Talk Series Abstracts 2002
Vision dynamics flap induced aberrations and subepithelial LASIK (sel.)
CVS Research Talk: Ioannis Pallikaris, Chairman, Ophthalmology, Heraklion University Hospital and the Vardiniyannion Eye Institute of Crete, Heraklion Greece
Subepithelial LASIK (SEL): A new refractive technique. Histological evaluation- Human study. Purpose: To develop a new technique for the mechanical separation of corneal epithelial layer with subsequent excimer laser ablation of stroma. To evaluate the efficiency of Subepithelial LASIK (SEL). Methods: 4 eyes underwent Subepithelial LASIK (SEL). The epithelial layer was separated from the stroma with the use of a modified epithelial separator. The epithelial flaps were examined with the help of light and electron microscopy. The histological findings were compared with those obtained with the conventional LASEK technique. (4 eyes: 15% and 30% of alcohol). Results: In SEL the basal layer of epithelial cells was separated from the corneal stroma at the level where lamina densa of the basement membrane contacts with the Bowman's membrane. The lamina densa and the lamina lucida as well as hemidesmosome structures demonstrated normal morphology almost along the whole length of basement membrane. Separations were not accompanied by blebbing (formation of cytoplasmic fragments) of basal epithelial cells, which was typical for LASEK technique. Basal epithelial cells of the flap showed minimal trauma and edema. Conclusion: SEL is an improved technique that may combine the advantages of LASIK and LASEK and reduce their disadvantages.
Receptive field properties of lateral geniculate cells in the owl monkey (aotus azarae): a comparative study
CVS Postdoc Talk: Bjørg Elisabeth Kilavik, University of Tuebingen Eye Hospital, Tuebingen Germany
The owl monkey is the only nocturnal anthropoid primate. We have compared several physiological properties of owl monkey lateral geniculate nucleus (LGN) cells with those of LGN neurons in diurnal monkeys. We studied the contribution of rods and cones to LGN cell responses under different retinal illuminance levels using a set of stimuli in which the rod and cone excitation modulation is varied. To measure the spatial properties, we used drifting gratings and bipartite field stimuli. We were particularly interested in measuring the receptive field sizes, the sensitivities and the influence of stimulus contrast on the two. Our results show that owl monkeys LGN cells have stronger rod inputs and larger receptive fields than diurnal primates, indicative for a larger spatial integration. But, basic properties such as saturation, the influence of contrast and the dependency of receptive field size on retinal eccentricity are similar as in other monkeys. From our results we conclude that during evolution, the owl monkey retina and LGN have undergone changes compatible with a more nocturnal lifestyle, including spatial integration and more prominent rod vision, without a change in the basic organization common to the visual system of all primates.
Can natural accommodation be restored in presbyopes?
BME Candidate: Adrian Glasser, Assistant Professor, College of Optometry, University of Houston, Houston TX
Accommodation is the mechanism whereby the focus of the eye is adjusted to maintain a clear image of objects at different distances. It is a dynamic, dioptric change in power of the eye resulting from a contraction of the ciliary muscle and a change in optical power of the crystalline lens. Presbyopia is the gradual age related loss of accommodation which in humans results in a loss of accommodation by about age 50. Presbyopia, affects everybody, is without treatment or cure and causes inconvenience, loss of productivity and considerable economic burden. Although bifocal spectacle lenses provide effective optical compensation for presbyopia, there is tremendous interest in understanding if accommodation can be surgically restored. To understand how and if accommodation can be restored first requires a sound empirical understanding of the accommodative mechanism, the accommodative optical and physical changes in the eye and the causes of presbyopia. My research is broadly directed at understanding these three areas with the long term goal of understanding how and if natural accommodation may be restored in presbyopes. Accommodation is stimulated in rhesus monkeys via an electrode surgically implanted in the Edinger-Westphal nucleus of the brain. Measurement of the dynamic accommodative optical changes in the eye show that peak velocity is linearly related to amplitude of the accommodative response. We have identified that accommodation can be elicited at 0.2-0.1 Hz for long periods with only small changes in the response properties and we are studying how pharmacological agents affect the dynamic accommodative response and how the aberrations of the eye change with accommodation. The optical and accommodative performance of the rhesus monkey crystalline lens is also studied in an in vitro preparation. Enucleated eyes are dissected and placed in a mechanical stretching apparatus and the optical changes in the lens are measured as a function of the applied stretch. These studies demonstrate how crystalline lens diameter, surface curvatures and optical power change during accommodation. This is a unique tool to study the accommodative performance of the crystalline lens, and to understand how intraocular accommodative lenses (IAL's) might perform when placed inside the lens capsular bag. One such IAL being tested in this way is created by injecting a polymer into the empty capsular bag to create a polymer refilled lens. Our research towards a better understanding the dynamic accommodative responses in the living eye and the physical changes that occur in the lens with accommodation provides new baseline information against which the performance of future IAL's may be compared.
