Neural Responses to Multielectrode Stimulation of Healthy and Degenerate Retina.

Purpose: Simultaneous stimulation of multiple retinal electrodes in normally sighted animals shows promise in improving the resolution of retinal prostheses. However, the effects of simultaneous stimulation on degenerate retinae remain unknown. Therefore, we investigated the characteristics of cortical responses to multielectrode stimulation of the degenerate retina. Methods: Four adult cats were bilaterally implanted with retinal electrode arrays in the suprachoroidal space after unilateral adenosine triphosphate (ATP)-induced retinal photoreceptor degeneration. Functional and structural changes were characterized by using electroretinogram a-wave amplitude and optical coherence tomography. Multiunit activity was recorded from both hemispheres of the visual cortex. Responses to single- and multielectrode stimulation of the ATP-injected and fellow control eyes were characterized and compared. Results: The retinae of ATP-injected eyes displayed structural and functional changes consistent with mid- to late-stage photoreceptor degeneration and remodeling. Responses to multielectrode stimulation of the ATP-injected eyes exhibited shortened latencies, lower saturated spike counts, and higher thresholds, compared to stimulation of the fellow control eyes. Electrical receptive field sizes were significantly larger in the ATP-injected eye than in the control eye, and positively correlated with the extent of degeneration. Conclusions: Significant differences exist between cortical responses to stimulation of healthy and degenerate retinae. Our results highlight the importance of using a retinal degeneration model when evaluating the efficacy of novel stimulation paradigms.

Modelling extracellular electrical stimulation: part 3. Derivation and interpretation of neural tissue equations.

OBJECTIVE: A common approach in modelling extracellular electrical stimulation is to represent neural tissue by a volume conductor when calculating the activating function as the driving term in a cable equation for the membrane potential. This approach ignores the cellular composition of tissue, including the neurites and their combined effect on the extracellular potential. This has a number of undesirable consequences. First, the two natural and equally valid choices of boundary conditions for the cable equation (i.e. using either voltage or current) lead to two mutually inconsistent predictions of the membrane potential. Second, the spatio-temporal distribution of the extracellular potential can be strongly affected by the combined cellular composition of the tissue. In this paper, we develop a mean field volume conductor theory to overcome these shortcomings of available models. APPROACH: This method connects the microscopic properties of the constituent fibres to the macroscopic electrical properties of the tissue by introducing an admittivity kernel for the neural tissue that is non-local, non-instantaneous and anisotropic. This generalizes the usual tissue conductivity. A class of bidomain models that is mathematically equivalent to this class of self-consistent volume conductor models is also presented. The bidomain models are computationally convenient for simulating the activation map of neural tissue using numerical methods such as finite element analysis. MAIN RESULTS: The theory is first developed for tissue composed of identical, parallel fibres and then extended to general neural tissues composed of mixtures of neurites with different and arbitrary orientations, arrangements and properties. Equations describing the extracellular and membrane potential for the longitudinal and transverse modes of stimulation are derived. SIGNIFICANCE: The theory complements our earlier work, which developed extensions to cable theory for the micro-scale equations of neural stimulation that apply to individual fibres. The modelling framework provides a number of advantages over other approaches currently adopted in the literature and, therefore, can be used to accurately estimate the membrane potential generated by extracellular electrical stimulation.

Modelling extracellular electrical stimulation: part 4. Effect of the cellular composition of neural tissue on its spatio-temporal filtering properties.

OBJECTIVE: The objective of this paper is to present a concrete application of the cellular composite model for calculating the membrane potential, described in an accompanying paper. APPROACH: A composite model that is used to determine the membrane potential for both longitudinal and transverse modes of stimulation is demonstrated. MAIN RESULTS: Two extreme limits of the model, near-field and far-field for an electrode close to or distant from a neuron, respectively, are derived in this paper. Results for typical neural tissue are compared using the composite, near-field and far-field models as well as the standard isotropic volume conductor model. The self-consistency of the composite model, its spatial profile response and the extracellular potential time behaviour are presented. The magnitudes of the longitudinal and transverse components for different values of electrode-neurite separations are compared. SIGNIFICANCE: The unique features of the composite model and its simplified versions can be used to accurately estimate the spatio-temporal response of neural tissue to extracellular electrical stimulation.