Lower Fractional Anisotropy in the Gray Matter of Amygdala-Hippocampus-Nucleus Accumbens Circuit in Methamphetamine Users: an In Vivo Diffusion Tensor Imaging Study

The basolateral amygdala (BLA), hippocampal ventral subiculum, and nucleus accumbens (NAc) comprise the amygdala-hippocampus-NAc (AHN) circuit, which is implicated in drug seeking and reward. The goal of this study was to evaluate microstructural changes and relevant clinical features of the AHN circuit gray matter (GM) in methamphetamine (MA) users using diffusion tensor imaging (DTI). Thirty MA users and 30 age-matched normal volunteers underwent 3-T MR imaging to obtain structural T1-weighted images and DTI data. Freesurfer software was used to automatically segment the NAc and subiculum. A Julich probability map was employed to parcellate the BLA. Fractional anisotropy (FA) and mean diffusivity (MD) maps were generated and non-linearly coregistered to structural space. DTI measures of the AHN circuit GM were compared between MA users and controls using repeated measures analysis of variance. Correlation analyses were performed between DTI measures and clinical characteristics. Anatomical correlations between the NAc and BLA/subiculum in both groups were assessed using correlation analyses. The MA group had significant lower FA in the bilateral BLA, subiculum, and NAc. Higher total MA dose corresponded with lower FA in all three structures. Hamilton Anxiety Rating Scale scores negatively correlated with the right subiculum FA. Lower left BLA FA was associated with higher thinking disorder and hostile-suspicion factor scores. Left BLA FA was significantly associated with bilateral NAc FA in MA users. Those findings provided neuroimaging evidence of MA-induced microstructural impairment in the AHN circuit GM. Enhanced anatomical correlations between the left BLA and bilateral NAc may be part of the mechanism of MA intake relapse and for development of psychosis.