Funded Awards

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Investigator
Banghart, Matthew Ryan (contact) Chang, Geoffrey A
Institute
University Of California, San Diego
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Neuropeptides, a special class of neuromodulator, can initiate biochemical signaling events that change neuronal physiology in diverse and subtle ways, but current methodologies to study them lack spatiotemporal precision. Matthew Banghart and Geoffrey Chang are developing genetically-encoded optical sensors that can quantify the presence of neuropeptides in brain tissue. Their strategy is to fuse fluorescent reporters to nanobodies that bind neuropeptides and generate an optical signal. By overcoming the challenge of converting peptide binding to an optical signal, this novel approach will improve spatiotemporal precision by permitting micron- and millisecond-scale measurements. After first testing the method in brain slices, the team ultimately plans to use the resulting probes in vivo to identify behaviors linked to peptide release.
Investigator
Blurton-jones, Mathew Mark Gandhi, Sunil (contact) Spitale, Robert C
Institute
University Of California-irvine
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Interventional Tools
  • Monitor Neural Activity
Summary

Recent work has revealed the need for a robust system to accurately model the dynamic nature of human microglia in the brain in health and disease. Dr. Gandhi and team aim to validate a novel mouse xenotransplantation platform, XMG, using human induced pluripotent stem cell-derived microglia as a promising model system which they intend to disseminate publicly. The group will compare the transcriptional landscape of XMG to endogenous microglia from mice and humans, as well as use cutting edge multiphoton imaging technique to measure calcium activity and insulin response of XMG following acute insult. Further, the group will query changes in the function of XMG in the context of a pathological state resembling Alzherimer’s disease in the mouse. Developing this novel XMG system may advance the ability to study human microglia in vivo and provide far-reaching insights into microglial biology.

Investigator
Wickersham, Ian R
Institute
Massachusetts Institute Of Technology
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Monitor Neural Activity
  • Interventional Tools
Summary
In vivo genetic modification within a specific cell type generally requires production of transgenic or knockout animal models, a time- and resource-consuming process. Wickersham and colleagues will use high-throughput techniques to develop a novel set of viral vectors to allow selective transgene expression in targeted neuronal subpopulations in wild-type mammals. These tools will expand the possibility of optogenetic control, recording, and genomic modification of neural circuits to uncover their organization in healthy and dysfunctional brains, with potential therapeutic use in humans for mental and neurological disorders.
Investigator
Ellington, Andrew D (contact) Zemelman, Boris V
Institute
University Of Texas, Austin
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
The ability to manipulate defined neuron populations has revolutionized in vivo investigations of brain circuitry. Although optogenetics has captured much of the attention in this realm, so-called "chemical genetic" strategies utilizing artificial receptor-ligand pairs have been highly successful, and have the advantage that they can access cell populations scattered across the brain. Using such strategies, specific neural populations that are genetically modified to express an artificial receptor can be manipulated by administering the corresponding chemical ligand to the animal, providing control of specific brain circuits. Ellington and Zemelman propose a new class of artificial receptors that directly couple ion channel activation to receptor binding, and unlike the most popular designer receptor techniques, do not rely on the intracellular signaling pathways of the host organism for their effects.
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 an established diagnostic tool. However, while mapping dynamic anatomical and functional connectivity in the human brain is essential, adult MRI systems are not well-suited for clinical use in infants and children. Working with Advanced Imaging Research Inc., Dr. Ravi Srinivasan and team propose to create a compact MRI system that provides MRI systems to infants, children, and adults in any hospital department. The group will develop, test, and refine a compact MRI system with strong connectome gradients, thus alleviating cost and safety burdens that can be posed by large adult whole-body MRIs. The success of the project could stimulate development of mobile mental health and stroke assessment systems, thereby improving accessibility to MRI systems.

Investigator
Shcherbakova, Daria
Institute
Albert Einstein College Of Medicine, Inc
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Interventional Tools
  • Monitor Neural Activity
Summary

Observing activity across the entire brain should help increase understanding of how it responds to stimuli and leads to behavior. Available technology limits what can be seen by restricting observations to small areas, slowly recording activity, and damaging the brain. Dr. Shcherbakova’s team will develop novel technology that will allow for recording of neuronal activity in the entire mouse brain using noninvasive near-infrared light (NIR). The researchers will develop a NIR optogenetic system of light-inducible protein-protein interaction (PPI), combining a calcium-induced PPI and a NIR-induced PPI to drive gene expression of fluorescent proteins or other optogenetic tools in activated neurons. The system will be optimized in cultured cells and primary neurons, then validated in vivo, targeting the primary motor cortex of mice. This tool will allow researchers to study circuit activity during behavior in freely moving animals, advancing our understanding of how the brain processes information in health and disease.

Investigator
Meng, Ellis (contact); Song, Dong
Institute
University Of Southern California
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

Polymer microelectrode arrays are electrical recording devices made of flexible materials. These materials reduce tissue damage and improve the long-term stability of the recording setup. The Meng and Song labs aim to establish a service that will manufacture and test out arrays that are customized to researchers’ needs. The service may help researchers use the latest electrical recording devices for studying a variety of neurological disorders.

