating ion channel activities, or initiating biochemical reactions within cells. Conventionally, photo-stimulation on light-sensitive proteins is performed by serially scanning a laser focus or via 2D projection, which is limited by relatively low spatiotemporal resolution. In this work, we present a programmable two-photon stimulation method based on a digital micromirror device (DMD) and binary holography to perform the activation of photoactivatable green fluorescent protein (PAGFP) in live cells. This method achieved grayscale and 3D selective PAGFP activation with subcellular resolution. In the experiments, we demonstrated the 3D activation capability and investigated the diffusion dynamics of activated PAGFP on the cell membrane. A regional difference in cell membrane diffusivity was observed, indicating the great potential of our approach in interrogating the spatiotemporal dynamics of cellular processes inside living cells.

Miniature battery-free epidural cortical stimulators.

Miniaturized neuromodulation systems could improve the safety and reduce the invasiveness of bioelectronic neuromodulation. However, as implantable bioelectronic devices are made smaller, it becomes difficult to store enough power for long-term operation in batteries. Here, we present a battery-free epidural cortical stimulator that is only 9 millimeters in width yet can safely receive enough wireless power using magnetoelectric antennas to deliver 14.5-volt stimulation bursts, which enables it to stimulate cortical activity on-demand through the dura. The device has digitally programmable stimulation output and centimeter-scale alignment tolerances when powered by an external transmitter. We demonstrate that this device has enough power and reliability for real-world operation by showing acute motor cortex activation in human patients and reliable chronic motor cortex activation for 30 days in a porcine model. This platform opens the possibility of simple surgical procedures for precise neuromodulation.

Ultra-low frequency magnetic energy focusing for highly effective wireless powering of deep-tissue implantable electronic devices.

The limited lifespan of batteries is a challenge in the application of implantable electronic devices. Existing wireless power technologies such as ultrasound, near-infrared light and magnetic fields cannot charge devices implanted in deep tissues, resulting in energy attenuation through tissues and thermal generation. Herein, an ultra-low frequency magnetic energy focusing (ULFMEF) methodology was developed for the highly effective wireless powering of deep-tissue implantable devices. A portable transmitter was used to output the low-frequency magnetic field (<50Hz), which remotely drives the synchronous rotation of a magnetic core integrated within the pellet-like implantable device, generating an internal rotating magnetic field to induce wireless electricity on the coupled coils of the device. The ULFMEF can achieve energy transfer across thick tissues (up to 20cm) with excellent transferred power (4-15mW) and non-heat effects in tissues, which is remarkably superior to existing wireless powering technologies. The ULFMEF is demonstrated to wirelessly power implantable micro-LED devices for optogenetic neuromodulation, and wirelessly charged an implantable battery for programmable electrical stimulation on the sciatic nerve. It also bypassed thick and tough protective shells to power the implanted devices. The ULFMEF thus offers a highly advanced methodology for the generation of wireless powered biodevices.

Research on Tremor Suppression Strategies Under a Constant Current Peripheral Electrical Stimulation Device for Parkinson's Disease.

Tremor, a prevalent symptom in Parkinson's patients, is conventionally treated with medications and craniotomy. However, the associated side effects and high surgical costs pose challenges for some individuals. In this study, a lightweight constant current electrical stimulator was developed, which is driven by the FPGA to control the underlying logic and has multiple programmable stimulation parameters. Clinical experiments involving patients with Parkinson's-related resting tremor symptoms were conducted to assess the efficacy of peripheral electrical stimulation. Two Co-contraction Avoidance Stimulation (CAS) strategies targeting nerves and muscles were proposed to reduce tremors. Four Parkinson's disease (PD) patients were recruited to verify the effectiveness of these strategies. Kinematic data recorded by inertial sensors showed that the radial nerve and muscle intervention strategies reduced the average angular velocity amplitude of finger joints during resting tremor by 75.92% and 82.41%, respectively. Notably, under low-frequency pulse stimulation (100 Hz) focused on muscle interference, a low-intensity current of no more than 8 mA maintained a tremor suppression rate of 59.91% even 5 minutes post-stimulation. Based on the experimental results, it is concluded that the constant current electrical stimulator developed in this study can effectively suppress tremor under specific stimulation strategies. These findings have significant implications for the development of lightweight, wearable tremor suppression devices. The stimulator's adaptability, coupled with its precise control parameters, demonstrates promise for advancing non-invasive and cost-effective tremor management in Parkinson's patients.

