Wireless Stimulation Research Articles

Investigation of stereotactic surgery for avian brain stimulation by a fully implanted wireless system.

The authors' goal was to study avian motor brain mapping via wireless stimulation to induce certain behaviors. In this paper, the authors propose an electrode design that is suitable for avian brain stimulation as well as a stereotactic implant procedure for the proposed electrode. An appropriate breed for avian brain study was chosen. A fully implantable remote-controlled electrical stimulation system was inserted to minimize discomfort. A suitable electrode design and stereotactic surgery method based on the electrode design were investigated. Using a wireless stimulation system, flapping and rotation behaviors were induced by stimulating the ventral part of the nucleus intercollicularis and formatio reticularis medialis mesencephali both on the ground and during flight. The authors were able to implant the entire brain stimulation system inside the avian body without any surgical complications. Postoperative observations suggested that the bird did not find the implant uncomfortable.

Selective Wireless Stimulation of Rat Sciatic Nerve.

Chronic stability of functional performance is a significant challenge to the success of implantable devices for neural stimulation and recording. Integrating wireless technology with typical microelectrode array designs is one approach that may reduce instances of mechanical failure and improve the long-term performance of neural devices. We have investigated the long-term stability of Wireless Floating Microelectrode Arrays (WMFAs) implanted in rat sciatic nerve, and their ability to selectively recruit muscles in the hind limb via neural stimulation. Thresholds as low as 4.1 μA were able to generate visible motion of the rear paw. Each implanted device (n=6) was able to selectively recruit plantar flexion and dorsiflexion of the rear paw, and selective stimulation of both movements was achieved throughout the study period. The evoked limb motion was electrode specific and was dependent on location within the fascicular structure of the nerve. Motor thresholds and movement patterns remained stable for more than 8 weeks after device implantation. No major changes in limb function were observed between the implanted and contralateral limb, or between implanted animals and control group animals. The results of this study show that WFMAs with intrafascicular electrodes implanted in a healthy peripheral nerve can provide stable and selective motor recruitment, without altering overall limb function.

863Leadless endocardial pacing improves symptoms in patients with failed conventional CRT implant in long term follow up

Abstract Funding Acknowledgements EBR Systems, Inc OnBehalf WiSE-CRT and LV-SELECT study and POST-M REGISTRY Background The WiSE-CRT (Wireless stimulation endocardial) system has advantages over conventional epicardial CRT. Whenever conventional CRT failed to implant or failed to echocardiographic response, the WiSE-CRT was implanted as part of the WiSE CRT study (N = 13), as part of the LV-SELECT study (N = 35) or as part of the POST-M REGISTRY (N = 117) over the last 8 years. All these studies have reported high rates of clinical and echocardiographic response compared to conventional CRT. Objectives The purpose of this analysis was to determine the safety and clinical response in the largest available number of implanted patients (pts) with long term follow up of 2 years and the first, second and third generation of WiSE-CRT devices. Method All pts undergoing a WiSE-CRT implantation as part of the WiSE CRT study (N = 13), as part of the LV-SELECT study (N = 35) or as part of the POST-M REGISTRY (N = 117) were analysed (N = 165). Pts were followed-up for 24 months and considered CRT responders if an improvement in NYHA ≥ 1 class from baseline (pre-implant) was achieved. Results In total, 165 pts were implanted, demographics include: 68.2 ± 9.6 year’s old, 81.8% male, 49.7% with history of AFib and 54.5% non-ischaemic aetiology. The mean intrinsic QRS duration was 165.0 ± 32.3 msec (28 pts pace-maker dependent). 161 pts had the system successfully implanted with no major complications, 3 (1.8%) pts developed a pericardial effusion and 1 (0.6%) electrode was lost during implantation and recovered surgically. During the 24-month follow-up period, 20 (12.1%) pts died from any cause, 4 (2.4%) pts developed TIA or Stroke and 15 (9.1%) pts had pocket or transmitter infection. There was a significant improvement in NYHA functional class in 63.6% pts and an average improvement of -26.1 (-45.1, -7.1) msec in QRS duration. Conclusion Despite a history of failed conventional CRT implantation, pts undergoing CRT upgrades with a WiSE-CRT have a high success rate and a complication rate similar to previously described. In addition endocardial LV pacing led to symptomatic improvements in 64% of patients reaching the 24 month of follow up. Abstract Figure 1: Forest Plot NYHA Responder Rat

