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, neuroscientists, biophysicists, surgeons, and computer scientists that are experts in all computational and experimental aspects necessary to fill the existing gaps in multi-scale modeling. This new 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. Our research effort will capitalize on our accomplishments in the realm of retinal and cortical prostheses, and use these as test beds for the multiscale predictive modeling methods that we will develop within the proposed activity.

Public Health 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 profoundly affect the way we design neurostimulating electrodes and provide a deep understanding of the optimal shape and size of electrodes, waveform characteristics and timing differences between stimulating currents in adjacent electrodes, and current levels to name a few.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01GM104604-02
Application #
8545197
Study Section
Special Emphasis Panel (ZEB1-OSR-C (M3))
Program Officer
Swain, Amy L
Project Start
2012-09-15
Project End
2017-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$548,380
Indirect Cost
$88,265
Name
University of Utah
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Hendrickson, Phillip J; Yu, Gene J; Song, Dong et al. (2016) A Million-Plus Neuron Model of the Hippocampal Dentate Gyrus: Critical Role for Topography in Determining Spatiotemporal Network Dynamics. IEEE Trans Biomed Eng 63:199-209
Loizos, Kyle; RamRakhyani, Anil Kumar; Anderson, James et al. (2016) On the computation of a retina resistivity profile for applications in multi-scale modeling of electrical stimulation and absorption. Phys Med Biol 61:4491-505
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Gilbert, Andrew; Loizos, Kyle; RamRakhyani, Anil Kumar et al. (2015) A 3-D admittance-level computational model of a rat hippocampus for improving prosthetic design. Conf Proc IEEE Eng Med Biol Soc 2015:2295-8
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Boshuo Wang; Weiland, James D (2015) Resistivity profiles of wild-type, rd1, and rd10 mouse retina. Conf Proc IEEE Eng Med Biol Soc 2015:1650-3
Hendrickson, Phillip J; Yu, Gene J; Song, Dong et al. (2015) Interactions between Inhibitory Interneurons and Excitatory Associational Circuitry in Determining Spatio-Temporal Dynamics of Hippocampal Dentate Granule Cells: A Large-Scale Computational Study. Front Syst Neurosci 9:155
Somogyi, Endre T; Bouteiller, Jean-Marie; Glazier, James A et al. (2015) libRoadRunner: a high performance SBML simulation and analysis library. Bioinformatics 31:3315-21
Allam, Sushmita L; Bouteiller, Jean-Marie C; Hu, Eric Y et al. (2015) Synaptic Efficacy as a Function of Ionotropic Receptor Distribution: A Computational Study. PLoS One 10:e0140333

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