| The world is aging and,as increasing size of the elderly population,the age-related cognitive decline has become a focus topic of social concern,especially Alzheimer’s disease(AD)has become a growing serious global public health problem.Repetitive transcranial magnetic stimulation(rTMS)is a well-established noninvasive and nondestructive technique for neuromodulation that can be used to modulate neuronal excitability and enhance cortical function.Thus,it provides a possible method to delay the cognitive dysfunction caused by aging.In recent years,growing evidence suggested that rTMS can play a positive role in the improvement of cognitive performance in patients with AD and mild cognitive impairment(MCI).Aging increases the risk of dementia,and many cognitive abilities decline significantly with aging.Therefore,by studying the effect and regulation of rTMS on brain function and cognitive aging in healthy senior citizens,we can have more comprehensive and in-depth understanding of the intervention mechanism of rTMS,and provide reliable basis for the rTMS clinical treatment of AD and MCI.Whereas,the research on the mechanism of action of rTMS to improve cognitive function mainly focuses on young people,so far,there were no systematic studies to explore the regulatory effects of rTMS intervention on cognitive function in healthy senior citizens,especially the changes in brain function and brain network.In the present study,bilateral dorsolateral prefrontal cortex(DLPFC)was chosen as the rTMS target site because it is a key element of many high-order brain functions including inhibition execution function,attention function,working memory,episodic memory and cognitive flexibility.Functional magnetic resonance imaging(fMRI)was used to investigate whether the intervention of high frequency rTMS(HF-rTMS)administered to bilateral DLPFC would influence the cognitive function,brain structure and brain functional network of healthy senior citizens,and whether the changes of the connection strength of brain functional network were related to the improvement of cognitive function.First,in order to assess whether rTMS intervention can improve the cognitive function of the healthy senior citizens,this study assessed the cognitive function of the senior citizens before and after rTMS intervention through a series of cognitive psychology tests including Stroop color-word test(SCWT),auditory verbal learning test(AVLT),trail making test(TMT)and digit span subtest(DST).The results showed that HF-rTMS can significantly improve the episodic memory,working memory and the ability to suppress interference.To explore changes in brain functional networks using methods based on independent component analysis(ICA),we found that HF-rTMS regulates the in-network functional connectivity(FC)of the default mode network(DMN),right frontoparietal netwaork(RFPN)and salience network(SAN).In addition,there were significant correlations between changes in FC within these networks and improvements in cognitive function.These results suggested that HF-rTMS improved related cognitive functions through the modulation of brain networks in the healthy senior citizens.Subsequently,we targeted the hippocampus network,which is closely related to cognitive function,especially memory function.We investigated the volume alterations of hippocampal subfields at different ages and assessed the correlations with cognitive function changes,and whether HF-rTMS intervention affects and regulates the level of FC in specific subregions of the hippocampus.The findings indicated that HF-rTMS improved the FC between the left DLPFC and the left hippocampus,and there were significant correlations between changes in left DLPFC-hippocampus FC and improvements in cognitive function.The results of the study on the hippocampal subregions showed that the intervention and regulation of HF-rTMS on the granular cell layer of dentate gyrus(GC-DG)in the left hippocampal subregion showed significant intergroup differences.Furthermore,we speculate that the parasubiculum may be a potential biomarker for dementia disorders.Finally,we discussed the important participant role of the cerebellum in cognitive function.We investigated the volume alterations in cerebellar lobules at different ages and assess their correlations with reduced cognitive abilities,and whether HF-rTMS intervention affects and regulates the level of FC in the specific cerebellar lobules.The findings indicated that HF-rTMS modulated the cerebellum-brain functional connections of the right lobule VI and right lobule crus I.Moreover,the FC of right lobule crus I were significantly associated with memory recall scores.Our findings confirmed that lower gray matter volumes of the cerebellum were associated with worse memory function,and they suggested that the volume changes in bilateral lobule VI,lobule crus I and right lobule IV might be considered as biomarkers for aging-related memory decline.In addition,our results also found that HF-rTMS may not lead to changes in gray matter(gray matter volume,cortical thickness and local gyrus index),structural covariant network and functional network connectivity(FNC).In conclusion,this study proposed magnetic resonance imaging(MRI)biomarkers related to brain aging and cognitive intervention by HF-rTMS,which has high reference value for early intervention of cognitive aging and clinical treatment of AD and MCI. |
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