Abstract 112: Galvanotactic Smart Bandage For Wireless Wound Healing

Background: Approximately thirty million people in the United States suffer from diabetes. The prevalence of diabetic foot ulcers (DFUs) in this population is 13%. There is a pressing need to develop effective therapies to treat chronic wounds robustly. Current standard of care wound dressings are passive and cannot actively respond to variations in the wound environment. Smart bandages are well positioned to address these challenges with their ability to integrate (bio)sensors for real-time monitoring and active wound care treatment. Current smart bandage technologies have demonstrated significant promise in their ability to sense physiological conditions. This includes detecting pH of the wound, temperature, oxygen, moisture, mechanical and electrical changes. To our knowledge there have not been significant advancements in incorporating sensing technologies to deliver active wound care. We believe this can be achieved using a multidisciplinary approach combining electrical and chemical engineering with the fundamentals of cellular and biomolecular processes in wound healing directed towards high resolution, in situ tissue regeneration. Methods: A flexible printed wireless stimulator was designed and fabricated to deliver directional energy across a wound gradient. Subsequently a low impedance PEDOT:PSS electrode was designed to optimize the skin and stimulator interface, producing a robust gel with tunable adhesion properties. The smart bandage was evaluated in an excisional diabetic and C57BL6/J murine wound healing model. A parabiosis model was used to evaluate circulating cell migration into the wound bed. Single cell analyses were performed to evaluate changes in cell populations as a direct result of induced electrical stimulation. In vitro validation was performed to elucidate in vivo results. Results: Wireless electrical stimulation resulted in significantly accelerated wound closure, when compared to controls, in both a diabetic and C57BL6/J murine excisional wound healing model. Complete epidermal recovery was observed, with a thicker collagen network and increased dermal thickness. Greater neovascularization and appendage formation were observed in the treatment groups. Single cell analyses revealed higher proliferation and remodeling regulatory markers expressed across treated groups. In vitro co-culture validation experiments demonstrated accelerated proliferation, mitotic rate and tube formation when compared to controls. Conclusion: Our data demonstrates the functionality of a robust wireless interface for wound healing. This novel treatment modality will integrate AI processing components for the development of a closed-loop functional stimulator. By combining the domain expertise of nanofabrication, mechanotransduction, fibrosis and molecular/cellular analyses, we are developing a novel chronically stable and robust smart bandage that will pave the way for the next generation of palliative wound care.

Extracellular Photovoltage Clamp Using Conducting Polymer‐Modified Organic Photocapacitors

AbstractOptoelectronic control of physiological processes accounts for new possibilities ranging from fundamental research to treatment of disease. Among nongenetic light‐driven approaches, organic semiconductor‐based device platforms such as the organic electrolytic photocapacitor (OEPC) offer the possibility of localized and wireless stimulation with a minimal mechanical footprint. Optimization of efficiency hinges on increasing effective capacitive charge delivery. Herein, a simple strategy to significantly enhance the photostimulation performance of OEPC devices by employing coatings of the conducting polymer formulation poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate), or PEDOT:PSS is reported. This modification increases the charge density of the stimulating photoelectrodes by a factor of 2–3 and simultaneously decreases the interfacial impedance. The electrophysiological effects of PEDOT:PSS‐derivatized OEPCs on Xenopus laevis oocyte cells on membrane potential are measured and voltage‐clamp techniques are used, finding an at‐least twofold increase in capacitive coupling. The large electrolytic capacitance of PEDOT:PSS allows the OEPC to locally alter the extracellular voltage and keep it constant for long periods of time, effectively enabling a unique type of light‐controlled membrane depolarization for measurements of ion channel opening. The finding that PEDOT:PSS‐coated OEPCs can remain stable after a 50‐day accelerated ageing test demonstrates that PEDOT:PSS modification can be applied for fabricating reliable and efficient optoelectronic stimulation devices.

A Wireless Neuroprosthesis for Patients with Drug-refractory Epilepsy: A Proof-of-Concept Study.

