39 research outputs found

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

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    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

    Evolution of optogenetic microdevices

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    Implementation of optogenetic techniques is a recent addition to the neuroscientists\u27 preclinical research arsenal, helping to expose the intricate connectivity of the brain and allowing for on-demand direct modulation of specific neural pathways. Developing an optogenetic system requires thorough investigation of the optogenetic technique and of previously fabricated devices, which this review accommodates. Many experiments utilize bench-top systems that are bulky, expensive, and necessitate tethering to the animal. However, these bench-top systems can make use of power-demanding technologies, such as concurrent electrical recording. Newer portable microdevices and implantable systems carried by freely moving animals are being fabricated that take advantage of wireless energy harvesting to power a system and allow for natural movements that are vital for behavioral testing and analysis. An investigation of the evolution of tethered, portable, and implantable optogenetic microdevices is presented, and an analysis of benefits and detriments of each system, including optical power output, device dimensions, electrode width, and weight is given. Opsins, light sources, and optical fiber coupling are also discussed to optimize device parameters and maximize efficiency from the light source to the fiber, respectively. These attributes are important considerations when designing and developing improved optogenetic microdevices

    Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals

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    Monitoring representative fractions of neurons from multiple brain circuits in behaving animals is necessary for understanding neuronal computation. Here we describe a system that allows high channel count recordings from a small volume of neuronal tissue using a lightweight signal multiplexing head-stage that permits free behavior of small rodents. The system integrates multi-shank, high-density recording silicon probes, ultra-flexible interconnects and a miniaturized microdrive. These improvements allowed for simultaneous recordings of local field potentials and unit activity from hundreds of sites without confining free movements of the animal. The advantages of large-scale recordings are illustrated by determining the electro-anatomical boundaries of layers and regions in the hippocampus and neocortex and constructing a circuit diagram of functional connections among neurons in real anatomical space. These methods will allow the investigation of circuit operations and behavior-dependent inter-regional interactions for testing hypotheses of neural networks and brain function

    A wireless electro-optic platform for multimodal electrophysiology and optogenetics in freely moving rodents

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    This paper presents the design and the utilization of a wireless electro-optic platform to perform simultaneous multimodal electrophysiological recordings and optogenetic stimulation in freely moving rodents. The developed system can capture neural action potentials (AP), local field potentials (LFP) and electromyography (EMG) signals with up to 32 channels in parallel while providing four optical stimulation channels. The platform is using commercial off-the-shelf components (COTS) and a low-power digital field-programmable gate array (FPGA), to perform digital signal processing to digitally separate in real time the AP, LFP and EMG while performing signal detection and compression for mitigating wireless bandwidth and power consumption limitations. The different signal modalities collected on the 32 channels are time-multiplexed into a single data stream to decrease power consumption and optimize resource utilization. The data reduction strategy is based on signal processing and real-time data compression. Digital filtering, signal detection, and wavelet data compression are used inside the platform to separate the different electrophysiological signal modalities, namely the local field potentials (1–500 Hz), EMG (30–500 Hz), and the action potentials (300–5,000 Hz) and perform data reduction before transmitting the data. The platform achieves a measured data reduction ratio of 7.77 (for a firing rate of 50 AP/second) and weights 4.7 g with a 100-mAh battery, an on/off switch and a protective plastic enclosure. To validate the performance of the platform, we measured distinct electrophysiology signals and performed optogenetics stimulation in vivo in freely moving rondents. We recorded AP and LFP signals with the platform using a 16-microelectrode array implanted in the primary motor cortex of a Long Evans rat, both in anesthetized and freely moving conditions. EMG responses to optogenetic Channelrhodopsin-2 induced activation of motor cortex via optical fiber were also recorded in freely moving rodents

    Sleep studies in mice - open and closed loop devices for untethered recording and stimulation

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    Sleep is an important biological processes that has been studied extensively to date. Research in sleep typically involves mice experiments that use heavy benchtop equipment or basic neural loggers to record ECoG/EMG signals which are then processed offline in workstations. These systems limit the complexity of experiments that can be carried out to only simple open loop recordings, due to either the tethered setup used, which restricts animal movements, or the lack of devices that can offer more advanced features without compromising its portability. With rising popularity in exploring more physiological features that can affect sleep, such as temperature, whose importance has been highlighted in several papers [1][2][3] and advances in optogenetic stimulation, allowing high temporal and spatial neural control, there is now an unprecedented demand for experimental setups using new closed loop paradigms. To address this, this thesis presents compact and lightweight neural logging devices that are not only capable of measuring ECoG and EMG signals for core sleep analysis but also capable of taking high resolution temperature recordings and delivering optogenetic stimulus with fully adjustable parameters. Together with its embedded on-board automatic sleep stage scoring algorithm, the device will allow researchers for the first time to be able to quickly uncover the role a neural circuit plays in sleep regulation through selective neural stimulation when the animal is under the target sleep vigilance state. Original contributions include: the development of two novel multichannel neural logging devices, one for core sleep analysis and another for closed loop experimentation; the development and implementation of a lightweight, fast and highly accurate automatic on-line sleep stage scoring algorithm; and the development of a custom optogenetic coupler that is compatible with most current optogenetic setups for LED-Optical fibre coupling.Open Acces

    Dissection of Affective Catecholamine Circuits Using Traditional and Wireless Optogenetics

