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E L Smith

Publications and source records attributed to E L Smith.

At least 55 records · Page 3Linked to original sources

Nasotemporal directional bias of V1 neurons in young infant monkeys.

PURPOSE: Optokinetic nystagmus (OKN) in young infants typically shows a temporal-to-nasal asymmetry under monocular viewing conditions. The neural basis for this asymmetry has been a matter of debate. One idea is that the OKN asymmetry reflects a similar asymmetry in the directional sensitivity of primary visual cortical (V1) neurons. An alternative hypothesis is that the OKN asymmetry is due to an immaturity in the ability of cortical neurons to influence the activity of subcortical structures that directly control OKN. We addressed this issue by studying the directional sensitivity of V1 neurons in young infant monkeys. METHODS: The neuronal activity of V1 units was recorded from anesthetized and paralyzed rhesus monkeys ranging in age from 6 days to 8 weeks using standard extracellular single-unit recording methods. For comparison, V1 units from normal adult monkeys were also studied. Using drifting sinusoidal gratings of the optimal spatial frequency and a moderate contrast, we measured the responsiveness of individual units to 24 directions of stimulus movement. The preferred stimulus direction and the magnitude of the directional response bias were determined by a vector summation method. RESULTS: No clear signs of nasotemporal asymmetries in direction tuning were found in our cell population from infant monkeys. However, the overall directional sensitivity and the peak monocular response amplitudes of these units were significantly lower, and binocular suppression was greater during the first 4 weeks of life than in adults. CONCLUSIONS: The OKN asymmetry in young infants may be more closely associated with the lower overall directional sensitivity and the subnormal responsiveness of V1 neurons rather than with an obvious asymmetry in the directional properties of V1 neurons.

Action Potentials↗

Postnatal development of binocular disparity sensitivity in neurons of the primate visual cortex.

In macaque monkeys, the age at which neurons in the primary visual cortex (V1) become sensitive to interocular image disparities, a prerequisite for stereopsis, is a matter of conjecture. To resolve this fundamental issue in binocular vision development, we measured the responsiveness of individual V1 neurons in anesthetized and paralyzed infant monkeys as a function of the relative, interocular, spatial phase of dichoptic sine-wave gratings. We found that an adult-like proportion of units were sensitive to interocular image disparity as early as the sixth postnatal day, several weeks before the onset age for stereopsis in monkeys. The ocular dominance distributions of cells in infant monkeys were also indistinguishable from those of adults. Thus, at or only a few days after birth, V1 neurons are capable of combining neural signals from the two eyes as in adults and are sensitive to interocular image disparities. However, the monocular spatial-frequency response properties of these disparity-sensitive units were immature, and their overall responsiveness was far lower than that in adults. During the first 4 postnatal weeks, both the spatial frequency response properties and the peak response amplitude rapidly improved, which resulted in a corresponding increase in the absolute sensitivity of individual units to interocular disparity. The results demonstrate that early binocular vision development in monkeys is not constrained by a paucity of disparity-sensitive V1 neurons but, instead, by the relative immaturity of the spatial response properties and the overall unresponsiveness of existing disparity-sensitive neurons.

Animals↗

Stereopsis and disparity vergence in monkeys with subnormal binocular vision.

The surgical treatment for strabismus in infants generally results in microtropia or subnormal binocular vision. Although the clinical characteristics of these conditions are well established, there are important questions about the mechanisms of binocular vision in these patients that can best be investigated in an appropriate animal model. In the present psychophysical investigations, spatial frequency response functions for disparity-induced fusional vergence and for local stereopsis were studied in macaque monkeys, who demonstrated many of the major visual characteristics of patients whose eyes were surgically aligned during infancy. In six rhesus monkeys, unilateral esotropia was surgically induced at various ages (30-184 days of age). However, over the next 12 months, all of the monkeys recovered normal eye alignment. Behavioral measurements at 4-6 years of age showed that the monkeys' prism-induced fusional vergence responses were indistinguishable from those of control monkeys or humans with normal binocular vision. Investigations of stereo-depth discrimination demonstrated that each of the experimental monkeys also had stereoscopic vision, but their stereoacuities varied from being essentially normal to severely stereo-deficient. The degree of stereo-deficiency was not related to the age at which surgical esotropia was induced, or to the presence or absence of amblyopia, and was not dependent on the spatial frequency of the test stimulus. Altogether, these experiments demonstrate that a temporary, early esotropia can affect the binocular disparity responses of motor and sensory components of binocular vision differently, probably because of different sensitive periods of development for the two components.