837 Responsive Neurostimulation of the Thalamus for the Treatment of Refractory Epilepsy

INTRODUCTION: One-third of patients with epilepsy experience seizures despite antiepileptic medications. Some of these refractory patients may not be candidates for surgical resection. The Responsive Neurostimulation System (RNS) is a closed-loop device that uses programmable detection and stimulation. METHODS: We performed a prospective single-center study of consecutive refractory epilepsy patients who underwent RNS system implantation in the anterior (ANT) and centromedian (CM) thalamic nuclei from September 2015 to December 2020. Patients were followed postoperatively to evaluate seizure freedom and complications. RESULTS: Twenty-three patients underwent placement of 36 RNS thalamic leads (CM = 27 leads, ANT = 9 leads). Mean age at implant was 18.8 ± 11.2 years. Two patients (8.7%) developed infections: 1 improved with antibiotic treatments alone, and 1 required removal with eventual replacement of the system. Mean follow-up was 22.3 months. Based on overall reduction of seizure frequency, 2 patients (8.7%) had no- to &lt;25% improvement, 6 patients (26.1%) had 25-49% improvement, 14 patients (60.9%) had 50-99% improvement, and 1 patient (4.3%) became seizure-free. All patients reported significant improvement in seizure duration and severity, and 17 patients (74%) reported improved post-ictal state. There was a trend for subjects with foci located in the temporal lobe to achieve better outcomes after thalamic RNS compared to those with extratemporal foci. Seizure etiology was syndromic in 12 cases (52.2%). CONCLUSIONS: Thalamic RNS achieved ≥50% seizure control in ∼65% of patients. Infections were the most common complication. This therapeutic modality may be particularly useful for patients affected by aggressive epilepsy syndromes since a young age, those whose seizure foci are located in the mesial temporal lobe, and those who have failed prior surgical interventions.

Remotely Programmable Deep Brain Stimulator Combined with an Invasive Blood Pressure Monitoring System for a Non-Tethered Rat Model in Hypertension Research.

The control circuits of blood pressure have a strong neural regulatory element important in the pathogenesis of essential drug-resistant hypertension. Targeting lower medullary neural control mechanisms of blood pressure by electrical stimulation could be beneficial, and therefore, a novel device is needed. This paper presents a remotely programmable deep brain stimulator with an invasive continuous blood pressure monitoring system in a non-tethered rat model. The device is designed for lower medullary deep brain stimulation research with minimal interference to a daily animal routine. Electrodes were implanted in the caudal ventrolateral medulla. Animal survivability, catheter patency rates, and device data drift were evaluated. Eight out of ten rats survived the surgery and testing period with no or mild temporary neurological compromise. The study revealed that carotid catheters filled with heparinized glycerol ensure better catheter patency rates and blood pressure transduction. There was no significant drift in the device's pressure sensitivity during the experiment. To our knowledge, this is the first experimental study to show considerable animal survival after lower medullary implantation. Combining the ability to measure and monitor invasive blood pressure with a closed-loop brain pulse generator in a single device could be of potential value in future hemodynamic animal research.

Benchtop and bedside validation of a low-cost programmable cortical stimulator in a testbed for bi-directional brain-computer-interface research.

