1985 — 1986 |
Lang, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Fear Modification: Imagery, Cognition, and Control
The continuing goal of the project is to study neurotic anxiety and fear, its development, assessment of effects on health and performance, and therapeutic modification. The current focus of this project is emotional imagery. A theoretical conception of this phenomenon has been developed, based on research and scholarship in the fields of Cognitive Psychology and Psychophysiology. The image is viewed as an information structure in the brain which may be assessed through the measurement of propositionally defined, patterns of physiological arousal. Experiments are proposed which will explicate the roles of instigating text structure, imagery training, individual differences in imagery ability, suggestibility, trait anxiety, and type of neurotic disorder in determining the quality and intensity of imagery experience. A focus of this analysis is on the study of emotion as it is instigated through imagery instructions in a therapeutic context. Our broad purpose is to describe the conditions under which affective reactions are evoked by symbolic stimuli and to explore the mechanism by which emotional imagery is the vehicle of emotional behavior change.
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1 |
1986 — 1988 |
Lang, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Emotion and Aging in Women: Psychophysiology of Imagery
Our goal is to study the psychophysiological patterns of expressed emotions in aging women. The research is intended to examine affective behavior across the lifespan, exploring how changes in emotional responses are related to health and effective functioning. The specific experiments focus on emotional imagery, as it is prompted by narrative descriptions of events, and as such imagery processing is determined by real or conjectural memorial experience. The theory driving this research integrates concepts from cognitive psychology and psychophysiology. Emotions are viewed as action sets or behavioral dispositons (including verbal, overt operant, and covert physiological elements). An affective disposition is represented in memory as a network of concepts, defining context and response. Response concepts are linked to an efferent program which is partially activated during imagery. Thus, emotional pattern can be monitored physiologically during image processing. Two major experiments and their sequelae are proposed, to be conducted in a psychophysiology laboratory, with computer controlled presentation of taped emotional stimulus material, and automated measurement of affective ratings, facial expression, and autonomic and somatomotro responses. Emotional and control imagery will be studied in women who range in age from the third to the ninth decades of life. For women in the 45 to 59 cohort, pre-, peri-, and post-menopausal sub-groups will be separately considered, evaluating the specific impact on emotional expression of this major hormonal transition. The first experiment emphasizes fear and anxiety imagery; the second experiment will explore a range of emotions (anger, grief, fear, and pleasure), with stimulus materials tailored to the subjects' experience, and based on a preliminary interview/survey of emotional content over the lifespan. The importance of several moderator variables will be assessed: "matching" of script material to actual experience, recency of emotional experience, imagery ability, imagery "training", menstral cycle period, disposition to PMS, trait anxiety and emotionality. The results are expected to contribute importantly to understanding how general aging factors and hormonal change with aging impact on women" health, productivity, and effective social funcitoning.
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1 |
1987 — 1991 |
Lang, Peter J |
R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Fear Measurement: Imagery, Cogintion and Behavior |
1 |
1988 — 1999 |
Lang, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Startle Probe in the Study of Emotion
The aim of the proposed research is to explore the startle probe as a procedure for investigating emotional experience. Affect- related modulation of the startle response is conceptualized in terms of an efferent-oriented information processing model, in which the response dispositions activated during an emotional experience are seen as priming the reaction (here, the amplitude and latency of the eyeblink) to a startle stimulus. In this view, supported by preliminary data, similar startle effects will occur whether a foreground affective state is induced by external stimuli (e.g., slides) or by internal processing of affective memories (e.g., imagery). Accordingly, two parallel experimental series, one employing slides and the other imagery, are planned to provide converging evidence regarding this affective priming hypothesis, as contrasted to an alternate interpretation based on attentional factors: Specifically, the research will explore changes in startle response due to the affective nature of the foreground stimulus and the match/mismatch of the foreground stimulus and startle probe modalities. The significance of this research lies in the potential of the startle probe as a tool to investigate such issues in emotion research as dimensional vs. state-specific viewpoints, the function of arousal, and the relationship of physiological response to cognitive and affective processes.
