Resting-State Functional Magnetic Resonance Imaging Study Of Brain In Type 2 Diabetes Mellitus With Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy(DPN),the common complication of type 2 diabetes mellitus(T2DM),involves motor,sensory and autonomic nerves,leading to considerable pain and disability,which seriously impacts on the living quality.Studies have shown extensive changes in brain structure,function,and connectivity in DPN patients.However,the exact neurobiological mechanism of these alterations in brain function in DPN patients remains unclear.Based on the resting-state functional magnetic resonance imaging(rs-fMRI),this study investigated the alterations in brain functional activities in DPN patients from local neural activity of brain regions to macro functional networks.The local neural activity was analyzed by low frequency amplitude(ALFF),fractional low frequency amplitude(fALFF)and regional homogeneity(ReHo).At the functional network level,functional connectivity(FC)and graph theory were used to construct and analyze brain networks respectively.This study more comprehensively revealed the neurobiological mechanism of brain functional changes in DPN patients.It is of great theoretical significance and clinical value to explore the changes of brain functional activities in DPN patients.The paper consists of two parts,and the abstract is as follows:Part 1 Resting-state functional MRI study of altered brain function in diabetic peripheral neuropathyObjective:Brain functional alterations in T2DM with DPN associated with cognition and motor dysfunction remain largely unknown.Therefore,we aimed to investigate intrinsic resting-state functional brain activity in DPN patients.Materials and methods:A total of 28 DPN patients,43 T2DM without DPN(Non-DPN,NDPN)and 32 healthy controls(HCs)were recruited from the Department of Endocrinology of Shandong Provincial Hospital between February 2021 and March 2022.General clinical data acquisition,cognitive and mental scales,and neural and motor function evaluation were performed for all subjects.Rs-fMRI scans were performed and ALFF,fALFF and ReHo values were calculated.One-way analysis of covariance(ANCOVA)was applied to evaluate above indicators among the three groups,and the mean ALFF/fALFF/ReHo values of altered brain regions were then correlated to clinical features of T2DM patients.We extracted the mean ALFF/fALFF/ReHo values of significantly altered brain clusters after the post hoc test and used receiver operating characteristic(ROC)curves to evaluate the potential of each value as neuroimaging biomarkers to distinguish DPN patients,NDPN patients and controls.Results:Compared with NDPN group,the DPN group showed significantly decreased ALFF values in the right orbital superior frontal gyrus(ORBsup),medial superior frontal gyrus(SFGmed)and incresead ALFF values in the left inferior temporal gyrus(ITG)and decreased fALFF values in the right SFGmed.Compared with HCs,the NDPN group showed increased ALFF values in the right ORBsup,middle frontal gyrus,left orbital middle frontal gyrus and decreased fALFF values in the right middle temporal gyrus(MTG).According to the ROC curve analysis,the mean ALFF/fALFF values of the right SFGmed and the mean ALFF values of the left ITG and right ORBsup can distinguish DPN from NDPN patients.Notably,the mean ALFF values of the right ORBsup were significantly negatively correlated with Toronto Clinical Scoring System(TCSS)scores and gait speed in T2DM.Conclusion:DPN patients have abnormal brain activity in sensorimotor and cognitive brain areas,which may implicate the underlying neurophysiological mechanisms in intrinsic brain activity.Part 2 Topological changes of resting-state functional connectivity brain network in diabetic peripheral neuropathyObjective:The purpose of this study was to investigate whether and how the functional brain network topology changed in T2DM with DPN patients.Materials and methods:We recruited 28 DPN patients and 43 T2DM without DPN(NDPN)from the Department of Endocrinology of Shandong Provincial Hospital from February 2021 to March 2022.In addition,32 HCs were recruited.General clinical data acquisition,cognitive and mental scales,and neural and motor function evaluation were performed for all subjects.Rs-fMRI was performed on all subjects and whole-brain,region of interest(ROI)level FC networks were constructed.Then,we used graph theory to analyze the changes of global and nodal topological attributes.The global attributes include global efficiency(Eglob),local efficiency(Eloc),shortest path length(Lp),clustering coefficient(Cp),normalized Lp(γ),normalized Cp(λ)and smallworldness(σ).Nodal topological attributes include nodal efficiency(Enodal)and nodal betweenness centrality(Bnodal).Finally,One-way ANCOVA was performed to compare the differences among the three groups and partial correlation analysis was performed between altered Eloc and clinical parameters.Results:We found that both T2DM patients and healthy controls showed efficient small-world organization in FC networks.However,NDPN patients exhibited a significantly decreased Lp compared with HCs.Compared with HCs,T2DM showed a partial reorganization of hub distributions,and the similar hub regions included bilateral median cingulate and paracingulate gyri(DCG),left middle occipital gyrus(MOG)and MTG,right superior temporal gyrus(STG)and inferior temporal gyrus(ITG).In addition,compared with the HCs group,the DPN group and the NDPN group had 9 and 4 unique hubs,respectively,which were mainly distributed in the default mode network(DMN),attention and visual function areas.Compared with NDPN group,DPN group showed significantly decreased Enodal mainly in bilateral superior occipital gyrus(SOG),right cuneus,MTG and left inferior parietal gyrus(IPL)and no region showed significantly increased Enodal.It was worth noting that none of the brain regions with significantly decreased Enodal of DPN group were located in the hub regions.Furthermore,the altered Enodal of the right SOG showed a significantly negative correlation with TCSS scores in T2DM patients.The altered Enodal of the right postcentral gyrus(PoCG)and MTG were significantly positively correlated with Montreal Cognitive Assessment(MoCA)scores in T2DM patients.Conclusion:The results demonstrated that disruptions occurred in brain functional network of DPN patients,which provided theoretical support for understanding the neurophysiological mechanism and effective prevention and treatment of DPN.