The Temporal Variability Of Functional Connectivity Between Hippocampi And The Whole Brain In Alzheimer’s Disease

Background and Objective AD usually begins insidiously,with episodic memory disturbance and progresses towards a more general impairment in memory,executive function,language,visuospatial function and other cognitive and behavioral domains.In the last few decades,brain functional connectivity(FC)has been extensively assessed using resting-state functional magnetic resonance imaging(RS-f MRI),which is able to identify temporally correlated brain regions known as RS functional networks.Fundamental insights into the pathophysiology of Alzheimer’s disease have been provided by studies in this field.However,most of these studies were based on the hypothesis of temporal stationarity of RS functional networks,despite recent evidence suggests that the spatial patterns of RS networks may change periodically over the time of an f MRI scan acquisition.For this reason,dynamic functional connectivity(d FC)analysis has been recently implemented and proposed in order to consider the temporal fluctuations of FC.These approaches hold promise to provide fundamental information for the identification of pathophysiological and diagnostic markers in Alzheimer’s disease.The hippocampal complex is affected early in Alzheimer’s disease(AD).Increasingly,altered functional connectivity of the hippocampus is recognized as an important feature of preclinical AD.We aimed to investigate the temporal variability of functional connectivity between hippocampi and the whole brain and to examine the correlation of the variability with cognitive performance in Alzheimer’s disease(AD).Materials and Methods Patients with Alzheimer’s disease were recruited from the memory clinic and inpatient departments of Neurology,First Affiliated Hospital of Anhui Medical University,while the healthy individuals from the patients’ families or community volunteers with age and gender matching were enrolled in the case-control study.A total of 37 subjects were enrolled,including 18 AD patients and 19 normal controls(NC).Their cognitive abilities were evaluated with mini-mental state examination(MMSE).The data of 3D structural MRI and resting-state functional MRI were collected using GE Signa 3.0T magnetic resonance imaging scanner at the same time.Imaging professionals applied Data Processing Assistant for resting-state f MRI(DPARSFV)software(http://rfmri.org/DPARSF)to preprocess the resting-state Data.The brain was then divided into 90 brain regions using the anatomical automatic labeling(ALL)template,with 45 regions in each hemisphere.The bilateral hippocampus were defined as the regions of interest.The sliding time window image analysis method was applied to dynamic resting state functional connectivity data based on the Dynamic BC package(v1.1,http://www.restfmri.net/forum/Dynamic BC),and calculated the temporal variability of functional connectivity between each regions of interest(e.g.,the bilateral hippocampi)and the whole brain.Then,the differences between the two groups of hippocampi and whole-brain dynamic functional connectivity were compared.The relationship between the abnormal dynamic functional connection(z value)and cognitive variables(MMSE score)were tested by Pearson correlation analysis.Results Compared the temporal variability of functional connectivity of both groups,there was statistically significant differences between the left hippocampus and the right caudate nucleus in AD groups(GRF multiple comparison,voxel P < 0.005,cluster P < 0.05),however,no statistically significant differences between the temporal variability of functional connectivity and the cognitive scores(P > 0.05).Also,there was no statistically significant differences(P > 0.05)between the right hippocampus and the whole brain.Conclusions This study investigated the characteristics of dynamic functional connectivity in Alzheimer’s patients based on RS-f MRI.There existed enhanced temporal variability of dynamic functional connectivity between the left hippocampus and the right caudate nucleus in AD,which provided new horizons for understanding the pathological mechanism of AD and further elucidated the role of hippocampal dysfunction in the pathogenesis of AD.In AD patients,the decreased activity of hippocampus-caudate nucleus and enhanced temporal variability suggested that patients with memory and cognitive impairment had the pathological mechanisms of unstable functional connection regulation under resting state and overloaded compensation or inefficient information exchange within and between brain functional networks.This impairment may be the pathological basis of cognitive and episodic memory impairment.