The Characteristics Of Cerebral Glucose Metabolism And Functional Connectivity In Heroin-dependent Individuals:An Integrated PET/fMRI Study

BackgroundHeroin dependence is a serious public health problem in the world.At present,the number of heroin-dependent individuals（HDIs）is increasing,the forms of abuse are complicated,and the treatment gap is serious.In addition to social factors,the neurological mechanism of heroin dependence is still unclear,which is the biggest bottleneck restricting prevention and treatment at the medical level.Modern neuroimaging techniques have greatly promoted the understanding of the neural mechanism of heroin dependence,including PET describing the metabolic and biochemical characteristics of the brain in HDIs,and MRI describing the structural and functional characteristics of the brain in HDIs.Previous f MRI studies have found abnormal functions of brain networks such as default mode network（DMN）in HDIs.PET studies have preliminarily found that the HDIs have abnormal brain glucose metabolism characteristics compared with the healthy controls（HCs）.However,the relationship between the glucose metabolism and functional connectivity in the brain of the HDIs is not very clear,and elucidating their relationship is conducive to further understanding of the neural mechanism of heroin dependence.It has been confirmed that glucose metabolism is positively correlated with functional connectivity in brain network-related regions in healthy people.Recent studies have found that patients with functional encephalopathy such as Alzheimer’s disease have abnormal relationships between glucose metabolism and functional connectivity in brain network-related regions compared with the HCs.We hypothesize that there is a relationship between brain glucose metabolism and functional connectivity among brain networks in the HDIs.Accordingly,the study was operated by an integrated Positron Emission Tomography/Magnetic Resonance Imaging（PET/MRI）which can simultaneously collect f MRI data and ¹⁸F-fludeoxyglucose(¹⁸F-FDG)metabolism data.The HDIs were taken as the observed objects to collect and analyze the characteristics of glucose metabolism in the brain,and the brain regions with abnormal glucose metabolism in the brain were taken as the seed points.The group differences of global brain functional connectivity in brain regions with abnormal glucose metabolism in HDIs were further analyzed.In order to provide objective neuroimaging experimental data for further analysis of the neuropathological mechanism of heroin dependence from both metabolic and functional perspectives.ObjectiveTo explore the characteristics of cerebral glucose metabolism in HDIs and its relationship with the function of large brain network from the perspectives of metabolism and function,in order to provide objective imaging data for studying the neuropathological mechanism of heroin dependence.MethodsExperiment 1:Thirty-six HDIs and 30 matched healthy controls（HCs）were recruited in this study,the heroin use history,spontaneous and drug cue-induced craving cores of all HDIs were collected.¹⁸F-FDG PET/MRI scans were performed on all subjects and ¹⁸F-FDG PET data of their brains were collected.The Dpabi software was used to compare and observe the differences of glucose metabolism in brain regions between the two groups by using the two-sample t test.The Pearson correlation analysis was used to analyze the correlation between drug use history,spontaneous craving and cue-induced craving scores and brain glucose metabolism of HDIs.The statistical threshold is set as P<0.05.Experiment 2:Thirty-five HDIs and 28 matched healthy controls（HCs）were recruited in this study,the heroin use history,spontaneous and drug cue-induced craving cores of all HDIs were collected.The brain regions with abnormal glucose metabolism obtained in experiment 1 were used as seed points to obtain the global brain functional connectivity values of the two groups of subjects.The Dpabi software was used to observe and analyze the differences between groups in the global brain functional connectivity of the brain regions with abnormal glucose metabolism in HDIs by using the two-sample t test.The Pearson correlation analysis was used to analyze the correlation between drug use history,spontaneous craving and cue-induced craving scores and Pearson correlation analysis was used to analyze the correlation between drug use history,spontaneous craving and cue-induced craving scores and the functional connectivity values of different brain regions in HDIs.The statistical threshold is set as P<0.05.ResultsExperiment 1:The HDIs showed widespread hypometabolism in the bilateral temporal[the middle temporal gyrus（MTG）,superior temporal gyrus]and the bilateral parietal（angular gyrus,supramarginal gyrus,inferior parietal lobe,Rolandic operculum,and left insula）,but obvious hypermetabolism in the brainstem and left cerebellum（single-voxel level,P<0.001;cluster-level voxel,P<0.05;corrected with GRF）.Furthermore,HDIs showed a positive correlation between the duration of heroin use and glucose metabolism of the left MTG（single-voxel level,P<0.001;cluster-level voxel,P<0.05;corrected with GRF）.Experiment 2:The HDIs showed the hypometabolism of the right MTG which is included in the DMN was accompanied by decreased coupling with the left superior frontal gyrus and the right superior parietal gyrus which are included in the ECN（single-voxel level,P<0.001;cluster-level voxel,P<0.05;corrected with GRF）.In addition,there was no significant correlation between the functional connectivity of the brain regions with abnormal metabolism and the usage history of heroin,spontaneous craving and cue-induced craving scores in heroin addicts（P>0.05）.Conclusions1.HDIs were characterized by widespread bilateral hypometabolism in DMN brain regions（the temporal and parietal regions）,but obvious hypermetabolism in the brainstem and left cerebellum due to long-term heroin use.2.The hypometabolism in the self-referential-related DMN regions in HDIs might attenuate their relationships with the inhibitory-control-related ECN regions.These findings highlight the importance of evaluating the metabolic and functional profiles of the right MTG in future studies on the treatment of heroin dependence.