Funded Awards

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Investigator
Shapiro, Mikhail (contact) Tsao, Doris Ying
Institute
California Institute Of Technology
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Summary

Controlling specific neural circuits across large-scale areas is vital to improve our understanding of the nervous system. Drs. Shapiro, Tsao, and collaborators aim to further develop Acoustically Targeted Chemogenetics (ATAC) to modulate neural circuits non-invasively in non-human primates (NHPs) with spatiotemporal and cell-type specificity, starting in the visual cortex of macaques. The group will develop AAV viruses optimized for chemogenetic receptor delivery using in vivo evolution in mice and NHP, in addition to the development of ultrasound methods to target focused ultrasound-blood brain barrier opening in NHPs. ATAC will then be used to modulate face recognition neurons and sensorimotor circuits in NHPs.  Successful development of ATAC for NHPs will improve the study of neural circuits, and potentially help uncover new therapies for neuropsychiatric disease.

Investigator
Goodman, Wayne K
Institute
Baylor College Of Medicine
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Summary
Deep brain stimulation (DBS) is currently a treatment option for patients with obsessive-compulsive disorder (OCD), but there is room for improvement both in terms of increasing treatment effectiveness and reducing unwanted side effects. In this project, Goodman and his team aim to utilize next-generation DBS systems that can record, stimulate, and make real-time adjustments to stimulation parameters based on the patient’s brain activity. Specifically, they propose to develop a stimulation paradigm that will allow the DBS system to automatically adjust stimulation to better control OCD-related distress while minimizing unwanted DBS-induced hypomania, which they will test in an early feasibility study with a small number of OCD patients. This work may help refine DBS therapy for neuropsychiatric and neurological diseases and disorders more broadly.
Investigator
Molnar, Alyosha
Institute
CORNELL UNIVERSITY
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Interventional Tools
Summary

Conventional multi-electrode recordings monitor neural activity with high temporal precision but require chronically invasive wiring. The finer spatial resolution achieved by optical imaging techniques comes at the cost of significantly worse temporal resolution. Molnar, Xu, Goldberg, and McEuen will develop a new class of neuron-sized electrophysiological recording devices by combining modern imaging with implanted optoelectronics. They will develop free-floating, implantable microscale optoelectronically transduced electrodes (MOTEs) that use light to harvest power, synchronize, and uplink measured electrophysiological data. The system should support simultaneous imaging and electrical recording of neural activity from hundreds of sites in behaving rodents, enabling minimally invasive neurobiological experiments currently unattainable.

Investigator
Srinivasan, Ravi
Institute
Advanced Imaging Research, Inc.
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Circuit Diagrams
  • Interventional Tools
  • Monitor Neural Activity
Summary

Magnetic resonance imaging (MRI) is a safe, non-invasive diagnostic imaging tool that provides detailed information about major organs of the body, including the brain. But, effective diagnosis depends on the quality of the MR image, and increasing magnet field strength or receiver channels can be burdensome in cost and maintenance. In a collaboration with Advanced Imaging Research Inc., Dr. Srinivasan and team propose to maximize MRI image quality with the intention of alleviating the burden placed on high-cost, high-magnet field-based MRI systems. The group plans to improve the signal-to-noise ratio within MRI systems by increasing the radio-frequency (RF) coil efficiency. The success of the project could significantly reduce scan time and facilitate disease diagnosis.

Investigator
Chen, Wei (contact) Yang, Qing X
Institute
University Of Minnesota
Year Funded
2014
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
  • Human Neuroscience
Summary
Dr. Chen's team will achieve unprecedented higher resolution magnetic resonance imaging and spectroscopy scanning by integrating ultra-high dielectric constant material and ultra-high-field techniques.
Investigator
Roberts, Todd F
Institute
Ut Southwestern Medical Center
Year Funded
2016
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
  • Theory & Data Analysis Tools
Summary
The execution of learned sequential motor behaviors is thought to be supported by precise sequences of neuronal activity in the brain. Dr. Roberts seeks to identify brain circuits important for learning vocal behaviors, and has pioneered several techniques in songbirds, including viral vector methods, two-photon microscopy, optogenetic studies, and in vivo calcium imaging. The Roberts Lab will employ a newly developed two-photon digital holographic system for optogenetic stimulation, along with targeted whole-cell recordings, to map the functional organization of circuits. This all-optical interrogation of circuits involved in generating precisely timed sequential vocal behaviors could be used to identify how sequences of neuronal activity underlying complex learned behaviors are generated in the brain.
Investigator
Dayton, Paul A Pinton, Gianmarco (contact)
Institute
Univ Of North Carolina Chapel Hill
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
  • Human Neuroscience
Summary
To achieve real-time imaging of the human brain, improvements to ultrasound technology must overcome the challenge of penetrating the thick skull barrier. In a public-private partnership, Gianmarco Pinton and researchers at the University of North Carolina in Chapel Hill are partnering with Verasonics to develop transcranial contrast enhanced super-resolution imaging (TCESR). TCESR corrects for skull-induced aberrations, allowing for ultrasound imaging of in-vivo animal microvasculature and local blood flow. These advancements have the potential to unlock ambulatory ultrasound monitoring of real-time brain blood flow, something that is currently impossible with other neuroimaging methodologies. TCESR could have significant clinical and scientific applications by enabling visualization of microvasculature deep within the brain.
Investigator
Mitra, Robi D
Institute
Washington University
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Monitor Neural Activity
  • Interventional Tools
Summary
Currently, methods that seek to link transient gene expression events to specific brain functions typically require genomic analysis of a population of cells, resulting in the destruction of those cells. This makes it difficult to directly connect molecular changes in a neuron with knowledge of subsequent biological outcomes, such as memory formation, brain development, or neurodegeneration. Mitra and his colleagues will develop a transformative technology called "Calling Cards" that provides a permanent genetic record of molecular events associated with gene expression, which can be read out by DNA sequencing at a later time after relevant biological outcomes have occurred. The data collected with this technique will deepen the understanding of processes such as brain development, memory formation and the progression of neurodegenerative disease.
Investigator
Opitz, Alexander
Institute
University Of Minnesota
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
  • Theory & Data Analysis Tools
Summary

