Envisioning a Woman Scientist.

I entered science at a particularly lucky time. By the mid-1960s, women were being encouraged to pursue serious scientific careers. During the 60-year span of my career, women have become equal partners with men in scientific research, particularly in the biological sciences. There also has been abundant funding for research, which allowed me to succeed in a "soft-money" position at Smith-Kettlewell Eye Research Institute, a place that was especially supportive for a woman scientist with children. In this article, I describe the findings that I think represent the most interesting and enduring scientific work from my career.

Attention deficits in Amblyopia.

Amblyopia is a neuro-developmental abnormality associated with deficits in a broad range of both low-level and high-level visual tasks. This is particularly true in strabismic amblyopia where fixation is unstable and there is an increased frequency of microsaccades. In light of the close association between eye movements and attention, we propose a novel hypothesis: that the cost of unstable fixation in amblyopia is a deficit in selective attention. The increased latency for saccades and manual response time with amblyopic-eye viewing is consistent with attention being distracted by unwanted fixational eye movements. We review other attention deficits in amblyopia and discuss whether they are explained by fixation instability, or whether they involve a form of neglect or suppression of the visual input from the amblyopic eye.

Classification and diversity of amblyopia.

Amblyopia is a developmental disorder that affects the spatial vision of one or both eyes in the absence of an obvious organic cause; it is associated with a history of abnormal visual experience during childhood. Subtypes have been defined based on the purported etiology, namely, strabismus (misaligned eyes) and/or anisometropia (unequal refractive error). Here we consider the usefulness of these subclassifications.

Both saccadic and manual responses in the amblyopic eye of strabismics are irreducibly delayed.

Abnormal early visual development can result in a constellation of neural and visual deficits collectively known as amblyopia. Among the many deficits, a common finding is that both saccadic and manual reaction times to targets presented to the amblyopic eye are substantially delayed when compared to the fellow eye or to normal eyes. Given the well-known deficits in contrast sensitivity in the amblyopic eye, a natural question is whether the prolonged reaction times are simply a consequence of reduced stimulus visibility. To address this question, in Experiment 1 we measure saccadic reaction times (RT) to perifoveal stimuli as a function of effective stimulus contrast (i.e., contrast scaled by the amblyopic eye's contrast threshold). We find that when sensory differences between the eyes are minimized, the asymptotic RTs of our anisometropic amblyopes were similar in the two eyes. However, our results suggest that some strabismic amblyopes have an irreducible delay at the asymptote. That is, even when the sensory differences of the stimulus were accounted for, these observers still had large interocular differences (on average, 77 ms) in saccadic reaction time. In Experiment 2, to assess the role of fixation on saccadic reaction time we compared reaction time with and without a foveal target (the "gap effect"). Our results suggest that, while removing the fixation target does indeed speed up reaction time in the amblyopic eye, the gap effect is similar in the two eyes. Therefore, the gap effect does not eliminate the irreducible delay in the amblyopic eye. Finally, in Experiment 3 we compared the interocular differences in saccadic and manual reaction times in the same observers. This allowed us to determine the relationship between the latencies in the two modalities. We found a strong correlation between the differences in saccadic and manual reaction times; however, the manual RT difference is about half that of saccadic RT, suggesting that there may be two separable effects on saccadic reaction time: (a) a central problem with directing actions to a target, related to disengagement of attention at the fovea, which results in delays in both saccadic and manual reaction times, and (b) a further delay in saccadic reaction times because of the motor refractory period from a previous saccade or microsaccade, made in an attempt to stabilize the amblyopic eye of strabismics.

Saccadic latency in amblyopia.

We measured saccadic latencies in a large sample (total n = 459) of individuals with amblyopia or risk factors for amblyopia, e.g., strabismus or anisometropia, and normal control subjects. We presented an easily visible target randomly to the left or right, 3.5° from fixation. The interocular difference in saccadic latency is highly correlated with the interocular difference in LogMAR (Snellen) acuity-as the acuity difference increases, so does the latency difference. Strabismic and strabismic-anisometropic amblyopes have, on average, a larger difference between their eyes in LogMAR acuity than anisometropic amblyopes and thus their interocular latency difference is, on average, significantly larger than anisometropic amblyopes. Despite its relation to LogMAR acuity, the longer latency in strabismic amblyopes cannot be attributed either to poor resolution or to reduced contrast sensitivity, because their interocular differences in grating acuity and in contrast sensitivity are roughly the same as for anisometropic amblyopes. The correlation between LogMAR acuity and saccadic latency arises because of the confluence of two separable effects in the strabismic amblyopic eye-poor letter recognition impairs LogMAR acuity while an intrinsic sluggishness delays reaction time. We speculate that the frequent microsaccades and the accompanying attentional shifts, made while strabismic amblyopes struggle to maintain fixation with their amblyopic eyes, result in all types of reactions being irreducibly delayed.

