Methods

1. Counterbalanced 15 mg Cortisol * Placebo R L MRI Simulation Screening Visit Memory Test + + Phone Screen 3.0 Tesla GE SIGNA Scanner quiet FMRI Stimuli Presentation 2s lonely † 4-8s 2s exhilarated 4-8s 2 runs; approx. 12 min The relationship between cortisol and memory: Preliminary analysis on the role of affective state and the amygdala Allison L. Jahna,b, Simone Kernb, Richard J. Davidsona, b, Jerry L. Halversona, Clemens Kirschbaumc, and Heather C. Abercrombiea University of Wisconsin-Madison Departments of Psychology & Psychiatrya, The Waisman Laboratory for Brain Imaging and Behaviorb, Technical University of Dresdenc • Methods • AVOTEC goggle system & Eprime Presentation Software for stimuli display • SRET (Self-Referent Encoding Task) participants asked to decide whether descriptive words are self-referent by making a dichotomous button press. Each scan has different sets of words matched for valence and arousal. • Memory session: recognition memory assessed 4-6 days after scanning session RESULTS Memory Data for Low & High PA Amygdala ROI for Low & High PA Contrast: Negative Word Trials – (Neutral + Positive Word Trials) Background Historically, cortisol has been considered harmful to cognition and health. However, animal and human data suggest that moderate cortisol elevations can be beneficial. Cortisol release affects cognitive processes such as memory. Research is divided with some studies finding that cortisol impairs memory and others finding that cortisol facilitates memory (Maheu et al. 2004; Abercrombie et al. 2003). Interestingly, research suggests that the beneficial effects of cortisol on memory depend on the emotional state of the individual (Okuda et al., 2004; Abercrombie et al., 2006). These studies suggest that state negative affect plays a permissive role in the effects of cortisol on memory. Animal data suggests that amygdala activation, specifically the basolateral region of the amygdala, is necessary for the beneficial effects of cortisol on memory. To date, this is the first human investigation of the role of the amygdala in the effects of cortisol on memory. Hypotheses: We hypothesize that a moderate dose of cortisol given in the late afternoon (when endogenous levels are low) will be related to increases in brain activation in the amygdala compared to placebo. We hypothesize that this effect will be associated with emotional state. Finally, we hypothesize that changes in emotional state will be related to changes in memory for words encoded during elevated cortisol. Beginning approx. 4:30pm *Significance p < 0.05 Interaction: F (1,12) = 6.16, p < 0.05 Average Percent Signal Change Left Ventral Amygdala Time Course Left Ventral Amygdala • Participants • Data collection is ongoing • 17 Participants (5 Women; Age-M:28.72; SD:7.21; 3 participants dropped from analysis; 1 for abnormal levels of cortisol on the cortisol scan day; 1 experimenter error; 1 abnormal memory values on the memory testing day) • Right handed; Free of general health issues; Free of psychiatric disorders † Trend p < 1.0 Conclusion While these analyses are preliminary, we find support for increased brain activation in the ventral amygdala after the administration of cortisol only in individuals with low positive affect. This effect was found in response to negative words compared to neutral and positive. Also, we find that individuals with low positive affect also show greater memory for words encoded during cortisol administration – and that this effect is more evident when examining memory for negatively valenced words. Future directions: We hypothesize that cortisol will alter brain activation in other regions such as the hippocampus, parahippocampal gyrus, and prefrontal cortex. Activation in these regions may be especially important because of their association with memory and emotion. We are also collecting data on emotion and arousal ratings of the stimuli in the scanner. Thus, we will examine the relationship among memory, changes in brain activation, and affective responses. MRI Methods & Analysis Quadrature Birdcage Coil for T1 high resolution anatomical & BOLD Sagital Acquisition; Flip Angle: 90 degrees; TR: 2000 ms; TE: 30 ms Slices per Volume: 30; Voxel Size: 3.75 x 3.75x 4mm with 1 mm gap AFNI: Slice timing correction, Motion correction, Spatial smoothing: 6mm Normalization to Talairach space Extraction of amygdala ROI in AFNI with predefined masks GLM: Gamma Variate Function; percent signal change from baseline for Negative Word Trials – (Neutral + Positive Word Trials) • Group Selection • Positive and Negative Affect Schedule (Watson, Clark, & Tellegen, 1988) • Due to low variation in negative affect scores we used positive affect as an index of affective state • Median split: 7 Low Positive Affect (Low PA; 3 women); 7 High Positive Affect (High PA; 2 women) References: Abercrombie HC, Kalin NH, Thurow ME, Rosenkranz MA, Davidson RJ (2003). Cortisol variation in humans affects memory for emotionally laden and neutral information. Beh Neuroscience 117:505-16. Abercrombie, H.C., Speck, N.S., & Monticelli, R.M. (2006). Endogenouscortisol elevations are related to memory facilitation only inindividuals who are emotionally aroused. PNEC 31:187-96. Maheu FS, Joober R., Beaulieu S, Lupien SJ (2004). Differential Effects of Adrenergic and Corticosteroid Hormonal Systems on Human Short- and Long-Term Declarative Memory for Emotionally Arousing Material. Beh Neuroscience 118:420-8. Okuda S, Roozendaal B, McGaugh JL (2004). Glucocorticid effects on object recognition memory require training-associated emotional arousal. PNAS 101:853-8. Watson D, Clark LA, Tellegen A (1988). Development and Validation of Brief Measures of Positive and Negative Affect: The PANAS Scales. J Personality & Social Psych 54:1063-70. This research was supported in part by a NARSAD Young Investigator Award given to Heather Abercrombie.