Biomedical subjects

Edward J Tehovnik

Publications and source records attributed to Edward J Tehovnik.

15 recordsLinked to original sources

PubMed2006

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.

Animals↗

PubMed2006

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.

Analysis of Variance↗

PubMed2005

Mapping cortical activity elicited with electrical microstimulation using FMRI in the macaque.

Over the last two centuries, electrical microstimulation has been used to demonstrate causal links between neural activity and specific behaviors and cognitive functions. However, to establish these links it is imperative to characterize the cortical activity patterns that are elicited by stimulation locally around the electrode and in other functionally connected areas. We have developed a technique to record brain activity using the blood oxygen level dependent (BOLD) signal while applying electrical microstimulation to the primate brain. We find that the spread of activity around the electrode tip in macaque area V1 was larger than expected from calculations based on passive spread of current and therefore may reflect functional spread by way of horizontal connections. Consistent with this functional transynaptic spread we also obtained activation in expected projection sites in extrastriate visual areas, demonstrating the utility of our technique in uncovering in vivo functional connectivity maps.

Action Potentials↗

PubMed2005

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.

Animals↗

PubMed2005

Neural mechanisms underlying target selection with saccadic eye movements.

In exploring the visual scene we make about three saccadic eye movements per second. During each fixation, in addition to analyzing the object at which we are looking, a decision has to be made as to where to look next. Although we perform this task with the greatest of ease, the computations to perform the task are complex and involve numerous brain structures. We have applied several investigative tools that include single-cell recordings, microstimulation, pharmacological manipulations and lesions to learn more about the neural control of visually guided eye saccadic movements. Electrical stimulation of the superior colliculus (SC), areas V1 and V2, the lateral intraparietal sulcus (LIP), the frontal eye fields (FEF) and the medial eye fields (MEF) produces saccadic eye movements at low current levels. After ablation of the SC, electrical microstimulation of V1, V2, and LIP no longer elicits saccadic eye movements whereas stimulation of the FEF and MEF continues to be effective. Ablation of the SC but not of the FEF eliminates short-latency saccadic eye movements to visual targets called "express saccades," whereas lesions of the FEF selectively interfere with target selection. Bilateral removal of both the SC and the FEF causes major, long lasting deficits: all visually elicited saccadic eye movements are eliminated. In intact monkeys, subthreshold electrical microstimulation of the FEF and MEF as well as the lower layers of V1 and V2 and of some subregions of LIP greatly facilitates the choice of targets presented in the receptive fields of the stimulated neurons. By contrast, stimulation of the upper layers of V1 and V2 and other sub-regions of LIP produces a dramatic interference in target selection. Examination of the role of inhibitory circuits in eye-movement generation reveals that local infusion of muscimol, a GABA (gamma-aminobutyric acid) agonist, or bicuculline, a GABA antagonist, interferes with target selection in V1. On the other hand, infusion of bicuculline into the FEF produces facilitation in target choice and irrepressible saccades. It appears therefore that inhibitory circuits play a central role in visual analysis in V1 and in the generation of saccadic eye movements in the FEF. It is proposed that two major streams can be discerned in visually guided eye-movement control, the posterior from occipital and parietal cortex that reaches the brainstem via the SC and the anterior from the FEF and MEF that has direct access to the brainstem oculomotor centers.

Animals↗

PubMed2005

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.

Animals↗

PubMed2004

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.

Animals↗

PubMed2004

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.

Animals↗

PubMed2004

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.

Action Potentials↗

PubMed2003

Using ocular dominance to infer the depth of the visual input layers of V1 in behaving macaque monkey.

The goal of this study was to use the ocular dominance properties of multiple unit activity in area V1 of the visual cortex of the behaving rhesus monkey to infer the depth of the visual input layers. Multiple unit activity was examined with a recording electrode at different depths (in 100 micrometer increments) within V1 for responses to a visual stimulus presented to the dominant and non-dominant eye. The cortical depth at which there was a maximal difference in unit firing rate between the dominant and non-dominant eye was used to infer the depth of the visual input layers of V1. This depth was found to vary from 0.8 to 1.2 mm below the cortical surface. This range of depths overlaps with the approximate location of lamina IVc, which is the major recipient of visual fibres from the lateral geniculate nucleus.

Animals↗

PubMed2003

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 microA) 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.

Animals↗

PubMed2003

Behavioural state affects saccadic eye movements evoked by microstimulation of striate cortex.

We examine how behavioural conditions affect the manner in which electrical stimulation of striate cortex (V1) influences the generation of saccadic eye movements. Monkeys were trained (i) to acquire a fixation spot and remain fixated for juice reward and (ii) to acquire a fixation spot and generate a saccade to a visual target for reward. Electrical stimulation was delivered at various times during the execution of these tasks. For stimulation trials, pulses were delivered at 200 Hz using a 100- or 200-ms train duration. Currents as high as 1500 micro A were not sufficient to evoke saccades from V1 when monkeys were actively fixating a visual target, whereas current < 100 micro A was sufficient to evoke saccades when monkeys were not actively fixating. By interleaving trials in which a visual target was presented in the receptive field of stimulated neurons with nontarget stimulation trials, saccades could be evoked from V1 during the nontarget stimulation trials with currents as low as 2 micro A. The position of the visual target on the interleaved trials affected the probability of saccade evocation on the nontarget stimulation trials. Additional factors that affected the evoked saccades were time of reward delivery, ratio of stimulation to nonstimulation trials, and whether stimulation was delivered on the interleaved trials in which a target was positioned in the receptive field of the stimulated neurons. We argue that the behavioural state of an animal acts on the nigra-collicular pathway to lower the current threshold for the elicitation of saccades from V1.

Animals↗

PubMed2003

Cortical inhibitory circuits in eye-movement generation.

The role inhibitory circuits play in target selection with saccadic eye movements was examined in area V1, the frontal eye fields (FEF) and the lateral intraparietal sulcus (LIP) of the Rhesus Macaque monkey by making local infusions of the GABA agonist muscimol and antagonist bicuculline. In V1, both agents greatly interfered with target selection and visual discrimination of stimuli placed into the receptive field of the affected neurons. In the FEF, bicuculline facilitated target selection without affecting visual discrimination and generated many spontaneous saccades. Muscimol in the FEF interfered with saccadic eye-movement generation. In the LIP, bicuculline was ineffective and muscimol had only a small effect. These findings suggest that in the FEF GABAergic inhibitory circuits play a central role in eye-movement generation whereas in V1 these circuits are essential for visual analysis. Inhibitory circuits in the LIP do not appear to play a central role in target selection and in visual discrimination.

Anesthetics, Local↗

PubMed2002

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

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.

Animals↗

PubMed2002

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 (> or = 30 micro A) in the superficial layers and lowest (< or = 10 micro A) 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.

Animals↗