Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

Dual-side and three-dimensional microelectrode arrays fabricated from ultra-thin silicon substrates

A method for fabricating planar implantable microelectrode arrays was demonstrated using a process that relied on ultra-thin silicon substrates, which ranged in thickness from 25 to 50 µm. The challenge of handling these fragile materials was met via a temporary substrate support mechanism. In order to compensate for putative electrical shielding of extracellular neuronal fields, separately addressable electrode arrays were defined on each side of the silicon device. Deep reactive ion etching was employed to create sharp implantable shafts with lengths of up to 5 mm. The devices were flip-chip bonded onto printed circuit boards (PCBs) by means of an anisotropic conductive adhesive film. This scalable assembly technique enabled three-dimensional (3D) integration through formation of stacks of multiple silicon and PCB layers. Simulations and measurements of microelectrode noise appear to suggest that low impedance surfaces, which could be formed by electrodeposition of gold or other materials, are required to ensure an optimal signal-to-noise ratio as well a low level of interchannel crosstalk

A neural probe with up to 966 electrodes and up to 384 configurable channels in 0.13 μm SOI CMOS

In vivo recording of neural action-potential and local-field-potential signals requires the use of high-resolution penetrating probes. Several international initiatives to better understand the brain are driving technology efforts towards maximizing the number of recording sites while minimizing the neural probe dimensions. We designed and fabricated (0.13-μm SOI Al CMOS) a 384-channel configurable neural probe for large-scale in vivo recording of neural signals. Up to 966 selectable active electrodes were integrated along an implantable shank (70 μm wide, 10 mm long, 20 μm thick), achieving a crosstalk of −64.4 dB. The probe base (5 × 9 mm2) implements dual-band recording and a 1

Bidirectional Neural Interface Circuits with On-Chip Stimulation Artifact Reduction Schemes

Bidirectional neural interfaces are tools designed to “communicate” with the brain via recording and modulation of neuronal activity. The bidirectional interface systems have been adopted for many applications. Neuroscientists employ them to map neuronal circuits through precise stimulation and recording. Medical doctors deploy them as adaptable medical devices which control therapeutic stimulation parameters based on monitoring real-time neural activity. Brain-machine-interface (BMI) researchers use neural interfaces to bypass the nervous system and directly control neuroprosthetics or brain-computer-interface (BCI) spellers. In bidirectional interfaces, the implantable transducers as well as the corresponding electronic circuits and systems face several challenges. A high channel count, low power consumption, and reduced system size are desirable for potential chronic deployment and wider applicability. Moreover, a neural interface designed for robust closed-loop operation requires the mitigation of stimulation artifacts which corrupt the recorded signals. This dissertation introduces several techniques targeting low power consumption, small size, and reduction of stimulation artifacts. These techniques are implemented for extracellular electrophysiological recording and two stimulation modalities: direct current stimulation for closed-loop control of seizure detection/quench and optical stimulation for optogenetic studies. While the two modalities differ in their mechanisms, hardware implementation, and applications, they share many crucial system-level challenges. The first method aims at solving the critical issue of stimulation artifacts saturating the preamplifier in the recording front-end. To prevent saturation, a novel mixed-signal stimulation artifact cancellation circuit is devised to subtract the artifact before amplification and maintain the standard input range of a power-hungry preamplifier. Additional novel techniques have been also implemented to lower the noise and power consumption. A common average referencing (CAR) front-end circuit eliminates the cross-channel common mode noise by averaging and subtracting it in analog domain. A range-adapting SAR ADC saves additional power by eliminating unnecessary conversion cycles when the input signal is small. Measurements of an integrated circuit (IC) prototype demonstrate the attenuation of stimulation artifacts by up to 42 dB and cross-channel noise suppression by up to 39.8 dB. The power consumption per channel is maintained at 330 nW, while the area per channel is only 0.17 mm2. The second system implements a compact headstage for closed-loop optogenetic stimulation and electrophysiological recording. This design targets a miniaturized form factor, high channel count, and high-precision stimulation control suitable for rodent in-vivo optogenetic studies. Monolithically integrated optoelectrodes (which include 12 µLEDs for optical stimulation and 12 electrical recording sites) are combined with an off-the-shelf recording IC and a custom-designed high-precision LED driver. 32 recording and 12 stimulation channels can be individually accessed and controlled on a small headstage with dimensions of 2.16 x 2.38 x 0.35 cm and mass of 1.9 g. A third system prototype improves the optogenetic headstage prototype by furthering system integration and improving power efficiency facilitating wireless operation. The custom application-specific integrated circuit (ASIC) combines recording and stimulation channels with a power management unit, allowing the system to be powered by an ultra-light Li-ion battery. Additionally, the µLED drivers include a high-resolution arbitrary waveform generation mode for shaping of µLED current pulses to preemptively reduce artifacts. A prototype IC occupies 7.66 mm2, consumes 3.04 mW under typical operating conditions, and the optical pulse shaping scheme can attenuate stimulation artifacts by up to 3x with a Gaussian-rise pulse rise time under 1 ms.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147674/1/mendrela_1.pd