ObjectiveAcute or protracted cortical recording may be necessary for patients with drug-refractory epilepsy to identify the ictogenic regions before undergoing resection. Currently, these invasive recording techniques present certain limitations, one of which is the need for cables connecting the recording electrodes placed in the intracranial space with external devices displaying the recorded electrocorticographic signals. This equates to a direct connection between the sterile intracranial space with the non-sterile environment. Due to the increasing likelihood of infections with time, subdural grids are typically removed a few days after implantation, a limiting factor in localizing the epileptogenic zone if seizures are not frequent enough to be captured within this time-frame. Furthermore, patients are bound to stay in the hospital, connected by the wires to the recording device, thus increasing substantially the treatment costs. To address some of the current shortcomings of invasive monitoring, we developed a neuroprosthesis made of a subdural silicone grid connected to a wireless transmitter allowing prolonged electrocorticografic recording and direct cortical stimulation. This device consists of a silicone grid with 128-platinum/iridium contacts, connected to an implantable case providing wireless recording and stimulation. The case also houses a wirelessly rechargeable battery for chronic long-term implants. We report the results of the first human proof-of-concept trial for wireless transmission of electrocorticographic recordings using a device suited for long-term implantation in three patients with drug-refractory epilepsy. MethodsThree patients with medically refractory epilepsy underwent the temporary intraoperative placement of the subdural grid connected to the wireless device for recording and transmission of electrocorticographic signals for a duration of five minutes before the conventional recording electrodes were placed or the ictal foci were resected.ResultsWireless transmission of brain signals was successfully achieved. The wireless electrocorticographic signal was judged of excellent quality by a blinded neurophysiologist.ConclusionsThis preliminary experience reports the first successful placement of a wireless electrocorticographic recording device in humans. Long-term placement for prolonged wireless electrocorticographic recording in epilepsy patients will be the next step.

Telemetry-controlled simultaneous stimulation-and-recording device (SRD) to study interhemispheric cortical circuits in rat primary somatosensory (SI) cortex

BackgroundA growing need exists for neuroscience platforms that can perform simultaneous chronic recording and stimulation of neural tissue in animal models in a telemetry-controlled fashion with signal processing for analysis of the chronic recording data and external triggering capability. We describe the system design, testing, evaluation, and implementation of a wireless simultaneous stimulation-and-recording device (SRD) for modulating cortical circuits in physiologically identified sites in primary somatosensory (SI) cortex in awake-behaving and freely-moving rats. The SRD was developed using low-cost electronic components and open-source software. The function of the SRD was assessed by bench and in-vivo testing.ResultsThe SRD recorded spontaneous spiking and bursting neuronal activity, evoked responses to programmed intracortical microstimulation (ICMS) delivered internally by the SRD, and evoked responses to external peripheral forelimb stimulation.ConclusionsThe SRD is capable of wireless stimulation and recording on a predetermined schedule or can be wirelessly synchronized with external input as would be required in behavioral testing prior to, during, and following ICMS.

A Fully Implantable Wireless Stimulation System for Pigeon Navigation.

Navigation of freely moving animals has been studied for potential application to emergency situations and hazardous environments. A fully implantable stimulation system for remote animal navigation was proposed and applied to living pigeons. The animal navigation system, consisting of an external controller and a neural stimulator, was designed based on the anatomy of the pigeons. Depth electrodes were fabricated based on the anatomy of target pigeon brain regions. The fabricated neural stimulators received data wirelessly from the external controller and generated biphasic current pulses with preset parameters of amplitude, duration, and rate. The average impedance of the fabricated electrodes was 12.0∠-13.05° kΩ at 1 kHz. The neural stimulator was implanted on the dorsal side, and the depth electrodes were inserted into the formatio reticularis medialis mesencephali (FRM). When successive current pulses with an amplitude of 400 μA, a rate of 58 Hz, and a duration of 80 μs were applied to the target regions at 0.85 s intervals, turning/circling behaviors were induced for 6.2 s. The feasibility of the proposed wireless stimulation system was demonstrated in vivo.

Stimulation and Repair of Peripheral Nerves Using Bioadhesive Graft-Antenna.