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    Parsing the complexity of the mammalian brain has challenged neuroscientists for thousands of years. In the early 21st century, advances in materials science and neuroscience have enabled unprecedented control of neural circuitry. In particular, cell-type selective manipulations, such as those with optogenetics and chemogenetics, routinely provide answers to previously intractable neurobiological questions in the intact, behaving animal. In this two-part dissertation, I first introduce new minimally invasive, wireless technology to perturb neural activity in the ventral tegmental area dopaminergic system of freely moving animals. I report a series of novel devices for studying and perturbing intact neural systems through optogenetics, microfluidic pharmacology, and electrophysiology. Unlike optogenetic approaches that rely on rigid, glass fiber optics coupled to external light sources, these novel devices utilize flexible substrates to carry microscale, inorganic light emitting diodes (μ-ILEDs), multimodal sensors, and/or microfluidic channels into the brain. Each class of device can be wirelessly controlled, enabling studies in freely behaving mice and achieving previously untenable control of catecholamine neural circuitry. In the second part of this dissertation, I apply existing cell-type selective approaches to dissect the role of the locus coeruleus noradrenergic (LC-NE) system in anxiety-like and aversive behaviors. The LC-NE system is one of the first systems engaged following a stressful event. While LC-NE neurons are known to be activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated until now. I demonstrate that increased tonic activity of LC-NE neurons is both necessary and sufficient for stress-induced anxiety; a behavior which is driven by LC projections to the basolateral amygdala. Furthermore, this activity and behavior is elicited by corticotropin releasing hormone-containing afferent inputs into the LC from the central amygdala. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. Together these two objectives provide a rich technological toolbox for neuroscientists and yield important knowledge of how small catecholamine structures with widespread forebrain innervation can selectively mediate higher order behaviors

    Implantable Neural Probes for Electrical Recording and Optical Stimulation of Cellular Level Neural Circuitry in Behaving Animals.

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    In order to advance the understanding of brain function, it is critical to monitor how neural circuits work together and perform computational processing. For the past few decades, a wide variety of neural probes have been developed to study the electrophysiology of the brain. This work is focused on two important objectives to improve the brain-computer interface: 1) to enhance the reliability of recording electrodes by optimizing the shank structure; 2) to incorporate optical stimulation capability in addition to electrical recording for applications involving optogenetics. For the first objective, a flexible 64-channel parylene probe was designed with unique geometries for reduced tissue reactions. In order to provide the mechanical stiffness necessary to penetrate the brain, the miniaturized, flexible probes were coated with a lithographically patterned silk fibroin, which served as a biodegradable insertion shuttle. Because the penetration strength is independent from the properties of the probe itself, the material and geometry of the probe structure can be optimally designed without constraints. These probes were successfully implanted into the layer-V of motor cortex in 6 rats and recorded neural activities in vivo for 6 weeks. For the second objective, either optical waveguides or μLEDs were monolithically integrated on the probe shanks for optogenetic applications. Compared to existing methods, this work can offer high spatial-temporal resolution to record and stimulate from even subcellular neural structures. In the experiments using wild type animals, despite optimized recording of spontaneous neural activities, the cells never responded to illumination. In contrast, for the ChR2 expressed animals, light activation of neural activities was extremely robust and local, which phase-locked to the light waveform whenever the cell was close to the light source. In particular, the probes integrated with μLEDs were capable of driving different neural circuit behaviors using two adjacent μLEDs separated only by a 60-μm-pitch. With 3 μLEDs integrated at the tip of each of the 4 probe shanks, this novel optogenetic probe can provide more than 480 million (12!) different spiking sequences at the sub-cellular resolution, which is ideal to manipulate high density neural network with versatility and precision.PhDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111604/1/wufan_1.pd

    Bidirectional optogenetic control of inhibitory neurons in freely-moving mice

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    Objective: Optogenetic manipulations of excitable cells enable activating or silencing specific types of neurons. By expressing two types of exogenous proteins, a single neuron can be depolarized using light of one wavelength and hyperpolarized with another. However, routing two distinct wavelengths into the same brain locality typically requires bulky optics that cannot be implanted on the head of a freely-moving animal. Methods: We developed a lens-free approach for constructing dual-color head-mounted, fiber-based optical units: any two wavelengths can be combined. Results: Here, each unit was comprised of one 450 nm and one 638 nm laser diode, yielding light power of 0.4 mW and 8 mW at the end of a 50 micrometer multimode fiber. To create a multi-color/multi-site optoelectronic device, a four-shank silicon probe mounted on a microdrive was equipped with two dual-color and two single-color units, for a total weight under 3 g. Devices were implanted in mice expressing the blue-light sensitive cation channel ChR2 and the red-light sensitive chloride pump Jaws in parvalbumin-immunoreactive (PV) inhibitory neurons. The combination of dual-color units with recording electrodes was free from electromagnetic interference, and device heating was under 7{\deg}C even after prolonged operation. Conclusion: Using these devices, the same cortical PV cell could be activated and silenced. This was achieved for multiple cells both in neocortex and hippocampus of freely-moving mice. Significance: This technology can be used for controlling spatially intermingled neurons that have distinct genetic profiles, and for controlling spike timing of cortical neurons during cognitive tasks.Comment: 11 pages, 9 figure
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