Warren M. Slocum

Eye fields in the frontal lobes of primates.

Two eye fields have been identified in the frontal lobes of primates: one is situated dorsomedially within the frontal cortex and will be referred to as the eye field within the dorsomedial frontal cortex (DMFC); the other resides dorsolaterally within the frontal cortex and is commonly referred to as the frontal eye field (FEF). This review documents the similarities and differences between these eye fields. Although the DMFC and FEF are both active during the execution of saccadic and smooth pursuit eye movements, the FEF is more dedicated to these functions. Lesions of DMFC minimally affect the production of most types of saccadic eye movements and have no effect on the execution of smooth pursuit eye movements. In contrast, lesions of the FEF produce deficits in generating saccades to briefly presented targets, in the production of saccades to two or more sequentially presented targets, in the selection of simultaneously presented targets, and in the execution of smooth pursuit eye movements. For the most part, these deficits are prevalent in both monkeys and humans. Single-unit recording experiments have shown that the DMFC contains neurons that mediate both limb and eye movements, whereas the FEF seems to be involved in the execution of eye movements only. Imaging experiments conducted on humans have corroborated these findings. A feature that distinguishes the DMFC from the FEF is that the DMFC contains a somatotopic map with eyes represented rostrally and hindlimbs represented caudally; the FEF has no such topography. Furthermore, experiments have revealed that the DMFC tends to contain a craniotopic (i.e., head-centered) code for the execution of saccadic eye movements, whereas the FEF contains a retinotopic (i.e., eye-centered) code for the elicitation of saccades. Imaging and unit recording data suggest that the DMFC is more involved in the learning of new tasks than is the FEF. Also with continued training on behavioural tasks the responsivity of the DMFC tends to drop. Accordingly, the DMFC is more involved in learning operations whereas the FEF is more specialized for the execution of saccadic and smooth pursuit eye movements.

Saccadic eye movements evoked by microstimulation of striate cortex.

Experiments were performed to assess the excitability of neural elements activated while inducing saccadic eye movements electrically from different cortical layers of striate cortex (area V1) in rhesus monkeys. Excitability was assessed by measuring current thresholds, saccadic latencies, chronaxies, and the effectiveness of anode‐first vs. cathode‐first pulses. Minimum current thresholds for the evocation of saccades (i.e. less than 5 µA) were observed when the deepest layers of V1 were stimulated. The shortest saccadic latencies were also observed at these depths. The shortest latency at 10 times the threshold current was 49 ms on average. The chronaxies of the elements mediating saccades were less in deep V1 (i.e. 0.17 ms) than in superficial V1 (i.e. 0.23 ms). Anode‐first pulses were more effective at evoking saccades from superficial V1, whereas cathode‐first pulses were more effective at evoking saccades from deep V1. These results indicate that the excitability properties of superficial and deep V1 are distinct for the generation of saccades. Moreover, the excitability of elements mediating saccades in V1 of monkeys is comparable to that of elements mediating phosphenes in human V1.

Behavioural conditions affecting saccadic eye movements elicited electrically from the frontal lobes of primates.

We assessed the effects of varying the time at which electrical stimulation was delivered to the dorsomedial frontal cortex (DMFC) and the frontal eye fields (FEF) relative to the onset of a visual target. Monkeys were required to fixate the visual target to obtain a drop of apple juice as reward. We found that the probability of eliciting saccades increased with increases in the delay of electrical stimulation relative to target onset. Also, the current threshold to evoke saccades decreased as electrical stimulation was delivered later following target onset. There were major differences in the magnitude of this effect with stimulation of the DMFC versus the FEF. The current threshold to evoke saccades from the DMFC was 16 times greater when electrical stimulation was delivered 200 ms after target onset as compared to when it was delayed 200 ms after target offset. In contrast, the current threshold to evoke saccades from the FEFs was only three times greater when stimulation was delivered under similar conditions. These results suggest that the FEF are more closely connected with the saccade generator for the execution of saccadic eye movements than is the DMFC, even though both regions have direct projections to brainstem oculomotor centres.

Differential effects of laminar stimulation of V1 cortex on target selection by macaque monkeys

We explored the effects of microstimulation on target selection by delivering stimulation at different depths within V1 (striate cortex) of the rhesus monkey (Macaca mulatta). Stimulation evoked saccadic eye movements that terminated in the receptive‐field location of the activated neurons. The current thresholds for saccade evocation were highest (≥ 30 µA) in the superficial layers and lowest (≤ 10 µA) in the deep layers. To study target selection, one visual target was presented in the receptive‐field location of the stimulated neurons and a second visual target was presented outside this location. Microstimulation delivered in concert with the appearance of the two targets decreased the probability that a monkey would select the target placed in the receptive‐field location when the upper layers of V1 were stimulated, and it increased this probability when the lower layers were stimulated. We suggest that microstimulation of the upper layers of V1 disrupts visual signals from retina en route to higher cortical areas, whereas microstimulation of the lower layers activates V1 efferents that innervate the oculomotor system.

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.

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.

Saccades induced electrically from the dorsomedial frontal cortex: evidence for a head-centered representation

The amplitude and direction of saccadic eye movements evoked electrically from the dorsomedial frontal cortex (DMFC) of monkeys vary with starting eye position. This observation has been used to argue that the DMFC codes saccadic eye movements in head-centered coordinates. Whether the amplitude and direction of the evoked saccades are also affected by changes in head position has never been demonstrated. Such a result would argue against a head-centered representation, and instead would suggest a representation anchored to another body part. Tests were conducted on rhesus monkeys to determine whether changing the position of the head with respect to the trunk or changing the position of the head with respect to the gravitational axis alters saccadic parameters. The amplitude and direction of saccadic eye movements remained invariant to such manipulations. These findings confirm the claim that the DMFC encodes saccadic eye movements in head-centered coordinates.

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 μA 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 μA) 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.

Microstimulation of macaque V1 disrupts target selection: effects of stimulation polarity

Abstract. Microstimulation of the intermediate layers of V1 in rhesus monkeys disrupts target selection with saccadic eye movements. To study target selection, one visual target was presented in the receptive-field location of the stimulated neurons and a second target was presented outside this location. Microstimulation delivered with the appearance of the two targets decreased the probability that the monkey would select the target placed in the receptive-field location when intermediate layers of V1 were stimulated. This interference effect was more pronounced when anodal-first pulse pairs were used as compared to when cathodal-first pulse pairs were used. The superior effectiveness of anodal pulses suggests that the interference effect is due to activation of axonal terminals residing within intermediate V1.

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.