Physiology and Pathophysiology of Sodium Channel Inactivation.

Voltage-gated sodium channels are present in different tissues within the human body, predominantly nerve, muscle, and heart. The sodium channel is composed of four similar domains, each containing six transmembrane segments. Each domain can be functionally organized into a voltage-sensing region and a pore region. The sodium channel may exist in resting, activated, fast inactivated, or slow inactivated states. Upon depolarization, when the channel opens, the fast inactivation gate is in its open state. Within the time frame of milliseconds, this gate closes and blocks the channel pore from conducting any more sodium ions. Repetitive or continuous stimulations of sodium channels result in a rate-dependent decrease of sodium current. This process may continue until the channel fully shuts down. This collapse is known as slow inactivation. This chapter reviews what is known to date regarding, sodium channel inactivation with a focus on various mutations within each NaV subtype and with clinical implications.

Training-induced cortical plasticity compared between three tongue-training paradigms.

The primary aim of this study was to investigate the effect of different training types and secondary to test gender differences on the training-related cortical plasticity induced by three different tongue-training paradigms: (1) therapeutic tongue exercises (TTE), (2) playing computer games with the tongue using the Tongue Drive System (TDS) and (3) tongue-protrusion task (TPT). Forty-eight participants were randomized into three groups with 1h of TTE, TDS, or TPT. Stimulus-response curves of motor evoked potentials (MEPs) and motor cortex mapping for tongue muscles and first dorsal interosseous (FDI) (control) were established using transcranial magnetic stimulation at three time-points: (1) before tongue-training, (2) immediately after training, (3) 1h after training. Subject-based reports of motivation, fun, pain and fatigue were evaluated on 0-10 numerical rating scales after training. The resting motor thresholds of tongue MEPs were lowered by training with TDS and TPT (P<0.011) but not by TTE (P=0.167). Tongue MEP amplitudes increased after training with TDS and TPT (P<0.030) but not with TTE (P=0.302). Men had higher MEPs than women in the TDS group (P<0.045) at all time-points. No significant effect of tongue-training on FDI MEPs was observed (P>0.335). The tongue cortical motor map areas were not significantly increased by training (P>0.142). Training with TDS was most motivating and fun (P<0.001) and TTE was rated the most painful (P<0.001). Fatigue level was not different between groups (P>0.071). These findings suggest a differential effect of tongue-training paradigms on training-induced cortical plasticity and subject-based scores of fun, motivation and pain in healthy participants.

Optimization of data coils in a multiband wireless link for neuroprosthetic implantable devices.

We have presented the design methodology along with detailed simulation and measurement results for optimizing a multiband transcutaneous wireless link for high-performance implantable neuroprosthetic devices. We have utilized three individual carrier signals and coil/antenna pairs for power transmission, forward data transmission from outside into the body, and back telemetry in the opposite direction. Power is transmitted at 13.56 MHz through a pair of printed spiral coils (PSCs) facing each other. Two different designs have been evaluated for forward data coils, both of which help to minimize power carrier interference in the received data carrier. One is a pair of perpendicular coils that are wound across the diameter of the power PSCs. The other design is a pair of planar figure-8 coils that are in the same plane as the power PSCs. We have compared the robustness of each design against horizontal misalignments and rotations in different directions. Simulation and measurements are also conducted on a miniature spiral antenna, designed to operate with impulse-radio ultra-wideband (IR-UWB) circuitry for back telemetry.

Modeling and optimization of printed spiral coils in air, saline, and muscle tissue environments.

Printed spiral coils (PSCs) are viable candidates for near-field wireless power transmission to the next generation of high-performance neuroprosthetic devices with extreme size constraints, which will target intraocular and intracranial spaces. Optimizing the PSC geometries to maximize the power transfer efficiency of the wireless link is imperative to reduce the size of the external energy source, heating of the tissue, and interference with other devices. Implantable devices need to be hermetically sealed in biocompatible materials and placed in a conductive environment with high permittivity (tissue), which can affect the PSC characteristics. We have constructed a detailed model that includes the effects of the surrounding environment on the PSC parasitic components and eventually on the power transfer efficiency. We have combined this model with an iterative design method that starts with a set of realistic design constraints and ends with the optimal PSC geometries. We applied our design methodology to optimize the wireless link of a 1-cm (2) implantable device example, operating at 13.56 MHz. Measurement results showed that optimized PSC pairs, coated with 0.3 mm of silicone, achieved 72.2%, 51.8%, and 30.8% efficiencies at a face-to-face relative distance of 10 mm in air, saline, and muscle, respectively. The PSC, which was optimized for air, could only bear 40.8% and 21.8% efficiencies in saline and muscle, respectively, showing that by including the PSC tissue environment in the design process the result can be more than a 9% improvement in the power transfer efficiency.

