Steven Yantis, B.S., Ph.D. - US grants

The use of reaction time is ubiquitous in behavioral research. It has been applied in studies of perception, memory, language, reasoning, and action. Patterns of reaction time have revealed aspects of the detailed structure of human cognitive architecture. However, the use and interpretation of reaction time in behavioral research requires an appropriate metamodel of the dynamic properties of information processing. In particular, use of reaction-time methodologies and detailed modelling of cognitive processes require knowledge of whether the movement of information between processes involves the transmission of discrete quanta of information or a continuous flow of information. The disposition of this dichotomy has profound consequences for the interpretation of reaction time data and for the temporal properties of information processing architectures. Conventional reaction time techniques are not sufficient to distinguish between the discrete and continuous models. The proposed research overcomes the limitations of previous procedures in directly addressing the discrete/continuous problem. Two domains of visual information processing are isolated and an adaptive priming procedure is used to study visual information processing dynamics. The procedure involves providing subjects with partial advance (priming) information relevant to an imperative task. Reaction times are then measured as a function of the nature of the partial advance information and the moment in time that it is provided in advance of the imperative stimulus. Under models postulating discrete transmission of information between processes, reaction times from certain priming conditions should form a family of mixture distributions. Continuous models predict the absence of mixture distributions. Through the mathematical analysis of reaction time distributions in different conditions, discrete and continuous models can be tested. Two related but distinct series of experiments are proposed, concerned with (a) the dynamics of manual response preparation and (b) the dynamics of visual attention allocation. The experiments will advance our knowledge of the dynamic properties of these substantive domains, and test the predictions of the discrete and continuous classes of models. The importance of information-processing models and the interpretations they afford for reaction time procedures are central to research on mental health. The results of the proposed research concerning the structure and properties of normal human cognition will contribute substantially to the construction of models of mental health disorders and to the development of diagnostic instruments and treatment procedures.

The function of vision is to extract information from the input image that can be used to achieve current goals (e.g., accurate object identification, efficient navigation). The computational structure of the visual system is commonly viewed as a hierarchy of representational levels (e.g. Marr, 1982), ranging from an early "raw" visual code to an abstract object-model representation. Visual attention is a process that intelligently selects features or objects from one or more early representations and delivers them to higher processes which then generate more abstract representations. Attention can be active and goal-directed or passive and stimulus-driven. The proposed experiments test hypotheses about the mechanisms subserving goal-directed and stimulus-driven attentional selection. In the proposed project, (1) we examine how stimulus-driven "attentional interrupts" from motion, flicker, and featural singletons are serviced by the visual system; (2) we propose a model of visual selection that incorporates a parallel random-walk mechanism, and carry out experiments to test various aspects of the model; (3) we examine how early perceptual organization mechanisms interact with attentional mechanism using a new multielement visual tracking task; and (4) we probe the representational basis for attentional selection, testing object-based and location-based accounts. The proposed experiments will provide new evidence concerning the appropriate architecture for visual selection, and will contribute to the overall objective of deriving a comprehensive theory of intermediate-level vision. In addition to its basic-research implications, such a theory is required to guide further advances in our understanding and treatment of pathologies of the visual system at all levels, including neurological disorders from closed-head injuries and stroke as well as deficits due to biochemical imbalances.

The function of vision is to extract information from the input image that can be used to achieve current goals (e.g., accurate object identification, efficient navigation). The computational structure of the visual system is commonly viewed as a hierarchy of representational levels (e.g. Marr, 1982), ranging from an early "raw" visual code to an abstract object-model representation. Visual attention is a process that intelligently selects features or objects from one or more early representations and delivers them to higher processes which then generate more abstract representations. Attention can be active and goal-directed or passive and stimulus-driven. The proposed experiments test hypotheses about the mechanisms subserving goal-directed and stimulus-driven attentional selection. In the proposed project, (1) we examine how stimulus-driven "attentional interrupts" from motion, flicker, and featural singletons are serviced by the visual system; (2) we propose a model of visual selection that incorporates a parallel random-walk mechanism, and carry out experiments to test various aspects of the model; (3) we examine how early perceptual organization mechanisms interact with attentional mechanism using a new multielement visual tracking task; and (4) we probe the representational basis for attentional selection, testing object-based and location-based accounts. The proposed experiments will provide new evidence concerning the appropriate architecture for visual selection, and will contribute to the overall objective of deriving a comprehensive theory of intermediate-level vision. In addition to its basic-research implications, such a theory is required to guide further advances in our understanding and treatment of pathologies of the visual system at all levels, including neurological disorders from closed-head injuries and stroke as well as deficits due to biochemical imbalances.

