Modulation Of Repetitive Transcranial Magnetic Stimulation On Resting State Brain Network Of Mild Cognitive Impairment

Objective:To assess the efficacy of repetitive transcranial magnetic simulation(rTMS)on mild cognitive impairment(MCI)and investigate the modulation on functional brain network by using resting-state functional magnetic resonance imaging(rs-fMRI).Methods:Thirty-eight participants met the diagnostic criteria of MCI were recruited from geriatric disease screening of the Second Clinical Medical College of North Sichuan Medical College and the surrounding community hospitals and randomly assigned to the real stimulation group(18 patients)or sham stimulation group(20 patients).A consecutive 10-day of rTMS treatment was given to all of the included patients with the following same parameters:high-frequency of 10Hz rTMS over left dorsolateral prefrontal cortex(L-DLPFC)with 90%of rest motor threshold and 1,500 pulsed per day.The coil of sham group did not produce the true and effective rTMS stimulation.Each patient received a structured cognitive assessment and underwent rs-fMRI examination at baseline and after 10-day of rTMS treatment.After finishing the experiment,the seed-based functional network analysis method was applied to construct the whole brain resting-state functional network with the stimulation site(L-DLPFC)as the region of interest.Afterwards,the comparison of cognitive scores,functional networks before and after treatment in each group and between groups after treatment were all conducted.The correlation between the alteration of functional connectivity and cognitive score was also calculated to explore the modulation mechanism of rTMS to MCI patients.Results:(1)At baseline,no significant difference was observed in age,gender,years of education,and all of the cognitive assessments between real and sham groups.(2)Compared to the baseline,the MCI patients in the real stimulation group showed significantly improved overall global cognition(Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment-Basic(MoCA-B)),memory function(immediate memory of Auditory Verbal Learning Test(AVLT-I),short-delay free recall AVLT-SD),long-delay free recall(AVLT-LD),and recognition recall function(AVLT-R)),language function(Boston Naming Test(BNT)and Animal Verbal Fluency Test(AFT)),and executive function(Trail Making Test(TMT-A/B))after 10 days of rTMS treatment.Only significantly changed AVLT-I,AVLT-LD memory function were detected in the sham group.Except for the AFT and TMT-B,pronounced changes of all the other cognitive assessment scores were found in the real group relative to the sham group.(3)The real group showed significantly increased functional connectivity in the left orbitalis middle frontal gyrus,superior frontal gyrus,and bilateral anterior cingulate cortex with L-DLPFC and showed significantly decreased functional connectivity in the right middle temporal gyrus with L-DLPFC after rTMS intervention.In the sham group,significantly increased functional connectivity between L-DLPFC and left precuneus,right middle frontal gyrus,right inferior frontal gyrus,right medial superior frontal gyrus,right medial middle frontal gyrus,left anterior cingulate cortex were also observed;significantly decreased functional connectivity was found between L-DLPFC and right parietal cortex.The comparison of the functional connectivity between real and sham groups revealed significantly higher functional connectivity between L-DLPFC and bilateral anterior cingulate cortex,left insula,left middle frontal gyrus,and left inferior frontal gyrus in the real group.The weaker functional connectivity between L-DLPFC and right middle temporal gyrus,right lingual gurus,right hippocampus,right parahippocampus,left precuneus,right superior parietal cortex,right inferior parietal cortex,right middle frontal gyrus,right supramarginal gyrus,and right angular gyrus was detected as well in the real group relative to sham group.(4)The correlation analysis showed significant positive correlation between the functional connectivity change of left orbitalis middle frontal gyrus and MoCA-B score changes;and showed significant negative correlation with TMT-B score change.Both AVLT-I and AVLT-LR showed significant negative correlation with the functional connectivity between right middle temporal gyrus and L-DLPFC.Besides,positive correlation was found between the functional connectivity change of bilateral anterior cingulate cortex and TMT-A score change.After rTMS intervention,the functional connectivity between L-DLPFC and left middle frontal gyrus showed positive correlation with MMSE,AVLT-I,AVLT-SD,AVLT-LD,and AVLT-R.The functional connectivity between L-DLPFC and right middle temporal gyrus,right inferior parietal cortex showed negative correlation with AVLT-I and AVLT-R separately.Conclusion:rTMS could significantly improve the cognitive function of MCI patients,especially for the global cognitive function,memory function,language naming function,and simple executive function.The effect on resting-state functional network manifested in the modulation on default mode network,salience network,executive control network and frontoparietal network.