A Closed-Loop Deep Brain Stimulation Device With a Logarithmic Pipeline ADC.

This dissertation is a summary of the research on integrated closed-loop deep brain stimulation for treatment of Parkinson’s disease. Parkinson's disease is a progressive disorder of the central nervous system affecting more than three million people in the United States. Deep Brain Stimulation (DBS) is one of the most effective treatments of Parkinson’s symptoms. DBS excites the Subthalamic Nucleus (STN) with a high frequency electrical signal. The proposed device is a single-chip closed-loop DBS (CDBS) system. Closed-loop feedback of sensed neural activity promises better control and optimization of stimulation parameters than with open-loop devices. Thanks to a novel architecture, the prototype system incorporates more functionality yet consumes less power and area compared to other systems. Eight front-end low-noise neural amplifiers (LNAs) are multiplexed to a single high-dynamic-range logarithmic, pipeline analog-to-digital converter (ADC). To save area and power consumption, a high dynamic-range log ADC is used, making analog automatic gain control unnecessary. The redundant 1.5b architecture relaxes the requirements for the comparator accuracy and comparator reference voltage accuracy. Instead of an analog filter, an on-chip digital filter separates the low frequency neural field potential signal from the neural spike energy. An on-chip controller generates stimulation patterns to control the 64 on-chip current-steering DACs. The 64 DACs are formed as a cascade of a single shared 2-bit coarse current DAC and 64 individual bi-directional 4-bit fine DACs. The coarse/fine configuration saves die area since the MSB devices tend to be large. Real-time neural activity was recorded with the prototype device connected to microprobes that were chronically implanted in two Long Evans rats. The recorded in-vivo signal clearly shows neural spikes of 10.2 dB signal-to-noise ratio (SNR) as well as a periodic artifact from neural stimulation. The recorded neural information has been analyzed with single unit sorting and principal component analysis (PCA). The PCA scattering plots from multi-layers of cortex represent diverse information from either single or multiple neural sources. The single-unit neural sorting analysis along with PCA verifies the feasibility of the implantable CDBS device for to in-vivo neural recording interface applications.Ph.D.Electrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60733/1/milaca_1.pd

A 6-bit, two-step, successive approximation logarithmic ADC for biomedical applications

This paper presents the design and realization of a novel low-power 6-bit successive approximation logarithmic ADC for biomedical applications. A two-step successive approximation method is proposed to obtain a piecewise-linear approximation of the desired logarithmic transfer function. The proposed ADC has been designed and simulated using process parameters from a standard 0.35 μm 2P4M CMOS technology with a single 1.8 V power supply voltage. Simulation results show that, at a sampling rate of 25 kS/s, the proposed ADC consumes 4.36 μW to 14.6 μW (proportional to input amplitudes). The proposed ADC achieves 18.6 pJ/conversion-step, maximum INL of 0.45 LSB, an ENOB of 4.97-bits, and SNDR of 31.7 dB with 1 V full-scale input range

VLSI Circuits for Bidirectional Neural Interfaces

Medical devices that deliver electrical stimulation to neural tissue are important clinical tools that can augment or replace pharmacological therapies. The success of such devices has led to an explosion of interest in the field, termed neuromodulation, with a diverse set of disorders being targeted for device-based treatment. Nevertheless, a large degree of uncertainty surrounds how and why these devices are effective. This uncertainty limits the ability to optimize therapy and gives rise to deleterious side effects. An emerging approach to improve neuromodulation efficacy and to better understand its mechanisms is to record bioelectric activity during stimulation. Understanding how stimulation affects electrophysiology can provide insights into disease, and also provides a feedback signal to autonomously tune stimulation parameters to improve efficacy or decrease side-effects. The aims of this work were taken up to advance the state-of-the-art in neuro-interface technology to enable closed-loop neuromodulation therapies. Long term monitoring of neuronal activity in awake and behaving subjects can provide critical insights into brain dynamics that can inform system-level design of closed-loop neuromodulation systems. Thus, first we designed a system that wirelessly telemetered electrocorticography signals from awake-behaving rats. We hypothesized that such a system could be useful for detecting sporadic but clinically relevant electrophysiological events. In an 18-hour, overnight recording, seizure activity was detected in a pre-clinical rodent model of global ischemic brain injury. We subsequently turned to the design of neurostimulation circuits. Three critical features of neurostimulation devices are safety, programmability, and specificity. We conceived and implemented a neurostimulator architecture that utilizes a compact on-chip circuit for charge balancing (safety), digital-to-analog converter calibration (programmability) and current steering (specificity). Charge balancing accuracy was measured at better than 0.3%, the digital-to-analog converters achieved 8-bit resolution, and physiological effects of current steering stimulation were demonstrated in an anesthetized rat. Lastly, to implement a bidirectional neural interface, both the recording and stimulation circuits were fabricated on a single chip. In doing so, we implemented a low noise, ultra-low power recording front end with a high dynamic range. The recording circuits achieved a signal-to-noise ratio of 58 dB and a spurious-free dynamic range of better than 70 dB, while consuming 5.5 μW per channel. We demonstrated bidirectional operation of the chip by recording cardiac modulation induced through vagus nerve stimulation, and demonstrated closed-loop control of cardiac rhythm