Dynamics and cortical distribution of neural responses to 2D and 3D motion in human.

The perception of motion-in-depth is important for avoiding collisions and for the control of vergence eye-movements and other motor actions. Previous psychophysical studies have suggested that sensitivity to motion-in-depth has a lower temporal processing limit than the perception of lateral motion. The present study used functional MRI-informed EEG source-imaging to study the spatiotemporal properties of the responses to lateral motion and motion-in-depth in human visual cortex. Lateral motion and motion-in-depth displays comprised stimuli whose only difference was interocular phase: monocular oscillatory motion was either in-phase in the two eyes (lateral motion) or in antiphase (motion-in-depth). Spectral analysis was used to break the steady-state visually evoked potentials responses down into even and odd harmonic components within five functionally defined regions of interest: V1, V4, lateral occipital complex, V3A, and hMT+. We also characterized the responses within two anatomically defined regions: the inferior and superior parietal cortex. Even harmonic components dominated the evoked responses and were a factor of approximately two larger for lateral motion than motion-in-depth. These responses were slower for motion-in-depth and were largely independent of absolute disparity. In each of our regions of interest, responses at odd-harmonics were relatively small, but were larger for motion-in-depth than lateral motion, especially in parietal cortex, and depended on absolute disparity. Taken together, our results suggest a plausible neural basis for reduced psychophysical sensitivity to rapid motion-in-depth.

Bridging the gap: global disparity processing in the human visual cortex.

The human stereoscopic system is remarkable in its ability to utilize widely separated features as references to support fine depth discrimination. In a search for possible neural substrates of this ability, we recorded high-density EEG and used a distributed inverse technique to estimate population-level disparity responses in five regions of interest (ROIs): V1, V3A, hMT+, V4, and lateral occipital complex (LOC). The stimulus was a central modulating disk surrounded by a correlated "reference" annulus presented in the fixation plane. We varied a gap separating the disk from the annulus parametrically from 0 to 5.5° as a test of long-range disparity integration. In the V1, LOC, and hMT+ ROIs, the responses with gaps >0.5° were equal to those obtained in a control condition where the surround was composed of uncorrelated noise (no reference). By contrast, in the V4 and V3A ROIs, responses with gaps as large as 5.5° were still significantly higher than the control. As a test of the spatial distribution of the disparity reference information, we manipulated the properties of the stimulus by placing noise between the center and the surround or throughout the surround. The V3A ROI was particularly sensitive to disparity noise between the center and annulus regions, suggesting an important contribution of disparity edge detectors in this ROI.

Disparity-specific spatial interactions: evidence from EEG source imaging.

Using cortical source estimation techniques based on high-density EEG and fMRI measurements in humans, we measured how a disparity-defined surround influenced the responses to the changing disparity of a central disk within five visual ROIs: V1, V4, lateral occipital complex (LOC), hMT+, and V3A. The responses in the V1 ROI were not consistently affected either by changes in the characteristics of the surround (correlated or uncorrelated) or by its disparity value, consistent with V1 being responsive only to absolute, not relative, disparity. Correlation in the surround increased the responses in the V4, LOC, and hMT+ ROIs over those measured with the uncorrelated surround. Thus, these extrastriate areas contain neurons that are sensitive to disparity differences. However, their evoked responses did not vary systematically with the surround disparity. Responses in the V3A ROI, in contrast, were increased by correlation in the surround and varied with its disparity. We modeled these V3A responses as attributable to a gain modulation of the absolute disparity response, where the gain amplitude is proportional to the center-surround disparity difference. An additional experiment identified a nonlinear center-surround interaction in V3A that facilitates the responses when center and surround are misaligned but suppresses it when they share the same disparity plane.

Perceived global flow direction reveals local vector weighting by luminance.

