# Sex differences in the neural correlates underlying impairments in response inhibition and salience attribution in cocaine addiction

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $681,089

## Abstract

National studies show that drug use rates have increased in the last decade among women, comprising a
major public health concern in the US. However, women are greatly underrepresented in neuroimaging
studies, and the paucity of studies that explicitly target sex comparisons in addicted populations contributes to
a gap in the study of the sex specific neurobiological mechanisms underlying drug addiction. Over the last
decade, in a series of magnetic resonance imaging (MRI) studies (conducted with previous support including
R01DA023579, R01DA020949), we have thoroughly mapped the clinical symptoms of cocaine addiction to the
neural networks underlying impairments in Response Inhibition and Salience Attribution (iRISA). This model
proposes that the drug assumes heightened salience at the expense of non-drug related reinforcement as
associated with abnormalities in reward processing and concomitant decreases in inhibitory control, together
increasing addiction severity (including craving, a proxy of relapse) in susceptible individuals. The iRISA model
highlights the role of the dopaminergically innervated prefrontal cortex (PFC) and its connections to mesolimbic
and striatal subcortical regions as assessed functionally and structurally. However, the majority of this
neuroimaging research has been accomplished in male individuals with cocaine use disorders (iCUD). In the
current project we aim to expand the reach of iRISA by comparing equal numbers of male to female iCUD; to
test this model’s generalizability (vs. drug specificity effects), we will also include individuals with opioid use
disorder (iOUD). We will conduct functional MRI during reward processing, inhibitory control and cue-reactivity
tasks, and, to inspect generalizability of results beyond task-related activations, during resting-state. Beyond
functional activations and connectivity, anatomical scans will assess the underlying gray matter integrity.
Across all aims, healthy controls will be included to establish norms. We hypothesize female iCUD to differ
from male iCUD, or female controls, in a pattern indicative of enhanced vulnerability to iRISA inclusive of
compensatory PFC activations and abnormalities in structural measures; iCUD vs. iOUD comparisons will be
exploratory. The novelty of this proposal is further enhanced by an exploratory aim to compare, in a within-
subjects design, menstrual cycle (and hormonal) effects and by developing sophisticated machine-learning
algorithms to incorporate data from all imaging modalities to yield an automated group classification and
addiction severity (including craving) prediction tool. Considering that the majority of research in addiction
occurs in males, clarification of the sex differences in the neural underpinnings of iRISA could reinforce the
importance of studying both genders and suggest that different treatment strategies may be effective in women
(potentially of most impact when timed vis-à-vis menstrual cycle), contributing to...

## Key facts

- **NIH application ID:** 10786037
- **Project number:** 5R01DA048301-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Rita Z Goldstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $681,089
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786037

## Citation

> US National Institutes of Health, RePORTER application 10786037, Sex differences in the neural correlates underlying impairments in response inhibition and salience attribution in cocaine addiction (5R01DA048301-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10786037. Licensed CC0.

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