Funded Awards

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Investigator
Butson, Christopher R Giacino, Joseph Thomas Henderson, Jaimie M Machado, Andre Guelman Schiff, Nicholas D (contact)
Institute
Weill Medical Coll Of Cornell Univ
Year Funded
2015
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Summary
Traumatic brain injury (TBI) afflicts hundreds of thousands of Americans each year, producing chronic cognitive disabilities that lack effective treatment. Preliminary studies with TBI patients and non-human primates suggest that these cognitive disabilities may be due to disrupted circuit function in the brain, specifically involving impaired connections between the thalamus and the frontal cortex. Working with a group of TBI patients who can function independently but remain limited by chronic cognitive impairment, Schiff and colleagues aim to build on these studies, using the latest device technology to deliver deep brain stimulation to the thalamus. The researchers hope to obtain a variety of behavioral and electrophysiological data to inform development of a next-generation device therapy for cognitive impairment associated with TBI.
Investigator
Lee, Wei-chung Allen
Institute
Harvard Medical School
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Monitor Neural Activity
  • Interventional Tools
Summary
Understanding cell type-specific neuronal connectivity may help indicate how the brain is altered in nervous system disorders. Lee’s team will use a high-throughput technology for electron microscopy volume image acquisition—capable of up to two orders of magnitude faster acquisition compared to current methods—and comprehensively characterize the cell types and connectivity within the cerebellum. They will reconstruct cerebellar network anatomy computationally and explore the organizational principles underlying cerebellar circuits. The tools and datasets will be released publicly, and may help uncover the role of specific circuit elements in nervous system function.
Investigator
Shih, Yen-yu Ian
Institute
Univ Of North Carolina Chapel Hill
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Monitor Neural Activity
  • Integrated Approaches
  • Human Neuroscience
Summary
Blood oxygen level dependent (BOLD) functional MRI is widely used to study human brain function. However, the cellular and molecular mechanisms underlying the BOLD signal remain poorly understood, though many neuroscientists believe the signal reflects contributions from both neurons and astrocytes. Shih and his colleagues will employ cutting-edge tools called Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to tease out the specific contributions of certain types of astrocytes and neurons to the BOLD signal by selectively activating one group while inactivating the other, and vice versa. The researchers will then repeat their experiments in animal models of chronic neuroinflammation to provide insight into how the BOLD signal is disrupted by diseases involving neuroinflammation.
Investigator
Tsankova, Nadejda Mincheva
Institute
Icahn School Of Medicine At Mount Sinai
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Interventional Tools
  • Monitor Neural Activity
Summary

To better understand human-specific glial diversity, Dr. Tsankova’s lab has endeavored to improve isolation methods of glial cells from human brain tissue, via cell-specific immunotagging techniques to isolate nuclear RNA and chromatin from frozen brain. Building off this work, the team aims to profile the epigenetic and molecular features of developing and adult human astrocyte and oligodenroglial lineages. They will use high throughput technologies like Tn5-HiC, ChIP-, RNA-, and ATAC-seq to characterize the chromatin structure, transcriptional factor binding activity, and differentiation kinetics across different developmental stages of human astrocytes and oligodenroglial progenitors. These epigenetic and functional datasets should enable the creation of an integrated map of glial plasticity, providing a reference tool for comparative studies of human health and disease.

Investigator
Haider, Bilal
Institute
GEORGIA INSTITUTE OF TECHNOLOGY
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary

The role of attention in sensory perception is an important question in neuroscience, especially when trying to understand and create better treatments for disorders like schizophrenia, autism spectrum disorders, and attention deficit disorders. Dr. Haider and team will utilize transgenic mice and combine high-density local field potential and neural activity recordings in the visual cortex, patch-clamp recordings from cortical and thalamic synaptic connections, cell-type specific optogenetics, and a well-characterized spatial attention task to elucidate the neural mechanisms of attention at multiple levels: specific cells, synapses, and circuits. 

Investigator
Jafarpour, Anna
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

Typically, we experience the world as a continuous sequence of events; but when recalling memories, we remember segmented episodes. The hippocampus and prefrontal cortex (PFC) play a role in segmenting, linking, and retrieving memories of associated events, but the neural circuit mechanism of this process is not well understood. Dr. Jafarpour aims to use intracranial encephalography (iEEG) to identify the neural dynamics in the hippocampal-PFC circuit that support the encoding of sequences of words. By combining iEEG with advanced analytical techniques, natural language processing models, and research with patients with hippocampal lesions, this project will offer insights into the neural basis of speech encoding and memory formation. The work may inform the development of neural prosthetics for use by patients with memory impairments.

