The Study Of Low Frequency Amplitude And Functional Connection Of Left Calcarine In Type 2 Diabetes Mellitus

Part one:Amp Iitude of low frequency fluctuation and fractional ampiitude of low frequency fluctuation in Type 2 diabetes mellitus:a rs-fMRI studyObjectiveResting-state functional magnetic resonance imaging(rs-fMRI)was used to investigate the changes of amplitude of low frequency fluctuation(ALFF)and fractional amplitude of low frequency fluctuation(fALFF)in type 2 diabetes mellitus,and to explore the correlation between the changes of brain function,clinical biochemical indicators and cognitive function,and to find out the potential neuroimaging changes before clinical cognitive dysfunction in patients with T2DM,which provided a new basis for early clinical intervention and individualized treatment to improve the prognosis of diabetic encephalopathy.MethodsFrom January 2017 to December 2018,41 patients with type 2 diabetes in the endocrine clinic or in-patient department of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine were selected as the experimental group(T2DM group),24 males and 17 females.The American Diabetes Association(ADA)in 2014 was used as the diagnostic and classification criteria.Healthy control group(HC)consisted of 40 healthy adults,23 males and 17 females.Age,sex and education level were matched with those of patients with T2DM.All the subjects were right-handed.In this study,a number of neurocognitive scales were completed in both the T2DM and HC groups,including MoCA-B,AVLT,TMT-A,TMT-B,Grooved pegboard test,DST,CDT and SDT,to evaluate the neurocognitive function.Before receiving MRI scans,all the subjects completed neurological examination,blood biochemical examination and cognitive function scale evaluation,and collected information such as height,weight,blood pressure and other clinical history.Blood biochemical exanination including fasting blood glucose(FBG),fasting insulin(FINS),glycosylated hemoglobin Ale(HbAlc),total cholesterol(TC),triglyceride(TG)and low density lipoprotein(LDL).The machine is GE SIGNA EXCITE 3.OT magnetic resonance imaging scanner.All subjects were scanned with conventional and experimental sequences to collect raw data.Conventional sequences were used for intracranial organic diseases(such as tumors,infections,cerebrovascular accidents,congenital brain abnormalities and obvious variations such as arachnoid cysts and cisterns Magna occipitalis),including T1WI,T2WI and T2 Flair;experimental sequences included 3D-T1WI high resolution whole brain structural imaging and resting BOLD imaging.DPARSF 4.4 Advanced Edition batch processing tool was used to preprocess resting MR raw data of all subjects,based on MATLAB R2012a platform.The processing steps are as follows:(1)data format conversion(2)deletion of the previous time points scanned image(3)Slice Timing(4)Realignment(5)spatial standardization(normalization)processing(6)spatial smoothing(7)removing linear detrends(8)Filter.Using REST data analysis toolkit VI.8,double-sample t-test was carried out on ALFF and fALFF statistical parameter maps of two groups of subjects.Brain mask(91mm X109 mn X91 mm)with REST Vl.8 was used as registration template.Brain area maps(P≤0.01 and cluster size>10)with significant difference between ALFF and fALFF were obtained.Three-dimensional localization of these brain regions was carried out,and the AAL partition was used as a template to organize and list the information of specific brain regions,the number of clusters and the size of T value.With appropriate statistical methods,the differences of demographic data,biochemical examination and cognitive function score between the two groups were compared,and the correlation between clinical biochemical data and neurocognitive function related scale score was analyzed,P<0.05 considered that there was statistical significance.Result:1.Population statistics,clinical biochemical indicators and neuroco gnitive function scale scoreThere was no significant difference in age,sex and education between the two groups.BMI(P=0.003),Systolic blood pressure(P=0.000)and diastolic blood pressure(P=0.026)in the T2DM group were significantly higher than those in the HC group.In T2DM group,fasting blood glucose was(7.84±1.97)mmol/L,fasting insulin FINS was(9.17+9.20)uIU/ml,glycosylated hemoglobin HbAlc was(8.69±1.97)%,triglyceride was(1.87±1.45)mmol/L,cholesterol was(4.53±1.19)mol/L,and LDL was(3.31±1.09)mmol/L.MoCA-B score(,P=0.007)and AVLT immediate recall score(P=0.040)in T2DM group were significantly lower than those in HC group.TMT-B(P=0.020),Grooved Pegboard-R(P=0.002)and Grooved Pegboard-L(P=0.011)were significantly longer than those in HC group.There were no significant differences in AVLT short-term delayed recall score,AVLT long-term delayed recall and AVLT recognition,TMT-A,clock drawing test,digital breadth test score(forward and inverse)and digital symbol test between T2DM and HC groups.There was a significant negative correlation between glycosylated hemoglobin and AVLT immediate memory score,delayed 5 minutes and delayed 15 minutes.Systolic blood pressure level was positively correlated with AVLT delayed 15 minutes.Other clinical indicators,such as BMI,diastolic blood pressure,fasting blood sugar,fasting insulin,triglyceride,low density lipoprotein and cholesterol,were not significantly correlated with the neurocognitive function related scale.2.Differences in ALFF and fALFF values between T2DM and HC groupsCompared with HC group,the brain areas with elevated ALFF value in T2DM group mainly included left paracentral lobule,left angular gyrus,left superior temporal gyrus,right posterior cerebellar lobe and right middle temporal gyrus.The decrease included left posterior central gyrus,left medial