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1 |
1991 — 1993 |
Lang, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Startle Probe in the Study of Emotion
The overall purpose of this project is to extend a series of highly successful experiments testing the hypothesis that the reflexive startle response is modulated by emotional state. The new experiments will critically examine the biphasic model of emotion. In this view, emotions are motivationally driven by reciprocal brain states, either appetitive (favoring approach, attachment, and consummatory behavior) or aversive (favoring avoidance, escape, and defense). Furthermore, the response system as a whole (from cognitions to exteroceptive reflexes) is tuned according to the current status of this central affect-motivational organization. Thus, reflexes associated with an appetitive set should be enhanced, if activated when the subject is already engaged in a positive emotional response; conversely, the startle reflex to a sudden noise is an aversive, defensive response, and would be augmented if it occurred in the context of an ongoing aversive emotion. Inhibition of startle in an appetitive context is also postulated. Specific experiments testing this view manipulate parameters of probe startle stimuli, and examine variations in emotional foregrounds and subject populations. The research is intended to determine: (1) if reflex modulation occurs for both visual and auditory startle probes, in both pictorial and auditory emotional foregrounds; (2) if these effects are in any way constrained by probe intensity or aversiveness; and, further, this work will (3) pursue the significance of lateralized probes for theories of the hemispheric processing of emotion; and (4) begin to determine if the affect-startle effect is unique to startle probes, or is a general phenomena of defensive reflexes. The research will manipulate characteristics of the emotional foregrounds tested by the probe methodology: to determine (1) if the affect-startle effect is consistent at different intensities of foreground emotion and (2) if reflex augmentation is consistent across different negatively valent emotional states; and, further, (3) to explore the effect during emotional memory imagery; and (4) to begin an examination of individual temperament differences in emotional state modulation of the startle reflex.
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1 |
1991 — 1993 |
Lang, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Emotion and Aging: Cognitive Psychophysiology
Our goal is to study the psychophysiological patterns of expressed emotions in aging women. The research is intended to examine affective behavior across the lifespan, exploring how changes in emotional responses are related to health and effective functioning. The specific experiments focus on emotional imagery, as it is prompted by narrative descriptions of events, and as such imagery processing is determined by real or conjectural memorial experience. The theory driving this research integrates concepts from cognitive psychology and psychophysiology. Emotions are viewed as action sets or behavioral dispositons (including verbal, overt operant, and covert physiological elements). An affective disposition is represented in memory as a network of concepts, defining context and response. Response concepts are linked to an efferent program which is partially activated during imagery. Thus, emotional pattern can be monitored physiologically during image processing. Two major experiments and their sequelae are proposed, to be conducted in a psychophysiology laboratory, with computer controlled presentation of taped emotional stimulus material, and automated measurement of affective ratings, facial expression, and autonomic and somatomotro responses. Emotional and control imagery will be studied in women who range in age from the third to the ninth decades of life. For women in the 45 to 59 cohort, pre-, peri-, and post-menopausal sub-groups will be separately considered, evaluating the specific impact on emotional expression of this major hormonal transition. The first experiment emphasizes fear and anxiety imagery; the second experiment will explore a range of emotions (anger, grief, fear, and pleasure), with stimulus materials tailored to the subjects' experience, and based on a preliminary interview/survey of emotional content over the lifespan. The importance of several moderator variables will be assessed: "matching" of script material to actual experience, recency of emotional experience, imagery ability, imagery "training", menstral cycle period, disposition to PMS, trait anxiety and emotionality. The results are expected to contribute importantly to understanding how general aging factors and hormonal change with aging impact on women" health, productivity, and effective social funcitoning.