An original wireless stimulator for peripheral nerves based on a metal loop (diameter ≈1 mm) that is powered by a transcranial magnetic stimulator (TMS) and does not require circuitry components is reported. The loop can be integrated in a chitosan scaffold that functions as a graft when applied onto transected nerves (graft‐antenna). The graft‐antenna is bonded to rat sciatic nerves by a laser without sutures; it does not migrate after implantation and is able to trigger steady compound muscle action potentials for 12 weeks (CMAP ≈1.3 mV). Eight weeks postoperatively, axon regeneration is facilitated in transected nerves that are repaired with the graft‐antenna and stimulated by the TMS for 1 h per week. The graft‐antenna is an innovative and minimally‐invasive device that functions concurrently as a wireless stimulator and adhesive scaffold for nerve repair.

Behavioral validation of a wireless low-power neurostimulation technology in a conditioned place preference task

Objective. Neurostimulation technologies are important for studying neural circuits and the connections that underlie neurological and psychiatric disorders. However, current methods come with limitations such as the restraint on movement imposed by the wires delivering stimulation. The objective of this study was to assess whether the e-Particle (EP), a novel wireless neurostimulator, could sufficiently stimulate the brain to modify behavior without these limitations. Approach. Rats were implanted with the EP and a commercially available stimulating electrode. Animals received rewarding brain stimulation, and performance in a conditioned place preference (CPP) task was measured. To ensure stimulation-induced neuronal activation, immediate early gene c-fos expression was also measured. Main results. The EP was validated in a commonly used CPP task by demonstrating that (1) wireless stimulation via the EP induced preference behavior that was comparable to that induced by standard wired electrodes and (2) neuronal activation was observed in projection targets of the stimulation site. Significance. The EP may help achieve a better understanding of existing brain stimulation methods while overcoming their limitations. Validation of the EP in a behavioral model suggests that the benefits of this technology may extend to other areas of animal research and potentially to human clinical applications.

Photoconductive Micro/Nanoscale Interfaces of a Semiconducting Polymer for Wireless Stimulation of Neuron-Like Cells.

We report multiscale structured fibers and patterned films based on a semiconducting polymer, poly(3-hexylthiophene) (P3HT), as photoconductive biointerfaces to promote neuronal stimulation upon light irradiation. The micro/nanoscale structures of P3HT used for neuronal interfacing and stimulation include nanofibers with an average diameter of 100 nm, microfibers with an average diameter of about 1 μm, and lithographically patterned stripes with width of 3, 25, and 50 μm, respectively. The photoconductive effect of P3HT upon light irradiation provides electrical stimulation for neuronal differentiation and directed growth. Our results demonstrate that neurons on P3HT nanofibers showed a significantly higher total number of branches, while neurons grown on P3HT microfibers had longer and thinner neurites. Such a combination strategy of topographical and photoconductive stimulation can be applied to further enhance neuronal differentiation and directed growth. These photoconductive polymeric micro/nanostructures demonstrated their great potential for neural engineering and development of novel neural regenerative devices.

Leadless endocardial ultrasound based left ventricular stimulation : WISE CRT System: alternative to conventional methods

There are still several limitations in delivering cardiac resynchronisation therapy (CRT). After 6months, 20-40% of patients fail to have clinical benefit due to various reasons. Endocardial stimulation rather than conventional epicardial pacing has been shown to be more physiological, improves electrical stimulation of the left ventricle (LV), has less dispersion of electrical activity and results in better resynchronisation. The WiSE™ CRT System ("Wireless stimulation endocardial system"; EBR Systems, Sunnyvale, CA, USA) provides an option for wireless, LV endocardial pacing triggered by aconventional right ventricular pacing spike from aco-implant. The feasibility of the WiSE™ CRT System has been successfully demonstrated in apopulation of failed cardiac resynchronisation patients with either failed implantation of aconventional system, nonresponse to conventional therapy or upgrade from pacemaker or defibrillator, where aconventional system was not an option. The WiSE™ CRT System is an innovative technology with promising safety, performance and preliminary efficacy.

