Scott O. Murray - US grants

DESCRIPTION (Adapted from applicant?s abstract) This project proposes to investigate how the human visual system uses motion cues to construct three-dimensional (3D) representations of object shape. One of the most salient cues that the visual system can use to recover 3D shape information is the relative 2D motion of an object?s parts. However, it is unclear which visual areas are involved in extracting shape information from motion cues. Motion information is typically confined to the dorsal visual pathway and information about object shape is typically associated with the ventral visual pathway. Thus, determining where information about motion and form are brought together in the visual cortex is a fundamental first step in understanding how the brain uses motion to construct 3D representations of object shape. We propose to identify the brain regions involved by using fMRI in a series of experiments, each examining a different feature of structure-from-motion stimuli including motion transparency, depth, and object shape. The final set of experiments will evaluate the degree to which structure-from-motion perception relies on a common visual-form area versus the degree to which motion-specific regions are involved.

DESCRIPTION (provided by applicant): The human visual system is faced with the computationally difficult problem of recognizing objects despite potentially large changes in image position, scale, viewpoint, and illumination. The ability to maintain 'object constancy' is crucial to our survival, allowing us to perceive and interact with a stable, predictable, and familiar environment. Despite its importance, how the visual system achieves object constancy is largely unknown. We propose a series of behavioral and functional MRI (fMRI) experiments aimed at characterizing the neural mechanisms underlying object recognition during changes in viewing conditions. In the first series of experiments, we aim to characterize neural responses to image transformations including rotation, scale, and position. The second set of experiments will build on the results of the first by assessing the role of attention and expectation on behavioral and neural responses. The final set of experiments will attempt to specify the role of learning and experience in the development of object perceptions and transformation-invariant neural responses. In all of the experiments, we will use a novel fMRI adaptation technique to characterize tuning functions in specified visual areas.

This award provides funds to permit the University of Washington to acquire a 3T magnetic resonance imaging (MRI) scanner for basic-science brain imaging research. This instrument will be housed in a dedicated MRI research facility in the Health Sciences building where it will support a primary group of over 30 basic-science MRI users at UW whose ongoing research success depends critically on access to a 3T MRI scanner. These multidisciplinary researchers originate from multiple different departments that include Psychology, Speech and Hearing Science, Music, Computer Science, Physiology and Biophysics, Linguistics, Neurosurgery, Neurology, Bioengineering and Radiology. Thus, this 3T facility will provide campus-wide support to neuroscience researchers in the Schools of the Arts and Sciences, Education, Engineering, Medicine, the Health Sciences, the School of Public Health and the Graduate School (Psychology). In addition to the current MR researchers, there are many other neuroscientists at UW who have expressed interest in using the 3T facility for their research when available. Thus, addition of a 3T MRI facility will expand the functional brain MRI research efforts at UW in the future. It will also be a resource accessible to researchers from other regional institutions.

Functional brain imaging (fMRI) is an important new research tool used to define how the brain operates to control motor and cognitive tasks and how these functions may be affected by abnormal development or disease. The 3T MRI will be utilized for many fMRI studies some of which include visual system analysis to understand how the brain operates to simultaneously process diverse types of visual input that includes spatial information (location) as well as feature information (color, shape, motion, direction, etc) to interpret a visual scene. Studies of fMRI involving language and cognition will investigate how the brain codes successes and errors during trial-and-error learning to see whether these neural coding events can be used to predict how well people learn. Neuroimaging using structural MRI and MR spectroscopy (MRS) to measure brain metabolite changes will be used to compare brains of young children with normal development to those with Autism. Quantitative MRI/MRS analyses of grey matter and regional volumetric and chemical changes over time (age 3 to age 10) will be correlated with behavioral developmental changes to address questions regarding the time course of brain development and its relationship to typical and atypical behavior.

The University of Washington is strongly committed to interdisciplinary science and education, as evidenced by strong cross-campus research ties, interdisciplinary training programs such as the Graduate Program in Neurobiology and Behavior, and discipline-spanning research centers such as the Integrated Brain Imaging Center (IBIC), Institute for Learning and Brain Science (ILABS), Virginia Merrill Bloedel Hearing Research Center (VMBHRC), Center on Human Development and Disability (CHDD), and Washington National Primate Research Center (WaNPRC). The proposed 3T facility will operate in this tradition, providing new opportunities not only for disciplinary and cross-disciplinary research, but also for graduate and post-graduate training, educational outreach, recruitment of new faculty in neuroimaging, and involvement by female students and researchers, and those from underrepresented groups.

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

When we open our eyes we instantly -- without any apparent effort -- have a detailed three-dimensional (3D) representation of our environment. However, the subjective ease of vision actually hides a set of very difficult computational problems that our brains are exceptionally good at solving. Foremost among these problems is how the brain deals with the inherent ambiguity in the retinal image. Because vision entails the projection of a 3D world onto a 2D surface, any given image on our retina could be caused by an infinite set of possible 3D configurations in our environment. In this project the investigators attempt to study this type of ambiguity by focusing on the perception of object size. There is an infinite set of object sizes and distances that could give rise to any specific retinal image size. A fundamental challenge to understanding size perception is specifying how distance information -- which is not explicitly represented in the retinal image -- is combined with retinal size information to achieve an accurate and stable representation of object size. The investigators will use functional magnetic resonance imaging (fMRI) and event-related potential (ERP) techniques to understand the role of 3D context in the neural processing of object size. The overarching framework of the research is that distance information is combined with retinal size information in early stages of the visual system. A series of experiments are proposed that focus on how representations of retinal size in early visual cortex are affected by 3D context. Specifically, the experiments will examine the relationship between perceived size and neural activity in early visual cortex, assessing the influence of top-down effects such as attention. The experiments will also examine the timing of 3D contextual effects using time-sensitive ERP measures.

