David J. Heeger - US grants

In order to diagnose and cure central visual losses (e.g., in a patient who is unable to properly perceive visual motion) we must first gain an understanding of the neural processing in visual cortex. The long-term goal of this research is to develop a detailed, quantitative, predictive model of cell function in primary visual cortex. We will have succeeded when/if we can record from a cell while presenting a fixed set of visual stimuli (to measure model parameters), and then be able to predict the cell's response to any visual stimulus. The computational/theoretical research proposed in this application is designed to complement empirical research by clarifying the interpretation of experimental results and by making a number of empirically testable predictions thereby suggesting new experiments. Specifically, we aim to: (1) Reconcile the controversy regarding the origin of selectivity of simple and complex cells; (2) Reconcile the controversy over the role of intracortical (e.g., cross-orientation) suppression; (3) Explain the variability, from cell to cell, of contrast-response data.

DESCRIPTION (provided by applicant): Over the past few years, we have come to learn that early visual cortex does not act as a passive image processing machine simply devoted to representing bottom up sensory signals. Rather, the bottom-up sensory signals in visual cortex interact with strong top-down signals related to attention and working memory, so that the neural substrates of visual perception involve recurrent interactions among early visual areas including primary visual cortex (V1) and a number of widely separated cortical areas in the temporal parietal and frontal lobes. The proposed experiments aim to measure the neuronal correlates of perception, attention, and working memory, and then to characterize how these three processes interact to drive perceptual decisions. Aim 1 will use a combination of psychophysics, functional magnetic resonance imaging (fMRI), and evoked potentials to measure and characterize the activity in early visual cortex that is correlated with perception during a visual detection task, and to test the hypothesis that this precept-related activity derives from a combination of bottom-up and top-down signals. Aim 2 will use psychophysics (contrast detection) and fMRI to study the neuronal correlates of attention in early visual cortex, first to test the hypothesis that the attentional signals in early visual cortex are involved in the maintenance of sustained attention, and second to test the hypothesis that trial-to-trial correlation between performance and cortical activity is driven by trial-to-trial variability in uncertainty. Aim 3 will use psychophysics (threshold-difficulty contrast and spatial frequency discrimination tasks that involve comparing two stimuli that ate separated in time by a delay period) and fMRI to test the hypothesis that early visual cortex plays a role in visual working memory. We will explore two alternative possible roles for early visual cortex in working memory. First, early visual areas might exhibit sustained delay-period activity implying that visual cortex is involved in holding the memory itself. Second, if these areas do not exhibit sustained delay period activity, they may nonetheless be reactivated at the end of the delay period, suggesting that they are involved in comparing the incoming sensory signals with the memory of a previously presented stimulus. Although these experiments will focus on understanding visual processing n subjects with normal vision, the knowledge gained about the function of human visual cortex and the experimental protocols that will be developed will both be directly applicable to the study of visual deficits including amblyopia.

Work has focused during the past year on a number of fast imaging applications for body imaging. There has been a strong emphasis on the improvement of the so-called comprehensive cardiac exam. Magnetic resonance imaging has the potential of providing information about the heart unparalleled by any other exam. Current workups for cardiac disease usually require multiple tests, some of which are invasive. These tests include echocardiography, coronary angiography and radionuclide imaging, with and without stress. In order for MRI to provide the comprehensive cardiac exam, it must be able to characterize myocardial function and myocardial perfusion and identify coronary artery diseases. In the past, MR techniques were available for each of these tasks, but usually not in a fashion that they could all be performed in sequence at one sitting. Recent advances in fast imaging and the coupling of these capabilities with new novel intravascular contrast agents has allowed all of the elements for the comprehensive cardiac exam to meet this requirement. Myocardial perfusion is obtained in a first pass multi-slice study where transit of contrast through the myocardium can visualize areas of decreased myocardial perfusion. At equilibrium, these intravascular contrast agents allow fast 3D cine images to evaluate the entire heart with attention to myocardial function and motion to be evaluated in approximately 3-5 min. Because of the intravascular nature of this contrast agent, the relative contrast remains constant over a reasonable period of time allowing coronary artery imaging to be performed with high contrast. Our work will continue to take advantage of the improvements in scanner performance coupled with contrast agents to provide unique non-invasive data about the cardiovascular system.

