Karen Dobkins - US grants

The ability to perceive visual motion is one of the most fundamental and essential facets of vision. While much has been learned over the years about the psychophysics and neurophysiology of motion processing in adults, little is known about its development in infants. The long-term objective of this research is to characterize the development of visual motion perception in human infants, and to understand how underlying neural mechanisms can account for the progression from an immature to an adult-like state. To this end, visual psychophysical experiments are conducted in infants 1-6 months of age, and the results are modeled in terms of known or hypothetical neural mechanisms. Data are collected from infants using simple observational techniques that rely on the fact that infants preferentially state at a patterned stimulus rather than a blank field and that infants exhibit directionally-appropriate eye movements in response to moving targets. Together, we use these techniques to ask questions regarding the development of 1) direction and speed discrimination 2) motion integration across visual space and 3) chromatic (red/green) input to motion processing. The study of infant motion processing is particularly appealing as much is known about the neural basis of motion processing in adults. Thus, discovering the time course of development for different aspects of motion processing will improve our understanding of the neural development of specific visual areas known to be involved in motion processing. From the clinical standpoint, assessment of motion processing capacities could potentially be used to diagnose damage to motion processing areas during development. For example, there are recent claims that the reading disorder "dyslexia" is correlated with damage to specific motion-related areas of the brain. In virtue of such findings, it is quite possible that early detection of dyslexia could be aided by simple tests of motion processing capabilities. In addition, development of motion mechanisms may be particularly susceptible to environmental factors as suggested from studies (in animals) demonstrating abnormal development of motion processing as a result of altered early visual experience. Thus, assessment of the normal development of visual functions, such as motion processing, is likely to play an important role in clinical diagnosis and in monitoring the effects of treatment in infants and children with visual disabilities.

This project investigates the perceptual consequences of altered sensory input early in development, by studying visual perception in deaf adults who have been auditorily deprived since birth and who have acquired a visual language (American Sign Language, ASL) for communication. It has long been thought (mostly through anecdotal evidence) that the deaf `see` better (and that the blind `hear` better); however, only a handful of studies have attempted to characterize systematically the visual capacity of deaf signers. To investigate this issue, deaf and hearing subjects will be tested on a variety of visual tasks. In particular, visual motion processing will be assessed for several reasons. One, motion is a fundamental aspect of visual processing and much is known about its neural basis. Two, results from animal studies suggest that the motion system may be especially susceptible to changes following altered sensory input. Three, motion of the hands is an integral part of the acquisition and comprehension of ASL, and thus there is reason to believe that the increased reliance on such motion cues may enhance and/or alter motion perception in the deaf. Visual perceptual experiments will involve testing various dimensions of motion (and other visual) processing capabilities, in order to elucidate which specific aspects of visual processing are altered in the deaf. Once the types of visual stimuli/tasks yielding the greatest perceptual differences between hearing and deaf subjects have been determined, human brain imaging techniques (such as functional Magnetic Resonance Imaging or Magnetic Source Imaging) will be employed to localize neural areas or structures underlying the perceptual differences. In addition, brain imaging studies may reveal differences across specific brain areas in susceptibility to, and ability to compensate for, early sensory deprivation. These experiments will advance our knowledge regarding the degree to which developing sensory areas of the brain can reorganize themselves in response to altered sensory input, with implications for principles of visual development in general. Moreover, the experiments should shed light on the processing levels at which neural responsivity and connectivity are influenced by input from the sensory environment. The results may also be useful in designing compensatory programs for sensory-deprived persons, who could be trained to exploit those aspects of sensory processing that are most adaptive in response to altered early sensory input.

Consider creating (a) a computer system to help physicians make a diagnosis using all of a patient's medical data and images along with millions of case histories; (b) intelligent buildings and cars that are aware of their occupants activities; (c) personal digital assistants that watch and learn your habits -- not only gathering information from the web but recalling where you had left your keys; or (d) a computer tutor that watches a child as she performs a science experiment. Each of these scenarios requires machines that can see and learn, and while there have been tremendous advances in computer vision and computational learning, current computer vision and learning systems for many applications (such as face recognition) are still inferior to the visual and learning capabilities of a toddler. Meanwhile, great strides in understanding visual recognition and learning in humans have been made with psychophysical and neurophysiological experiments. The intellectual merit of this proposal is its focus on creating novel interactions between the four areas of: computer and human vision, and human and machine learning. We believe these areas are intimately intertwined, and that the synergy of their simultaneous study will lead to breakthroughs in all four domains.

