Exploring Neural Mechanism Of Impairment In Episodic Memory And Attention In Amnestic Mild Cognitive Impairment: A Simultaneous EEG-fMRI Study

BackgroundMild cognitive impairment(MCI)is a high-risk population of dementia,especially amnestic mild cognitive impairment(aMCI),which is considered to mainly progressed to Alzheimer's disease(AD).Therefore,the aMCI is considered as a critical stage of early AD,and the research on the mechanism of cognitive impairment of aMCI patients is helpful for the early diagnosis and treatment of AD.Episodic memory deficit is the core cognitive dysfunction of aMCI.Successful episodic retrieval acts as a prerequisite for recalling events,and memory retrieval includes two processes: familiarity and recollection.Event-related potential(ERP)research has found that in the recognition memory task,the early old/new effect is associated with familiarity,whereas the late old/new effect is related to recollection.In addition,studies have found that the old/new effects are reduced in MCI patients.However,due to the low spatial resolution of ERP(centimeter level),it is difficult to accurately locate the intracranial origin of the ERP old/new effects.In contrast,functional magnetic resonance imaging(fMRI)has a higher spatial resolution.However,changes in brain activation during episodic memory retrieval in MCI patients are inconsistent,and a meta-analysis has found that the memory retrieval pattern appears preserved in MCI patients,rather than being disrupted along with the behavioral episodic memory impairment.The inconsistent results may be due to the low temporal resolution of fMRI,which is insufficient to accurately distinguish the brain activation pattern of different cognitive components during episodic memory retrieval.Current evidence suggests that attention impairment is present early in MCI,and the scores of attention function in MCI may predict the development of AD.Oddball task-induced event-related P300 component reflects attentional resource allocation.Studies have found reduced P300 amplitudes and longer P300 latencies in MCI patients,which may be a sensitive biomarker of cognitive decline in MCI patients.However,due to the low spatial resolution of ERP,it is difficult to accurately locate the intracranial origin of P300,and it is difficult to determine whether the intracranial origin of P300 component in aMCI patients has changed.Although fMRI can locate the brain activity during the oddball task,fMRI enables observation of the average response evoked by stimuli and cannot specifically identify P300 component.Simultaneous electroencephalography(EEG)-fMRI technique can combine the high temporal resolution of ERP and the high spatial resolution of fMRI to provide a better method for studying cognitive function.Therefore,this study used simultaneous EEG-fMRI technique to explore the neural mechanism of impairment in episodic memory and attention in aMCI.In addition,meta-analyses found that P300 latency is prolonged with the progression of AD disease,and it has high sensitivity and specificity when distinguishing MCI and AD from healthy elderly.Moreover,the evidence consistently indicates that the grey matter volume is reduced in MCI patients.However,it is still unknown whether the delayed P300 latency is related to the reduced gray matter volume in MCI.Therefore,this study combined ERP and structural MRI to explore the potential brain structural basis of delayed P300 latency in aMCI patients.Part ? Exploring neural mechanism of impairment in episodic memory in amnestic mild cognitive impairment: A simultaneous EEG-fMRI study Objective: Simultaneous EEG-fMRI was used to determine whether temporal dynamics of brain activity during episodic retrieval are disturbed in aMCI.Methods: Twenty-six aMCI and Twenty-nine normal controls(NC)completed neuropsychological tests and a word-list memory retrieval task during simultaneous EEG-fMRI.The following strategy was used to analyze the simultaneous ERP-fMRI data: 1)the retrieval success activation pattern was detected with fMRI analysis,2)the early and late old/new effect components of episodic retrieval activity were identified using ERP analysis,3)the fMRI-constrained EEG analysis explored temporal dynamics of brain activity in the retrieval success pattern,4)the EEG-informed fMRI analysis detected the brain activation related to the early and late old/new effect components.Results: The two groups exhibited similar retrieval success patterns in the bilateral precuneus(Pcu)/ posterior cingulate cortex,left inferior parietal lobule(IPL),and left lateral prefrontal cortex(LPFC)(voxel-wise p < 0.005,cluster size > 15).In the fMRI-constrained ERP analysis,the aMCI group did not exhibit the old/new effects in the IPL and LPFC as the NC group showed.In the EEG-informed fMRI analysis,the aMCI group showed decreased brain activity in the Pcu and left hippocampus related to ERP early and late old/new effect components,respectively(voxel-wise p < 0.005,cluster size > 15).Conclusions: Therefore,this study identified disturbed temporal dynamics of episodic retrieval activity with a preserved spatial activity pattern in aMCI.The early and late old/new effect components informed fMRI analysis is helpful to accurately distinguish brain activation related to familiar and recollection processes in aMCI patients.Simultaneous EEG-MRI technique with high temporal and spatial resolution is an important means to develop early sensitive biological markers for AD. 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Exploring neural mechanism of impairment in attention in amnestic mild cognitive impairment: A simultaneous EEG-fMRI study Objective: Simultaneous EEG-fMRI was used to investigate whether brain activity related to P300 component is impaired in aMCI patients.Methods: Thirty aMCI and thirty-one NC subjects completed neuropsychological tests and a visual oddball task during simultaneous EEG-fMRI.The following strategy was used to analyze the simultaneous ERP-fMRI data: 1)the activation pattern during the oddball task was detected with fMRI analysis,2)the P300 component was identified using ERP analysis,3)the single-trial EEG-informed fMRI analysis detected the brain activation related to P300 component.Results: The fMRI-only analysis showed increased activation in the right supramarginal gyrus(SMG)and right inferior frontal gyrus(IFG)in the aMCI group as compared with the NC group(corrected by Alpha Sim,? = 0.05,voxel-wise p <0.005,cluster size > 16),and brain activation of the two regions were negatively correlated with response time(RT)in all subjects(right SMG: r =-0.311,p = 0.019;right IFG:r =-0.388,p = 0.003).The single-trial EEG-informed fMRI analysis further showed decreased brain activities in the right hippocampus and left postcentral gyrus(Po CG)related to P300 component in the aMCI subjects relative to the NC group(corrected by Alpha Sim,? = 0.05,voxel-wise p < 0.005,cluster size > 16).Conclusions: The P300 component informed fMRI analysis is helpful to accurately locate brain activation related to P300 in aMCI patients,and provide evidence for attentional impairment in aMCI patients.Part ? Exploring the structural basis of impairment in attention in amnestic mild cognitive impairment: A combined ERP and structural MRI studyObjective: This study was to investigate the relationship between the altered P300 latency and grey matter volume in aMCI patients combining ERP with structural magnetic resonance imaging(MRI).Methods: Thirty-four aMCI and 34 NC completed neuropsychological tests.All subjects completed a visual oddball task during EEG recording and underwent structural MRI scan.Both tests were finished in the same day.Results: As compared with the NC group,the aMCI group exhibited delayed P300 latency in parietal cortex(t66 = 2.45,p = 0.017)and reduced grey matter volumes in bilateral temporal pole and left hippocampus/parahippocampal gyrus(corrected by Alpha Sim,? = 0.05,voxel-wise p < 0.005,cluster size > 46).A remarkable negative correlation was found between delayed P300 latency and reduced left hippocampal volume only in the aMCI group(r =-0.416,p = 0.014).Interestingly,the mediating analysis found P300 latency significantly mediated the association between right SMG volume and information processing speed indicated by Stroop Color and Word Test A scores(Z scores)(indirect effect,? = 0.183,95% CI = [0.005,0.510]).Conclusions: The association between delayed P300 latency and reduced left hippocampal volume in aMCI subjects suggests that reduced left hippocampal volume may be the potential structural basis of delayed P300 latency.