Defensins at the ocular surface—just antimicrobial peptides?
Ophthalmology Candidate: Alison McDermott, College of Optometry, University of Houston, Houston TX
Defensins are a family of peptides best known for their ability to form pores in microbial cell membranes so leading to death of the organism. Two classes of defensin are found in human tissue. a-defensins are found in white blood cells and certain intestinal cells whereas b-defensins are expressed by epithelial tissue. To date, four human b-defensins (hBD-1 through 4) have been identified. Ocular surface epithelia (corneal and conjunctival) have been shown to express hBD-1 constitutively. The expression of hBD-2 and hBD-3 is variable and is upregulated in response to inflammatory mediators and bacterial products. Undoubtedly the defensins expressed by the ocular surface epithelia have a role to play in defense against pathogenic microorganisms, however there is evidence to suggest other functions. Defensins have been shown to stimulate migration, proliferation and cytokine/growth factor production in a number of cell types. These cell behaviors are integral parts of the corneal epithelial wound healing process which leads us to ask the question "are defensins involved in wound healing?". Using an in vitro model of corneal wound healing we have shown that expression of hBD-1 is unchanged whereas that of hBD-2 is markedly upregulated in regenerating epithelial cells. Recent in vivo studies using a rat model of healing have shown similar patterns of expression for rBD-1 and rBD-2, the rat homologues of hBD-1 and -2. Studies with cultured corneal epithelial cells suggest that upregulation of hBD-2 expression is mediated by inflammatory cytokines such as interleukin-1 by a pathway involving the transcription factor NF-kB. Preliminary functional studies suggest that whilst defensins do not modulate corneal cell migration they can stimulate proliferation. Thus it is possible that defensins, particularly hBD-2, are involved in epithelial wound healing.
Large scale astronomical optics
Colloquium Speaker: Jerry Nelson, Professor of Astronomy and Astrophysics, University of California, Santa Cruz; Director, NSF Science and Technology Center for Adaptive Optics
Several groups in the astronomical community are seriously studying the possibility of building 30-100m ground based optical telescopes. In this talk I will give a bit of history of large telescopes and their technical challenges. This will be done along with a few remarks on the challenge of building large systems in general. I will present some details of the California Extremely Large Telescope (CELT) design study. CELT is a proposal for the University of California and Caltech to build a 30-m ground based telescope. As time permits I may also discuss some of the scientific opportunities, and the particular challenges and scientific returns from using adaptive optics on a 30-m telescope.
Adaptive optics for astronomy and vision science
Colloquium Speaker: Jerry Nelson, Professor of Astronomy and Astrophysics, University of California, Santa Cruz; Director, NSF Science and Technology Center for Adaptive Optics
(AO) is a powerful tool used to improve the angular resolution of ground based telescopes. Recent results in astronomical adaptive optics will be discussed as well as the future of adaptive optics and the potential for the use of adaptive optics on future telescopes. AO is also a powerful tool for high resolution imaging of the human retina. The current state of AO in vision science will be discussed. Recent results from the University of Houston's AO scanning laser ophthalmoscope will be presented. This system has the capability of imaging the human retina on a microscopic scale in real time, allowing scientists and clinicians to monitor the location and movement of individual cells, capillaries, photoreceptors and blood cells in the eye.
Deciphering the geometric code for face perception
CVS Research Talk: Hugh Wilson, ORDCF Professor of Biological & Computational Vision, York University, Toronto CA; & Fran Wilkinson , Professor and Chair, Department of Psychology, Atkinson Faculty of Liberal and Professional Studies, York University, Toronto CA
A major goal of research on human form vision is to understand the sequence of operations that transform local contour orientation information extracted in primary visual cortex (V1) into global information about objects such as faces. Previous work has shown that intermediate levels of form vision (V4) analyze ellipsoidal, radial, and other configurations in the image. Based on this, we have devised a novel class of synthetic faces described in front or 20° side views by 37 geometric parameters each. Synthetic faces are also bandpass filtered to the optimal frequency range for discrimination. Psychophysical experiments using 4-dimensional "face cubes" have shown that discrimination thresholds are lowest near the mean face for each gender and higher farther away, which may provide a quantitative explanation for the "other race" effect. New data suggest that synthetic faces are analyzed into principal components (PCA) by the brain. We will also describe ongoing work on transformation between front and side views, size constancy, and preliminary insights into prosopagnosia using synthetic faces.
