Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Neuropsychopharmacology. 2023 Jul;48(8):1217-1224. doi: 10.1038/s41386-023-01575-7. Epub 2023 Apr 11.
Repeated spaced TMS protocols, also termed accelerated TMS protocols, are of increasing therapeutic interest. The long-term potentiation (LTP)-like effects of repeated spaced intermittent theta-burst transcranial magnetic stimulation (iTBS) are presumed to be N-Methyl-D-Aspartate receptor (NMDA-R) dependent; however, this has not been tested. We tested whether the LTP-like effects of repeated spaced iTBS are influenced by low-dose D-Cycloserine (100 mg), an NMDA-R partial-agonist. We conducted a randomized, double-blind, placebo-controlled crossover trial in 20 healthy adults from August 2021-Feb 2022. Participants received repeated spaced iTBS, consisting of two iTBS sessions 60 minutes apart, to the primary motor cortex. The peak-to-peak amplitude of the motor evoked potentials (MEP) at 120% resting motor threshold (RMT) was measured after each iTBS. The TMS stimulus-response (TMS-SR; 100-150% RMT) was measured at baseline, +30 min, and +60 min after each iTBS. We found evidence for a significant Drug*iTBS effect in MEP amplitude, revealing that D-Cycloserine enhanced MEP amplitudes relative to the placebo. When examining TMS-SR, pairing iTBS with D-Cycloserine increased the TMS-SR slope relative to placebo after both iTBS tetani, and this was due to an increase in the upper bound of the TMS-SR. This indicates that LTP-like and metaplastic effects of repeated-spaced iTBS involve NMDA-R, as revealed by two measures of corticospinal excitability, and that low-dose D-Cycloserine facilitates the physiological effects of repeated spaced iTBS. However, extension of these findings to clinical populations and therapeutic protocols targeting non-motor regions of cortex requires empirical validation.
重复间隔经颅磁刺激（rTMS）方案，也称为加速 rTMS 方案，具有越来越大的治疗意义。重复间隔经颅磁刺激（rTBS）的长时程增强（LTP）样效应被认为是 N-甲基-D-天冬氨酸受体（NMDA-R）依赖性的；然而，这尚未得到验证。我们测试了重复间隔 rTBS 的 LTP 样效应是否受到低剂量 D-环丝氨酸（100mg）的影响，D-环丝氨酸是 NMDA-R 部分激动剂。我们于 2021 年 8 月至 2022 年 2 月在 20 名健康成年人中进行了一项随机、双盲、安慰剂对照交叉试验。参与者接受了重复间隔 rTBS，由两个间隔 60 分钟的 rTBS 组成，刺激初级运动皮层。每次 rTBS 后，测量运动诱发电位（MEP）的峰峰值幅度，刺激强度为 120%静息运动阈值（RMT）。在基线、rTBS 后+30 分钟和+60 分钟时测量 TMS 刺激反应（TMS-SR；100-150%RMT）。我们发现 MEP 幅度存在药物*iTBS 效应的证据，表明 D-环丝氨酸相对于安慰剂增强了 MEP 幅度。当检查 TMS-SR 时，与安慰剂相比，rTBS 与 D-环丝氨酸联合使用后，两次 rTBS 强直刺激后 TMS-SR 斜率增加，这是由于 TMS-SR 上限增加所致。这表明，两种皮质脊髓兴奋性测量方法均表明，重复间隔 rTBS 的 LTP 样和类塑效应涉及 NMDA-R，而低剂量 D-环丝氨酸促进了重复间隔 rTBS 的生理效应。然而，将这些发现扩展到临床人群和针对皮质非运动区域的治疗方案需要经验验证。