Bi-directional brain-computer interfaces (BD-BCI) to restore movement and sensation must achieve concurrent operation of recording and decoding of motor commands from the brain and stimulating the brain with somatosensory feedback. A custom programmable direct cortical stimulator (DCS) capable of eliciting artificial sensorimotor response was integrated into an embedded BCI system to form a safe, independent, wireless, and battery powered testbed to explore BD-BCI concepts at a low cost. The BD-BCI stimulator output was tested in phantom brain tissue by assessing its ability to deliver electrical stimulation equivalent to an FDA-approved commercial electrical cortical stimulator. Subsequently, the stimulator was tested in an epilepsy patient with subcortical electrocorticographic (ECoG) implants covering the sensorimotor cortex to assess its ability to elicit equivalent responses as the FDA-approved counterpart. Additional safety features (impedance monitoring, artifact mitigation, and passive and active charge balancing mechanisms) were also implemeneted and tested in phantom brain tissue. Finally, concurrent operation with interleaved stimulation and BCI decoding was tested in a phantom brain as a proof-of-concept operation of BD-BCI system. The benchtop prototype BD-BCI stimulator's basic output features (current amplitude, pulse frequency, pulse width, train duration) were validated by demonstrating the output-equivalency to an FDA-approved commercial cortical electrical stimulator (R 2 > 0.99). Charge-neutral stimulation was demonstrated with pulse-width modulation-based correction algorithm preventing steady state voltage deviation. Artifact mitigation achieved a 64.5% peak voltage reduction. Highly accurate impedance monitoring was achieved with R 2 > 0.99 between measured and actual impedance, which in-turn enabled accurate charge density monitoring. An online BCI decoding accuracy of 93.2% between instructional cues and decoded states was achieved while delivering interleaved stimulation. The brain stimulation mapping via ECoG grids in an epilepsy patient showed that the two stimulators elicit equivalent responses. This study demonstrates clinical validation of a fully-programmable electrical stimulator, integrated into an embedded BCI system. This low-cost BD-BCI system is safe and readily applicable as a testbed for BD-BCI research. In particular, it provides an all-inclusive hardware platform that approximates the limitations in a near-future implantable BD-BCI. This successful benchtop/human validation of the programmable electrical stimulator in a BD-BCI system is a critical milestone toward fully-implantable BD-BCI systems.

A Fully Implantable and Programmable Epidural Spinal Cord Stimulation System for Rats with Spinal Cord Injury.

Epidural spinal cord stimulation (ESCS) is a potential treatment for the recovery of the motor function in spinal cord injury (SCI) patients. Since the mechanism of ESCS remains unclear, it is necessary to study the neurophysiological principles in animal experiments and standardize the clinical treatment. In this paper, an ESCS system is proposed for animal experimental study. The proposed system provides a fully implantable and programmable stimulating system for complete SCI rat model, along with a wireless charging power solution. The system is composed of an implantable pulse generator (IPG), a stimulating electrode, an external charging module and an Android application (APP) via a smartphone. The IPG has an area of 25×25 mm2 and can output 8 channels of stimulating currents. Stimulating parameters, including amplitude, frequency, pulse width and sequence, can be programmed through the APP. The IPG was encapsulated with a zirconia ceramic shell and two-month implantable experiments were carried out in 5 rats with SCI. The main focus of the animal experiment was to show that the ESCS system could work stably in SCI rats. The IPG implanted in vivo can be charged through the external charging module in vitro without anesthetizing the rats. The stimulating electrode was implanted according to the distribution of ESCS motor function regions of rats and fixed on the vertebrae. The lower limb muscles of SCI rats can be activated effectively. The two-month SCI rats needed greater stimulating current intensity than the one-month SCI rats The results indicated that the stimulating system provides an effective and simplified tool for studying the ESCS application in motor function recovery for untethered animals.

Non-Invasive Electroretinogram Recording with Simultaneous Optogenetics to Dissect Retinal Ganglion Cells Electrophysiological Dynamics

Electroretinography (ERG) is a non-invasive electrophysiological recording technique that detects the electrical signaling of neuronal cells in the visual system. In conventional ERG recordings, the signals are considered a collective electrical response from various neuronal cell populations, including rods, cones, bipolar cells, and retinal ganglion cells (RGCs). However, due to the limited ability to control electrophysiological responses from different types of cells, the detailed information underlying ERG signals has not been analyzed and interpreted. Linking the features of ERG signals to the specific neuronal response will advance the understanding of neuronal electrophysiological dynamics and provide more evidence to elucidate pathological mechanisms, such as RGC loss during the progression of glaucoma. Herein, we developed an advanced ERG recording system integrated with a programmable, non-invasive optogenetic stimulation method in mice. In this system, we applied an automatic and unbiased ERG data analysis approach to differentiate a, b wave, negative response, and oscillatory potentials. To differentiate the electrophysiological response of RGCs in ERG recordings, we sensitized mouse RGCs with red-light opsin, ChRmine, through adeno-associated virus (AAV) intravitreal injection. Features of RGC dynamics under red-light stimulation were identified in the ERG readout. This non-invasive ERG recording system, associated with the programmable optogenetics stimulation method, provides a new methodology to dissect neural dynamics under variable physiological and pathological conditions in vivo. With the merits of non-invasiveness, improved sensitivity, and specificity, we envision this system can be further applied for early-stage detection of RGC degeneration and functional progression in neural degenerative diseases, such as glaucoma.

