Electrical induction of vision.

We assess what monkeys see during electrical stimulation of primary visual cortex (area V1) and relate the findings to visual percepts evoked electrically from human V1. Discussed are: (1) the electrical, cytoarchitectonic, and visuo-behavioural factors that affect the ability of monkeys to detect currents in V1; (2) the methods used to ascertain what monkeys see when electrical stimulation is delivered to V1; (3) a corticofugal mechanism for the induction of visual percepts; and (4) the quantity of information transferred to V1 by electrical stimulation. Experiments are proposed that should advance our understanding of how electrical stimulation affects macaque and human V1. This work contributes to the development of a cortical visual prosthesis for the blind. We dedicate this work to the late Robert W. Doty.

Visual and auditory cue integration for the generation of saccadic eye movements in monkeys and lever pressing in humans.

This study examined how effectively visual and auditory cues can be integrated in the brain for the generation of motor responses. The latencies with which saccadic eye movements are produced in humans and monkeys form, under certain conditions, a bimodal distribution, the first mode of which has been termed express saccades. In humans, a much higher percentage of express saccades is generated when both visual and auditory cues are provided compared with the single presentation of these cues [H. C. Hughes et al. (1994) J. Exp. Psychol. Hum. Percept. Perform., 20, 131-153]. In this study, we addressed two questions: first, do monkeys also integrate visual and auditory cues for express saccade generation as do humans and second, does such integration take place in humans when, instead of eye movements, the task is to press levers with fingers? Our results show that (i) in monkeys, as in humans, the combined visual and auditory cues generate a much higher percentage of express saccades than do singly presented cues and (ii) the latencies with which levers are pressed by humans are shorter when both visual and auditory cues are provided compared with the presentation of single cues, but the distribution in all cases is unimodal; response latencies in the express range seen in the execution of saccadic eye movements are not obtained with lever pressing.

New methods devised specify the size and color of the spots monkeys see when striate cortex (area V1) is electrically stimulated.

Creating a prosthetic device for the blind is a central future task. Our research examines the feasibility of producing a prosthetic device based on electrical stimulation of primary visual cortex (area V1), an area that remains intact for many years after loss of vision attributable to damage to the eyes. As an initial step in this effort, we believe that the research should be carried out in animals, as it has been in the creation of the highly successful cochlear implant. We chose the rhesus monkey, whose visual system is similar to that of man. We trained monkeys on two tasks to assess the size, contrast, and color of the percepts created when single sites in area V1 are stimulated through microelectrodes. Here, we report that electrical stimulation within the central 5° of the visual field representation creates a small spot that is between 9 and 26 min of arc in diameter and has a contrast ranging between 2.6% and 10%. The dot generated by the stimulation in the majority of cases was darker than the background viewed by the animal and was composed of a variety of low-contrast colors. These findings can be used as inputs to models of electrical stimulation in area V1. On the basis of these findings, we derive what kinds of images would be expected when implanted arrays of electrodes are stimulated through a camera attached to the head whose images are converted into electrical stimulation using appropriate algorithms.

The integration of disparity, shading and motion parallax cues for depth perception in humans and monkeys.

A visual stimulus display was created that enabled us to examine how effectively the three depth cues of disparity, motion parallax and shading can be integrated in humans and monkeys. The display was designed to allow us to present these three depth cues separately and in various combinations. Depth was processed most effectively and most rapidly when all three cues were presented together indicating that these separate cues are integrated at yet unknown sites in the brain. Testing in humans and monkeys yielded similar results suggesting that monkeys are a good animal model for the study of the underlying neural mechanisms of depth perception.

Microstimulation of visual cortex to restore vision.

