Neuronal correlates of amblyopia in the visual cortex of macaque monkeys with experimental strabismus and anisometropia.

Amblyopia is a developmental disorder of pattern vision. After surgical creation of esotropic strabismus in the first weeks of life or after wearing -10 diopter contact lenses in one eye to simulate anisometropia during the first months of life, macaques often develop amblyopia. We studied the response properties of visual cortex neurons in six amblyopic macaques; three monkeys were anisometropic, and three were strabismic. In all monkeys, cortical binocularity was reduced. In anisometropes, the amblyopic eye influenced a relatively small proportion of cortical neurons; in strabismics, the influence of the two eyes was more nearly equal. The severity of amblyopia was related to the relative strength of the input of the amblyopic eye to the cortex only for the more seriously affected amblyopes. Measurements of the spatial frequency tuning and contrast sensitivity of cortical neurons showed few differences between the eyes for the three less severe amblyopes (two strabismic and one anisometropic). In the three more severely affected animals (one strabismic and two anisometropic), the optimal spatial frequency and spatial resolution of cortical neurons driven by the amblyopic eye were substantially and significantly lower than for neurons driven by the nonamblyopic eye. There were no reliable differences in neuronal contrast sensitivity between the eyes. A sample of neurons recorded from cortex representing the peripheral visual field showed no interocular differences, suggesting that the effects of amblyopia were more pronounced in portions of the cortex subserving foveal vision. Qualitatively, abnormalities in both the eye dominance and spatial properties of visual cortex neurons were related on a case-by-case basis to the depth of amblyopia. Quantitative analysis suggests, however, that these abnormalities alone do not explain the full range of visual deficits in amblyopia. Studies of extrastriate cortical areas may uncover further abnormalities that explain these deficits.

Functional organization of owl monkey lateral geniculate nucleus and visual cortex.

The nocturnal, New World owl monkey (Aotus trivirgatus) has a rod-dominated retina containing only a single cone type, supporting only the most rudimentary color vision. However, it does have well-developed magnocellular (M) and parvocellular (P) retinostriate pathways and striate cortical architecture [as defined by the pattern of staining for the activity-dependent marker cytochrome oxidase (CO)] similar to that seen in diurnal primates. We recorded from single neurons in anesthetized, paralyzed owl monkeys using drifting, luminance-modulated sinusoidal gratings, comparing receptive field properties of M and P neurons in the lateral geniculate nucleus and in V1 neurons assigned to CO "blob," "edge," and "interblob" regions and across layers. Tested with achromatic stimuli, the receptive field properties of M and P neurons resembled those reported for other primates. The contrast sensitivity of P cells in the owl monkey was similar to that of P cells in the macaque, but the contrast sensitivities of M cells in the owl monkey were markedly lower than those in the macaque. We found no differences in eye dominance, orientation, or spatial frequency tuning, temporal frequency tuning, or contrast response for V1 neurons assigned to different CO compartments; we did find fewer direction-selective cells in blobs than in other compartments. We noticed laminar differences in some receptive field properties. Cells in the supragranular layers preferred higher spatial and lower temporal frequencies and had lower contrast sensitivity than did cells in the granular and infragranular layers. Our data suggest that the receptive field properties across functional compartments in V1 are quite homogeneous, inconsistent with the notion that CO blobs anatomically segregate signals from different functional "streams."

The influence of fixational eye movements on the response of neurons in area MT of the macaque.

We analyzed the relationship between eye movements and neuronal responses recorded from area MT in alert monkeys trained to maintain visual fixation during the presentation of moving patterns. The monkeys made small saccades which moved the eyes with velocities that spanned the sensitivity range of MT neurons. The saccades evoked changes in the neuronal response that depended upon (1) the level of stimulus-evoked activity amidst which the saccade occurred and (2) the direction of the saccade relative to the preferred direction of the neuron. Most notably, saccades were able to suppress stimulus-evoked activity when they caused retinal image flow that opposed the neuron's preference and were able to elicit a response or enhance weak activity when they caused flow in the neuron's preferred direction. On average, the disturbance lasted 40 ms beginning about 40 ms following saccade onset. Using these parameters, we simulated synthetic spike trains from an imaginary pair of similarly tuned neurons and determined that the interneuronal correlation due to saccades should be negligible at all but the lowest ongoing firing rates. This conclusion was supported from our data by the observation that response variance for single MT spike trains was not measurably reduced during periods of stable gaze compared to periods when eye movement exceeded a stability criterion (0.1 deg during 0.5 s). While the intrusions caused by saccades are too short-lived and infrequent to account for the variability of MT neuronal response (counter to the finding in V1 of Gur et al., 1997), the clear directional signal that they carry in area MT suggests that motion perception is not blocked during saccades by suppression at early stages in the visual pathway.

