Funded Awards

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Investigator
COX, ROBERT WILLIAM (contact); NIELSON, DYLAN MILES
Institute
U.S. NATIONAL INSTITUTE OF MENTAL HEALTH
Year Funded
2018
FOA Number
Status
Active
1R24MH117467-01
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
  • Theory & Data Analysis Tools
Summary

AFNI (Analysis of Functional NeuroImages) is an open-source software package for neuroimaging analysis and visualization of both functional and structural MRI as well as other modalities. Drs. Cox and Nielson propose to extend this widely used software package by offering containerization, cloud accessibility and web-accessible visualization. The software extension could support evolving BRAIN Initiative standards for human neuroimaging data organization and experiment specification. The project makes it possible for public integration testing of the software package, thus enabling end-user feedback and wider adoption and dissemination within the neuroimaging community.

Investigator
Cohen, Adam Ezra
Institute
Harvard University
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Interventional Tools
  • Monitor Neural Activity
Summary

Different neurons show widely varying patterns of gene expression and widely varying patterns of electrical spiking. It is not currently possible to predict the electrical spiking properties of a cell from its pattern of gene expression. Cohen’s team seeks to develop tools to record gene expression and spiking patterns in thousands of neurons by combining two novel technologies: all-optical electrophysiology and BRAIN Initiative-funded fluorescent in situ hybridization, MERFISH. They will create correlated brain-wide maps of gene expression and neuronal firing, first in rodent acute brain slices and then in the zebrafish spinal cord in vivo . These maps may ultimately help elucidate the roles of genes in governing neural function in health and disease.

Investigator
Chen, Wei (contact) Zhu, Xiao-hong
Institute
University Of Minnesota
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
Summary

Advancing the image sensitivity and resolution of magnetic resonance (MR) imaging technologies is fundamental towards capturing a comprehensive view of the healthy human brain. Dr. Wei Chen and colleagues propose the development and validation of radiofrequency (RF) coil technology, combining it with spatiospectral CorrElation (SPICE) technique to improve the quality of MR imaging (MRI) and MR- spectroscopic imaging (MRSI) for human brain studies. Their approach aims to improve image sensitivity, while minimizing absorption of RF power in neural tissue, as well as exploit their previously developed SPICE technique to boost signal-to-noise ratio and image resolution. By pioneering this neuroengineering solution to improve the quality and resolution of these MR imaging technologies, these researchers will enable ultrahigh-resolution mapping of neural activity, circuits, and dynamics.

Investigator
Vu, An
Institute
Northern California Institute
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
Summary

The need for improved non-invasive imaging is paramount in order to reveal the underpinnings of both the diseased and healthy human brain. Dr. Vu and colleagues will develop a Stimulus-Locked K-Space (SLIK) approach to achieve meso-resolution imaging for whole human brain fMRI. They will incorporate and evaluate commercially available motion mitigation and navigator-based dynamic B0 correction techniques. This novel technology will build upon existing commercialized 7 Tesla scanners, and therefore, following its development, could be readily disseminated to the neuroscience community.

Investigator
Choi, Hannah
Institute
University Of Washington
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

The mammalian brain has unique abilities to process various sensory inputs from the environment, based on efficient and complex brain network structures and dynamics. However, the precise connections between the brain’s intricate wiring and its rich network dynamics are unclear, as is our understanding of how the brain’s connectivity and dynamics relate to underlying neural coding principles. Leveraging the Allen Institute’s Mouse Brain Connectivity Atlas, Dr. Choi will explore these issues, ultimately aiming to help close the gap between brain biophysiology and neural coding principles, with a focus on predictive coding theory using data-driven mathematical models.

Investigator
Dieudonne, Stephane Lin, Michael Z. (contact)
Institute
Stanford University
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Genetically encoded voltage indicators (GEVIs) are light-emitting proteins that report neuronal action potentials with high spatiotemporal precision, but they have limitations, including the fact that their kinetics are too fast for typical two-photon laser scanning microscopy. Improvements to GEVI brightness, responsivity, wavelengths, and localization would facilitate action potential detection, as would enhanced imaging capabilities that are matched to the properties of specific GEVIs of interest. Lin’s team proposes to integrate the above-mentioned GEVI improvements with development of a new generation of multiphoton optical hardware that will dramatically accelerate targeted scanning, enabling high-speed imaging of hundreds of individual, genetically-defined neurons. The group will apply these improved technologies to study patterns of fast neuronal activity in vivo, during behavior. This project could enable new insights into neural circuit function in health and disease.
Investigator
Louis, Matthieu R. P. J. C. G.
Institute
University Of California Santa Barbara
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary

We still do not understand fully how animals process sensory inputs from a noisy environment, yet this is a crucial function that the nervous system must perform to make correct behavioral decisions. Dr. Louis and colleagues propose to create a model of how the nervous system converts noisy sensory information into something that can be used to navigate the environment. Specifically, they are studying the behavior of fly larvae and their response to olfactory inputs,  i.e. their attraction to food odors, to study how environmental inputs are processed in the brain. This information will then be tested to uncover how stimuli from a noisy environment is translated into behavioral decisions.