DESCRIPTION (provided by applicant): Many of the most important achievements over the last decade in Neuroscience have been dependent on the development of new empirical methods, driven by interdisciplinary collaborations. Of particular significance has been the development and application of techniques for imaging brain structure and function. We propose to hold a conference on "Imaging the Brain: Neurons, Networks and Behavior" at New York University on September 5-7, 2003. This conference will focus on how the use of brain imaging techniques is leading to a deeper understanding of human behavior, perception, cognition, and emotion in terms of the detailed biophysical, cellular, and molecular mechanisms of brain function. The conference will include a diverse group of research presentations on the use of imaging to study the brain at scales ranging from cortical systems to synapses. We propose to have an opening address by Marcus Raichle, following by four sessions: Functional organization of sensory systems, (Amiram Grinvald, David Van Essen, Brian Wandell, Leslie Ungerleider); Frontotemporal interactions in memory (Eleanor Maguire, Anthony Wagner, Mark D'Esposito, Randall Mclntosh); Activity-dependent functional connectivity (Karel Svoboda, Kimberley MacAIlister, Venkatesh Murthy, F Kimura); Technological innovations (Richard Buxton, Mark Schnitzer, Peter Basser, Russell Jacobs, Daniel Silverman, Wim Vanduffel). Each session will be followed by a panel discussion/debate. The conference will be advertised broadly in the neuroscience community, while focusing specifically on institutions on the east coast and the NYC area. Prior to the meeting dates, we will make available on the Internet a publication of each speaker's presentation, with included graphics. We also propose to videotape the talks and discussions/debates and make them available for viewing on the Internet. Past participants of the Summer Undergraduate Research Program, sponsored by the Center for Neural Science at NYU over the past 10 years, will be invited to attend this Symposium. Minorities and women who accept this invitation will be provided with a travel stipend.

DESCRIPTION (provided by applicant): Short-term maintenance of information is a fundamental aspect of human cognition that is compromised by a wide variety of mental health disorders including: Schizophrenia, ADHD, substance abuse disorders, Alzheimer's disease, Parkinson's disease, and AIDS related dementia. A deeper understanding of the basic neural mechanisms underlying short-term maintenance will lead to improved diagnostic, prognostic, and therapeutic procedures for these disorders. The proposed research will focus on three types of short-term maintenance: sensory attention, motor intention, and working memory. It is widely believed that sustained neural activity during a delay interval is the mechanism by which the brain performs these three cognitive processes. Posterior parietal cortex (PPC) has emerged as a particular focus for research on sustained delay-period activity related to attention, intention, and working memory. The proposed experiments will use fMRI to measure cortical activity in human subjects while they perform three closely related but complementary tasks that differ in their dependence on sensory attention, motor intention, and working memory. In the first task, subjects will perform an eye movement to a remembered location. In the second task, subjects will detect a luminance decrement at a cued location. In the third task, subjects will detect a small shift in the remembered location of a target. These three tasks place differential demands on intention, attention, and working memory. The first task emphasizes motor intention;in this task subjects will make eye movements to remembered locations whereas in the other two tasks they will have to accurately hold fixation. The second task emphasizes sensory attention;in this task subjects will attend to targets that are constantly illuminated whereas in the other two tasks they will remember the locations of targets that are no longer visible. The third task emphasizes spatial working memory;in this task subjects will remember the location of a target for later comparison whereas no spatial comparison is involved in the other two tasks. These three tasks will be used to achieve two central aims concerning the homology between human and monkey PPC and the functional role of human PPC in sensory attention, motor intention, and working memory. The first aim is to define each of several cortical areas, using experimental protocols that measure topographic representations of attention, intention, and working memory. The second aim is to test the hypothesis that these now pre-defined human cortical areas are functionally homologous to cortical areas in monkey PPC (particularly monkey area LIP), and to test the hypothesis that behavioral performance of each of the three tasks depends on the level of delay-period activity in these human cortical areas.

