Wen Li - US grants

ECCS-1055269
Wen Li, Michigan State University
CAREER: Toward Biocompatible, Bi-directional, and Multi-channel Magnetic Neural Implants

ABSTRACT

The objective of this research is to fully realize biocompatible magnetic microsystems that permit seamless interfacing with nervous systems for studying and treating neural injuries and/or diseases. The approach is to integrate microcoil arrays and control microelectronics on a single platform for bi-directional and multi-site electromagnetic neural communication, utilizing flexible and biocompatible polymers as main structural and packaging materials to minimize bioreactivity and biofouling.

Intellectual Merit: Invention of new biomedical implants capable of monitoring and manipulating localized bio-electromagnetic fields will help reveal unknown cause-effect relationships between electrical and magnetic signals in biological systems. The developed polymer-based microfabrication and integration technologies can be broadly applicable to other bioimplants. In-depth understanding of neural responses to localized magnetic fields will lay the foundation for new neural-machine-interfaces in neurophysiology and clinical neurology, and ultimately neural implants that provide bi-directional electromagnetic guidance cues to enable neural circuit re-growth and lost neural function restoration.

Broader Impacts: The proposed research will create valuable tools to advance neuroscience and lead to new neural prostheses and therapies. Direct benefits to the society include the reduction of national healthcare cost and life quality improvement for patients suffering neural injuries and diseases. This work will offer multidisciplinary research experiences for undergraduate and graduate students, promote university curriculum development, and assist in supporting and retaining female and minority students through early exposure to science and engineering. Integrated outreach programs combining open-lab tours, summer camps, and teacher training will effectively convert state-of-art science into educational resources accessible to local K-12 schools and communities.

DESCRIPTION (provided by applicant): Anxiety is characterized by heightened response to threat. However, the precise etiologic basis of anxiety disorders remains obscure. Differing from prevailing amygdala-centric views of threat processing and anxiety pathophysiology, this application proposes a neurosensory account, highlighting a sensory pathway to anxiety. Based on accruing new evidence from our laboratory and other groups, we posit that the biological significance of a stimulus can be stored in the sensory system such that the affective value is decoded as soon as the input registers with the sensory brain, paralleling and often preceding limbic- based threat evaluation. As one of the first operations in the cognitive stream, biased sensory perception of threat can then influence downstream processes, directly or indirectly contributing to a variety of cognitive and emotional anomalies observed in anxiety. Representing one of the first lines of research on basic sensory processing of threat in anxiety, this program would provide new insights into basic threat analysis and anxiety genesis, and thus help to innovate clinical treatment for anxiety disorders. Towards that end, this proposal will employ a cognitive-affective neuroscience approach to firstly define sensory encoding of threat in anxiety with two conceptual emphases: 1) to accentuate highly specialized sensory representations of individual threat subtypes, which could inform the neural basis for distinct and sometimes contradictory responses and reflexes to different threats, and account for the heterogeneous symptomology of anxiety disorders (Specific Aim 1); and 2) to evaluate threat perception of multi- and cross-modal (vs. unimodal) sensory input, which, by optimally simulating real-life sensory experience, holds great promise for revealing novel multifaceted and modality-specific sensory biases of threat in anxiety (Specific Aim 2). Secondly, the planned research will mechanistically specify the impact of initial perceptual bias to threat on subsequent emotional and cognitive processes, giving rise to various anxiety symptoms (in particular, negative interpretation, excessive social avoidance and selective attention to threat; Specific Aim 3). In six independent experiments, we will employ a unique and fully developed constellation of expertise and techniques (functional magnetic resonance imaging, fMRI; brain event- related potentials, ERPs; autonomic physiology; psychophysics; and anxiety assessment and provocation) to determine the neural underpinnings of sensory perception of threat and its behavioral consequences, varying as a function of anxiety. The project findings will create a body of knowledge that is likely to challenge the dominant limbic-centered conceptualization of anxiety, promoting a shift to a multi-system, multi-path theorization.