WIRELESS HIGH FREQUENCY SPINAL CORD STIMULATION FOR THE TREATMENT OF POST-HERPETIC OCULAR NEURALGIA: A CASE REPORT

Background: High frequency wireless Spinal Cord Stimulation (SCS) at the C1-C2 vertebral levels provides analgesia for the treatment of refractory ocular pain on the left side secondary to post-herpetic neuralgia. Objective: To assess analgesic effects of minimally invasive wireless neuromodulation in the treatment of chronic pain due to post-herpetic neuralgia. Study Design: This observational, prospective case report was designed to illustrate the effectiveness of relieving chronic, intractable pain utilizing wireless spinal cord stimulation at multiple frequencies for the treatment of post-herpetic neuralgia. Setting: Private Practice Interventional Pain Clinic. Methods: This is a single case study of a 62-yearold patient who experienced an episode of shingles with rash over the left frontal and lateral ocular margin. After the rash subsided, the patient began suffering from severe pain in the left eye. The patient was placed on a 10-day course of valacyclovir, gabapentin, which was discontinued secondary to sedation intolerance, pregabalin titrated to 300 mg/day and oxycodone, all of which were ineffective in relieving the pain. The patient received a stellate ganglion block injection on 6 occasions, experiencing pain relief of only up to one-day after each injection. Stellate ganglion radiofrequency ablation was also unsuccessful. With original Visual Analog Scale (VAS) score of 9/10, inability to sleep and incapacity to perform activities of daily living (ADLs), the patient had Stimwave Freedom wireless stimulators placed sequentially at the C1-C2 vertebral levels. Results: Programming at low frequencies from 40-120 Hz was unsuccessful in reducing left eye pain. Stimulation was increased to high frequency on the Stimwave SurgeTM adjustable waveform, and within 12 hours, the patient noted significant decrease in pain. At 3 days post-procedure, the patient’s VAS score was 1/10. The patient had permanent placement of the devices, and at 8-month follow-up, VAS scores were 0-2/10, and the patient’s mood, sleep and ability to perform ADLs all improved substantially. Limitations: The study was limited by the novelty of the device. Although the doctor who implanted the device is very experienced, more cases of the use of the wireless Stimwave Freedom apparatus are necessary to establish its long-term effectiveness and safety. More clinical trials investigating the utilization of multiple frequencies are also required. Conclusions: Epidural placement of 2, wireless sequentially placed octopolar stimulators with a minimally invasive technique at high frequency stimulation was safe and effective. Key words: post-herpetic neuralgia, ocular, spinal cord stimulation, wireless, shingles, trigeminal nerve, high frequency

Stimulation of the Left Ventricular Endocardium for Cardiac Resynchronization Therapy in Non-Responders and Previously Untreatable Patients (SOLVE CRT) Clinical Study

Background CRT shows benefit in patients with depressed LVEF, Heart Failure symptoms and prolonged intraventricular conduction, however, 30-40% of CRT patients do not respond to therapy and 8-10% do not receive CRT due to anatomical constraints. Endocardial stimulation promises to improve therapy response, but placing traditional leads endocardially presents safety concerns. The SOLVE CRT Study aims to evaluate the safety and efficacy of the WiSE CRT (Wireless Stimulation Endocardially) System for CRT. Therapy The WiSE CRT System uses ultrasound to WIRELESSLY transmit power to an electrode in a CUSTOMIZED LV pacing location ENDOCARDIALLY, accomplishing synchronous RV & LV pacing = BiV pacing for CRT SOLVE CRT Patient Population CRT NON-RESPONDERS or, PREVIOUSLY UNTREATABLE due to failed CS lead implantation, or CS lead programmed off or, HIGH RISK UPGRADES with contraindications to CS lead implant Design Multi-center, randomized, two-arm, double blinded, prospective trial with 350 PATIENTS at up to 45 INVESTIGATONAL SITES in the U.S., Europe, and Australia. Study begins in 2018 and continues until FDA approval estimated in Q4 2020. Control patients cross-over after 6 month primary endpoint evaluation Endpoints - PRIMARY SAFETY - Freedom from Type 1 Complications reported through 6 months compared to a performance goal - PRIMARY EFFICACY - LVESV Mean Change, LVESV Distribution Shift, Clinical Composite (NYHA, Health Status (KCCQ), Death and HF Event) - SECONDARY EFFICACY - Acoustic Pacing Capture Threshold (APCT) measured at 6 months, Acoustic Pacing Capture Threshold Stability (APCT Stability) measured at pre-discharge through 6 months - TERTIARY EFFICACY - NT-proBNP Mean Change, Proportion of subjects with a greater than 5% improvement in EF from baseline to 6 months, Mean change in intrinsic QRS duration from baseline to 6 months, Percent subjects with at least 1 NYHA Class improvement from baseline to 6 months.