Amblyopia↗

Binocular spatial phase tuning characteristics of neurons in the macaque striate cortex.

We employed microelectrode recording techniques to study the sensitivity of individual neurons in the striate cortex of anesthetized and paralyzed monkeys to relative interocular image disparities and to determine the effects of basic stimulus parameters on these cortical binocular interactions. The visual stimuli were drifting sine wave gratings. After the optimal stimulus orientation, spatial frequency, and direction of stimulus movement were found, the cells' disparity tuning characteristics were determined by measuring responses as a function of the relative interocular spatial phase of dichoptic grating pairs. No attempts were made to assess absolute position disparities or horizontal disparities relative to the horopter. The majority (approximately 70%) of simple cells were highly sensitive to interocular spatial phase disparities, particularly neurons with balanced ocular dominances. Simple cells typically demonstrated binocular facilitation at the optimal phase disparity and binocular suppression for disparities 180 degrees away. Fewer complex cells were phase selective (approximately 40%); however, the range of disparity selectivity in phase-sensitive complex cells was comparable with that for simple cells. Binocular interactions in non-phase-sensitive complex cells were evidenced by binocular response amplitudes that differed from responses to monocular stimulation. The degree of disparity tuning was independent of a cell's optimal orientation or the degree of direction tuning. However, disparity-sensitive cells tended to have narrow orientation tuning functions and the degree of disparity tuning was greatest for the optimal stimulus orientations. Rotating the stimulus for one eye 90 degrees from the optimal orientation usually eliminated binocular interactions. The effects of phase disparities on the binocular response amplitude were also greatest at the optimal spatial frequency. Thus a cell's sensitivity to absolute position disparities reflects its spatial tuning characteristics, with cells sensitive to high spatial frequencies being capable of signaling very small changes in image disparity. On the other hand, stimulus contrast had relatively little effect on a cell's disparity tuning, because response saturation occurred at the same contrast level for all relative interocular phase disparities. Thus, as with orientation tuning, a cell's optimal disparity and the degree of disparity selectivity were invariant with contrast. Overall, the results show that sensitivity to interocular spatial phase disparities is a common property of striate neurons. A cell's disparity tuning characteristics appear to largely reflect its monocular receptive field properties and the interocular balance between excitatory and inhibitory inputs. However, distinct functional classes of cortical neurons could not be discriminated on the basis of disparity sensitivity alone.

Action Potentials↗

Binocular combination of contrast signals by striate cortical neurons in the monkey.

With the use of microelectrode recording techniques, we investigated how the contrast signals from the two eyes are combined in individual cortical neurons in the striate cortex of anesthetized and paralyzed macaque monkeys. For a given neuron, the optimal spatial frequency, orientation, and direction of drift for sine wave grating stimuli were determined for each eye. The cell's disparity tuning characteristics were determined by measuring responses as a function of the relative interocular spatial phase of dichoptic stimuli that consisted of the optimal monocular gratings. Binocular contrast summation was then investigated by measuring contrast response functions for optimal dichoptic grating pairs that had left- to right-eye interocular contrast ratios that varied from 0.1 to 10. The goal was to determine the left- and right-eye contrast components required to produce a criterion threshold response. For all functional classes of cortical neurons and for both cooperative and antagonistic binocular interactions, there was a linear relationship between the left- and right-eye contrast components required to produce a threshold response. Thus, for example for cooperative binocular interactions, a reduction in contrast to one eye was counterbalanced by an equivalent increase in contrast to the other eye. These results showed that in simple cells and phase-specific complex cells, the contrast signals from the two eyes were linearly combined at the subunit level before nonlinear rectification. In non-phase-specific complex cells, the linear binocular convergence of contrast signals could have taken place either before or after the rectification process, but before spike generation. In addition, for simple cells, vector analysis of spatial summation showed that the inputs from the two eyes were also combined in a linear manner before nonlinear spike-generating mechanisms. Thus simple cells showed linear spatial summation not only within and between subregions in a given receptive field, but also between the left- and right-eye receptive fields. Overall, the results show that the effectiveness of a stimulus in producing a response reflects interocular differences in the relative balance of inputs to a given cell, however, the eye of origin of a light-evoked signal has no specific consequence.

