CSEA RESEARCH PROJECTS
The primary CSEA research projects funded by NIMH address a series of critical questions on the nature of affective stimulus processing, in consideration of the broad spectrum of relevant psychological, social, and biobehavioral issues. The projects provide connected, complementary knowledge, testing shared hypotheses at different levels of complexity. The research is presented below in a "bottom up" fashion, starting from research extending the basic neural foundations of motivation and emotion, as established in animal research, followed by the larger effort of translating this work into the arena of human experimentation.
Relevance to mental health— Emotional dysfunction is characteristic of almost all ‘functional’ psychopathology— from neurosis (e.g., dysthymia, anxiety disorders) and substance abuse to psychopathy and psychosis (e.g., depression and schizophrenia). Advances in the assessment and treatment of these disorders depend on progress in emotion research. That is, insight into basic mechanisms in emotion is fundamental to the scientific understanding of emotion’s pathology. In general, the proposed research with human beings will employ healthy adult participants. However, several experiments will be focused on sub-clinical populations that have specific fears, higher than average levels of generalized anxiety, depression, or traits consistent with psychopathy. These experiments in particular are expected to immediately contribute meaningfully to the understanding of the related pathologies, as are preliminary efforts to address individual difference measurement with clinical populations. Founded on the results of the proposed basic research, other paradigms that show translational promise can then be explored in the clinical arena.
Project 1. Role of the Medial Nucleus of the Amygdala in Fear Inhibition
Principal Investigator. Michael Davis, PhD
Site. Emory University, Atlanta, GA
The broad aim of this research is to explicate in rodents a hypothesized neuronal network that is involved in the inhibition of fear. The network includes the medial nucleus of the amygdala, BNST, ventral subiculum, lateral septum, ventro-medial hypothalamus and intercalated cells—as previously determined with Fos-protein marking of neuronal activation. In determining the network’s anxiolytic effects, morphine, buspirone and diazepam is infused locally into the medial nucleus of the amygdala. The role of opiate receptors in the medial nucleus is evaluated as it modulates extinction and conditioned inhibition of fear potentiated startle. An assessment will also be made of the neuropeptide Y (NPY) cells in the basal-lateral amygdala (and GABA at this site), and of the various network areas identified above. Finally, functional MRI is used to assess network activation during CS (odor) fear retention, extinction, and conditioned inhibition in anesthetized rats. These later experiments will be performed at the Florida Brain Institute, using their 11 Tesla magnet. Blood pressure changes associated with conditioning will be measured in the magnet, and changes in potentiated startle will be assessed outside the magnet in unanesthetized rats.
Project 2. The Defense System: Activation, Extinction, and Motive Gradients
Principal Investigator. Peter J. Lang, PhD
Site. University of Florida, Gainesville, FL
The project addresses basic reflex functions (autonomic and somatic) mediated by the brain’s defense motive system. Three sets of experiments with human participants are proposed that have the following broad aims: (1) to determine autonomic and somatic correlates of the primitive defense occasioned by “looming” stimuli-- signaling imminent collision and evoking a reflex similar to startle— and furthermore, to define brain structures critical in processing “looming” stimuli and in mediating the defense response; (2) to assess the effects of repeated aversive stimulation and elucidate conditions that promote the habituation or sensitization of psychophysiological indices of unpleasant emotion, and to asses related changes in brain function (3) to determine patterns of change (defense reflex physiology and brain activation patterns) on avoidance gradients that define increasing imminence of threat. The research examines what can be considered fundamental features of aversive stimulus processing—reflex reactions that are similar in animals and humans. In pursuing these aims, research begins in the psychophysiological laboratory with measurement of autonomic and somatic reflex responses. High-density EEG in also recoded in this context to determine co-incident electro-cortical events and locate dipole sources. Subsequent experiments track BOLD activity in the MR scanner, to better determine the brain structures and circuits that mediate emotion’s reflexes.
