Multi-metric resting-state fMRI reveals brain network abnormalities underlying cognitive impairment in male patients during methamphetamine abstinence.

BACKGROUND

Methamphetamine (MA) use disorder leads to persistent cognitive impairment, but the underlying neural mechanisms during abstinence remain unclear. This study aimed to investigate brain functional abnormalities in male methamphetamine-abstinent patients and their associations with cognitive impairment using multiple resting-state fMRI metrics.

METHODS

Twenty-five male MA-abstinent patients (Disease Group, DG) and twenty-nine healthy controls (Healthy Control Group, HC) were recruited, and rs-fMRI data were collected. Multimodal analysis methods, including regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuations (fALFF), seed-based functional connectivity (FC), and independent component analysis (ICA), were employed to assess local spontaneous activity, hippocampal-centered functional connectivity, and large-scale resting-state network abnormalities. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). Group differences were compared using independent-samples t-tests, and brain-behavior relationships were analyzed using partial correlation and interaction models.

RESULTS

Compared with the HC group, the DG group showed reduced fALFF in several regions, including the left fusiform gyrus and right inferior frontal gyrus pars triangularis, using a voxel-level threshold of p < 0.005 combined with cluster-level FWE correction at p < 0.05. Reduced ReHo was also observed in the right inferior frontal gyrus pars triangularis using a voxel-level threshold of p < 0.05 combined with cluster-level FWE correction at p < 0.05. Seed-based functional connectivity analysis revealed widespread enhanced right hippocampal functional connectivity in the DG group using a voxel-level threshold of p < 0.005 combined with cluster-level FWE correction at p < 0.05. ICA identified abnormal functional connectivity in the default mode, auditory, and somatomotor networks, with all findings surviving cluster-level FWE correction at p < 0.05. Right hippocampus-right inferior temporal gyrus connectivity was strongly positively correlated with MoCA total score in the DG group (r = 0.765, p < 0.001), and this association was significantly stronger in the DG group than in the HC group.

CONCLUSION

Male MA-abstinent patients exhibit multi-layered brain functional abnormalities involving local activity, functional connectivity, and large-scale networks. These abnormalities, together with the disease-specific associations between right hippocampal functional connectivity and cognitive performance, suggest a potential role for right hippocampal networks in cognitive impairment during methamphetamine abstinence in men.