George R. Mangun - US grants

When subjects selectively attend to visual stimuli, the event-related potentials (ERPs) elicited by attended stimuli exhibit early sensory-evoked Pl (100 ms) and Nl (180 ms) peaks of enhanced amplitude. This pattern suggests that the mechanism of spatial selective attention involves, in part, an increase in information flow in the visual pathways via a 'gating' or 'gain control, process. At present, however, only minimal information is available regarding either the neural generators of these early attention-sensitive ERP peaks or the relationship between ERP attention effects and perceptual processing. Proposed are a series of ERP experiments investigating the mechanisms of visual selective attention. First, in healthy subjects, the neural bases of spatial selection will be investigated by analysis of (i) scalp voltage and current density distributions and (ii) dipole models of the attention-sensitive Pl and Nl peaks elicited by different classes of visual stimuli. Second, the perceptual significance of the early, attention-related ERP enhancements will be investigated in a series of experiments that seek to correlate signal detection measures (d') with the magnitudes of ERP attention effects. Third, experiments will investigate the spatial selectivity of the early Pl and Nl attention effects. ERPs to letter stimuli will be compared as functions of their (i) distance from the current spatial focus of attention in two-dimensional space and their (ii) similarity to the attended-location events in color. Lastly, related experiments in commissurotomy patients will investigate (i) the contributions of callosally mediated activity to the attention-sensitive ERPs and (ii) the hemispheric specialization of color selection. Understanding the basic mechanisms of selective attention will aid in identifying the physiological bases of cognitive and mental disorders such as schizophrenia, attention deficit disorder, dementia and learning disability.

The goals of the present project are to investigate the neural mechanisms of selective attention and attention orienting in patients with either focal cortical damage or complete cerebral commissurotomy, as well as in normal control subjects. In a series of experiments this project will investigate the brain systems that mediate selective attention to spatial locations, to different classes of stimulus features such as color, movement and spatial frequency, and to conjunctions of features (objects). Evidence from animal and human studies indicate that the parietal cortex is principally involved in aspects of spatial cognition while the inferotemporal projection system is involved in the representation of stimulus features and objects. We hypothesize that, in part, attentional selection modulates activity in the cortical areas that code a particular visual feature or dimension, and we therefore predict that spatial aspects of attention require the integrity of the parietal cortex while attention to features and objects is a function of the occipito-inferotemporal projection pathway. Moreover, it has been hypothesized that differential specializations of the two hemispheres for spatial versus feature- and object-based perception exist such that the left hemisphere is biased towards object representation while the right hemisphere is dominant for spatial processing. We will utilize behavioral measures of attention (response time and accuracy) and electrophysiological measures (i.e., ERPs) of parietal and infero- temporal visual processing in studies of patients with parietal-only versus temporo-parietal cortex lesions of both the left and right hemispheres to investigate the role of these brain areas in spatial, feature-based, and object-based attention. Studies in commissurotomy patients will also investigate the hypothesized hemispheric asymmetries in spatial and object-based selective attention, as well as hemispheric specializations in the processing of global versus local levels of stimuli. Investigations of subcortical and cortical interactions during attention in the commissurotomy patients will continue our work in this area. Previous results have demonstrated that under many conditions the cortically separated hemispheres of commissurotomy patients can act independently during visual search for target items in large arrays of distractors, while continuing to demonstrate interhemispheric interactions in perceptual-motor processing. We will attempt to identify the critical conditions that determine whether or not the two cerebral hemispheres can perform independently during attentional processing. These studies will help to identify cortical systems and hemispheric specializations in attentional processing as well as the contributions of subcortical systems to the integration of attentional processes in the human brain.

When subjects selectively attend to visual stimuli, the event-related potentials (ERPs) elicited by attended stimuli exhibit early sensory-evoked Pl (100 ms) and Nl (180 ms) peaks of enhanced amplitude. This pattern suggests that the mechanism of spatial selective attention involves, in part, an increase in information flow in the visual pathways via a 'gating' or 'gain control, process. At present, however, only minimal information is available regarding either the neural generators of these early attention-sensitive ERP peaks or the relationship between ERP attention effects and perceptual processing. Proposed are a series of ERP experiments investigating the mechanisms of visual selective attention. First, in healthy subjects, the neural bases of spatial selection will be investigated by analysis of (i) scalp voltage and current density distributions and (ii) dipole models of the attention-sensitive Pl and Nl peaks elicited by different classes of visual stimuli. Second, the perceptual significance of the early, attention-related ERP enhancements will be investigated in a series of experiments that seek to correlate signal detection measures (d') with the magnitudes of ERP attention effects. Third, experiments will investigate the spatial selectivity of the early Pl and Nl attention effects. ERPs to letter stimuli will be compared as functions of their (i) distance from the current spatial focus of attention in two-dimensional space and their (ii) similarity to the attended-location events in color. Lastly, related experiments in commissurotomy patients will investigate (i) the contributions of callosally mediated activity to the attention-sensitive ERPs and (ii) the hemispheric specialization of color selection. Understanding the basic mechanisms of selective attention will aid in identifying the physiological bases of cognitive and mental disorders such as schizophrenia, attention deficit disorder, dementia and learning disability.