Investigator
Wei, Wei
Institute
UNIVERSITY OF CHICAGO
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary

Understanding how sensory information is extracted by anatomically and functionally defined neural circuits exemplifies one of the many remaining questions surrounding neural circuit function. Using the visual direction-selective circuit in the mouse retina, Dr. Wei and colleagues will perform circuit analyses incorporating a variety of approaches: synapse-specific circuit manipulation, multiphoton calcium imaging, patch clamp electrophysiology, connectomic circuit tracing, and theoretical analysis of information encoding. Results from this work may have broad implications in understanding fundamental principles of neural computation by a well-defined neural circuit.

Investigator
Luo, Zhihao
Institute
Princeton University
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
Dr. Luo will use optogenetic tools to inactivate specific brain structures while simultaneously recording neuronal activity across other brain areas in the rat during evidence accumulation tasks. This research could uncover the neural circuits that support the gradual accumulation of evidence during decision making.
Investigator
Aksay, Emre (contact) Goldman, Mark S Seung, Hyunjune Sebastian
Institute
Weill Medical Coll Of Cornell Univ
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary
Understanding how brain circuit-level changes mediate behavioral changes requires detailed knowledge of circuit-wide activity patterns before, during, and after learning. Aksay’s team will study the dynamics of learning by revealing the changes in circuit activity patterns underlying a newly learned behavior. Specifically, they will study the adaptive tuning of the persistent neural activity underlying visual gaze-holding behavior in the zebrafish oculomotor system. The researchers will simultaneously record throughout the oculomotor brainstem and cerebellum during learning, perform anatomical reconstructions at electron microscopic resolution of the imaged circuits, incorporate these data into computational models to make predictions for sites of plasticity, and test those predictions through optical perturbations and electrophysiology. This work could serve as a blueprint for understanding cerebellar involvement in numerous behaviors.
Investigator
Crickmore, Michael A
Institute
Boston Children's Hospital
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary

How is a decision made whether or not to switch behaviors? This project aims to use experimental and computational approaches to study how information from competing motivations is processed and integrated to decide whether or not to switch behavior, i.e., to stop one behavior and start another. This work conducted in the Crickmore lab will make use of the Drosophila model to study motivational regulation. The findings will be used to generate circuit and computational models that can provide better insight into motivation.

Investigator
REYNOLDS, JOHN H et al.
Institute
SALK INSTITUTE FOR BIOLOGICAL STUDIES
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary

Each cortical neuron in the brain receives inputs from, potentially, thousands of other cells but produces only one collective response. It is unknown how neurons combine assorted inputs, which often come from many sources -- including sensory stimuli -- into a single response.  Drs. Brunel, Miller, and Reynolds will use visual and experimental optogenetic stimulation to compare responses in the visual cortexes of mice and monkeys as the neurons receive a variety of inputs. The team will also examine how inputs from specific types of neurons influence responses elicited in the cells with which they are communicating.  These findings may increase our understanding of brain circuit function in healthy brains and may provide clues to disorders in which critical circuits are disrupted.

Investigator
Ngai, John J.
Institute
University Of California Berkeley
Year Funded
2014
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
Summary
To understand what makes neurons distinct, Dr. Ngai's team will explore one major type of mouse brain cell, pinpointing genes responsible for differentiating them into subtypes and will also test whether each subtype has unique functions, using a new technique that labels them with tagged genes.
Investigator
Scanziani, Massimo
Institute
University Of California San Diego
Year Funded
2014
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
Summary
Dr. Scanziani's team will record neuronal responses to different visual stimuli to discover how individual brain cell activity is linked to expression of specific genes.
Investigator
Troyk, Philip R
Institute
Illinois Institute Of Technology
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Summary
Blindness can have a negative impact on quality of life, and is associated with relatively high rates of depression and social isolation, and relatively low levels of employment. The IntraCortical Visual Prosthesis (ICVP) team led by Dr. Troyk has worked to develop an ICVP that can compensate for blindness by stimulating the visual centers of the brain. This project aims to provide proof of principle with a small number of human volunteers, to demonstrate that the ICVP successfully produces visual sensory perception and to assess the utility of the induced visual percepts.
Investigator
Xu, Chris
Institute
Cornell University
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Interventional Tools
  • Monitor Neural Activity
Summary

The Xu lab aims to help researchers use multiphoton microscopy for watching electrical neural circuit activity in real time. In this project, they plan to develop an adaptive excitation source that will make multiphoton microscopy much faster at imaging activity. They will work with researchers at Cornell and Stanford Universities and at the HHMI Janelia Research Campus to test out and fine tune this new system. The system may help researchers explore how circuits control the brain under healthy and disease conditions.