DESCRIPTION (provided by applicant): The blood-brain barrier (BBB) restricts the passive diffusion of many drugs into the brain and constitutes a significant obstacle in the pharmacological treatment of central nervous system (CNS) disorders. Approximately 98% of new small-molecule drugs and almost 100% of large-molecule drugs such as recombinant proteins and gene-based medicines with proven CNS activity have BBB penetration problems. Therefore, our long term goal is to elucidate the regulatory mechanisms associated with the maintenance of the BBB function as a prerequisite to the development of protocols that can be used to facilitate therapeutic drugs entering the CNS for the treatment of neurological disease. We hypothesize that low concentrations of a prototypic BBB disruptor (the lipophilic cholinesterase inhibitor, chlorpyrifos, CPF) facilitate passage of exogenous substances across the BBB by short-term (temporary and reversible) alteration of BBB integrity. The hypothesis is based on our following observations from our preliminary studies: 1). low, nontoxic concentrations of CPF and its metabolites transverse the BBB. 2). CPF and its metabolites contribute to the alteration of BBB integrity and structure, as evidenced by altered tight junction proteins and electric resistance in vitro. 3). CPF disrupts BBB tight junction protein and transien receptor potential channels gene expression in a short-term and reversible way in vitro. Based on these observations, the focus of this R03 proposal is on the molecular and biochemical mechanisms by which the CPF affects the disruption of the BBB in vivo. There are 2 specific aims in the proposal: (1) To determine the time-related effects of low dose CPF treatment on the alteration of BBB-tight junction (BBB-TJ) proteins. (2) To identify the signaling pathways involved in the disruption of BBB-TJ following low dose CPF treatment. The methods to be employed will include three levels of experiments to achieve our goal and to prove our hypothesis. (1) At the functional level, Evan blue dye will be used to evaluate BBB disruption. (2) At the cellular level, Western blot, immunofluorescence assays, ELISA, and enzymatic activities will be used to analyze BBB protein profiles after CPF treatment. (3) At the molecular level, quantitative real-time PCR will be used to verify BBB protein level changes correlating to gene changes. In addition, MR imaging technique will be used to evaluate brain water content after CPF treatment. The data obtained from the proposed studies will significantly advance our understanding of the underlying molecular mechanisms associated with the maintenance of BBB function, and also will be very useful for devising strategies associated with use of low dose, safe lipophilic compounds as an effective pretreatment to allow therapeutic drug delivery to the CNS for treatment of Alzheimer's disease, Parkinson's disease, stroke, schizophrenia, epilepsy and other conditions of the CNS.

PI: Li

Proposal No: 1264772

Technical Description and Intellectual Merit: Optic nerve injuries due to diseases (e.g. glaucoma) or trauma often result in lifelong disabilities, and at present most are incurable. Retrograde degeneration of ganglion cells following optic nerve injuries is believed to result primarily from a reduction in the transport of neurotrophic materials these neurons obtain from their target neurons in the visual thalamus. Current neurotrophic factor-based treatments are inadequate to provide long-term neuroprotection and can produce abnormal dendritic morphology in both transduced and non-transduced nerve cells. The objective of this proposed research is to investigate an innovative strategy for treatment of optic nerve injuries, combining neurotrophic therapy of the eye with optical stimulation of the visual cortex to promote endogenous neuroprotection and preservation of retinal ganglion cells (RGC) and retinal function. It is hypothesized that combined treatment of both the eye and visual cortex provides a more significant and sustained level of neuroprotection as compared to treating the eye alone. Specifically, optical stimulation of cortical neurons across different layers will be achieved via a novel three-dimensional (3-D) Opto-µECoG (electrocorticography) interface, which consists of multiple micro light emitting diode (µ-LED) light sources, out-of-plane microscale polymer waveguides, and transparent µECoG electrodes on a single flexible polymer platform. Integration of individually addressable µ-LED chips with waveguides will help minimize the LED light scattering within brain tissue to achieve high-spatial resolution and precise light delivery to the target neurons. The transparent epidural ECoG electrodes will permit real-time monitoring of light-induced neural activity in visual cortex. The functionality and reliability of the engineered Opto-µECoG interface will be evaluated using both in-vitro primary cortical slices and in vivo rat models. Light-induced activation of the visual thalamus will be assessed, as indicated by enhanced electrical activity of neurons in the visual thalamus as well as up-regulated levels of BDN Fandits associated anti-apoptotic proteins (ERK 1,2, PI3K/Akt, and CREB).Enhanced neuroprotection and preservation of vision following the combined treatment will also be investigated ina rat model with optic nerve trauma, by comparing electroretinographic responses from animal eyes and vision-evoked potentials from visual cortex. The ultimate goal is the development of optogenetics-based treatment strategies not only for optic neuropathies, but also for other brain injuries in general. The PIs have established collaborations and complementary research expertise in the areas of biomedical microelectrome chanical systems (BioMEMS), neural engineering, and neurophysiology, which make this project viable in its execution.