DESCRIPTION (Adapted from applicant's abstract): Visual selective attention is a powerful brain mechanism that enables relevant sensory information to be effectively processed, while minimizing interference from irrelevant, distracting events. Despite more than three decades of psychophysical and physiological research, remarkably little is known about the neural mechanisms of this fundamental cognitive process in humans. In particular, precisely how various stages of visual processing are affected by selective spatial attention remains unclear. This proposal will investigate visual selective attention using a combined ERP and fMRI approach that permits both the functional anatomy (fMRI) and time course (ERPs) of attentional processes to be elucidated. The overall goal is to understand the role of selective attention in information processing in the human visual cortex, and to identify the detailed functional architecture of the systems involved. The mechanisms of voluntary spatial attention wi]l be investigated, and the relationship of spatial attention to feature, object and motion processing will be addressed. The proposed experiments have direct theoretical consequences for current physiological models of attentional selection by providing key evidence about both the anatomical locus and time course of attention-related modulations of neural processing in the intact human brain. In addition, because a combined ERP and fMRI approach is to be used, the relationship of electrocortical activity to changes in regional cerebral blood flow (CBF) during information processing will also be studied. Because deficits in attentional processes accompany various psychiatric, neurological and developmental disorders, investigations of the basic properties of human brain attention systems represent important core knowledge in the ongoing struggle to characterize, diagnose and treat such conditions in humans.

DESCRIPTION (Adapted from applicant's abstract): Visual selective attention is a powerful brain mechanism that enables relevant sensory information to be effectively processed, while minimizing interference from irrelevant, distracting events. Despite more than three decades of psychophysical and physiological research, remarkably little is known about the neural mechanisms of this fundamental cognitive process in humans. In particular, precisely how various stages of visual processing are affected by selective spatial attention remains unclear. This proposal will investigate visual selective attention using a combined ERP and fMRI approach that permits both the functional anatomy (fMRI) and time course (ERPs) of attentional processes to be elucidated. The overall goal is to understand the role of selective attention in information processing in the human visual cortex, and to identify the detailed functional architecture of the systems involved. The mechanisms of voluntary spatial attention wi]l be investigated, and the relationship of spatial attention to feature, object and motion processing will be addressed. The proposed experiments have direct theoretical consequences for current physiological models of attentional selection by providing key evidence about both the anatomical locus and time course of attention-related modulations of neural processing in the intact human brain. In addition, because a combined ERP and fMRI approach is to be used, the relationship of electrocortical activity to changes in regional cerebral blood flow (CBF) during information processing will also be studied. Because deficits in attentional processes accompany various psychiatric, neurological and developmental disorders, investigations of the basic properties of human brain attention systems represent important core knowledge in the ongoing struggle to characterize, diagnose and treat such conditions in humans.

DESCRIPTION (provided by applicant): Selective attention is a cognitive ability that enables the processing of relevant stimuli while minimizing interference from irrelevant and/or distracting events. An overall goal of the research proposed here is to elucidate the neural mechanisms of attentional processes in order to test specific models of voluntary attention and provide basic science information relevant to the diagnosis and treatment of disorders that include deficits of attention. In conjunction with psychophysical measures, event-related potentials (ERPs) and oscillatory activity in the electroencephalogram (EEG) will provide high temporal resolution measures of neural activity supporting attentional control and stimulus selection. Functional magnetic resonance imaging (fMRI) will be employed to identify the neuroanatomical systems and networks involved in attentional control and selection. This application has three specific aims: (1) Determine how changes in background neural activity in visual cortex during preparatory attention influence selective sensory processing and performance;(2) Determine the role of preparatory attention in establishing the locus of attentional selection during ascending sensory processing;and (3) Determine the mechanisms of target facilitation and distractor inhibition processes in attentional selection. Throughout the proposed research, the combined use of EEG/ERPs and fMRI will provide complementary measures of the time course and functional anatomy of attentional mechanisms.

