Objective To explore the differences in heartbeat-evoked response (HER) under drug-related cues and neutral cues in individuals with heroin use disorder (HUD), and analyze the correlation between HER potentials and immediate cue-induced craving scores.

Methods Fifty HUD participants were recruited from the Chang’an Compulsory Isolation Drug Rehabilitation Center in Shaanxi Province from June to September 2024. Simultaneous acquisition of 64-channel electroencephalography (EEG) and electrocardiogram signals was performed. Twenty alternating segments of drug-related and neutral cue videos were presented, and participants rated their subjective craving after each segment using visual analogue scale (VAS) scores. Scalp EEG data were source analyzed to obtain cortical EEG signals and corresponding HER. Short-time Fourier transform was used to calculate the power spectral density (PSD) of EEG within a time window from 100 ms before the R-peak to 500 ms after it, using the R-peak as the time zero point. Cluster-based permutation testing was used to analyze PSD differences between drug-related and neutral cues in the HUD individuals. Pearson correlation analysis was performed to evaluate the correlation between HER potentials and VAS scores.

Results In the 350–420 ms time window, HER potentials in the left posterior parietal, temporal, and posterior cingulate cortices were significantly lower under drug-related cues compared to neutral cues (P＜0.01); in the 140–210 ms time window, HER potentials in the right prefrontal cortex were significantly higher under drug-related cues compared to neutral cues (P＜0.01). Correlation analysis showed that HER potentials in the left temporal and left posterior cingulate cortices were significantly negatively correlated with VAS scores (P＜0.05). Drug-related cues enhanced PSD of γ power (30–100 Hz) in salience network (fronto-insular), parietal and occipital regions (P＜0.05). PSD integrations of low-γ power (40–60 Hz) in parietal region (350–400 ms) and high-γ power (70–100 Hz) in left salience network (fronto-parietal) and occipital regions (300–350 ms) were positively correlated with VAS scores (P＜0.05).

Conclusions Drug-related cues may modulate cortical activity related to heartbeat perception in HUD individuals, and such dynamic changes in both time and frequency domains are stably associated with subjective craving.