Human Interleukin-1β Profile and Self-Reported Pain Monitoring Using Clear Aligners with or without Acceleration Techniques: A Case Report and Investigational Study.

There is a growing demand for more aesthetic, comfortable, and faster orthodontic treatments, and clear aligners emerged as a solution to fulfill this need. However, the effectiveness of clear aligners to treat complex malocclusions is yet contentious. The use of acceleration methods could improve the efficacy of clear aligners by stimulating cells' mechanobiology through numerous pathways, but this hypothesis is still poorly explored. We aimed to monitor the release profile of an inflammatory marker-the interleukin-1β-and to evaluate its relationship with self-reported pain scores with and without the use of acceleration techniques during an orthodontic treatment requiring difficult tooth movements with clear aligners. Case Report. Here, we report a case of a 46-year-old female patient who presented functional and aesthetic complaints. Intraoral examination revealed a diminished overjet and overbite, rotation of teeth 45 and 24, absence of teeth 25, 35, and 36, buccolingual dislocation of tooth 21, a tendency to a Class III malocclusion, and a 2 mm left deviation of the lower midline. This study is divided into three stimulation phases: no stimulation, mechanical vibration stimulation, and photobiomodulation. Interleukin-1β levels in gingival crevicular fluid samples from the pressure side of six selected teeth were evaluated at four time points after the orthodontic treatment onset. Pain monitoring in those teeth was performed using a visual analogue scale at the same time points. Interleukin-1β protein production peaked 24 h after treatment onset. Complex movements were associated with increased self-reported pain. Clear aligners show limitations in solving complex tooth movements, even when combined with acceleration. The development of customized and programmable stimulation microdevices integrated into "smart aligners," which could be designed to specifically stimulate the direction of movement and stimulation parameters and could constitute a solution to optimize the orthodontic tooth movement with clear aligners.

A programmable culture platform for hydrostatic stimulation and in situ pH sensing of lung cancer cells with organic electrochemical transistors

In this work, we present a programmable dynamic cell culture stimulation platform designed to work in a CO 2 incubator, compatible with a standard multi-well plate. An epithelial lung cell culture can be mechanically stimulated with a cyclic increase of the hydrostatic pressure inside the culture chamber in the range 1–12 kPa, trying to mimic the human respiration rate. An in situ live pH-monitoring system based on PEDOT:PSS Organic ElectroChemical Transistors was also designed, fabricated and characterized, in order to merge both the stimulated cell culture and the pH sensing in a compact platform. • A culture chamber for the stimulation of lung cells by means of the cyclic increaseof its internal pressure was fabricated. • The tightness of the chamber and its reliability have been tested. • PEDOT:PSS based Organic ElectroChemical Transistors were fabricated by using photolithographic steps. • OECTs were tested in NaCl 0.1 M solution and in cell culture medium, showing good electrical response. • Cell proliferation tests were carried out inside the chamber, showing identical proliferation with respect to control. • pH tests have been carried out with OECTs, showing high sensitivity below pH 4.

Responsive Neurostimulation of the Thalamus for the Treatment of Refractory Epilepsy.