Scalable Bundle Design for Massively Parallel Neuronal Recordings <i>In Vivo</i>

Neural coding consists of precise interactions between related neurons. New techniques are needed to measure the time sensitive interactions within entire neural networks to understand how the brain functions. Extracellular recording is the oldest method of measuring neural activity and can sample at a temporal resolution to resolve fast spiking neurons. If scaled to a sufficiently large number of simultaneous recorded neurons, this technique would be an excellent candidate for such large scale recording. I propose the combined use of glass ensheathed microwire bundle electrodes and an infrared camera readout integrated circuit to collect massively parallel neuronal recordings in vivo. This design will allow for the recording of high quality signals because of the non-intrusive dimensions, low stray capacitance, and enhanced surface impedance of the electrodes, as well as the high signal to noise amplification of the camera electronics. Here the construction of a system to record neural activity is described and its electrical properties are characterized. The results demonstrate the ability to successfully connect fabricated bundle electrodes to the indium bumps of the readout integrated circuit chip and to record voltage waveforms with a signal to noise ratio to resolve simulated spikes. In vivo experiments in the olfactory bulb of anaesthetized mice have resulted in recordings of action potentials from single units. The spike rate of these units increases with odor presentation and is pharmacologically inhibited which demonstrates the biological origin of the recorded activity. To further advance this technology, the stability and rate of connection to the readout electronics need to improve and insertion of electrode bundles with hundreds of more recording sites needs to be optimized. This promising design has several distinct advantages over existing fluorescence imaging and extracellular recording neurotechnologies for large scale neuronal recording

MR-compatible Electrophysiology Recording System for Multimodal Imaging

Simultaneous acquisition of functional magnetic resonance imaging (fMRI) and electrophysiological recordings is an emerging multimodal neuroimaging strategy for studying brain functions. However, the strong magnetic field generated during fMRI greatly degrades the electrophysiological signal quality during simultaneous acquisition. Here, I developed a low powered, miniaturized, system – “ECHO” which delivers a hardware and software solution to overcome the challenges presented by multimodal imaging. The device monitors fluctuations in electromagnetic field during fMRI and synchronizes amplification and sampling of electrophysiological signals to minimize effects of gradient and RF artifacts (electromagnetic artifacts). Furthermore, I introduced a concept of wirelessly transmitting recorded data through the MRI receiver coil. ECHO transmits the data at a frequency visible to the MRI receiver coil, after which the transmitted data is readily separable from the MRI image in the frequency domain. The MR-compatibility of the recorder was evaluated through a series of experiments with a phantom to study its effects on the MRI image quality. To further evaluate the effectiveness of ECHO, I recorded electrocardiogram and local field potential (evoked potential) in live rats during concurrent fMRI acquisition. In summary, ECHO offers a ‘plug and play’ solution to capture artifact-free electrophysiological data without the need of expensive amplifiers or synchronization hardware which require physical connection to the MRI scanner. This device is expected to make multimodal imaging more accessible and be applied for a broad range of fMRI studies in both the research and clinical fields

Sensor Developments for Electrophysiological Monitoring in Healthcare

Recent years have seen a renewal of interest in the development of sensor systems which can be used to monitor electrophysiological signals in a number of different settings. These include clinical, outside of the clinical setting with the subject ambulatory and going about their daily lives, and over long periods. The primary impetus for this is the challenge of providing healthcare for the ageing population based on home health monitoring, telehealth and telemedicine. Another stimulus is the demand for life sign monitoring of critical personnel such as fire fighters and military combatants. A related area of interest which, whilst not in the category of healthcare, utilises many of the same approaches, is that of sports physiology for both professional athletes and for recreation. Clinical diagnosis of conditions in, for example, cardiology and neurology remain based on conventional sensors, using established electrodes and well understood electrode placements. However, the demands of long term health monitoring, rehabilitation support and assistive technology for the disabled and elderly are leading research groups such as ours towards novel sensors, wearable and wireless enabled systems and flexible sensor arrays