| BackgroundAlzheimer's disease(AD)is the most common type of dementia in senile individuals,characterized by progressive and irreversible cognitive decline.Amnestic mild cognitive impairment(aMCI)is thought to be an earlier stage of AD.Previous researches mainly focused on the cognitive declines and their underlying neural mechanisms of AD.However,the neural mechanisms of preserved cognition in incipient AD are not well understood yet.With the development of multi-modal MRI and analysis methods,which can provide multi-dimension perspectives,such as structure,function,metabolism,and network changes of the whole brain,it provides novel methods to investigate the pathogenesis mechanisms of AD.Emotional stimuli are more easily remembered than neutral stimuli,a phenomenon known as the emotional enhancement of memory(EEM).Previous studies of emotional memory of AD mainly focused on behaviors;however,the influence factors and the underlying neural mechanisms are inadequately understood.Besides,the differences of emotional memory and neural modulation pathways between AD and normal aging are not clearly understood.Since the high morbidity and limited treatment of AD,it will be very helpful if the neural pathway of emotional memory could be found,so that we may use the EEM effect of emotion on memory to improve the memory performance of AD patients.ObjectiveTo investigate the influence factors and the neural mechanisms of emotional memory of AD patients and normal aging by utilizing emotional memory tests and multi-modal MRI techniques.(1)Research 1:To investigate whether the EEM is absent during disease progression of AD,and to investigate the relationships between emotional memory and brain structure changes of AD.(2)Research 2:To investigate the probable influence factors of emotional memory,and to investigate the relationships between emotional memory and the related brain functional network changes during disease progression of AD.(3)Research 3:To investigate the relationships between emotional memory and the gray matter atrophy,and between emotional memory and the related brain functional network changes during normal aging.Methods(1)Research 1:Twenty-one AD patients,20 aMCI patients and 25 normal controls were included in this study.Positive,neutral and negative emotional pictures were used during the incidental encoding phase and the Recognition paradigm was used during the retrieval phase.The imaging protocol included T1-weighted three-dimensional structure sequence and diffusion tensor imaging.Voxel-based morphometry(VBM)and tract-based spatial statistics(TBSS)methods were used to determine macro-gray matter and micro-white matter changes of patients.The correlation analyses were conducted between brain structure indices of limbic system and the behavioral scores of emotional memory.(2)Research 2:Thirty-one AD patients,24 aMCI patients and 23 normal controls were included in this study.Positive-high-arousal(PH),positive-low-arousal(PL),neutral(N),negative-high-arousal(NH)and negative-low-arousal(NL)pictures were used during the incidental encoding phase and the Recognition-Remember/Know paradigm was used during the retrieval phase.Resting state functional magnetic resonance imaging(rs-fMRI)data were acquired.The resting state emotional memory network was built using graph-theoretical method.Both global and regional network measures were calculated to reflect brain network changes of AD and aMCI patients.The correlation analyses were conducted between the global and regional network properties and the behavioral scores of emotional memory.(3)Research 3:Twenty-five normal old controls and 30 normal young controls were included in this study.Positive-high-arousal(PH),positive-low-arousal(PL),neutral(N),negative-high-arousal(NH)and negative-low-arousal(NL)pictures were used during the incidental encoding phase and the Recognition-Remember/Know paradigm was used during the retrieval phase.The imaging protocol included T1-weighted three-dimensional structure sequence and rs-fMRI sequence.Gray matter volume changes were analyzed by VBM method and the resting state emotional memory network was built using graph-theoretical method.The correlation analyses were conducted between the brain structure indices/network properties and the behavioral scores of emotional memory.Results(1)Research 1:Compared with neutral pictures,the NC group benefited from the emotional stimuli of both negative and positive images.aMCI patients benefited only from positive stimuli.The EEM effect was lost in AD patients.Compared with NC,AD patients showed remarkable gray matter atrophy in the medial temporal lobe structures,such as the amygdala,hippocampus and parahippocampal gyrus.Other limbic brain areas such as thalamus,cingulate gyrus,precuneus,orbital and medial frontal lobe were also atrophied significantly.Besides,there were additional gray matter loss in parietal lobe,occipital lobe and insula.AD patients also showed a widespread pattern of white matter impairment,including the fornix,corpus callosum,uncinate fasciculus,cingulum,posterior thalamic radiation,corona radiata,internal capsule,external capsule,superior and inferior longitudinal fasciculus.The atrophied gray matter of aMCI patients were mainly located in the medial temporal lobe structures,medial frontal lobe,cingulate gyrus and basal ganglia areas.And the impaired white matter fibers were located in corpus callosum,cingulum,uncinate fasciculus,corona radiata and internal capsule areas.The volumes of amygdala,insula,medial frontal lobe,cingulum gyrus and precuneus were correlated with emotional memory of AD patients.And significant correlations or tendencies were also found with the white matter integrity and emotional memory in the cingulum bundle,uncinate fasciculus,corpus callosum,crus of fornix and stria terminalis.For aMCI patients,the positive correlations between the volume of right amygdala and between the FA value of right uncinate fasciculus and the recognition sensitivity of positive pictures were found.(2)Research 2:The EEM effect was only detected during the "recollection“process.Compared with neutral pictures,the NC group benefited from PH,NH and NL pictures.For aMCI patients,the EEM effects were preserved for high arousal emotional pictures.For AD patients,the EEM effects were completely lost.Notably,compared with NC,there was significantly decrease of the recognition sensitivity of recollection process rather than familiarity in aMCI patients.For AD patients,both the recognition sensitivity of recollection and familiarity were impaired.At a global level,AD patients showed significantly higher normalized clustering coefficient,small-worldness,and normalized local efficiency.At a regional level,there were disrupted neural circuits,consisting of abnormal nodes(increased or decreased nodal properties)and edges(decreased functional connectivity strength).The node degree and node efficiency of left dorsal caudate and left lateroventral fusiform were increased in aMCI patients.The amygdala,hippocampus and entorhinal cortex showed significant correlations with the recollection and familiarity processes of emotional memory in AD and aMCI patients.(3)Research 3:The patterns of emotional memory and EEM effects were similar in old and young groups.The atrophied brain areas during aging included temporal gyrus,parahippocampal gyrus,insula,middle cingulate gyrus,frontal lobe,basal ganglia areas and sensorimotor cortex.There were no significant differences of global network properties and functional connectivity strength between old and young groups.Conclusion(1)Research 1:aMCI patients preserve the EEM effect of positive pictures;however the EEM effect is lost in AD patients.Atrophied gray matter volumes and damaged white matter connections of limbic networks are associated with impaired emotional memory and EEM effect in AD patients.(2)Research 2:Emotional memory is influenced by the arousal,valence and means of retrieval methods.The EEM effects of high-arousal-positive and high-arousal-negative pictures are remained in aMCI patients.And there exist some degrees of compensatory mechanisms of the emotional memory functional network in aMCI patients.The EEM effect is lost in AD patients,and may be associated with the regularization shift of emotional memory related network,function changes of vital nodes and decreased connections of neural circuits of both intra-and inter-hemispheres.(3)Research 3:The patterns of emotional memory and EEM effects are similar in old and young groups.Vital brain areas associated with emotional memory are spared during aging.And the properties of emotional memory functional network also remain stable during normal aging.In summary,with the help of multi-modal MRI techniques and advanced analysis methods,we have explored the changes of emotional memory and the related neural mechanisms during AD and normal aging process,providing underlying clues and theoretical supports for the possible use of the EEM effect to improve the memory performance of AD patients in the future.In addition,the utilization of emotional memory tests and MRI images may facilitate the early diagnosis and detection of AD patients. |
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