Altered Functional Connectivity Of The Cingulate Subregions In Alzheimer's Disease

Objective: In this study,we aimed to explore the changes in functional connectivity in the sub-regions of the cingulate cortex in patients with Alzheimer's disease and to explore the correlations between FC changes and the clinical behavioral assessments of the patients.Materials and Methods: The 39 subjects in this study were recruited from 56 ADNI-2 centers in the United States and Canada during the year 2011 to 2013,including 23 Alzheimer patients and 16 healthy elder controls.Magnetic resonance imaging(MRI)data(including three dimensional high resolution T1 images and resting state functional magnetic resonance images)were obtained using a Siemens 3.0 Tesla MRI scanner.1.The rs-f MRI data were preprocessed.2.The ROI-based rs FC analyses were carried out between nine cingulate cortex sub-regions and the whole brain.3.The rs FC values of the brain regions with significant intergroup FC differences were extracted,and the Pearson correlation coefficients between the rs FCs and clinical behavior scores were calculated,with age,sex,and education years regressed.Results: Without global signal regression,we only found decreased whole-brain functional connectivity of the cingulate cortex subregions in Alzheimer's patients.The cingulate sub-regions with reduced functional connectivity included the bilateral p ACC(area32),left RSC,right s ACC,and right a MCC(area32).The brain regions with reduced rs FC with the s ACC were central executive network,including the the dorsolateral prefrontal lobe;sensorimotor network,including the precentral gyrus;and the default mode network,with the anterior part of the inferior temporal gyrus and inferior parietal lobe mainly involved.The brain network with reduced rs FC with the p ACC(area32)included the default mode network(the anterior part of the middle and inferior temporal gyrus).The a MCC(area 32)showed decreased rs FC with the central executive network(DLPFC).RSC demonstrated reduced connectivity with the default mode network(anterior part of the middle temporal gyrus).After regressing out the global mean signal,we identified significant differences in the whole-brain functional connectivity of the cingulate cortex sub-regions between patients with Alzheimer's disease and the healthy elder controls.The patients showed both increased and decreased rs FC alterations.The CC sub-regions with increased whole-brain functional connectivity included the bilateral p ACC(area24),v PCC and the right s ACC.The sub-regions with decreased whole-brain functional connectivity included the bilateral p ACC(area24),p ACC(area32),and right s ACC.The s ACC in patients with Alzheimer's diseases demonstrated increased rs FC with the affective network(OFC)and decreased rs FC with the central executive network(DLPFC).The p ACC(area24)showed increased rs FC with the subcortical nuclei of the hippocampus and thalamus,while decreased rs FC with the central executive network(DLPFC).The p ACC(area32)demonstrated reduced rs FC with the central executive network(DLPFC),and the default mode network(anterior part of the middle/inferior temporal gyrus).The v PCC showed increased rs FC with the default mode network(precuneus).In this study,we did not find significant correlation between the rs FC changes of the CC sub-regions and the clinical behavioral scores of the patients.One of the possible reasons is that the sample size is not big enough to uncover the effect.It is also possible that the rs FC alterations of CC sub-regions in the patients do not significantly correlated with the clinical assessments we used.Conclusion: In the present study,we employed a ROI-based rs FC analysis method to explore the whole-brain rs FC alterations of the CC sub-regions in the patients with Alzheimer's disease.We identified significant decreaed rs FC in the patients,which is in accordance with their impaired cognitive functions and the cognition regulatory abilities.It is worth noting that when regressing out the global mean signal,we found some increased rs FC,mainly between the CC sub-regions and the affective network.This is probably associated with the hyper-activation of the affective network in negative events of the patients.The increased and decreased rs FC with the default mode network implied that the rs FC alteration might be bi-directional in that in the condition of illness,the CC demonstrated increased rs FC with some networks and decreased one with other networks.The significance of such reformation of the module structure requires further investigation.