2002 — 2006 |
Nitschke, Jack B |
K08Activity Code Description: To provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas within health profession's institutions of the country. |
Functional Neuroimaging in Anxiety and Fear @ University of Wisconsin Madison
DESCRIPTION: (provided by applicant) With a background in electrophysiological and neuropsychological measures for the study of anxiety, fear, and depression, the candidate is now actively moving into functional neuroimaging of these affective phenomena. Thus, the training plan focuses on functional neuroanatomy and fMRI methodology. The immediate objective of neurobiologically distinguishing anticipatory and reactivity processes in anxiety put forward in this proposal is in direct service of his long-term goals of using neuroscience research to inform the conceptualization of anxiety, fear, and depression pathology and to contribute to the mitigation of the suffering and social liability associated with such psychopathology. A continuing dilemma in the field is the ambiguous use of constructs such as anxiety and fear. Anxiety is often employed as a unitary construct encompassing a variety of affective phenomena, including worry, fear, phobias, obsessions, and post-traumatic stress. Rather than to defend a particular definition on logical grounds, this proposal attempts to isolate anticipatory and reactivity processes as constituent subcomponents of anxiety that are firmly rooted in experimental operationalization. The 4 proposed fMRT Experiments are designed to interrogate the neural circuitry governing the anticipation of and reactivity to aversive and phobic pictures, including 4 target structures: ventral anterior cingulate cortex (ACC), orbital frontal cortex (OFC), medial prefrontal cortex (PFC), and insula. The ventral ACC is hypothesized to be relatively specific to anticipation of negative future outcomes, due to its involvement in response conflict. Based on their respective roles in the regulation, evaluation, and autonomic control of emotion, different areas of the medial PFC, OFC, and insula are hypothesized to be activated during anticipation of and reactivity to aversive/phobic stimuli. Replication of amygdala activation to the pictures is also expected, but the focus here is on the 4 less studied structures of this circuitry. In particular, the proposed research will attempt to fill in two gaps in existing knowledge: 1) the circuitry governing anticipation of aversive pictures and 2) the impact of anxiety disorders on brain structures mediating the anticipation of aversive and phobic stimuli. The research facilities available in this laboratory and the stimulation provided by faculty, scientists, postdoctoral fellows, students, and staff are ideally suited for the proposed studies and the candidate?s development.
|
0.958 |
2005 — 2009 |
Nitschke, Jack B |
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. |
Neuroanatomy of Anticipation in Anxiety Disorders @ University of Wisconsin Madison
DESCRIPTION (provided by applicant): Anxiety and mood disorders are debilitating conditions that cause tremendous personal suffering and engender a high societal and economic burden. A central feature of these disorders is excessive anticipation of potentially aversive outcomes. While anticipation is critical for successful preparation and adaptation to aversive events, dysfunction in this system can interfere markedly with social and occupational functioning. By investigating the neurobiology of this anticipatory system, neural areas associated with specific functions of anticipation, such as autonomic processing, negative affect, and behavioral withdrawal, can be identified and targeted by psychological or biological treatments. In addition, the proposed event-related functional magnetic resonance imaging (fMRI) studies capitalize on 2 key characteristics of anticipation: uncertainty about the future and an inability to control it. Building on prior research using an anticipation paradigm with 1 warning symbol that predicts aversive pictures and another predicting neutral, the first study will manipulate uncertainty (i.e., predictability of picture content) by including an ambiguous warning symbol that is followed by either aversive or neutral pictures. The second study will manipulate uncontrollability by including a condition in which a behavioral response can shorten picture duration. The influence of uncertainty and uncontrollability on key neural areas in the proposed model for aversive anticipation will be tested with healthy volunteers in the first 2 studies. For the final study, both paradigms will be used with relevant clinical populations-generalized anxiety disorder, social anxiety disorder (social phobia), and major depressive disorder-to determine how the normative circuitry identified in the first 2 studies is aberrant in anxiety and mood disorders. The primary prediction is that there is a neural signature for anxiety disorders that corresponds to a general dysfunction in anticipatory processes engaged by potential aversive outcomes, especially in situations of uncertainty and uncontrollability. In sum, the emphasis of this application on the capacity to anticipate impending danger is a novel approach to the study of affective disorders that is geared toward basic knowledge about the neurobiology of healthy defense mechanisms (e.g., anticipation that results in adaptive response) as well as understanding how dysfunction in this system occurs.
|
0.958 |
2008 — 2012 |
Nitschke, Jack B |
K02Activity Code Description: Undocumented code - click on the grant title for more information. |
Brain Mechanisms of Anticipatory Processing in Anxiety Disorders @ University of Wisconsin Madison
[unreadable] DESCRIPTION (provided by applicant): Anxiety disorders are a debilitating form of mental illness that affect many people and carry a high societal and economic burden. A central feature of these disorders is the excessive anticipation of potential adverse outcomes. Considerable work in the candidate's and others' labs has identified multiple brain areas recruited during the anticipation of aversive events. The primary research objectives of this application are to probe these areas for abnormalities during anticipation in anxiety disorder patients and to examine the impact of uncertainty and uncontrollability, which figure prominently in anxiety. The planned research will also assess functional associations and white matter connections among the brain networks identified. In service of that, training in functional and structural connectivity methods is the major focus of the career development plan. These rapidly developing areas examining connectivity are an obvious next step for the candidate's research program and career development and will be crucial in his efforts to continue contributing to our developing knowledge base about brain function in anxiety. The environment is ideal for the pursuit of these research and career development objectives, with outstanding facilities, collaborators, and resources as well as a high degree of support from both the Department of Psychiatry and the Waisman Center. The proposed research will examine anticipatory function in generalized anxiety disorder and social anxiety disorder using a picture paradigm designed and developed in the candidate's laboratory over the past 7 years. The high levels of comorbidity with depression for these two anxiety disorders will be systematically investigated by including patients with major depressive disorder. The discovery of neural abnormalities in anticipatory processes should add to the body of work already being used in developing new clinical tools for directly targeting specific brain regions in anxiety and depression, such as transcranial magnetic stimulation, epidural electrocortical stimulation, and deep brain stimulation. Psychotherapy clients may benefit from greater focus of intervention strategies on anticipatory processes relevant to their symptoms. Research findings from the proposed project might have implications for determining which individuals would be likely to benefit from a particular treatment, building on recent findings by the candidate and his colleagues that greater anticipatory activity in the anterior cingulate predicts better response to an 8-week medication trial. [unreadable] [unreadable] [unreadable]
|
0.958 |