Ординатура / Офтальмология / Английские материалы / Artificial Sight Basic Research, Biomedical Engineering, and Clinical Advances_Humayun, Weiland, Chader_2007
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It should be noted that the method could incorporate arbitrary lumped impedances at any point of the impedance mesh to account for contact capacitances or any other effects that can be described by means of localized impedances. Furthermore, the method can be characterized by a “multiresolution” grid, where the size of the cells is chosen to fit the model to be simulated with fine resolution in regions of interest and relatively coarse resolution elsewhere [34].
Computational Challenges
As mentioned earlier, the size of the computational space can easily become too large to be handled with uniform cells. An approach to processing large models is to use a multi-resolution impedance method [33], where larger voxels are used in homogeneous regions of the model, and small voxels are used in regions with material boundaries, where detail is needed. In retinal models, the use of multi-resolution models can reduce the number of voxels from 30% to over 80% depending on the level of detail in the model. Building an optimized multi-resolution model is a complex process. Figure 15.16 shows a simplified way of creating a multi-resolution model from a uniformly discretized model. As electric properties change at material boundaries, it is important to keep small voxels at the boundaries to minimize numerical errors.
To process larger models, there are additional techniques that can be used. In some cases simulations can be performed in 2D instead of 3D. While those results are often qualitative in nature, preliminary results from simulations performed by our group indicate that some configurations allow the scaling of data obtained using 2D simulations into 3D values with an acceptable error margin. In particular, current density values taken far from the current return and close to the symmetry plane of the electrode array, in configurations with electrode arrays larger than 4 × 4, can be scaled well from 2D to 3D.
Figure 15.16. Procedure to obtain a multi-resolution model.
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Some circuit techniques can be used to reduce the size of the model’s equivalent electric circuit. For instance, if the impedance value between two nodes is very small in comparison with surrounding impedance values, it can be approximated with a value of zero. While this generates a small error in the calculation, it also lumps two circuital nodes together, reducing the rank of the resulting impedance matrix by one.
In addition to optimizing the model representation, numerical methods used can be tuned to use less computing resources. In general, since in this type of simulation the resulting transfer function of the linear system can be represented as a large sparse symmetric matrix, and taking advantage of the fact that sparse matrices can be stored in compact data structures, computing storage space can be saved by solving the linear system using iterative methods that keep the matrix sparse.
Results
There are several different types of information that can be obtained using a current spread simulation through the impedance method or similar methods. One matter of interest is to relate the current density recorded in the ganglion cell layer of the retina with the particular electrode array geometry and intensity of injected currents. Further, the effect that the location of the electrode arrays’ current return has on the ganglion cell layer excitation pattern may be studied with this type of simulation. Models with resolution fine enough to describe the geometrical characteristics of actual retinal cells can also be developed. Results below show how current spread simulations can provide information about the response to excitation by stimulating electrode arrays.
The current spread simulation provides the quantitative data needed to understand what would be the excitation pattern – and thus possibly the visual pattern – induced by a particular electrode arrangement and activation pattern.
The simulation results in Figure 15.17 show a transversal cut of a retinal model excited by an electrode array, and the resulting current densities inside the ganglion cell layer of the retina. The 4 × 4 electrode array is composed of electrodes measuring 75 m per side and is backed by a dielectric material. Individual electrodes are 75 m apart. Each electrode is injecting a current of 200 A. The resolution of the model is 2 m.
The location of the current return changes the current path and affects the current density in the ganglion cell layer. As in the previous simulation, Figure 15.18 shows a transversal cut of a retinal model excited by an electrode array, and the resulting current densities inside the ganglion cell layer of the retina. The setup of the model is the same as the previous simulation, with the exception of the current return placement, which is not centered over the electrode array in this case.
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Figure 15.17. Impedance method simulation results: (a) logarithmic colorplot represents current densities in slice of 3D retinal model (lighter = more current). (b) Line plot showing current densities for a cross section through the ganglion cell layer. The effect of the current injected by each individual electrode can be seen as a peak in the current density value, aligned with the spatial position of each electrode.
Knowing the current densities in the retinal tissue could help understanding how effectively the implant will operate. It also helps answering a number of questions regarding the design of implantable electrode arrays, including determining a proper location for the implant to be placed, measuring efficiency of different shapes and sizes of electrodes to be used, calculating the optimal inter-electrode spacing, finding a convenient location for the current return, and verifying that the implant will provide safe levels of current to the surrounding tissue.
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Figure 15.18. Impedance method simulation results: (a) logarithmic colorplot represents current densities in slice of 3D retinal model (lighter = more current). Note the higher current densities closer to the current return (top). (b) Line plot showing current densities for a cross section through the ganglion cell layer. While the four peaks can be differentiated, current density is higher in the leftmost peak, which is closer to the current return.