Our goal in this IGERT is therefore to train a new generation of scientists and engineers who are as versed in the mathematical and physical foundations of computer vision and computational learning as they are in the biological and psychological basis of natural vision and learning. On the one hand, students will be trained to propose a computational model for some aspect of biological vision and then design experiments (fMRI, single cell recordings, psychophysics) to validate this model. On the other hand, they will be ready to expand the frontiers of learning theory and embed the resulting techniques in real-world machine vision applications. The broader impact of this program will be the development of a generation of scholars who will bring new tools to bear upon fundamental problems in human and computer vision, and human and machine learning.

We will develop a new curriculum that introduces new cross-disciplinary courses to complement the current offerings. In addition, students accepted to the program will go through a two-week boot camp, before classes start, where they will receive intensive training in machine learning and vision using MatLab, perceptual psychophysics, and brain imaging. We will balance on-campus training with summer internships in industry.

IGERT is an NSF-wide program intended to meet the challenges of educating U.S. Ph.D. scientists and engineers with the interdisciplinary background, deep knowledge in a chosen discipline, and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to catalyze a cultural change in graduate education by establishing innovative new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries. In this sixth year of the program, awards are being made to institutions for programs that collectively span the areas of science and engineering supported by NSF

With National Science Foundation support, Dr. Dobkins and colleagues will conduct a three-year study to investigate the perceptual and neural consequences of early-onset sensory deprivation. The study of deaf individuals, who have been auditorily deprived since birth and who rely upon a visual language (i.e., American Sign Language, ASL) for communication, affords a unique opportunity to investigate how and the degree to which sensory processing within the remaining senses (specifically vision) is modified as a result of altered sensory experience. It has long been thought (mostly through anecdotal evidence) that the deaf "see" better (and that the blind "hear" better). However, owing to the difficult nature of communication between hearing researchers and deaf subjects (who speak different languages and are part of different cultures), surprisingly little is known about visual processing in the deaf. To investigate this issue, we use both psychophysical techniques (i.e., asking subjects to report about stimuli presented to them on a video monitor, e.g., "did the stimulus move up or down?") and brain imaging techniques (which localize and measure neural activity elicited by visual stimuli) to characterize differences in visual processing between deaf and hearing subjects. In our prior NSF studies, we focused on visual motion processing, with the notion that motion may be particularly important to deaf subjects, since 1) ASL comprehension relies heavily on the motion of the hands and 2) in the absence of auditory cues, deaf subjects may rely on motion in their periphery to help orient them to objects entering their visual field. The results of these studies revealed a robust right visual field / left hemisphere dominance for motion processing in deaf signers, which can potentially be accounted for by proposing that perceptual processes required for the comprehension of language (motion processing in the case of ASL) get recruited by the left, language-dominant hemisphere. In the current proposal, we expand on these findings by testing deaf and hearing subjects on motion processing, as well as two other domains of vision, namely color and form processing. In addition, as an extension of our previous attentional studies, we will investigate whether attentional resources differ between deaf and hearing subjects, particularly in the peripheral visual fields. Finally, in combination with these visual studies, we will conduct linguistic studies that examine the degree to which language is lateralized to the left hemisphere within individual subjects. This will allow us to investigate further the proposed link between the deaf's visual and linguistic experience. The intellectual merits of this proposed activity include advancing our knowledge of how developing sensory areas of the brain reorganize themselves in response to altered sensory input, which should have implications for principles of brain development in general. From the clinical standpoint, the results may be useful in designing compensatory programs for auditorily-deprived persons, who could be trained to exploit those aspects of sensory processing that are most adaptive in response to altered sensory input. Moreover, with the frequency of cochlear implants on the rise, our findings may be helpful in designing special features for these prosthetic devices in deaf individuals.
The broader impacts of these projects include a strong outreach component; by their very nature, they include people from an underrepresented group (i.e., deaf people) as subjects. They also attract deaf people to be trained as researchers in our laboratory. Finally, in addition to reaching a broad audience (including researchers in the fields of psychophysics, neuroscience, development and linguistics) through conferences and journal publications, the results of these projects are brought to both undergraduate and graduate students at UC San Diego through the PI's teaching of courses such as "Sensation and Perception" and "Physiological Psychology".