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1 |
1992 — 1995 |
Lang, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Emotion and Aging--Cognitive Psychophysiology
Our goal is to study the psychophysiological patterns of expressed emotions in aging women. The research is intended to examine affective behavior across the lifespan, exploring how changes in emotional responses are related to health and effective functioning. The specific experiments focus on emotional imagery, as it is prompted by narrative descriptions of events, and as such imagery processing is determined by real or conjectural memorial experience. The theory driving this research integrates concepts from cognitive psychology and psychophysiology. Emotions are viewed as action sets or behavioral dispositons (including verbal, overt operant, and covert physiological elements). An affective disposition is represented in memory as a network of concepts, defining context and response. Response concepts are linked to an efferent program which is partially activated during imagery. Thus, emotional pattern can be monitored physiologically during image processing. Two major experiments and their sequelae are proposed, to be conducted in a psychophysiology laboratory, with computer controlled presentation of taped emotional stimulus material, and automated measurement of affective ratings, facial expression, and autonomic and somatomotro responses. Emotional and control imagery will be studied in women who range in age from the third to the ninth decades of life. For women in the 45 to 59 cohort, pre-, peri-, and post-menopausal sub-groups will be separately considered, evaluating the specific impact on emotional expression of this major hormonal transition. The first experiment emphasizes fear and anxiety imagery; the second experiment will explore a range of emotions (anger, grief, fear, and pleasure), with stimulus materials tailored to the subjects' experience, and based on a preliminary interview/survey of emotional content over the lifespan. The importance of several moderator variables will be assessed: "matching" of script material to actual experience, recency of emotional experience, imagery ability, imagery "training", menstral cycle period, disposition to PMS, trait anxiety and emotionality. The results are expected to contribute importantly to understanding how general aging factors and hormonal change with aging impact on women" health, productivity, and effective social funcitoning.
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1 |
1992 — 1993 |
Lang, Peter J |
R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Fear Measurement;Imagery Psychophysiology and Behavior
The objective of this research is to continue study of a new, integrative theory of imagery and motion, with particular emphasis on its implications for health and performance, and more specifically for the psychopathology of anxiety. The deduced experimental series aims to elucidate the conditions under which affective reactions are evoked by symbolic stimuli, to compare fear responses induced through imagery with those prompted by objective stimuli, to compare fear responses induced through imagery with those prompted by objectives stimuli, to show how differences in the organizations of image representations in memory and the patient's capacity for image generation relate to differences in the anxiety disorders, and to suggest how emotional imagery can serve as a vehicle for emotional change. The proposed experiments examine the psychophysiology of memory retrieval for emotionally evocative text, assessing the relevant subject, content, attentional, and processing mode variables which may define the nature of emotional memory, and which are held to be significant parameters of clinical anxiety. Thus, the project first emphasizes basic research in the validation of a working theory, and secondly applied research, as the implications of the theory lead to specific predictions for the psychopathology of anxiety, its differential diagnosis and therapy prognosis.
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1 |
1994 — 1996 |
Lang, Peter J |
R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Fear Measurement--Imagery, Psychophysiology and Behavior |
1 |
1994 — 2009 |
Lang, Peter J |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Center For the Study of Emotion and Attention
The broad aim of the Center is to study emotional stimulus processing in all its directly measurable manifestations, i.e., as affective report, behavior, and patterns of expressive physiology (facial, visceral, and neuromuscular), and to understand the relation of these processing measures to functional changes in the brain. An important further aim is to study the interaction of emotional reactivity with attentional demands-as attention is modulated by stimulus characteristics, motivational state, and behavioral and social context. Proposed research examines continuity and difference in affective responding over different channels of sensory input, instructions, symbolic or virtual representation, presentation medium, assessing individual differences as well as general response patterns. Findings are interpreted in the view that the brain is an organ for processing information and in consideration of developing knowledge of the brain s functional anatomy and neurophysiology. A theoretical model of emotion and motivation, based on neuroscience research with animals, guide analyses of human affect. Connecting links are sought through human electrocortical (EEG) and brain imaging (fMRI) studies. The center organization includes six primary research projects that range in content from research on the animal model of emotion, to studies of affective picture and language processing, and social/emotional factors in temperament and personality. The Center also includes an international group of affiliated investigators, and three Cores that serve the project: Research Administration and Training, Science Technology, and Media Cores. The Center provides broad services to field of emotion research, developing stimulus materials and advancing laboratory technology, training research apprentices, fostering scientific communication, generally facilitating emotion studies within this country and internationally. The Center investigators have a special concern with translational research-the moving of basic scientific knowledge on emotion into the mental health arena. Thus, there is a sub-focus on maladaptive emotional states, characterized by exaggerated intensity or persistence, as in the anxiety disorders, and on the converse condition, apparent deficit in emotional responding, as in psychopathy.
