An Ultra High-Frequency 8-Channel Neurostimulator Circuit With [Formula: see text] Peak Power Efficiency.

In order to recruit neurons in excitable tissue, constant current neural stimulators are commonly used. Recently, ultra high-frequency (UHF) stimulation has been proposed and proven to have the same efficacy as constant-current stimulation. UHF stimulation uses a fundamentally different way of activating the tissue: each stimulation phase is made of a burst of current pulses with adjustable amplitude injected into the tissue at a high (e.g., [Formula: see text]) frequency. This paper presents the design, integrated circuit (IC) implementation, and measurement results of a power efficient multichannel UHF neural stimulator. The core of the neurostimulator is based on our previously proposed architecture of an inductor-based buck-boost dc-dc converter without the external output capacitor. The ultimate goal of this work is to increase the power efficiency of the UHF stimulator for multiple-channel operation, while keeping the number of external components minimal. To this end, a number of novel approaches were employed in the integrated circuit design domain. More specifically, a novel zero-current detection scheme is proposed. It allows to remove the freewheel diode typically used in dc-dc converters to prevent current to flow back from the load to the inductor. Furthermore, a gate-driver circuit is implemented which allows the use of thin gate-oxide transistors as high-voltage switches. By doing so, and exploiting the fundamental working principle of the proposed current-controlled UHF stimulator, the need for a high-voltage supply is eliminated and the stimulator is powered up from a [Formula: see text] input voltage. Both the current detection technique and the gate driving circuit of the current implementation allow to boost the power efficiency up to [Formula: see text] when compared to previous UHF stimulator works. A peak power efficiency of [Formula: see text] is achieved, while 8 independent channels with 16 fully configurable electrodes are used. The circuit is implemented in a [Formula: see text] HV process, and the total chip area is [Formula: see text].

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 channel's 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.

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.

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).

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.

Cerebellar output controls generalized spike-and-wave discharge occurrence.

OBJECTIVE: 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. METHODS: Two unrelated mouse models of generalized absence seizures were used: the natural mutant tottering, which is characterized by a missense mutation in Cacna1a, and inbred C3H/HeOuJ. While simultaneously recording single CN neuron activity and electrocorticogram in awake animals, we investigated to what extent pharmacologically increased or decreased CN neuron activity could modulate GSWD occurrence as well as short-lasting, on-demand CN stimulation could disrupt epileptic seizures. RESULTS: We found that a subset of CN neurons show phase-locked oscillatory firing during GSWDs and that manipulating this activity modulates GSWD occurrence. Inhibiting CN neuron action potential firing by local application of the γ-aminobutyric acid type A (GABA-A) agonist muscimol increased GSWD occurrence up to 37-fold, whereas increasing the frequency and regularity of CN neuron firing with the use of GABA-A antagonist gabazine decimated its occurrence. A single short-lasting (30-300 milliseconds) optogenetic stimulation of CN neuron activity abruptly stopped GSWDs, even when applied unilaterally. Using a closed-loop system, GSWDs were detected and stopped within 500 milliseconds. INTERPRETATION: CN neurons are potent modulators of pathological oscillations in thalamocortical network activity during absence seizures, and their potential therapeutic benefit for controlling other types of generalized epilepsies should be evaluated.

Does enriched acoustic environment in humans abolish chronic tinnitus clinically and electrophysiologically? A double blind placebo controlled study.

Animal research has shown that loss of normal acoustic stimulation can increase spontaneous firing in the central auditory system and induce cortical map plasticity. Enriched acoustic environment after noise trauma prevents map plasticity and abolishes neural signs of tinnitus. In humans, the tinnitus spectrum overlaps with the area of hearing loss. Based on these findings it can be hypothesized that stimulating the auditory system by presenting music compensating specifically for the hearing loss might also suppress chronic tinnitus. To verify this hypothesis, a study was conducted in three groups of tinnitus patients. One group listened just to unmodified music (i.e. active control group), one group listened to music spectrally tailored to compensate for their hearing loss, and a third group received music tailored to overcompensate for their hearing loss, associated with one (in presbycusis) or two notches (in audiometric dip) at the edge of hearing loss. Our data indicate that applying overcompensation to the hearing loss worsens the patients' tinnitus loudness, the tinnitus annoyance and their depressive feelings. No significant effects were obtained for the control group or for the compensation group. These clinical findings were associated with an increase in current density within the left dorsal anterior cingulate cortex in the alpha2 frequency band and within the left pregenual anterior cingulate cortex in beta1 and beta2 frequency band. In addition, a region of interest analysis also demonstrated an associated increase in gamma band activity in the auditory cortex after overcompensation in comparison to baseline measurements. This was, however, not the case for the control or the compensation groups. In conclusion, music therapy compensating for hearing loss is not beneficial in suppressing tinnitus, and overcompensating hearing loss actually worsens tinnitus, both clinically and electrophysiologically.