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经颅磁刺激评估清醒恒河猴的皮质兴奋性:募集曲线的转化见解

Assessment of cortical excitability in awake rhesus macaques with transcranial magnetic stimulation: Translational insights from recruitment curves.

作者信息

Padányi Anna, Knakker Balázs, Lendvai Balázs, Hernádi István

机构信息

Grastyán E. Translational Research Centre, University of Pécs, Hungary; Medical School, University of Pécs, Hungary.

Grastyán E. Translational Research Centre, University of Pécs, Hungary.

出版信息

Neuroimage. 2025 Aug 1;316:121306. doi: 10.1016/j.neuroimage.2025.121306. Epub 2025 Jun 4.

DOI:10.1016/j.neuroimage.2025.121306
PMID:40480401
Abstract

Cortical excitability (CE) is commonly assessed via motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (sp-TMS). While the motor threshold (MT) remains the most widely used measure of CE, it provides a limited, one-dimensional measure based on a fixed MEP amplitude criterion. In contrast, the recruitment curve (RC) offers a more comprehensive characterization of corticospinal recruitment dynamics. To date, the few available preclinical TMS studies measuring RC in non-human primates have been conducted under anaesthesia with limited translational relevance. Hence, we characterised CE in 20 sessions of 4 awake rhesus macaques by recording RCs at nine stimulation intensity levels and parametrising them using exponentiated sigmoid functions. The traditional 100 µV MEP MT criterion level (SI) aligned most closely with the inflection point of the RC sigmoid fit and was consistent with relative frequency-based traditional MT (tradMT) measured in separate sessions. The onset of the logarithmic recruitment phase of the sigmoid (lower ankle point) was found at 0.9 × SI/tradMT. Well-formed MEPs were measured below the SI/tradMT, but not below the lower ankle point, which is a physiologically relevant response threshold. Thus, in rhesus macaques the 100-µV criterion may be suitable to approximate the RC inflection point, but not the physiological motor threshold. The overall RC shape was consistent with previous human data, however, plateau MEP amplitudes were substantially smaller than those reported in humans. These results lay the groundwork for the adaptation of TMS protocols and CE metrics to non-human primates that is necessary for translationally valid research.

摘要

皮质兴奋性(CE)通常通过单脉冲经颅磁刺激(sp-TMS)诱发的运动诱发电位(MEP)来评估。虽然运动阈值(MT)仍然是最广泛使用的CE测量指标,但它基于固定的MEP振幅标准提供了一种有限的一维测量方法。相比之下,募集曲线(RC)能更全面地表征皮质脊髓募集动态。迄今为止,在非人类灵长类动物中测量RC的少数现有临床前TMS研究是在麻醉状态下进行的,其转化相关性有限。因此,我们通过在9个刺激强度水平记录RC并使用指数化S形函数对其进行参数化,对4只清醒恒河猴的20次实验中的CE进行了表征。传统的100 μV MEP MT标准水平(SI)与RC S形拟合的拐点最接近,并且与在单独实验中测量的基于相对频率的传统MT(tradMT)一致。S形曲线对数募集阶段的起始点(较低的拐点)出现在0.9×SI/tradMT处。在SI/tradMT以下但在较低拐点以下未测量到波形良好的MEP,较低拐点是一个生理相关的反应阈值。因此,在恒河猴中,100 μV标准可能适合于近似RC拐点,但不适合于生理运动阈值。整体RC形状与先前的人类数据一致,然而,平台期MEP振幅明显小于人类报告的振幅。这些结果为将TMS方案和CE指标应用于非人类灵长类动物奠定了基础,这对于具有转化有效性的研究是必要的。

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