Animals↗

Residual binocular interactions in the striate cortex of monkeys reared with abnormal binocular vision.

We investigated the nature of residual binocular interactions in the striate cortex (V1) of monkey models for the two most common causes of visual dysfunction in young children, specifically anisometropia and strabismus. Infant rhesus monkeys were raised wearing either anisometropic spectacle lenses that optically defocused one eye or ophthalmic prisms that optically produced diplopia and binocular confusion. Earlier psychophysical investigations had demonstrated that all subjects exhibited permanent binocular vision deficits and, in some cases, amblyopia. When the monkeys were adults, the responses of individual V1 neurons were studied with the use of microelectrode recording techniques while the animals were anesthetized and paralyzed. The manner in which the signals from the two eyes were combined in individual cells was investigated by dichoptically stimulating both eyes simultaneously with drifting sine wave gratings. In both lens- and prism-reared monkeys, fewer neurons had balanced ocular dominances and greater numbers of neurons were excited by only one eye. However, many neurons that appeared to be monocular exhibited clear binocular interactions during dichoptic stimulation. For the surviving binocular neurons, the maximum binocular response amplitudes were lower than normal; fewer neurons, particularly complex cells, were sensitive to relative interocular spatial phase disparities; and the remaining disparity-sensitive neurons exhibited lower degrees of binocular interaction. In prism-reared monkeys, an unusually high proportion of complex cells exhibited binocular suppression during dichoptic stimulation. Binocular contrast summation experiments showed that for both cooperative and antagonistic binocular interactions, contrast signals from the two eyes were combined by individual neurons in a normal linear fashion in both lens- and prism-reared monkeys. The observed binocular deficits appear to reflect a reduction in functional inputs from one eye and/or spatial imprecision in the monocular receptive fields rather than an aberrant form of binocular interaction. In the prism-reared monkeys, the predominance of suppression suggests that inhibitory connections were, however, less susceptible to diplopia and confusion than excitatory connections. Overall, there were many parallels between V1 physiology in our monkey models and the residual vision of humans with anisometropia or strabismus.

Animals↗

Experimental glaucoma: perimetric field defects and intraocular pressure.

PURPOSE: To investigate the relationship between intraocular pressure (IOP) and the progression of visual field defects caused by experimental glaucoma in Macaca mulatta monkeys. METHODS: Perimetric fields were measured by behavioral methods in 18 rhesus monkeys during the course of unilateral glaucoma produced by argon laser treatment of the trabecular meshwork. The monkeys' IOPs were measured by applanation tonometry. Visual field defects were quantified by the mean deviation perimetric index from Humphrey Field Analyzer C24-2, model 630 (Humphrey Allergan, San Leandro, CA, U.S.A.), full-threshold data. RESULTS: The monkeys' eyes demonstrated considerable variability in their susceptibility to pressure-induced neural damage. For 10 of the monkeys, significant field defects were correlated with the increases in their IOPs and the defects progressed monotonically to end-state glaucoma. For the other monkeys, the mean deviation index was not well correlated with IOP; some eyes withstood pressures in excess of 35 mm Hg for several months before significant reduction in visual sensitivity. However, once they began, the rate of progression of field defects was similar across subjects. CONCLUSIONS: Laser ablation of the trabecular meshwork in monkeys provides a model for investigations of the effects of IOP that are not confounded by other ocular or visual disorders. Behavioral perimetry showed the same intersubject variability in the effects of elevated IOP on visual field sensitivities of monkeys that are common with high-tension glaucoma or ocular hypertension in patients. Thus, these investigations provide additional support for the use of the model for a wide variety of clinical investigations on glaucoma.