DESCRIPTION (provided by applicant): When the two eyes view dissimilar patterns, one experiences a perceptual phenomenon called binocular rivalry. Instead of seeing both patterns superimposed, they are perceived in alternation. What makes this phenomenon remarkable is the dissociation between a constant physical stimulation and fluctuating perceptual experience. Because of this dissociation, binocular rivalry presents an opportunity for studying visual awareness, one of the deepest mysteries facing biomedical science. In spite of widespread interest, and an impressive volume of high-quality work on this topic, many of the central questions concerning the neural processing underlying binocular rivalry remain open. Particularly controversial is the role of primary visual cortex (V1) in rivalry. To address this controversy, we propose to capitalize on an interesting aspect of the perceptual phenomenon; during an alternation, one sees a traveling wave in which the dominance of one pattern emerges locally and expands progressively as it renders the other pattern invisible. Our experiments are designed to measure and characterize the neural basis of these perceptual waves. The proposed experiments will apply a combination of empirical methods (psychophysics and fMRI in humans; optical imaging, electrophysiology, pharmacology, and electrical stimulation in the awake monkey) to explain this perceptual phenomenon in terms of the underlying neural mechanisms and to test the following hypotheses: (1) that competition between the two rival stimuli is implemented by neural circuits in primary visual cortex (V1), i.e., that neural circuits in V1 play a causal role in triggering transitions during rivalry; (2) that for the consequences of this neural competition to be perceived, activity must advance to higher visual areas; and (3) that attention, mediated by feedback from higher visual areas, plays a crucial role in promoting neural activity from V1 to higher visual areas. We will then be in a position to develop and refine a computational theory of the neural processing in V1 that supports these traveling waves, and a theory that elaborates the role of V1 in visual awareness. The neural competition underlying perceptual alternations during rivalry is believed to be closely related to the strabismic suppression. Hence, the proposed experiments will provide useful information and will establish novel experimental protocols that can, in future work; be applied to further our understanding of strabismus and amblyopia.

DESCRIPTION (provided by applicant): When the two eyes view dissimilar patterns, one experiences a perceptual phenomenon called binocular rivalry. Instead of seeing both patterns superimposed, they are perceived in alternation. What makes this phenomenon remarkable is the dissociation between a constant physical stimulation and fluctuating perceptual experience. Because of this dissociation, binocular rivalry presents an opportunity for studying visual awareness, one of the deepest mysteries facing biomedical science. In spite of widespread interest, and an impressive volume of high-quality work on this topic, many of the central questions concerning the neural processing underlying binocular rivalry remain open. Particularly controversial is the role of primary visual cortex (V1) in rivalry. To address this controversy, we propose to capitalize on an interesting aspect of the perceptual phenomenon; during an alternation, one sees a traveling wave in which the dominance of one pattern emerges locally and expands progressively as it renders the other pattern invisible. Our experiments are designed to measure and characterize the neural basis of these perceptual waves. The proposed experiments will apply a combination of empirical methods (psychophysics and fMRI in humans; optical imaging, electrophysiology, pharmacology, and electrical stimulation in the awake monkey) to explain this perceptual phenomenon in terms of the underlying neural mechanisms and to test the following hypotheses: (1) that competition between the two rival stimuli is implemented by neural circuits in primary visual cortex (V1), i.e., that neural circuits in V1 play a causal role in triggering transitions during rivalry; (2) that for the consequences of this neural competition to be perceived, activity must advance to higher visual areas; and (3) that attention, mediated by feedback from higher visual areas, plays a crucial role in promoting neural activity from V1 to higher visual areas. We will then be in a position to develop and refine a computational theory of the neural processing in V1 that supports these traveling waves, and a theory that elaborates the role of V1 in visual awareness. The neural competition underlying perceptual alternations during rivalry is believed to be closely related to the strabismic suppression. Hence, the proposed experiments will provide useful information and will establish novel experimental protocols that can, in future work; be applied to further our understanding of strabismus and amblyopia.

Some of the deepest mysteries facing science in the 21st century concern the higher functions of the central nervous system: perception, memory, attention, learning, language, emotion, personality, social interaction, decision-making, motor control, and consciousness. All psychiatric disorders (e.g., anxiety disorders and depression), neurological diseases (e.g., Parkinson's disease and Alzheimer's disease), and developmental disorders (e.g., dyslexia and autism) are characterized by dysfunction of the neural systems in the brain. In fact, all aspects of human behavior are controlled by the human brain. Functional magnetic resonance imaging (fMRI) has revolutionized neuroscience over the past decade. It is allowing a new era of research, complementary to more invasive techniques for measuring neuronal activity in animals, to explore the function and dysfunction of the human brain. FMRI uses an MRI scanner, like those that can be found in medical clinics and hospitals around the country, but reprogrammed to yield a picture of brain function as well as brain anatomy.