The role of attention in sensory processing in monkey visual cortex
Colloquium Speaker:John Maunsell, Investigator & Professor of Neuroscience, Howard Hughes Medical Institute and Baylor College of Medicine
Attention to a visual stimulus increases the responses of cortical neurons to that stimulus. We examined how attention affects the relationship between neuronal responses and behavioral performance by measuring both while rhesus monkeys performed a motion detection task. The animals detected motion that appeared in locations that were either relatively well or relatively poorly attended. We recorded responses from neurons in two cortical visual areas that process motion: the middle temporal area (MT) and the ventral intraparietal area (VIP). In both areas attention affected the relationship between neuronal response and behavioral performance. Attention had less of an effect on the responses of MT neurons than it did on the animals' behavior. The responses of VIP neurons, in contrast, were more affected by attention than was behavior. A close relationship between neuronal and behavioral performance may therefore persist over changes in attentional state only within limited regions of visual cortex
Colour and stereo scanning laser ophthalmoscopy
Faculty Candidate Research Talk: Fred Reinholz, Optical Engineer, Lions Eye Institute, Lasers and Bioengineering Group, Perth, AU
Traditionally, fundus photography is one of the most important tools for the diagnosis of eye diseases in a clinical setting. The fundus photographs are usually in colour and can also be acquired in form of stereo pairs. Scanning laser ophthalmoscopy shows numerous advantages over fundus photography, including a higher contrast, real-time display and immediate accessibility of a digital image, or the possibility to acquire images without applying mydriatics. Furthermore, with a confocal arrangement it is possible to perform optical sectioning. The analysis of a stack of optical sections allows the extraction of 3-D images or topological data. Despite these advantages the routine use of scanning laser ophthalmoscopes (SLO) at present is uncommon. Partly, this situation is due to some technical limitations (compared to film based fundus cameras) of most commercially available SLOs, namely the limited field of view, the monochromatic nature of the image and the need to compute stereo pairs. At the Centre of Ophthalmology and Visual Science of the University of Western Australia in Perth we have set up bench top prototype SLOs to study their imaging properties, to modify the optical arrangements, to carry out imaging experiments, and to perform pilot studies. Two modifications are of particular interest:
- Up to four illumination and detection channels can be operated independently and simultaneously. It is therefore possible to launch blue, green, and red lasers (which are combined using dichroic mirrors to form a "white" laser beam) into the SLO and to detect the reflected intensities of these three colours. As a result a "true" colour image if the retina can be acquired.
- 2. A pair of "toggling" mirrors was incorporated into the beam path between the scanning unit and the ophthalmic mirror. After each frame the toggling mirrors switch the entry position of the laser beam between the right and the left side of the pupil. As a result stereo pairs of the fundus can be acquired and displayed online. In this talk a short introduction to scanning laser ophthalmoscopy will given. The distinctive technical features of our setup will be emphasized. Human and animal fundus images will be presented to demonstrate the capabilities of our instrument.
Shared brainstem pathways for saccadic and smooth pursuit eye movements
Colloquium Speaker: Ed Keller, Associate Director, The Smith-Kettlewell Eye Research Institute
There has been a long tradition to divide the oculomotor system into several subsystems. In particular, it has been believed that saccades and smooth pursuits are produced by different brainstem pathways. According to this notion saccades were produced by the saccadic burst generator in the paramedian pontine reticular formation while pursuit was generated by cerebellar/vestibular nucleus pathways. These separate pathways come together at the level of the motoneurons, which are well known to be shared. Krauzlis and colleagues (Science, 1997) challenged this traditional view when they showed that some neurons in the superior colliculus (SC) send a common signal specifying motor error without specifying which subsystem, the saccadic or pursuit, will correct the error. Since that time, we have reexamined some of the neurons in the saccadic burst generator, thought to be previously involved only in saccadic responses, to determine to what level in the brainstem the shared circuitry for pursuit and saccades seen in the SC extends. We have reconfirmed our previous finding in the monkey that the SC does not project directly to excitatory burst neurons (EBNs) in the burst generator, but does have monosynaptic connections to many long lead burst neurons (LLBNs) intermixed anatomically with EBNs. More recently we have shown that another class of neuron in the burst generator called omnipause neurons (OPNs) also participate in pursuit eye movements as well as in saccadic movements. Finally, we find that some LLBNs, identified to discharge during saccadic eye movements, also show sustained periods of activity during pursuit eye movements. We conclude that present models of the brainstem oculomotor pathways will have to be revised to include shared elements for both pursuit and saccades.