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1 |
1994 |
Lang, Peter J |
S15Activity Code Description: Undocumented code - click on the grant title for more information. |
Small Instrumentation Grant
biomedical equipment purchase;
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1 |
1995 — 1998 |
Lang, Peter J |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Multimediated Emotion--Physiology, Affect and Behavior
The goal of this project is to assess similarities and differences in affective and attentional responses to various types of media prompts-- pictures, sounds, texts, and films -- in the context of tasks involving either actual stimulus perception or memory retrieval. This investigation of attentional and affective responses in the processing of media prompts to emotional experience will determine 1) physiological, behavioral, and verbal indices of affect and attention, 2) their relationship to system strategic parameters of valence and intensity, 3) variations in reactivity with context-dependent tactical task requirements and stimulus attributes, 4) covariation among response systems, and 5) interaction/independence of attentional and affective influences on responses across and within each subsystem. The construction of this large, systematic data base will provide a foundation for understanding emotion in terms of both specific experimental inductions (i.e., using pictures, sounds, texts, moving images, etc.) and tasks (i.e., perception of memory), which can be utilized in future investigations that seek to address specific questions, populations, and issues in emotion research. In addition, understanding the mechanisms involved in emotional processing will be elucidated by this systematic, programmatic approach.
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1 |
1997 — 2001 |
Lang, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Fear and the Anxiety Disorders: Brain and Behavior
DESCRIPTION (Applicant's Abstract): The plan of experiments emphasizes basic research on emotion as a framework for comparative clinical studies of phobic and anxious patients. The guiding theory of emotion is derived from animal research on functional brain activity in states of appetitive and defensive motivation. Work by Davis, LeDoux, Fanselow and others has defined a subcortical fear circuit, including the sensory thalamus, amygdala, and periaqueductal central gray. The startle reflex, and autonomic reactivity, are augmented in fearful animals, and this effect depends on an intact fear circuit (e.g., lesions of the amygdala eliminate potentiation). Research conducted on this project has demonstrated a parallel startle potentiation and autonomic change in human beings in fear conditioning, fear imagery, and while attending to unpleasant pictures and auditory stimulation. Exaggerated startle reactions also characterized specific anxiety diagnoses, and may vary with generality of psychopathology. The new basic research examines conical and subcortical reactivity (including brain sites of the animal model) in humans, using both scalp and subdural electrophysiological recording and functional magnetic resonance imaging to determine if fearful and aversive stimuli occasion hypothesized regional patterns of brain activity. Standardized picture stimuli (IAPS) and text evoked imagery, shown to reliably produce emotion related ANS and reflex responses, are presented to subjects in the magnet to determine if there are regional blood oxygen level differences between neutral, pleasant, and aversive stimuli, and how these effects are modulated by arousal. A parallel set of experiments will utilize the EEG to examine cortical responses (ERP and slow-wave) to these same stimuli. Subsequent EEG and fMRI studies will examine phobic subjects (volunteers selected from the normal population) while they view pictures of and/or mentally image, phobic and non-phobic objects. The new clinical research effort includes major anxiety patient assessment studies, using mental imagery and picture paradigms, and multi-measure psychophysiological recording. Comparative analyses are made among anxiety disorders. The sample includes simple and social phobia, panic, post-traumatic stress, obsessive- compulsive, and generalized anxiety disorders. It is planned that the new neural imaging techniques will be added to this clinical protocol, as procedures develop in the basic studies. Goals of the project are to sharpen psychophysiological distinctions between fear (as in phobia), a phasic defensive reaction to a specific stimulus, and anxiety (as in GAD), a more persistent tonic defensive set with components of inhibition and depression. and furthermore, to evaluate memorial, cognitive style, and temperament differences among anxiety disorders, to sharpen differential diagnosis and assess the significance of depressive co-morbidity.
