Michael I. Posner - US grants

Posner With National Science Foundation support, the University of Oregon will purchase a Dual Purkinje Eye Tracking system and related accessories. Developed by Stanford Research Institute and Forward Technologies, the eyetracker determines the direction of eye gaze over a large two-dimensional visual field. It operates with infrared light and does not interfere with normal vision. The system is accurate to 1 minute of arc and outputs a signal every millisecond. This temporal as well as spatial accuracy are essential in tracking smooth pursuit eye movements. Dr. Michael Posner and his colleagues will use the instrument to pursue three lines of research. The first involves a study of communication between identified neural areas in reading. Previous studies have shown that specific neural areas are involved in processing visual, phonological and semantic codes of visually presented words. Under the planned research, studies will be extended to actual reading situations. Eye movement will be monitored and brain electrical activity recorded. A second set of experiments involves the role of attention in language production. The eye tracking system will be used to measure allocation of attention in real time while subjects produce descriptions of animated events they witness. A final area of research involves perceptual-motor transformations in the visual motion domain. In instances where apparent motion of a stimulus differs substantially in velocity from its real motion, the investigators wish to discover which course the eye actually tracks.

Future progress in cognitive neuroscience research will rely increasingly on the application of systems for high-performance computation and high-volume data management to address the challenges of integrated neuroimaging, multi-modality sensor fusion, and cognitive modeling.
With a Major Research Instrumentation award from the National Science Foundation, the University of Oregon will establish the Integrated COgnitive Neuroscience, Informatics, and Computation (ICONIC) Grid, composed of parallel computing clusters, large-scale data servers, workstations, and interactive visualization devices. Connected by a high-bandwidth campus network linking the Department of Psychology, the Center for Neuroimaging , the Neuroinformatics Center, the Department of Computer and Information Science, and the Computational Science Institute, the ICONIC Grid will enhance Oregon's excellence in cognitive neuroscience with needed computing power to solve neuroimaging problems of tissue/feature segmentation, dense-array EEG source localization, multi-modal MRI integration, and functional components analysis. The ICONIC Grid will be organized as a distributed computing environment to promote grid-style collaboration among cognitive neuroscience research groups. Computer science research in high-performance parallel and distributed computing, scientific databases, informatics, and interactive visualization will enhance the ICONIC Grid for highly productive use as a computational science tool.

The interchange between cognitive neuroscience and computational science is now important at both theoretical and empirical levels. For several decades, cognitive psychology has drawn from concepts of cybernetics and information processing in the development of models of human mental function. However, it is in the integration of psychological with neural evidence that the methodological demands for computational advances have become particularly intense. Many investigators in cognitive neuroscience now recognize the limitations of individual brain imaging methods, such as in the temporal or spatial resolution, or practical implementation of the technology. The result is an increasing demand for integrated imaging and analysis, in which convergent methods are brought to bear on a particular issue of brain mechanisms.

The University of Oregon began the decade with a bold Brain, Biology, and Machine Initiative (BBMI) to promote interdisciplinary research between neuroscience, cognitive science, molecular biology, genomics, and computational science. The establishment of the Center for Neuroimaging , which houses a new Siemans Allegra 3-Tesla fMRI machine, and the Neuroinformatics Center, were Oregon's first steps towards integrative cognitive neuroscience. The ICONIC Grid is the next critical piece of the puzzle providing an essential resource to further advancements in cognitive neuroscience research, collaboration, education, and outreach.

The broader impact of the ICONIC Grid will be important for the University's educational goals, for minority recruitment and retention, and for extending advances in computation to medical advances in society. With on-campus access to both advanced imaging facilities and the computational and visualization infrastructure that processes and presents the experimental data, students in Psychology will be exposed to a state-of-the-art problem-solving environment for cognitive neursocience education. New Psychology curricula are planned for providing students training in the use of such tools. Similarly, the CIS department's academic objectives in parallel and distributed computing, computational science, networking, human-computer interaction, and visualization will benefit greatly from hands-on access to parallel cluster and distributed grid technology.