The proposed studies are unique in that they use well-established behavioral and neuroimaging techniques to reevaluate the processing of size, a fundamental object property, in the context of 3D scenes. Understanding how this property is computed will significantly advance our knowledge of how the visual system operates in the 3D world in which we live. In addition, the research project will fit into a larger framework of cognitive neuroscience education and training at the investigator's institution. Specific undergraduate and graduate coursework will incorporate many of the techniques used in this project, which will help students to acquire knowledge of the theory and methodologies underlying state-of-the-art brain imaging research. Finally, the investigator's institution has embarked on a major expansion of facilities and personnel related to cognitive neuroscience and brain imaging research. The proposed project will form a major component of this expansion, the Brain Imaging Innovation Initiative, which is a multifaceted training and research effort aimed at undergraduate, graduate, and post-doctoral students and faculty interested in developing expertise in brain imaging research.

The goal of this project is to use behavioral and single-unit recording techniques to understand the role of three-dimensional (3D) context in the neural processing of object size. Estimating the size of an object highlights a fundamental computational problem in vision: the inherent ambiguity in the retinal image. For any given retinal image there are an infinite number of combinations of object sizes and viewing distances that could give rise to that image. A fundamental challenge is to understand how distance information - which is not explicitly represented in the retinal image - is combined with retinal size information to achieve an accurate and stable representation of object size. The overarching framework of this proposal is that distance information is combined with retinal size information in early stages of the visual system. Convergent evidence from behavioral, fMRI, and ERP experiments in humans have shown that object size is represented in the primary visual cortex. These results are inconsistent with the primary visual cortex passively reflecting the stimulus on the retina, but rather suggest that high-level signals related to 3D scene interpretation may be fed back to primary visual cortex to adjust the amount of tissue allocated to represent visual objects. To extend these findings, our proposed experiments pursue these results in an animal model using psychophysical measurements and single-neuron electrophysiological recordings. Two specific aims are proposed: 1) single-unit recording to investigate the changes in receptive field structure of individual visual cortical neurons as a function of 3D context and 2) psychophysical measurements of size illusions in the same animal model used in specific aim 1. Together these specific aims will shed light on the processes that underlie size perception, which are critical for interacting with a 3D world, and will provide a bridge between vision studies in human and non-human subjects.

? DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is a complex disorder of brain development characterized by difficulties in social interaction, communication, and repetitive behaviors and is often accompanied by disruptions of sensory processing. One recent and potentially unifying neurobiological explanation posits that ASD is caused by disruptions in the excitatory/inhibitory (E/I) balance within the brain. Consistent with the E/I explanation, recent genetic and neuroscience research in animal models suggest that inhibitory neurotransmitter gamma- aminobutyric acid (GABA) signaling may be significantly disrupted in ASD. However, the role of GABA in ASD remains largely untested in humans. We propose to test the hypothesis that changes in cortical levels of GABA give rise to over- and under- responsiveness of neural circuits leading to key sensory and motor symptoms of ASD. Critically, GABA signaling is highly amenable to pharmacological treatment. Thus, understanding how GABA signaling is altered in ASD will open up new pharmacological treatment possibilities. We will use state- of-the-art magnetic resonance spectroscopy (MRS) techniques to measure concentrations of GABA in adults with an ASD and neurotypical control subjects in visual, motor, and auditory cortices. We will use fMRI measures of evoked sensory and motor responses to characterize neural responsiveness in these regions along with clinical measures of sensory-sensitivity and motor-related symptoms. Finally, we will use fMRI to measure the strength of a well-established inhibitory neural circuit in the visual system: surround suppression. By elucidating the functioning of inhibitory signaling, our results will significantly advance understanding of the neurobiological causes of ASD.

PROJECT SUMMARY/ABSTRACT This proposal will test a novel, computationally-motivated hypothesis about neural dysfunction in autism spectrum disorder (ASD). ASD is a heterogeneous neurodevelopmental disorder of unknown etiology. However, a unifying theme of numerous proposals is that there is a pervasive disruption of neural excitatory/inhibitory (E/I) balance. A major limitation of the E/I hypothesis is that it describes a property of individual neurons; how that property scales up to neural circuits and how it relates to behavior ? the level at which ASD is described ? is not well specified. Neural computational models offer a way to bridge the divide between single-unit properties and behavior, and bring the necessary specificity to test possible changes in E/I in ASD. One well-established neural computation that directly relates to E/I is ?divisive normalization?, a computational framework that characterizes neural responses as the ratio of net excitatory relative to net suppressive input. Here we aim to test the hypothesis that ASD involves disrupted divisive normalization using vision as a model system. We will test two possible mechanisms of weakened divisive normalization. The first is the traditionally posited disruption of local, within-area circuits that mediate suppressive drive. The second is a novel hypothesis based on recent empirical findings in our lab. We have shown enhanced suppressive feedback of responses from higher stages to lower stages of visual processing in individuals with ASD. We suggest this enhanced suppressive feedback reduces responses of neurons that would otherwise participate in divisive normalization. This hypothesis makes specific predictions about the conditions under which disrupted divisive normalization will be observed in ASD. We will test these predictions using a combination of functional MRI, ERP, and diffusion MRI.