IntroductionOne-third of patients with epilepsy continue to have seizures despite antiepileptic medications. Some of these refractory patients may not be candidates for surgical resection primarily because the seizure onset zones (SOZs) involve both hemispheres or are located in eloquent areas. The NeuroPace Responsive Neurostimulation System (RNS) is a closed-loop device that uses programmable detection and stimulation to tailor therapy to a patient's individual neurophysiology. Here, we present our single-center experience with the use of RNS in thalamic nuclei to provide long-term seizure control in patients with refractory epilepsy.MethodsWe performed a prospective single-center study of consecutive refractory epilepsy patients who underwent RNS system implantation in the anterior (ANT) and centromedian (CM) thalamic nuclei from September 2015 to December 2020. Patients were followed postoperatively to evaluate seizure freedom and complications.ResultsTwenty-three patients underwent placement of 36 RNS thalamic leads (CM = 27 leads, ANT = 9 leads). Mean age at implant was 18.8 ± 11.2 years (range 7.8–62 years-old). Two patients (8.7%) developed infections: 1 improved with antibiotic treatments alone, and 1 required removal with eventual replacement of the system to recover the therapeutic benefit. Mean time from RNS implantation to last follow-up was 22.3 months. Based on overall reduction of seizure frequency, 2 patients (8.7%) had no- to <25% improvement, 6 patients (26.1%) had 25–49% improvement, 14 patients (60.9%) had 50–99% improvement, and 1 patient (4.3%) became seizure-free. All patients reported significant improvement in seizure duration and severity, and 17 patients (74%) reported improved post-ictal state. There was a trend for subjects with SOZs located in the temporal lobe to achieve better outcomes after thalamic RNS compared to those with extratemporal SOZs. Of note, seizure etiology was syndromic in 12 cases (52.2%), and 7 patients (30.4%) had undergone resection/disconnection surgery prior to thalamic RNS therapy.ConclusionThalamic RNS achieved ≥50% seizure control in ~65% of patients. Infections were the most common complication. This therapeutic modality may be particularly useful for patients affected by aggressive epilepsy syndromes since a young age, those whose seizure foci are located in the mesial temporal lobe, and those who have failed prior surgical interventions.

Magnetoelectric Bio-Implants Powered and Programmed by a Single Transmitter for Coordinated Multisite Stimulation.

This paper presents a hardware platform including stimulating implants wirelessly powered and controlled by a shared transmitter for coordinated leadless multisite stimulation. The adopted novel single-transmitter, multiple-implant structure can flexibly deploy stimuli, improve system efficiency, easily scale stimulating channel quantity and relieve efforts in device synchronization. In the proposed system, a wireless link leveraging magnetoelectric effects is co-designed with a robust and efficient system-on-chip to enable reliable operation and individual programming of every implant. Each implant integrates a 0.8-mm2 chip, a 6-mm2 magnetoelectric film, and an energy storage capacitor within a 6.2-mm3 size. Magnetoelectric power transfer is capable of safely transmitting milliwatt power to devices placed several centimeters away from the transmitter coil, maintaining good efficiency with size constraints and tolerating 60-degree, 1.5-cm misalignment in angular and lateral movement. The SoC robustly operates with 2-V source amplitude variations that spans a 40-mm transmitter-implant distance change, realizes individual addressability through physical unclonable function IDs, and achieves 90% efficiency for 1.5-to-3.5-V stimulation with fully programmable stimulation parameters.

Remotely Programmable Deep Brain Stimulator Combined with Invasive Blood Pressure Monitoring System for Non-Tethered Rat Model in Hypertension Research

Remotely Programmable Deep Brain Stimulator Combined with Invasive Blood Pressure Monitoring System for Non-Tethered Rat Model in Hypertension Research

Impact of adaptive gastric electrical stimulation on weight, food intake, and food intake rate in dogs.

Gastric electrical stimulation (GES) has been studied for decades as a promising treatment for obesity. Stimulation pulses with fixed amplitude and pulse width are usually applied, but these have limitations with regard to overcoming habituation to GES and inter-subject variation. This study aims to analyze the efficacy of an adaptive GES protocol for reducing food intake and maintaining lean weight in dogs. Six beagle dogs were implanted with a remotely programmable gastric stimulator. An adaptive protocol was designed to increase the stimulation energy proportionally to the excess of food consumption, with respect to the dogs' maintenance energy requirements. After surgery and habituation to experimental conditions, the dogs went through both a control and a stimulation period of 4weeks each, in a randomized order. The stimulation parameters were adapted daily. Body weight, food intake, food intake rate, and postprandial cutaneous electrogastrograms (EGG) were recorded to assess the effect of adaptive GES. Adaptive GES decreased food intake and food intake rate (p<0.05) resulting in weight maintenance. In the absence of GES, the dogs gained weight (p<0.05). Postprandial EGG dominant frequency was accelerated by GES (p<0.05). The strategy of adapting the stimulation energy was effective in causing significant mid-term changes. Adaptive GES is effective for reducing food intake and maintaining lean weight. The proposed adaptive strategy may offer benefits to counter habituation and adapt to inter-subject variation in clinical use of GES for obesity.