Animals↗

Loss of stereopsis in monkeys following prismatic binocular dissociation during infancy.

Prismatic binocular dissociation was used during infancy to mimic conditions of strabismus in macaque infants. Prisms worn continuously produce a diplopia unfavorable for the maintenance and development of the binocular visual system. Prism-reared monkeys were tested as young adults and found to be permanently stereoblind for dynamic random dot stereograms. Control monkeys did comparably to humans on such tests. It is concluded that short periods of diplopia attendant with strabismus are sufficient to produce permanent stereoblindness.

Age of Onset↗

Judgments by monkeys of apparent depth in dynamic random-dot stereograms.

Young macaques discriminated apparent depths of targets embedded in dynamic random dot stereograms; a test of stereopsis. In a 'same/different' paradigm, the discrimination took longer if the pair of stimuli appeared to be in same depth plane, than when they appeared to be located in a different depth plane. The decision time was an inverse function of the disparity difference. Apparent depth discrimination performance decreased as a function of disparity, with no differences in judgments regarding crossed or uncrossed disparities.

Animals↗

Binocularity in prism-reared monkeys.

Prismatic binocular dissociation in infant monkeys mimicked a concomitant squint. Within 3 weeks, the numbers of binocular neurons in the primary visual cortex were reduced by half and did not recover with up to 5 years of subsequent unrestricted binocular visual experience. The monkeys failed to show binocular summation for spatial contrast sensitivity tasks and were unable to utilise horizontal binocular disparities in random-dot stereograms-two indices of stereoblindness. Electrophysiological analysis of the V1 and V2 cortices showed a dramatic reduction in binocular neurons. Analysis of interocular spatial phase tuning functions showed a conspicuous loss of excitatory binocular drive in V1 neurons which was sufficient to account for many of the defects in binocular function.

Animals↗

Motor and sensory fusion in monkeys: psychophysical measurements.

Motor and sensory fusion, the basic processes of binocularity, must be present for bifoveal fixation with true fusion and stereopsis during ordinary viewing. The characteristics of motor and sensory fusion have been established for patients with normal and subnormal binocular vision; the present report describes our psychophysical studies of these processes in the macaque monkey. Three recent investigations of motor and sensory fusion in monkeys are described. The studies involved: (1) the comparability of motor and sensory fusion in monkeys and humans with normal binocular vision, (2) the effects of an early period of abnormal binocular vision on motor and sensory fusion in monkeys, and (3) the contrast sensitivity for binocular disparity in monkeys with stereo-deficiencies. The results of these studies demonstrated an excellent homology between the normal binocular vision of monkeys and humans. We also found that a period of esotropia during infancy caused deficiencies in sensory fusion, but not motor fusion. In some monkeys, the sensory deficiency persisted over the entire range of binocular disparities that were compatible with stereopsis, while other subjects demonstrated normal stereo-sensitivity for the largest fusible binocular disparities. The stereo-deficiencies of these monkeys, along with other visual attributes, suggest that their binocular vision is a viable model for the binocularity of patients with subnormal binocular vision or the monofixation syndrome.

Animals↗

Extended-wear, soft, contact lenses produce hyperopia in young monkeys.

To investigate the effects of experimentally induced defocus on eye growth and refractive development, one eye of four infant rhesus monkeys was fit with either a +3.0 D (N = 2) or -3.0 D (N = 2) extended-wear, soft, contact lens, and the other eye was fit with a zero-powered, control lens. The lens rearing regimen was started between 12 and 22 days of age and continued for 24 to 64 days. Hyperopic shifts in refractive error were found in all eyes, including the eyes treated with plano lenses. In addition to these absolute hyperopic shifts, 1.5 to 3.25 D of axial anisometropia were produced in all four monkeys, with the eyes wearing the powered lenses becoming relatively more hyperopic than the control eyes wearing the plano lenses. The induced hyperopia and anisometropia decreased rapidly after lens removal. The reapplication of the lenses at later ages in two animals produced smaller, but similar, changes. It appears that in very young primates extended-wear, soft, contact lenses can alter eye growth and refractive development through both visual and nonvisual mechanisms.

