Suzanne P. McKee - US grants

DESCRIPTION: Physiologically based models of human stereomatching have proposed two ways to remove depth ambiguity in the responses of single units. In one, the disparity range is related to the spatial scale of the detector. In the second, different scales interact to remove residual depth ambiguity. The investigator proposes a set of psychophysical experiments to test whether these rules are used in human vision. A second set of experiments will test whether large diplopic disparities are processed by different mechanisms than those involved with fine stereoacuity. An understanding of normal stereovision is a prerequisite for an understanding of abnormal development of binocular vision, effects which include both strabismic and anisometropic amblyopia.

Binocular correspondence is the study of how the two monocular images are correctly fused in normal binocular vision, creating a sense of depth and permitting the detection of small disparity differences as in fine stereoacuity. Psychophysical experiments on a repetitive stimulus, the ambiguous stereogram of the "wallpaper effect", will be used to probe the operations of normal fusion. The basic stimulus for the proposed research is a small grid of bright points displayed haploscopically. Manipulation of the disparity of the edges of this display can force the fusion of this target in several different depth planes, without the intervention of changes in convergence. Two theoretical models of fusion will serve as a framework for the proposed experiments. Specifically, the proposed research will examine three questions: 1) If the edge effects are propagated via cooperative interactions between local disparity detecting neural elements, what are the spatial and temporal arrangements which produce the change in the apparent depth of this target? 2) If the edge effects represent disparity responses of low spatial frequency channels, how do the low spatial frequency channels surpress the disparity signals of higher spatial frequency channels? 3) If fusional processes depend on interactions between competing disparities, how is the stereoacuity for a target lying one plane affected by adjacent targets lying in other depth planes? This research will supply fundamental information about normal binocular fusion. A preliminary study on patients with abnormal fusion, also part of the proposed research plan, will examine how abnormal binocular mechanisms respond to these grid stimuli.

The research program at the Smith-Kettlewell Eye Research Institute includes projects on oculomotor processing, binocular vision, image motion processing, the development of spatial and temporal vision in human infants, surgical techniques in strabismus, psychophysical measurements in amblyopic observers, neural plasticity, retinal aspects of temporal processing, diagnostic use of flicker measurements in glaucoma, and special techniques for measuring local ERG's. All of these projects have benefitted greatly from past support of CORE modules. Continued support for the Electronics Services Module (hardware design and manufacture), the Computer Software Services Module (software development and maintenance) and the Administrative and Secretarial Module (manuscript and grant typing) is requested. These services are an integral part of the resources of this institution, providing assistance to both on-going and pilot projects and encouraging the collaborative arrangements that have long been typical of Smith-Kettlewell research.

Neurophysiological studies have shown how disparity-tuned neurons in primary visual cortex make the initial disparity measurements. However, the response of these neurons bears little relation to human depth perception. While the disparity-tuned neurons code absolute disparity, and are little affected the context of stimuli falling within their receptive fields, depth perception depends heavily on relative disparity, and is greatly influenced by the surrounding disparity field. How does this transformation from the disparity signals to the signals that generate perceived depth occur? One aspect of human stereopsis that is probably limited by these primary neurons is stereoacuity. Yet, stereoacuity may also be influenced by stimulus conditions that profoundly affect perceived depth. Stereoacuity can thus serve as a psychophysical probe for how the signals generated by disparity-tuned neurons are combined in subsequent processing stages. In the proposed research, we will measure how the surrounding context (long-range interactions and depth contrast) affects stereoacuity, since context has important effects on perceived depth. In addition, we will examine use stereo transparency measurements to estimate the pooling area for disparity signals, as well as how these signals are combined. The experiments in this proposal will examine stereo processing in normal human observers. About 5 percent of the population suffers from oculomotor (strabismus) or refractive (anisometropia) disorders that threaten the development of normal stereopsis. While most individuals can cope with the loss of stereopsis, abnormal binocular development is also frequently associated with a deficit in the acuity of one eye (amblyopia) -- a more serious problem. These studies of normal observers will provide basic knowledge about normal stereopsis, a prerequisite for understanding abnormalities of the binocular system.

