The end goal of this multiscale modeling research is to bridge the gap existing between three-dimensional, full- wave, macro-modeling of electrical and magnetic biointeractions (global modeling) and cellular-level modeling strategies. Our research team is composed of engineers and neuroscientists that are experts in all computational and experimental aspects necessary to fill the existing gaps in multi-scale modeling. This multi-university effort to predict spatio-temporal distributions of active neurons based on current densities created by multi-electrode electrical stimulation depends on having a set of core models of molecular (receptor-channel kinetics), synaptic, neuron, and multi-neuron activity. These models and their inputs and outputs must be integrated into a global model of the extracellular media/matrix including relevant multi- electrode arrays. Successful modeling at these levels will allow hypotheses about space-time patterns of electrical stimulation to produce predictions about the number and distribution of activated inputs (based on known spatial distributions of afferent axons). The linked molecular, synaptic, neuron, multi-neuron, and global model will provide the basis for emerging predictions of the spatio-temporal distribution of active neurons and thus, the spatio-temporal distributions of spike train activity that encode all information in the nervous system. Further, we believe the proposed multiscale modeling framework constitutes an ideal platform capable of generating novel insights into the pathogenic mechanisms precipitating abnormal hippocampal function. Although the proposed research is focused on the hippocampal system, our effort will capitalize on our multiscale modeling accomplishments during the performance period of our original multiscale modeling U01 grant, in the realm of both retinal and cortical prostheses.

Public Health Relevance

The relevance of this research to the public health consists of the development of a generalizable engineering approach to the optimization of existing and proposed neural interfaces, which will produce enormous benefit to the neurologically disabled. We expect that the results of this work will constitute an ideal platform capable of generating novel insights into the pathogenic mechanisms precipitating abnormal hippocampal function as well as profoundly affect the way we design neurostimulating electrodes. !

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01EB025830-07
Application #
9781719
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Peng, Grace
Project Start
2012-09-15
Project End
2022-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Southern California
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Bingham, Clayton S; Loizos, Kyle; Yu, Gene J et al. (2018) Model-Based Analysis of Electrode Placement and Pulse Amplitude for Hippocampal Stimulation. IEEE Trans Biomed Eng 65:2278-2289