Controlling Nerve Growth with an Electric Field Induced Indirectly in Transparent Conductive Substrate Materials.

Innovative neurostimulation therapies require improved electrode materials, such as poly(3,4-ethylenedioxythiophene) (PEDOT) polymers or IrOx mixed ionic-electronic conductors and better understanding of how their electrochemistry influences nerve growth. Amphibian neurons growing on transparent films of electronic (metal) conductors and electronic-ionic conductors (polymers and semiconducting oxides) are monitored. Materials are not connected directly to the power supply, but a dipole is created wirelessly within them by electrodes connected to the culture medium in which they are immersed. Without electrical stimulation neurons grow on gold, platinum, PEDOT-polystyrene sulfonate (PEDOT-PSS), IrOx , and mixed oxide (Ir-Ti)Ox , but growth is not related to surface texture or hydrophilicity. Stimulation induces a dipole in all conductive materials, but neurons grow differently on electronic conductors and mixed-valence mixed-ionic conductors. Stimulation slows, but steers neurite extension on gold but not on platinum. The rate and direction of neurite growth on PEDOT-PSS resemble that on glass, but on IrOx and (Ir-Ti)Ox neurites grow faster and in random directions. This suggests electrochemical changes induced in these materials control growth speed and direction selectively. Evidence that the electric dipole induced in conductive material controls nerve growth will impact electrotherapies exploiting wireless stimulation of implanted material arrays, even where transparency is required.

Therapeutic electrical stimulation of injured peripheral nerve tissue using implantable thin-film wireless nerve stimulators.

Electrical stimulation of peripheral nerve tissue has been shown to accelerate axonal regeneration. Yet existing methods of applying electrical stimulation to injured peripheral nerves have presented significant barriers to clinical translation. In this study, the authors examined the use of a novel implantable wireless nerve stimulator capable of simultaneously delivering therapeutic electrical stimulation of injured peripheral nerve tissue and providing postoperative serial assessment of functional recovery. Flexible wireless stimulators were fabricated and implanted into Lewis rats. Thin-film implants were used to deliver brief electrical stimulation (1 hour, 20 Hz) to sciatic nerves after nerve crush or nerve transection-and-repair injuries. Electrical stimulation of injured nerves via implanted wireless stimulators significantly improved functional recovery. Brief electrical stimulation was observed to increase the rate of functional recovery after both nerve crush and nerve transection-and-repair injuries. Wireless stimulators successfully facilitated therapeutic stimulation of peripheral nerve tissue and serial assessment of nerve recovery. Implantable wireless stimulators can deliver therapeutic electrical stimulation to injured peripheral nerve tissue. Implantable wireless nerve stimulators might represent a novel means of facilitating therapeutic electrical stimulation in both intraoperative and postoperative settings.

Measuring Nanoscale Heating using Silicon Photonic Thermometry

Genetically encoded ion channels that respond to magnetic fields -‘Magnetogenetics’ — enable wireless stimulation of specific neurons deep in the brain and provide a powerful tool for studying neural correlates of behavior in freely moving animals. Recently, several magnetogenetic proteins were constructed using heat-sensitive channels such as TRPV1/4 attached to biogenic iron storage protein, ferritin. Magnetic fields have been proposed to activate these channels via a thermal mediated pathway. Ferritin can be heated in an alternating magnetic field through relaxation losses or in a low frequency field via the magnetocaloric effect. Classical heat transfer laws predict that because nanoparticles dissipate heat quickly and efficiently to the surroundings, the small amount of heat produced in ferritin would not be sufficient to gate channels. However, experimental evidence has emerged recently that suggest that temperatures of magnetically heated iron oxide nanoparticles are many degrees higher than that of the bulk, and that the heat dissipates much slower than expected. The actual dissipation rates have been shown to depend on whether the nanoparticles are in a suspension or on the surface of a cell membrane. Here, we propose a novel method for measuring temperature in the vicinity of magnetic nanoparticles and their heat dissipation rates using silicon photonic thermosensors. This method relies on temperature dependent optical properties of silicon. A change in temperature changes the resonant wavelength condition of a silicon micro-resonator. Temperature near the surface of nanoparticles attached to these resonators can then be measured based on this optical readout. This approach allows us to measure the heat dissipation rates of nanoparticles present on a surface. Silicon resonators have been shown to have temperature sensitivities of few tens of mK and response times of 6 μs, making them suitable candidates for precise measurement of nanoscale heating.