Broader Impacts: The scientific impacts of this research include: 1) investigation of a transformative treatment strategy for neural protection and restoration in eyes with glaucoma, 2) development of optogenetics-based engineering tools for seamless communication with neurons, and 3) in-depth understanding of the mechanisms of trauma-induced cellular degeneration and neuroprotection. While it is specifically tailored for glaucoma treatment, the proposed treatment strategy can also be used to treat trauma-induced optic nerve injuries and other brain injuries such as sensory deficits, Parkinson's disease, and depression. The most pronounced long-term benefits of this work to society include a reduction of healthcare cost and quality of life improvement for a sizeable, and growing, population affected by the above conditions. In addition to its scientific impacts, this work will offer unique research experiences for undergraduate and graduate students to understand technical details of different disciplines and develop multiple, translational, biomedical skills. To reach larger audiences, the results will be shared with students through science fairs, with scientific communities through conference presentations and journal publications, and with the public through exhibits. The integrated outreach program will be very effective due to the visually appealing nature of microscale devices and systems. The curriculum development and improvement will provide tremendous opportunities to introduce interdisciplinary topics and hands-on experimental experiences to students at multiple levels. The results of the educational programs will be assessed through internal and external evaluators and disseminated through conferences (e.g. ASEE, FIE and MEMS) and in-house programs, such as Frontiers in Science, at MSU. These efforts will encourage more students to pursue careers in research and ultimately produce skilled and knowledgeable workforces for biomedical, neural science, and engineering.

Plasma density is one of the fundamental quantities of the magnetosphere-ionosphere (M-I) coupling that affects the growth and propagation of various plasma wave modes, magnetic reconnection rate, and ionospheric conductance; all of which strongly influence energy and mass transport in the M-I system. By taking advantage of simultaneous satellite-ground conjunctions in recent years, this award will help determining the source region of dayside density modulations, specifically addressing three outstanding scientific questions: Where does the enhanced density originate? How do enhanced density regions evolve in time? And what is the typical size of the enhanced density regions?

The plasma density in the dayside magnetosphere is highly structured, and this structure can have a large impact on the excitation of whistler-mode waves that in turn scatter plasma sheet electrons drifting from the nightside and accelerate electrons in the Earth's radiation belts. It has been recently found that whistler-mode waves drive structured patches of the diffuse aurora; this can be used to highlight enhanced density regions in the dayside magnetosphere. The dayside 'aurora-wave-density' correlations lead to questions about the origin of enhanced plasma density patches and their propagation in the dayside magnetosphere. Satellite observations alone have difficulties separating spatial and temporal effects in tracing the motion of enhanced density regions, but ground-based 2D auroral imaging could offer an excellent technique for monitoring the shape and motion of diffuse aurora that is driven by precipitating energetic electrons interacting with whistler-mode waves.

