Endogenous progesterone blurs frontostriatal representations of emotion control in healthy young women.

BACKGROUND: Fluctuations in ovarian hormones are associated with changes in mood and emotional well-being. However, the neural mechanisms linking endocrine states and affective regulation remain poorly understood. We aimed to investigate how endogenous estradiol and progesterone modulate brain representations underlying emotion-action control in healthy young women. METHODS: A total of 116 naturally cycling women performed an approach-avoidance task with emotional facial expressions during functional magnetic resonance imaging. Multivoxel pattern analyses were used to examine the neural encoding of emotion-action contingencies, i.e., classifying task conditions from multivariate activation patterns. We then tested whether salivary concentrations of estradiol and progesterone were associated with classification accuracy in various brain regions. RESULTS: Participants responded more slowly and less accurately when approaching angry faces or avoiding happy ones, reflecting control over automatic emotional tendencies. Multivoxel decoding revealed that task conditions could be reliably distinguished from activation patterns in the lateral frontal pole (FPl), striatum, central insula, dorsal and ventral cerebellum, primary visual cortex, and periaqueductal gray. Importantly, higher progesterone levels were correlated with reduced classification accuracy in the FPl (r=-.26, p=.006) and striatum (r=-.26, p=.007), and lower FPl decodability was linked to poorer mood during the preceding week (r=-.25, p=.011). Moreover, decoding accuracy in the FPl fully mediated the indirect association between progesterone and worse mood (R2=7.1%). CONCLUSIONS: These findings suggest that progesterone-related alterations in frontostriatal affective representations may contribute to mood variation.