| Objective:The purpose of this study was to compare the changes of acute brain function between baseline and single dose risperidone provocation state in patients with schizophrenia(SZ)and healthy controls(HC)by 18F-fludeoxyglucose(18F-FDG)simultaneous positron emission tomography and magnetic resonance imaging(PET/MRI),and to explore the value of these changes in identifying pathophysiology and imaging markers of SZ.Methods:A total of 13 chronic SZ patients who were hospitalized in The Third People’s Hospital of Wenjiang District,Chengdu between January 2021 and August 2021 were included,and 23 HC who received physical examinations at West China Hospital of Sichuan University during the same period were recruited.Sign the informed consent form before joining the group,and collect the basic information such as name,gender,age,education years,smoking and alcohol history,family history and patient course.All subjects underwent two 18F-FDG PET/MRI examinations at baseline and single dose risperidone provocation state,positron emission tomography(PET)images,resting-state blood oxygen level dependent(BOLD)images and high resolution T1-weighted image(HRT1WI)were collected.Images were automatically reconstructed by a post-processing workstation.SPM based on MATLAB was used to preprocess and statistically analyze PET images,taking the cerebellum as the reference area,the difference of baseline standardized uptake value ratio(SUVR)between SZ and HC was analyzed by independent two samples t-test,paired samples t-test was used to analyze the differences of SUVR before and after drug provocation within the SZ and the HC,and the results were corrected by false discovery rate(FDR).DPABI and GRETNA based on MATLAB are used for preprocessing and statistical analysis of BOLD images.After preprocessing,the cerebrum was divided into 90 regions of interest(ROI)using automated anatomical labeling(AAL)template,and the brain function network was constructed,the difference of brain network global properties between SZ and HC was analyzed by independent two samples t-test,paired samples t-test was used to analyze the differences of brain network global properties before and after drug provocation within the SZ and the HC.Correlation analysis was performed between the global properties of brain function network differences and the SUVR of brain regions with differences in glucose metabolism.Results:1.After screening by exclusion criteria,6 chronic SZ patients(4 males,2 females,aged 33～57 years)and 13 HC(6 males,7 females,aged 24～65 years)were included in the follow-up images preprocessing and statistical analysis.2.Independent two samples t-test showed that there was significant difference in average blood drug concentration between groups(P<0.01),and there was no significant difference in education years between groups(P>0.05).Mann-Whitney test showed that there was no significant difference in age between the groups(P>0.05).Fisher’s exact test showed that there was no significant difference in gender and smoking and alcohol history between the groups(P>0.05).3.Paired samples t-test in the SZ group showed that there was no significant difference in SUVR in any brain area before and after taking the drug(P>0.001).A between-group independent two samples t-test showed that compared with HC,SZ was found to have significantly lower SUVR(P<0.001)in the following multiple clusters:right middle frontal gyrusright superior frontal gyrus-right inferior frontal gyrus,triangular part(MNI coordinates:30,46,22),bilateral superior frontal gyrus,medial-bilateral anterior cingulate and paracingulate gyrus-bilateral internal frontal gyrus,orbital part(MNI coordinates:-6,48,16),left middle frontal gyrus-left superior frontal gyrus(MNI coordinates:-22,46,32),right insula-right inferior frontal gyrus,orbital part-right lateral inferior frontal gyrus,triangular part-right Rolandic operculum-right inferior frontal gyrus,opercular part(MNI coordinates:38,8,4),left supramarginal gyrus-left Inferior parietal,but supramarginal and angular gyrus-left superior temporal gyrus-left posterior central gyrus(MNI coordinates:-58,-24,42),bilateral anterior cingulate gyrus-bilateral medial cingulate gyrus-left superior frontal gyrus,medial-left supplementary motor area(MNI coordinates:-8,30,24),left orbitofrontal cortex(MNI coordinates:-44,32,-14),left inferior frontal gyrus,opercular part-left insula-left Temporal pole:superior temporal gyrus-left Rolandic operculum-left superior temporal gyrus-left inferior frontal gyrus,triangular part-left inferior frontal gyrus,orbital partleft precentral gyrus(MNI coordinates:-50,8,2),right middle frontal gyrus-right central anterior gyrus-right superior frontal gyrus(MNI coordinates:34,2,56);there was no significant increase of SUVR found in SZ(P>0.001).Paired samples t-test in the HC group showed that the SUVR in the right hippocampus-right parahippocampal gyrus-right fusiform gyrus(MNI coordinates:34,-28,-20)cluster of the drug provocation state scan was significantly higher than the baseline state(P<0.001);and there was no significant reduction area of SUVR in the drug provocation state(P>0.001).4.The drug provocation state gamma(γ)in the SZ group was significantly higher than the baseline state(P<0.05),and the drug provocation state sigma(σ)tends to be higher than the baseline state(P=0.054);the baseline γ in the SZ group was significantly lower than that in the HC group(P<0.01),and the baseline σ of SZ group tends to be lower than that in the HC group(P=0.053);there was no significant difference in clustering efficiency(Cp),characteristic path length(Lp),lambda(λ),global efficiency(Eg),local efficiency(Eloc)and synchronization(S)(P>0.05).5.There was no significant Pearson correlation between the SUVR of meaningful right hippocampus-right parahippocampal gyrus-right fusiform gyrus in HC group and meaningful frontotemporal extensive regions-limbic system partial regions-bilateral insular-left temporo parietal junction region between SZ and HC group and the y of meaningful brain function global properties(P>0.05).Conclusions:1.The acute brain glucose metabolism changes in HC induced by a single dose of risperidone were located in the right hippocampus-right parahippocampal gyrus-right fusiform gyrus,suggesting that there may be a risperidone target in this region.2.The differences in baseline brain glucose metabolism between SZ and HC are located in the extensive frontotemporal lobe,part of the limbic system,bilateral insula and left temporo-parietal junction,which may be related to the pathophysiology of SZ,it can be further explored and developed as an imaging marker of SZ in the future.3.There were no significant acute change in brain glucose metabolism in SZ patients before and after taking the drug,which may be related to the small sample size,variable duration of disease,and insufficient responsiveness to 1mg of risperidone in chronic patients.4.The global topological properties γ and σ of the brain function network showed significant differences and trend of differences in the comparison between the baseline groups and within the SZ group,respectively.It is speculated that there is a risk of randomization in the small world of the brain network in patients with SZ,which is mainly caused by reduced local processing capacity,and risperidone can reduce this risk.5.The glucose metabolism in right hippocampus-right parahippocampal gyrus-right fusiform gyrus and fronto temporal extensive regions-limbic systempartial regions-bilateral insular-left temporoparietal junction region is not significant correlated with the y of brain function network global properties.Further research is needed in the future. |
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