superior frontal gyrus,left anterior euneiform lobe,left cortex around talus fissure,right middle occipital gyrus,right lingual gyrus,right posterior cerebellar lobe and right anterior central gyrus.Compared with HC group,the increased fALFF values in T2DM group mainly included bilateral paracentral lobules,left angular gyrus,left middle temporal gyrus and right inferior orbital frontal gyrus.The brain regions with decreased fALFF value mainly included bilateral occipital lobe(cortex around talus fissure),bilateral lingual gyrus,right suboccipital gyrus,right central posterior gyrus,etc.Conclusion1.In resting state,the spontaneous activity of multiple brain regions in patients with type 2 diabetes mellitus was abnormal,and the values of ALFF and fALFF changed.The changes of brain regions were mainly related to the default-mode network.2.It is suggested that the changes of ALFF and fALFF values of spontaneous brain activity are mostly located in bilateral occipital lobes,and bilateral occipital lobes are correlated with visual function,suggesting that diabetic patients may have visual central injury.The changes of ALFF and fALFF may predict the long-term visual impairment in diabetic patients.3.HbAlc,systolic blood pressure and AVLT test scores were correlated,suggesting that changes in HbAlc and blood pressure levels could affect memory function in type 2 diabetes mellitus.Part two:The left calcarine functional connectivity in Type 2 diabetes mellitus:a rs-fMRI studyObjectiveUsing rs-fMRI technique,the functional connectivity analysis method based on region of interest(ROI)was used to construct the whole brain functional connectivity with the left calcarine as the ROI area,and to explore the correlation between the functional connectivity changes and neurocognitive function in type 2 diabetes mellitus.To evaluate the role of rs-fMRI imaging technology in elucidating the potential neuroimaging mechanism of brain injury in patients with T2DM,and to provide a new basis for early clinical intervention and individualized treatment to improve the prognosis of diabetic encephalopathy.MethodsFrom January 2017 to December 2018,41 patients with type 2 diabetes mellitus in the endocrine clinic or in-patient department of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine were selected as the experimental group(T2DM group).There were 41 patients in the T2DM group,including 24 males,17 females,40 in the HC group,23 males and 17 females.The inclusion and exclusion criteria of T2DM group and HC group were the same as the first part of the study.The related neurological function scales are the same as the first part,including MoCA-B,AVLT,MMSE,TMT-A,TMT-B,Grooved pegboard,DST,digital symbol test,SDT and clock drawing test(CDT).The cognitive function of all subjects was assessed.The machine is GE SIGNA EXCITE 3.0T.All subjects were scanned with conventional oblique axial T1WI,T2WI and T2FLAIR sequences to exclude organic lesions.The experimental sequence is the same as the first part,including 3D T1 and BOLD sequences,and the parameters of each sequence are the same as the first part.DPARSF 4.4 Advanced Edition batch processing tool was used to preprocess resting MR raw data of all subjects on MATLAB R2012a platform.The processing steps are as follows:(1)data format conversion(2)deletion of the previous time points scanned image(3)Slice Timing(4)Realignment(5)spatial standardization(normalization)processing(6)spatial smoothing(7)removing linear detrends(8)local characteristic analysis.Resting-state functional connectivity analysis includes ICA-based functional connectivity analysis and ROI-based functional connectivity analysis.In this study,ROI-based functional connectivity analysis was used.According to the results of the first part of the study,the left talus fissure pericortex(AAL43)was selected as the region of interest.Using REST data analysis toolkit VI.8,the statistical parameter maps of brain functional connectivity of the two groups were tested by double-sample t-test.Using the brain mask(91mm*109 mm*91mm)of REST VI.8 as registration template,the brain regions maps with significant differences in functional connectivity between the two groups were compared(P≤0.01 and cluster size>10,after correction).Three-dimensional localization of these brain regions was carried out,and the AAL partition was used as a template to organize and list the information of specific brain regions,the number of clusters and the size of T value.ResultCompared with HC group,the areas of increased brain functional connectivity in T2DM group included bilateral posterior cerebellar lobe,left angular gyrus,right cingulate gyrus,right hippocampus and right straight gyrus,and the areas of decreased brain functional connectivity were bilateral talus fissure pericortex,bilateral middle occipital gyrus,bilateral central posterior gyrus,bilateral lingual gyrus and bilateral cerebellar vermis.Conclusion1.The increase or decrease of left talus fissure and the functional connectivity of the whole brain are mostly symmetrical distribution,mainly with the decrease of functional connectivity.2.The brain areas with impaired functional connectivity in the T2DM group were mainly bilateral occipital lobes,which were consistent with the decrease of ALFF and fALFF values in bilateral occipital lobes.It confirmed that there were abnormal brain functions in bilateral occipital lobes in the T2DM group,suggesting the possibility of early visual central injury in diabetic patients.3.The left angular gyrus of type 2 diabetes mellitus has abnormal activation and enhanced functional connectivity.As the visual reading center of language center,the left angular gyrus suggests the possibility of dyslexia in type 2 diabetes mellitus.