Minimizing activation of overlying axons with epiretinal stimulation: The role of fiber orientation and electrode configuration

PLoS One. 2018 Mar 1;13(3):e0193598. doi: 10.1371/journal.pone.0193598. eCollection 2018.

Abstract

Currently, a challenge in electrical stimulation of the retina with a visual prosthesis (bionic eye) is to excite only the cells lying directly under the electrode in the ganglion cell layer, while avoiding excitation of axon bundles that pass over the surface of the retina in the nerve fiber layer. Stimulation of overlying axons results in irregular visual percepts, limiting perceptual efficacy. This research explores how differences in fiber orientation between the nerve fiber layer and ganglion cell layer leads to differences in the electrical activation of the axon initial segment and axons of passage.

Approach: Axons of passage of retinal ganglion cells in the nerve fiber layer are characterized by a narrow distribution of fiber orientations, causing highly anisotropic spread of applied current. In contrast, proximal axons in the ganglion cell layer have a wider distribution of orientations. A four-layer computational model of epiretinal extracellular stimulation that captures the effect of neurite orientation in anisotropic tissue has been developed using a volume conductor model known as the cellular composite model. Simulations are conducted to investigate the interaction of neural tissue orientation, stimulating electrode configuration, and stimulation pulse duration and amplitude.

Main results: Our model shows that simultaneous stimulation with multiple electrodes aligned with the nerve fiber layer can be used to achieve selective activation of axon initial segments rather than passing fibers. This result can be achieved while reducing required stimulus charge density and with only modest increases in the spread of activation in the ganglion cell layer, and is shown to extend to the general case of arbitrary electrode array positioning and arbitrary target volume.

Significance: These results elucidate a strategy for more targeted stimulation of retinal ganglion cells with experimentally-relevant multi-electrode geometries and achievable stimulation requirements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anisotropy
  • Axons / physiology*
  • Computational Biology / methods*
  • Electric Stimulation
  • Humans
  • Mammals
  • Models, Neurological
  • Retinal Ganglion Cells / physiology*
  • Visual Prosthesis

Grants and funding

TE was supported by an Australian Postgraduate Award from the Australian Government and The University of Melbourne, and the Gowrie Scholarship Fund of the Australian National University. TE and RRK acknowledge the support of IBM Research, Melbourne. IBM Research, Melbourne provided support in the form of a salary for RRK and an internship for TE for part of the period during which this research was completed, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. HM acknowledges funding from the Australian Research Council Centre of Excellence for Integrative Brain Function (project number CE140100007). ANB acknowledges the support of the Australian Research Council’s Discovery Projects funding scheme (project number DP140104533). DBG, HM and ANB acknowledge the support of the Australian National Health and Medical Research Council’s Project Grant funding scheme (NHMRC Grant APP1106390). This research was supported by Melbourne Bioinformatics on its Peak Computing Facility at The University of Melbourne (grant number VR0138).