The proposed investigation will use a creative approach for understanding dayside magnetospheric density evolution by using Antarctic-based auroral observations. In particular, South Pole is an ideal dayside auroral observatory due to its longest polar night in the world. The wave-particle interaction producing whistler-mode waves will be used as a tool for imaging dayside plasma density structures using correlated South Pole all-sky auroral imager and THEMIS spacecraft observations. This research may influence not only its own field of diffuse auroral studies, but also related fields such as dayside magnetospheric dynamics, wave particle interactions, and excitation of plasma waves.

This interesting and important scientific research provides an ideal opportunity to train a graduate student, further scientific collaboration and cooperation in Antarctica, and create a list of THEMIS-South Pole auroral imager 'dayside conjunction' events and respective geomagnetic field mapping results for the use by a broader geospace science community.

ECCS Prop. No. 1407880

Proposal Title:

Implantable, Wireless, and Power-Efficient Trimodal Neural Interface for Electro-Optogenetic Manipulation of Visual Cortex in Small Freely Behaving Animals

Award Goal
This proposal aims to realize an integrated, wireless, trimodal opto-electro neural interface to tackle the critical challenge of high-resolution spatiotemporal mapping and closed-loop control of visual cortex, which will enable better understanding of the structure and function of brain networks during visual processing of small, freely behaving animals.

Nontechnical Abstract

Blindness has affected millions of people worldwide, and at present is incurable. A cortically-based visual prosthesis is believed to provide a therapeutic solution for all causes of blindness. However, restoration of visual senses to a useful level has not yet been achieved with cortical implants, mainly due to the complex organization of visual cortex and visual preprocessing in the retina and the lateral geniculate nucleus. Therefore, the objective of this proposal is to realize a novel neural interface for high-resolution stimulation and recording of neural activity in visual cortex, which will enable better understanding of the structure and function of neural networks during visual processing. The proposed technology development of this research will yield novel and enabling tools for seamless communication with brain networks of small animals, by which neuroscientists could significantly move fundamental neuroscience knowledge forward. The developed ultra-low-power microelectronics and advanced microfabrication techniques can be applicable to other implantable devices and biomedical systems. In addition, the proposed project will offer unique training opportunities for students at multiple levels. Integrated outreach activities will effectively convert state-of-the-art science and technologies into educational resources accessible to local K-12 schools and communities. To reach broader audiences, the results will be disseminated through science fairs, publication, workshops and conferences.

Technical Abstract
As the core of this proposal, a wireless, trimodal neural interface will be developed to form the most comprehensive interface with the central nervous system of awake, freely behaving animal subjects. In particular, a multichannel opto-electro array will incorporate epidural light emitting diodes, intracortical microscale waveguide, and microelectrodes in a single platform, capable of optogenetic/electrical stimulation and electrical recording of neural activity of specific cell populations. Implantable, ultra-low-power microelectronic system-on-a-chip will be able to receive and process neural recording data and drive the optical/electrical neural stimulating array. Wireless telemetry links will be implemented to transfer power and data efficiently between the external data-acquisition/control units and implanted neural interface. These key components will be integrated on a mechanically flexible substrate and encapsulated by a hybrid biopolymer package. The integrated wireless neural interface will be implanted and characterized in the primary visual cortex of anesthetized and freely behaving rats, in order to validate its efficacy for wireless neural recording and stimulation. The proposed research activities will be conducted by a collaborative team with complementary research expertise in the areas of bioMEMS, microelectronics, and neurophysiology. Achievement of the goals of this research will pave the road towards the development of a fully functional, cortically-based visual neuroprosthetic system capable of generating artificial vision for completely blind individuals. While the proposal is specifically tailored for studying the visual function of the brain, the developed technologies can also be used for functional mapping and controlling of other regions of the brain and nervous system, particularly those related to motor functions (e.g. spinal cord and peripheral nervous systems).

