White Matter Microstructure And Cognitive Changes In Abstinent Methamphetamine Dependent Individuals: A Longitudinal Study

Objective: Using neuropsychological tests and diffusion tensor imaging(DTI),our study aimed to investigate cognitive and white matter microstrucutre deficits in methamphetamine(MA)abstinents.How these deficits change with abstinence was also explored.Method: Thirty MA dependent individuals who had abtained from substances in the past 5.5 months and 29 drug-na?ve controls(HC)were recruited.All participants underwent baseline cognitive tests and MRI scans in the same period of time.Six months later,follow-up tests and scans were conducted in MA group.Cogstate neuropsychological tests battery and stroop test were included in congnitive tests.Diffusion weighted image and T1 strucutral image were collected by a 3-T MR scanner.DTI-TBSS was used to analyze cross-sectional imaging data.Fractional anisotropy(FA),which reflects directional coherence of fibre tracts,was the main outcome measure.Utilizing baseline TBSS results as regions of interests,we traced their change trend through abstinence.We also presented the application of voxel-based connectivity measured by probabilistic tractography to obtain a connectivity index along a white matter pathyway to targeted grey matter regions.Results: MA and HC did not show any difference in cognitive performeances.There were also no changes through baseline to follow-up cognitive tests in MA group.In terms of FA,a gender by group interaction effect was found in the baseline.Compared with HC males,the male MA abstinents had lower FA in right internal capsule(0.647 ± 0.017 vs.0.610 ± 0.020,p < 0.001),whose FA reduced to 0.596 ± 0.022(p < 0.001)in the follow-up.The male MA patients had significantly higher connectivity index between right anterior limb of internal capsule and right inferior frontal gyrus than male controls(p = 0.021).The strengthened connectivity remained unchanged in the follow-up.Compared with HC females,the female MA abstinents had higher FA in right parietal and temporal regions(0.535 ± 0.019 vs.606 ± 0.027,p < 0.001),followed by a drop to 0.566 ± 0.034(p < 0.001)in the follow-up.Conclusion: MA patients do not show cognitive deficits after they have abstained from MA for 5.5 months.Gender may matters in MA related white matter microstructure abnormality.Male MA abstinents manifest DTI index changes in basal ganglia area,while femal MA abstinents manifest opposite change direction in parietal-temporal white matters.After abstaining from MA for 12.6 months,male MA abstinents’ white matter deficits do not recover towards controls’ level but MA females show a recovery to normal level.The strengthened connectivity between right internal capsule and right inferior frontral gyrus in MA males may reflect prefrontal cortex’s compensatory regulation of subcortical white matter deficits.