Arbitrary-Waveform Electro-Optical Intracranial Neurostimulator With Load-Adaptive High-Voltage Compliance.

A hybrid 16-channel current-mode and the 8-channel optical implantable neurostimulating system is presented. The system generates arbitrary-waveform charge-balanced current-mode electrical pulses with an amplitude ranging from 50 [Formula: see text] to 10 mA. An impedance monitoring feedback loop is employed to automatically adjust the supply voltage, yielding a load-optimized power dissipation. The 8-channel optical stimulator drives an array of LEDs, each with a maximum of 25 mA current amplitude, and reuses the arbitrary-waveform generation function of the electrical stimulator. The LEDs are assembled within a custom-made 4×4 ECoG grid electrode array, enabling precise optical stimulation of neurons with a 300 [Formula: see text] pitch between the LEDs and simultaneous monitoring of the neural response by the ECoG electrode, at different distances of the stimulation site. The hybrid stimulation system is implemented on a mini-PCB, and receives power and stimulation commands inductively through a second board and a coil stacked on top of it. The entire system is sized at 3×2 . 5×1 cm3 and weighs 7 grams. The system efficacy for electrical and optical stimulation is validated in-vivo using separate chronic and acute experiments.

Closed-Loop Neurostimulators: A Survey and A Seizure-Predicting Design Example for Intractable Epilepsy Treatment.

First, existing commercially available open-loop and closed-loop implantable neurostimulators are reviewed and compared in terms of their targeted application, physical size, system-level features, and performance as a medical device. Next, signal processing algorithms as the primary strength point of the closed-loop neurostimulators are reviewed, and various design and implementation requirements and trade-offs are discussed in details along with quantitative examples. The review results in a set of guidelines for algorithm selection and evaluation. Second, the implementation of an inductively-powered seizure-predicting microsystem for monitoring and treatment of intractable epilepsy is presented. The miniaturized system is comprised of two miniboards and a power receiver coil. The first board hosts a 24-channel neurostimulator system on chip fabricated in a [Formula: see text] CMOS technology and performs neural recording, on-chip digital signal processing, and electrical stimulation. The second board communicates recorded brain signals as well as signal processing results wirelessly. The multilayer flexible coil receives inductively-transmitted power. The system is sized at 2 × 2 × 0.7 [Formula: see text] and weighs 6 g. The approach is validated in the control of chronic seizures in vivo in freely moving rats.

Electronic Sleep Stage Classifiers: A Survey and VLSI Design Methodology.

First, existing sleep stage classifier sensors and algorithms are reviewed and compared in terms of classification accuracy, level of automation, implementation complexity, invasiveness, and targeted application. Next, the implementation of a miniature microsystem for low-latency automatic sleep stage classification in rodents is presented. The classification algorithm uses one EMG (electromyogram) and two EEG (electroencephalogram) signals as inputs in order to detect REM (rapid eye movement) sleep, and is optimized for low complexity and low power consumption. It is implemented in an on-board low-power FPGA connected to a multi-channel neural recording IC, to achieve low-latency (order of 1 ms or less) classification. Off-line experimental results using pre-recorded signals from nine mice show REM detection sensitivity and specificity of 81.69% and 93.86%, respectively, with the maximum latency of 39 [Formula: see text]. The device is designed to be used in a non-disruptive closed-loop REM sleep suppression microsystem, for future studies of the effects of REM sleep deprivation on memory consolidation.

Low-Radiation Cellular Inductive Powering of Rodent Wireless Brain Interfaces: Methodology and Design Guide.

This paper presents a general methodology of inductive power delivery in wireless chronic rodent electrophysiology applications. The focus is on such systems design considerations under the following key constraints: maximum power delivery under the allowable specific absorption rate (SAR), low cost and spatial scalability. The methodology includes inductive coil design considerations within a low-frequency ferrite-core-free power transfer link which includes a scalable coil-array power transmitter floor and a single-coil implanted or worn power receiver. A specific design example is presented that includes the concept of low-SAR cellular single-transmitter-coil powering through dynamic tracking of a magnet-less receiver spatial location. The transmitter coil instantaneous supply current is monitored using a small number of low-cost electronic components. A drop in its value indicates the proximity of the receiver due to the reflected impedance of the latter. Only the transmitter coil nearest to the receiver is activated. Operating at the low frequency of 1.5 MHz, the inductive powering floor delivers a maximum of 15.9 W below the IEEE C95 SAR limit, which is over three times greater than that in other recently reported designs. The power transfer efficiency of 39% and 13% at the nominal and maximum distances of 8 cm and 11 cm, respectively, is maintained.