This review argues that one reason why a functional visuo-cortical prosthetic device has not been developed to restore even minimal vision to blind individuals is because there is no animal model to guide the design and development of such a device. Over the past 8 years we have been conducting electrical microstimulation experiments on alert behaving monkeys with the aim of better understanding how electrical stimulation of the striate cortex (area V1) affects oculo- and skeleto-motor behaviors. Based on this work and upon review of the literature, we arrive at several conclusions: (1) As with the development of the cochlear implant, the development of a visuo-cortical prosthesis can be accelerated by using animals to test the perceptual effects of microstimulating V1 in intact and blind monkeys. (2) Although a saccade-based paradigm is very convenient for studying the effectiveness of delivering stimulation to V1 to elicit saccadic eye movements, it is less ideal for probing the volitional state of monkeys, as they perceive electrically induced phosphenes. (3) Electrical stimulation of V1 can delay visually guided saccades generated to a punctate target positioned in the receptive field of the stimulated neurons. We call the region of visual space affected by the stimulation a delay field. The study of delay fields has proven to be an efficient way to study the size and shape of phosphenes generated by stimulation of macaque V1. (4) An alternative approach to ascertain what monkeys see during electrical stimulation of V1 is to have them signal the detection of current with a lever press. Monkeys can readily detect currents of 1-2 microA delivered to V1. In order to evoke featured phosphenes currents of under 5 microA will be necessary. (5) Partially lesioning the retinae of monkeys is superior to completely lesioning the retinae when determining how blindness affects phosphene induction. We finish by proposing a future experimental paradigm designed to determine what monkeys see when stimulation is delivered to V1, by assessing how electrical fields generated through multiple electrodes interact for the production of phosphenes, and by depicting a V1 circuit that could mediate electrically induced phosphenes.

Depth-dependent detection of microampere currents delivered to monkey V1.

Monkeys can detect electrical stimulation delivered to the striate cortex (area V1). We examined whether such stimulation is layer dependent. While remaining fixated on a spot of light, a rhesus monkey was required to detect a 100-ms train of electrical stimulation delivered to a site within area V1. A monkey signaled the delivery of stimulation by depressing a lever after which he was rewarded with a drop of apple juice. Control trials were interleaved during which time no stimulation was delivered and the monkey was rewarded for not depressing the lever. Biphasic pulses were delivered at 200 Hz, and the current was typically at or < 30 muA using 0.2-ms cathode-first biphasic pulses. For some experiments, the pulse duration was varied from 0.05 to 0.7 ms and anode-first pulses were used. The current threshold for detecting cathode-first pulses 50% of the time was the lowest (< 10 muA) when stimulation was delivered to the deepest layers of V1 (between 1.0 and 2.5 mm below the cortical surface). Also, the shortest chronaxies (< 0.2 ms) and the shortest latencies (< 200 ms) for detecting the stimulation were observed at these depths. Finally, anode-first pulses were most effective at evoking a detection response in superficial V1 and cathode-first pulses were most effective at evoking a detection response in deep V1 (> 1.75 mm below the cortical surface). Accordingly, the deepest layers of V1 are the most sensitive for the induction of a detection response to electrical stimulation in monkeys.

Background luminance affects the detection of microampere currents delivered to macaque striate cortex.

Monkeys detect electrical microstimulation delivered to the striate cortex (area V1). We examined whether the ability of monkeys to detect such stimulation is affected by background luminance. While remaining fixated on a spot of light centered on a monitor, a monkey was required to detect a 100 ms train of electrical stimulation delivered to a site within area V1 situated from 1 to 1.5 mm below the cortical surface. A monkey signaled the delivery of stimulation by depressing a lever after which it was rewarded with a drop of apple juice. Control trials were interleaved during which time no stimulation was delivered and the monkey was rewarded for not depressing the lever. Biphasic pulses were delivered at 200 Hz and the current ranged from 2 to 30 microA using 0.2 ms anode-first biphasic pulses. The background luminance level of the monitor could be varied from 0.005 to 148 cd/m(2). It was found that, for monitor luminance levels below 10 cd/m(2), the current threshold to evoke a detection response increased. We discuss the significance of this result with regard to phosphenes elicited from human V1 and in relation to visual perception.

Conditions that alter saccadic eye movement latencies and affect target choice to visual stimuli and to electrical stimulation of area V1 in the monkey.