DESCRIPTION (provided by applicant): We will design an objective test, based on the Visual Evoked Potential (VEP), to measure amblyopic suppression. Our basic tool is the VEP monocular response to periodic vernier onset/offset transitions in bar stimuli, and its suppression during dichoptic stimulation with matching contours. What is unique about this approach is that it identifies which eye is being suppressed as well as the visual acuity of each eye. Although we will develop and validate this test in adult subjects, our dichoptic visual display system has been specifically designed for ultimate use with infants and pre-verbal children. We also will use a new multi-channel recording system (Geodesic Sensor Net) to explore the neural basis for the differences between normal and abnormal binocular processing. About 4% of all children suffer from strabismus and/or anisometropia during early development. These abnormalities place an individual at risk for a variety of visual deficiencies. The most serious outcome is amblyopia in one eye. Amblyopia refers to a loss of visual acuity, without obvious organic cause, that cannot be corrected by wearing spectacles or contact lenses. Perhaps one third of strabismics and anisometropes suffer some loss in visual acuity. The proposed test could assist with the diagnosis of amblyopia in infancy, as well as in monitoring progress during treatment, thereby improving the chance of a favorable outcome.

[unreadable] DESCRIPTION (provided by applicant): This study answers fundamental questions of large-scale neural networks in the human brain supporting crossmodal cognition. To reveal how auditory and visual stimuli and motor acts are arbitrarily combined as a result of crossmodal learning and integrated to supramodal symbolic representations, we will study the neural representations of the letters of the Roman alphabet. These consist of four unimodal representations (visual, auditory, and motor representations for writing and speaking) and learned connections between these, that is, the processes that underlie their audiovisual recognition and motor production. Accurate experimental control is facilitated by the fact that letters exhibit all the necessary properties of symbolic crossmodal representations but in a physically simple and exact format carrying no semantic associations that could confound the neurophysiological interpretation of results. Combined 3-Tesla functional magnetic resonance imaging (fMRI) and 306-channel magnetoencephalographic / 128-channel electroencephalographic (MEG/EEG) techniques with simultaneous behavioral recordings will be applied to pinpoint the exact underlying neural mechanisms. This approach combines the advantages of spatially accurate fMRI with temporally specific MEG/EEG, enabling accurate spatiotemproal characterization of brain activity totally noninvasively. To directly observe how large-scale neurocognitive networks evolve during crossmodal associative learning, we will also conduct fMRI/MEG/EEG measurements before and after our subjects are taught (previously unfamiliar) Japanese kana-letters. The specific aims are to elucidate structure, function, and oscillatory mechanisms of fully established crossmodal neural networks based on previous extensive associative learning (Roman letters) and currently evolving networks representing novel crossmodal associations (Japanese letters). We will characterize the relative roles of deep brain nuclei, cerebellum, medial temporal lobe, and sensory-specific and multisensory association cortices in such networks. The multidimensional experimental design allows isolation of neural mechanisms utilized by perception, working memory, memory encoding, and recall. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Disparity tuning is a pervasive property of neurons in almost all visual areas in primate cortex. We will use a novel neuroimaging technique to examine the flow of disparity information from V1 to extra- striate areas in human cortex. This technique relies on source localization using high density EEG coupled to structural and functional MRI anatomical measurements. We will measure the neural response to repetitive changes in disparity in four widely separated cortical areas, V1, V3A, V4 and hMT+ - all known to be important in primate disparity processing. Our first aim examines the sensitivity of the cortical response in these four areas to dynamic random dots, modulated by horizontal or by vertical disparity. We will also explore the response to anti-correlated random dots which are known to drive single units in many cortical areas. Our second aim evaluates the contribution of disparity-modulation to surface segmentation. We will compare the response patterns produced by monocularly modulated changes in figure-ground segmentation to those generated by disparity modulated changes in figure-ground segmentation. Our third aim explores how the loss of stereopsis affects the cortical responses of the strabismic observer. We will specifically look for the cortical locus of strabismic suppression, as well as for the locus of the motion asymmetry that is a defining characteristic of infantile esotropia. PUBLIC HEALTH RELEVANCE Strabismus is a developmental abnormality that affects 3 - 5% of the population, resulting in the loss of stereopsis. The proposed research will measure the cortical response associated with two anomalies of strabismus: strabismic suppression and the motion asymmetry previously observed in VEP measurements. The motion asymmetry is a useful marker for judging the efficacy of treatment, particularly surgery, so understanding its cortical origin will enhance its utility.