Seizure Suppression Efficacy of Closed-Loop Versus Open-Loop Deep Brain Stimulation in a Rodent Model of Epilepsy.

We assess and compare the effects of both closed-loop and open-loop neurostimulation of the rat hippocampus by means of a custom low-power programmable therapeutic neurostimulation device on the suppression of spontaneous seizures in a rodent model of epilepsy. Chronic seizures were induced by intraperitoneal kainic acid injection. Two bipolar electrodes were implanted into the CA1 regions of both hippocampi. The electrodes were connected to the custom-built programmable therapeutic neurostimulation device that can trigger an electrical stimulation either in a periodic manner or upon detection of the intracerebral electroencephalographic (icEEE) seizure onset. This device includes a microchip consisting of a 256-channel icEEG recording system and a 64-channel stimulator, and a programmable seizure detector implemented in a field-programmable gate array (FPGA). The neurostimulator was used to evaluate seizure suppression efficacy in ten epileptic rats for a total of 240 subject-days (5760 subject-hours). For this purpose, all rats were randomly divided into two groups: the no-stimulation group and the stimulation group. The no-stimulation group did not receive stimulation. The stimulation group received, first, closed-loop stimulation and, next, open-loop stimulation. The no-stimulation and stimulation groups had a similar seizure frequency baseline, averaging five seizures per day. Closed-loop stimulation reduced seizure frequency by 90% and open-loop stimulation reduced seizure frequency by 17%, both in the stimulation group as compared to the no-stimulation group.

320-channel active probe for high-resolution neuromonitoring and responsive neurostimulation.

We present a 320-channel active probe for high-spatial-resolution neuromonitoring and responsive neurostimulation. The probe comprises an integrated circuit (IC) cell array bonded to the back side of a pitch-matched microelectrode array. The IC enables up to 256-site neural recording and 64-site neural stimulation at the spatial resolution of 400 µ m and 200 µ m, respectively. It is suitable for direct integration with electrode arrays with the shank pitch of integer multiples of 200 µm. In the presented configuration, the IC is bonded with a 8 × 8 400 µ m-pitch Utah electrode array (UEA) and up to additional 192 recording channels are used for peripheral neuromonitoring. The 0.35 µ m CMOS circuit array has a total die size of 3.5 mm × 3.65 mm. Each stimulator channel employs a current memory for simultaneous multi-site neurostimulation, outputs 20 µA-250 µA square or arbitrary waveform current, occupies 0.02 mm (2), and dissipates 2.76 µ W quiescent power. Each fully differential recording channel has two stages of amplification and filtering and an 8-bit single-slope ADC, occupies 0.035 mm (2) , and consumes 51.9 µ W. The neural probe has been experimentally validated in epileptic seizure propagation studies in a mouse hippocampal slice in vitro and in responsive neurostimulation for seizure suppression in an acute epilepsy rat model in vivo .

A low-power high-sensitivity CMOS mixed-signal seizure-onset detector.

In this paper, we present a new seizure detection algorithm and the associated CMOS circuitry implementation. The proposed low-power seizure detector is a good candidate for an implantable epilepsy prosthesis. The device is designed for patient-specific seizure detection with a one variable parameter. The parameter value is extracted from a single seizure that is subsequently excluded from the validation phase. A two-path system is also proposed to minimize the detection delay. The algorithm is first validated using MATLAB® tools and then implemented and validated using circuits designed in a standard 0.18-µm CMOS process with a total power dissipation of 7.08 µW. A total of 13 seizures from two drug-resistant epileptic patients are assessed using the proposed algorithm and resulted in 100% sensitivity and a mean detection delay of 9.7 s after electrical onset.