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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08MH063984-05
Application #
7119538
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Wynne, Debra K
Project Start
2002-09-23
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2008-08-31
Support Year
5
Fiscal Year
2006
Total Cost
$142,651
Indirect Cost
Name
University of Wisconsin Madison
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Oathes, Desmond J; Hilt, Lori M; Nitschke, Jack B (2015) Affective neural responses modulated by serotonin transporter genotype in clinical anxiety and depression. PLoS One 10:e0115820
McFarlin, Daniel R; Kerr, Deborah L; Nitschke, Jack B (2013) Upsampling to 400-ms resolution for assessing effective connectivity in functional magnetic resonance imaging data with Granger causality. Brain Connect 3:61-71
Grupe, Daniel W; Oathes, Desmond J; Nitschke, Jack B (2013) Dissecting the anticipation of aversion reveals dissociable neural networks. Cereb Cortex 23:1874-83
Tromp, Do P M; Grupe, Daniel W; Oathes, Desmond J et al. (2012) Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder. Arch Gen Psychiatry 69:925-34
Sarinopoulos, I; Grupe, D W; Mackiewicz, K L et al. (2010) Uncertainty during anticipation modulates neural responses to aversion in human insula and amygdala. Cereb Cortex 20:929-40
Nitschke, Jack B; Sarinopoulos, Issidoros; Oathes, Desmond J et al. (2009) Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. Am J Psychiatry 166:302-10
Oathes, Desmond J; Nitschke, Jack B (2008) State of the union between cognitive neuroscience and emotion. Expert Rev Neurother 8:1025-7
Nitschke, Jack B; Sarinopoulos, Issidoros; Mackiewicz, Kristen L et al. (2006) Functional neuroanatomy of aversion and its anticipation. Neuroimage 29:106-16
Nitschke, Jack B; Dixon, Gregory E; Sarinopoulos, Issidoros et al. (2006) Altering expectancy dampens neural response to aversive taste in primary taste cortex. Nat Neurosci 9:435-42
Sarinopoulos, Issidoros; Dixon, Gregory E; Short, Sarah J et al. (2006) Brain mechanisms of expectation associated with insula and amygdala response to aversive taste: implications for placebo. Brain Behav Immun 20:120-32

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