This award provides funds to permit New York University to acquire new instrumentation to upgrade an existing magnetic resonance imaging (MRI) scanner for basic-science brain imaging research. The new instrumentation will be incorporated into the facilities of the NYU Center for Brain Imaging (CBI), which is a shared research center that houses a Siemens Allegra 3 Tesla MRI scanner along with all of the ancillary equipment needed to perform fMRI research. CBI is located on the ground floor of the building that houses the Psychology, Neural Science, and Physics Departments. There are over 150 users of this facility (faculty, postdocs, graduate students, and lab techs) in 8 departments in the Faculty of Arts and Sciences (Psychology, Neural Science, Chemistry, Physics, Economics, Linguistics, English, Political Science), 3 departments in the School of Medicine (Neurology, Psychiatry, Radiology) and a department in the School of Education (Physical Therapy). The research is supported by over 25 federal research grants.

The new instrumentation will provide CBI users with improvements in the signal-to-noise ratio, spatial resolution, temporal resolution, and brain coverage that will enable experiments that are currently impossible or infeasible. Specifically, with the funding from this award CBI will purchase a new 8-channel receiver system and new RF coils. The RF coils act more or less like the antenna of an MRI scanner to "listen" to brain tissue and measure of brain activity. Increasing the number of channels allows for the use of more RF coils (more antennas) that improves the quality of the received signals.

. The new instrumentation will, therefore, greatly leverage the highly collaborative, multidisciplinary program of research, teaching, and training in the Center for Brain Imaging. Research training in CBI at the undergraduate, pre- and post-doctoral levels will be enhanced by the new instrumentation. Teaching will also be strengthened; the participating departments offer a series of courses at the undergraduate and graduate levels that will make use of the new instrumentation. The participating departments are committed to attracting women and under-represented groups at all levels. The proposed instrumentation will surely help in recruiting, because it will enable CBI (and the participating departments) to keep current with some of the latest advances in MRI and fMRI technology, and enable the research and training to be cutting edge, thereby increasing visibility. Finally, the instrumentation will contribute to the development of new interdisciplinary fields based on the technological advance of fMRI.

DESCRIPTION (provided by applicant): When the two eyes view dissimilar patterns, one experiences a perceptual phenomenon called binocular rivalry. Instead of seeing both patterns superimposed, they are perceived in alternation. What makes this phenomenon remarkable is the dissociation between a constant physical stimulation and fluctuating perceptual experience. Because of this dissociation, binocular rivalry presents an opportunity for studying visual awareness, one of the deepest mysteries facing biomedical science. In spite of widespread interest, and an impressive volume of high-quality work on this topic, many of the central questions concerning the neural processing underlying binocular rivalry remain open. Particularly controversial is the role of primary visual cortex (V1) in rivalry. To address this controversy, we propose to capitalize on an interesting aspect of the perceptual phenomenon;during an alternation, one sees a traveling wave in which the dominance of one pattern emerges locally and expands progressively as it renders the other pattern invisible. Our experiments are designed to measure and characterize the neural basis of these perceptual waves. The proposed experiments will apply a combination of empirical methods (psychophysics and fMRI in humans;optical imaging, electrophysiology, pharmacology, and electrical stimulation in the awake monkey) to explain this perceptual phenomenon in terms of the underlying neural mechanisms and to test the following hypotheses: (1) that competition between the two rival stimuli is implemented by neural circuits in primary visual cortex (V1), i.e., that neural circuits in V1 play a causal role in triggering transitions during rivalry;(2) that for the consequences of this neural competition to be perceived, activity must advance to higher visual areas;and (3) that attention, mediated by feedback from higher visual areas, plays a crucial role in promoting neural activity from V1 to higher visual areas. We will then be in a position to develop and refine a computational theory of the neural processing in V1 that supports these traveling waves, and a theory that elaborates the role of V1 in visual awareness. The neural competition underlying perceptual alternations during rivalry is believed to be closely related to the strabismic suppression. Hence, the proposed experiments will provide useful information and will establish novel experimental protocols that can, in future work;be applied to further our understanding of strabismus and amblyopia.

