# Elucidating How Menstrual Cycle Phase Influences Neurocognitive Processes Underlying Risk-Taking in Women with Opioid Use Disorder

> **NIH NIH F31** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $47,217

## Abstract

Project Summary/Abstract
Women have been underrepresented in neuroimaging studies of opioid use disorder (OUD) and even fewer
neuroimaging studies have targeted female-specific health factors, such as the menstrual cycle. This is
concerning because women have disproportionately higher rates of relapse and treatment drop out, and cycling
levels of estrogen are known to impact drug-craving, with hormone levels around ovulation potentially increasing
vulnerability of relapse, though the neural mechanism leading to this result is unclear. Recent preclinical work
has shown a clear interaction between ovarian hormone changes, dopamine-dependent circuitry, and sensitivity
to reward cues and addictive substances. Parallel data in healthy women shows an uptick in subjects’ propensity
for risk-taking, a dopamine sensitive neurocognitive process, surrounding ovulation, the phase of the menstrual
cycle when estrogen is the highest. This suggests dopamine modulation of substance-use related behavior
during this time, but longitudinal studies examining dopamine-dependent behaviors in parallel with the menstrual
cycle in women with OUD remain lacking. To address this, I will conduct a serial and longitudinal fMRI study of
risky decision-making in women with OUD and comparison controls across a full menstrual cycle (8
sessions/person). Computational modeling will be used to quantify risk-taking propensity through known-risk
tolerance (a person-specific parameter of risk-taking propensity when the probability of reward is known) and
ambiguity tolerance (a separable mechanism when the exact probability of reward is unknown). Previous work
in my laboratory has found ambiguity tolerance to be a more state-sensitive measure, finding its fluctuation is
predictive of opioid reuse, and thus a focus of this study. Aim 1 will identify the relationship between intra-
individual changes in cycling hormone levels (estrogen and progesterone) and risk-taking (through known-risk
and ambiguity tolerance), hypothesizing an increase in ambiguity tolerance during ovulation. Success of this aim
could provide potential behavioral risk markers for drug-reuse in women with OUD informing sex-specific
interventions. Aim 2 will assess the relationship between menstrual cycle phases and changing neural signatures
of the subjective value of risky and ambiguous options, based on person- and session-specific trial-by-trial
valuation based on computational risk-taking propensity. As neural signals of subjective value are dopamine-
dependent, increased sensitivity, as hypothesized, in canonical value regions (e.g. ventral striatum) surrounding
ovulation may be indicative of stronger dopamine modulation during this time. Thus, this research will identify
underlying hormonal and neural mechanisms contributing to sex differences in clinical features of OUD. By
completing the proposed research aims, training goals, and experiential learning activities, I will gain training in
neuroeconomic theory, ...

## Key facts

- **NIH application ID:** 10997609
- **Project number:** 1F31DA061610-01
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Francesca LoFaro
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $47,217
- **Award type:** 1
- **Project period:** 2024-11-05 → 2027-11-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997609

## Citation

> US National Institutes of Health, RePORTER application 10997609, Elucidating How Menstrual Cycle Phase Influences Neurocognitive Processes Underlying Risk-Taking in Women with Opioid Use Disorder (1F31DA061610-01). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/10997609. Licensed CC0.

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