Non-invasive brain stimulation methods, like transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS), modulate brain activity in a safe and painless manner. Several BRAIN Initiative projects are combining these non-invasive brain stimulation methods with neuroimaging methods. Dr. Opitz and team will develop a computational tool that integrates empirically validated finite element method (FEM) models with imaging data, by extending and scaling the SimNIBS (Simulation of Non-Invasive Brain Stimulation) software platform. The SimNIBS is the leading open source software platform for generating FEM-based models of the electric field distribution produced by TMS, tDCS, and tACS. The resultant analysis package will allow rapid visualization and analysis of non-invasive brain stimulation (NIBS) BRAIN Initiative data, which could be more broadly used by the general neuroscience community.

Investigator
BASSO, MICHELE A et al.
Institute
UNIVERSITY OF CALIFORNIA LOS ANGELES
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Interventional Tools
  • Monitor Neural Activity
Summary

Drs. Basso and Golshani will design, manufacture, optimize, and test a two-channel, wireless miniaturized microscope for monitoring primate brain cell activity in real time. The system will be based on the miniaturized microscopes, called Miniscopes, they developed for studying mouse brains in action. To do this, they will increase the size and sensitivity of imaging sensors and objective lenses, increase battery power, develop a microscope synchronization system, and incorporate drug and light delivery systems.  All innovations will be shared freely with the community of Miniscope users. With these microscopes, Drs. Basso and Golshani hope to help scientists move one step closer to understanding the neural circuit problems underlying human brain diseases.

Investigator
Geisler, Wilson S Seidemann, Eyal J (contact) Zemelman, Boris V
Institute
University Of Texas, Austin
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Advanced optical methods for reading and writing neural information using genetically-encoded reporters and actuators have become powerful tools for studying neural circuits. However, these tools are generally optimized for rodents, which provide a suboptimal model for human perception because of their vastly different sensory representations and perceptual capabilities. The goal of this proposal by Seidemann and his colleagues is to develop and optimize an optical-genetic toolbox for reading and writing neural population codes in brains of awake, behaving higher mammals. As part of this project, the researchers will test new genetic methods for cell-type and activity dependent targeting of transgenes to specific neurons, design a two-photon microscope that will cover a larger area of the cortex, and develop methods for patterned optical stimulation to mimic neuronal population codes in the visual cortex. This new set of tools will pave the way for optogenetic studies in higher mammals, which will enable a deeper understanding of how the human brain processes information.
Investigator
Hashemi, Kevan
Institute
Open Source Instruments, Inc.
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Circuit Diagrams
  • Interventional Tools
  • Monitor Neural Activity
Summary

Epileptic seizures can be halted or reduced by optogenetic activation of selected inhibitory neurons. By monitoring electroencephalography (EEG) data in real time, seizures can be identified at their onset and correcting pulses of optogenetic stimulation may be applied. Working with Open Source Instruments Inc., Dr. Kevan Hashemi and team propose the development of a fully implantable, wireless EEG monitor that can detect EEG events in real-time and apply correcting pulses of closed-loop optogenetic stimulation. The group will develop the necessary hardware, adapt an algorithm to classify EEG events, and test the device's ability to detect seizures in mice. The success of the project could inform creation of a medical instrument that aborts focal seizures in humans who suffer from epilepsy.

Investigator
Hannon, Gregory J
Institute
Cold Spring Harbor Laboratory
Year Funded
2014
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Monitor Neural Activity
  • Interventional Tools
Summary
Dr. Hannon's group will develop optogenetic techniques that use pulses of light to control genes and isolate proteins in specific cell types in the brain for molecular studies.
Investigator
Kuzum, Duygu
Institute
University Of California, San Diego
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Interventional Tools
  • Monitor Neural Activity
Summary

A major goal of neuroscience is to record the activity of all neurons in an area of an intact brain to understand the relationship between neural activity and behavior. However, current technologies do not allow direct and simultaneous access to every neuron in a three-dimensional brain area. Instead, Kuzum’s team proposes to ‘virtually’ record from neurons in a given volume of tissue with a Virtual Array. They will develop a framework to computationally increase the number of recorded neurons in data from simultaneous electrophysiology and two-photon calcium imaging (at multiple cortical depths), without the need for direct optical or electrical access to each neuron. Advanced computation will identify the time and place of action potentials. If successful, virtual arrays could lead to mapping the neural circuit dysfunctions that cause disorders and could facilitate development of targeted treatments.

