Scholarlink

<p>Although 10-Hz repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved treatment for depression, we do not understand the mechanisms through which rTMS induces therapeutic change. Two competing theories suggest that 10-Hz rTMS induces N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP), and/or removal of inhibitory gamma-aminobutyric acid receptors (GABARs). We examined these two proposed mechanisms of action in the human motor cortex in a double-blind, randomized, four-arm crossover study in six healthy subjects. We tested plasticity with motor-evoked potentials (MEPs) and learning with serial reaction time task (SRTT) before and after 10-Hz rTMS in the presence of four drugs separated by 1 week each: placebo, d-cycloserine (DCS 100 mg), DCS 100 mg + NMDAR partial antagonist dextromethorphan (DXM 150 mg), and lorazepam (LZP 2.5 mg). NMDAR agonism by DCS enhanced rTMS-induced cortical excitability relative to placebo. This facilitation was specifically blocked by combining DCS with DXM. LZP administration resulted in a significant reduction of MEP amplitudes after rTMS. Results suggest that 10-Hz rTMS-induced plasticity works primarily through NMDAR dependent modulation with LTP-like mechanisms as opposed to GABAergic reduction. Our pilot study is the first to compare NMDAR v. GABAR in rTMS-induced plasticity and found the safety and feasibility of a 4-arm crossover protocol with each drug combined with the full 3000 pulse 10-Hz rTMS protocol. Our results may guide future clinical translation leveraging mechanistic understanding to improve therapeutic efficacy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Exploration of NMDA and GABA receptor-mediated plasticity induced by 10-Hz repetitive transcranial magnetic stimulation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月17日

查看全文
  • Jamie Kweon,
  • Hakjoo Kim,
  • Prem Ganesh,
  • Megan M. Vigne,
  • Andrew M. Fukuda,
  • Boyu Ren,
  • Linda L. Carpenter,
  • Joshua C. Brown

摘要

Although 10-Hz repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved treatment for depression, we do not understand the mechanisms through which rTMS induces therapeutic change. Two competing theories suggest that 10-Hz rTMS induces N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP), and/or removal of inhibitory gamma-aminobutyric acid receptors (GABARs). We examined these two proposed mechanisms of action in the human motor cortex in a double-blind, randomized, four-arm crossover study in six healthy subjects. We tested plasticity with motor-evoked potentials (MEPs) and learning with serial reaction time task (SRTT) before and after 10-Hz rTMS in the presence of four drugs separated by 1 week each: placebo, d-cycloserine (DCS 100 mg), DCS 100 mg + NMDAR partial antagonist dextromethorphan (DXM 150 mg), and lorazepam (LZP 2.5 mg). NMDAR agonism by DCS enhanced rTMS-induced cortical excitability relative to placebo. This facilitation was specifically blocked by combining DCS with DXM. LZP administration resulted in a significant reduction of MEP amplitudes after rTMS. Results suggest that 10-Hz rTMS-induced plasticity works primarily through NMDAR dependent modulation with LTP-like mechanisms as opposed to GABAergic reduction. Our pilot study is the first to compare NMDAR v. GABAR in rTMS-induced plasticity and found the safety and feasibility of a 4-arm crossover protocol with each drug combined with the full 3000 pulse 10-Hz rTMS protocol. Our results may guide future clinical translation leveraging mechanistic understanding to improve therapeutic efficacy.