The Geospace Environment Modeling (GEM) Program is a broad-based, community-initiated research program on the physics of the Earth's magnetosphere and the coupling of the magnetosphere to the atmosphere and to the solar wind. The work of GEM is accomplished in a series of campaigns and focus groups that solve specific problems leading to the construction of a global Geospace General Circulation Model (GGCM) with predictive capability. This project will contribute essential results to this goal pertaining to understanding the role of plasma waves in energizing and transporting particles and plasma in the near-Earth space environment. In addition, the project supports the research of an early-career tenure-track faculty member and contributes to the research training of another early-career female scientist and a graduate student.

This investigation utilizes both spacecraft observations from THEMIS and Van Allen Probes and the HOTRAY wave ray-tracing computer code to study the modulation of plasma wave intensity by thermal plasma density variations in the inner magnetosphere. The specific science questions to be addressed include: (1) How do thermal plasma density variations cause modulation in the intensity of chorus, hiss and magnetosonic waves? and (2) How do the waves excited by these density variations affect radiation belt and ring current? The investigation is relevant to the GEM Focus Groups on "Storm-Time Inner Magnetosphere-Ionosphere Convection", and "Scientific Magnetic Mapping & Techniques".

PROJECT SUMMARY Boron-doped diamond (BDD) is considered to be an ideal candidate for sensing dynamic changes in neurotransmitters and neurophysiological signals, because of its unique combination of electrical conductivity, a broad potential window, a low background baseline, resistance to molecular adsorption, biocompatibility, and chemical inertness. While BDD based electrodes have demonstrated potential for rapid detection of neurotransmitters with high sensitivity, one major challenge of implantable diamond sensors is mechanical property mismatch between rigid diamond (with a Young's modulus of ~1012 Pa) and soft tissues (with a Young's modulus of ~103-105 Pa), which can increase risks of negative neural response, glial scar formation, inflammation, and mechanically induced trauma. To address this critical issue, previously, our team had developed flexible BDD microelectrodes by transferring patterned BDD structures from a solid silicon substrate onto soft polymer substrates. We demonstrated that the hybrid BDD/polymer films have a Young's modulus of over ten times lower than solid BDD, and are capable of sensing dopamine concentrations using fast-scan cyclic voltammetry. Building on our preliminary studies, the goal of this research is to design and develop a fully implantable, mechanically flexible, hybrid diamond-polymer microsensor platform for electrophysiology recording and electrochemical sensing of brain activity with high sensitivity, selectivity, and spatiotemporal resolution. For proof of concept studies, this R21 application will focus on: 1) synthesizing, characterizing, and optimizing thin BDD films with desired electrical properties; 2) revising and optimizing wafer-level microfabrication, pattern transferring, and integration/packaging processes for building the proposed sensors; and 3) evaluating the feasibility of a 16-channel sensor prototype for rapid, real-time recording of neurotransmitters and neurophysiology signals in living animal brains. The proposed project will be carried out by a multidisciplinary team combining investigators from different areas of diamond material synthesis and processing, microelectromechanical system (MEMS) fabrication and packaging, and neurophysiology. The successful completion of this pilot study will pave the way for future development and optimization of a large-scale, high-density, flexible sensor platform for in-situ monitoring electrophysiological and electrochemical signals in various biological models (from rodents to non-human primates) and disease conditions.

This award renews an exemplary Research Experiences for Teachers (RET) Site focusing on smart sensors and sensing systems at Michigan State University (MSU). The RET Site will continue to develop a strong partnership between MSU and schools in the greater Lansing-Detroit area to advance pre-college science and engineering education by training a cadre of leaders of middle and high school teachers in the areas of Science, Technology, Engineering, and Mathematics (STEM). The RET site will expose teachers to leading engineering research spanning biological and chemical sensors, robotics sensors, micro and nano-electro mechanical sensors, microelectronic sensing circuitry, human-computer interaction, biomechanics, innovative sensing materials and manufacturing techniques, and will connect them to the profound changes that sensors and sensing technologies are having on the daily lives and quality of life of all citizens. The interdisciplinary nature of the research theme will provide a fertile ground for developing creative and appealing middle and high school lessons and teaching activities in biology, physics, chemistry, and technology that align with state and national curricular standards.

