Distinct EEG cue-reactivity profiles associated with virtual-reality treatment responses in methamphetamine use disorder.

Methamphetamine use disorder (MUD) is associated with abnormal neural cue-reactivity dynamics that contribute to craving and relapse vulnerability. Using electroencephalography (EEG), virtual reality (VR)-based cue exposure, and VR intervention, we examined Cue-Rest spectral modulation across addiction-related neural systems before and after treatment. Principal Component Analysis(PCA)-based subgrouping method identified two distinct EEG cue-reactivity profiles characterized by relatively higher versus lower Cue-Rest spectral modulation patterns. During VR-cue exposure, widespread abnormalities were observed across delta, theta, alpha, beta, and gamma-band systems involving prefrontal, cortico-striatal, default mode network (DMN), orbitofrontal(OFC), and temporo-limbic networks. The first MUD profile demonstrated greater positive Cue-Rest spectral modulation across nearly all analyzed neural systems relative to the second profile, suggesting preserved neural cue responsivity, whereas the second subgroup showed attenuated or blunted modulation profiles. Following VR treatment, the first profile exhibited widespread reductions in low-frequency and high-frequency Cue-Rest spectral modulation across prefrontal, dorsolateral prefrontal (DLPFC) , cortico-striatal, DMN, and temporo-limbic regions, suggesting substantial modulation of cue-reactivity-related neural activity following treatment. In contrast, the second profile showed comparatively limited longitudinal EEG modulation despite significant reductions in subjective craving-related behavioral responses. Both profiles showed robust decreases in craving, drug-use urge, and drug liking following treatment. These findings demonstrate substantial heterogeneity in methamphetamine (METH) cue-reactivity dynamics and suggest that VR-related neurophysiological treatment responses differs according to baseline EEG cue-reactivity profiles, supporting EEG the potential utility of EEG spectral modulation measures for characterizing treatment-related neural changes in MUD.