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1 |
1999 — 2002 |
Lang, Peter J |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Human Brain Function in Emotional Perception
The aim of this project is to investigate the brain s response to affective stimuli: 1) to assess the validity of the animal model of motivation defined by Davis, LeDoux, Morgenson, and others, as a design for human brain function in emotion; 2) to evaluate current views of differential cortical activation in human emotion, and examine their relationship to the motivational view; 3) to determine the brain s response to stimuli that vary along the motivational parameters of pleasure and arousal, and 4) to assess differences and covariations between spatially sensitive (fMRI) and temporally sensitive (EEG measures of motivational activation in the brain. An integrative analytic effort will aim to capitalize on each measures unique advantages. In this procedure, emotionally evocative stimuli are presented in different media (i.e., pictures, sounds, or texts) that share the same affective content, in order to define consistently active neuroanatomical regions that reflect affective processes, as opposed to sites unique to modality of input or language mediation. Affect content is operationally defined both by scaled evaluative judgements of pleasure and arousal and by psychophysiological response.
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1 |
2005 — 2009 |
Lang, Peter J |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Core 1: Research Training and Administration Core (Pg 108) |
1 |
2005 — 2009 |
Lang, Peter J |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Project 1: Role of the Medial Nucleus of the Amygdala in Fear (Pg 159) |
1 |
2005 — 2009 |
Lang, Peter J |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Project 2: the Defense System: Activation, Extinction, and Motive (Pg 179) |
1 |
2009 — 2010 |
Lang, Peter J |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Attention Capture in Fear, Anxiety, and Depression
DESCRIPTION (provided by applicant): The aim of the present research is to assess attention capture, sustained attention, and defensive reflex engagement during emotional perception in anxiety patients diagnosed with and without co-morbid major depression, and in healthy control participants. Previous studies suggest that anxious, depressed, and control participants differ variously in affective processing: 1) in early and later stages of processing, 2) in response to intact or degraded affective cues, and 3) and in the modulation of attentional (e.g., RT) or emotional (e.g., startle blink) indices. Whereas fearful, anxious patients generally show rapid attention capture and strong emotional engagement in response to threat cues, relative to controls, results for depressed patients are mixed. Here, we use a multi-modal measurement array (brain, reflex, and reaction time) to address attentional and emotional engagement in socially anxious patients -- both depressed and non-depressed -- as these processes develop chronometrically during picture perception. The overall hypothesis is that whereas fearful anxiety is characterized by robust activation of the brain's defense system, quickly attracting attentional resources and mobilizing the organism to confront even half-perceived threats;comorbid depression represents a more chronic stage in the development of affective pathology in which attention and emotion are uncoupled, possibly reflecting top down effects of perseverative rumination that delays or diverts external focus, or indicative of a general systemic disorder, based on a history of chronic stress, that blunts defensive reflexes and coping actions. To assess potential differences in a single paradigm, the temporal development of attention and emotion are assessed using an acoustic probe methodology that efficiently assesses these processes when participants view affective cues: (1) The blink reflex to a startling acoustic probe is a robust measure of the degree to which the brain's defensive system is engaged;(2) the P3 component of the event-related potential (ERP) to an acoustic probe provides a direct, brain-based measure of sustained attention allocation;and (3) reaction time (RT) to an acoustic probe reflects early attention capture. Because acoustic probes are easily presented at various temporal delays after picture onset, the probe methodology opens a chronometric window on the developing trajectories of both attention to threatening cues and emotional reactivity. PUBLIC HEALTH RELEVANCE: Heightened attention and emotion to aversive events is often described as underlying the persistence of anxiety and depression in patients diagnosed with these disorders. The proposed research explores the time course of attention capture and emotional engagement when socially anxious patients diagnosed with or without comorbid depression are confronted with threatening cues. A variety of existing hypotheses regarding differences and deficits in anxiety and depression are assessed in a single psychophysiological session that could help to address perplexing patterns found in past studies as well as to illuminate basic mechanisms in co-morbid pathology that are fundamental for developing new assessment and/or therapeutic techniques.
