Association Between Cognitive Function And Multimodal MRI Metrics In Men With Methamphetamine Use Disorder

Objective:Methamphetamine（MA）is an illicit psychostimulant that is subject to abuse worldwide with intense neurotoxicity.Despite mounting evidence on MA-induced damage on cognitive impairment,it remains a matter of debate and the brain imaging mechanism behind it has not been fully elucidated.Therefore,this study attempts to study methamphetamine use disorder（MUD）from the perspective of neuropsychology and neuroimaging:（1）To investigate the cognitive impairments in men with MUD using a standardized neurocognitive test battery.（2）To examine the changes in gray matter,white matter,and local spontaneous neural activity in men with MUD using multimodal magnetic resonance imaging,and their relationship with cognitive function,trying to understand the brain structure and functional basis of cognitive impairment in men with MUD.Methods:This study recruited patients from the Hunan Kangda Voluntary Drug Rehabilitation Center who met the diagnostic criteria of MUD based on the Diagnostic and Statistical Manual of Mental Disorders,the Fifth Edition（DSM-5）through face-to-face clinical interviews.Healthy controls（HC）were recruited from the community.A self-administered questionnaire was used to collect the general demographic and clinical data and a set of standardized neurocognitive tests called MATRICS Consensus Cognitive Battery（MCCB）was used to evaluate cognitive functions.Structural magnetic resonance imaging（s MRI）,diffusion tensor imaging（DTI）,and resting state functional magnetic resonance（rs-f MRI）were performed using a 3.0T MRI scanner.After the inclusion/exclusion criteria and quality control of the data,88 samples were finally included,that is,45 MUD and 43 HC.In study 1,the differences in ten cognitive subtests as well as four common DTI indicators namely fractional anisotropy（FA）,mean diffusivity（MD）,axial diffusivity（AD）,and radial diffusivity（RD）were compared between the two groups.Linear regression was then performed to examine the relationship between white matter microstructure and cognitive function.In study 2,the s MRI data was processed and analyzed.Voxel-based morphometry（VBM）and surface-based morphometry（SBM）analysis were used to compare gray matter volume and cortical thickness differences between the two groups with the s MRI data.Linear regression was then performed to examine the relationship between gray matter volume/cortical thickness and cognitive functions.In study 3,the rs-f MRI data was processed and analyzed.Regional homogeneity（Re Ho）and low-frequency upgrade（ALFF）were compared between the two groups,and linear regression was performed to further explore the relationship between Re Ho/ALFF and cognitive function.Results:（1）Cognitive function:men with MUD had lower DSST scores（41.00±2.79）than HC（52.90±2.24）,lower CPT-IP scores（35.40±2.67）than HC（53.00±2.14）,lower HVLT-R scores（37.70±2.62）than HC（49.60±2.10）,and lower NAB-Mazes scores（45.10±2.21）than HC（54.20±1.71）（all p<0.05,with Bonferroni correction）.（2）White matter microstructure:（1）patients with MUD had higher AD（F（1,81）=11.29,p=0.024）,MD（F（1,81）=17.44,p=0.001）and RD（F（1,81）=15.05,p=0.002）values of the left superior longitudinal fasciculus（SLF）than HC.Other white matter fiber tracts,including the FA of the left SLF,showed no significant results after Bonferroni correction.（2）Regression analysis showed that the RD value of the left SLF was negatively associated with DCST（β=-0.40,p=0.0013）and NAB-Mazes（β=-0.28,p=0.024）.（3）Gray matter structure:MUD showed smaller gray matter volume in the lateral middle frontal gyrus,right insula,left posterior central gyrus and bilateral parietal inferior marginal gyrus than HC(P_FDR-corr<0.05,cluster>100);（2）The cortical thickness of the left inferior frontal gyrus triangle and left inferior frontal gyrus insula in MUD was significant thinner than that of HC(P_FDR-corr<0.05,cluster>100);（3）DSCT linear regression showed an interaction between group and left inferior frontal gyrus insula（β=-0.43,p=0.04）and left precentral gyrus（β=0.58,p=0.01）on DSCT.For NAB-Mazes,the cortical thickness in the left inferior frontal gyrus insula was positively correlated with NAB-Mazes scores（β=0.43,p=0.02）,and its interaction with group was significant（β=-0.68,p=0.001）;For CPT,the left superior frontal gyrus was negatively correlated with CPT scores（β=-0.31,p=0.03）.（4）Brain function:（1）MUD had lower Re Ho value of the superior temporal gyrus and the left lingual gyrus than HC(P_FDR-corr<0.05);（2）MUD had higher ALFF values of the bilateral fusiform gyrus and left putamen((P_FDR-corr<0.05),and lower ALFF values of the bilateral postcentral gyrus and left middle cingulate gyrus than HC(P_FDR-corr<0.05).（3）Regression analysis showed that the Re Ho value of the right postcentral gyrus was positively associated with NAB-Mazes（β=0.453,p=0.014）,and the ALFF value of the left putamen was negatively associated with DSCT（β=-0.380,p=0.027）,CPT（β=-0.345,p=0.037）and NAB-Mazes（β=-0.510,p=0.024）.Conclusion:（1）MUD was associated with a variety of cognitive deficits,mainly in processing speed,attention,language learning,and reasoning and problem-solving abilities.（2）MUD had altered left SLF microfibers,which was associated with reduced processing speed and problem-solving ability.（3）MUD exhibited changes in gray matter morphology in a wide range of brain regions,and cortical thickness changes in the frontal cortex may be the neuroanatomical basis of cognitive deficits in MUD.（4）MUD showed changes of spontaneous neural activity,and the intensity of spontaneous neural activity in the left putamen is closely related to cognitive function.