Abstract：
BACKGROUND: Neuro-navigated repetitive transcranial magnetic stimulation (rTMS) of the left angular gyrus has been broadly investigated for the treatment of amnestic mild cognitive impairment (aMCI). Although abnormalities in two hippocampal networks, the anterior-temporal (AT) and posterior-medial (PM) networks, are consistent with aMCI and are potential therapeutic targets for rTMS, the underlying mechanisms of the therapeutic effects of rTMS on hippocampal network connections remain unknown. Here, we assessed the impact of left angular gyrus rTMS on activity in these networks and explored whether the treatment response was due to the distance between the clinically applied target (the group average optimal site) and the personalized target in patients with aMCI.
METHODS: Sixty subjects clinically diagnosed with aMCI participated in this study after 20 sessions of sham-controlled rTMS targeting the left angular gyrus. Resting-state functional magnetic resonance imaging and neuropsychological assessments were performed before and after rTMS. Functional connectivity alterations in the PM and AT networks were assessed using seed-based functional connectivity analysis and two-factor repeated measures analysis of variance (ANOVA). We then computed the correlations between the functional connectivity changes and clinical rating scales. Finally, we examined whether the Euclidean distance between the clinically applied and personalized targets predicted the subsequent treatment response.
RESULTS: Compared with the sham group, the active rTMS group showed rTMS-induced deactivation of functional connectivity within the medial temporal lobe-AT network, with a negative correlation with episodic memory score changes. Moreover, the active rTMS lowers the interdependency of changes in the PM and AT networks. Finally, the Euclidean distance between the clinically applied and personalized target distances could predict subsequent network lever responses in the active rTMS group.
CONCLUSIONS: Neuro-navigated rTMS selectively modulates widespread functional connectivity abnormalities in the PM and AT hippocampal networks in aMCI patients, and the modulation of hippocampal-AT network connectivity can efficiently reverse memory deficits. The results also highlight the necessity of personalized targets for fMRI.
METHODS: Sixty subjects clinically diagnosed with aMCI participated in this study after 20 sessions of sham-controlled rTMS targeting the left angular gyrus. Resting-state functional magnetic resonance imaging and neuropsychological assessments were performed before and after rTMS. Functional connectivity alterations in the PM and AT networks were assessed using seed-based functional connectivity analysis and two-factor repeated measures analysis of variance (ANOVA). We then computed the correlations between the functional connectivity changes and clinical rating scales. Finally, we examined whether the Euclidean distance between the clinically applied and personalized targets predicted the subsequent treatment response.
RESULTS: Compared with the sham group, the active rTMS group showed rTMS-induced deactivation of functional connectivity within the medial temporal lobe-AT network, with a negative correlation with episodic memory score changes. Moreover, the active rTMS lowers the interdependency of changes in the PM and AT networks. Finally, the Euclidean distance between the clinically applied and personalized target distances could predict subsequent network lever responses in the active rTMS group.
CONCLUSIONS: Neuro-navigated rTMS selectively modulates widespread functional connectivity abnormalities in the PM and AT hippocampal networks in aMCI patients, and the modulation of hippocampal-AT network connectivity can efficiently reverse memory deficits. The results also highlight the necessity of personalized targets for fMRI.
摘要：
背景：左角回的神经导航重复经颅磁刺激（rTMS）已被广泛研究用于治疗遗忘型轻度认知障碍（aMCI）。虽然在两个海马网络异常，前颞(AT)和后内侧(PM)网络，与aMCI一致，是rTMS的潜在治疗靶点，rTMS对海马网络连接的治疗作用的潜在机制仍然未知.这里,我们评估了左角回rTMS对这些网络活动的影响,并探讨了治疗反应是否归因于aMCI患者临床应用目标(组平均最佳部位)与个性化目标之间的距离.
方法：在20次针对左角回的假对照rTMS治疗后，60名临床诊断为aMCI的受试者参与了这项研究。在rTMS前后进行静息状态功能磁共振成像和神经心理学评估。使用基于种子的功能连通性分析和双因素重复测量方差分析（ANOVA）评估PM和AT网络中的功能连通性改变。然后，我们计算了功能连通性变化与临床评定量表之间的相关性。最后,我们检查了临床应用目标和个性化目标之间的欧氏距离是否可以预测后续治疗反应.
结果：与假手术组相比，活跃的rTMS组显示rTMS诱导的内侧颞叶-AT网络内的功能连接失活，与情景记忆得分变化呈负相关。此外，活动rTMS降低了PM和AT网络中变化的相互依赖性。最后,临床应用目标距离和个性化目标距离之间的欧氏距离可以预测活动rTMS组随后的网络杠杆反应.
结论：神经导航rTMS选择性调节aMCI患者PM和AT海马网络中广泛的功能连接异常，调节海马-AT网络连接可以有效逆转记忆障碍。结果还强调了功能磁共振成像个性化目标的必要性。
方法：在20次针对左角回的假对照rTMS治疗后，60名临床诊断为aMCI的受试者参与了这项研究。在rTMS前后进行静息状态功能磁共振成像和神经心理学评估。使用基于种子的功能连通性分析和双因素重复测量方差分析（ANOVA）评估PM和AT网络中的功能连通性改变。然后，我们计算了功能连通性变化与临床评定量表之间的相关性。最后,我们检查了临床应用目标和个性化目标之间的欧氏距离是否可以预测后续治疗反应.
结果：与假手术组相比，活跃的rTMS组显示rTMS诱导的内侧颞叶-AT网络内的功能连接失活，与情景记忆得分变化呈负相关。此外，活动rTMS降低了PM和AT网络中变化的相互依赖性。最后,临床应用目标距离和个性化目标距离之间的欧氏距离可以预测活动rTMS组随后的网络杠杆反应.
结论：神经导航rTMS选择性调节aMCI患者PM和AT海马网络中广泛的功能连接异常，调节海马-AT网络连接可以有效逆转记忆障碍。结果还强调了功能磁共振成像个性化目标的必要性。