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1 |
2012 — 2015 |
Lang, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
From Fear to Anxious Misery: Developing a Defense Circuit Dimensional Classifier
DESCRIPTION (provided by applicant): Pathological anxiety is commonly conceptualized as an exaggerated fear state in which hyper- excitability of fear circuits...is expressed as hypervigilance and increased behavioral responsivity to fearful stimuli (e.g., Rosen et al., 1998)-essentially an amplification of normal fear/defense circuit function. However, our previous research has shown that anxiety patients differ substantially in fear reactivity, within and across diagnoses, as measured by the magnitude of the probe startle reflex during fear imagery challenge (Cuthbert et al., 2003; Lang, McTeague & Cuthbert, 2005, 2007; Lang & McTeague, 2009). Thus, specific phobics show robust probe startle potentiation during fear imagery, while patients with more complex disorders (e.g, panic disorder, generalized anxiety disorder) characteristically show blunted reflex responses. Importantly, similar differences are also found within DSM diagnoses: Overall, fear potentiation decreases as the symptom picture is progressively more severe, comorbid, with higher scores on measures of negative affectivity-despite ratings of high, often much higher, fear during challenge (McTeague, Lang, et al., 2009, 2010, 2011). Considering that research both with animals and humans confirms that fear-circuit activation (amygdala mediated) potentiates the startle reflex, our research invites the novel hypothesis that the defense circuit is compromised/dysregulated in highly distressed anxiety patients. Thus, we examine reactivity to a fear imagery challenge in a broad sample of patients as they present for treatment at our health-center affiliated Fear and Anxiety Disorders Clinic (FADC). Functional MRI (fMRI) is used to asses fear/defense circuit function during fear imagery challenge, testing the hypothesis that alterations in normal defense circuit function mediates a dimension of fear reactivity that ranges from hyper-reactivity to hypo-reactivity in probe startle magnitude. A second broad aim is to test the hypothesis that increased circuit dysregulation and reflex blunting are reliably related to increased self-reports indexing a dimension of negative affectivity, as well as inversely related to treatment outcome success. The general research plan is therefore to develop biological classifiers for a dimension of pathology that cuts across anxiety/mood spectrum disorders. The approach is consistent with the NIMH Research Domain Criteria initiative (e.g, as described by Insel & Cuthbert 2009) implemented in RFA- MH-12-100. PUBLIC HEALTH RELEVANCE: Anxiety disorder diagnoses (DSM-IV) are founded primarily on clinicians' observations of behavior and their assessment of the patient's report of symptoms at interview-with no support from quantitative, biological tests that are keys to the evaluation an treatment of most illnesses. The proposed research plan is to develop quantitative, biological markers (in reflex response and brain circuit function) defining a fundamental dimension of psychopathology, negative affectivity, that cuts across anxiety spectrum disorders, that can relate more closely to developing genetic research, provide for improved prognosis, and contribute to better targeted treatment development.
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1 |
2012 — 2017 |
Lang, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Anxiety, Comorbidity, Negative Affect, and Fear Circuit Activation
DESCRIPTION (provided by applicant): Consistent with NIMH's Research Domain Criteria initiative (Insel & Cuthbert, 2009), the primary research goal is to advance the development of neurobiological measures of anxiety spectrum disorder, defining quantitative dimensions of pathology that advance understanding of the anxiety diathesis. The work's focus is the brain's amygdala-centered fear/defense circuit, as defined by basic laboratory neuroscience, which mediates a range of obligatory survival reflexes, including the potentiated startle response, and is generally held to be hyper-active in anxiety disorders. Our previous research indicates, however, that anxiety patients differ widely in their reflex reactivity during fear memory imagery (Cuthbert et al., 2003; Lang et al., 2005, 2007; Lang & McTeague, 2009). While most phobic patients show marked increases in probe startle magnitude during fear imagery, a high percentage of patients with more generalized anxiety disorders fail to show significant potentiation. Paradoxically, fear potentiation decreases progressively as the disorder is more severe, co-morbid, with greater negative affect-despite verbal reports of high, often much higher, fear during imagery (McTeague et al., 2009, 2010). Thus, we hypothesize a spectrum-wide, diagnosis cross-cutting dimension of fear-circuit regulation/dysregulation, and here use social anxiety disorder