Previous studies from our laboratory characterized a fearful/anxious endophenotype in rhesus monkeys that is. relevant to understanding normal human anxiety, as well as anxiety disorders. During the last funding period, we established a technique to selectively and reliably lesion the primate amygdala with ibotenic acid. The investigators' data are among the first to use modern lesioning techniques with sophisticated behavioral measures to address mechanisms underlying emotional processing in primates. Results demonstrate an important role for the amygdala in the processing of acutely fearful stimuli but a lack of amygdala involvement in mediating the dispositional behavioral, emotional, and physiological characteristics associated with fearful/anxious temperament. Orbitofrontal regions are bi-directional linked with the amygdala and the proposed studies will examine the role of orbitofrontal cortex in emotional processing, as well as the functional interaction between the amygdala and orbitofrontal cortex. Using ibotenic acid lesions and positron emission tomography, the investigators will explore the hypothesis that right orbitofrontal regions are primarily involved in mediating the behavioral and emotional responses associated with fearful/anxious temperament. The findings from these studies will be highly relevant to humans, addressing the role of amygdala orbitofrontal interactions in mediating normal emotion and psychopathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH046729-09
Application #
6200319
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Project Start
1990-07-01
Project End
2004-06-30
Budget Start
2000-07-10
Budget End
2001-06-30
Support Year
9
Fiscal Year
2000
Total Cost
$499,009
Indirect Cost
Name
University of Wisconsin Madison
Department
Psychiatry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Fox, Andrew S; Oler, Jonathan A; Birn, Rasmus M et al. (2018) Functional Connectivity within the Primate Extended Amygdala Is Heritable and Associated with Early-Life Anxious Temperament. J Neurosci 38:7611-7621
Zhao, Gengyan; Liu, Fang; Oler, Jonathan A et al. (2018) Bayesian convolutional neural network based MRI brain extraction on nonhuman primates. Neuroimage 175:32-44
Kalin, Ned H (2018) Corticotropin-Releasing Hormone Binding Protein: Stress, Psychopathology, and Antidepressant Treatment Response. Am J Psychiatry 175:204-206
Alisch, Reid S; Van Hulle, Carol; Chopra, Pankaj et al. (2017) A multi-dimensional characterization of anxiety in monozygotic twin pairs reveals susceptibility loci in humans. Transl Psychiatry 7:1282
Shackman, A J; Fox, A S; Oler, J A et al. (2017) Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology. Mol Psychiatry 22:724-732
Oler, Jonathan A; Tromp, Do P M; Fox, Andrew S et al. (2017) Connectivity between the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the non-human primate: neuronal tract tracing and developmental neuroimaging studies. Brain Struct Funct 222:21-39
Kalin, Ned H (2017) Mechanisms underlying the early risk to develop anxiety and depression: A translational approach. Eur Neuropsychopharmacol 27:543-553
Kalin, Ned H; Fox, Andrew S; Kovner, Rothem et al. (2016) Overexpressing Corticotropin-Releasing Factor in the Primate Amygdala Increases Anxious Temperament and Alters Its Neural Circuit. Biol Psychiatry 80:345-55
Fox, Andrew S; Oler, Jonathan A; Shackman, Alexander J et al. (2015) Intergenerational neural mediators of early-life anxious temperament. Proc Natl Acad Sci U S A 112:9118-22
Cavanagh, James F; Shackman, Alexander J (2015) Frontal midline theta reflects anxiety and cognitive control: meta-analytic evidence. J Physiol Paris 109:3-15

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