DESCRIPTION (provided by applicant): The abuse of illicit drugs such as cocaine and MDMA inflicts tremendous damage on society. According to the Department of Health and Human Services, approximately 35 million persons 12 or older use an illicit drug within each year, and more than 3.8 million were dependent on or abusers of illicit drugs in 2003. Although drug prevention advertisements have been used for decades and are an important part of anti-drug policy, there is considerable controversy over how effective these ads are at deterring drug use, and there is a growing need for the development of new innovative assessment tools. We propose that functional magnetic resonance imaging (fMRI) can provide insights into the effectiveness of substance abuse prevention messages, and can provide a useful complement to existing explicit and implicit measures of ad effectiveness. We will combine methods from marketing research with fMRI, galvanic skin response, and eye movement data, to determine engagement in and effectiveness of anti-drug ads. We propose using a novel inter-subject correlation (ISC) analysis that we have recently shown to be a powerful tool for exploring the function and organization of the human brain during natural viewing of complex stimuli (e.g., films in our previous research;advertisements in the current application). The proposed experiments will provide a detailed characterization of the activation patterns associated with engagement in the ads, distinguish between the engagement level and the effectiveness of each ad, and identify interventions for enhancing the effectiveness of prevention messages. Moreover, the proposed research provides an opportunity for characterizing correlations between individual differences in personality traits with individual differences in neural processing. Finally, the proposed research is a platform for studying the basic neural processes underlying engagement. The abuse of illicit drugs such as cocaine and MDMA inflicts tremendous damage on society. The proposed research plan is aimed at characterizing the neural correlates of the engagement level and effectiveness of different substance abuse prevention messages. We propose to combine methods from marketing research neuroscience research to develop new tools for assessing the effectiveness of different prevention messages. Such tools have the potential to ensure that prevention messages are effective and that taxpayers'dollars are efficiently used.

DESCRIPTION (provided by applicant): Attention has played a central role in perception research since the dawn of experimental psychology. Over the past 20 years, the neurophysiological basis of visual attention has become an active area of research, and the field of visual psychophysics has developed rigorous methods for measuring and characterizing the effects of attention on visual performance, yielding an explosion of findings. These experiments have documented a bewildering variety of empirical phenomena, some of which appear to be mutually contradictory. One example concerns the interaction between attention and visual stimulus contrast. The results of some experiments suggest that attention increases neuronal responses multiplicatively by applying a fixed response gain factor. Other results suggest a change in contrast gain. Still other results suggest that attention may have a fixed additive effect, which can be approximated as a combination of both response gain and contrast gain changes. These ostensibly contradictory empirical findings have been paralleled by theoretical ideas that have been taken to represent alternative models of attention. We propose to develop and test a computational theory, called the normalization model of attention, and to unify/reconcile various alternative, and seemingly conflicting, empirical findings and theoretical models of the effects of attention on neuronal activity in visual cortex. We aim: (1) to show that the proposed model can exhibit response gain changes, contrast gain changes, and additive-like combinations of response and contrast gain changes, depending on the stimulus conditions and the spread of the attention field;(2) to test the hypothesis that the effect of attention on behavioral performance and perceptual appearance systematically shifts from a change in response gain to contrast gain by manipulating the stimulus size and the spatial extent of the attention field;and (3) to test the hypothesis that attention modulates activity in visual cortex as predicted by the model, and to link attentional modulation of cortical activity (as measured with functional magnetic resonance imaging) with attentional modulation of behavioral performance (as measured psychophysically). The proposed research will utilize convergent information gained from various techniques (computational theory, previous electrophysiology experiments, and novel psychophysics and functional imaging experiments) to contribute to our understanding of how the brain processes visual information, how neural activity is related to visual attention and perception, and how visual processing interacts with other brain systems underlying cognition, in particular, attention. PUBLIC HEALTH RELEVANCE: The experimental protocols and theoretical principles that we develop for studying vision and attention in healthy human subjects will be readily applicable to patient populations. A better understanding of visual attention will lead to a better understanding of factors limiting peripheral vision, which are critical when central vision is compromised due to macular degeneration and related visual deficits. Basic knowledge of visual attention has implications for our understanding of several neuropsychological disorders, including unilateral neglect, schizophrenia and ADHD, and for informing the development of diagnostic tests of these disorders.