In this study, we examined procedures that alter saccadic latencies and target selection to visual stimuli and electrical stimulation of area V1 in the monkey. It has been shown that saccadic eye movement latencies to singly presented visual targets form a bimodal distribution when the fixation spot is turned off a number of milliseconds prior to the appearance of the target (the gap period); the first mode has been termed express saccades and the second regular saccades. When the termination of the fixation spot is coincident with the appearance of the target (0 ms gap), express saccades are rarely generated. We show here that a bimodal distribution of saccadic latencies can also be obtained when an array of visual stimuli is presented prior to the appearance of the visual target, provided the elements of the array overlap spatially with the visual target. The overall latency of the saccadic eye movements elicited by electrical stimulation of area V1 is significantly shortened both when a gap is introduced between the termination of the fixation spot and the stimulation and when an array is presented. However, under these conditions, the distribution of saccadic latencies is unimodal. When two visual targets are presented after the fixation spot, introducing a gap has no effect on which target is chosen. By contrast, when electrical stimulation is paired with a visual target, introducing a gap greatly increases the frequency with which the electrical stimulation site is chosen.

How the parallel channels of the retina contribute to depth processing.

Reconstructing the third dimension in the visual scene from the two dimensional images that impinge on the retinal surface is one of the major tasks of the visual system. We have devised a visual display that makes it possible to study stereoscopic depth cues and motion parallax cues separately or in concert using rhesus macaques. By varying the spatial frequency of the display and its luminance and chrominance, it is possible to selectively activate channels that originate in the primate retina. Our results show that (i) the parasol system plays a central role in processing motion parallax cues; (ii) the midget system plays a central role in stereoscopic depth perception at high spatial frequencies, and (iii) red/green colour selective neurons can effectively process both cues but blue/yellow neurons cannot do so.

Depth from shading and disparity in humans and monkeys.

A stimulus display was devised that enabled us to examine how effectively monkeys and humans can process shading and disparity cues for depth perception. The display allowed us to present these cues separately, in concert and in conflict with each other. An oddities discrimination task was used. Humans as well as monkeys were able to utilize both shading and disparity cues but shading cues were more effectively processed by humans. Humans and monkeys performed better and faster when the two cues were presented conjointly rather than singly. Performance was significantly degraded when the two cues were presented in conflict with each other suggesting that these cues are processed interactively at higher levels in the visual system. The fact that monkeys can effectively utilize depth information derived from shading and disparity indicates that they are a good animal model for the study of the neural mechanisms that underlie the processing of these two depth cues.

What delay fields tell us about striate cortex.

It is well known that electrical activation of striate cortex (area V1) can disrupt visual behavior. Based on this knowledge, we discovered that electrical microstimulation of V1 in macaque monkeys delays saccadic eye movements when made to visual targets located in the receptive field of the stimulated neurons. This review discusses the following issues. First, the parameters that affect the delay of saccades by microstimulation of V1 are reviewed. Second, the excitability properties of the V1 elements mediating the delay are discussed. Third, the properties that determine the size and shape of the region of visual space affected by stimulation of V1 are described. This region is called a delay field. Fourth, whether the delay effect is mainly due to a disruption of the visual signal transmitted through V1 or whether it is a disturbance of the motor signal transmitted between V1 and the brain stem saccade generator is investigated. Fifth, the properties of delay fields are used to estimate the number of elements activated directly by electrical microstimulation of macaque V1. Sixth, these properties are used to make inferences about the characteristics of visual percepts induced by such stimulation. Seventh, the disruptive effects of V1 stimulation in monkeys and humans are compared. Eighth, a cortical mechanism to account for the disruptive effects of V1 stimulation is proposed. Finally, these effects are related to normal vision.

Delaying forelimb responses by microstimulation of macaque V1.

Electrical microstimulation of macaque V1 has previously been shown to delay saccadic eye movements made to a punctate visual target placed in the receptive field of the stimulated neurons. It remains unclear whether this delay effect is specific to the oculomotor system or whether the effect can be demonstrated in the skeletomotor system as well. To address this question, a rhesus monkey was trained to depress a left or right lever with its respective hand in response to a visual target presented in the left or right hemifield. On 50% of trials, a 100 ms train of stimulation consisting of 100 microA, 0.2-ms anode-first pulses was delivered to the neurons before the onset of the visual target. Stimulation of V1 delayed the execution of the lever response when the visual target was positioned within the receptive field of the stimulated neurons. We suggest that the delay effect induced by microstimulation of V1 is largely due to a disruption of the visual signal as it is transmitted along the geniculostriate pathway.

