Abstract
Hormonal changes across the menstrual cycle have been shown to influence reward-related motivation and impulsive behaviors. Here, with the aim of examining the neural mechanisms underlying cognitive control of impulsivity, we compared event-related monetary delay discounting task behavior and concurrent functional magnetic resonance imaging (fMRI) revealed brain activity as well as resting state (rs)-fMRI activity, between women in the mid-luteal phase (LP) and women in the late follicular phase (FP). The behavioral data were analyzed and related to neural activation data. In the delay discounting task, women in the late FP were more responsive to short-term rewards (i.e., showed a greater discount rate) than women in the mid-LP, while also showing greater activity in the dorsal striatum (DS). Discount rate (transformed k) correlated with functional connectivity between the DS and dorsal lateral prefrontal cortex (dlPFC), consistent with previous findings indicating that DS-dlPFC circuitry may regulate impulsivity. Our rs-fMRI data further showed that the right dlPFC was significantly more active in the mid-LP than in late FP, and this effect was sensitive to absolute and relative estradiol levels during the mid-LP. DS-dlPFC functional connectivity magnitude correlated negatively with psychometric impulsivity scores during the late FP, consistent with our behavioral data and further indicating that relative estradiol levels may play an important role in augmenting cognitive control. These findings provide new insight into the treatment of conditions characterized by hyper-impulsivity, such as obsessive compulsive disorder, Parkinson disease, and attention deficit hyperactivity disorder. In conclusion, our results suggest that cyclical gonadal hormones affect cognitive control of impulsive behavior in a periodic manner, possibility via DS-dlPFC circuitry.
Highlights
It has been posited that observed influences of menstrual cycle phase in women on rewardrelated impulsivity reflect alterations in brain dopamine function and downstream effects of those alterations on dopamine efferent targets in the basal ganglia and frontal cortex (Xiao and Becker, 1994; Jackson et al, 2006)
A paired samples t-test showed a significant difference in transformed k values between the late follicular phase (FP) and mid-luteal phase (LP) (t1,15 = −2.14, p = 0.049 < 0.05, d = 0. 43), with a significantly greater mean discount rate being observed in the late FP (−1.32 ± 0.49) than in the mid-LP (−1.51 ± 0.46) (Figure 1)
Using the delay discounting task, which assesses intertemporal choice similar to the task used by McClure et al (2004), we demonstrated that delay discounting behavior in women was affected by menstrual phase, such that the discount rate was significantly greater in the late FP than in the mid-LP, and this augmented discount rate was associated with enhanced activity in the dorsal striatum (DS)
Summary
It has been posited that observed influences of menstrual cycle phase in women on rewardrelated impulsivity reflect alterations in brain dopamine function and downstream effects of those alterations on dopamine efferent targets in the basal ganglia and frontal cortex (Xiao and Becker, 1994; Jackson et al, 2006). Female rats exhibit their maximal cocaine self-administration levels shortly after estradiol peaks, and exogenous administration of estradiol enhances the acquisition of cocaine self-administration in ovariectomized female rats (Lynch et al, 2001; Jackson et al, 2006) These findings suggest that the proclivity of female mammals to wait for a higher reward is reduced in the late FP relative to the mid-LP
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