Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, Centre for Gastrointestinal Sciences, School of Medical Sciences, The University of Manchester, Manchester, UK.
Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, School of Medical Sciences, The University of Manchester, Manchester, UK.
Neurogastroenterol Motil. 2019 Jul;31(7):e13612. doi: 10.1111/nmo.13612. Epub 2019 Apr 29.
Recent studies have reported substantial variability in response to repetitive transcranial magnetic stimulation (rTMS). We hypothesized that an individual's genetic predisposition may contribute to such variability in the pharyngeal motor cortex. This study aimed to investigate the response to 1 and 5 Hz rTMS paradigms on pharyngeal motor cortex in healthy participants and its relationship with genetic predisposition.
Forty-one healthy participants (25.4 ± 4.6 years old) received either or both 1 Hz (n = 39) and 5 Hz rTMS (n = 40) over pharyngeal motor cortex. Pharyngeal and thenar motor-evoked potentials were recorded at baseline and for 1 hour post-rTMS. The participants were then classified according to their response. The associations between rTMS response and gender, time of day of the stimulation, and eight prespecified single nucleotide polymorphisms (SNPs) were analyzed.
There was no direction-specific response to either paradigm (1 Hz: F[3.69, 129.21] = 0.78, P = 0.56; 5 Hz: F[4.08, 146.85] = 1.38, P = 0.25). Only 13% of participants showed the expected bidirectional response (inhibition for 1 Hz and excitation for 5 Hz). Significant associations were found between response and COMT (1 Hz: P = 0.03) and DRD2 (1 Hz: P = 0.02; 5 Hz: P = 0.04) polymorphisms. Carriers of minor allele G from SNP rs6269 (COMT) were more likely to show inhibitory or excitatory outcomes after 1 Hz rTMS. By contrast, carriers of minor allele A from SNP rs1800497 (DRD2) were more likely to show no response to 1 Hz rTMS and inhibition after 5 Hz rTMS.
CONCLUSIONS & INFERENCES: Two SNPs from COMT and DRD2 genes may partially explain the response variability to rTMS in the pharyngeal motor system. Further research should focus on stratified approaches for neurostimulatory dysphagia treatment using rTMS.
最近的研究报告显示，重复经颅磁刺激（rTMS）的反应存在很大的可变性。我们假设个体的遗传倾向可能导致咽运动皮层的这种可变性。本研究旨在探讨健康参与者咽运动皮层对 1Hz 和 5Hz rTMS 范式的反应及其与遗传倾向的关系。
41 名健康参与者（25.4±4.6 岁）接受 1Hz（n=39）或 5Hz rTMS（n=40）刺激咽运动皮层。在 rTMS 前后记录咽和鱼际运动诱发电位。根据反应将参与者分类。分析 rTMS 反应与性别、刺激时间和 8 个预设单核苷酸多态性（SNP）之间的关系。
两种范式均无方向特异性反应（1Hz：F[3.69, 129.21]=0.78, P=0.56；5Hz：F[4.08, 146.85]=1.38, P=0.25）。只有 13%的参与者表现出预期的双向反应（1Hz 抑制，5Hz 兴奋）。在 COMT（1Hz：P=0.03）和 DRD2（1Hz：P=0.02；5Hz：P=0.04）多态性中发现反应与 SNP 之间存在显著关联。SNP rs6269（COMT）中的 G 等位基因的携带者在接受 1Hz rTMS 后更有可能表现出抑制或兴奋的结果。相比之下，SNP rs1800497（DRD2）中的 A 等位基因的携带者在接受 1Hz rTMS 后更有可能没有反应，而在接受 5Hz rTMS 后表现出抑制。
来自 COMT 和 DRD2 基因的两个 SNP 可能部分解释了咽运动系统对 rTMS 反应的可变性。进一步的研究应侧重于使用 rTMS 对神经刺激性吞咽困难进行分层治疗的方法。
