A FMRI Study Of Spontaneous Cortical And Subcortical Activity Alterations In Type 2 Diabetes Mellitus With Depression

Objective: The current study aimed to investigate the alteration of cortical and subcortical spontaneous neural activity in type 2 diabetes mellitus(T2DM)patients with depression.Methods: The demographic data,clinical variables,neuropsychological tests,and functional and anatomical magnetic resonance imaging of depressed T2DM(n = 47)of nondepressed T2DM(n = 59)and healthy controls(n = 41)were collected and evaluated.Independent-sample t-tests or one-way analysis of variance followed by Bonferroni post-hoc test was used for continuous variables with normal distribution and homogeneity of variances.Accordingly,the Kruskal-Wallis test or Mann-Whitney U test was performed for the nonnormal distribution data.The Chi-square test was applied for categorical variables.The resting-state functional indicators,including amplitude of low frequency fluctuation(ALFF),fractional ALFF and degree centrality(DC)of the cerebral cortex and subcortical regions,were evaluated using a surface-based analysis method with highly sensitivity,specificity and accuracy of region alignment.Then,the same indicators of cerebral cortex and subcortical regions were calculated again using the traditional volume-based analysis method to validate the results of surface-based analysis method.Moreover,correlation analysis and stepwise multiple linear regression analysis were performed between the abnormal spontaneous cortical or subcortical activity values and clinical variables,neuropsychological tests of depressed T2 DM and non-depressed T2 DM patients.The receiver operator characteristic curve was plotted was calculated to validate the diagnostic performance of different brain regions.Results: Abnormal neural activities in the bilateral posterior cingulate cortex and hippocampus were observed in depressed and non-depressed T2 DM and the right putamen of the depressed T2 DM.Interestingly,the subcortical DC of the right hippocampus and putamen were higher in depressed than non-depressed T2 DM.Furthermore,the cortical ALFF in posterior cingulate cortex,subcortical DC in the putamen of depressed T2 DM,and hippocampus of non-depressed T2 DM was correlated with cognitive scores.In contrast,the cortical fractional ALFF in posterior cingulate cortex of non-depressed T2 DM was correlated with depression scores.Further validation by volume-based analysis revealed abnormal spontaneous activity in the default mode,attention,sensorimotor,visual network and subcortical regions of T2 DM.Additionally,the abnormal spontaneous activity values in the depressed T2 DM was related to cognition and depression score,and the non-depressed T2 DM was associated with cognition,anxiety,and depression scores.Conclusions: The abnormalities of spontaneous cortical activity in posterior cingulate cortex and subcortical activity in the hippocampus might represent the neurobiological feature of cerebral dysfunction in T2 DM.Notably,the altered subcortical activity in the right putamen might mainly associate with negative emotion in T2 DM,which could be a promising biomarker for recognizing early cerebral dysfunction in depressed T2 DM.This study provided a novel insight into the neuropathophysiological mechanism of brain dysfunction in T2 DM with depression.