This study aimed at better understanding the neurochemistry underlying transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) measurements as it pertains to GABAergic activity following administration of allosteric GABA_A receptor agonist lorazepam. Seventeen healthy adults (8 females, 26.0 ± 5.4 years old) participated in a double-blind, crossover, placebo-controlled study, where participants underwent TMS and MRS two hours after drug intake (placebo or lorazepam; 2.5 mg). Neuronavigated TMS measures reflecting cortical inhibition and excitation were obtained in the left primary motor cortex. Sensorimotor cortex and occipital cortex MRS data were acquired using a 3T scanner with a MEGA-PRESS sequence, allowing water-referenced [GABA] and [Glx] (glutamate + glutamine) quantification. Lorazepam administration decreased occipital [GABA], decreased motor cortex excitability and increased GABA_A-receptor mediated motor cortex inhibition (short intracortical inhibition (SICI)). Lorazepam intake did not modulate sensorimotor [GABA] and TMS measures of intra-cortical facilitation, long-interval cortical inhibition, cortical silent period, and resting motor threshold. Furthermore, higher sensorimotor [GABA] was associated with higher cortical inhibition (SICI) following lorazepam administration, suggesting that baseline sensorimotor [GABA] may be valuable in predicting pharmacological or neuromodulatory treatment response. Finally, the differential effects of lorazepam on MRS and TMS measures, with respect to GABA, support the idea that TMS measures of cortical inhibition reflect synaptic GABAergic phasic inhibitory activity while MRS reflects extrasynaptic GABA.

本研究旨在更好地了解经颅磁刺激 (TMS) 和磁共振波谱 (MRS) 测量的神经化学，因为它与施用变构 GABA _{A后的 GABA 能活性有关}受体激动剂劳拉西泮。17 名健康成人（8 名女性，26.0 ± 5.4 岁）参加了一项双盲、交叉、安慰剂对照研究，参与者在服用药物（安慰剂或劳拉西泮；2.5 mg）后两小时接受 TMS 和 MRS。在左侧初级运动皮层中获得了反映皮层抑制和兴奋的神经导航 TMS 测量值。使用具有 MEGA-PRESS 序列的 3T 扫描仪获取感觉运动皮层和枕叶皮层 MRS 数据，允许以水为参考的 [GABA] 和 [Glx]（谷氨酸 + 谷氨酰胺）量化。劳拉西泮给药降低枕骨 [GABA]、降低运动皮层兴奋性和增加 GABA _A-受体介导的运动皮层抑制（短皮质内抑制（SICI））。劳拉西泮摄入量不调节感觉运动 [GABA] 和 TMS 测量皮质内促进、长间隔皮质抑制、皮质静默期和静息运动阈值。此外，较高的感觉运动 [GABA] 与劳拉西泮给药后较高的皮质抑制 (SICI) 相关，这表明基线感觉运动 [GABA] 在预测药理学或神经调节治疗反应方面可能很有价值。最后，劳拉西泮对 MRS 和 TMS 测量的不同影响，关于 GABA，支持 TMS 测量皮质抑制反映突触 GABA 能阶段抑制活性，而 MRS 反映突触外 GABA 的观点。