We have all had moments when an object or event reminds us of an experience we would prefer not to think about. When this happens, people often attempt to exclude the unpleasant memory from awareness. These efforts to control memory are an unfortunately ubiquitous occurrence after a traumatic experience. However, there is great variability in people's memory control ability. Whereas some can keep unwanted reminders from awareness, other less fortunate individuals suffer chronic distraction from these memories, undermining their ability to cope in the aftermath of trauma. What causes some people's attention to be captured so persistently by intrusive remindings? Answering this question requires that we understand the nature of attention itself, and, in particular, the nature of the cognitive and neural systems that orient attention to memories.

With support from the National Science Foundation, Michael Anderson at the University of Oregon will examine the mechanisms that focus attention on memories, building on a wealth of cognitive and neurobiological research on visual attention. This prior work shows that there are two forces that determine where attention is in the visual world: internal mechanisms by which we intentionally focus on a particular region in space, and reflexive mechanisms that capture attention and orient it to suddenly appearing stimuli. This project examines whether the neural systems that shift attention to stimuli with abrupt onsets in the visual world are also engaged to orient attention to an unwanted memory. The role of the hippocampus will help distinguish attention guided by memory from that guided by vision. This project will also examine whether intentional control over reflexive shifts of attention in memory is accomplished by inhibitory mechanisms mediated by the prefrontal cortex that suppress memories in the hippocampus, and the reflexive orienting system itself. The research combines traditional cognitive methods, a new approach to measuring intrusive memories, and functional magnetic resonance imaging (fMRI) to understand the neurocognitive basis of mnemonic reflexive orienting and its regulation by inhibition. If correct, this view will forge a highly specific connection between research on attention and long-term memory, and will specify a rich framework in which to understand how human beings control unwanted memories. Such insights are not merely of theoretical significance, but of profound practical importance in ameliorating the conditions of those suffering from intrusive memories. For numerous people experiencing traumas large (e.g. Hurricane Katrina) and small, the need to control unwanted memories is unfortunately all too clear. Basic research specifying the cognitive and neurobiological mechanisms of memory control will inform theories of clinical syndromes characterized by disordered thought control such as post-traumatic stress disorder (intrusive flashbacks), depression (unwanted ruminations), attention deficit / hyperactivity disorder (distractability), obsessive compulsive disorder (obsessive thoughts) and addiction (craving related thoughts).