Aging↗

The scotopic electroretinogram of macaque after retinal ganglion cell loss from experimental glaucoma.

PURPOSE: This study describes the dark-adapted electroretinograms (ERGs) of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension. METHODS: Monocular experimental glaucoma was produced by argon laser trabeculoplasty, and visual fields were assessed with behavioral static perimetry. Electroretinographic responses to brief ganzfeld flashes under fully dark-adapted conditions were recorded using DTL fiber electrodes in anesthetized animals. The authors quantified retinal layer thickness and cell loss in 1-micron radial sections and inspected optic nervous under the light microscope. RESULTS: At the lowest intensities, a sensitive negative component of the scotopic ERG, which normally peaks approximately 200 msec after stimulus onset, was present in the control eyes but was reduced greatly or was virtually absent in the experimental eyes of monkeys with severe visual field loss. A previously unreported sensitive positive component of the scotopic ERG remained in both eyes. In the control eyes, the positive component gave rise to a sharp peak approximately 120 msec after stimulus onset, but in the experimental eyes, because of the absence of the more delayed sensitive negative potential, it was sustained, lasting as long as 700 msec. Scotopic a- and b-waves and oscillatory potentials in the experimental eyes were not consistently different from control eyes. Ganglion cell and optic nerve loss in the experimental eyes was substantial, and there was little other obvious retinal damage. CONCLUSIONS: A sensitive negative component is reduced or absent from the dark-adapted ERGs of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension.

Animals↗

Dose-response relationship between physical loading and mechanical competence of bone.

A dose-response relationship between mechanical loading and bone can be inferred by the fact that bone response is proportional to the applied load in cell and organ culture and in animal models where a known load at a given magnitude and frequency is applied. Proportional responses have been observed in second messengers, growth factors, bone matrix, and bone strength. In the human model, however, the determination of a dose-response relationship is hindered by the lack of appropriate technology to directly evaluate the mechanical load and the skeletal competence. In vitro loading of bone does not duplicate the in vivo physiologic conditions, in particular the neuromuscular responses to the loads applied to the skeleton. While animal studies aid in determining the mechanisms of bone response to mechanical loading and dietary interactions, they do not obviate the need for human clinical trials to evaluate the effects of physical activity on both skeletal competence and fall prevention. The literature reviewed shows that physical activity increases the competence of the skeleton to resist fracture by the maintenance and improvement of bone mineral density (BMD) and neuromuscular competency, thus reducing skeletal fragility, pre-disposition to falls, and fall impact.

Animals↗

Behavioral studies of local stereopsis and disparity vergence in monkeys.

Investigations on macaque monkeys have provided much of our knowledge of the neural mechanisms of binocular vision, but there is little psychophysical data on the accuracy of vergence responses or the precision of stereoscopic depth perception in these primates. We have conducted comparative behavioral studies of binocular disparity processing in rhesus monkeys and humans via measurements of prism-induced fixation disparities (disparity vergence) and relative depth discrimination for spatially localized stimuli (local stereopsis). The results of these studies demonstrated a remarkable similarity in both the oculomotor and the sensory aspects of binocular vision in the two species when the stimulus dimensions were specified in visual angles, which were independent of interocular separation. The disparity vergence functions for the two species revealed fusion responses over the same range of prism-induced vergence and comparable vergence errors for stimuli near their fusional limits. Disparity vergence responses were independent of the spatial frequency of the binocular fusion stimulus. Stereothresholds as a function of the spatial frequency of the difference-of-Gaussian stimuli were of the same form, with equivalent stereoacuities, in monkey and human observers. The presence of substantial vergence errors had only a small effect on the precision of stereoscopic depth perception. We conclude that, after compensation for the differences in the lateral separation of their eyes, the operating characteristics of disparity vergence and stereoscopic vision are virtually identical in rhesus monkeys and humans and, consequently, the performance limits for these visual functions must be determined by anatomical and/or neural constraints that are similar in both species.

Animals↗