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 #
4U01GM104604-05
Application #
9120372
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Brazhnik, Paul
Project Start
2012-09-15
Project End
2017-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Utah
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Hu, Eric; Mergenthal, Adam; Bingham, Clayton S et al. (2018) A Glutamatergic Spine Model to Enable Multi-Scale Modeling of Nonlinear Calcium Dynamics. Front Comput Neurosci 12:58
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
Loizos, Kyle; Marc, Robert; Humayun, Mark et al. (2018) Increasing Electrical Stimulation Efficacy in Degenerated Retina: Stimulus Waveform Design in a Multiscale Computational Model. IEEE Trans Neural Syst Rehabil Eng 26:1111-1120
Hu, Eric Y; Bouteiller, Jean-Marie C; Dong Song et al. (2016) Development of a detailed model of calcium dynamics at the postsynaptic spine of an excitatory synapse. Conf Proc IEEE Eng Med Biol Soc 2016:6102-6105
Yu, Gene J; Dong Song; Berger, Theodore W (2016) Place field detection using grid-based clustering in a large-scale computational model of the rat dentate gyrus. Conf Proc IEEE Eng Med Biol Soc 2016:1405-1408
Wang, Boshuo; Weiland, James D (2016) Analysis of the Peak Resistance Frequency Method. IEEE Trans Biomed Eng 63:2086-2094
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
Robinson, Brian S; Berger, Theodore W; Dong Song (2016) Monte Carlo validation of spike-timing-dependent plasticity identification from spiking activity. Conf Proc IEEE Eng Med Biol Soc 2016:1624-1627
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
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

Showing the most recent 10 out of 34 publications