RET participants will attend a 6-week summer institute to participate in cutting-edge research projects with mentoring from engineering faculty who lead vibrant sensor and sensing related research programs. Working with principal investigators, faculty mentors, and a curriculum development specialist, teachers will develop innovative, standards-compliant curriculum modules and participate in a number of professional development activities. The teacher-created modules and lessons will be disseminated nationally through TeachEngineering.org, a nationally recognized repository for searchable, standards-based engineering curricula. Extensive follow-up activities are planned throughout the academic year to ensure the translation of lab experience into classroom practice, and to foster and strengthen long-term partnership between engineering faculty and the local school districts. A third-party professional program evaluator will track and evaluate the program and provide feedback for improvement. The evaluator will also conduct longitudinal studies on participants to assess the longer-term impact of the RET program.

Waves exist in space plasmas just as in the oceans and the atmosphere. In these plasmas, collisions between charged particles are rare. As a result, plasma waves are a major means of transferring energy from one charged particle population to another. Charged particles "surf" the waves. To first order, those that are moving slightly faster than the waves are energized, while those moving slower lose energy to the waves causing them to grow. There are a wide variety of plasma waves with different properties and different source mechanisms. Three of these (plasmaspheric hiss, chorus, and electromagnetic ion cyclotron (EMIC) waves) are widely believed to play significant roles in the depletion of the electron radiation belts but how this happens and how each contributes with local time and radial distance are still-open and strongly debated questions of fundamental importance. During their interactions with the waves, electrons are scattered out of their trapped orbits and sent on trajectories into the dense atmosphere where they are lost through collisions. The work will independently examine experimental observations and, most importantly, use theoretical tools to understand the interactions leading to the precipitation. The science questions to be addressed in this proposal are particularly important, since electron precipitation leads to chemical changes in the upper atmosphere, and is critical in regulating ring current and radiation belt electron dynamics. The grant will support the further training and development of a promising female early-career scientist. The results will be useful to the broader space physics and upper atmosphere communities, to researchers studying the chemistry of the middle atmosphere, and for space environment applications, such as active mitigation techniques for both natural and artificial radiation in space.

Testing theoretical ideas about particular wave-particle interactions and the variations in the space environment that effect them has been difficult because the waves are measured at large radial distances in the magnetosphere while the electron precipitation that they produce must be viewed from low-earth orbit. To complicate matters, the mix of plasma waves depends on the radial distance and magnetic local time but in addition is an as yet to be determined function of the severity of space weather storming, and the phase of the storm. The principal investigator (PI) has developed an innovative technique to analyze the physical relationship between wave intensity and wave-driven electron pitch angle scattering loss, which can be directly implemented using conjugate observations from near-equatorial and low-altitude satellites. This project, which uses both theory and observation, will provide a definitive understanding of the quantitative contribution of each type of plasma wave to electron precipitation within various energy ranges and in different L-MLT regions. The results will provide a highly important contribution to our wider understanding of the mechanisms that regulate the hazardous radiation environment surrounding the Earth.

The Geospace Environment Modeling (GEM) Program is a broad-based, community-initiated research program on the physics of the Earth's magnetosphere and the coupling of the magnetosphere to the atmosphere and to the solar wind. The work of GEM is accomplished in a series of campaigns and focus groups that solve specific problems leading to the construction of a global Geospace General Circulation Model (GGCM) with predictive capability. This project will contribute essential results to this goal pertaining to understanding the role of plasma waves in energizing and transporting particles and plasma in the near-Earth space environment. In addition, the project supports the research of an early-career tenure-track faculty member and contributes to the research training of another early-career female scientist and a graduate student.

This investigation utilizes both spacecraft observations from THEMIS and Van Allen Probes and the HOTRAY wave ray-tracing computer code to study the modulation of plasma wave intensity by thermal plasma density variations in the inner magnetosphere. The specific science questions to be addressed include: (1) How do thermal plasma density variations cause modulation in the intensity of chorus, hiss and magnetosonic waves? and (2) How do the waves excited by these density variations affect radiation belt and ring current? The investigation is relevant to the GEM Focus Groups on "Storm-Time Inner Magnetosphere-Ionosphere Convection", and "Scientific Magnetic Mapping & Techniques".