DESCRIPTION (provided by applicant): The representation of any stimulus can be seen as a unique and distributed pattern of activity in a large population of neurons. These neural representations are thought to undergo a series of transformations across processing stages in visual cortex, and to depend on behavioral demands. The nature of these transformations reveals important insights into the computational mechanisms underlying the formation of behaviorally meaningful neural representations from incoming sensory signals. In this proposal, the focus is on measuring the neural representations and characterizing the transformations for a specific visual modality: color. The representation of color takes on many different forms. For example, humans discriminate between many thousands of hues but use only a handful of discrete color categories. This makes color an ideal candidate to investigate distributed neural representations. The novel empirical and theoretical approaches in the current proposal aim to significantly advance understanding of 1) how the human visual system represents color, 2) how this distributed neural representation is transformed across the hierarchy of visual cortical areas 3) the dependence of these representations on behavioral demands, and 4) the dependence on context. Aim 1 experiments will test the hypothesis that the neural representation of color is transformed as chromatic signals ascend the visual system. Neural color spaces will be derived from functional magnetic resonance imaging (fMRI) measurements, using novel experimental protocols and multivariate data analysis techniques. These neural color spaces will be compared with perceptual color spaces derived from psychophysical measurements of color discrimination and categorization. Aim 1 experiments will also test the hypothesis that neural representations of color depend on behavioral demands. The proposed experiments will distinguish between two specific computational hypotheses: 1) that neural color spaces change for different behavioral tasks, indicating a change in the underlying selectivity and tuning of the neurons, versus 2) a (possibly selective) increase in response gain, with no evidence for a change in the color space. Aim 2 experiments will test the hypothesize that changes in color perception, due to a dramatic visual illusion, are correlated with corresponding shifts in the underlying neural representation, and that the extent of the shift in the neural representation varies between visual areas, depending on the neural color space in each visual area. Ultimately, color provides a model for more complex neural representations (e.g., those underlying face and object recognition, control of movement, etc.) and the findings will provide general insights about distributed neural processes and representations. Consequently, the proposed research will provide information about how the brain transforms an incoming set of signals (of any modality) into a set of meaningful representations that subserve a multitude of tasks.

? DESCRIPTION (provided by applicant): Primary visual cortex (V1) is likely the best studied sensory cortical area, and is a model for understanding broad principles of cortical processing. Similarly, orientation in V1 is likely one of the simplest and best studied cortical sensory features. Orientation is used as a model for understanding more complex feature processing in other cortical areas, and oriented V1-like receptive fields play an important role in successful computational models of vision. Yet even something as basic as the map of orientation on V1 is inadequately understood. We propose a multidisciplinary series of theoretical and empirical studies to characterize orientation selectivity from the scale of columns to that of retinotopic maps. We will test the hypothesis that coarse-scale biases in orientation preferences are fundamental to understanding the link between orientation-selective neural activity in V1 and orientation perception. We will distinguish and separately measure 3 different processes (stimulus vignetting, cardinal/radial gain fields, and asymmetric surround suppression) that might contribute to coarse-scale orientation biases. Doing so will enable us to characterize the cardinal/radial gain fields in V1 (i.e., the intrinsic representation of the stimulus orientation), independent of the edge effects (from stimulus vignetting and surround suppression), and determine the extent to which the gain field predict a perceptual phenomenon called the oblique effect. We will settle the controversy about fMRI decoding of stimulus orientation by quantifying the relative contribu- tions of fine- (i.e., columnar) vs. intermediate- (i.e., vascular pooling) v. coarse (i.e., stimulus vignetting, asymmetric surround suppression, cardinal/radial gain fields) scale biases in orientation preferences. Resolving the source of the orientation preferences in fMRI measurements from V1 will guide the interpretation of thousands of studies based on multivariate statistical analyses in other brain areas. We will develop and implement a model of the responses of an entire population of neurons in V1, that will enable simulations of all variety of methods: single- and multi-unit firing rates, calcium imaging, optical imaging, and fMRI responses, implemented so that it can be run on any stimulus image, including the stimulus aperture. Amongst other applications, the model will be used to establish the extent to which stimulus vignetting is a confound in vision and visual neuroscience research; almost every study in our field utilizes a stimulus aperture, but ignores the potential impact of the aperture. Variou disorders have been associated with differences in the topography and functional architecture of visual cortex, and/or with differences in visual sensitivity across the visual field. The experimental protocols that we propose will be readily applicable to patient populations. Consequently, the experimental protocols and theoretical principles that we propose will be widely applicable in basic as well as translational research.