Investigator
Sommer, Friedrich T
Institute
University Of California Berkeley
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
  • Theory & Data Analysis Tools
Summary

Innovative recording techniques have uncovered interactions between individual neurons and cell populations that comprise complex and poorly- defined neural dynamics underlying computations and brain functions. Dr. Sommer proposes combining new tools to analyze this neuronal activity with a theoretical framework of the associated computations. After decoding behavior in mice from hippocampal recordings during exploration and replay and local field potentials from visual cortex, the group will extract “place components” or the position of the animal from the activity data. Subsequently, the team will establish a theoretical framework that, at the computational level, will describe computations underlying brain function in terms of high-dimensional representations, and at the mechanistic level will describe how the operations and representations are mapped onto biological mechanisms. Future users will be able to use this framework to design computations, explore multiple potential mechanisms, create a simulation of an experiment, and compare simulation data to a real experiment.

Investigator
Golshani, Peyman (contact) Khakh, Baljit Markovic, Dejan Silva, Alcino J.
Institute
University Of California Los Angeles
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Currently, technologies to image large populations of neurons over time in awake, behaving animals are limited, as commercial microscopes require animals to be tethered, have only one imaging channel, and are prohibitively expensive. Golshani and colleagues propose to develop and test a new, miniaturized wireless microscope with two channels to measure and optogenetically manipulate activity of genetically labeled neurons in behaving animals. The system design and coding will be made open source immediately, allowing other researchers to probe neuronal activity across model systems with higher specificity at low costs as the project progresses.
Investigator
Craddock, Richard Cameron Milham, Michael Peter (contact)
Institute
Child Mind Institute, Inc.
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

Novel neuromodulation, recording, and imaging techniques applied to human and non- human primate brains generate datasets that require tools for organizing, processing and analyzing data that are widely available and easy to use. Drs. Milham and Craddock plan to extend C-PAC (Configurable Pipeline for the Analysis of Connectomes), building a configurable data analysis pipeline that incorporates various statistical analysis, machine learning, and network analytic techniques. In addition to adapting methods used in human imaging for non-human primate data, the project will implement a toolbox for alignment of electrophysiological data with brain imaging data. The resulting software enables high- throughput, semiautomated and end-to-end processing and analysis of structural and functional MRI data that are accessed locally or via the cloud.

Investigator
Verkhusha, Vladislav
Institute
Albert Einstein College Of Medicine, Inc
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Interventional Tools
Summary
Genetically encoded calcium indicators (GECIs) developed from fluorescent proteins (FPs) can be used to image intracellular calcium dynamics and provide a robust readout of neuronal responses to action potentials, and as a result, these proteins have revolutionized the way neural activity is recorded in the brain. Current GECIs are based on green and red fluorescent proteins, but because visible light is subject to strong scattering inside the brain, these proteins are only useful for recording activity close to the brain surface. Near-infrared (NIR) GECIs would provide a major increase in the depth at which these signals can be recorded, because they can be imaged with longer wavelength light, which is much less susceptible to scattering than light at visible wavelengths. Verkhusha’s team developed NIR GECIs that will be imaged with modern adaptive optics imaging techniques, allowing non-invasive, cellular-resolution imaging deep in the cortex and hippocampus. If successful, this research will provide highly sought-after deep-tissue optical probes and help advance researchers’ understanding of information processing in the brain.
Investigator
Jasanoff, Alan
Institute
Massachusetts Institute Of Technology
Year Funded
2014
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Dr. Jasanoff's team will synthesize calcium-sensing contrast agents that will allow functional magnetic resonance imaging (fMRI) scans to reveal activity of individual brain cells.
Investigator
Brunel, Nicolas Hull, Court A Lisberger, Stephen G (contact) Medina, Javier F
Institute
Duke University
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary

The cerebellum plays critical roles in learning and performing coordinated, well-timed movements. The majority of research on the cerebellum has focused on Purkinje cells. This project aims to use optogenetics, machine-learning, electrophysiology, imaging, and computer modeling to investigate the entire cerebellar circuit including all relevant cell types to gain a better understanding of how the cerebellum functions to support motor learning.

