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
目的探讨针刺联合重复经颅磁刺激疗法(transcranial magnetic stimulation,TMS)对帕金森患者认知功能的改善效果。方法选择2021年5月—2023年4月于丽水市中医院就诊的87例帕金森患者,依照随机数字表法将其分为A组(43例)与B组(44例)。A...目的探讨针刺联合重复经颅磁刺激疗法(transcranial magnetic stimulation,TMS)对帕金森患者认知功能的改善效果。方法选择2021年5月—2023年4月于丽水市中医院就诊的87例帕金森患者,依照随机数字表法将其分为A组(43例)与B组(44例)。A组给予TMS治疗,B组在此基础上联合针刺治疗。两组均治疗8周,比较两组临床疗效、治疗前及治疗8周后P300潜伏期、波幅、血清脑神经递质5-羟色胺(5-hydroxytryptamine,5-HT)、去甲肾上腺(norepinephrine,NE)、神经营养因子-3(neurotrophic factor-3,NT-3)、胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、过氧化氢酶(catalase,CAT)、丙二醛(malondialdehyde,MDA)、谷胱甘肽(glutathione,GSH-px)、髓过氧化物酶(myeloperoxidase,MPO)、简易智力状态评分量表(mini-mental state rating scale,MMSE)评分、统一帕金森病评定量表(unified Parkinson′s disease rating scale,UPDRS)评分、中医证候积分。结果与A组比较,B组临床总有效率更高;与治疗前比较,治疗8周后两组P300潜伏期均缩短,B组短于A组;与治疗前比较,治疗8周后两组波幅、MMSE、UPDRS评分、5-HT、NE、NT-3、IGF-1、CAT、MDA水平均增高,B组高于A组;与治疗前比较,治疗8周后两组中医证候积分、GSH-px、MPO水平均下降,B组低于A组;差异有统计学意义(P<0.05)。结论针刺联合TMS用于帕金森治疗可有效提升临床疗效,缓解相关症状,修复神经损伤,改善认知功能,且可降低氧化应激反应。展开更多
s Western Yunnan is located at the boundary of collision or underthrusting zone of Eurasian plate and is influenced by many times tectonic movements. With very complex geological environment and tectonic background, i...s Western Yunnan is located at the boundary of collision or underthrusting zone of Eurasian plate and is influenced by many times tectonic movements. With very complex geological environment and tectonic background, it is one of the seismically active areas. In the paper, the teleseismic records were selected from 16 national, local and mo-bile stations, including 4 very-wide-band mobile stations of PASSCAL. And nearly 2 000 receiver functions were extracted. Two measuring lines are 650 km and 450 km, respectively and across some major tectonic units in Western Yunnan. It is indicated that Nujiang might be a seam characterized by underthrusting. The western and eastern boundaries of Sichuan-Yunnan rhombus block, i.e., Honghe and Xiaojiang faults, might be an erection seam or collision belt. Panxi tectonic zone still has the characteristics of continental rift valley, that is, the surface is hollow and the upper mantle is upwarping. The tectonic situation in Western Yunnan is of certain regulation with the interlacing distribution of orogenic zone and seam. The crustal thickness decreases gradually from the north to the south and the S wave velocity is globally lower here.展开更多
By using integral transform methods, the Green(s functions of horizontal harmonic force applied at the interior of the saturated half-space soil are obtained in the paper. The general solutions of the Biot dynamic equ...By using integral transform methods, the Green(s functions of horizontal harmonic force applied at the interior of the saturated half-space soil are obtained in the paper. The general solutions of the Biot dynamic equations in frequency domain are established through the use of Hankel integral transforms technique. Utilizing the above- mentioned general solutions, and the boundary conditions of the surface of the half-space and the continuous conditions at the plane of the horizontal force, the solutions of the boundary value problem can be determined. By the numerical inverse Hankel transforms method, the Green(s functions of the harmonic horizontal force are obtainable. The degenerate case of the results deduced from this paper agrees well with the known results. Two numerical examples are given in the paper.展开更多
The method of determining the structures and parameters of radial basis function neural networks(RBFNNs) using improved genetic algorithms is proposed. Akaike′s information criterion (AIC) with generalization error t...The method of determining the structures and parameters of radial basis function neural networks(RBFNNs) using improved genetic algorithms is proposed. Akaike′s information criterion (AIC) with generalization error term is used as the best criterion of optimizing the structures and parameters of networks. It is shown from the simulation results that the method not only improves the approximation and generalization capability of RBFNNs ,but also obtain the optimal or suboptimal structures of networks.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.
基金State Key Basic Research Development and Programming Project of China (G1998040700).
文摘s Western Yunnan is located at the boundary of collision or underthrusting zone of Eurasian plate and is influenced by many times tectonic movements. With very complex geological environment and tectonic background, it is one of the seismically active areas. In the paper, the teleseismic records were selected from 16 national, local and mo-bile stations, including 4 very-wide-band mobile stations of PASSCAL. And nearly 2 000 receiver functions were extracted. Two measuring lines are 650 km and 450 km, respectively and across some major tectonic units in Western Yunnan. It is indicated that Nujiang might be a seam characterized by underthrusting. The western and eastern boundaries of Sichuan-Yunnan rhombus block, i.e., Honghe and Xiaojiang faults, might be an erection seam or collision belt. Panxi tectonic zone still has the characteristics of continental rift valley, that is, the surface is hollow and the upper mantle is upwarping. The tectonic situation in Western Yunnan is of certain regulation with the interlacing distribution of orogenic zone and seam. The crustal thickness decreases gradually from the north to the south and the S wave velocity is globally lower here.
基金State Natural Science Foundation (59879012) and Doctoral Foundation from State Education Commission (98024832).
文摘By using integral transform methods, the Green(s functions of horizontal harmonic force applied at the interior of the saturated half-space soil are obtained in the paper. The general solutions of the Biot dynamic equations in frequency domain are established through the use of Hankel integral transforms technique. Utilizing the above- mentioned general solutions, and the boundary conditions of the surface of the half-space and the continuous conditions at the plane of the horizontal force, the solutions of the boundary value problem can be determined. By the numerical inverse Hankel transforms method, the Green(s functions of the harmonic horizontal force are obtainable. The degenerate case of the results deduced from this paper agrees well with the known results. Two numerical examples are given in the paper.
文摘The method of determining the structures and parameters of radial basis function neural networks(RBFNNs) using improved genetic algorithms is proposed. Akaike′s information criterion (AIC) with generalization error term is used as the best criterion of optimizing the structures and parameters of networks. It is shown from the simulation results that the method not only improves the approximation and generalization capability of RBFNNs ,but also obtain the optimal or suboptimal structures of networks.