[This application has been revised and substantively improved on the basis of reviewers'recommendations. Changes within the proposal are highlighted by a different font (compared to this original font) and are bracketed. The following improvements should be apparent in the present proposal: Many studies from the original proposal have been dropped, and the project has been streamHned. It is difficult to resist being overly ambitious, as was true of the original submission, when proposing five years of experiments from a large and productive research team that is excited about our collaborative opportunities, both among ourselves and with the other investigators in this program who are studying complementary phenomena. On the one hand, the rhesus monkeys tested in these studies complete, as a group, almost 100,000 trials per week across tasks and studies, providing an ample foundation for the present investigations as well as the studies proposed by other researchers in this program. Similarly, this project team tested an average of over 500 undergraduate volunteers per year in the last four years. We certainly want to generate the most science possible across the proposed 5-year funding period. On the other hand, we acknowledge that the more studies that are described in a single proposal, the less clear the details of those studies can be, the less coherent the proposal appears, and the harder it becomes to see the theme that ties the studies together. In organizing the remaining experiments, we have sharpened our construct definitions by ensuring that the tasks in Study 1 reflect the control of attention (selection of some stimuli rather than others) for processing. There is of course a longstanding debate regarding whether attention is selection of stimuli for processing (early selection), or selection of a response (late selection). In light of the reviewers'comments, we avoided this debate in the present proposal by choosing early-selection tasks (tests of how well individuals select some stimuli and ignore others). We moved response-selection tasks, together with other tests of cognitive control, into Study 2. Several very interesting cognitive tests related to executive functioning (including planning, monitoring, and statistical learning were deleted from Studies 2 and 3 so as to maintain theme of "the control of attention" across the project. Although we agree with the reviewer who described these tasks as clever and compelling, we also agreed with the reviewers who saw them as peripheral to the central theme. Study 3 was consequently refocused on the reciprocal role of attention and learning[unreadable]which seems critical, given our desire to understand how learning establishes the experiential and executive constraints that vie for control over attention (i.e., of anchoring "executive" in behavior rather than allowing it to remain an undefined homunculus. This study also supports our translational effort to identify particular t3rpes of training (including symbol training) that might alter the control of attention. The net result of these reductions in experiments, together with the decision to move the details of the fMRI testing and analyses to the Core where they belong, provided space for elaborating on the brain-behavior experiments we will tackle during this funding period. We have attempted to show that it is timely to study these cognitive competencies using neuroimaging technologies. We have also added to the preliminary studies to build the foundation for this entire proposal. At the same time, we did add several experiments that were specifically recommended by the reviewers or by our review of the recent literature, including (a) a replication of two previous findings (Ei.i) using conditions that calibrate baseline performance levels across species;(b) addition of the eyes-looking task to complete the possible comparisons within the cognitive-control study E2.1;and (c) addition of CPT-AX testing to distinguish between proactive and reactive responding, consistent with a recent model of cognitive control. The results of Ei.i could potentially change the design of each subsequent experiment. In this revision, we believe that we've achieved a good balance by including the studies that have the greatest probability of addressing our specific aims, and by eliminating relatively uninformative or potentially redundant tests of specific populations or with specific measures. We recognize that one confusing element of the original proposal pertained to which participant groups would be tested on which specific studies. In part, this is a result of our desire to base those decisions on the results of earlier experiments. For example, we don't want to administer a task to children or chimpanzees until it has been shown to be a good task, in the sense of producing meaningful variations as a result of the independent-variable manipulations, in testing with undergraduate participants or monkeys. It is neither practical nor scientifically necessary to test every group (naive and experienced macaques, capuchins, chimpanzees, children, undergraduates with and without ADHD) on every task and condition. However, we want understand attention control from comparative, developmental, neuropsychological, and of course cognitive perspectives, and thus it is necessary to test multiple groups. Additionally, to control for the influence of different levels of motivation, training, and so forth, it is necessary to produce converging evidence by using multiple tasks. Taking all of this into consideration, the final proposal is summarized below: Study 1. The determinants of attention: What controls selection of cues that compete for processing? Subjects = Rhesus monkeys. Capuchin monkeys, undergraduate volunteers;chimpanzees, children and adults with ADHD possible on a subset of tasks, contingent on initial findings;neuroimaging studies likely with a subset of tasks, contingent on initial findings (e.g., fMRI and TCD with humans of Stroop-like selection, ANT, CPT;TMS witii monkeys of anti-saccade, ANT) a. Stroop-like selection: Ei.i=numerical Stroop;Ei.3=ANT;Ei.4= multi-modal "Stroop", social Stroop (E1.4), global/local, bullseye flanker b. Attention scanning: Ei.i=anti-saccade;Ei.2=dual-task paradigms;Ei.3=ANT c. Attention sustaining: Ei.3=CPT, MOT, ANT Study 2. How does attention control relate to other aspects of cognitive control? Subjects = Rhesus monkeys. Capuchin monkeys, undergraduate volunteers;chimpanzees, children and adults with ADHD possible on a subset of tasks, contingent on initial findings;;neuroimaging studies possible with a subset of tasks, contingent