Advances in closed-loop deep brain stimulation devices

BACKGROUND: Millions of patients around the world are affected by neurological and psychiatric disorders. Deep brain stimulation (DBS) is a device-based therapy that could have fewer side-effects and higher efficiencies in drug-resistant patients compared to other therapeutic options such as pharmacological approaches. Thus far, several efforts have been made to incorporate a feedback loop into DBS devices to make them operate in a closed-loop manner. METHODS: This paper presents a comprehensive investigation into the existing research-based and commercial closed-loop DBS devices. It describes a brief history of closed-loop DBS techniques, biomarkers and algorithms used for closing the feedback loop, components of the current research-based and commercial closed-loop DBS devices, and advancements and challenges in this field of research. This review also includes a comparison of the closed-loop DBS devices and provides the future directions of this area of research. RESULTS: Although we are in the early stages of the closed-loop DBS approach, there have been fruitful efforts in design and development of closed-loop DBS devices. To date, only one commercial closed-loop DBS device has been manufactured. However, this system does not have an intelligent and patient dependent control algorithm. A closed-loop DBS device requires a control algorithm to learn and optimize the stimulation parameters according to the brain clinical state. CONCLUSIONS: The promising clinical effects of open-loop DBS have been demonstrated, indicating DBS as a pioneer technology and treatment option to serve neurological patients. However, like other commercial devices, DBS needs to be automated and modernized

Design and Development of Smart Brain-Machine-Brain Interface (SBMIBI) for Deep Brain Stimulation and Other Biomedical Applications

Machine collaboration with the biological body/brain by sending electrical information back and forth is one of the leading research areas in neuro-engineering during the twenty-first century. Hence, Brain-Machine-Brain Interface (BMBI) is a powerful tool for achieving such machine-brain/body collaboration. BMBI generally is a smart device (usually invasive) that can record, store, and analyze neural activities, and generate corresponding responses in the form of electrical pulses to stimulate specific brain regions. The Smart Brain-Machine-Brain-Interface (SBMBI) is a step forward with compared to the traditional BMBI by including smart functions, such as in-electrode local computing capabilities, and availability of cloud connectivity in the system to take the advantage of powerful cloud computation in decision making. In this dissertation work, we designed and developed an innovative form of Smart Brain-Machine-Brain Interface (SBMBI) and studied its feasibility in different biomedical applications. With respect to power management, the SBMBI is a semi-passive platform. The communication module is fully passive—powered by RF harvested energy; whereas, the signal processing core is battery-assisted. The efficiency of the implemented RF energy harvester was measured to be 0.005%. One of potential applications of SBMBI is to configure a Smart Deep-Brain-Stimulator (SDBS) based on the general SBMBI platform. The SDBS consists of brain-implantable smart electrodes and a wireless-connected external controller. The SDBS electrodes operate as completely autonomous electronic implants that are capable of sensing and recording neural activities in real time, performing local processing, and generating arbitrary waveforms for neuro-stimulation. A bidirectional, secure, fully-passive wireless communication backbone was designed and integrated into this smart electrode to maintain contact between the smart electrodes and the controller. The standard EPC-Global protocol has been modified and adopted as the communication protocol in this design. The proposed SDBS, by using a SBMBI platform, was demonstrated and tested through a hardware prototype. Additionally the SBMBI was employed to develop a low-power wireless ECG data acquisition device. This device captures cardiac pulses through a non-invasive magnetic resonance electrode, processes the signal and sends it to the backend computer through the SBMBI interface. Analysis was performed to verify the integrity of received ECG data

A HIGHLY-SCALABLE DC-COUPLED DIRECT-ADC NEURAL RECORDING CHANNEL ARCHITECTURE WITH INPUT-ADAPTIVE RESOLUTION

This thesis presents the design, development, and characterization of a novel neural recording channel architecture with (a) quantization resolution that is adaptive to the input signal's level of activity, (b) fully-dynamic power consumption that is linearly proportional to the recording resolution, and (c) immunity to DC offset and drifts at the input. Our results demonstrate the proposed design's capability in conducting neural recording with near lossless input-adaptive data compression, leading to a significant reduction in the energy required for both recording and data transmission, hence allowing for a potential high scaling of the number of recording channels integrated on a single implanted microchip without the need to increase the power budget. The proposed channel with the implemented compression technique is implemented in a standard 130nm CMOS technology with overall power consumption of 7.6uW and active area of 92×92µm for the implemented digital-backend

A HIGHLY-SCALABLE DC-COUPLED DIRECT-ADC NEURAL RECORDING CHANNEL ARCHITECTURE WITH INPUT-ADAPTIVE RESOLUTION

This thesis presents the design, development, and characterization of a novel neural recording channel architecture with (a) quantization resolution that is adaptive to the input signal's level of activity, (b) fully-dynamic power consumption that is linearly proportional to the recording resolution, and (c) immunity to DC offset and drifts at the input. Our results demonstrate the proposed design's capability in conducting neural recording with near lossless input-adaptive data compression, leading to a significant reduction in the energy required for both recording and data transmission, hence allowing for a potential high scaling of the number of recording channels integrated on a single implanted microchip without the need to increase the power budget. The proposed channel with the implemented compression technique is implemented in a standard 130nm CMOS technology with overall power consumption of 7.6uW and active area of 9292m for the implemented digital-backend

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