John M. Henderson - US grants

The longterm objectives of this proposal are: 1) to define the regulating mechanisms of hepatic and systemic hemodynamics in liver disease, and determine in which patients pharmacologic manipulation is beneficial to hepatic function: and 2) to initiate study of the hemodynamics of the denervated, transplanted liver. The first objective will be achieved in two phases. Firs, a prospective randomized trial will be conducted in patients with alcoholic cirrhosis after distal splenorenal shunt. This will test the hypothesis that reduction of the systemic hyperdynamic response with propranolol will lower intrahepatic resistance sufficient to allow maintenance of portal flow and hepatic function, with improved survival. In parallel to this study, propranolol, verapamil, ketanserin and the nitrates, drugs which lower intrahepatic resistance, will be evaluated in stable patients with cirrhosis. This phase will test the hypothesis that reduction of intrahepatic resistance will improve portal perfusion and hepatic function. Methodologic studies focus on measurement of portal flow and peripheral vascular resistance. These will use Doppler/ultrasound, magnetic resonance imaging, and angiodynography. Differentiation of peripheral (limb) vascular resistance from total systemic vascular resistance will help elucidate mechanisms of pharmacologic manipulation. The transplanted liver is denervated, and hence the neural control of blood flow is lost. Liver blood flow and portal venous flow will be measured in transplant patients to test the hypothesis that blood flow is increased, and this is primarily through increased hepatic arterial flow. Studies will be conducted in a pig model of liver denervation to define the altered hepatic and systemic hemodynamics, and the response to hypovolemic shock. Cirrhosis has a high morbidity/mortality with variceal bleeding and liver failure. Improved regulation of the abnormal hemodynamics, which are the common denominator to this morbidity, should significantly enhance patient care. The increased application of liver transplant mandates the need for careful study of the pathophysiology of the hemodynamic alterations after transplant and their longterm impact on graft function. These two objectives have common ground in the regulating mechanisms o liver blood flow in health and disease.

Vision is a dynamic process involving continuous changes to the proximal stimulus. Objects move, disappear behind occluding surfaces and then reappear, and are displaced across the retina due to eye, head, and body movements. The purpose of the proposed research is to investigate the nature of the maintenance and combination of information over time and space during dynamic visual object identification. The main focus is to test the hypothesis that the maintenance and combination of object information is a product of two processes, the construction and reviewing of temporary episodic representations (object tokens), and the activation of prestored long-term representations (object types). A secondary focus is to determine whether the maintenance and combination of object information over time and space operates similarly across saccadic eye movements and within a single eye fixation. In order to investigate these issues, three paradigms will be employed. The transsaccadic preview paradigm will provide data concerning the maintenance and combination of object information across saccades. The simulated-saccade preview paradigm will provide data concerning the degree to which the results from the transsaccadic paradigm are contingent on the execution of an eye movement. The within-fixation preview paradigm will provide data concerning the issue of information maintenance and combination in central vision during a single eye fixation. Together, the proposed studies will provide data with which to constrain models of dynamic visual object identification.

When we view the visual world, our eyes flit from one location to another about three times per second, in movements called saccades. Useful visual information is acquired only during fixations, brief periods of time when gaze rests on an object or scene feature. The cognitive and neural processes that direct saccades and fixations through a scene in real time fall under the term 'gaze control'. This project focuses on unraveling how human gaze control operates during active real-world scene perception.

This project approaches human gaze control by starting with the insight that understanding eye movement timing will provide key insight into the underlying cognitive and neural systems that control gaze. The research combines innovative eye-tracking methods with a working computational model that simulates eye movement control. In this research program, the empirical and computational threads are complementary and synergistic. On the one hand, we can test our understanding of gaze control by determining whether the model can produce eye movements that look like those produced by people. On the other hand, insights from the model can be used as a tool to enhance our theoretical understanding of gaze control, and these insights can be further tested with new experiments.

The results from this project will enhance basic scientific understanding of how humans perceive and understand the visual world. The project also has wide-ranging implications for the creation of new display technologies and machine interfaces that can be controlled by eye movements. And the results are relevant for the design of new artificial vision systems that actively track and focus on relevant information in the environment.

Project Summary  Real-­world scenes contain far more information that we can perceive and comprehend at any given moment. A  key mechanism for making real-­world scene perception tractable is visual attention?the mechanism of  preferentially processing only part of the scene at any given time. What we attend to in a scene determines  what we see, understand, and remember. Attention is guided by both the visual properties of the scene itself  and by our knowledge about similar scenes and the world in general. How knowledge is used to guide  attention through a meaningful scene remains largely unknown. The central idea behind this proposal is to  address this fundamental scientific question by focusing on two critical aspects of scene knowledge:  knowledge about where a given object is likely to appear in a scene, and knowledge about which regions and  objects in a scene are meaningful and informative. The studies aim to determine how spatial and meaning  constraints are used to guide attention in scenes.   This proposed research is innovative in combining high-­resolution eyetracking with novel experimental  paradigms for manipulating and measuring knowledge-­based constraints. First, a new fusion of spatial learning  methods with eyetracking is used to study the influence of spatial knowledge on attentional guidance. Second,  new quantitative scene-­rating and information-­theoretic metrics are used to index meaning in scenes, providing  a new theoretical approach to scene meaning and new empirical tools for investigating meaning. Third, real-­ time scene manipulation based on the viewer?s eye movements is combined with manipulations of spatial and  meaning constraints to investigate how quickly knowledge about a scene becomes available to guide attention.  The project is significant in challenging current models to explain the role of knowledge in guiding attention in  scenes. The experiments are designed to advance the field regardless of the outcome, and will provide rich  and theoretically constraining results that may have a transformative effect on current theory. In addition, the  proposed research has important translational implications because deficits in attention and perception are  suffered by many psychiatric and neurological populations. By understanding how knowledge influences the  guidance of attention in real scenes, the proposed studies can ultimately lead to the development of targeted  rehabilitation strategies for the real world that better capitalize on both disrupted and spared functions. 

