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Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic
Vaenusha Murugan1, Yasmin Aishah Mohamad Hisham1, Reshiika Poorvi2
1Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Background:
Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics.
Objective:
This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction.
Methods:
A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively.
Results:
Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity.
Conclusion:
fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.
Insights
Methamphetamine use disorder involves disrupted brain networks, with cue reactivity decreasing and control systems re-engaging during abstinence. This highlights potential for targeted interventions in addiction recovery.
Area of Science:
- Neuroscience
- Addiction Research
- Neuroimaging
Background:
- Methamphetamine use disorder (MUD) is characterized by severe craving and relapse risk, often exacerbated by drug cues.
- Functional magnetic resonance imaging (fMRI) studies reveal altered brain network activity in MUD, but findings are inconsistent.
- Understanding how abstinence impacts these neural alterations is crucial for addiction treatment.
Purpose of the Study:
- To systematically review how abstinence influences brain network alterations related to cue reactivity and craving in methamphetamine users.
- To integrate task-based and resting-state fMRI findings within addiction neurobiological models.
- To synthesize evidence on neural changes associated with MUD and recovery.
Main Methods:
- Systematic literature search of major databases (PubMed, Scopus, Web of Science, Ovid) up to August 2025.
- Inclusion of fMRI studies examining cue reactivity or craving in abstinent methamphetamine users, adhering to PRISMA 2020 guidelines.
- Narrative synthesis of extracted data on brain activation, connectivity, and behavior-brain associations.
Main Results:
- Task-based fMRI showed heightened activation in reward, salience, and control networks during cue exposure, decreasing with longer abstinence.
- Resting-state fMRI revealed disrupted intrinsic connectivity in default mode, salience, and frontoparietal networks.
- These disruptions correlated with craving severity and persistent imbalances in MUD.
Conclusions:
- MUD involves widespread network disruptions affecting reward, salience, and control systems.
- Abstinence shows partial restoration of brain network integrity, indicating potential for recovery.
- Findings support the development of targeted interventions for MUD based on neurobiological recovery processes.
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