Investigator
Ascoli, Giorgio A Dong, Hong-wei (contact) Lim, Byungkook
Institute
University Of Southern California
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
Summary
Better anatomical characterization of neurons is needed if we want to identify and distinguish the different cell types in the brain. Dong and colleagues plan to classify neurons based on their spatial anatomy, connections with other neurons, and morphology using multiple neuronal retro- and anterograde tracing methods that will identify connected neurons. This team will first focus on 300 well-defined regions within the limbic system of the adult mouse, a circuit that is important for homeostasis and behavioral motivation, taking high-resolution images and creating high-throughput, three-dimensional reconstructions of these neurons. These data will provide a more complete anatomical picture of the limbic system, and this method can be applied in the future to study additional circuits throughout the brain.
Investigator
Dragoi, Valentin (contact) Janz, Roger Spudich, John Lee
Institute
University Of Texas Hlth Sci Ctr Houston
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Monitor Neural Activity
  • Interventional Tools
Summary
Examining neural circuits requires the ability to activate and silence individual neurons and subsequently assess the impact on circuit function and the circuit's overall influence on behavior. While genetically encoded molecular tools for selectively controlling the activity of neurons with light have been successfully implemented in mice, these tools have had limited success in non-human primates (NHPs). The researchers plan to modify a new class of recently discovered, light-activated molecular tools with superior light sensitivity to work well in NHPs. In addition, they will test a new, possibly more efficient, method of delivering these molecular tools via viral vectors into the neurons of awake, behaving NHPs.
Investigator
Wickersham, Ian R
Institute
Massachusetts Institute Of Technology
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Monitor Neural Activity
  • Interventional Tools
Summary
Using a modified rabies virus, neuroscientists can identify and manipulate neurons directly upstream from any targeted group of neurons in the brain. However, while this retrograde monosynaptic tracing system is now well established, an anterograde counterpart—one that would allow identification and manipulation of neurons directly downstream from a target cell group—has never been constructed. Wickersham and his team propose three different methods for creating an anterograde tracing system. Any one of the methods would greatly expand the types of anatomical and functional studies that can be performed in a large variety of animals, including primates.
Investigator
Roskies, Adina L
Institute
Dartmouth College
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
  • Theory & Data Analysis Tools
Summary

Deep brain stimulation (DBS), a method of modulating brain circuit function, is FDA-approved for certain brain disorders such as Parkinson’s Disease. The NIH BRAIN Initiative aims to launch neurotechnological developments that include new ways of directly affecting brain circuit function. Use of these novel interventions warrants careful consideration about ways in which brain stimulation may affect personal identity, autonomy, authenticity and, more generally, agency. In this project, Dr. Roskies and her team will develop an assessment tool to measure changes in agency due to direct brain interventions, and establish a database to catalogue these changes in agency in various patient populations receiving DBS. These efforts have the potential to facilitate improvements in therapeutic approaches and informed consent and will be used to develop a framework for further neuroethical thought about brain interventions, allowing us to better identify, articulate, and measure effects on agency.

Investigator
Devergnas, Annaelle Gross, Robert E (contact) Gutekunst, Claire-anne N Mahmoudi, Babak
Institute
Emory University
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Summary
Dominant hemisphere mesial temporal lobe epilepsy (MTLE) is a form of epilepsy for which it is particularly difficult to control seizures. In this project, Gross and colleagues will test a next-generation deep brain stimulation (DBS) device and a novel stimulation paradigm in a non-human primate model of MTLE. If they are successful in controlling seizures in this model, the team will advance to an early clinical feasibility study in a small number of MTLE patients, measuring seizure reduction and memory testing for safety. Success in this small clinical study could lay the foundation for a clinical trial utilizing this novel DBS method in patients with MTLE, and possibly other forms of epilepsy.
Investigator
Bock, Davi
Institute
University Of Vermont & St Agric College
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
Summary

Advancements in 3D electron microscopy have provided a wealth of neuronal circuit data for the whole fruit fly brain, but current, manual analysis techniques are very slow and tedious. Dr. Bock and his team aim to disseminate their whole-brain EM data via the web-based circuit-mapping and analysis platform CATMAID, as well as develop new automated tools and software to investigate circuit structure. Fruitfly neurobiologists accessing CATMAID will be able to perform morphology-based neuron searches for segmentation-assisted circuit reconstructions, eventually using this software to guide additional infrastructure development. The proposed research should accelerate circuit mapping in the fruit fly brain, extend to other model systems, and allow individual labs to form and manage collaborations on a managed server.