Niranjan Khadka1, Dennis Q Truong2, Preston Williams3, John H Martin4, Marom Bikson5. 1. Department of Biomedical Engineering, The City College of New York, New York, NY, USA. Electronic address: nironzan@gmail.com. 2. Department of Biomedical Engineering, The City College of New York, New York, NY, USA. 3. Department of Molecular, Cellular, and Biomedical Sciences, City University of NY School of Medicine, New York, NY, 10031, USA. 4. CUNY Graduate Center, New York, NY, 10031, USA; Department of Molecular, Cellular, and Biomedical Sciences, City University of NY School of Medicine, New York, NY, 10031, USA. 5. Department of Biomedical Engineering, The City College of New York, New York, NY, USA. Electronic address: bikson@ccny.cuny.edu.
Abstract
BACKGROUND: Quasi-uniform assumption is a general theory that postulates local electric field predicts neuronal activation. Computational current flow model of spinal cord stimulation (SCS) of humans and animal models inform how the quasi-uniform assumption can support scaling neuromodulation dose between humans and translational animal. NEW METHOD: Here we developed finite element models of cat and rat SCS, and brain slice, alongside SCS models. Boundary conditions related to species specific electrode dimensions applied, and electric fields per unit current (mA) predicted. RESULTS: Clinically and across animal, electric fields change abruptly over small distance compared to the neuronal morphology, such that each neuron is exposed to multiple electric fields. Per unit current, electric fields generally decrease with body mass, but not necessarily and proportionally across tissues. Peak electric field in dorsal column rat and cat were ∼17x and ∼1x of clinical values, for scaled electrodes and equal current. Within the spinal cord, the electric field for rat, cat, and human decreased to 50% of peak value caudo-rostrally (C5-C6) at 0.48 mm, 3.2 mm, and 8 mm, and mediolaterally at 0.14 mm, 2.3 mm, and 3.1 mm. Because these space constants are different, electric field across species cannot be matched without selecting a region of interest (ROI). COMPARISON WITH EXISTING METHOD: This is the first computational model to support scaling neuromodulation dose between humans and translational animal. CONCLUSIONS: Inter-species reproduction of the electric field profile across the entire surface of neuron populations is intractable. Approximating quasi-uniform electric field in a ROI is a rational step to translational scaling.
BACKGROUND: Quasi-uniform assumption is a general theory that postulates local electric field predicts neuronal activation. Computational current flow model of spinal cord stimulation (SCS) of humans and animal models inform how the quasi-uniform assumption can support scaling neuromodulation dose between humans and translational animal. NEW METHOD: Here we developed finite element models of cat and rat SCS, and brain slice, alongside SCS models. Boundary conditions related to species specific electrode dimensions applied, and electric fields per unit current (mA) predicted. RESULTS: Clinically and across animal, electric fields change abruptly over small distance compared to the neuronal morphology, such that each neuron is exposed to multiple electric fields. Per unit current, electric fields generally decrease with body mass, but not necessarily and proportionally across tissues. Peak electric field in dorsal column rat and cat were ∼17x and ∼1x of clinical values, for scaled electrodes and equal current. Within the spinal cord, the electric field for rat, cat, and human decreased to 50% of peak value caudo-rostrally (C5-C6) at 0.48 mm, 3.2 mm, and 8 mm, and mediolaterally at 0.14 mm, 2.3 mm, and 3.1 mm. Because these space constants are different, electric field across species cannot be matched without selecting a region of interest (ROI). COMPARISON WITH EXISTING METHOD: This is the first computational model to support scaling neuromodulation dose between humans and translational animal. CONCLUSIONS: Inter-species reproduction of the electric field profile across the entire surface of neuron populations is intractable. Approximating quasi-uniform electric field in a ROI is a rational step to translational scaling.
Authors: Carlos A Sánchez-León; Isabel Cordones; Claudia Ammann; José M Ausín; María A Gómez-Climent; Alejandro Carretero-Guillén; Guillermo Sánchez-Garrido Campos; Agnès Gruart; José M Delgado-García; Guy Cheron; Javier F Medina; Javier Márquez-Ruiz Journal: Sci Rep Date: 2021-02-04 Impact factor: 4.379