Wendy Heller - US grants

In the project described in this proposal, I am examining the relationship between brain activity, as measured by EEG alpha, and the ability to perform a narrative task in depressed and anxious individuals. In my previous research, I have used behavioral methods to infer brain/behavior relationships (e.g., tachistoscopic presentation of stimuli to either the right or left visual field). This work has led to a model of brain functioning in emotion (Heller, 1990; 1993) that makes specific predictions about brain activity during depression and anxiety, with implications for the performance of behavioral tasks. In order to test the model, it became important to measure brain activity more directly. Therefore, I plan to examine patterns of EEG activity in conjunction with measuring behavioral functions with a narrative task. Evidence from studies employing EEG, blood flow and neuropsychological assessment suggests that different patterns of brain activity are associated with depression and anxiety. However, the results have been inconsistent, particularly with regard to the posterior region of the right hemisphere. One reason for this lack of clarity is likely to be that studies have not carefully separated depressed individuals with and without anxiety and vise versa. In the present study, I will examine brain activity in individuals in whom the degree of both depression and anxiety has been ascertained. It is hypothesized that depression and anxiety will each provide a unique contribution to the level of regional brain activity. In particular, high levels of anxiety are predicted to be correlated with high activity of right posterior regions; conversely, high levels of depression will be correlated with low right posterior activity. Since the patterns are hypothesized to be opposite, people who are both anxious and depressed are expected to display levels of activity midway between depressed and anxious subjects. In addition, because the right posterior region plays an important role in processing narrative information, level of activity in this area is predicted to correlate with performance on the behavioral task, with reduced activity associated with poorer performance. Given the fact that anxiety and depression often occur, it is likely that by clearly differentiating the degree to which each is present, we will be better able to discern the underlying patterns of brain activity that characterize these emotional states. The results may thus shed light on the failure in previous research to find consistent results for brain activity, particularly as measured over posterior regions. Furthermore, the behavioral task is of particular interest because narrative interchange is the most common mode of psychotherapy. The results are therefore likely to have implications regarding treatment efficacy in depressed and anxious individual.

DESCRIPTION (provided by applicant): This project will continue to examine the interaction of psychological and neural mechanisms involved in cognitive dysfunction in psychopathology, emphasizing the impact of emotion on attentional processing in anxiety and depression. Anxiety and depression are characterized by cognitive biases leading to functional impairments. Anxiety has been strongly associated with an attentional bias to threatening stimuli. In depression, deficits have been described for explicit memory, executive functions, and visuospatial skills. Biases in attention, memory, and judgment have also been documented. Despite these well-documented effects of affective disorder on cognition, much less is known about the effects of emotion on the specific brain regions involved in cognition. Although we and others have described a number of theoretical possibilities regarding the interaction of emotion and cognition in the brain, lack of data renders these hypotheses speculative. The present project brings together scientists investigating brain function using different methods (behavioral performance, EEG/ERPs, fMRI) in an effort to examine concurrently the brain structures involved in attention and emotion. The project is guided by two well developed and complementary models: a clinically-based neuropsychological model of emotion in psychopathology extensively investigated by Heller, Miller, and colleagues, and a normative model of attention developed by Banich, Webb, and colleagues. The integration of these models allows us to generate specific hypotheses about patterns of regional brain activity in anxiety and depression and their role in attentional processing. With very promising results, we have begun comparing performance and regional brain activity measures during the classic color-word Stroop task to the same variables during an emotional Stroop task, a paradigm that has received much attention in recent anxiety research. In the emotional Stroop, individuals ignore the content of threatening words while attending to and identifying the ink color in which the words appear. These paradigms have been extensively piloted in the initial funding period of this project and in the next project period will be employed with clinical samples with DSM-IV disorders. The proposed convergence of hemodynamic and electrophysiological methods across these two versions of the Stroop will enable us to test hypotheses about the interaction of neural networks involved in emotion and attention across a range of mood and psychopathology.

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Positive affect improves, but depression impairs, performance on tasks of executive function (Levin et al., in press). Extreme emotions are not necessary for these effects: even mild conditions of positive affect or feeling down have observable influences on the way in which people process information. We have argued that the mechanism of these effects depends on emotion-dependent changes in regional brain activity that either enhance or impair performance, depending on the role that a particular brain region plays in the implementation of a task. To date, however, there has been no systematic evaluation of the impact of specific emotional states on executive function, nor has there been an assessment of the brain activity involved. The present project, based at U. Illinois, will examine both state and trait contributions of emotion to executive function and has two specific aims. In the first, the effects of state emotion on brain activity will be assessed by inducing mood measuring fMRI during the color-word Stroop task. Our model of regional brain activity during emotional processing will be integrated with Banich's cascade model of attentional control. In addition, we will examine the effect of simulated emotional states on the computational model developed in Project 1. The second aim is to integrate our model of brain organization for different emotions with U. Colorado colleagues'model delineating subcomponents of executive function (inhibition, shifting, and updating). Neuroimaging findings suggest that there are both common and distinct neural networks involved across the domains (Collette et al., 2005). Activity in these same neural networks has been implicated in our models of emotional experience and regulation. These data suggest that different emotions may be asssociated with distinct patterns of impaired or enhanced executive function. The focus of Aim 2 is to examine the influence of trait emotion on executive function by selecting people who score high on affective dimensions that we have shown to be associated with distinct patterns of brain activity as measured by fMRI and ERPs. Understanding the ways that both state and trait affect might influence cognitive processes and associated patterns of brain activity will provide insight into common everyday experiences as well as emotion/cognition interactions associated with individual differences in personality traits that might be related to current or future depressive episodes.

DESCRIPTION (provided by applicant): Support is requested for the continuation of a research training program in cognitive psychophysiology. The training program responds to the increasing penetration of psychophysiological techniques into many domains of the behavioral and biological sciences. Psychophysiological techniques include electromagnetic, hemodynamic, and optical neuroimaging methods, as well as measures of more peripheral bodily functions (such as eye movement, heart rate, electrodermal activity, and electromyography, in all of which we have expertise). Scientists trained in many subdisciplines of psychology, psychiatry, neurocience, bioengineering, radiology, physics, and other fields are adopting these measurement approaches to attack mental illness. There is a pressing and even accelerating need to provide training in cognitively sophisticated psychophysiology for basic, clinical, and translational scientists. The program faculty are active scientists with diverse backgrounds and interests, based in the Departments of Psychology, Psychiatry, Bioengineering, Statistics, and Electrical and Computer Engineering as well as the interdepartmental Neuroscience Program and the Beckman Institute, emphasizing fMRI, ERP, and optical methods and their integration with each other and with other methods, especially MEG and eye movement. The training program brings the core faculty members and their graduate students and postdocs together in an exceptionally rich environment, in terms of both diverse scholarship and excellent facilities, that provides thorough training in cognitive psychophysiology through coursework and an intensive research apprenticeship, augmented in the next funding cycle by broadened exposure to psychopathology and training in advanced biosignal processing for studying the implementation of the mind by the brain and its disruption in mental illness. Sixteen core faculty will be available to 4 predoc and 3 postdoc trainees. Relevance: Training in cognitive psychophysiology directly addresses NIMH priorities for understanding brain mechanisms in mental illness. Assessment and intervention strategies will benefit to the extent we identify brain implementations of abnormal psychological phenomena.