Brain Network Modulation Mechanisms Of Transcranial Direct Current Stimulation On Cognitive Improvement In Patients With Mild Cognitive Impairment

Objective:To investigate the effects of Transcranial Direct Current Stimulation(tDCS)on different cognitive dimensions and Functional Connectivity(FC)of cognitive related resting state networks in patients with Mild Cognitive Impairment(MCI).And to explore the neural mechanism of cognitive improvement.Methods:In this parallel randomized controlled design,40 MCI patients were randomly assigned into real and sham stimulation group,with 20 patients in each group.All subjects received 20min per day,10 days of anodic tDCS over the left Dorsolateral Prefrontal Cortex(DLPFC),with the cathode over right superior orbital margin.The current intensity of real group was 2 mA.There was ineffective stimulation in sham group except for slight current at the beginning 30s and the ending 30s.Before and after treatment,each subject underwent cognitive scale assessment including overall cognitive function,memory,language and executive function,and a resting state functional magnetic resonance image scan.Independent Component Analysis(ICA)was used to extract the resting state functional networks related to cognitive functions.The changes and differences of functional networks before and after treatment and the correlations with cognitive scores were compared and analyzed.Results:(1)Finally,a total of 36 MCI patients(19 in real group and 17 in sham group)were included.The gender,age,education,mood and daily life score between the two groups had no significant differences(P>0.05);(2)Compared with baseline,Mini-mental State Examination(MMSE),Montreal Cognitive Assessment scale(MoCA),20-minute delay recall of Auditory Verbal Learning Test(AVLT-N5),Boston Naming Test(BNT)scales of real group were significantly improved.Trail Making Test(TMT-A/B)were significantly decreased(P<0.05).AVLT-N5,recognition(AVLT-N7),Animal Verbal Fluency Test(AFT)and BNT of sham group were significantly improved after treatment(P<0.05).After treatment,MMSE,MoCA,AVLT-N5 and AVLT-N7 scores of real group were significantly higher than sham group,and TMT-B scores were lower than sham group.The changes of AVLT-N5,AVLT-N7,BNT and TMT-B scores before and after treatment in real group were significantly higher than those in sham group(P<0.05);(3)Four cognitive function related networks were extracted:Default Mode Network(DMN),Salience Network(SN),left and right Frontoparietal Network(FPN).In DMN,the FC of real group were significantly decreased in right precuneus and posterior cingulate gyrus after treatment.The FC of sham group was significantly decreased in bilateral posterior cingulate gyrus.After treatment,the FC of real group was significantly lower than sham group in left middle occipital gyrus.And the changes of zFC values in right precuneus of real group were positively correlated with the changes of TMT-A scores(r=0.480,P=0.027);In SN,FC of real group were significantly increased in right insula,left anterior cingulate gyrus and right inferior frontal gyrus after treatment.There was no significant change in FC in sham group.After treatment,FC of real group were significantly higher than sham group in bilateral anterior cingulate gyrus,right precentral gyrus,right posterior cingulate gyrus and right parahippocampal gyrus.There were significant positive correlations between zFC values of right inferior frontal gyrus and BNT scores(r=0.469,P=0.049),zFC values of right posterior cingulate gyrus and MMSE,AFT scores(r=0.480,P=0.044;r=0.544,P=0.020);In left FPN,FC of real group were increased significantly in left middle frontal gyrus and middle occipital gyrus after treatment.FC of sham group decreased significantly in left middle occipital gyrus.After treatment,FC of real group were significantly higher than sham in left middle frontal gyrus,inferior frontal gyrus and inferior parietal lobule.And there was no correlation with cognitive scores;In right FPN,FC of real group was significantly increased in right inferior frontal gyrus after treatment.FC of sham group were significantly decreased in right middle frontal gyrus and inferior parietal lobule.After treatment,FC of real group were significantly higher than sham group in right middle frontal gyrus,inferior frontal gyrus and superior parietal lobule.And the zFC values of real group in right inferior frontal gyrus were positively correlated with AVLT-N5 scores(r=0.476,P=0.046),the changes of zFC values in right inferior frontal gyrus of real group were positively correlated with the changes of MMSE and AVLT-N5 scores(r=0.485,P=0.042;r=0.518,P=0.028).Conclusions:(1)Ten days of anodal tDCS stimulation over the left DLPFC can effectively improve the cognitive functions of MCI patients,especially in memory and executive functions;(2)tDCS can simultaneously regulate the functional connectivity of DMN,SN,1FPN and rFPN in MCI patients,realizing the repair of multiple brain network abnormalities and neural plasticity,which may be a potential neural mechanism for treatment;(3)tDCS can not only cause network changes in the stimulus region,but also in the networks with anatomical or functional connections to the stimulated site,indicating that the cognitive networks are not isolated,and there are connections among the networks to jointly maintain cognitive functions.