BackgroundRepetitive transcranial magnetic stimulation(rTMS),as a non-invasive and painless non-pharmacological treatment,can effectively improve cognitive function in patients with mild cognitive impairment(MCI).The hippocampus is a key brain region for memory and emotion processing in individuals,especially the anterior and posterior hippocampal subregions have been shown to be associated with emotion and memory.However,it is unclear whether rTMS long-duration continuous intervention treatment affects the hippocampal subregional networks and behavioral significance in MCI patients.ObjectiveTo investigate the changes of hippocampal subregional brain networks at different follow-up periods after rTMS treatment by stimulating the left dorsolateral prefrontal cortex(DLPFC)and their correlation with behaviors in MCI patients.MethodsA total of 17 MCI patients and 18 cognitive normal(CN)patients matched for gender,age,and education were included in this study.MCI patients received stimulation treatment at the left DLPFC five times a week for 12 weeks and completed pre-and post-treatment and 2-year follow-up records.Neuropsychological cognitive scale assessments and magnetic resonance imaging(MRI)data were obtained in the CN group at baseline and in MCI patients before and after treatment and at the 2-year follow-up.First,the functional networks of hippocampal subregions were constructed using the seed-based functional connectivity(FC)method.Second,paired-samples t-test was used to analyze the changes in the functional network of hippocampal subregions before and after rTMS treatment.Oneway ANOVA was used to explore the changes in hippocampal sub-regional functional networks at different time points after rTMS intervention.Finally,the correlations between the functional networks of hippocampal subregions and behavioral scores in MCI patients was explored by partial correlation analysis.ResultsFirst,compared with the CN group,the Auditory Verbal Learning Test-Immediate Recall(AVLT-IR)scores of MCI patients decreased significantly at baseline and increased significantly after rTMS treatment.The AVLT-IR scores of MCI patients did not differ significantly from baseline,but still showed an increasing trend compared to the baseline period.Second,there were significant differences in FC in the right superior temporal gyrus,left middle temporal gyrus,bilateral superior frontal gyrus,bilateral middle frontal gyrus,right cisternal gyrus,and right cingulate gyrus during the 2-year follow-up period.However,during the 2-year follow-up period,it was observed that the FC of the above-mentioned brain regions deviated from the CN group and showed a reverse trend.Third,the changes in the intensity of FC in the relevant brain regions within the hippocampal subregional networks of MCI patients were significantly correlated with the changes in AVLT-IR scores at short and long-term follow-up.ConclusionsA 12-week long course of high-frequency rTMS treatment may improve cognitive function in MCI patients by modulating the FC patterns of hippocampal subregional networks.The changes in the functional networks of hippocampal subregions bilaterally were significantly associated with the improvement of AVLT-IR,suggesting that the changes in the FC patterns of hippocampal subregions at different follow-up periods after rTMS treatment are important for monitoring the cognitive function progress of MCI patients.These findings provide a new research direction for clinical monitoring of longterm effects after rTMS intervention in the MCI patients. |