Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,n...Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.展开更多
随机振动台根据功率谱密度(PSD,Power Spectral Density)生成的信号为高斯信号,而实际振动环境有时是非高斯的,因此随机振动实验常常无法准确模拟产品在真实振动环境下的失效情况.通过两个案例分别对均方根值(RMS,Root Mean Square)不...随机振动台根据功率谱密度(PSD,Power Spectral Density)生成的信号为高斯信号,而实际振动环境有时是非高斯的,因此随机振动实验常常无法准确模拟产品在真实振动环境下的失效情况.通过两个案例分别对均方根值(RMS,Root Mean Square)不随时间变化和随时间变化的非高斯随机振动进行了模拟方法研究.案例1利用Hermite多项式法对高斯信号进行了转换,在保证功率谱密度不变的同时得到了具有指定峭度的RMS不随时间变化的非高斯信号,但该方法对于输入的峭度有限制,当输入峭度大于10时,误差达到了20%.案例2利用一种新方法对实测的RMS随时间变化的非高斯振动进行了模拟,模拟后得到的非高斯信号和实测信号具有相同的功率谱密度、峭度以及概率分布,验证了新方法的准确性.展开更多
文摘Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.
文摘随机振动台根据功率谱密度(PSD,Power Spectral Density)生成的信号为高斯信号,而实际振动环境有时是非高斯的,因此随机振动实验常常无法准确模拟产品在真实振动环境下的失效情况.通过两个案例分别对均方根值(RMS,Root Mean Square)不随时间变化和随时间变化的非高斯随机振动进行了模拟方法研究.案例1利用Hermite多项式法对高斯信号进行了转换,在保证功率谱密度不变的同时得到了具有指定峭度的RMS不随时间变化的非高斯信号,但该方法对于输入的峭度有限制,当输入峭度大于10时,误差达到了20%.案例2利用一种新方法对实测的RMS随时间变化的非高斯振动进行了模拟,模拟后得到的非高斯信号和实测信号具有相同的功率谱密度、峭度以及概率分布,验证了新方法的准确性.
