It is well-documented that stressful and arousing events activate the locus-coeruleus-norepinephrine (LC-NE) system, which is a primary source of central norepinephrine. The LC-NE system and other factors such as aging and sex hormone levels have been implicated in modulating cognitive behaviors. However, there is limited research on how age and sex hormones affect the LC-NE system and arousal-mediated cognition. One cognitive process that is likely modulated by the LC-NE system is arousal-biased competition (ABC). ABC theory postulates that arousal modulates the strength of competing mental representations and enhances the perception of high priority information while decreasing the perception of low priority information; subsequently, ABC processes strengthen memory consolidation for these high priority stimuli. There is still much to be investigated with ABC theory, especially with respect to long-term memory processes. Therefore, this proposal will test how age and sex hormone levels modulate neural activity underlying physiological arousal and arousal-cognition interactions in an arousal-biased competition (ABC) paradigm. The experiments proposed here will test the hypothesis that neural activity underlying noradrenergic (NE) responding to handgrip are modulated by age and sex hormone levels (Aim 1). We will then test the hypotheses that the neural circuitry identified in Aim 1 are activated under other conditions of arousal (Aim 2a), that age and sex hormone levels affect the degree to which arousal modulates the encoding and long-term memory of salient and non-salient images (Aim 2b), and that these selective enhancement and impairment effects are driven by interactions between the neural circuitry identified in Aim 1, the broader salience network, and the hippocampus (Aim 2c). This proposal will be the first to test the relationship between physiological indices of arousal (pupil dilation, sAA), activity in the salience network (dorsal anterior cingulate, bilateral anterior insula, brainstem, amygdala) and locus coeruleus, and short and long-term memory for salient stimuli. This study will also reveal potential influences of sex hormones and age on the neurophysiological processes which underlie arousal-biased competition. Results from this study will provide important information about how arousal influences information processing and memory consolidation for women throughout early and late life.

Public Health Relevance

This project will examine the influence of age and sex steroid hormones on the locus coeruleus- norepinephrine system. Since this system is activated during stressful and arousing events and modulates cognition, it is important to understand whether physiological arousal and neurobiological mechanisms associated with this system differ in women. Activity of the locus coeruleus-norepinephrine system under arousal and associated cognitive functions have never been investigated with respect to sex hormone status and age, which will be the focus of this proposal.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AG047840-02
Application #
8985603
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wagster, Molly V
Project Start
2014-12-01
Project End
2016-03-31
Budget Start
2015-12-01
Budget End
2016-03-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Other Specialized Schools
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90032
Clewett, David; Sakaki, Michiko; Huang, Ringo et al. (2017) Arousal amplifies biased competition between high and low priority memories more in women than in men: The role of elevated noradrenergic activity. Psychoneuroendocrinology 80:80-91
Nielsen, Shawn E; Barber, Sarah J; Chai, Audrey et al. (2015) Sympathetic arousal increases a negative memory bias in young women with low sex hormone levels. Psychoneuroendocrinology 62:96-106