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Microstimulation with Chronically Implanted Intracortical Electrodes
Douglas McCreery
Neural Engineering Program
Huntington Medical Research Institutes
Abstract: Stimulating microelectrodes that penetrate into the brain afford a means of accessing the basic functional units of the central nervous system. Microstimulation in the region of the cerebral cortex that subserve vision may be an alternative, or an adjunct, to a retinal prosthesis, and may be particularly attractive as a means of restoring a semblance of high-resolution central vision. There also is the intriguing possibility that such a prosthesis could convey higher order visual percepts, many of which are mediated by neural circuits in the secondary or “extra-striate” visual areas that surround the primary visual cortex. The technologies of intracortical stimulating microelectrodes and investigations of the effects of microstimulation on neural tissue have advanced to the point where a cortical-level prosthesis is at least feasible. The imperative of protecting neural tissue from stimulationinduced damage imposes constraints on the selection of stimulus parameters, as does the requirement that the stimulation not greatly affect the electrical excitability of the neurons that are to be activated. The latter is especially likely to occur when many adjacent microelectrodes are pulsed, as will be necessary in a visual prosthesis. However, data from animal studies indicates that these restrictions on stimulus parameter are compatible with those that can evoke visual percepts in humans and in experimental animals. These findings give cause to be optimistic about the prospects for realizing a visual prosthesis utilizing intracortical microstimulation.
Introduction
The feasibility of a visual prosthesis to restore vision to a blind person using intracortical microstimulation (ICMS) in the visual cortex was first studied in a 42-year-old woman who had been totally blind for 22 years secondary to glaucoma [1]. Thirty-eight microelectrodes were implanted in the right visual cortex, near the occipital pole, for a period of 4 months. Visual percepts reported
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as small spots of light, called phosphenes, were produced by 34 of the 38 implanted microelectrodes. Threshold currents for phosphene generation with trains of biphasic pulses were as low as 1.9 A, and most of the microelectrodes had thresholds below 25 A. The phosphenes’ brightness could be modified with stimulus amplitude, frequency, and pulse duration. The phosphenes did not flicker during the stimulation and ended quickly when the stimulation was terminated. The apparent size of phosphenes ranged from a “pin-point” to a “nickel” (20-mm-diameter coin) held at arm’s length. Distinct phosphenes could be elicited by microelectrode spaced as closely as 500 m, suggesting that a prosthesis based on ICMS might restore vision with good spatial detail.
The Anatomy and Physiology of the Visual System, as they Relate to a Cortical Visual Prosthesis
The axons of the optic nerve and tract project onto the lateral geniculate nucleus of the thalamus, which in turn projects in an orderly fashion onto the striate cortex at the posterior (occipital) pole of the brain. This “visuotopic” projection from the retina onto the striate cortex creates a map of the corresponding half of the visual field in the cortex. The macula lutea, the portion of the retina that mediates high-resolution vision and thus the perception of spatial detail, is represented in the posterior part of the striate cortex, while more peripheral regions of the retina (the visual field) are represented more anteriorly (Figure 16.1). The macula occupies only a small portion of the retina but is represented by a disproportionately large region of the cerebral cortex, which is commensurate with its role in the perception of fine spatial detail; this “cortical magnification factor” reflects the high density of photoreceptors in and around the macula. The small size of the macula (a few mm in diameter) may make it difficult to develop a retinal prosthesis that can deliver electrical stimulation into this region with sufficient spatial detail so as to convey to a blind person a facsimile of the high-resolution vision that this region subserves in a sighted person. However, due to the cortical magnification factor, the macula is represented by many square centimeters of cerebral cortex. Further, since this region is located at the extreme posterior pole of the brain, surgical access is relatively easy, so a cortical prosthesis that incorporates a large number of intracortical microelectrodes may offer the best prospects for restoring useful central vision to blind person. However, the topology of the cortical projection of more peripheral regions of the visual field is much less favorable for a cortical-level prosthesis, since they project onto cortical regions deeper within the central sulcus between the cerebral hemispheres and into the depths of the calcarine sulci of both hemispheres.
There also is the intriguing possibility that such a prosthesis could convey higher order visual percepts, many of which are mediated by neural circuits in the “secondary” or “extra-striate” visual areas that surround the primary visual cortex. For example, the perception of the speed and direction of a moving object in the visual field appears to be mediated in the middle temporal cortex, usually designated as visual area MT or V5 [2]. The high spatial selectivity afforded by ICMS is well suited to access this neuronal circuitry. Thus microstimulation
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Figure 16.1. Diagrammatic representation of the visuotopic projection of the retina onto the human striate cortex, which occupies a large part of the occipital lobe. Central vision is represented in a large region at the posterior pole of the brain, whereas peripheral vision is represented more anteriorly (Adapted from [28] ).
with 10 A current pulses in area MT of a Rhesus monkey appeared to impart a sense of directed motion to an object in the visual field [3, 4]. However, when the stimulus current was increased to 80 A (and thus was able to activate neurons throughout a greater volume of tissue surrounding the microelectrode), The monkey’s performance indicated that the percept of motion in a particular direction was much more ambiguous. These observations suggested that the percept of directed motion was mediated by direct activation of a highly localized population of neurons in area MT.
Microelectrodes for Chronic Intracortical Microstimulation
If a neural prosthesis based on ICMS is to restore a useful facsimile of central vision, or is to convey higher order visual perception into the extra-striate cortex, it must include a large number of microelectrodes and also must accommodate the somewhat irregular geometry of the cerebral cortex. The local curvature and irregularities of the brain can be accommodated by implanting a large number of arrays, each with a small footprint. Figure 16.2a shows such an intracortical microstimulating array that was fabricated in our laboratory [5, 6]. The microelectrodes extend from an epoxy superstructure that is 3 mm in diameter, and can be of various lengths. In addition to the 16 working microelectrodes, the array contains 3 longer stabilizing pins, which help to prevent torsion and traction