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The Journal of Neuroscience, October 5, 2005, 25(40):9309-9316; doi:10.1523/JNEUROSCI.2239-05.2005

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Behavioral/Systems/Cognitive
Hormonal Cycle Modulates Arousal Circuitry in Women Using Functional Magnetic Resonance Imaging

Jill M. Goldstein,1,2,3 Matthew Jerram,1,3 Russell Poldrack,4 Todd Ahern,2 David N. Kennedy,3,5 Larry J. Seidman,2,3 and Nikos Makris3,5

1Department of Psychiatry, Harvard Medical School, Department of Psychiatry and Medicine, Brigham and Women's Hospital, Division of Women's Health, Connors Center for Women's Health and Gender Biology, Boston, Massachusetts 02115, 2Department of Psychiatry at Beth Israel Deaconess Hospital, Public Psychiatry Division at Massachusetts Mental Health Center and Massachusetts General Hospital, Boston, Massachusetts 02215, 3Athinoula Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Massachusetts Institute of Technology, Charlestown, Massachusetts 02129, 4Department of Psychology, University of California at Los Angeles, Los Angeles, California 90095, and 5Harvard Medical School, Departments of Neurology and Radiology, Center for Morphometric Analysis, Massachusetts General Hospital, Charlestown, Massachusetts 02129

Sex-specific behaviors are in part based on hormonal regulation of brain physiology. This functional magnetic resonance imaging (fMRI) study demonstrated significant differences in activation of hypothalamic-pituitary-adrenal (HPA) circuitry in adult women with attenuation during ovulation and increased activation during early follicular phase. Twelve normal premenopausal women were scanned twice during the early follicular menstrual cycle phase compared with late follicular/midcycle, using negative valence/high arousal versus neutral visual stimuli, validated by concomitant electrodermal activity (EDA). Significantly greater magnitude of blood oxygenation level-dependent signal changes were found during early follicular compared with midcycle timing in central amygdala, paraventricular and ventromedial hypothalamic nuclei, hippocampus, orbitofrontal cortex (OFC), anterior cingulate gyrus (aCING), and peripeduncular nucleus of the brainstem, a network of regions implicated in the stress response. Arousal (EDA) correlated positively with brain activity in amygdala, OFC, and aCING during midcycle but not in early follicular, suggesting less cortical control of amygdala during early follicular, when arousal was increased. This is the first evidence suggesting that estrogen may likely attenuate arousal in women via cortical-subcortical control within HPA circuitry. Findings have important implications for normal sex-specific physiological functioning and may contribute to understanding higher rates of mood and anxiety disorders in women and differential sensitivity to trauma than men.

Key words: fMRI; emotion; arousal; hypothalamus; amygdala; women; HPA


Received June 2, 2005; revised August 23, 2005; accepted August 24, 2005.




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