Active High Power Conversion Efficiency Rectifier With Built-In Dual-Mode Back Telemetry in Standard CMOS Technology.

In this paper, we present an active rectifier with high power conversion efficiency (PCE) implemented in a 0.5- mum 5 V standard CMOS technology with two modes of built-in back telemetry; short- and open-circuit. As a rectifier, it ensures a PCE > 80%, taking advantage of active synchronous rectification technique in the frequency range of 0.125-1 MHz. The built-in complementary back telemetry feature can be utilized in implantable microelectronic devices (IMD), wireless sensors, and radio frequency identification (RFID) applications to reduce the silicon area, increase the data rate, and improve the reading range and robustness in load shift keying (LSK).

A low-noise receiver for multichannel wireless neural recording.

We present a high performance wideband receiver for multichannel wireless implantable neural recording systems (WINeR) utilizing pulse width modulation of time division multiplexed (PWM-TDM) samples. The receiver consists of a 50 MHz approximately 1 GHz tunable down-converter with 75 MHz bandwidth, frequency shift keying and PWM demodulators, and a high throughput USB interface. Several IF gain stages, passive LC filters, and an FPGA-based time-to-digital converter (TDC) with time interval resolution of 428 ps have significantly enhanced the receiver performance and extended its receiving range. A 2 MB SDRAM is used as a buffer between the TDC and USB to ensure continuous throughput for the digitized raw data at data rates up to 10 Mb/s. The receiver performance is evaluated with a 6-channel WINeR transmitter, showing that the entire system input referred noise with this receiver is 9.8 and 12.7 microV(rms) at 0.5 and 3.5 m distances, respectively, which are equivalent to 8.2 and 7.9 bits of resolution at 640 ksample/s.

Design and optimization of printed spiral coils for efficient transcutaneous inductive power transmission.

The next generation of implantable high-power neuroprosthetic devices such as visual prostheses and brain computer interfaces are going to be powered by transcutaneous inductive power links formed between a pair of printed spiral coils (PSC) that are batch-fabricated using micromachining technology. Optimizing the power efficiency of the wireless link is imperative to minimize the size of the external energy source, heating dissipation in the tissue, and interference with other devices. Previous design methodologies for coils made of 1-D filaments are not comprehensive and accurate enough to consider all geometrical aspects of PSCs with planar 3-D conductors as well as design constraints imposed by implantable device application and fabrication technology. We have outlined the theoretical foundation of optimal power transmission efficiency in an inductive link, and combined it with semi-empirical models to predict parasitic components in PSCs. We have used this foundation to devise an iterative PSC design methodology that starts with a set of realistic design constraints and ends with the optimal PSC pair geometries. We have executed this procedure on two design examples at 1 and 5 MHz achieving power transmission efficiencies of 41.2% and 85.8%, respectively, at 10-mm spacing. All results are verified with simulations using a commercial field solver (HFSS) as well as measurements using PSCs fabricated on printed circuit boards.

In vitro and in vivo testing of a wireless multichannel stimulating telemetry microsystem.

An inductively powered 64-site current microstimulating system, Interestim-2B, with a modular architecture and minimal number of off-chip components has been developed for neural prosthesis applications. Interestim-2B can generate any arbitrary current waveform and supports a variety of monopolar and bipolar stimulation protocols. A common analog line provides access to each site potential, and exhausts residual stimulus charges. In situ site impedance measurement capability helps indicate the defective sites in chronic stimulations. This paper also summarizes some of the in vitro and in vivo experimental results using a 16-site implant.