Optogenetics, the use of light-gated ion channels or pumps to excite or inhibit the transient activity of genetically targeted neurons by pulses of light, has proved its enormous potential for understanding neuronal circuit mechanisms underlying brain functions and behavior, and ultimately, for providing therapeutics to treat numerous neurological and psychiatric disorders. Despite the rapid development of optogenetics tools over the past decade, tethered optical devices pose significant limitations in experimental animals and even more so in potential clinical applications. This proposed research will address fundamental challenges in tethered optogenetics systems, by developing a distributed, wireless (untethered and battery-less), implantable optical stimulator architecture that is more power efficient, significantly safer, and more practical for translation to clinical applications. The successful completion of the project will yield a new neural interface tool to significantly expand the utility of the rapidly growing field of optogenetics, which has become the frontier in brain science research, gene therapy, and new drug discovery for a variety of neural diseases. In addition, the project will train graduate students in multidisciplinary research and broaden K-12 education in Science, Technology, Engineering, and Mathematics (STEM) through integrated outreach activities, including the NSF sponsored Research Experiences for Teachers (RET) Program at Michigan State University.

The proposed wireless optogenetics stimulator will integrate a mm-sized, Parylene-coated system-on-a-chip (SoC) with an embedded receiver coil, surface-mount storage capacitors, and microscale light-emitting diodes (microLEDs) to selectively stimulate the target neural tissue. Researchers will tackle inefficiencies in wireless power delivery to the neural tissue using: 1) a four-coil telemetry link including an implantable high quality factor resonator to enhance wireless power coupling efficiency; 2) a built-in mirror to reflect backside illumination of microLED for improving light throughput; and 3) a switched-capacitor stimulation (SCS) structure of the SoC to directly charge an array of storage capacitors from the inductive link and periodically discharge them into a microLED without loading the inductive link. A single wireless stimulator enables localized optical stimulation of targeted neurons with high spatiotemporal resolution, while a cluster of such implants enables easy access to large-scale neuronal circuits with minimal invasiveness and movement restriction. The proposed device also enables a significantly safer and more practical solution for potential translation of optogenetics into behaving animal research and clinical applications. Removing the chronic physical trauma of tethering can effectively minimize tissue damage and enable efficient and stable chronic wireless optical stimulation. Moreover, the distributed, epidural implantation strategy permits selective stimulation of any desired area in the cortex. This new paradigm will offer neuroscience community an unprecedented level of flexibility with unlimited experiment duration in an enriched, untethered environment, without requiring small animal subjects to carry bulky batteries around.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

The jointly funded NSF/NASA ELFIN mission consists of two identical CubeSats on a polar (~ 93 degree inclination), nearly circular, low-Earth orbit. ELFIN was launched on September 15, 2018 and is currently operating within the geospace environment. This funding will address the prime mission objective of analyzing the data currently being collected by ELFIN to advance understanding of wave-particle interactions and their effect on relativistic electrons in the outer radiation belt. Two undergraduate students, a graduate student, and three early career scientists will be supported. ELFIN data products are integrated into courses at UCLA and in public outreach events in the Los Angeles area.

The project will utilize ELFIN, together with its conjunctions with other, equatorial Heliophysics missions to address the efficacy of EMIC wave precipitation, and the relative contribution of EMIC, whistlers and kinetic Alfvén waves in the observed relativistic electron scattering (100s of keV to a few MeV energy). The specific science objectives are: (1) Are EMIC waves responsible for 0.5-2MeV electron precipitation?
(2) Are waves other than EMIC waves (principally chorus waves and kinetic Alfvén waves (KAWs)), also responsible for significant relativistic electron scattering? (3) What are the typical precipitation rates associated with various wave types as function of geomagnetic conditions?

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.