Altered Parietal-Motor Connections in Alzheimer's Disease Patients
Altered Parietal-Motor Connections in Alzheimer's Disease Patients
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DOI：
10.3233/jad-2012-121144
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Koch, Giacomo
中科院分区：
文献类型：
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作者：
Bonni, Sonia;Lupo, Federica;Koch, Giacomo
阿尔茨海默病（AD）的特征是皮质-皮质功能连接的改变，可能是由于不同皮质区域之间传入和传出连接的丧失。本研究采用双焦点经颅磁刺激（TMS）对15例AD患者和12例健康对照者的顶叶-额叶功能连通性进行了研究。在右侧后顶叶皮层（PPC）上施加不同强度的条件反射刺激（静息运动阈值的90%和110%）。然后在2 ~ 15 ms的不同刺激间隔（ISIs）记录同侧初级运动皮层的运动诱发电位（MEPs）。结果表明，在健康受试者中，在同侧PPC上施加90%而不是110% RMT强度的调节性TMS脉冲能够增加右侧M1的兴奋性。这种功能相互作用在ISI = 6 ms时达到峰值。相反，在AD患者中，只有当TMS的强度为RMT的110%时，顶叶-运动连接的促进模式才明显，并在ISI = 8 ms时达到峰值。此外，在AD患者中，使用胆碱酯酶抑制剂治疗并没有引起这种连接强度的任何显著改变。在随后的分析中，我们发现，在AD患者中，110% RMT时PPC条件反射引起的影响与情景记忆和执行功能的神经心理学测量相关，这意味着认知表现较好的患者连接受损较少。我们的研究结果表明，阿尔茨海默病患者的顶叶-额叶皮质-皮质功能连通性发生改变，为阿尔茨海默病症状的断开性解释提供了进一步的证据。
Alzheimer's disease (AD) is characterized by altered functional cortico-cortical connectivity likely due to loss of afferent and efferent connections between different cortical areas. Here we explored parieto-frontal functional connectivity in 15 AD patients and 12 healthy control subjects by means of bifocal transcranial magnetic stimulation (TMS). Conditioning stimuli were applied over the right posterior parietal cortex (PPC) at different intensities (90% and 110% of resting motor threshold, RMT). Motor evoked potentials (MEPs) were then recorded from the ipsilateral primary motor cortex at different interstimulus intervals (ISIs) ranging between 2 and 15 ms. Results showed that in healthy subjects, a conditioning TMS pulse applied over the ipsilateral PPC at 90%, but not at 110%, of RMT intensity was able to increase the excitability of the right M1. This functional interaction peaked at ISI = 6 ms. Conversely, in AD patients the facilitatory pattern of parieto-motor connections was evident only when TMS was delivered at an intensity of 110% of RMT with a peak at ISI = 8 ms. Moreover in AD patients, treatment with cholinesterase inhibitors did not induce any significant modification in the strength of the connection. In subsequent analyses, we found that, in AD patients, the effects induced by PPC conditioning at 110% RMT correlated with neuropsychological measures of episodic memory and executive functions, implying that patients with better cognitive performance had less impaired connectivity. Our findings reveal that parieto-frontal cortico-cortical functional connectivity is altered in AD patients, providing further evidence for a disconnection-based interpretation of AD symptoms.