Sex differences and exogenous estrogen influence learning and brain responses to prediction errors

Gina Joue, Karima Chakroun, Janine Bayer, Jan Gläscher, Lei Zhang, Johannes Fuss, Nora Hennies, Tobias Sommer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Animal studies show marked sex differences as well as effects of estrogen (E2) in the mesocorticolimbic dopaminergic (DA) pathways, which play a critical role in reward processing and reinforcement learning and are also implicated in drug addiction. In this computational pharmacological fMRI study, we investigate the effects of both factors, sex and estrogen, on reinforcement learning and the dopaminergic system in humans; 67 male and 64 naturally cycling female volunteers, the latter in their low-hormone phase, were randomly assigned, double-blind, to take E2 or placebo. They completed a reinforcement learning task in the MRI scanner for which we have previously shown reward prediction error (RPE)-related activity to be dopaminergic. We found RPE-related brain activity to be enhanced in women compared with men and to a greater extent when E2 levels were elevated in both sexes. However, both factors, female sex and E2, slowed adaptation to RPEs (smaller learning rate). This discrepancy of larger RPE-related activity yet smaller learning rates can be explained by organizational sex differences and activational effects of circulating E2, which both affect DA release differently to DA receptor binding capacities.
Original languageEnglish
Pages (from-to)2022-2036
Number of pages15
JournalCerebral Cortex
Volume32
Issue number9
Early online date15 Oct 2021
DOIs
Publication statusPublished - 1 May 2022

Keywords

  • 501030 Cognitive science
  • 501030 Kognitionswissenschaft
  • 301406 Neuropharmacology
  • 301406 Neuropharmakologie
  • 501011 Cognitive psychology
  • 501011 Kognitionspsychologie
  • 301402 Neurobiology
  • 301402 Neurobiologie
  • COCAINE
  • D-AMPHETAMINE
  • DOPAMINE D2 RECEPTORS
  • ESTRADIOL
  • MENSTRUAL-CYCLE
  • MODULATION
  • NUCLEUS-ACCUMBENS CORE
  • REWARD
  • SEEKING BEHAVIOR
  • STRIATUM
  • dopamine
  • estrogen
  • fMRI
  • reinforcement learning
  • sex differences
  • ventral striatum

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