No abstract

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.

We review integrated circuits for low-frequency noise and offset rejection as a motivation for the presented digitally-assisted neural amplifier design methodology. Conventional AC-coupled neural amplifiers inherently reject input DC offset but have key limitations in area, linearity, DC drift, and spectral accuracy. Their chopper stabilization reduces low-frequency intrinsic noise at the cost of degraded area, input impedance and design complexity. DC-coupled implementations with digital high-pass filtering yield improved area, linearity, drift, and spectral accuracy and are inherently suitable for simple chopper stabilization. As a design example, a 56-channel 0.13 [Formula: see text] CMOS intracranial EEG interface is presented. DC offset of up to ±50 mV is rejected by a digital low-pass filter and a 16-bit delta-sigma DAC feeding back into the folding node of a folded-cascode LNA with CMRR of 65 dB. A bank of seven column-parallel fully differential SAR ADCs with ENOB of 6.6 are shared among 56 channels resulting in 0.018 [Formula: see text] effective channel area. Compensation-free direct input chopping yields integrated input-referred noise of 4.2 μV over the bandwidth of 1 Hz to 1 kHz. The 8.7 [Formula: see text] chip dissipating 1.07 mW has been validated in vivo in online intracranial EEG monitoring in freely moving rats.

In this paper, we present the design and implementation of a wireless wearable electronic system dedicated to remote data recording for brain monitoring. The reported wireless recording system is used for a) simultaneous near-infrared spectrometry (NIRS) and scalp electro-encephalography (EEG) for noninvasive monitoring and b) intracerebral EEG (icEEG) for invasive monitoring. Bluetooth and dual radio links were introduced for these recordings. The Bluetooth-based device was embedded in a noninvasive multichannel EEG-NIRS system for easy portability and long-term monitoring. On the other hand, the 32-channel implantable recording device offers 24-bit resolution, tunable features, and a sampling frequency up to 2 kHz per channel. The analog front-end preamplifier presents low input-referred noise of 5 μ VRMS and a signal-to-noise ratio of 112 dB. The communication link is implemented using a dual-band radio frequency transceiver offering a half-duplex 800 kb/s data rate, 16.5 mW power consumption and less than 10(-10) post-correction Bit-Error Rate (BER). The designed system can be accessed and controlled by a computer with a user-friendly graphical interface. The proposed wireless implantable recording device was tested in vitro using real icEEG signals from two patients with refractory epilepsy. The wirelessly recorded signals were compared to the original signals recorded using wired-connection, and measured normalized root-mean square deviation was under 2%.

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 .