DESCRIPTION: This K05 Senior Scientist Award proposal is intended to enhance the P.I.'s percent research effort in studies of the neural mechanisms of attentional processes in humans. Attentional mechanisms include the control systems for top-down (voluntary) and bottom-up (reflexive) attention, as well as the modulatory effects these control systems exert on perceptual processes. The goal of this proposal is to combine psychophysical measures, event-related potential (ERP) recording and functional magnetic resonance imaging (fiviRI) in healthy and patient populations to investigate attentional mechanisms. Three main areas of investigation are proposed: (1) Attentional control mechanisms are proposed to involve a variety of brain systems that support different computational operations, yet, little evidence links specific brain system to distinct attentional functions. This proposal will investigate attentional control processes in a variety of paradigms for feature and form-based attention in cortical and subcortical systems using ERP and event-related fMRI methods to isolate activity related to specific aspects of attentional task performance. (2) It is now well accepted that attention can influence neuronal processing in visual cortex, but little is actually known about how these effects are engaged in sensory cortex, or how processing in early visual areas are modulated by various forms of elementary (feature-based) and higher-order (form-based) attentional selection. This proposal will investigate the functional properties of feature and form-based selective attention in functionally-defined visual areas. (3) Neurological damage leads to a variety of attentional disorders. The present proposal will investigate attentional processing in patients with cortical lesions using ERPs to provide a link between neuropsychological research in patients, and psychophysical and functional imaging studies in healthy persons; this research will focus on attentional control mechanisms. A theme of this proposal is the combined use of ERPs and fMRI to provide complementary measures of attentional processes that emphasize temporal and spatial aspects of neural activity, respectively. This proposal will permit the P.I. to dedicate greater effort toward investigating attentional mechanisms, and to advance research productivity by taking full advantage of the P.I.'s new research environment at Duke University. Deficits in attentional function accompany psychiatric and neurological diseases, and thus investigations of the basic mechanisms of brain attention mechanisms will yield essential core knowledge in the effort to characterize, diagnose and treat such conditions in humans.

DESCRIPTION (provided by applicant): The goal of the proposed conference is to bring together researchers from various disciplines to discuss a common topic: how we make decisions and carry them out. Decision-making is central to human cognition, and as such is of interest both to those who strive to understand how the brain subserves the mind, as well as to those who strive to understand how the choices that we make impact our societal and economic infrastructure - and vice versa. Ultimately, understanding the capacity of healthy individuals to make decisions will be of critical importance for understanding how this capacity fails in substance abuse and a variety of neurological disorders. The confirmed speakers for this conference will be presenting research and theories from the various perspectives of psychology, cognitive and systems neuroscience, economics, management, and political science. A key goal of this conference is to foster cross-fertilization between these different perspectives in order to generate novel questions and insights into decision-making. The speakers will describe work from the neuronal level to the behavioral level in the developing organism and the adult. Data will be presented both from healthy individuals and drug abusers.

Visual selective attention is a core cognitive ability that enables humans and animals to focus on behaviorally relevant stimuli while minimizing interference from irrelevant and/or distracting events. Several current theoretical models have proposed that cortical brain regions interact with subcortical brain structures to form a control network for voluntary attention. This control network exerts modulatory influences over the transmission of the visual signals in the sensory pathways that result in attentional filtering of visual inputs. In particular, the pulvinar, a subcortical thalamic structure, has been implicated as a key part of the attentional control network, but relatively little is known about the neurophysiological mechanisms involved. With support from the National Science Foundation, Dr. George R. Mangun and Dr. W. Martin Usrey of the University of California at Davis will explore the neural mechanisms of attentional control, especially with respect to the role of the subcortical pulvinar nuclei of the thalamus. This project will combine studies in humans and monkeys. In healthy human volunteers, brain scanning using functional and structural magnetic resonance imaging will be used to identify the neuroanatomical systems involved in attentional processing and to assess the role of the pulvinar in attentional control. In awake monkeys, electrical recordings from the pulvinar and early visual cortical areas will be used to investigate the mechanisms of attentional processing at the level of single brain cells and small networks of neurons.

