Effects of Blood Estrogen Level on Cortical Activation Patterns during Cognitive Activation as Measured by Functional MRI

Modulation of the blood estrogen level as it occurs during the menstrual cycle has a strong influence on both neuropsychological and neurophysiological parameters. One of currently preferred hypotheses is that the menstrual cycle hormones modulate functional hemispheric lateralization. We examined six male and six female subjects by functional magnetic resonance imaging (fMRI) to image cortical activation patterns associated with cognitive and motor activation to determine whether these changes during the menstrual cycle can be visualized. Female subjects, who did not use oral contraceptives, were scanned twice, once during the menses and once on the 11/12 day of the menstrual cycle. A word-stem-completion task, a mental rotation task and a simple motor task were performed by all subjects. Our data provide evidence that the menstrual cycle hormones influence the overall level of cerebral hemodynamics to a much stronger degree than they influence the activation pattern itself. No differences were seen between male subjects and female subjects during the low estrogen phase. During both neuropsychological tasks blood estrogen level had a profound effect on the size but not on the lateralization or the localization of cortical activation patterns. The female brain under estrogen showed a marked increase in perfusion in cortical areas involved in both cognitive tasks, whereas the hemodynamic effects during the motor tasks were less pronounced. This might be due to differences in neuronal or endothelian receptor concentration, differences in synaptic function, or, most likely, changes in the cerebrovascular anatomy in different cortical regions.

[1]  A. Hull,et al.  Pregnancy-induced changes in ovine cerebral arteries. , 1992, The American journal of physiology.

[2]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[3]  S. Petersen,et al.  Human Brain Mapping 6:203–215(1998) � Functional MRI Studies of Word-Stem Completion: Reliability Across Laboratories and Comparison to Blood Flow Imaging With PET , 2022 .

[4]  S. Resnick,et al.  Effects of Estrogen Replacement Therapy on PET Cerebral Blood Flow and Neuropsychological Performance , 1998, Hormones and Behavior.

[5]  Geoff Sanders,et al.  Verbal and music dichotic listening tasks reveal variations in functional cerebral asymmetry across the menstrual cycle that are phase and task dependent , 1998, Neuropsychologia.

[6]  B. McEwen,et al.  Ovarian steroids and the brain , 1997, Neurology.

[7]  O. Güntürkün,et al.  Menstrual cycle affects functional cerebral asymmetries , 1995, Neuropsychologia.

[8]  N. Hagino,et al.  Long-term estrogen replacement therapy in female patients with dementia of the Alzheimer type: 7 case reports. , 1995, Dementia.

[9]  Mark S. Cohen,et al.  Changes in cortical activity during mental rotation. A mapping study using functional MRI. , 1996, Brain : a journal of neurology.

[10]  R W Cox,et al.  Language processing is strongly left lateralized in both sexes. Evidence from functional MRI. , 1999, Brain : a journal of neurology.

[11]  L. Ellis,et al.  Males, females, and behavior : toward biological understanding , 1998 .

[12]  L. Katz,et al.  Cerebral organization of component processes in reading. , 1996, Brain : a journal of neurology.

[13]  G. Dı́az-Véliz,et al.  Ketanserin Effects on Rat Behavioral Responses: Modifications by the Estrous Cycle, Ovariectomy and Estradiol Replacement , 1997, Pharmacology Biochemistry and Behavior.

[14]  D. Krause,et al.  Chronic estrogen treatment increases levels of endothelial nitric oxide synthase protein in rat cerebral microvessels. , 1999, Stroke.

[15]  Armin Thron,et al.  Cortical activation patterns during complex motor tasks in piano players and control subjects. A functional magnetic resonance imaging study , 2000, Neuroscience Letters.

[16]  P A Bandettini,et al.  Relationship between Finger Movement Rate and Functional Magnetic Resonance Signal Change in Human Primary Motor Cortex , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  Elizabeth Hampson,et al.  Variations in sex-related cognitive abilities across the menstrual cycle , 1990, Brain and Cognition.

[18]  L. Katz,et al.  Sex differences in the functional organization of the brain for language , 1995, Nature.

[19]  R. Traystman,et al.  Estrogen Increases cGMP in Selected Brain Regions and in Cerebral Microvessels , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  Christina L. Williams Estrogen Effects on Cognition across the Lifespan , 1998, Hormones and Behavior.

[21]  B. McEwen,et al.  Clinically relevant basic science studies of gender differences and sex hormone effects. , 1998, Psychopharmacology bulletin.

[22]  A. Wisniewski SEXUALLY-DIMORPHIC PATTERNS OF CORTICAL ASYMMETRY, AND THE ROLE FOR SEX STEROID HORMONES IN DETERMINING CORTICAL PATTERNS OF LATERALIZATION , 1998, Psychoneuroendocrinology.

[23]  G. Sanders,et al.  Estrogen and Memory in a Transsexual Population , 1998, Hormones and Behavior.

[24]  H. Weiss,et al.  Effects of cyclic GMP on microvascular permeability of the cerebral cortex. , 1999, Microvascular research.

[25]  B. Mcewen,et al.  Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat [published erratum appears in J Neurosci 1992 Oct;12(10):following table of contents] , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  Karl J. Friston,et al.  Regionally Specific Sensitivity Differences in fMRI and PET: Where Do They Come From? , 2000, NeuroImage.

[27]  G. Dı́az-Véliz,et al.  Effect of oxotremorine on the acquisition of a conditioned avoidance response is modified by the estrous cycle, ovariectomy, and estradiol replacement in rats , 1995, Pharmacology Biochemistry and Behavior.

[28]  B R Rosen,et al.  Functional magnetic resonance imaging and transcranial magnetic stimulation , 1997, Neurology.

[29]  G. Dı́az-Véliz,et al.  Behavioral Effects of Dopamine Agonists and Antagonists Influence of Estrous Cycle, Ovariectomy, and Estrogen Replacement in Rats , 1999, Pharmacology Biochemistry and Behavior.

[30]  I. Silverman,et al.  Differences in the Relationship of Menstrual Cycle Phase to Spatial Performance on Two- and Three-Dimensional Tasks , 1997, Hormones and Behavior.

[31]  D. Kimura Sex differences in the brain. , 1992, Scientific American.