DESCRIPTION (provided by applicant): The ability to perceive visual motion is one of the most fundamental and essential facets of vision. While much has been learned over the years about the psychophysics and neurophysiology of motion processing in adults, little is known about its development in infants. The long-term objective of this research is to characterize the development of visual motion perception in human infants, and to understand how underlying neural mechanisms can account for the progression from an immature to an adult-like state. To this end, visual psychophysical experiments are conducted in infants 1-5 months of age, and the results are modeled in terms of known or hypothetical neural mechanisms. Data are collected from infants using simple observational techniques that rely on the fact that infants preferentially stare at a patterned stimulus rather than a blank field and that infants exhibit directionally appropriate eye movements in response to moving targets. Together, we use these techniques to ask questions regarding the development of: (1) direction and speed discrimination; (2) motion integration across visual space; (3) chromatic (red/green) input to motion processing; and 4) contextual effects on motion processing. The study of infant motion processing is particularly appealing as much is known about the neural basis of motion processing in adults. Thus, discovering the time course of development for different aspects of motion processing will improve our understanding of the neural development of specific visual areas known to be involved in motion processing. From the clinical standpoint, assessment of motion processing capacities could potentially be used to diagnose damage to motion processing areas during development. For example, there is recent evidence that dyslexia (e.g., Livingstone et al., 1991; Galaburda & Livingstone, 1993; Demb et al., 1997; 1998), autism (Spencer, et al., 2000; Gepner & Mestre, 2002; Blake et al., 2003) and Williams Syndrome (Atkinson et al., 1997) are associated with damage to motion-related areas of the brain. In virtue of such findings, it is quite possible that early detection of these disorders could be aided by simple tests of motion processing capabilities. Thus, assessment of the normal development of visual functions, such as motion processing, is likely to play an important role in clinical diagnosis and in monitoring the effects of treatment in infants and children with visual disabilities.

[unreadable] DESCRIPTION (provided by applicant): Autism spectrum disorders (ASD) are pervasive developmental disorders characterized by abnormalities in a variety of social, communicative, and emotional behaviors, which occur in 0.67 percent of the population (Centers for Disease Control and Prevention, February 2007 report). Because ASD is not diagnosed reliably before the second or third year of life, the best way to investigate development of the disorder involves studying infant siblings of children with ASD (High-Risk infants), who have a significantly increased risk (10- to 20-fold) of developing ASD. Although only a minority (~9 percent) of High-Risk infants is predicted to ultimately develop ASD, the remaining ~91 percent can nonetheless be expected to exhibit symptoms of the broader autism phenotype (i.e., sub-clinical atypicalities that are seen in the relatives of individuals with ASD). The current proposal studies High-Risk infants from ages 6 to 36 months, tracking their development in comparison to control infants to look for abnormalities associated with ASD. Taking a neuro-developmental approach and employing a variety of techniques, the proposal tests hypotheses regarding specific brain areas/systems we believe may be abnormal early in the development of ASD, as follows: 1) At 6 months, we test the possibility of abnormal processing within the Magnocellular subcortical visual pathway, by using perceptual techniques to assess M pathway function (vs. Parvocellular pathway function as a control). 2) At 7 months, we test the possibility of abnormal motion processing within the dorsal cortical pathway, by measuring perceptual responses to biological motion stimuli (vs. form stimuli as a control). 3) At 7 and 10 months, we test the possibility of abnormal face processing within the ventral cortical pathway, by measuring perceptual responses and event related potentials (ERPs) elicited by face stimuli (vs. object stimuli as a control), as well as positive vs. negative facial expressions of emotion. 4) At 18 months, we use behavioral and ERP methods to test for abnormalities in social/emotional processing, which is likely to involve the amygdala and prefrontal cortex. 5) Over the course of the study, several standardized tests are administered to assess social, communicative, and cognitive skills, including those that are used to diagnose ASD. We have great hope that these studies will shed light on the neuro-developmental origins of ASD (and the broader autism phenotype), and aid in early diagnosis of the disorder. Autism spectrum disorders (ASD) are developmental disorders characterized by differences in a variety of social, communicative, and emotional behaviors, which occur in 0.67 percent of the population. Because ASD is not diagnosed reliably before the second or third year of life, the only current way to study development of the disorder involves working with infant siblings of children with ASD, who have a significantly increased risk (i.e., 10- to 20-fold) for developing ASD. Our laboratory group works with these infants from ages 6 to 36 months, tracking their development to look for atypicalities that may be early signs of ASD, which we believe will shed light on how ASD develops, as well as aid in early diagnosis of the disorder. [unreadable] [unreadable] [unreadable]

