title: Progesterone mediates brain functional connectivity changes during the menstrual cycle-a pilot resting state MRI study.
abstract: The growing interest in intrinsic brain organization has sparked various innovative approaches to generating comprehensive connectivity-based maps of the human brain. Prior reports point to a sexual dimorphism of the structural and functional human connectome. However, it is uncertain whether subtle changes in sex hormones, as occur during the monthly menstrual cycle, substantially impact the functional architecture of the female brain. Here, we performed eigenvector centrality (EC) mapping in 32 longitudinal resting state fMRI scans of a single healthy subject without oral contraceptive use, across four menstrual cycles, and assessed estrogen and progesterone levels. To investigate associations between cycle-dependent hormones and brain connectivity, we performed correlation analyses between the EC maps and the respective hormone levels. On the whole brain level, we found a significant positive correlation between progesterone and EC in the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral sensorimotor cortex. In a secondary region-of-interest analysis, we detected a progesterone-modulated increase in functional connectivity of both bilateral DLPFC and bilateral sensorimotor cortex with the hippocampus. Our results suggest that the menstrual cycle substantially impacts intrinsic functional connectivity, particularly in brain areas associated with contextual memory-regulation, such as the hippocampus. These findings are the first to link the subtle hormonal fluctuations that occur during the menstrual cycle, to significant changes in regional functional connectivity in the hippocampus in a longitudinal design, given the limitation of data acquisition in a single subject. Our study demonstrates the feasibility of such a longitudinal Resting-state functional Magnetic Resonance Imaging (rs-fMRI) design and illustrates a means of creating a personalized map of the human brain by integrating potential mediators of brain states, such as menstrual cycle phase.
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany ; Clinic of Cognitive Neurology, University of Leipzig Leipzig, Germany ; Leipzig Research Center for Civilization Diseases, University of Leipzig Leipzig, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Arélin
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Mueller
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Barth
authors.affiliation: Centre for Addiction and Mental Health Research Imaging Centre and Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health and the Department of Psychiatry, University of Toronto Toronto, ON, Canada.
authors.forename: Paraskevi V
authors.initials: PV
authors.lastname: Rekkas
authors.affiliation: Clinical Chemistry and Molecular Diagnostics, Institute for Laboratory Medicine, University Hospital Leipzig Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Burmann
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany ; Clinic of Cognitive Neurology, University of Leipzig Leipzig, Germany ; Leipzig Research Center for Civilization Diseases, University of Leipzig Leipzig, Germany ; Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig Leipzig, Germany ; Berlin School of Mind and Brain, Mind and Brain Institute, Humboldt University Berlin Berlin, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Villringer
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany ; Clinic of Cognitive Neurology, University of Leipzig Leipzig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Sacher
keywords: RS-fMRI; estradiol; functional connectivity; menstrual cycle; progesterone