Predicting individual incubation of opioid craving by whole-brain functional connectivity

Study authors Ying Duan and Pei-Jung Tsai

Hot Off the Press – March 18, 2026

Published in PNAS by Ying Duan, Pei-Jung Tsai and Yihong Yang, et al. of the NIDA IRP Magnetic Resonance Imaging and Spectroscopy Section.

Summary

This study is a trans-branch collaboration between groups of Drs. Yihong Yang and Yavin Shaham at NIDA-IRP. Relapse driven by craving remains a challenge in treating opioid use disorder (OUD). In this study, we used longitudinal fMRI and machine-learning based predictive modeling to identify a whole-brain connectivity pattern that predicts incubation of oxycodone craving in rats after voluntary abstinence. Connectivity changes during abstinence successfully predicted craving magnitude, measured by changes in lever pressing under extinction testing. The predictive connectivity pattern encompassed circuits across cortical, basal ganglia, insular, hippocampus and sensorimotor systems related to reward, motivation, stress and habit formation. Pharmacological inactivation of the dorsal medial striatum, a hub in the connectivity network, altered the connectivity pattern, demonstrating its causal and treatment-sensitive nature. These findings reveal a brain-wide marker of craving and provide a translational framework for developing potential interventions targets and monitoring therapeutic outcomes in OUD.

Publication Information

Duan, Ying; Tsai, Pei-Jung; Ma, Zilu; Fredriksson, Ida; Wang, Danni; Lu, Hanbing; Shaham, Yavin; Yang, Yihong

Predicting individual incubation of opioid craving by whole-brain functional connectivity Journal Article

In: Proc Natl Acad Sci U S A, vol. 123, no. 11, pp. e2531921123, 2026, ISSN: 1091-6490.

Abstract | Links

@article{pmid41805566,

title = {Predicting individual incubation of opioid craving by whole-brain functional connectivity},

author = {Ying Duan and Pei-Jung Tsai and Zilu Ma and Ida Fredriksson and Danni Wang and Hanbing Lu and Yavin Shaham and Yihong Yang},

url = {https://pubmed.ncbi.nlm.nih.gov/41805566/},

doi = {10.1073/pnas.2531921123},

issn = {1091-6490},

year  = {2026},

date = {2026-03-01},

urldate = {2026-03-01},

journal = {Proc Natl Acad Sci U S A},

volume = {123},

number = {11},

pages = {e2531921123},

abstract = {A high risk of relapse triggered by craving during abstinence remains a main challenge in opioid addiction treatment. Multiple brain regions have been implicated in opioid craving, but the brain-wide neural mechanisms underlying this process remain poorly understood. Using resting-state fMRI and connectome-based predictive modeling, we identified a whole-brain connectome that predicted the time-dependent increases (incubation) in oxycodone craving in individual rats after voluntary abstinence induced by exposure to an electric barrier. Incubation of oxycodone craving was operationally defined as the increase in nonreinforced lever pressing during relapse tests from early (day 1) to late (day 15) abstinence (incubation score). We found that changes in whole-brain functional connectivity during abstinence, but not during oxycodone self-administration, predicted the incubation score. Greater decreases in functional connectivity were associated with higher incubation scores. The predictive connectome involved complex interactions across multiple brain systems, including frontal-striatal, frontal-insula, insula-striatal, and hippocampal and sensorimotor circuits. To test causality of the predictive connectome, we examined the effect of pharmacological inactivation of dorsomedial striatum (DMS), which significantly decreased oxycodone seeking after electric barrier-induced abstinence. DMS inactivation increased connectivity strength within the predictive connectome, supporting a causal role of this connectome in incubation of oxycodone craving. The predictive connectome did not predict food-reward seeking after electric barrier-induced abstinence, indicating specificity to oxycodone craving. Our findings identify a brain-wide connectome marker that predicts individual differences in the incubation of opioid craving and provide potential targets for developing personalized interventions and monitoring therapeutic outcomes in opioid addiction treatment.},

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pubstate = {published},

tppubtype = {article}

}