Global flow occurs when random dots, each selecting their direction of motion randomly each frame from a distribution of directions spanning up to 180°, appear to move as a whole in the mean direction of the components. This percept arises because the visual system integrates the many independent local motion signals over space and time. Through a series of direction discrimination experiments with random-dot cinematograms (RDCs), we show that varying the luminance of dots over a suprathreshold range profoundly affects perceived direction; the brightest dots appear to be weighted more and dimmer dots weighted less when determining perceived global direction. This effect is not observable if all dots in the display have the same luminance but only when the display contains dots with different luminance values. The results are consistent with energy models of motion detectors whose responses are contrast dependent. A Monte Carlo simulation of global direction discrimination employing a 12-mechanism line-element model that weighted the local motion vectors by the normalized squared contrast of the component dots (a proxy for contrast energy) captured well the features of the experimental data.

Disparity-tuned population responses from human visual cortex.

We used source imaging of visual evoked potentials to measure neural population responses over a wide range of horizontal disparities (0.5-64 arcmin). The stimulus was a central disk that moved back and forth across the fixation plane at 2 Hz, surrounded either by binocularly uncorrelated dots (disparity noise) or by correlated dots presented in the fixation plane. Both disk and surround were composed of dynamic random dots to remove coherent monocular information. Disparity tuning was measured in five visual regions of interest (ROIs) [V1, human middle temporal area (hMT+), V4, lateral occipital complex (LOC), and V3A], defined in separate functional magnetic resonance imaging scans. The disparity tuning functions peaked between 2 and 16 arcmin for both types of surround in each ROI. Disparity tuning in the V1 ROI was unaffected by the type of surround, but surround correlation altered both the amplitude and phase of the disparity responses in the other ROIs. Response amplitude increased when the disk was in front of the surround in the V3A and LOC ROIs, indicating that these areas encode figure-ground relationships and object convexity. The correlated surround produced a consistent phase lag at the second harmonic in the hMT+ and V4 ROIs without a change in amplitude, while in the V3A ROI, both phase and amplitude effects were observed. Sensitivity to disparity context is thus widespread in visual cortex, but the dynamics of these contextual interactions differ across regions.

Visual deficits in anisometropia.

Amblyopia is usually associated with the presence of anisometropia, strabismus or both early in life. We set out to explore quantitative relationships between the degree of anisometropia and the loss of visual function, and to examine how the presence of strabismus affects visual function in observers with anisometropia. We measured optotype acuity, Pelli-Robson contrast sensitivity and stereoacuity in 84 persons with anisometropia and compared their results with those of 27 persons with high bilateral refractive error (isoametropia) and 101 persons with both strabismus and anisometropia. All subjects participated in a large-scale study of amblyopia (McKee et al., 2003). We found no consistent visual abnormalities in the strong eye, and therefore report only on vision in the weaker, defined as the eye with lower acuity. LogMAR acuity falls off markedly with increasing anisometropia in non-strabismic anisometropes, while contrast sensitivity is much less affected. Acuity degrades rapidly with increases in both hyperopic and myopic anisometropia, but the risk of amblyopia is about twice as great in hyperopic than myopic anisometropes of comparable refractive imbalance. For a given degree of refractive imbalance, strabismic anisometropes perform considerably worse than anisometropes without strabismus--visual acuity for strabismics was on average 2.5 times worse than for non-strabismics with similar anisometropia. For observers with equal refractive error in the two eyes there is very little change in acuity or sensitivity with increasing (bilateral) refractive error except for one extreme individual (bilaterally refractive error of -15 D). Most pure anisometropes with interocular differences less than 4D retain some stereopsis, and the degree is correlated with the acuity of the weak eye. We conclude that even modest interocular differences in refractive error can influence visual function.

The precision of binocular and monocular depth judgments in natural settings.

We measured binocular and monocular depth thresholds for objects presented in a real environment. Observers judged the depth separating a pair of metal rods presented either in relative isolation, or surrounded by other objects, including a textured surface. In the isolated setting, binocular thresholds were greatly superior to the monocular thresholds by as much as a factor of 18. The presence of adjacent objects and textures improved the monocular thresholds somewhat, but the superiority of binocular viewing remained substantial (roughly a factor of 10). To determine whether motion parallax would improve monocular sensitivity for the textured setting, we asked observers to move their heads laterally, so that the viewing eye was displaced by 8-10 cm; this motion produced little improvement in the monocular thresholds. We also compared disparity thresholds measured with the real rods to thresholds measured with virtual images in a standard mirror stereoscope. Surprisingly, for the two naive observers, the stereoscope thresholds were far worse than the thresholds for the real rods-a finding that indicates that stereoscope measurements for unpracticed observers should be treated with caution. With practice, the stereoscope thresholds for one observer improved to almost the precision of the thresholds for the real rods.

The time course of contrast masking reveals two distinct mechanisms of human surround suppression.

