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The Journal of Neuroscience, May 1, 2003, 23(9):3790

Menstrual Cycle-Dependent Neural Plasticity in the Adult Human Brain Is Hormone, Task, and Region Specific

Guillén Fernández^{1, 3}, Susanne Weis¹, Birgit Stoffel-Wagner², Indira Tendolkar⁴, Markus Reuber¹, Stefan Beyenburg¹, Peter Klaver¹, Jürgen Fell¹, Armin de Greiff⁵, Jürgen Ruhlmann⁶, Jürgen Reul⁶, and Christian E. Elger¹

Departments of ¹ Epileptology and ² Clinical Biochemistry, University of Bonn, 53105 Bonn, Germany, ³ F. C. Donders Centre for Cognitive Neuroimaging, 6500 HB Nijmegen, The Netherlands, ⁴ Department of Psychiatry, University of Cologne, 50924 Cologne, Germany, ⁵ Departments of Neurology and Neuroradiology, University of Essen, 45122 Essen, Germany, and ⁶ Department of Diagnostic and Therapeutic Neuroradiology, Medical Center Bonn, 53119 Bonn, Germany

In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-dependent differences in cognitive performance have almost exclusively been found in tasks probing lateralized neuronal domains, i.e., cognitive domains such as language, which are predominantly executed by one hemisphere. To search for neural correlates of hormonally mediated neural plasticity in humans, we thus conducted a functional magnetic resonance imaging study measuring brain activity related to a semantic decision task in the language domain. This was contrasted with a letter-matching task in the perceptual domain, in which we expected no steroid hormone-mediated effect. We investigated 12 young healthy women in a counterbalanced repeated-measure design during low-steroid menstruation and high-steroid midluteal phase. Steroid serum levels correlated with the volume and lateralization of particular brain activations related to the semantic task but not with brain activity related to the perceptual task. More specifically, bilateral superior temporal recruitment correlated positively with progesterone and medial superior frontal recruitment with both progesterone and estradiol serum levels, whereas activations in inferior and middle frontal cortex were unaffected by steroid levels. In contrast to these specific interactions, testosterone levels correlated nonselectively with overall activation levels by neural and/or vascular factor(s). In conclusion, our data demonstrate steroid hormone responsivity in the adult human brain by revealing neural plasticity in the language domain, which appears hormone, task, and region specific.

Key words: language; steroid; sex hormones; progesterone; estrogen; fMRI; menstrual cycle; neural plasticity; language dominance

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2393790-06$05.00/0

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