on initial findings (e.g., fMRI and TCD with humans of inhibition tasks, running memory;TMS with monkeys of Simon-task) a. Inhibition tasks: E2.i=dots, heart/flower, eyes-looking;E2.4=stop-signal b. Set-switching: E2.2=Shape School, WCST c. Working memory: E2.3=running memory, N-back, symmetry span Study 3. How does learning influence attention control, and how does attention influence learning? Subjects=Rhesus monkeys, Capuchin monkeys;humans and chimpanzees possible , contingent on initial findings a. Relational/Associative learning: E3.i=meaningful failures, meditational paradigm b. Training effects: E3.2=symbol training;E3.3= "executive" training The theme that binds these studies is the competition between stimulus events (e.g., attention capture), stimulus associations (e.g., conditioned or primed attention), and higher-order intentions (e.g., executive attention) for the control of selection and behavior. Although this specific model is not accepted in the literature, there is little reason for concern that the data would be impugned if the framework is rejected. This theoretical perspective echoes the longstanding and widely embraced distinction between top-down and bottom-up processing (a distinction known by many names) and is consistent with the recent effort in comparative cognition to understand cognitive control while acknowledging stimulus control. Our competition framework, inspired by neural-net connectionist modeling, finds theoretical kinship with numerous other theories (e.g., the race model of attention;Bundesen, 2000). Although the distinction between the capture of attention by environmental cues (like motion, sudden change, and dishabituation) and control of attention by experience (as in contention-scheduled, automatic, and primed processing) is unique to the present model, the experiments proposed here will permit empirical test of whether attention is influenced by variables falling into these three specific classes[unreadable]or perhaps into just two, or even just one category. In summary, one need not embrace the framework to find value in the studies. What seems unlikely to be fragile about the model is the assumption that multiple potential cues compete for attention (as reflected behavior) at any moment in time; that by varjdng the potency or strength of each of these cues and measuring the results on response latency, accuracy, and pattern, one can identify meaningful individual and group (including species) differences in the control of attention;that these characteristic differences in sensitivity to various competing constraints on attention may also be evident in the control of other cognitive operations;and that reliable variations in the control of attention should be manifest in different patterns of brain activity that correspond to the different patterns of behavioral response. At a large and diverse university like Georgia State where most of the human participants will be tested, concerns about the representativeness of the sample are limited. However, this proposal also extensively employs a colony of highly experienced resident animals at the Language Research Center, and so we are particularly concerned about the suggestion that these animals and their prior experience could seriously compromise the present results. Without doubt, we are able to test these monkeys and apes on tasks that would be difficult or impossible to administer to naive animals. Similarly, these animals have demonstrated some cognitive competencies that were heretofore thought beyond the range for monkeys or apes. Part of the reason we have such confidence in Our hypotheses that monkeys differ from humans in the capacity for executive control of attention is that these particular monkeys seem ideally trained and prepared for comparison with humans on computerized cognitive tasks. Each of the tasks proposed here builds on extant repertoires and prior experience, just as we assume that the humans will enter each test with a history of experiences in attending, learning, and problem solving that serves to prepare them. That said, we do intend to assess the role of experience, in part by testing relatively naive macaques on selected tasks. In sum, we believe that the monkeys'and chimpanzees'history of participation in cognitive research supports and is a strength of the current proposal. As the reviewers correctly note, the critical challenge of such a program of research[unreadable]indeed, of every scientific study of different groups, whether the groups are defined by species, age, culture, diagnostic category, performance level, or some other criterion[unreadable]is to ensure that the different groups are tested comparably. This team of investigators is highly experienced with such between-groups comparisons, although this alone does not change the difficulty of the task at hand. Individual and group differences in sensitivity to stimulus conditions, delay of reward, and similar variables are inherent in these comparisons, and indeed are a topic of study in this proposal. We have built several validity- and calibration-checks into these studies, and we've expanded the discussion of these in the proposal. Briefly, our confidence in the conclusions from these between-groups comparisons will be increased to the degree that (a) they reflect convergent evidence across tasks and manipulations (e.g., species differences in the capacity for the executive control of attention are seen in Stroop and vigilance tasks, and are similar for manipulations of incentive and for manipulations of concurrent workload);(b) within-subject differences serve as the foundation for between-groups comparisons (e.g., monkeys are not less attentive than chimpanzees, but compared to chimps the monkeys'attention was more affected by increases in stimulus-response association strength);(c) manipulations have similar effects across groups in baseline performance[unreadable]verifying that performance is not at ceiling or floor and that the manipulation is sufficiently large to influence behavior[unreadable]but different effects across groups in the critical stimulus-conflict conditions (e.g., stimulus movement improves target detection for children and adults, but is more disruptive for children than adults when nontarget stimuli move);and (d) training and/or instructions are provided to ensure that asymptotic or criterial performance is being compared for all groups. Without denjdng the challenge before us, we believe that the reviewers'suggestions have improved our ability to address our specific aims with studies that will withstand the judgment of the literature.