Optical engineering considerations when imaging living tissues
CVS Research Talk: Jim Zavislan, Associate Professor, Institute of Optics
Starting in the early 1990's confocal imaging systems have been developed to provide reflectance imaging of in-vivo or freshly excised tissue. These optimized systems allow for cellular resolution images to depths of at least 100 micrometers and often deeper. These systems provided a "window" to analyze the native structure of in-vivo or freshly excised. Clinical applications of this technology include clinical screening of lesions and adequacy of excision during surgery. I will describe the optics used in these imaging systems and the optical engineering considerations of their design. I will also discuss images from clinical applications.
Slowly reverberatory cortical microcircuits: working memory and decision-making
CVS Colloquium: Xiao-Jing Wang, Department of Physics and Center for Complex Systems, Brandeis University, Waltham MA
I will present a summary of recent experimental and computational work on the cellular and synaptic mechanisms of working memory in the cortex, with an emphasis on continuous attractor models for memory networks that encode and store an analog stimulus feature. Then, I will show that a recurrent network endowed with persistent activity is capable of integrating stimuli over time, and subserves perceptual decision-making such as in the visual motion discrimination experiment a la Newsome.
Anterior segment morphometry using optical coherence tomography (OCT)
CVS Research Talk: Jay Wang, Centre for Contact Lens Research, University of Waterloo
OCT is a non invasive imaging technique that can recreate a high resolution cross-sectional image of the anterior segment of the eye. In the talk, OCT measurements of topographical corneal and epithelial thickness and tear film will be demonstrated. The results of corneal thickness change after soft and hard lenses wear will be presented. Also I will report pre-corneal and pre- and post-lens tear film thickness measured with OCT.
CVS Research Talk: Hany Farid, Department of Computer Science and Center for Cognitive Neuroscience, Dartmouth College
It has been hypothesized that the human visual system can use temporal synchrony to bind image regions into unified objects, as proposed in some neural models. We present experimental results from a new dynamic stimulus suggesting that previous evidence for this hypothesis can be explained with the well-established mechanisms of early visual processing, thus obviating the need to posit new synchrony sensitive grouping mechanisms or processes.
Contrast conservation in human vision
CVS Research Talk: Jozsef Fiser, (in collaboration with Bex, P. J., and Makous, W. L.), U. of Rochester, Rochester NY
We studied the temporal and spatial characteristics of contrast perception with briefly presented suprathreshold gratings, plaids, noise, and natural scenes that changed suddenly halfway through their presentation. These component stimuli were of fixed contrast and variable duration, and observers matched them to static stimuli of variable contrast and fixed duration, in a 2-AFC paradigm. As duration increased, the matching contrast of the changing stimuli approached an asymptote. When the apparent contrasts of the component stimuli equaled their physical contrast (e. g., gratings), the asymptotic matching contrast equaled the sum of the two physical contrasts. When the apparent contrast of a stimulus differed from its physical contrast, e. g., plaids (Georgeson and Shackleton, 1994), the asymptotic matching contrast equaled the sum of the apparent contrasts, not that of the physical contrasts. However, unlike thresholds, these matches were unaffected by changes of orientation (90°) or phase reversal, in the case of gratings; or by substitution of an entirely new stimulus of the same contrast, in case of noise and natural scenes. Thus the visual system conserves contrast information from temporally contiguous suprathreshold images. These results require independent processing of shape and contrast information.
