Our work demonstrates that the rhesus monkey provides an excellent model to study mechanisms underlying human anxiety and fear. In our studies with rhesus monkeys, we found stable, brain (right frontal EEG asymmetry), endocrine (increased cortisol and CRH), and behavioral (prolonged dispositional freezing) characteristics related to anxiety that we termed the anxious endophenotype. These findings are particularly relevant to understanding the development of human psychopathology, since children with extremely inhibited temperament and similar biological features are at increased risk to develop anxiety disorders. One of our most pertinent findings in the monkeys was the relation between extreme right frontal EEG activity and extreme anxiety. These findings are consistent with human studies demonstrating an association between asymmetric right prefrontal brain electrical activity and negative affect. It is likely that different aspects of the anxious endophenotype are mediated by the interactions of limbic, brain stem, and cortical regions. In previous work, we systematically investigated the role of the amygdala in mediating the anxious endophenotype. Using selective ibotenic acid lesions, we found an important role for the amygdala in mediating acute fear-related responses to novel stimuli; however the data suggested that the amygdala does not play a major role in mediating the stable biological and behavioral traits associated with the anxious endophenotype. While lateral prefrontal cortex (LPFC) has been implicated in cognitive processes such as attention, anticipation, and working memory, recent studies suggest a role for LPFC in integrating emotional and cognitive information important in directing goal-related behavior. Evidence from our, and other, laboratories supports LPFC involvement in emotion processing and points to hemispheric specialization. We believe that studies examining the role of LPFC in emotion processing will provide new and important insights into prefrontal cortical mechanisms underlying the anxious endophenotype and will provide an opportunity to integrate findings related to the cognitive functions of this region with emotion regulation. Therefore, in rhesus monkeys, we will use a variety of techniques (emotion probes, selective ibotenic acid lesions, PET imaging, and intra-cerebral site specific administration pharmacology strategies) to systematically evaluate the contributions of LPFC in emotion processing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
1P50MH069315-01
Application #
6876314
Study Section
Special Emphasis Panel (ZMH1-BRB-P (06))
Project Start
2004-02-04
Project End
2008-12-31
Budget Start
2004-02-04
Budget End
2004-12-31
Support Year
1
Fiscal Year
2004
Total Cost
$408,858
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Nusslock, Robin; Shackman, Alexander J; McMenamin, Brenton W et al. (2018) Comorbid anxiety moderates the relationship between depression history and prefrontal EEG asymmetry. Psychophysiology 55:
Hilt, Lori M; Armstrong, Jeffrey M; Essex, Marilyn J (2017) Rumination and Moderators of Multifinality: Predicting Internalizing Symptoms and Alcohol Use During Adolescence. J Clin Child Adolesc Psychol 46:746-753
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Lapate, R C; Rokers, B; Tromp, D P M et al. (2016) Awareness of Emotional Stimuli Determines the Behavioral Consequences of Amygdala Activation and Amygdala-Prefrontal Connectivity. Sci Rep 6:25826
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Ruttle, Paula L; Maslowsky, Julie; Armstrong, Jeffrey M et al. (2015) Longitudinal associations between diurnal cortisol slope and alcohol use across adolescence: a seven-year prospective study. Psychoneuroendocrinology 56:23-8
Salomons, Tim V; Nusslock, Robin; Detloff, Allison et al. (2015) Neural emotion regulation circuitry underlying anxiolytic effects of perceived control over pain. J Cogn Neurosci 27:222-33

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