DESCRIPTION (provided by applicant): Tobacco addiction remains a major public health problem. The overall goal of this research project is to test whether one form of meditation training (integrative body mind training, IBMT) changes brain circuits involved in smoking addiction and if IBMT improves autonomic activity sensitive in smoking withdrawal symptoms. The proposed two-year project will therefore address three issues in nicotine addiction (i) whether short-term IBMT changes the brain connectivity between the anterior cingulate cortex (ACC) and striatum involved in smoking addiction (ii) if IBMT improves the parasympathetic activity indexed by heart rate variability (HRV) and skin conductance response (SCR) and (iii) if changes in this circuitry correlate with reduction of smoking and of withdrawal symptoms. Smokers will be chosen from extensive databases available at the Oregon Research Institute. Verification will use the Fagerstr"m Test for Nicotine Dependence (FTND), Tobacco Craving Questionnaire (TCQ) and interview to classify the level of addiction and frequency of smoking. Participants will be randomly assigned to IBMT or relaxation training groups. To ensure IBMT increases activity and connectivity in the ACC-Striatal circuit in this group we will conduct fMRI studies to scan participants at rest before and after 2-week training of IBMT and relaxation. Nicotine addiction also involves physiological changes, especially during nicotine withdrawal. Previous studies suggest that decreasing high-frequency HRV (lower parasympathetic activity) could be a biomarker for the withdrawal symptoms. IBMT has been found to improve parasympathetic activity indexed by greater high-frequency HRV and thus could help reduce the withdrawal symptoms resulting from malfunctions of the autonomic nervous system. Based on our previous work these changes should occur in two weeks. In addition a smoker in our current study showed this pattern after 5 days of IBMT and reported greatly reduced smoking habit and withdrawal symptoms in two weeks. In addition to brain imaging, each subject will also be assessed before and after training with the Attention Network Test (ANT), Adult Temperament Questionnaire (ATQ), Profiles of Mood States (POMS), FTND and TCQ to get the attention efficiency/self-regulation ability and mood states. These behavioral assays will provide the evidences for the intervention effects. Each person will be followed up with the behavioral assays 3 and 6 months after the training. To measure the success of the training on tobacco use we examine changes in the FTD and TCQ in each group, we conduct the correlation analysis between resting connectivity in the ACC-Striatal circuit and the scores of FTD and TCQ. If successful, these studies will provide an effective, inexpensive and harmless method of reducing tobacco addiction. PUBLIC HEALTH RELEVANCE: Tobacco addiction remains a major public health problem. The overall goal of this research project is to test whether one form of meditation training (integrative body mind training, IBMT) changes brain circuits involved in smoking addiction and if IBMT improves autonomic activity sensitive in smoking withdrawal symptoms. The proposed two-year project will therefore address three issues in nicotine addiction (i) whether short-term IBMT changes the brain connectivity between the anterior cingulate cortex (ACC) and striatum involved in smoking addiction (ii) if IBMT improves the parasympathetic activity indexed by heart rate variability (HRV) and skin conductance response (SCR) and (iii) if changes in this circuitry correlate with reduction of smoking and of withdrawal symptoms. Tobacco addiction remains a major public health problem. If successful, these studies will provide an effective, inexpensive and harmless method of reducing tobacco addiction.