[unreadable] Description (provided by applicant): The degree to which visual development is governed by "nature" vs. "nurture" has been a long-standing topic in vision research. Although much has been learned from animal studies in the last 50 years, relatively little is known about the factors influencing visual development in humans. The current proposal investigates whether factors related to visual experience ("nurture") vs. preprogrammed biological maturation ("nature"), or both, are important in shaping visual development. To this end, we propose visual psychophysical studies with four different subject populations that tease apart these factors. (A) Fullterm Infants and (B) Healthy Preterm Infants. If early visual experience is the dominant force in visual development, preterm infants should show the same developmental trajectories as fullterm infants when plotted in terms of postnatal age (i.e. age since birth). By contrast, if biological maturation is more influential, preterm infants should match fullterm babies when plotted in postconceptional age (i.e., age since conception). (C) Monozygotic vs. Dizygotic Twins. While both twin types share the same environment and parents, they differ in the degree of shared genetic makeup. We apply a biometrical twin model that can identify the proportion of "phenotypic" variance in visual performance that can be accounted for by shared environment versus genes. (D) Infants and Children with Early Abnormal Visual Input. Comparisons made between this group (cataract, strabismus, and anisometropia) and healthy controls will address the vulnerability of various aspects of visual processing to abnormal visual experience early in development. Three aims address different levels of visual processing: 1) Subcortical Pathway Processing: We ask if the three main retinogeniculate pathways, Magnocellular (M), Parvocellular (P) and Koniocellular (K), are equally or differentially affected by visual experience, by obtaining contrast sensitivities for luminance, red/green and blue/yellow stimuli, thought to be mediated by these pathways, respectively. 2) Subcortical Input to Cortical Motion Processing: We will obtain an estimate of the extent of P vs. M subcortical pathway input to motion processing using a "Motion/Detection" threshold ratio paradigm that measures the relative effects of chromatic (P pathway) vs. luminance (M pathway) contrast on motion processing. Previous results from our laboratory suggest that the relative P vs. M input to motion decreases with age, and here we will ask whether this re-weighting process is influenced more by visual experience or biological maturation. 3) Cortical Motion Processing: We will assess global motion processing, which is believed to be a higher-level cortical function. Unlike many previous studies, our global motion stimuli will be scaled to detectability for each subject, such that differences observed across ages/subject groups can be more definitively interpreted. The results of these projects, which will reveal what aspects of visual development are more vs. less amenable to effects of visual experience, may have important implications for treating children with congenital eye disorders. PUBLIC HEALTH RELEVANCE The degree to which visual development is governed by "nature" (i.e., pre-programmed biological maturation) vs. "nurture" (i.e., visual experience) has been a long-standing topic in vision research. The current proposal investigates this question by conducting infant visual psychophysical studies in subject populations that bear relevance: preterm infants, twin infants and infants born with congenital eye disorders. The results of these studies, which we hope will reveal what aspects of visual development are more vs. less amenable to effects of visual experience, may have important implications for treating children with visual disorders. [unreadable] [unreadable] [unreadable]

Background: Although there is general consensus of greater prevalence of GI distress in individuals with Autism Spectrum Disorders (ASD), the nature of the link is unknown. There is preliminary evidence to suggest that GI distress in ASD may be associated with Leaky-Gut (i.e. increased permeability of the intestinal mucosal barrier due to either delayed or abnormal development), as shown by a study showing higher-than-normal prevalence in ASD children 4 - 16 years of age (e.g., D'Eufemia et al., 1996). During normal digestion, the mucosal barrier is responsible for keeping digestive enzymes out of the intestinal wall. Our recent evidence shows that if these powerful degrading enzymes enter the wall of the intestine, they will cause major damage to the intestinal wall as well as central inflammation. Delayed sealing or dysfunction of the mucosal barrier during postnatal development could allow digestive enzymes in the intestinal lumen to move into the intestinal wall, degrade the intestinal wall itself (referred to as auto-digestion), and in turn, lead to inflammatory responses and GI distress. Additionally, dysfunctional development of the barrier system could lead to pancreatic enzymes and inflammatory mediators entering the bloodstream, where their presence could have far-reaching degrading effects. Objective/Hypothesis: We hypothesize that ASD may be associated with Leaky-Gut early in development, which combines, or interacts, with diet (breast-milk, formula, solid foods) to produce auto-digestion and inflammation in: 1) the intestine, which could explain the GI distress, and 2) in the bloodstream, which could reach and damage the developing brain, thus contributing to the onset of ASD itself. Specific Aims: To test our hypotheses, the current proposal is designed to track key aspects of GI function in High-Risk infants, i.e., infants who have an older sibling diagnosed with ASD: 1) signs of Leaky-Gut, 2) symptoms of GI distress (e.g., diarrhea, reflux, constipation), 3) diet (breast-milk vs. formula), 4) evidence of digestive enzymes and inflammatory markers of cell death in the bloodstream. These High-Risk infants have a 10- to 20-fold greater chance of developing ASD than the general population, and tracking early development in this cohort is an ideal way to catch the culprit in ASD. Study Design: The study is designed to collect urine samples from High-Risk infants (and for comparison, from Low-Risk controls, defined as infants from families without ASD history) at multiple time points in the first two years and urine and blood samples before and after transition from breast milk to formula feeding. The urine samples are used for a direct test of Leaky-Gut. The plasma samples will be assayed for evidence of digestive enzymes and inflammatory mediators. GI Symptomatology will be tracked via parent questionnaires. Diet history questionnaires/logs will monitor use of breast-milk vs. formula-milk. As part of our protocol already in place, we will administer early detection cognitive, visual, and behavioral tests as well as the ADOS/ADI at two and three years of age to determine whether an infant develops ASD.