We explored the time course of surround suppression and found clear evidence for two distinct mechanisms: one strong, transient, and largely monocular, the other weaker, sustained, and binocular. We measured detection thresholds for a Gabor target at 8 deg eccentricity surrounded by a large annulus of matching spatial frequency and orientation. At short stimulus durations surround suppression was very strong, but the suppression strength decreased precipitously for durations longer than approximately 100 msec. The strong transient component did not transfer between the eyes and occurred almost instantaneously (<1 frame delay, 12 msec) irrespective of the separation between target and surround. Both suppression components were tightly tuned to orientation, peaking at target orientation, but neither was tuned to target spatial phase. These results are in good agreement with surround suppression properties measured in macaque V1 neurons. The absence of interocular transfer, the strong orientation selectivity, and the high propagation speed incommensurate with slow horizontal connections in V1 suggest that the transient component of suppression originates between input layers and the subsequent layers in V1.

Disparity tuning of binocular facilitation and suppression after normal versus abnormal visual development.

PURPOSE: To study the pattern of facilitatory and suppressive binocular interactions in stereodeficient patients with strabismus and in healthy controls. METHODS: Visual evoked potentials were recorded in response to a Vernier onset/offset pattern presented to one eye, either monocularly or paired dichoptically with a straight vertical square-wave grating, which, when fused with the target in the other eye, gave rise to a percept of a series of bands appearing in depth from an otherwise uniform plane or with a grating that contained offsets that produced a standing disparity and the appearance of a constantly segmented image, portions of which moved in depth. RESULTS: Participants with normal stereopsis showed facilitative and suppressive binocular interactions that depended on which dichoptic target was presented. Patients with longstanding, constant strabismus lacked normal facilitative binocular interactions. The response to a normally facilitative stimulus was reduced below the monocular level when it was presented to the dominant eye of patients without anisometropia, consistent with classical strabismic suppression of the nondominant eye. The dominant eye of strabismic patients without anisometropia retained suppressive input from crossed but not uncrossed disparity stimuli presented to the nondominant eye. CONCLUSIONS: Abnormal disparity processing can be detected with the dichoptic VEP method we describe. Our results suggest that suppression in stereoblind, nonamblyopic observers is determined by a binocular mechanism responsive to disparity. In some cases, the sign of the disparity is important, and this suggests a mechanism that can explain diplopia in patients made exotropic after surgery for esotropia.

The role of binocular stereopsis in monoptic depth perception.

In his study of depth from monocular elements, Kaye (1978) [Kaye, M. (1978). Stereopsis without binocular correlation. Vision Research, 18(8), 1013-1022] reported that monocular stimuli, briefly presented to one eye in a stereoscopic display, generated reliable depth percepts. Here we replicate and extend Kaye's findings in an effort to identify the mechanism underlying the phenomenon. Our experiments show that the perception of depth is not a simple result of monocular local sign, for the percept of depth disappears when one eye is patched. In subsequent experiments we assess the possibility that the percept results from a very coarse stereoscopic match to either the centroid of the luminance distribution in the unstimulated eye or a simple match to the line of sight in the unstimulated eye. Our results consistently support the match-to-fovea account, and lead us to conclude that monoptic depth is a stereoscopic phenomenon.

Visual information throughout a reach determines endpoint precision.

People make rapid, goal-directed movements to interact with their environment. Because these movements have consequences, it is important to be able to control them with a high level of precision and accuracy. Our hypothesis is that vision guides rapid hand movements, thereby enhancing their accuracy and precision. To test this idea, we asked observers to point to a briefly presented target (110 ms). We measured the impact of visual information on endpoint precision by using a shutter to close off view of the hand 50, 110 and 250 ms into the reach. We found that precision was degraded if the view of the hand was restricted at any time during the reach, despite the fact that the target disappeared long before the reach was completed. We therefore conclude that vision keeps the hand on the planned trajectory. We then investigated the effects of a perturbation of target position during the reach. For these experiments, the target remained visible until the reach was completed. The target position was shifted at 110, 180 or 250 ms into the reach. Early shifts in target position were easily compensated for, but late shifts led to a shift in the mean position of the endpoints; observers pointed to the center of the two locations, as a kind of best bet on the position of the target. Visual information is used to guide the hand throughout a reach and has a significant impact on endpoint precision.

The wallpaper illusion explained.

