Age and sex effects on neural mechanisms underlying arousal and cognition

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DESCRIPTION (provided by applicant): 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.