Brian A. Wandell - US grants

Color constancy refers to the stability of object color appearance despite variations in the ambient lighting and surfaces present in an image. We propose to test a series of hypotheses about how human observers obtain a stable judgment of the color appearance of objects. In the initial period we plan to use multi-colored images presented on a CRT. The controlling software is designed to permit us to specify the spectral power distribution of the ambient lighting, and surface reflectance functions at different locations in the image. We will measure the achromatic locus (a curve in color space along which the display appears white) as a funciton of (1) the spatial position in the display, (2) the spectral power distribution of the ambient light used to generate the display, and (3) the selection of surface reflectance functions in the display. We play to use measurements of the achromatic locus to test two classes of theories of spatial integration of color information. Buchsbaum has suggested that the space average color of the display is the key image statistic that governs the system's color correction. Whittle and Challands (1969; Walraven, 1976) have suggested that the signal at the edges of the components of the image is the key image statistic that governs the system's color correction. We plan to use measurements of observer's ability to classify images to test a third color constancy algorithm. Maloney and Wandell (1986) suggested that color constancy can be obtained by using the spatial correlation of receptor responses.

This proposal aims to use fMRI as an index of human cortical activity when viewing colored objects. Color tuning will be measured in different regions of visual cortex. The neural basis of two main color phenomena will studied. The first question is how the visual system compensates for changes in the ambient illumination and computes a relatively constant color appearance for surfaces. The second study address the problem of why colored patterns at high temporal or spatial frequency appear achromatic.

magnetic resonance imaging; nervous system; eye; biomedical resource;

Introduction: Visual cortex performs an extensive series of computations. Some of the basic features of cortical vision have been worked out on monkey models, and we expect these to generalize to human. In the monkey the visual portion of cortex can be subdivided into more than 30 distinct visual areas. These visual areas are identified by their different patterns of inputs and outputs, as well as by general features of how the neurons within these areas respond to visual stimuli. Lesions of certain visual areas are devastating to visual function, while lesions of other areas result in very modest visual deficits, as if their function can be taken over by the remaining parts of the brain Methods: A study of the color sensitivity in one of the largest and most extensive visuals areas, primary visual cortex was made. The main significance of the color results is that it is possible to make quantitative measurements of how specific areas in human cortex respond to visual stimuli. This expands the scope of fMRI from one of localizing activity to measuring the level of the activity A new set of studies were initiated on the question of plasticity in human visual cortex. We have received funding to study the cortical response of amblyopes, these are individuals whose eyeball is intact and functioning, but who have very poor vision due to degraded cortical function. Amblyopia is a failure of visual plasticity: during childhood the signals from one eye do not properly reach visual cortex either because of strabismus (lazy eye) or anisotropia (poor optics). If the failure of these signals to reach cortex is not corrected during childhood, then quality of the visual input is out of the compliance range during the years of normal development and causes reduced visual sensitivity of cortical origin. Conclusion: We have initiated a set of studies on the cortical response in amblyopes, and we have found diminished signals from the amblyopic eye. We are now analyzing the effect of these diminished signals on the cortical organization of amblyopic observers.

DESCRIPTION (provided by applicant): Brain circuitry expands and matures at an extraordinary rate during the ages just prior to puberty. This is also the age range over which children develop many important cognitive skills, such as reading. With the advent of several new brain imaging technologies, it is now possible to make noninvasive measurements of brain development in regions that, in adult, are essential for skilled reading. Following individual children as they mature over the ages of 8 to 11 years, we propose to study the development of the functional responses in two specific reading-related brain regions. We also propose to track the anatomical development of these areas in individual children. One region, in the ventral occipital temporal cortex, selectively responds to simple orthographic patterns in adult readers. A second region, in the lateral occipital cortex, is powerfully activated during normal reading and is known to signal weakly in adults with poor reading skills. We will combine neuroimaging measurements of (a) functional responses to simple stimuli, (b) anatomical development of the neural circuitry, with (c) careful behavioral assessments of reading to better understand the connection between behavior and brain development. We expect anatomical and functional development in these two brain regions to correlate with the development of skilled reading. Further, we expect that the failure of normal development in one or both of these regions will help to diagnose potential difficulties in reading development.

[unreadable] DESCRIPTION (provided by applicant): During the last decade a range of technologies were invented that greatly expanded the scope of cognitive neuroscience. Using new technologies such as functional MRI (fMRI), diffusion tensor imaging (DTI), and transcranial magnetic stimulation (IMS), cognitive neuroscientists can now measure and influence the brain in ways that were previously impossible. During this period of new technologies and ideas, members of the Stanford Psychology Department and our collaborators have established a strong record of theoretical, empirical and clinical investigations of brain function. Here we propose creating a training program designed to educate predoctoral and postdoctoral students in cognitive neuroscience. The curriculum combines cognitive neuroscience theories, tools and applications. The program will train a new generation of students who will advance our understanding and treatment of mental health disorders. The training program is based on a rigorous curriculum in which students acquire a broad background in theories of cognitive neuroscience. They are also trained in the fundamentals various modern imaging technologies, including fMRI, DTI, TMS, MR-Spectroscopy and EEG. The program provides access to these tools in a structured environment so that trainees can understand the signals acquired with these different methods. As trainees develop their skills, they will participate in advanced seminars that encourage them to develop new theories, create new tools, and apply these theories and tools in the clinic. The training program is designed to serve the broad and complex NIMH mission, spanning scientific Discovery and application. The goal of our program is to inspire students to advance our understanding of brain, behavior, and psychological disorders. By communicating the remarkable opportunities and establishing a training environment that makes these opportunities available, we believe we can attract the best and the brightest individuals to research careers that serve the NIMH objectives. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Brain circuitry expands and matures at an extraordinary rate during the ages just prior to puberty, from 7-12 years. During this time, many children develop many important cognitive and visual skills that are essential for reading. Not all children develop the ability to read, and for some children their difficulty is likely to be due to improper development within a small number of regions located in visual cortex. With the development of new brain imaging technologies, it is possible to safely measure children's brain development. This set of studies will identify the portions of the central visual pathways that are essential for reading (in adult) and also trace the normal development of these pathways (in children). These studies combine measurements of brain function and structure with psychological test of reading and mental development. The study follows the development of a group of 55 children with a wide range of reading skills. We anticipate that the range of reading skill development will be mirrored in a range of brain development rates within the portions of the brain that are essential for reading. By measuring behavior and brain development together, in each of the 55 children, we hope to understand healthy cortical development and how deviations from normal development explain reading disabilities. Public Information: Brain circuitry expands and matures at an extraordinary rate during the ages just prior to puberty. This is also the age range over which children develop many important cognitive skills such as reading. We combine neuroimaging measurements of (a) functional responses to simple stimuli, (b) anatomical development of the neural circuitry, with (c) careful behavioral assessments of reading to better understand the connection between behavior and brain development.