Nueva versión en Windows del sistema AUDIX para la evaluación objetiva de la audición

El presente trabajo describe una nueva versión del sistema AUDIX, diseñada como una estación de trabajo informatizada, para la audiometría objetiva y subjetiva. El sistema, esta integrado por un ordenador (PC) con una serie de programas de cómputo (“software”) el cual se conecta mediante una interfaz universal (universal serial bus USB) con un bloque electrónico especializado (“hardware”). El bloque electrónico tiene dos amplificadores bioeléctricos y un estimulador acústico digital totalmente programable con dos canales independientes. Esto permite generar de manera simultánea por ambos oídos, estímulos complejos diferentes (mezcla de tonos modulados en amplitud). Los estímulos acústicos pueden ser presentados a través de audiófonos (suprauriculares o de inserción), vibrador óseo y/o altavoces. El software programado sobre una plataforma Windows, tiene 5 módulos diferentes para la adquisición y análisis de PEA transientes y de estado estable, audiometría conductual, administración de base de datos y calibración. La base de datos del sistema permite almacenar, borrar, extraer, crear y realizar copias de respaldo. Durante la adquisición de los PEA se utilizan diferentes métodos estadísticos como indicadores para la detección objetiva de las respuestas. Puede visualizarse en forma concurrente la actividad bioeléctrica de base (monitoreo de EEG) y el resultado de la promediación (PEA). Los resultados del examen electroaudiométrico son analizados fuera de línea de una manera flexible, generándose múltiples reportes gráficos y permitiendo la comparación automática con datos normativos. En el caso de los PEAee los resultados pueden ser presentados en el formato estándar de un audiograma convencional utilizando diferentes escalas (dB: HL, SPL, nHL). El sistema AUDIX ha sido validado ampliamente en la práctica clínica resultando de utilidad para la detección temprana de las pérdidas auditivas y la caracterización precisa de la audición en toda la gama de frecuencias audibles.

A programmable transcutaneous electrical nerve stimulation device based on arduino and remote control using a smartphone

A programmable transcutaneous electrical nerve stimulation device based on arduino and remote control using a smartphone

Opamp-Less Sub-μW/Channel Δ-Modulated Neural-ADC With Super-GΩ Input Impedance

The presented 16-channel $\Delta $ -modulated neural analog-to-digital converter (ADC) exhibits tolerance to input dc offsets of any value, up to the supply voltage. It employs a dynamic differential-difference comparator architecture with a super- $\text{G}\Omega $ input impedance ensuring negligible gate-leakage current and well-matched differential inputs resulting in more than 78 dB of rejection of common-mode signals and artifacts. The all-digital nature of the presented $\Delta $ -ADC enables sampling of input signals at high oversampling ratios (OSRs) making the front-end immune to stimulation artifacts with differential amplitudes up to a limit that is scalable by the OSR (e.g., 10 mVPP at OSR $=\,\,10$ k). Moreover, it allows the $\Delta $ -ADC to linearly scale down the power consumption required by the application’s recording bandwidth. The oversampled $\Delta $ -ADC achieves an effective number of bits (ENOB) of 9.7-bit and 2.6- $\mu \text{V}_{\mathrm {RMS}}$ integrated input-referred noise over 1 Hz to 500-Hz bandwidth. It uses no large passives or statically biased circuits, such as operational amplifiers (Opamps) saving both channel area (0.011 mm2) and power consumption (0.99 $\mu \text{W}$ ). Experimentally measured results validate the key features of the design and include in vivo recordings in freely moving guinea pigs. The fabricated prototype system-on-a-chip (SoC) hosts an array of 16-channel neural-ADC with in-channel digitally programmable high-compliance current-mode biphasic stimulators as well as wireless circuitry for data communication and power/command reception.