Marijn N. van Dongen

Cerebellar output controls generalized spike-and-wave discharge occurrence

Disrupting thalamocortical activity patterns has proven to be a promising approach to stop generalized spike‐and‐wave discharges (GSWDs) characteristic of absence seizures. Here, we investigated to what extent modulation of neuronal firing in cerebellar nuclei (CN), which are anatomically in an advantageous position to disrupt cortical oscillations through their innervation of a wide variety of thalamic nuclei, is effective in controlling absence seizures.

A Power-Efficient Multichannel Neural Stimulator Using High-Frequency Pulsed Excitation From an Unfiltered Dynamic Supply

This paper presents a neural stimulator system that employs a fundamentally different way of stimulating neural tissue compared to classical constant current stimulation. A stimulation pulse is composed of a sequence of current pulses injected at a frequency of 1 MHz for which the duty cycle is used to control the stimulation intensity. The system features 8 independent channels that connect to any of the 16 electrodes at the output. A sophisticated control system allows for individual control of each channels stimulation and timing parameters. This flexibility makes the system suitable for complex electrode configurations and current steering applications. Simultaneous multichannel stimulation is implemented using a high frequency alternating technique, which reduces the amount of electrode switches by a factor 8. The system has the advantage of requiring a single inductor as its only external component. Furthermore it offers a high power efficiency, which is nearly independent on both the voltage over the load as well as on the number of simultaneously operated channels. Measurements confirm this: in multichannel mode the power efficiency can be increased for specific cases to 40% compared to 20% that is achieved by state-of-the-art classical constant current stimulators with adaptive power supply.

Biphasic stimulator circuit for a wide range of electrode-tissue impedance dedicated to cochlear implants

This paper presents an implementation of a least voltage drop neural biphasic stimulator circuit applied in cochlear implants. Using a double loop negative feedback topology, the output impedance of the current generator is increased, while requiring only one effective drain-source voltage drop (Veff). This allows the circuit to convey more charge into the tissue. The circuit can provide a biphasic stimulation scheme from a single ended supply with an amplitude range of 10µA up to 1.05mA for a wide range of electrode-tissue impedances, RL=1kΩ∼10kΩ, CL=1nF∼10nF. The stimulation current is set by scaling a reference current using a two stage binary-weighted transistor DAC configuration (3 bits HV transistor DAC and 4 bits LV transistor DAC) to improve the speed of stimulation pulses and minimize the area of the circuit. Simulation results, using the AMS 0.18µm high-voltage CMOS process, show that the charge error within a cycle (600µs) is only 0.02%, equivalent to a DC current error of 3nA at the maximum stimulation current with a load of 10kΩ+10nF.

A least-voltage drop high output resistance current source for neural stimulation

This paper presents a feedback technique to increase the output resistance of a MOS current mirror circuit that requires only one effective drain-source voltage drop. The proposed circuit requires a few additional current braches to form two feedback loops. With its compact structure, the proposed circuit is suitable as a current generator for neural stimulation. Simulation results, using 0.35 μm AMIS I3T25 technology, show that the proposed current generator, applied for bi-phasic stimulation, can convey more charge to a series resistive-capacitive load compared to the widely use low-voltage cascode current source.

A switched-mode multichannel neural stimulator with a minimum number of external components

This work proposes a system design for neural stimulators. It eliminates the need for a DC-DC converter which is normally used to increase the battery voltage. Instead it combines the DC-DC converter and stimulator output stage into a single system block. The number of external components needed for the system is reduced to a single inductor only. The system offers high power efficiency operation (theoretical power efficiency of 100% and a simulated efficiency of around 60% over the full output range) by employing switched-mode operation. Furthermore the output has a current source character, making charge balanced stimulation relatively easy to implement. Finally it is also possible to stimulate multiple channels independently with this system. An example design is presented that can stimulate two channels with a maximum output voltage of 10 V, while being powered from a 3.5V battery.

Design of a versatile voltage based output stage for implantable neural stimulators

Neural stimulators have the potential of becoming very important devices for the treatment of a wide variety of diseases. One of the major problems with existing stimulators is the limited waveform adjustability. This precludes the use of sophisticated stimulation programs and thereby affects the efficacy of the therapy applied. For this reason a new type of stimulator is required. The physical principle underlying stimulation is based on elevating the tissue potential up to a particular level by injecting a particular amount of charge. Furthermore the injected charge needs to be canceled precisely in order to prevent tissue damage. Most existing stimulators use a current based architecture in which the charge is controlled by enabling the stimulator for a particular amount of time. Voltage based stimulation however yields a much higher power efficiency. A novel type of voltage based architecture using indirect current feedback of the tissue current is proposed. Using a current integrator with a very high dynamic range the injected charge can be controlled very precisely, while any arbitrary voltage waveform can be used for stimulation. Circuit simulations prove the feasibility of the approach and show a charge mismatch in the order of 0.1% paving the way to full charge balancing. Furthermore, they predict correct functionality over all process corners, including mismatch. The system only uses a single-ended supply and its quiescent power consumption is less than 15μW.