In the wallpaper illusion, a repetitive pattern appears to shift from one depth plane to the plane nearest fixation. We measured the timing of this shift for a 6 degrees wide, 3-cpd sinusoidal grating presented in a rectangular envelope; the edges (envelope) of the grating were presented at 20 arcmin of disparity (one period) behind the fixation plane. We asked observers to signal when the segment appeared to move from the edge plane forward to the fixation plane. Initially, the shift from the edge plane took 4-6 s, but after many trials, the shift became faster. Additional experiments demonstrated that the envelope was adapting, thereby permitting the alternative match. Our measurements for a range of spatial frequencies and disparities showed that these shifts to the fixation plane occurred only if the envelope disparity was more than one-half period of the carrier; that is, phase disparity >180 degrees. We also found that stereoacuity for the initial envelope-based match was poor, as might be expected for a target presented far off the fixation plane. However, once the perceived shift in depth occurred, stereoacuity improved fivefold without any change in the physical stimulus. We speculate that access to the most sensitive V1 neurons depends on the extrastriate processes that determine perceived depth--in this case, second-order envelope mechanisms.

Crowding and surround suppression: not to be confused.

Crowding and surround suppression share many similarities, which suggests the possibility of a common mechanism. Despite decades of research, there has been little effort to compare the two phenomena in a consistent fashion. A recent study by D. M. Levi, S. Hariharan, and S. A. Klein (2002) argues that the two are unrelated because crowding effects can be much stronger than suppression effects. Here we report experiments in which the same Gabor target was used both for orientation identification (crowding) and contrast detection (suppression) tasks. In agreement with early crowding studies (e.g., H. Bouma, 1973) we found, that an outward mask is much more effective than an inward mask for the orientation identification task. Notably, no such anisotropy was observed for the contrast detection task, commonly used to measure surround suppression. The anisotropic masking, which defines crowding, is observed only at fine scales (roughly within an octave of the acuity limit), whereas surround suppression is observed at all scales. Our results demonstrate that surround suppression and crowding are indeed two distinct phenomena. We used this characteristic anisotropy to show that a popular crowding paradigm in which target contrast is varied to measure crowding is confounding it with surround suppression. Surround suppression apparently dominates at low contrasts, which would explain some of the reported similarities between the two phenomena.

Initial visual information determines endpoint precision for rapid pointing.

We investigated how visual noise in the initial estimate of target location affects precision for rapid pointing. Visual localization thresholds (an error measure) rise systematically with eccentricity, doubling at eccentricities of a degree or less. Previous work, which we confirmed, has shown that the precision of pointing, measured by the standard deviation, to a single isolated target is relatively constant over small lateral extents near the midline, and that pointing error is substantially larger than visual error. We used target uncertainty (randomly chosen locations) to greatly increase visual noise so that we could explore the influence of visual noise on pointing error. We compared precision for comparable visual and pointing tasks as a function of target eccentricity. The target was presented for 110 ms at one of eight isoeccentric locations, chosen at random. Under these conditions, pointing error increased significantly with increasing target eccentricity. Beyond 4 degrees eccentricity, visual thresholds and pointing error were identical. Even when the target remained visible until the movement was completed, initial target eccentricity affected pointing error. The quality of visual information varies with task demands, and therefore so does its influence on endpoint precision. Our results demonstrate that the initial visual information about target location can limit endpoint precision, even over as small a range as 12 degrees in the central visual field (a lateral extent of +/-8.5 cm at the midline).

The effect of spatial configuration on surround suppression of contrast sensitivity.

Contrast sensitivity is known to be strongly influenced by the target surround, yet the role of the surround interaction in visual processing remains unclear. Previously, we have shown that the surround strongly suppresses contrast sensitivity in the periphery when the surround spatial frequency and orientation match those of the target (Petrov, Carandini, & McKee, 2005). Here, we explore how various spatial characteristics of the iso-oriented and frequency-matched surround, such as surround phase and spatial layout, affect suppression. We manipulated surround geometry (annulus ring, half annulus, and bow tie) and its separation from the target (both laterally and in depth) and varied the position of the half-annulus and bow-tie surrounds with respect to Gabor target's orientation and with respect to its location in the visual field (i.e., radial vs. tangential surrounds). We also compared monoptic, dichoptic, and binocular surround suppression. Except for a significant radial-tangential anisotropy, only the area of the surround and the lateral separation between the surround and target had a significant effect on the magnitude of suppression. We showed that, although suppression amplitude remains constant with stimulus eccentricity, the lateral extent of suppression scales in proportion to the eccentricity. The most surprising finding was that the extent of surround suppression does not scale with stimulus size or spatial frequency. We suggest that the properties of surround suppression are best explained by a mechanism that selects salient targets for subsequent saccades.