A key in understanding the etiology and interventional outcome of neuropsychiatric diseases is the ability to analyze the brain's functional circuitry through precisely controlled stimulation mechanism, while at the same time non-invasively monitoring changes in neuronal activity. The use of conventional stimulation electrodes is constrained by the lack of its ability to selectively target different neuronal populations. Likewise, electrode-based neural stimulation does not necessarily mimic endogenous neural activity, and a spatial propagation ofthe activity in a biologically realistic fashion cannot always be guaranteed. The monitoring of the resulting brain activity on the other hand includes the use of recording electrodes that wili provide high temporal resolution measurements. However, the lack of """"""""anatomical awareness"""""""" of recording electrodes is a limiting factor for the analysis of functional circuitry that involves multiple, and possibly elusive brain areas. Blood oxygenation level dependent (BOLD) functional MRI (fMRI) with Its non-Invasive, whole-brain coverage capability is promising for such large-scale neuronal monitoring. But current fMRI schemes struggle with problems of image distortions and lack of sufficient spatial resolution. The candidate of this K99, Pathway to Independence grant is a superbly trained MR scientist now seeking to bridge the gap between fMRI monitoring and targeted neural stimulation schemes that exist today. In this proposal, the candidate proposes a coordinated development of a highly innovative molecularly targeted neuro-optical stimulation method with a de novo distortion-free, high-resolution functional MRI technique the candidate has developed in recent years. With this new method, specific types of neurons can be molecularly targeted for interrogation, endogenous neuronal activation elicited, and the resulting pattern of neuronal activity monitored at an exceedingly high spatial resolution without distortions. This new capability to non-invasively monitor brain activity at high spatial resolution, while controlling the neuronal activity with high functional precision, will provide a powerful future tool for studying the mechanisms of neuropsychiatric diseases. This will lead to better understanding ofthe disease mechanism as well as the development of new treatments.

Public Health Relevance

The proposed study, upon success, wili provide new capability to non-invasively monitor brain activity at high spatial resolution, while controlling the neuronal activity with high functional precision, which will provide a powerful future tool for studying the mechanisms of neuropsychiatric diseases. This will lead to better understanding of the disease mechanism as well as the development of new treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Transition Award (R00)
Project #
5R00EB008738-04
Application #
8137689
Study Section
Special Emphasis Panel (NSS)
Program Officer
Liu, Guoying
Project Start
2010-09-01
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$239,868
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Choy, ManKin; Duffy, Ben A; Lee, Jin Hyung (2017) Optogenetic study of networks in epilepsy. J Neurosci Res 95:2325-2335
Bernal-Casas, David; Lee, Hyun Joo; Weitz, Andrew J et al. (2017) Studying Brain Circuit Function with Dynamic Causal Modeling for Optogenetic fMRI. Neuron 93:522-532.e5
Liu, Jia; Duffy, Ben A; Bernal-Casas, David et al. (2017) Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies. Neuroimage 147:390-408
Fang, Zhongnan; Van Le, Nguyen; Choy, ManKin et al. (2016) High spatial resolution compressed sensing (HSPARSE) functional MRI. Magn Reson Med 76:440-55
Lin, Peter; Fang, Zhongnan; Liu, Jia et al. (2016) Optogenetic Functional MRI. J Vis Exp :
Lee, Hyun Joo; Weitz, Andrew J; Bernal-Casas, David et al. (2016) Activation of Direct and Indirect Pathway Medium Spiny Neurons Drives Distinct Brain-wide Responses. Neuron 91:412-24
Weitz, Andrew J; Fang, Zhongnan; Lee, Hyun Joo et al. (2015) Optogenetic fMRI reveals distinct, frequency-dependent networks recruited by dorsal and intermediate hippocampus stimulations. Neuroimage 107:229-41
Duffy, Ben A; Choy, ManKin; Chuapoco, Miguel R et al. (2015) MRI compatible optrodes for simultaneous LFP and optogenetic fMRI investigation of seizure-like afterdischarges. Neuroimage 123:173-84
Byers, Blake; Lee, Hyun Joo; Liu, Jia et al. (2015) Direct in vivo assessment of human stem cell graft-host neural circuits. Neuroimage 114:328-37
Liu, Jia; Lee, Hyun Joo; Weitz, Andrew J et al. (2015) Frequency-selective control of cortical and subcortical networks by central thalamus. Elife 4:e09215

Showing the most recent 10 out of 16 publications