Association of Menstrual Cycle with Fronto-Striatal Connectivity and Delay Discounting.

The dorsal fronto-striatal circuit, particularly the pathway connecting the dorsolateral prefrontal cortex (dlPFC) and caudate, constitutes a core neural system for cognitive control and goal-directed behavior. While ovarian hormone fluctuations are known to influence this circuit, their precise impact on its role in decision-making remains poorly understood. Here, we leveraged the natural hormonal variation in the menstrual cycle to investigate how estradiol and progesterone shape dlPFC-caudate functional connectivity during a delay-discounting task. We discovered a state-dependent reconfiguration, characterized by the emergence of more negative connectivity for delayed rewards (vs. immediate rewards) in the mid-luteal phase and the dissipation of this pattern in the late follicular phase. Crucially, progesterone levels in the mid-luteal phase fine-tuned the circuit's behavioral relevance, altering the association between connectivity strength and individual discounting rates. Our findings demonstrate that naturally occurring hormonal fluctuations reversibly reconfigure the functional architecture of the dorsal fronto-striatal circuit, thereby orchestrating state-dependent shifts in human decision-making.