Among the most important and least understood properties of human brain function is that of top-down control of perceptual and cognitive operations. Cognitive control is what makes people intentional beings rather than stimulus-response automata. The aim of the proposed research is to investigate the neural basis of attentional control in the human visual system using functional magnetic resonance imaging (fMRI) and suitably designed cognitive paradigms. We have chosen to focus on the visual system because it is arguably the most well understood neural system (at least from a bottom-up perspective), and this knowledge base can be used to guide experiments that investigate top-down control. Much recent work in cognitive neuroscience has revealed the extent to which the neural response of early perceptual regions of the brain (e.g., V1, V4, MT, the Fusiform Face Area) can be modulated by top-down attentional control. However, while these studies of the effects of attentional control are crucial pieces to the puzzle, very few studies have focused on the source of attentional control signals. This is the primary focus of the proposed project. The specific aims of the project include (1) investigating the neural circuits that are involved in focused attention and in controlling shifts of attention between spatial locations; (2) investigating the control of object-based and feature-based selection, and determining whether they share an anatomical locus with that for location-based selection; and (3) investigating the frontal and posterior areas that control both task-shifting and attention-shifting. Together, the proposed project will significantly advance our understanding of how attentional control is exerted to modulate sensory input, and this in turn will contribute to theories of cognitive control throughout the brain.

DESCRIPTION (provided by applicant): The overall aim of this continuing project is to investigate the neural basis of cognitive control. In the first 4 years of the project, we have conducted several dozen experiments that have focused on the neural basis of attentional control using functional magnetic resonance imaging (fMRI) and suitably designed cognitive paradigms. We now propose experiments to extend this work into the domain of task switching. The extension is a natural one in that the control of attention shifts can be viewed as a special case of task switching. We conceptualize a task as a combination of (a) one or more relevant or attended sensory inputs (e.g., digits at different locations on a computer screen), (b) the cognitive operation(s) that must be performed on the inputs (e.g., decide if the digit is even or odd), (c) the rule that maps the outcome of the cognitive operation to a specific behavioral response (e.g., 'if even, move left;if odd, move right'), and (d) the motor response set (e.g., eye movements or manual button presses). Task switching is the deliberate replacement of one or more of these task components with another. The experiments we have conducted so far have provided insights about the neural mechanisms of attention switches (i.e., switching inputs) in isolation, and have permitted us to optimize our cognitive paradigms for fMRI. The proposed experiments extend these studies to the other task components (operations, mapping rules, and response sets) and to combinations of components. The specific aims of the project are (1) to investigate the neural circuits that are involved in controlling input, operation, mapping, and response set switches alone and in combination;(2) to investigate the control of switching to and from tasks that are automatic vs. controlled;(3) to investigate the role of between-task crosstalk and cue switches vs. task switches and (4) to correlate behavioral measures of task switching with cortical signatures of task switching. The proposed project will advance our understanding of the neural basis of cognitive control during task switching, and this in turn will contribute to our understanding of impairments of cognitive control caused by brain damage or drug abuse.