Processing of first- and second-order motion signals by neurons in area MT of the macaque monkey.

Extrastriate cortical area MT is thought to process behaviorally important visual motion signals. Psychophysical studies suggest that visual motion signals may be analyzed by multiple mechanisms, a "first-order" one based on luminance, and a "second-order" one based upon higher level cues (e.g. contrast, flicker). Second-order motion is visible to human observers, but should be invisible to first-order motion sensors. To learn if area MT is involved in the analysis of second-order motion, we measured responses to first- and second-order gratings of single neurons in area MT (and in one experiment, in area V1) in anesthetized, paralyzed macaque monkeys. For each neuron, we measured directional and spatio-temporal tuning with conventional first-order gratings and with second-order gratings created by spatial modulation of the flicker rate of a random texture. A minority of MT and V1 neurons exhibited significant selectivity for direction or orientation of second-order gratings. In nearly all cells, response to second-order motion was weaker than response to first-order motion. MT cells with significant selectivity for second-order motion tended to be more responsive and more sensitive to luminance contrast, but were in other respects similar to the remaining MT neurons; they did not appear to represent a distinct subpopulation. For those cells selective for second-order motion, we found a correlation between the preferred directions of first- and second-order motion, and weak correlations in preferred spatial frequency. These cells preferred lower temporal frequencies for second-order motion than for first-order motion. A small proportion of MT cells seemed to remain selective and responsive for second-order motion. None of our small sample of V1 cells did. Cells in this small population, but not others, may perform "form-cue invariant" motion processing (Albright, 1992).

Adaptation to contingencies in macaque primary visual cortex.

We tested the hypothesis that neurons in the primary visual cortex (V1) adapt selectively to contingencies in the attributes of visual stimuli. We recorded from single neurons in macaque V1 and measured the effects of adaptation either to the sum of two gratings (compound stimulus) or to the individual gratings. According to our hypothesis, there would be a component of adaptation that is specific to the compound stimulus. In a first series of experiments, the two gratings differed in orientation. One grating had optimal orientation and the other was orthogonal to it, and therefore did not activate the neuron under study. These experiments provided evidence in favour of our hypothesis. In most cells adaptation to the compound stimulus reduced responses to the compound stimulus more than it reduced responses to the optimal grating, and the responses to the compound stimulus were reduced more by adaptation to the compound stimulus than by adaptation to the individual gratings. This suggests that a component of adaptation was specific to (and caused by) the simultaneous presence of the two orientations in the compound stimulus. To test whether V1 neurons could adapt to other contingencies in the stimulus attributes, we performed a second series of experiments, in which the component gratings were parallel but differed in spatial frequency, and were both effective in activating the neuron under study. These experiments failed to reveal convincing contingent effects of adaptation, suggesting that neurons cannot adapt equally well to all types of contingency.

Effects of early-onset artificial strabismus on pursuit eye movements and on neuronal responses in area MT of macaque monkeys.

In humans, esotropia of early onset is associated with a profound asymmetry in smooth pursuit eye movements. When viewing is monocular, targets are tracked well only when they are moving nasally with respect to the viewing eye. To determine whether this pursuit abnormality reflects an anomaly in cortical visual motion processing, we recorded eye movements and cortical neural responses in nonamblyopic monkeys made strabismic by surgery at the age of 10-60 d. Eye movement recordings revealed the same asymmetry in the monkeys' pursuit eye movements as in humans with early-onset esotropia. With monocular viewing, pursuit was much stronger for nasalward motion than for temporalward motion, especially for targets presented in the nasal visual field. However, for targets presented during ongoing pursuit, temporalward and nasalward image motion was equally effective in modulating eye movement. Single-unit recordings made from the same monkeys, under anesthesia, revealed that MT neurons were rarely driven binocularly, but otherwise had normal response properties. Most were directionally selective, and their direction preferences were uniformly distributed. Our neurophysiological and oculomotor measurements both suggest that the pursuit defect in these monkeys is not due to altered cortical visual motion processing. Rather, the asymmetry in pursuit may be a consequence of imbalances in the two eyes' inputs to the "downstream" areas responsible for the initiation of pursuit.