CVS Research Talk: Krystel Huxlin, Ophthalmology, U. of Rochester, Rochester NY, Visual recovery after extrastriate lesion in the adult—role of visual retraining and possible neural substrates
Functional MRI in monkeys: imaging, connectivity, and electrophysiology investigations using a high-field scanner
CVS Colloquium Speaker: Nikos Logothetis, Managing Director, Max-Planck Institute for Biological Cybernetics, Tuebingen Germany
Since its early development in the late 40's Nuclear Magnetic Resonance (NMR) has become a powerful analytical tool for the investigation of the atomic nucleus and its environment, lending itself to applications ranging from chemical analysis or study of structures in solids to biomedical investigations. In the early 90's the potential of this technique for functional brain mapping was demonstrated; a fact that caused a great deal of excitement in both basic and clinical neuroscience. It was shown that by using the appropriate pulse sequences the NMR (or simply MR) imaging technique can be actually made sensitive to local magnetic susceptibility alterations produced by changes in the concentration of deoxyhemoglobin in venous blood vessels. This blood oxygenation level dependent (BOLD) contrast mechanism was successfully implemented in awake human subjects as well as in small animals such as rats and cats. In the first part of my talk I shall briefly describe some applications of spatially resolved fMRI in monkeys, including imaging with implanted RF coils. Such studies, in which voxels may contain as few as 600-800 cortical neurons, can help us understand how neural networks are organized, and how small cell assemblies contribute into the activation patterns revealed in fMRI. In the second part, I'll described experiments in which we simultaneously traced manganese chloride and wheat-germ-agglutinin conjugated to horseradish peroxidase (WGA-HRP) to evaluate the specificity of the former by tracing the neuronal connections of the basal ganglia of the monkey. By showing the sequential transport of Mn2+ from striatum to pallidum-substantia nigra and then to thalamus, we demonstrated MRI visualization of transport across at least two synapses in the CNS of the primate. Finally, in the last part, I shall present the first results regarding the neural basis of the BOLD signal. We have recorded local field potentials (LFPs), single, and multi unit activity (SUA, MUA) in the visual cortex of anesthetized monkeys, simultaneously with the collection of T2* weighted images. Our findings showed that visual stimulation causes a significantly stronger increase in the local field potentials (LFPs) than in the multiple unit activity (MUA), and that the linear transform model predicts the measured fMRI responses well, often explaining more than 90% of the variance in the fMRI signal. LFPs were better predictors than MUA. LFPs represent slow waveforms, including synaptic potentials, afterpotentials of somato-dendritic spikes, and voltage-gated membrane oscillations, that reflect the input of a given cortical areas as well as its local intracortical processing, including the activity of excitatory and inhibitory interneurons. MUA mostly represents the spiking of neurons, with single-unit recordings mainly reporting on the activity of the projection neurons that form the exclusive output of a cortical area. Thus, the fMRI signal is better correlated with the incoming input and the local processing in a given area rather than the spiking activity. This conclusion was supported by the additional observation that response adaptation - which may decouple the activity of projection neurons from that of interneurons - does not alter the BOLD response. Results from neurotransmitter injection during combined electrophysiology and fMRI experiments will be presented and discussed.
CVS Research Talk: Bruno Averbeck, U. of Rochester, Rochester NY, Neural noise and the code for target selection in the SMA
Probability matching in rhesus monkeys: a behavioral and neurophysiological analysis
CVS Colloquium Speaker: William T. Newsome, Howard Hughes Medical Institute and Department of Neurobiology, Stanford University School of Medicine
Psychophysicists and sensory physiologists generally approach the cognitive operation of decision-making in terms of the sensory stimulus. Psychologists and economists, however, have long known that decision-making is influenced not only by the sensory stimulus, but also by an organism's prior experience or beliefs concerning the "value" of the alternative choices, expressed in terms of likely positive or aversive consequences. Brain circuitry that mediates decision-making must presumably reflect both influences, and we have recently been able to demonstrate both effects at the behavioral and neurophysiological levels. To measure "subjective value" objectively, we have developed a probability matching paradigm for rhesus monkeys in which the animal's valuation is revealed through the proportion of choices allocated to alternative choices. In neurophysiological recordings, we have found that neurons in premotor areas of the brain exhibit characteristics one would expect of decision-making neural circuitry, including both sensory and "subjective value" effects. Our results to date suggest that signals from multiple sources within the brain converge onto "premotor" neurons to render simple behavioral decisions.
Variability in L:M ratio and genetic variability in the L/M cone pigment genes
CVS Research Talk: Joseph Carroll, Medical College of Wisconsin
The presence of three distinct class of photopigments, sensitive to the short- (S), middle- (M), and long- (L) wavelengths, provides the basis for trichromatic color vision. The behavior of the human photopigments is best described by their spectral sensitivity, i.e., the ability to absorb light as a function of wavelength. A novel technique was developed that gives accurate and highly reliable measurements of spectral sensitivity. Experiments were done to investigate spectral sensitivity functions of normal individuals, and they revealed enormous variation in the relative numbers of L and M cones in the normal retina. Furthermore, it appears that this variation is controlled by cis-acting elements within the L/M gene array—genetic variation in the L/M gene array would subserve the variability in L:M ratio. Accordingly, we find an enormous degree of variability in the L and M cone pigment genes. A detailed analysis of the genetic variation in the L and M pigments among color normals and individuals with color vision defects indicates that L/M gene variation is directly related to the presence of color vision defects. A model is presented that explains this relationship, and accounts for well-documented differences in the occurrence of color vision defects and L/M gene variation among different populations.
CVS Research Talk: Daphne Bavelier, The role of experience on visual skills: the case of deafness and video game playing
CVS Research Talk: Jim Fienup, U. of Rochester, Institute of Optics, Rochester NY, Phase retrieval and image reconstruction