DESCRIPTION (provided by applicant): This proposal on "Validation of Structure and Function in Computational Functional Anatomy" requests four years of continued funding for grant 1R01-EB00975-01. The long-term goal continues to develop Computational Anatomy (CA) methods for assigning functional MRI (fMRI) activity to anatomical coordinates. A central issue in fMRI research is the problem of precisely localizing regions of activation and associating these regions with anatomical labels. fMRI data tend to have both a low signal-to-noise ratio and a low spatial resolution compared with structural MRI data. There is also considerable biologically-based individual variability in the shape of the brain that is a significant confounding variable in associating fMRI activity with a specific brain region. One solution to this problem of individual variability is to transform the functional scan coordinates within the individual's structural scan by constraining anatomically the activation for a given individual to that individual's high resolution cortical structure. In the previous grant, this was achieved via the Large Deformation Diffeomorphic Metric Image Mapping (LDDMM Image) algorithm which increased the statistical power of assigning fMRI signals in a region of interests (ROI) such as the medial temporal lobe and the occipital cortex in memory and visual tasks respectively. The first major focus of our proposal is on the direct assignment of functional signals to cortical coordinate systems via ROI-LDDMM by extending our previous work to memory and vision activity in multiple and connected structures. FreeSurfer has emerged as a powerful tool for parcellating and reconstructing multiple cortical and subcortical structures leading to the second major focus of integrating LDDMM with FreeSurfer parcellation. MRIStudio has also emerged as a powerful tool for analyzing white matter anatomy leading to the third focus of enabling LDDMM to register scalar images derived from diffusion tensor imaging (DTI) data to provide greater statistical power in quantification of white matter anatomy. By integrating these innovative CA tools, we propose to significantly expand upon our initial goals via the following interrelated specific aims. Aim 1 will validate ROI-LDDMM and integration of Free Surfer-LDDMM for studying shape and segmentation of multiple subcortical structures. This will permit mapping of subcortical structures such as the thalamus and basal ganglia and will be applied in Aim 3. Aim 2 will validate the integration of LDDMM in MRIStudio for quantifying white matter fiber tracts connecting subcortical and cortical ROIs via multi-channel LDDMM mapping of DTI data. This will permit reliable assessment of white matter integrity in fiber tracts between predefined ROIs and be applied in Aim 3. Aim 3 will validate the reliability of functionally defined ROIs and structural white matter properties between them using (a) visual retinotopic mapping, (b) cognitive tasks, and (c) white matter anatomy between these functionally defined regions using DTI. The validated tools will be disseminated to the neuroimaging community under the auspices of the Biomedical Informatics Research Network (BIRN) via the C portal for LDDMM and MRIStudio. PUBLIC HEALTH RELEVANCE: Accurate functional and structural parcellation of activated structures will permit precise analysis of functional activation in the brain. Thus accurate location of brain activation in visuospatial attention and cognitive control will permit neuroscientists and clinicians greater understanding of functional connectivity in neurodevelopmental and neurodegenerative disorders.

DESCRIPTION (provided by applicant): This is a resubmission application for a Competing Renewal of a currently funded grant (R01-DA13165-10). The overall aim of this project is to investigate the psychological and neural basis of human cognitive control in healthy adults. Since the last competing review of this project, we have published 19 refereed publications that have elucidated the mechanisms of cognitive control in attention shifting and task switching using functional magnetic resonance imaging (fMRI) and suitably designed behavioral paradigms. Successful cognitive control requires both stability (maintained states of attention and memory despite distraction) and flexibility (to rapidly reconfigure attention and cognition in light of ongoing events). The proposed project will further explore these issues using novel methods and with a focus on both cortical and subcortical brain mechanisms. Aim 1 investigates purely voluntary acts of control-that is, task switching that is not prompted by a cue, but instead results from a purely voluntary decision. We will use a novel multivariate pattern analysis method we have developed (Multivoxel Pattern Time Course or MVPtc) that dynamically tracks multivoxel patterns of brain activity-and the corresponding states of attention or task engagement they engender-as these states unfold over time. This method permits us to relate brain activity with patterns of behavioral performance, as well as to explore functional connectivity within brain circuits that are associated with these cognitive states. In Aim 2 we examine the role of the basal ganglia in cognitive flexibility and stability during task switching, using both BOLD fMRI and PET dopamine imaging. We will elaborate upon recent evidence for the role of the basal ganglia- and specifically the dopamine system-in nonmotoric acts of cognitive control. Finally, in Aim 3, we will examine failures of cognitive control when distracting stimuli impair perceptual performance, with a particular emphasis on the role of experienced value and reward history on the degree to which a stimulus may capture attention. Using MVPtc, we will track fluctuations in the susceptibility to distraction by salient perceptual events or by stimuli previously associated with reward, and we will measure the degree to which top-down control can modulate attentional capture. Finally, we will use parallel PET dopamine imaging and BOLD fMRI to measure changes in striatal dopamine release evoked by salient or high-value stimuli, and correlate this with behavioral measures of distraction. Together these experiments will provide new insights about the brain mechanisms of cognitive control, a core human mental faculty that is subject to debilitating impairment due to afflictions such as drug and alcohol addiction, schizophrenia, Parkinson's and Huntington's Disease, OCD, and attention deficit hyperactivity disorder. This project will contribute to the basic-research foundation for clinical research into the causes and treatment of executive function impairments.