Project 3. Attention to Threat: Motivation and Memory
Principal Investigator. Margaret Bradley, PhD
Site. University of Florida, Gainesville, FL
It is hypothesized that differences in attention to motivationally relevant stimuli, in the absence of an instructional or task manipulation, represent a type of 'natural selective attention', in which cues that activate motivational systems associated with appetite and defense naturally arouse and direct attention. In the current project, the following question is critically addressed: Does instructed attention to non-motivationally relevant stimuli (i.e. emotionally neutral stimuli) result in activation of similar orienting responses, neural activity, and memory performance as found in motivated attention (attention to threat)? The research seeks support for one of two contrasting hypotheses: (1) Motivated and instructed attention utilize the same neural circuits, prompting similar physiological orienting responses, and electro-cortical and BOLD patterns of neural activity, with similar effects on memory performance; or (2) Motivated attention differs from instructed attention in engaging subcortical motivational circuits, prompting a qualitative difference in processing. The research further examines the relative priority of emotional stimuli, naturally selected for processing, when multiple stimuli occur in time or space, compared with the differential selection that occurs on the basis of other semantic (e.g., presence of people) or perceptual (e.g., image complexity) features.
Project 4. Trait Fear and Fearlessness in Humans
Principal Investigator. Christopher Patrick, PhD
Site. University of Minnesota, Minneapolis, MN
The research aims to increase understanding of the role of genetic factors in human fear. A foundation for this work is prior research demonstrating impairments in fear-potentiated startle among incarcerated psychopathic individuals (usually conceptualized as fearless). More recent studies have revealed similar impairments in community participants high in Fearless Dominance—a psychopathy-related bi-polar construct that indexes trait fear at its low pole. Three phases of research are proposed to extend this work, with the following aims in mind: (1) Psychometric measures of trait fear and fearlessness will be collected from a large community twin sample to evaluate genetic and environmental contributions to a latent fear dimension; (2) A subset of these twin pairs will be tested in the laboratory to establish fear-potentiated startle as a marker of this underlying trait fear dimension, and to determine the etiologic basis of this association; (3) Twin pairs will be selected to be low or high on both trait-fear scores and level of fear-potentiated startle. Functional brain activation patterns (fMRI), prompted by emotional stimuli, will be compared among participant groups. This research will contribute to our understanding of the biological underpinnings of trait fear and fearlessness in humans, and also advance conceptualization and measurement of the Fearless Dominance construct, as it relates to personality and psychopathology.
Project 5. Exploring the Fear Module of the Human Brain
Principal Investigator. Arne Öhman, PhD
Site. Karolinska Institute and Hospital, Stockholm, Sweden
The research aims to increase understanding of the brain network controlling human fear, to examine its relationship to conscious cognition, and assess its modification through learning. The project first studies individuals that are fearful of one animal (e.g., snakes) but not of another (e.g., spiders). In these brain imaging experiments (fMRI), fear stimuli are systematically degraded, using masking techniques (assessing awareness), or presented in a visual search task (assessing fear stimulus salience). Other studies will determine changes in brain activation as fear subsides after behavioral and pharmacological interventions. In the second part of the project, normal human participants will be aversively conditioned to fear-relevant stimuli (e.g., snakes) or fear-irrelevant stimuli (e.g., flowers). The research is designed to determine if the pattern of physiological reactivity varies with the participant’s awareness, i.e., do response patterns differ when language processing is absent, and presumably, only the basic fear network mediates learning. These measures will be used in a final series of brain imaging studies, to determine if brain networks differ for conscious (aware) and nonconscious (unaware) learning.
Project 6. Individual Differences in the Motivational Substrates of Emotion
Principal Investigator. John Cacioppo, PhD
Site. University of Chicago, Chicago, IL
The present proposal postulates two asymmetries in human affective information processing— positivity offset and the negativity bias—that are related to fundamental differences in the slopes of approach and avoidance gradients. It is proposed that these biases reflect differences in basic human temperament. Three affective stimulus-processing tasks have been developed to define these emotion/motivational characteristics in individuals, using psychophysiological measures to validate the dimensions. The tasks will then be studied in an fMRI experiment, to define patterns brain activation associated with positivity offset and negativity bias. It is subsequently planned to investigate how these implicit temperament measures differentiate among three groups of individuals: depressed, anxious, and age, ethnicity, & gender-matched healthy controls. A translational aim is to determine if individual differences in positivity offset and negativity bias differentiate affective style within the context of specific psychiatric conditions.