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

This award permits Dr. Brian Wandell and his collaborators at Stanford University to purchase a 3T functional magnetic resonance imaging scanner. The shared instrument will be the centerpiece of a new facility, The Center for Neurobiological Imaging, designed to advance scientific research and training on topics spanning human decision-making, cognition, perception, child development, education and emotion. The instrument will be used to support research that advances understanding of the human brain and also offer the opportunity to integrate teaching about brain functions and systems into the curricula of students in a variety of fields. The instrument will increase the efficiency and quality of a broad array of scientific research efforts that aim to understand human brain function, and ultimately apply this new knowledge to the development of effective social, economic, educational and legal systems. The research approach involves a partnership between basic scientists and engineers. The advances in imaging over the last fifteen years are still in an early phase and within the next ten years, scientists believe, it should be possible to measure the distributions of particular molecules within the brain, trace brain development in detail and measure properties of the neuroglia. The close proximity in the laboratory between magnetic resonance physicists, statisticians, psychologists and other social scientists will make it possible to explore collaboratively new imaging modalities and transform technical advances into scientific insights. The instrument and related software and analysis tools will also be used to train graduate students and post-doctoral fellows in advanced methods for understanding the human brain.

DESCRIPTION (provided by applicant): The brain is an intricate set of neural circuits that communicate and interact. These circuits are organized at the local spatial scale (microns) of synapses that connect nearby neurons and at the much larger spatial scale (centimeters) of axon bundles that connect widely separated regions of cortex. MRI is a noninvasive measurement method that is the only technique available for measuring axon bundle circuits and tissue properties at the micron scale in the living human brain. The grant proposes new methods to identify circuits in adult brains and then to measure the normal development of tissue properties in key axon bundles. Understanding the circuit characteristics and their healthy development is essential for the goals of monitoring healthy visual development, detecting disease, evaluating the efficacy of therapies, and understanding neural signals needed for proper visual perception. PUBLIC HEALTH RELEVANCE: The visual system comprises an intricate set of neural circuits that are organized at the micron scale of local groups of neurons and as well as the centimeter scale of axon bundles that connect neurons in different parts of cortex. This grant proposes new measurements and algorithms to identify axon bundles and measure tissue properties of these bundles in the visual parts of the brain. Identifying these circuits in adult brains and measuring their normal development in children will allow us to understand the circuit characteristics that are important for healthy visual development and normal visual perception, for detecting and monitoring disease (e.g. optic neuritis or multiple sclerosis) progression, and for evaluating the efficacy of therapies.

Thought and emotion are processed in the brain in large part by cortical neurons, small cells located in a thin (3-5mm) sheet on the surface of the brain. These neurons combine signals from different parts of the brain. The inputs and outputs of these neurons, the brain's wiring, are the axons. Some axons make short-range connections between neurons. They carry signals only a few tenths of a millimeter. Other axons make long-range connections. They carry the signals several centimeters between neurons in widely separated parts of cortex. In recent years, for the first time in human history, it has become possible to measure in the living human brain the path traveled by the long-range axons. With funding from the National Science Foundation, Dr. Brian Wandell of Stanford University is developing methods for measuring and identifying, noninvasively, the path followed by axons that travel a few centimeters. The new methods are based on magnetic resonance imaging data and specialized mathematical algorithms. This project is implementing a mathematical method to test the accuracy and improve the spatial resolution of these methods. This methodological advance will make it possible to make new brain measurements to identify the axons in visual cortex that carry the signals essential for seeing and reading. Experiments are being conducted to identify all the major white matter fiber tracts in the human visual cortex and also to identify specifically the tracts from visual to reading areas of the brain.

The long-range connections essential for vision are located in the posterior part of the brain. When we read, these visual signals are carried to more anterior parts of the brain. The neurons in these anterior regions interpret the shape of the letters and words, and are essential for skilled reading. The ability to resolve the reading pathways in individuals, including both the cortex and the axons, is within reach. This project is implementing new mathematical methods to identify these pathways in individual subjects. The first measurements are designed to understand the development of the long-range visual connections essential for seeing. A full wiring diagram of the relevant brain pathways and measurements of typical growth trajectories will make it possible to identify developmental abnormalities in individual children so that they can receive appropriate intervention. The methods will be applicable to many other parts of the brain, and there is a plan for wide dissemination of the analysis software.