The feasibility of producing a visual prosthesis for the blind using intracortical microstimulation (ICMS) of the visual cortex was studied in a 42-year-old woman who had been totally blind for 22 years secondary to glaucoma. Thirty-eight microelectrodes were implanted in the right visual cortex, near the occipital pole, for a period of 4 months. Percepts reported as small spots of light, called phosphenes, were produced with 34 of the 38 implanted microelectrodes. Threshold currents for phosphene generation with trains of biphasic pulses were as low as 1.9 microA, and most of the microelectrodes had thresholds below 25 microA. Phosphene brightness could be modified with stimulus amplitude, frequency and pulse duration. Repeated stimulation over a period of minutes produced a gradual decrease in phosphene brightness. Phosphenes did not flicker. The apparent size of phosphenes ranged from a "pin-point' to a "nickel' (20 mm diameter coin) held at arm's length. Phosphene size usually decreased as stimulation current was increased but increased slightly as the train length (TL) was increased. At levels of stimulation near threshold, the phosphenes were often reported to have colours. As the stimulation level was increased, the phosphenes generally became white, greyish or yellowish. Individual phosphenes appeared at different distances from the subject. When two phosphenes were simultaneously generated, the apparent distances of the individual phosphenes sometimes changed to make them appear to be at about the same distance. When three or more phosphenes were simultaneously generated, they became coplanar. Except for rare occasions, phosphenes extinguished rapidly at the termination of the stimulation train. When stimulation TLs were increased beyond 1 s, phosphenes usually disappeared before the end of the train. The duration of phosphene perception could be increased by interrupting a long stimulation train with brief pauses in stimulation. Intracortical microelectrodes spaced 500 microns apart generated separate phosphenes, but microelectrodes spaced 250 microns typically did not. This two-point resolution was about five times closer than has typically been achieved with surface stimulation. With some individual microelectrodes, a second closely spaced phosphene was sometimes produced by increasing the stimulation current. Phosphenes moved with eye movements. When up to six phosphenes were simultaneously elicited, they all moved with the same relative orientation during eye movements. All phosphenes were located in the left hemi-field with the majority above the horizontal meridian. There was a clustering of most of the phosphenes within a relatively small area of visual space. The potentially greater microelectrode density and lower power requirements of ICMS compared with surface stimulation appears encouraging for a visual prosthesis. However, further studies with blind subjects are required to optimize stimulation parameters and test complex image recognition before the feasibility of a visual prosthesis based on ICMS can be established.

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Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex.

A novel method for damage-free, artifact-free stimulation of neural tissue using pulsed, low-energy infrared laser light is presented. Optical stimulation elicits compound nerve and muscle potentials similar to responses obtained with conventional electrical neural stimulation in a rat sciatic nerve model. Stimulation and damage thresholds were determined as a function of wavelength using a tun- able free electron laser source =2 to 10 m and a solid state hol- mium:YAG laser =2.12 m. Threshold radiant exposure required for stimulation varies with wavelength from 0.312 J/cm 2 =3m to 1.22 J/cm 2 =2.1 m. Histological analysis indicates no dis- cernable thermal damage with suprathreshold stimulation. The largest damage/stimulation threshold ratios 6 were at wavelengths corre- sponding to valleys in the IR spectrum of soft tissue absorption 4 and 2.1 m. Furthermore, optical stimulation can be used to generate a spatially selective response in small fascicles of the sciatic nerve that has significant advantages e.g., noncontact, spatial resolution, lack of stimulation artifact over conventional electrical methods in diagnos- tic and therapeutic procedures in neuroscience, neurology, and neurosurgery. © 2005 Society of Photo-Optical Instrumentation Engineers. DOI: 10.1117/1.2121772

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Application of infrared light for in vivo neural stimulation.

The strength—duration time constant (τSD) is a property of nodal membrane and, while it depends on a number of factors, its measurement may shed light on axonal properties when taken in conjunction with measurements of axonal excitability. For example, τSD increases with demyelination as the exposed membrane is enlarged by inclusion of paranodal and internodal membrane, it decreases with hyperpolarization and it increases with depolarization. The present study was undertaken in 20 normal volunteers to compare strength—duration curves for compound sensory and muscle action potentials, to determine the most appropriate curve fitting equation for the data, and to examine the reproducibility of the calculated time constant on different days, for potentials of different amplitude and at different sites along the nerve. Using a computerized threshold-tracking system, stimulus intensity was adjusted to produce

an antidromic compound sensory action potential (CSAP) or an orthodromic muscle action potential of 30% of maximum. Stimulus duration was increased every minute in 20 μs steps from 20 μs to 1 ms. The time constant for compound sensory potentials (665±182 μs) was longer than that for compound EMG potentials (459±126 μs). Weiss's formula, which relates threshold charge to stimulus duration, provided an accurate fit for the experimental data, and the study validated that, using it, relatively few experimental measurements were required to calculate the time constant. In repeated studies on the same subject, time constants usually differed by <400 μs for sensory axons and <250 μs for motor axons. They were identical at different sites along the nerve and did not alter with the size of the compound action potential. These characteristics suggest that the determinations of strength-duration time constant could be suitable for clinical usage.

Strength-duration properties of human peripheral nerve

For more than a century, the traditional method of stimulating neural activity has been based on electrical methods, and it remains the gold standard to date. We report a technological breakthrough in neural activation in which low-level, pulsed infrared laser light is used to elicit compound nerve and muscle potentials in mammalian peripheral nerve in vivo. Optically induced neural action potentials are spatially precise, artifact free, and damage free and are generated by use of energies well below tissue ablation threshold. Thus optical stimulation presents a simple yet novel approach to contact-free in vivo neural activation that has major implications for clinical neurosurgery, basic neurophysiology, and neuroscience.

Optical stimulation of neural tissue in vivo.

Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex

The strength-duration curve is a plot of the lowest (threshold) current (I) required for stimulation versus pulse duration (d); it forms the basis for describing the excitability of a given tissue. It is extremely useful in all manner of studies in which excitable tissues are stimulated because it describes the manner in which the current required is changed when the pulse duration is changed. Moreover, it can be used to determine the charge and energy-duration relationships. It will be the objective of this communication to show how the essential constants can be obtained.

J. D. Bourland

Papers

The Strength-Duration Curve