Does a coupling capacitor enhance the charge balance during neural stimulation? An empirical study

Due to their DC-blocking characteristic, coupling capacitors are widely used to prevent potentially harmful charge buildup at the electrode–tissue interface. Although the capacitors can be an effective safety measure, it often seems overlooked that coupling capacitors actually introduce an offset voltage over the electrode–tissue interface as well. This work investigates this offset voltage both analytically and experimentally. The calculations as well as the experiments using bipolar-driven platinum electrodes in a saline solution confirm that coupling capacitors introduce an offset, while they barely contribute to the passive charge balancing. In particular cases, this offset is shown to reach potentially dangerous voltage levels that could induce irreversible electrochemical reactions. This work therefore suggests that when the use of coupling capacitors is required, the offset voltage should be analyzed for all operating conditions to ensure it remains within safe boundaries.

An implementation of a wavelet-based seizure detection filter suitable for realtime closed-loop epileptic seizure suppression

This paper presents the design and implementation of a real-time epilepsy detection filter that is suitable for closed-loop seizure suppression. The design aims to minimize the detection delay, while a reasonable average detection rate is obtained. The filter is based on a complex Morlet wavelet and uses an adaptive thresholding strategy for the seizure discrimination. This relatively simple configuration allows the algorithm to run on a cheap and readily available microprocessor prototyping platform. The performance of the filter is verified using both in vivo real-time measurements as well as simulations over a pre-recorded EEG dataset (29.75 hours with 1914 seizures). An average detection delay of 492 ms is achieved with a sensitivity of 96.03% and a specificity of 93.60%.

High frequency switched-mode stimulation can evoke post synaptic responses in cerebellar principal neurons

This paper investigates the efficacy of high frequency switched-mode neural stimulation. Instead of using a constant stimulation amplitude, the stimulus is switched on and off repeatedly with a high frequency (up to 100 kHz) duty cycled signal. By means of tissue modeling that includes the dynamic properties of both the tissue material as well as the axon membrane, it is first shown that switched-mode stimulation depolarizes the cell membrane in a similar way as classical constant amplitude stimulation. These findings are subsequently verified using in vitro experiments in which the response of a Purkinje cell is measured due to a stimulation signal in the molecular layer of the cerebellum of a mouse. For this purpose a stimulator circuit is developed that is able to produce a monophasic high frequency switched-mode stimulation signal. The results confirm the modeling by showing that switched-mode stimulation is able to induce similar responses in the Purkinje cell as classical stimulation using a constant current source. This conclusion opens up possibilities for novel stimulation designs that can improve the performance of the stimulator circuitry. Care has to be taken to avoid losses in the system due to the higher operating frequency.

Balancing accuracy, delay and battery autonomy for pervasive seizure detection

A promising alternative for treating absence seizures has emerged through closed-loop neurostimulation, which utilizes a wearable or implantable device to detect and subsequently suppress epileptic seizures. Such devices should detect seizures fast and with high accuracy, while respecting the strict energy budget on which they operate. Previous work has overlooked one or more of these requirements, resulting in solutions which are not suitable for continuous closed-loop stimulation. In this paper, we perform an in-depth design space exploration of a novel seizure-detection algorithm, which uses a complex Morlet wavelet filter and a static thresholding mechanism to detect absence seizures. We consider both the accuracy and speed of our detection algorithm, as well as various trade-offs with device autonomy when executed on a low-power processor. For example, we demonstrate that a minimal decrease in average detection rate of only 1.83% (from 92.72% to 90.89%) allows for a substantial increase in device autonomy (of 3.7x) while also facilitating faster detection (from 710 ms to 540 ms).A promising alternative for treating absence seizures has emerged through closed-loop neurostimulation, which utilizes a wearable or implantable device to detect and subsequently suppress epileptic seizures. Such devices should detect seizures fast and with high accuracy, while respecting the strict energy budget on which they operate. Previous work has overlooked one or more of these requirements, resulting in solutions which are not suitable for continuous closed-loop stimulation. In this paper, we perform an in-depth design space exploration of a novel seizure-detection algorithm, which uses a complex Morlet wavelet filter and a static thresholding mechanism to detect absence seizures. We consider both the accuracy and speed of our detection algorithm, as well as various trade-offs with device autonomy when executed on a low-power processor. For example, we demonstrate that a minimal decrease in average detection rate of only 1.83% (from 92.72% to 90.89%) allows for a substantial increase in device autonomy (of 3.7x) while also facilitating faster detection (from 710 ms to 540 ms).