Investigator
Starr, Philip Andrew
Institute
University Of California, San Francisco
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Summary
Deep brain stimulation (DBS) has an important clinical role in the management of movement disorders, including Parkinson’s disease (PD). However, current DBS therapy for PD relies on continuous stimulation, regardless of changes in brain circuit function related to changes in disease expression (i.e. oscillation between too little and too much movement). In this project, Starr and his team will use next-generation DBS devices to develop and test a method of automatically adjusting stimulation parameters based on brain signals that reflect the patient's clinical state, to optimize DBS for PD. In a small number of patients, they will measure local brain activity in each patient and use that information to develop individualized stimulation paradigms; these algorithms will then be programmed into the DBS devices, to demonstrate proof of principle for this novel, closed-loop DBS system.
Investigator
Foote, Kelly D Gunduz, Aysegul (contact)
Institute
University Of Florida
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Summary

Essential tremor (ET) is an incurable, degenerative brain disorder that results in increasingly debilitating tremor. Deep Brain Stimulation (DBS) is used as an effective treatment for ET, but the continuous brain stimulation provided by current DBS methods is likely unnecessary given the intermittent nature of ET symptoms, and may underlie DBS-induced side effects such as slurred speech and difficulty walking. It also may unnecessarily hasten the need for surgery to replace depleted DBS batteries. In this project, Gunduz and Foote propose to use modern DBS devices capable of recording and stimulating simultaneously, to continuously monitor brain activity and deliver stimulation only when necessary to control tremor. This work may provide proof-of-concept for the first chronic closed-loop DBS system for the treatment of a debilitating movement disorder in humans.

Investigator
Bialek, William Palmer, Stephanie E (contact) Schwab, David Jason
Institute
University Of Chicago
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
  • Theory & Data Analysis Tools
Summary

Behavioral neuroscience research produces large quantities of high- dimensional data requiring complicated interrogations. To uncover simpler underpinnings of complex neural recordings, Drs. Palmer, Bialek, and Schwab propose incorporating renormalization group (RG) techniques to a wide range of multi-unit, neural data. The statistical algorithms of their theoretical framework will be freely available and disseminated, as they should be relatively straightforward to apply regardless of discipline. This project could support tractable, efficient analysis of large datasets by enhancing future users’ ability to discern specific properties of neuronal populations critical to behaviors.

Investigator
Fins, Joseph J.
Institute
Weill Medical Coll Of Cornell Univ
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

Many traumatic brain injury (TBI) patients often experience chronic cognitive impairments that disrupt functioning and can interfere with societal reentry – current efforts aim to rapidly restore cognitive function to TBI patients. In doing so, a thorough understanding of the opportunities and challenges posed by rapid cognitive restoration is critical. To address this need, Dr. Joseph Fins and his team will interview patients and family members before implantation of thalamic deep brain stimulation (DBS) devices. These interviews will collect perspectives on risks and benefits, expectations and fears, as well as factors that are weighed during decision making. After implantation, interviews will collect perspectives on the impact of cognitive impairment and restoration. The project aims to develop legal theory that supports social reentry for TBI subjects who have achieved cognitive restoration, paving the way for maximizing patient-centered benefits of any therapeutic advance.

Investigator
Hamilton, Carol M
Institute
Research Triangle Institute
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

Recent tissue-clearing techniques and advances in microscopy have made it possible to produce 3D images of intact brains. to help ensure consistency in data collection and analysis, Dr. Hamilton and her team will develop a set of standards for3D imaging of whole brains for the neuroscience research community.. Dr. Hamilton’s group will convene a Working Group of experts who will work through a consensus process to establish standards that will be distributed to the research community. These standards should help improve the efficiency of imaging research and allow comparisons across studies.