Investigator
Kim, Young R
Institute
Massachusetts General Hospital
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Non-invasive imaging of human brain activity relies either on the correlation between neuronal activity and blood flow (for functional MRI) or on measurements of the activity of broad neural populations from fields that are generated very near the surface of the brain (for electroencephalography and magnetoencephalography). Kim proposes a new direct-detection method based on the ability of a "spinlock" MRI sequence that increases sensitivity to select magnetic fields, allowing direct access to neural population activity without relying on blood flow measurements as a proxy. This approach involves carefully controlled animal experiments to provide proof-of-concept, using optogenetics to induce synchronous neuronal firing with simultaneous silencing of blood flow signals to test the new stimulus-induced rotary saturation (SIRS) technique to directly image activity.
Investigator
Berke, Joshua D Chestek, Cynthia Anne (contact)
Institute
University Of Michigan At Ann Arbor
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Chestek and Berke will develop dense arrays of 8 micron carbon-fiber electrodes, which are stiff enough to insert into the brain, but sufficiently small to avoid damage which plagues research using traditional recording electrode arrays. In addition to use in electrical recording, the electrodes will be developed for voltammetric measurements of transmitters such as dopamine. Together, these technological advancements could allow multi-site, real-time simultaneous electrophysiological and transmitter measurements in behaving animals, providing a novel method to monitor neural microcircuits.
Investigator
Adolphs, Ralph (contact) Howard, Matthew A. Poldrack, Russell A
Institute
California Institute Of Technology
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
Summary
Limited treatment options exist for emotional disorders because we do not understand the neural systems by which emotions are processed. Adolphs and colleagues will study how emotion is caused  by activity in brain networks. They will electrically stimulate emotion-related brain regions, such as the amygdala, in awake neurosurgical patients, and use concurrent fMRI to image the whole-brain networks engaged by the stimulated structures. Psychophysiological, behavioral, and self-report measures of emotion will be collected to quantify how the stimulation-induced activation patterns associate with specific components of emotion. This work could inform interventions to treat mood disorders through deep-brain stimulation.
Investigator
Dong, Hong-wei Tao, Huizhong Whit Zhang, Li I (contact)
Institute
University Of Southern California
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
Summary

Systematic studies on the brain-spinal cord connectome are lacking despite great efforts to characterize neuronal cell types in the brain. Zhang’s multi- laboratories project aims to systematically characterize neuronal types in the mouse spinal cord based on their anatomy, connectivity, neuronal morphologies, molecular identities, and electrophysiological properties. Via multiple newly-developed techniques, including an anterograde/retrograde trans-synaptic tagging method to label neurons, gene expression bard coding, and a fast 3D light sheet microscopy method, the team will establish a complete cell-type based brain-spinal cord connectome database, which will be made accessible to the neuroscience community.

Investigator
Tasic, Bosiljka
Institute
Allen Institute
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Theory & Data Analysis Tools
Summary

To gain a complete understanding of how certain cell types work, researchers must be able to access those specific cells. Despite advances in single-cell transcriptomics, commonly used genetic tools and methodologies have variable expression, can lack specificity, and often take a long time to create. Dr. Tasic’s group aims to develop a set of adeno-associated viruses containing enhancers to target specific cell types following administration via an injection behind the eye to access the whole brain, in mice. The enhancers will be defined via RNA and epigenetic sequencing, before being screened for their specificity. Once made publicly available, this toolkit could offer a more efficient method to access specific cell classes, facilitating investigations into their roles in circuit function.

Investigator
Mao, Tianyi Zhong, Haining (contact)
Institute
Oregon Health & Science University
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Interventional Tools
  • Monitor Neural Activity
Summary

Monitoring endogenous synaptic proteins in neuronal subtypes of behaving animals is needed to better understand neural circuits underlying behavior, but current visualization methods can produce altered protein function and off-target effects. Here, Dr. Zhong, Mao, and labs aim to develop a novel genetic strategy called endogenous labeling via exon duplication (ENABLED) to label endogenous synaptic proteins for in vivo imaging. Expanding on their success of labeling PSD-95 in neurons, the team will optimize the ENABLED method to label several additional synaptic proteins in mice, with the goal of generating ENABLED mice in which synaptic proteins are labeled with different colors for simultaneous imaging. This work could provide new tools for researchers to advance our understanding of synaptic connectivity and plasticity under physiological conditions in behaving animals.

Investigator
Voss, Joel L (contact); Disterhoft, John F
Institute
Northwestern University At Chicago
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
  • Theory & Data Analysis Tools
Summary

Alzheimer’s disease, epilepsy and other neurological disorders can cause problems with how the brain learns. In this project, researchers in the Disterhoft and Voss labs will perform experiments on rodents and human subjects designed to understand the cellular effects of electrical stimulation on the hippocampus, a region known to be involved in learning and memory. As part of this project, they will examine the relationship between stimulation and hippocampal neuronal synchrony during theta activity rhythms. Their results may help researchers understand the underlying circuitry associated with the memory problems common in many brain disorders.