Leadless cardiac pacemakers: present and the future.

Pacing technology for many decades has been composed of a generator attached to leads that are usually transvenous. Recently, leadless pacemakers have been studied in clinical settings and now available for use in many countries. This includes the single-component Nanostim Leadless Cardiac Pacemaker and Micra Transcatheter Pacing System, as well as the multicomponent Wireless Stimulation Endocardial system. Clinical studies in single-component leadless pacing technology has shown that they can be successfully implanted with minimal complications. The follow-up studies also seem to confirm the findings from the initial clinical trials. These systems offer some advantages over a traditional pacing system comprised of a subcutaneous generator and transvenous leads. In many ways, these leadless systems are disruptive technologies that are changing the traditional pacemaker concept and preferred for some patients. Ongoing research is needed to better assess their long-term function, safety, and end-of-life strategies. In the future, multichamber leadless pacing is expected to be developed and perhaps obviating the need for transvenous leads and their associated complications.

Some Autonomic Deficits of Acute or Chronic Cervical Spinal Contusion Reversed by Interim Brainstem Stimulation.

Prolonged electrical stimulation of the hindbrain's nucleus raphe magnus (NRM) or of its major midbrain input region, the periaqueductal gray (PAG), was previously found in rats to promote recovery from sensory-motor and histological deficits of acute thoracic spinal cord injury (SCI). Here, some visceral deficits of acute and chronic midline cervical (C5) contusion are similarly examined. Cranially implanted wireless stimulators delivered intermittent 8 Hz, 30-70 μA cathodal pulse trains to a brainstem microelectrode. Injured controls were given inactive stimulators; rats without injuries or implants were also compared. Rectal distension or squeezing of the forepaws caused an exaggerated rise in mean arterial pressure in injured, untreated rats under anesthesia on post-injury week 6, probably reflecting autonomic dysreflexia (AD). These pressor responses became normal when 7 days of unilateral PAG stimulation was started on the injury day. Older untreated injuries (weeks 18-19) showed normal pressor responses, but unexpectedly had significant resting and nociceptive bradycardia, which was reversed by 3 weeks of PAG stimulation started on weeks 7 or 12. Subsequent chronic studies examined gastric emptying (GE), as indicated by intestinal transit of gavaged dye, and serum chemistry. GE and fasting serum insulin were reduced on injury weeks 14-15, and were both normalized by ∼5 weeks of PAG stimulation begun in weeks 7-8. Increases in calcitonin gene-related peptide, a prominent visceral afferent neurotransmitter, measured near untreated injuries (first thoracic segment) in superficial dorsal laminae were reversed by acutely or chronically initiated PAG stimulation. The NRM, given 2-3 weeks of stimulation beginning 2 days after SCI, prevented abnormalities in both pressor responses and GE on post-injury week 9, consistent with its relaying of repair commands from the PAG. The descending PAG-NRM axis thus exhibits broadly restorative influences on visceral as well as sensory-motor deficits, improving chronic as well as acute signs of injury.

A Sub-millimeter, Inductively Powered Neural Stimulator.

Wireless neural stimulators are being developed to address problems associated with traditional lead-based implants. However, designing wireless stimulators on the sub-millimeter scale (<1 mm3) is challenging. As device size shrinks, it becomes difficult to deliver sufficient wireless power to operate the device. Here, we present a sub-millimeter, inductively powered neural stimulator consisting only of a coil to receive power, a capacitor to tune the resonant frequency of the receiver, and a diode to rectify the radio-frequency signal to produce neural excitation. By replacing any complex receiver circuitry with a simple rectifier, we have reduced the required voltage levels that are needed to operate the device from 0.5 to 1 V (e.g., for CMOS) to ~0.25–0.5 V. This reduced voltage allows the use of smaller receive antennas for power, resulting in a device volume of 0.3–0.5 mm3. The device was encapsulated in epoxy, and successfully passed accelerated lifetime tests in 80°C saline for 2 weeks. We demonstrate a basic proof-of-concept using stimulation with tens of microamps of current delivered to the sciatic nerve in rat to produce a motor response.