Sleep is a major problem for parents of young children. This is demonstrated by the large number of best-selling books on "sleep training" geared toward new parents, and by the numerous courses offered to new parents focusing on helping them get a better handle on their infant's sleep. But despite the attention given to educating parents about how to teach their children to sleep, getting a good night sleep remains one of the most anxiety-provoking aspects of parenting. There are a large number of baby monitors currently on the market, but none provide direct information about sleep. The majority of devices provide an audio monitor so that parents can hear whether their baby is crying. But sound is a poor proxy for sleep. The proposed project will solve this problem by developing the high-fidelity baby sleep monitor for use at home by parents.

This I-Corps team will develop a consumer product that will provide better and more direct information about sleep. The team will leverage recent developments in both hardware and software to make measuring and monitoring sleep simple and cost effective, so that parents will be able to monitor their infant's sleep. The team will develop a product that provides parents with useful information about their baby?s sleep by comparing measurements from their baby with the rest of the database. The team intends to apply the technology in a wide range of neurometric consumer products including self-monitoring of sleep throughout the lifespan, monitoring arousal/vigilance of professional drivers (e.g.,truck drivers) and pilots, and monitoring arousal/vigilance of security personnel (e.g.,TSA).

Abstract The Functional Imaging Module supports vision research in the Center for Brain Imaging at New York University. CBI is a shared research center for research and teaching in visual and cognitive neuroscience at NYU. CBI is located on the ground floor and second floor of the same building that houses most of the vision core faculty. The CBI is now in its eleventh full year of operation, and members of the Core faculty are among its most active users. The Functional Imaging Module will enable NEI grantees and other vision researchers to develop, implement, and maintain technical advances, including software for real-time MRI image reconstruction to correct the image distortions in MR images, software for file format conversion, software for data quality assurance, the transition to a new Siemens Prisma MRI scanner, the development of awake monkey fMRI, and the development of MRI-compatible transcranial magnetic stimulation (TMS). The module will also support the nightly backup and databases for anatomical MRI, fMRI, EEG and MEG datasets. The module will leverage research support by stimulating collaborative research between members of the Core faculty, and by facilitating sharing techniques and instrumentation between members of the Core faculty. The technical developments will also be shared with vision scientists at other institutions. Finally, the module will contribute to recruiting and retaining faculty, postdocs, and graduate students, and skilled and experienced CBI staff. The Functional Imaging Module provides moderate or extensive support for 11 members of the Vision Core, including two young investigators and 9 NEI funded investigators, 7 of whom hold qualifying grants.

Project Summary Here, we propose to thoroughly characterize the origins of pairwise correlations in cortex using a synergistic mix of experimental methodologies, behavior, and computation in mice and macaques. We will elucidate the mechanistic underpinnings of normalization and test our hypothesis that changes in cortical pairwise correlations and other signature arise from ongoing cortical computations. In Aim 1 we will record from populations of neurons in the middle temporal visual area of trained, behaving monkeys to test the hypothesis that pairwise spike correlations, gamma oscillation and transient responses at the onset of visual stimuli arise in part from the dynamics of the circuits that normalize neuronal responses. These tests require measurements with a precision that is not feasible in mice. Conversely, the experiments in Aim 2 and 3 address questions that are not feasible in monkeys. In Aim 2 we will exploit the accessibility of mouse visual cortex by using both two-photon laser scanning microscopy and multielectrode arrays to comprehensively measure the relationship between normalization and pairwise correlations in populations of V1 neurons and measure how spatial separation within cerebral cortex affects that relationship. Finally, in Aim 3 we will establish the contributions of specific cell classes to normalization and pairwise correlations in mouse V1. We record the activity of pyramidal neurons and the three most thoroughly characterized classes of cortical interneuron (VIP, SST and PV) during normalization. We will then separately manipulate the activity of these cells classes to revealing the role that changes to the ratio of excitation and inhibition play in driving normalization. In this way, we will establish the role these neurons play in changing pairwise correlations within the excitatory pool of neurons. Results from all three Aims will be tied together using a new family of dynamic, recurrent circuit models of normalization to formalize the hypothesis that normalization imposes pairwise correlations and other activity signatures, and will use experimental data to constrain and refine these models.