Binocular immobilization induced by paralysis of the extraocular muscles of one eye: evidence for an interocular proprioceptive mechanism.

1. Spontaneous changes in the positions of both eyes were measured in anesthetized cats before and after infusion of paralytic or anesthetic agents directly into the extraocular muscle capsule behind one eye. 2. Before retrobulbar injection, large changes in eye position were observed in both eyes. The position changes of each eye were independent of each other and often in opposite directions. 3. Application of a paralytic agent into the orbit of one eye reduced the spontaneous position changes in that eye to a very low level. Unexpectedly, the changes in the position of the other, untreated eye were also greatly reduced. 4. Control experiments demonstrated that the binocular immobilization observed after monocular paralysis was not due to 1) leakage of the paralytic agent from the orbit of the treated eye to the orbit of the untreated eye or 2) systemic vascular transport of the paralytic agent. 5. Passive movement of the paralyzed eye did not induce movement of the untreated eye. 6. Application of a local anesthetic agent rather than a paralytic agent to one eye resulted in reversible reduction of movement only in the treated eye, but not in the untreated eye. 7. The results suggest that the reduction of movement in one eye produced by application of a paralytic agent to the other eye is mediated by an afferent neural signal derived from extraocular muscle proprioceptors possibly gated by a central motor control signal.

An improved retinal densitometer: design concepts and experimental applications.

A photon-counting retinal densitometer is described that has been designed optically and electronically for improved sensitivity and reliability. The device allows measurement of visual pigments through the undilated natural pupils of subjects at relatively low levels of measuring lights, and serves also as an adaptometer for direct comparisons between pigment bleaching or regeneration and light or dark adaptation. Instrumental control and data collection are by computer to permit rapid and simple data analysis and comparisons between subjects. The methods by which the sensitivity and reliability have been enhanced are described in detail, and some examples of experimental results are presented.

Schematic eyes for domestic animals.

Schematic and reduced eyes for the horse, cow, sheep, pig, cat, and dog were calculated from optical parameter values obtained from the literature. Calculations were performed with the aid of a computer program using standard Gaussian equations and a homogeneous lens model. Calculated schematic eyes had refractive states within 1.5 D of emmetropia; retinal image sizes ranged from 0.22 (cat and dog) to 0.44 (horse) mm/deg. The cat eye presented here is more nearly emmetropic than a previously published cat schematic eye. The effects of altering refractive indices, radii of curvature, and thicknesses of refractive components upon refractive state and retinal image size are examined. The largest differences resulted from changes made to refractive indices of the lens and vitreous and to the vitreous depth.

A BASIC computer program for schematic and reduced eye construction.

A simple computer program for calculating schematic and reduced eyes is presented. The user supplies distances from the front of the eye and radii of curvature of refractive surfaces (anterior and posterior cornea and lens), distance to retina, and refractive indices of ocular media (cornea, aqueous, lens, vitreous). These values are input to calculate the necessary parameters for construction of a schematic and reduced eye, using Gaussian formulae and assuming a homogenous lens. The program produces powers of optical components and of the whole eye, cardinal points of the eye, and estimates of refractive state and retinal image size. These values may be printed in tabular form or plotted to scale with a graphics plotter. The program simplifies construction of schematic eyes by allowing rapid recalculation of the eye after changing one or more input parameters.

Diurnal changes in human psychophysical luminance sensitivity.

Psychophysical luminance thresholds were taken from dark-adaptation curves representing two-hour intervals around the clock to identify diurnal changes in photopic and scotopic luminance sensitivity. Dark adaptation curves were obtained by tracking thresholds for a 2 deg achromatic stimulus located 10 deg temporal to the fovea of the left eye following a one min bleach. Test sessions were randomly distributed and each of the three subjects was tested twice at each time over a two-week period. The results showed small changes in both photopic and scotopic threshold over time of day. The amplitude of photopic threshold changes was small (0.1 log unit) and the time of peak sensitivity varied among individuals. Scotopic thresholds were highest at about 0230 hr, and the amplitude of threshold changes was larger (0.12-0.24 log unit). Oral temperatures measured at the time of threshold testing showed a moderate inverse correlation with thresholds; when temperature was low, thresholds were high. The threshold changes were not related to known rhythms in retinal physiology, but may be related to perceptual variables.