Project Summary Efficient cognitive processing relies on the brain?s ability to engage in prediction and to use forward modeling to anticipate cognitive events, including during language processing. The central goal of this proposal is to test two competing hypotheses concerning how age influences prediction during auditory and visual language processing. Current evidence is contradictory and sparse, reflecting the need for systematic investigation. The project has three Specific Aims: Aim1: Determine whether older adults predict words in manipulated sentence contexts less or more than younger adults do by examining prediction during reading, using both electrophysiology (EEG) and eyetracking methods. Aim2: Determine whether, during spoken language processing, older adults predict words in manipulated sentence contexts less or more than younger adults do, using EEG and Visual World eyetracking methods. Spoken language processing merits targeted investigation because evidence suggests older adults have specific problems with auditory input. Moreover, in the young adult literature on prediction in language processing, relatively few studies have focused on spoken language, so little is known about whether prediction differs in the two modalities. Aim3: Determine whether older adults predict upcoming words in connected passages less or more than younger adults do, using fixation-related fMRI and EEG methods in reading, with prediction assessed by continuous measures of lexical surprisal and entropy. Surprisal and entropy measures permit the investigation of more naturally varying levels of predictability, more natural distributions of predictable and less predictable information, and allow the investigation of how natural texts (i.e., stimuli not specifically created for an experiment) are comprehended. Innovations: The project is innovative in (1) the use of converging eyetracking, EEG, and fMRI methods to systematically evaluate the extent of prediction during older adults' language comprehension, emphasizing replication across techniques and modalities; (2) the use of continuously varying surprisal/entropy in connected text to index age differences in prediction; (3) the use of a novel technique developed by PI Henderson, Fixation-Related fMRI, to relate neural activation to word-by-word surprisal and entropy during natural reading. Significance: The experiments will yield high temporal resolution information about prediction in older adults during online reading and spoken comprehension, together with detailed information about the neural bases of prediction operations. The findings have important implications for theories of normal cognitive aging. Translational significance: A psychometrically valid assessment of everyday language skills will be used to evaluate the relationship between prediction skills and a measure that has been shown to predict impairments associated with Alzheimer?s disease. Overall, prediction in language processing is potentially a model system for enhancing our scientific understanding of how cognitive and neural decline associated with aging trades off against greater knowledge and experience.

Real-world scenes comprise a blooming, buzzing confusion of information. Yet at any given moment, we can only perceive and understand a small portion of that information. What we see and understand is quite literally determined by where we look. But what determines where we look? This project seeks to answer this important question. The project investigates the idea that the meaning of a scene plays the key role in guiding our eyes. If our hypothesis is correct, then we should find that meaning predicts where people look. Such a result will advance scientific knowledge of how our brains and minds work. The results will also be useful to applied areas of computer science and engineering, contributing to increased US economic competitiveness. High-tech applications include virtual and augmented reality, artificial vision and gaze-based input systems, baggage screening, medical image assessment, satellite image analysis, and other computer-based vision systems. The project will also contribute to training of culture- and gender-diverse students and researchers in these high-tech and scientific fields, advancing the development of a diverse, globally competitive workforce.

Attentional guidance during scene viewing draws on both the visual properties of the scene and its semantic content. Although the role of visual properties (e.g., physical salience) on attentional guidance has been extensively studied, far less is known about how the semantic content of a scene guides attention. Recent work in my lab indicates that the influence of physical saliency is reduced or even eliminated when semantic content is available to guide attention. These findings have opened up important new questions about how and when meaning guides attention in scenes. The central idea behind the current work is to address these questions with a set of targeted experiments. The proposed experiments will integrate new methods for representing the meaning of local objects and scene regions with high-resolution eyetracking to measure the influence of knowledge on attentional guidance in real-world scenes. The research includes experiments motivated by four goals: (1) To compare the roles of contextualized versus context-free local scene meaning in attentional guidance. (2) To evaluate the causal relationship between local scene meaning and attentional guidance. (3) To test the generality of guidance by scene meaning across tasks and viewing time. (4) To compare the roles of physical versus semantic features in scenes using search target templates. The research will establish the foundation for a new theoretical approach to the representation of scene meaning and attentional guidance in scenes. The ultimate objective is to develop a theory of attentional guidance in scenes based on guidance by meaning.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.