Whether driving a car, listening to safety instructions, or concentrating on correctly preparing tax returns, attention supports successful performance. How the brain enables attention is of central interest for understanding how humans and animals function in a complex, and often demanding, environment. This research will test a specific hypothesis about the brain mechanisms that support successful attention. The research will capitalize on combining investigations in different related species (humans and monkeys) and will therefore permit different levels of analysis to be integrated. The activity of single neurons, which cannot easily be studied in humans, will be investigated in monkeys, while widespread human brain networks will be studied using brain imaging in humans. Because the humans and monkeys will be required to perform the same tasks while their brains are being studied, the resulting data from each species and method will be able to be integrated and considered in a common analytical and theoretical framework. The information from this research will provide a basic understanding of an essential ability in human thought and action, and will also provide information that can be used in ameliorating disorders of attention and improving attentional abilities in patients and healthy individuals.

? DESCRIPTION (provided by applicant): The Summer Institute in Cognitive Neuroscience will bring together leaders in cognitive neuroscience and promising graduate students, post-doctoral researchers and early stage professors/scientists for an intensive two-week lecture and laboratory course aimed at topics on the cutting-edge of the discipline. This proposal seeks five years of funding for the program's continuation. This application adds a unique collaboration with the Kavli Foundation, which will enable interdisciplinary training in the mathematical, physical and engineering sciences to be added to the curriculum in cognitive neuroscience in order to help develop a new community of brain scholars with truly interdisciplinary training and skills. The Summer Institute focuses on leading the field in training in the latest advances, and exposes its participants to rapidly emerging methods and discoveries, including the acquisition of competencies in tools and techniques, and an understanding of translational science. Through a combination of lectures, debates, close interaction among Summer Institute attendees, and laboratories involving advanced techniques such as functional neuroimaging, transcranial magnetic stimulation, and electrophysiology, and an array of analytic methods and computational methods, participants are provided with a broad but rich exposure to modern techniques and approaches bisecting all fields bearing on the mind and brain. The intensely interdisciplinary nature of the Summer Institute is its most defining feature and valuable asset. The next 5 years of the Institute will continue its successful traditions while also providing innovations to significantly augment and enhance the program. These include the incorporation of both faculty and trainees from the mathematical, physical and engineering sciences into the training program, and the introduction of training to achieve competencies in tools and methods. The Summer Institute in Cognitive Neuroscience provides an essential service to the field by providing the nation's early career researchers and clinical scientists with unique training that fosters interdisciplinary perspectives and collaboration, and by encouraging cross-disciplinary exchange between established scientific leaders and early stage investigators. The Summer Institute contributes directly to the advancement of the field by calling attention to and advancin knowledge of issues at the frontiers of current discovery that are relevant to the mission of the NIMH in basic and translational research and training.

The sensory world is rich in information, but subjective experience and experimental demonstrations reveal that the nervous system is limited in how much of this confused mass of information it can effectively process at any moment in time. Selective attention provides a means by which organisms regulate the flow of sensory information by enhancing the processing of relevant information and inhibiting irrelevant or distracting events. Numerous studies in humans and animals have established that attentional control mechanisms influence visual information processing within the cerebral cortex. However, the neuronal mechanisms of selective attention remain poorly understood at the cellular and synaptic levels. Using a novel method for measuring the effects of attention on synaptic communication between identified neurons, Drs. W. Martin Usrey and George R. Mangun of the University of California, Davis are determining the influence of attention at the earliest stages of processing in the cerebral cortex. In so doing, they are testing several long-standing hypotheses about the spatial organization of voluntary attention, the interactions between target facilitation and distractor suppression mechanisms, the role of spatial scale in determining the locus of selection in voluntary attention, the role of thalamocortical mechanisms in reflexive attention, and the contributions of specific visual pathways to voluntary and reflexive visual attention.

The project will advance discovery and understanding while promoting teaching, training, and learning through graduate and postdoctoral scholar involvement in undergraduate research supervision related to the project. Via the University of California Davis Summer Undergraduate Research Program (SURP) and the Young Scholars Program (YSP), the PI and the Co-PI will also mentor undergraduate and promising high-school students interested in pursuing careers in science. These programs promote underrepresented groups and provide research opportunities for students from non-research colleges. The project will enhance international collaboration through exchange programs. The proposed research will strongly benefit society in education and health. Because selective attention is a core cognitive process, elucidating attentional mechanisms in humans remains a high priority in efforts to understand, diagnose and treat psychiatric conditions that involve deficits in attention, including attention deficit hyperactivity disorder (ADHD), autism, obsessive compulsive disorder (OCD) and schizophrenia. Ameliorating these disorders provide increased opportunities for advancing education and human productivity.

