A Study Of Hippocampal Neuronal Dynamics And Spontaneous Brain Activity Associated With Alzheimer's Disease

Alzheimer's disease(AD)is a neurodegenerative disease mainly characterized by memory impairment.At present,numerous important results about AD have been obtained in the field of scientific and medical research.However,due to the complexity of AD,there are still many scientific problems that need to be resolved regarding the pathological mechanism and diagnostic prediction of AD.This thesis,using relevant theories and methods of nonlinear dynamics and statistical analysis,explores the dynamics of hippocampal neuron related to AD and the characteristics of spontaneous brain activity in resting state from the neural computation and data-driven aspects,respectively.We expect this work would provide theoretical basis for the pathogenesis and early intervention and diagnosis of AD.The main contents and conclusions of this paper are as follows:1.The hippocampal neuronal model related to AD and its dynamics are investigated.In view of the important physiological significance of cholinergic for attention mechanism and memory function,this paper,by adding M-current IM and calcium ion-activated potassium ion current IAHP to characterize the cholinergic action receiving from the medial septum,constructs a modified hippocampal CAI pyramidal neuronal model with cholinergic action.Then,using the power spectrum analysis and firing rate of neuron,this paper numerically studies the effects of acetylcholine deficiency potentiated currents IM and IAHP as well as beta-amyloid(A?)deposition increased delay rectification potassium ion current IK on the dynamics of the modified pyramidal neuron.The results show that acetylcholine deficiency and A? deposition can increase the relative power within theta band and decrease the firing rate of the modified neuron,which is consistent with the results of existing electrophysiological experiments on AD.The intrinsic dynamic mechanism of the above phenomenon is further discussed using nonlinear dynamic method.It is found that acetylcholine deficiency and A? deposition can promote the hippocampal neuron to transition from limit cycle state to equilibrium attractor state,which is related to the increased relative power within theta band and the decreased firing rate.2.Based on rs-fMRI data,the differences of spontaneous brain activity in resting state between AD patients and normal people are characterized by combining multiple data analysis methods including regional homogeneity(ReHo),amplitude of low-frequency fluctuations(ALFF)and degree centrality(DC),so as to explore the characteristics of spontaneous brain activity in AD patients.The results of statistical analysis suggest that compared with the normal control(NC),patients with AD show significantly reduced ReHo value in bilateral Middle temporal gyrus(MTG),right Angular gyrus(ANG)and left Precuneus(PCUN);patients with AD show significantly reduced ALFF value in left PCUN;AD patients show significant decrease of DC value in right Olfactory cortex(OLF),left Inferior parietal,but supramarginal and angular gyri(IPL),left Heschl gyrus(HES),left Supramarginal gyrus(SMG),right Temporal pole-superior temporal gyrus(TPOsup)and right hippocampal(HIP).These indicate that the spontaneous brain activity of the above brain areas in AD patients is abnormally impaired,which is closely related to memory decline in AD patients.At the same time,the above phenomena imply that the damaged left PCUN is caused by a decrease in the importance of right OLF,which is manifested by the decline in memory in AD patients induced by impaired memory formation.3.Based on rs-fMRI data,the dynamics of spontaneous brain activity and its concordance in AD patients are discussed.First,this paper,combing the sliding window method and three analysis methods of rs-fMRI data(ReHo,ALFF and DC),characterizes the dynamic characteristics of spontaneous brain activity in AD patients and NC.The results of statistical analysis suggest that compared with NC,AD patients show significantly reduced dynamics of ReHo in left PCUN;AD patients show significantly increased dynamics of ALFF in bilateral Calcarine fissure and surrounding cortex(CAL);AD patients show significantly increased dynamics of DC in bilateral Thalamus(TAH),right Inferior frontal gyrus,opercular part(IFGoperc),left OLF,left Rolandic operculum(ROL),right Inferior frontal gyrus,triangular part(IFGtriang)and right Superior parietal gyrus(SPG).Then,with the help of the concordance among the dynamic indicates of ReHo,ALFF and DC,the integration at different functional levels is measured.The results of statistical analysis indicate that compared with NC,AD patients show significantly reduced concordance in right Caudate nucleus(CAU),and significantly increased concordance in left CAL,right IFGoperc,right Superior frontal gyrus,medial(SFGmed)and right Supplementary motor area(SMA).The results suggest that the dynamics of the spontaneous activity of some brain areas and its integration in AD patients are abnormal,which provides a comprehensive theoretical basis for neuroimaging in clinical early diagnosis and treatment of AD.