Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex.

Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex.
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DOI:
10.1113/jphysiol.2011.216978
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发表时间:
2011-12-01
期刊:
The Journal of physiology
影响因子:
--
通讯作者:
Rothwell JC
Rothwell JC
中科院分区:
其他
文献类型:
--
作者:
Stagg CJ;Bestmann S;Constantinescu AO;Moreno LM;Allman C;Mekle R;Woolrich M;Near J;Johansen-Berg H;Rothwell JC

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通过磁共振波谱(MRS)评估的区域GABA的个体间差异与人类的行为差异有关。然而,目前尚不清楚MRS测量区域内神经递质浓度与突触活动之间的关系。经颅磁刺激(TMS)技术提供了皮层兴奋或抑制的生理测量。在这里,我们研究了MRS和TMS测量同一个体中谷氨酸能和gaba能活性之间的关系。我们证明了mr评估的谷氨酸水平与TMS测量的全球皮质兴奋性之间的关系,表明mr测量的谷氨酸确实反映了谷氨酸能活动。然而,mrs评估的GABA水平与TMS测量的突触GABAA或GABAB活性之间没有明确的关系。经颅磁刺激法评估的GABA与经颅磁刺激方案之间的关系尚不清楚其生理基础。因此,我们推测该协议可能反映了突触外GABA音调。磁共振波谱(MRS)可以测量大脑中感兴趣区域内的神经递质浓度。mrs测量的GABA水平的个体间差异与许多区域的任务表现差异有关。然而,目前尚不清楚mrs评估的GABA测量与皮质兴奋性或GABA能突触活性之间的关系。因此,我们进行了两项研究,通过MRS和经颅磁刺激(TMS)测量皮层兴奋性和初级运动皮层GABA突触活性来评估神经递质水平之间的关系。我们提出了未校正的相关性,因此应该谨慎考虑p值。我们发现,经颅磁刺激输入输出曲线的斜率与经颅磁刺激评估的谷氨酸水平之间存在相关性(r = 0.803, P = 0.015),但经颅磁刺激评估的GABA水平与经颅磁刺激评估的突触GABAA活性(2.5 ms刺激间期(ISI)短间期皮质内抑制(SICI);实验1:r = 0.33, P = 0.31;实验2:r = -0.23, P = 0.46)或GABAB活性(长间隔皮质内抑制(LICI);实验1:r = -0.47, P = 0.51;实验2:r = 0.23, P = 0.47)。我们证明了mrs评估的GABA水平与抑制性TMS方案(1 ms ISI SICI)之间存在显著相关性,与2.5 ms ISI SICI具有不同的生理基础(r = -0.79, P = 0.018)。这一发现的解释具有挑战性,因为1毫秒ISI SICI的机制尚不清楚,但我们推测,我们的结果支持1毫秒ISI SICI反映了一种独特的GABA能抑制过程的可能性,可能是突触外GABA张力的抑制过程。
Inter-individual differences in regional GABA as assessed by magnetic resonance spectroscopy (MRS) relate to behavioural variation in humans. However, it is not clear what the relationship is between MRS measures of the concentration of neurotransmitters in a region and synaptic activity. Transcranial magnetic stimulation (TMS) techniques provide physiological measures of cortical excitation or inhibition. Here, we investigated the relationship between MRS and TMS measures of glutamatergic and GABAergic activity within the same individuals. We demonstrated a relationship between MRS-assessed glutamate levels and a TMS measure of global cortical excitability, suggesting that MRS measures of glutamate do reflect glutamatergic activity. However, there was no clear relationship between MRS-assessed GABA levels and TMS measures of synaptic GABAA or GABAB activity. A relationship was found between MRS-assessed GABA and a TMS protocol with less clearly understood physiological underpinnings. We speculate that this protocol may therefore reflect extrasynaptic GABA tone. Magnetic resonance spectroscopy (MRS) allows measurement of neurotransmitter concentrations within a region of interest in the brain. Inter-individual variation in MRS-measured GABA levels have been related to variation in task performance in a number of regions. However, it is not clear how MRS-assessed measures of GABA relate to cortical excitability or GABAergic synaptic activity. We therefore performed two studies investigating the relationship between neurotransmitter levels as assessed by MRS and transcranial magnetic stimulation (TMS) measures of cortical excitability and GABA synaptic activity in the primary motor cortex. We present uncorrected correlations, where thePvalue should therefore be considered with caution. We demonstrated a correlation between cortical excitability, as assessed by the slope of the TMS input–output curve and MRS-assessed glutamate levels (r = 0.803, P = 0.015) but no clear relationship between MRS-assessed GABA levels and TMS-assessed synaptic GABAA activity (2.5 ms inter-stimulus interval (ISI) short-interval intracortical inhibition (SICI); Experiment 1:r = 0.33, P = 0.31; Experiment 2:r = –0.23, P = 0.46) or GABAB activity (long-interval intracortical inhibition (LICI); Experiment 1:r = –0.47, P = 0.51; Experiment 2:r = 0.23, P = 0.47). We demonstrated a significant correlation between MRS-assessed GABA levels and an inhibitory TMS protocol (1 ms ISI SICI) with distinct physiological underpinnings from the 2.5 ms ISI SICI (r = –0.79, P = 0.018). Interpretation of this finding is challenging as the mechanisms of 1 ms ISI SICI are not well understood, but we speculate that our results support the possibility that 1 ms ISI SICI reflects a distinct GABAergic inhibitory process, possibly that of extrasynaptic GABA tone.
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