Deaf individuals must rely more than hearing individuals on visual information to understand what is happening in the world around them. As a result, the brains of deaf people typically reorganize to help them make better use of the available visual information. The questions addressed by this research project are whether and how greater reliance on visual information actually changes visual experiences. The project also investigates how differences between hearing and deaf people's visual processing develop across infancy, childhood, and adulthood.

There is evidence that aspects of vision are altered or enhanced in deaf people, providing evidence for plasticity of the human brain to compensate for the absence of sound. Yet, very little is known about how these alterations emerge during development. This project investigates the consequences of altered early sensory experience during development, measuring perceptual sensitivity to motion, form, faces, and objects. Deaf people may have altered processing of these aspects of vision for two reasons. First, lack of auditory input compels deaf people to rely more on their intact visual modality, and, second, many deaf people use a visual language (American Sign Language, ASL), which may enhance certain aspects of visual processing that convey critical linguistic information. To tease apart effects of deafness versus ASL language experience, the studies will compare visual sensitivity in Deaf and Hearing individuals who are either Signers or Nonsigners. Also, effects of deafness could occur during an early critical period rather than due to accumulated altered sensory experiences across the lifespan. To address this possibility, the project will also involve studying a group of "Hearing Restored" children who received cochlear implants around 12-18 months, following a period of auditory deprivation starting at birth. Results from these studies will reveal how sensory systems adjust to altered input and elucidate mechanisms of brain plasticity, which may have widespread implications for deaf and blind individuals, as well as for those who lose their hearing or sight later in life.

? DESCRIPTION (provided by applicant): While many studies have shown that vision is altered and/or enhanced in deaf people, it is not known how this develops. The current proposal is the first to study visual development in deaf people from infancy to adulthood, as well as in hearing restored (HR) children who received cochlear implants (CIs) by 18 months, a cohort that is increasingly on the rise. In Aim 1, we measure different visual abilities (including motion, form, face and object perception) in deaf and hearing infants (6 - 10 months), children (6 - 10 years) and adults, using comparable stimuli/paradigms across ages. Many deaf people use a visual language, American Sign Language (ASL), and thus to tease apart whether altered vision in deaf signers is due to deafness or to experience with ASL, we test a third control group of hearing signers, who were born to deaf signing parents and have roughly the same ASL experience as deaf people who also learned ASL early. In infants, we test these same three analogous groups (sign-exposed deaf infants, non-sign-exposed hearing infants, and sign-exposed hearing infants), as well as an additional control group, i.e., non-sign-exposed deaf infants. To test the effects of ASL further, we ask whether the degree of altered vision correlates with receptive ASL proficiency, as measured with standardized ASL tests. By understanding the developmental trajectory of altered vision due to deafness vs. ASL, we hope to elucidate mechanisms of developmental plasticity. Aim 2 asks whether there is an early critical period for the effects of deafness on visual perception, by investigating whether altered vision persists in HR children. We also measure receptive spoken language proficiency in HR children, which allows us to ask by when in development must auditory input be restored for auditory and speech processing to develop normally. This aim also addresses a growing concern in the CI field that altered early vision in deaf people may hinder the efficacy of the CI. Here, the idea is that if deafness leads to functional reallocation of auditory cortex for visual processing, this might prevent the auditory cortex from being properly stimulated by CIs. If this is true, we expect to find that HR individuals with the most altered vision will show the worse proficiency in receptive spoken language. The current proposal will be the first to test this maladaptive hypothesis early in development, and the results should have implications for optimizing best long-term language outcomes in CI children.