Phosphene induction by microstimulation of macaque V1.

Non-human primates are being used to develop a cortical visual prosthesis for the blind. We use the properties of electrical microstimulation of striate cortex (area V1) of macaque monkeys to make inferences about phosphene induction. Our analysis is based on well-established properties of V1: retino-cortical magnification factor, receptive-field size, and the characteristics of hypercolumns. We argue that phosphene size is dependent on the amount of current delivered to V1 and on the retino-cortical magnification factor. We suggest that to improve the correspondence between the site of stimulation within V1 and the visual field location of an elicited phosphene both eyes must be put under experimental control given that phosphene location is retinocentric and given that the vergence angle between the eyes might affect the position of a phosphene in depth. Knowing how electrical microstimulation interacts with cortical tissue to evoke percepts in behaving macaque monkeys is fundamental to the establishment of an effective cortical visual prosthesis for the blind.

Microstimulation of V1 delays visually guided saccades: a parametric evaluation of delay fields.

Electrical microstimulation of macaque striate cortex (area V1) delays the execution of saccadic eye movements made to a visual target placed in the receptive field of the stimulated neurons. The region of visual space within which saccades are delayed is called a delay field. We examined the effects of changing the parameters of stimulation and target size on the size of a delay field. Rhesus monkeys were required to generate a saccadic eye movement to a punctate and white visual target presented within or outside the receptive field of the neurons under study. On 50% of trials, a train of stimulation consisting of 0.2-ms anode-first pulses was delivered to the neurons before the onset of the visual target. Stimulations were performed in the operculum at 0.9-2.0 mm below the cortical surface. It was found that increases in current (50-100 microA), pulse frequency (100-300 Hz), or train duration (75-300 ms) increased the size of a delay field and increases in target size (0.1 degrees -0.2 degrees of visual angle) decreased the size of a delay field. Delay fields varied in size between 0.1 and 0.6 degrees of visual angle. These results are related to the properties of phosphenes induced by electrical stimulation of V1 in humans and compared to the interference effects observed following transcranial magnetic stimulation of human V1.

Delaying visually guided saccades by microstimulation of macaque V1: spatial properties of delay fields.

Electrical microstimulation of macaque primary visual cortex (area V1) is known to delay the execution of saccadic eye movements made to a punctate visual target placed into the receptive field of the stimulated neurons. We examined the spatial extent of this delay effect, which we call a delay field, by placing a 0.2 degrees visual target at various locations relative to the receptive field of the stimulated neurons and by stimulating different sites within the operculum of V1. A 100-ms train of stimulation consisting of current pulses at or less than 100 microA was delivered immediately before monkeys generated a saccadic eye movement to the visual target. The region of tissue activated was within 0.5 mm from the electrode tip. The depth of stimulation for a given site ranged from 0.9 to 2.0 mm below the cortical surface. The location of the receptive fields of the stimulated neurons ranged from 1.8 to 4.4 degrees of eccentricity from the center of gaze. Within this range, the size of the delay field increased from 0.1 to 0.55 degrees of visual angle. The shape of the field was roughly circular. The size of the delay field increased as the stimulation site was located further from the foveal representation of V1. These results are consistent with the finding that phosphenes evoked by electrical stimulation of human V1 are circular and increase in size as the stimulating electrode is placed more distant from the foveal representation of V1.

Microstimulation of V1 affects the detection of visual targets: manipulation of target contrast.

Electrical microstimulation of the striate cortex (area V1) in monkeys delays the execution of saccadic eye movements generated to a visual target located in the receptive field of the stimulated neurons. We have argued that this effect is because of disruption of the visual signal transmitted along the geniculostriate pathway. The delivery of electrical stimulation to V1 evokes a punctate light or dark phosphene in human subjects. If electrical stimulation of V1 in monkeys evokes a light or dark phosphene, then one might expect that the delay effect might vary according to whether monkeys are required to detect a light or a dark visual target. For instance, if the stimulation is activating V1 elements coding for a light visual stimulus but not a dark visual stimulus then stimulation may delay saccades generated to a light target but not to a dark target. We tested this idea by having monkeys generate saccadic eye movements to light or dark visual targets immediately after the stimulation was delivered to V1. We found that the delay effect induced by stimulation varied with target contrast, but remained invariant to whether a bright or dark visual target was presented in the receptive field of the stimulated neurons. The significance of these results is discussed with regard to using monkeys to develop a visual prosthesis for the blind.