Investigator
Dolinsky, Sergei Miyaoka, Robert S (contact)
Institute
University Of Washington
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
Summary
Currently, body imaging systems perform brain imaging, making it difficult to provide the necessary level of spatial and temporal resolution needed to understand brain function. Brain-only imaging systems include positron emission tomography (PET) and are referred to as neuroPET. Drs. Robert Miyaoka, Sergei Dolinsky, and a team of investigators seek to develop improvements in both image resolution and signal-to-noise ratio of neuroPET technology. The researchers will characterize neuroPET parameters, validate them through machine learning methods, and characterize performance of a prototype detector that is compatible with magnetic resonance imaging (MRI). By improving detector imaging technology that facilitates compatibility between PET and MRI, this work will improve image resolution to advance research into the development, function, and aging of the human brain.
Investigator
Bikson, Marom
Institute
City College Of New York
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Interventional Tools
  • Human Neuroscience
Summary
The use of transcranial direct current stimulation (tDCS), which delivers low-intensity current to the brain using electrodes placed on the scalp, is being investigated for diverse applications pertaining to neuropsychiatric treatment and rehabilitation. Because electrode placement for tDCS highly influences clinical efficacy and specificity, Dr. Marom Bikson and colleagues have developed high-definition tDCS which offers the potential for more precisely targeted stimulation. In this project, the team will develop open-source software that allows researchers to more easily upload brain scans and design a brain stimulation experiment to target a specific brain region. This new toolbox for the optimization of tDCS spatial precision will enhance the rigor, efficacy, and accessibility of tDCS research aimed at understanding the brain and treating disease.
Investigator
Crone, Nathan E Tandon, Nitin (contact)
Institute
University Of Texas Hlth Sci Ctr Houston
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
Summary
Current non-invasive methodologies limit our ability to understand the neural basis of cognitive processes due to poor temporal or spatial resolution, and typical intracranial EEG (icEEG) approaches provide fragmentary information. To address these limitations, Drs. Tandon and Crone will study human language function, working with epilepsy patients who have intracranial electrodes in place. The group will then modulate activity at identified nodes of brain activity using closed-loop direct cortical stimulation. This project could provide insight into language processing and organization in the brain using a novel method of modeling neural computation, and provide insight into the language impairments that can affect patients with a range of neurologic and psychiatric illnesses.
Investigator
Santamaria, Fidel
Institute
University Of Texas San Antonio
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
  • Theory & Data Analysis Tools
Summary

A central property of the nervous system is history dependence: its ability to change reaction rates based on previous activity. Though the phenomenon is prevalent across scales of neuronal organization, sensory modalities, and species, there is no unified theory for history dependence. For this project, Dr. Fidel Santamaria and team will apply mathematical approaches to history dependence, validate the significance of that approach, and establish collaborations to test the hypothesis across species and scales. Overall, this project aims to provide a unified theoretical framework and in doing so, pave the way toward applications to study, analyze, and design experiments of history-dependent neuronal activity across multiple scales, from synaptic plasticity to complex spiking patterns in neural networks.

Investigator
Drew, Michael R Martin, Stephen Zemelman, Boris V (contact)
Institute
University Of Texas, Austin
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Zemelman and colleagues will develop a system to label activated cell ensembles within the same animal in response to different behaviorally relevant stimuli over time. The system entails activity-dependent tagging of neurons based on the expression of select genes controlled by administering different antibiotic compounds at different times in the experiment. The antibiotics bind to and regulate specific "repressor proteins," giving them the ability to control gene expression. The team will also develop "caged" versions of each antibiotic, which can be uncaged via pulses of light for fast control of gene expression during rodent behaviors. This novel design will allow for faster temporal resolution of neuronal activation across brain regions and functions.
Investigator
Schwindt, Peter D. D.
Institute
Sandia Corp-sandia National Laboratories
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
Summary

Comprehensively studying the brain requires non-invasive neuroimaging methods at high spatiotemporal resolution that can capture the functions in naturalistic behaviors. Magnetoencephalography (MEG) is a promising approach, but its operation uses rigid helmet hardware that compromises signal and spatial resolution. Dr. Schwindt and a team of investigators plan to address these challenges by improving MEG sensors to develop a wearable, conformable, full-head coverage MEG system. After developing the sensor array, the group aims to enhance spatial resolution of the MEG system while accounting for heterogeneity in head shape, and finally validate the performance of the new system against traditional approaches. By providing a whole-head MEG system for people of all head sizes, this advance will enable the study of brain dynamics in increasingly naturalistic environments with cortical spatial resolution rivaling functional MRI.