as a model system to elucidate the phenomenon, studying healthy controls and three social anxiety subtypes: circumscribed, generalized, and generalized social anxiety with depression, assessing circuit function directly with functional Magnetic Resonance Imaging (fMRI) as it relates to reflex reactivity in the psychophysiology laboratory. The specific aims are 1) to determine if activation of fear/defense circuit structures and their functional connectivity differ in response to narrative imagery challenges across social anxiety subtypes; 2) to directly assess the relationship between reflex reactivity and fear/defense circuit activatio patterns and a clinical symptom picture characterized by high co-morbidity, chronicity, and high negative affect; 3) to more broadly evaluate potential differences in emotional reactivity across social anxiety subtypes by assessing appetitive, as well as defensive reactivity using fMRI and psychophysiology, and 4) to evaluate the prognostic value of reflex and fear/defense circuit bio-markers measured during in initial assessment in predicting questionaire-based outcome measures of clinical status following treatment. PUBLIC HEALTH RELEVANCE: Currently, the diagnosis of anxiety disorder depends almost entirely on patient-interview and the clinician's assessment the patient's symptom report. The clinician has available no neurobiological measures of anxiety disorder-as when an internist orders an electro- cardiogram of the heart to help interpret a patient's report of chest pain. The proposed research explores quantitative measures of brain function and reflex reactivity that could define a dimension of anxiety disorder severity, and thus potentially enhance the clinician's understanding of the patient, improving diagnosis significantly and guiding new treatments.
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1 |
2020 |
Keil, Andreas (co-PI) [⬀] Lang, Peter J |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Anxiety and Aversive Learning: Neural Mechanics of Generalization and Patterns of Disorder Pathology
Project Summary Emotional dysfunction is at the core of many psychiatric disorders, with epidemiological studies noting the growing prevalence of fear, anxiety, post-traumatic, and mood disorders in the United States. The overall goal of the proposed project is to characterize the neural mechanisms that underlie dysfunctional aversive learning in anxiety disorder patients. The failure to discriminate between threatening and safe contexts is at the core of many psychiatric problems, with overgeneralization proposed as a defining feature of anxiety disorders. In this project, we (1) translate a robust basic science paradigm testing different modes of aversive learning into the clinical arena, and (2) establish a quantitative approach for measuring inter- individual differences in aversive learning. The approach relies on a robust index of aversive learning -- the steady state visual evoked potential (ssVEP) -- which is measured by presenting a visual cue at a specific frequency (e.g., 15 times per second, 15 Hz) that then elicits neural activity at the same driving frequency. When a cue is reliably followed by an aversive event (i.e. CS+), the amplitude of the ssVEP is heightened, compared to the amplitude of the frequency at which a safe cue (i.e. CS-) is presented, providing an exquisite measure of fear learning. The current project assesses generalization learning in anxiety disorder patients, by presenting an aversively conditioned CS+ together with safe cues that vary in similarity to the CS+. Pilot data with healthy participants shows neural sharpening (i.e., good discrimination of CS+) in sensors placed over occipital cortex, and neural generalization (enhanced responses to safe cues most similar to the CS+) over parietal cortex, and the proposed study measures aversive learning in 100 participants (80 anxiety disorder patients and 20 healthy controls). Using the ssVEP (as well as startle and self-reports), aversive sharpening and generalization are computed for each participant and for each dependent measure using the norm (Euclidian distance) of the difference between weights modeling sharpening or generalization functions and each participant's z-transformed means across safe cues that vary in similarity to the CS+, producing a single quantitative index indicating the degree of generalization and sharpening for each measure. The project explores the overarching hypothesis that inter-individual differences in the generalization of aversive learning- - quantitatively elucidated using the ssVEP-- are dimensionally related to key features of psychopathology across diagnostic groups. Taken together, this project will provide key information regarding dysfunction in aversive learning, which plays a role in the etiology and maintenance of anxiety, as well as form the basis for developing a novel technique useful in clinical assessment and post-treatment contexts.
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