Are express saccades generated under natural viewing conditions?

To assess whether express saccades are generated under everyday conditions, we collected eye movement data from Rhesus monkeys engaged in free viewing under a variety of conditions. The durations of the fixation periods that occurred between saccades were calculated. The results show that while short-duration fixations within the range of express saccades occur quite commonly, the overall distribution is unimodal. This is the case even when all the object elements in the visual scene have the same contrast. The findings suggest that while saccades that fall within the express range occur commonly under natural viewing conditions, bimodal distributions of saccadic latencies are obtainable only under laboratory conditions.

Microstimulation of V1 input layers disrupts the selection and detection of visual targets by monkeys.

Electrical microstimulation delivered to primary visual cortex (V1) concurrently with the presentation of visual targets interferes with the selection of these targets. To determine the source of this interference, we stimulated the visual input layers of V1 as rhesus monkeys generated saccadic eye movements to visual targets presented at and outside the receptive field of the stimulated neurons. Columns of cells in V1 innervated by the left and right eye are segregated according to eye dominance, such that cells within a column respond best to visual stimuli presented to the ocular dominant eye. Interference was maximal when targets were presented to the ocular dominant eye, moderate when presented to the ocular inferior eye, and negligible when presented to both eyes. Thus, electrical microstimulation of the visual input layers of V1 disrupts the flow of visual information along the geniculostriate pathway. Knowing how electrical stimulation of V1 affects visual behaviour is necessary when using monkeys to develop a visual prosthesis for the blind.

Microstimulation of V1 delays the execution of visually guided saccades.

Electrical stimulation delivered to V1 concurrently with the presentation of a visual target interferes with both the selection and the detection of targets positioned in the receptive field of the stimulated neurons. In the present study, we examined the temporal course of this effect by delivering electrical stimulation to V1 of rhesus monkeys at various times before the appearance of a visual target. Each trial was initiated by the appearance of a fixation spot that, once acquired, was followed by the presentation of a visual target in the receptive field of the stimulated neurons. A monkey was reward after making a saccadic eye movement to the target. A delay in saccade generation was obtained when stimulation was delivered while an animal maintained fixation on the fixation spot. No delay occurred when the visual target was placed outside the receptive field of the stimulated neurons. The best parameters for inducing the saccadic delay were: (i). anode-first pulses (as opposed to cathode-first pulses) and (ii). train durations greater than 40 ms and frequencies greater than 100 Hz. The lowest current threshold for producing a saccadic delay occurred at 1.5 mm below the top of superficial V1. The chronaxies of the directly stimulated elements mediating the delay ranged from 0.13 to 0.24 ms. These values overlap with those that have been described for phosphene induction in human V1. We discuss how the elements mediating the saccadic delay might interrupt a visual signal as it passes along the geniculostriate pathway.

Behavioural state affects saccades elicited electrically from neocortex.

Reviewed is how behavioural context influences saccadic eye movements elicited electrically from the neocortex of monkeys. Factors found to affect stimulation-evoked saccades include (1) motor state, i.e. whether stimulation is delivered during free-viewing, or during or after active fixation, or before an animal is about to execute a saccade to a target location, and (2) reward delivery, i.e. the characteristics and timing of reward, which can promote or inhibit the evocation of saccades. We conclude that anyone using electrical stimulation in neocortex to study sensory and cognitive processes must control for the possibility that stimulation of cortex is merely generating a saccade vector whose expression is being obscured by the behavioural paradigm in use. Areas of neocortex from which saccades can be evoked using low currents (<100 microA) are surprisingly widespread and include regions traditionally considered within the sensory domain (e.g. V1, V2, V4, and MT), in addition to visuomotor regions such as the lateral intraparietal area, the dorsomedial frontal cortex, the frontal eye fields, and the prefrontal cortex. This is especially true once the behavioural state of a stimulated animal is put under experimental control.