Investigator
Alem, Orang
Institute
Fieldline, Inc.
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Circuit Diagrams
  • Interventional Tools
  • Monitor Neural Activity
Summary

Magnetoencephalography (MEG) is a powerful tool for non-invasive imaging of cortical activity with high temporal and spatial resolution. Unfortunately, MEG locations are sparse, largely because of high costs, maintenance, and limited usability due to rigid helmet configuration. To generate a high-density, high-performance, and wearable MEG helmet, Dr. Orang Alem and team will work with FieldLine Inc. on a few key innovations. The group will address technical challenges such as cross-talk between sensors, background field noise, and sensor calibration and localization. The success of this project could move this technology beyond the laboratory to the larger community of neuroscientists and clinicians, providing a turnkey high-density system that will have a significant impact in the field of biomagnetic research and diagnostics.

Investigator
Oralkan, Omer (contact) Sahin, Mesut
Institute
North Carolina State University Raleigh
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Understanding neural networks and communication between brain regions requires the decoding of electrical and chemical signals, but current methods often face a tradeoff in spatiotemporal precision. Omer Oralkan and Mesut Sahin propose the development of a tool that combines ultrasound neural stimulation and photo-acoustic recording of hemodynamic activity to monitor awake and behaving animals. Under this approach, high-frequency ultrasound allows for high stimulation precision, and a fast-repeating laser source permits high-resolution imaging of neurovascular responses that report neural activity. The success of this technological advance could pave the way for implantable, wireless dual-mode ultrasound/photoacoustic imaging devices that provide high spatiotemporal resolution of the entire brain using a minimally invasive approach.
Investigator
Miller, Michael I Mueller, Ulrich (contact)
Institute
Johns Hopkins University
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Theory & Data Analysis Tools
Summary

For a complete understanding of how the brain works, there is a need for a comprehensive parts list (all of the cells in the brain) along with knowledge of how those parts are connected. Current molecular technology has advanced the inventory of cell types in the brain, but detailed information about the circuits they form is limited. Dr. Mueller’s group will develop scalable and affordable cellular imaging and neuro-informatics tools, running preliminary experiments to connect the transcriptome to anatomy, in mice. Tools will be made available to researchers, to help accelerate the creation of detailed maps at cell resolution showing circuitry in whole brains.

Investigator
Rutt, Brian Keith
Institute
Stanford University
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
  • Human Neuroscience
Summary
Non-invasive methods for imaging the human brain are currently limited in spatial resolution, hindering our understanding of neuronal connectivity by blurring responses across millions of neurons. Brian Rutt proposes the development of next-generation, ultra-high-field (UHF) magnetic resonance imaging (MRI), allowing for the mapping of neural activations and connections containing only a few thousand neurons. To overcome obstacles of cost, size, and technical/physical limitations, he is partnering with General Electric and Tesla Engineering to design a UHF MRI prototype that is capable of acquiring whole-brain maps at microscopic spatial resolution. The development of a low-cost, compact UHF MRI system would allow for unprecedented spatial resolution of the human brain, providing a fine-grained window into the underlying principles by which brain networks give rise to human cognition.
Investigator
Gomez, Luis Javier
Institute
Duke University
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

Transcranial magnetic stimulation (TMS) is a noninvasive technique used to study brain function and can be used to treat some brain disorders. Researchers use computational simulations of TMS electrical fields to gain a better understanding of how TMS affects the brain. Existing simulations, however, are inherently variable due to factors that impact the accuracy and precision of the technique, such as differences in experimental set-up and coil placement. Dr. Gomez proposes to use a novel computational framework to measure and address the uncertainty and variability of TMS electrical fields. The project will increase the fidelity and reliability of TMS simulations. The results will benefit researchers and clinicians by enabling more precise control of the technique and may help improve medical uses of TMS.

Investigator
Chiong, Winston
Institute
University Of California, San Francisco
Year Funded
2017
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
Novel neurotechnologies hold promise for treating neuropsychiatric disorders, but also raise profound neuroethics issues including self-ownership of our thoughts, emotions, and actions. Engaging patients and researchers in the early stages of neurotechnology research and clinical translation can help ensure ethical development of the field. This research study will be embedded in one of two projects funded by the DARPA BRAIN Initiative to develop implantable brain stimulation devices that both monitor and adaptively stimulate brain areas involved in mood and behavior regulation. Dr. Chiong and an interdisciplinary team with expertise in neuroscience, clinical care, law, philosophy, and social science will assess neuroethics issues associated with the DARPA-funded brain stimulation project. The overall goal is to enable acceptability and adoption of new treatments for neuropsychiatric disorders, by recognizing and incorporating the perspectives of patients, researchers, and other stakeholders into the design of these novel neurotechnological therapies.
Investigator
Clark, Heather
Institute
NORTHEASTERN UNIVERSITY
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Interventional Tools
Summary

Current measurements of the brain-wide neurotransmitter acetylcholine rely on implanted electrodes or chemical sampling techniques, which offer either spatio-temporal resolution or chemical specificity. Clark and Flask will create novel magnetic resonance compatible nanosensors to measure acetylcholine across the blood brain barrier. These sensors will report acetylcholine levels in rodents by dual contrast magnetic resonance fingerprinting, producing a toolset for selective and quantitative measurement of the neurotransmitter. If successful, this project could open a new era for imaging neurotransmitter dynamics throughout the brain in animals and potentially in humans.