Paying attention to the world around us, deciding what to attend to and what to ignore, is a fundamental human ability. It affects how we perceive ourselves and our place in the environment. Deciding what to pay attention to is a critical component of everyday functioning. Two people viewing the same scene, such as a busy intersection, may have different perceptions and impressions about what is taking place. One may attend to the traffic cop waving her arms and directing traffic, while another looking in the same direction may attend to the bicycle that narrowly misses a racing taxicab.

The present program of research will focus on the willful direction of attention (what one chooses to attend to). The research aims to establish the neural correlates of voluntary attention in humans, by using simple laboratory tests, advanced methods to record and analyze human brain activity, and novel signal processing of the brain's electrical signals. Such information will inform us not only about how the normal healthy attention system operates, but also how it breaks down in cases of overload, disease, and brain damage.

A Novel Multimodal Approach for High-Resolution Brain Research

The objective of this research program is to develop a novel methodology and analytic strategy for simultaneous high-density intracranial electrophysiological recording, electrical brain stimulation, and optogenetic activation/deactivation during high-field functional magnetic resonance imaging, and to apply this integrated methodology to investigate neural mechanisms that mediate sensory processing and selective attention in macaque. The project will advance discovery and understanding while promoting teaching and training by involving graduate students and postdoctoral scholars in undergraduate research supervision related to the project. Because selective attention is a core cognitive process, elucidating attentional mechanisms close relatives to humans such as the macaque remains a high priority in efforts to understand, diagnose and treat psychiatric conditions that involve deficits in attention, such as attention deficit hyperactivity disorder (ADHD), autism, obsessive compulsive disorder (OCD) and schizophrenia.

All of our conscious perceptions and cognitive actions depend critically on the neural computations performed by cortical circuits, the network of connections made by neurons in the cerebral cortex. Given the central importance of cortical circuits in mediating complex behavior, it is critical that we have the tools necessary to study these circuits during behavior. No single method of recording brain activity is yet able to characterize both the functional anatomy and rapid temporal changes in neuronal activity with both high spatial and temporal resolution. However, by the integration of different methods with either high temporal or high spatial resolution, this research will develop tools capable of providing a view of the time course and functional anatomy of brain circuits supporting behavior.

PROJECT SUMMARY/ABSTRACT Selective attention is an essential cognitive ability that permits us to effectively process and act upon relevant information while ignoring distracting events. A network involving frontal and parietal cortex for top-down attentional control, referred to as the Dorsal Attention Network (DAN), is active during both spatial and non- spatial (feature-based) attention. However, we know very little about the fine structure of attentional control activity in the DAN, how this structure changes to represent different to-be-attended stimulus features, how the connectivity within the DAN, and between the DAN and sensory cortex shifts when attending different features, or how these top-down processes and their influence in sensory cortex unfold over time. This gap in our knowledge is a critical problem for our models and theories of attention, and because attentional deficits are involved in a wide variety of neuropsychiatric disorders including autism, attention deficit disorder, dementia, and schizophrenia. The working model guiding this research is that top-down attentional control, based on different to-be-attended stimulus attributes, is guided by a smaller-scale neural fine structure within the DAN and prefrontal cortex that makes specific connections with specialized areas of visual cortex coding the attended attributes. Moreover, the time course of activity within the DAN in relation to that in sensory cortex follows a top-down cascading model, being earliest in frontal, then parietal cortex, and finally sensory cortex for preparatory, voluntary, attentional control. To identify the functional networks for attentional control for different forms of attention, and to define their time courses, this project uses innovative simultaneous recording of electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data. Advanced signal processing and modeling, including multivariate pattern analysis (MVPA), graph theoretic connectivity analysis, and Granger causality analysis will be used to reveal the fine functional anatomy and time course of attentional control and selection. The project includes three experiments that vary the to-be-attended stimulus attributes from spatial location to stimulus features (color and motion), and pursues three aims. Aim 1 is to reveal the fine structure of top-down preparatory attentional control for different to-be-attended stimulus features. Aim 2 is to elucidate the specific connectivity between fine structures for preparatory attentional control in the DAN and their target sensory structures in sensory cortex. Aim 3 is to reveal the time course of top-down attentional control for different to-be-attended stimulus attributes.