经颅超声刺激调节猕猴执行反扫视任务时的单个神经元放电。

Transcranial ultrasonic stimulation modulates single-neuron discharge in macaques performing an antisaccade task.

机构信息

Institut du Cerveau et de la Moelle épinière, UMRS 975 INSERM, CNRS 7225, UMPC, Paris, France.

Institut Langevin Ondes et Images, ESPCI ParisTech, CNRS 7587, UMRS 979 INSERM, Paris, France.

出版信息

Brain Stimul. 2017 Nov-Dec;10(6):1024-1031. doi: 10.1016/j.brs.2017.07.007. Epub 2017 Jul 26.

Abstract

BACKGROUND

Low intensity transcranial ultrasonic stimulation (TUS) has been demonstrated to non-invasively and transiently stimulate the nervous system. Although US neuromodulation has appeared robust in rodent studies, the effects of US in large mammals and humans have been modest at best. In addition, there is a lack of direct recordings from the stimulated neurons in response to US. Our study investigates the magnitude of the US effects on neuronal discharge in awake behaving monkeys and thus fills the void on both fronts.

OBJECTIVE/HYPOTHESIS: In this study, we demonstrate the feasibility of recording action potentials in the supplementary eye field (SEF) as TUS is applied simultaneously to the frontal eye field (FEF) in macaques performing an antisaccade task.

RESULTS

We show that compared to a control stimulation in the visual cortex, SEF activity is significantly modulated shortly after TUS onset. Among all cell types 40% of neurons significantly changed their activity after TUS. Half of the neurons showed a transient increase of activity induced by TUS.

CONCLUSION

Our study demonstrates that the neuromodulatory effects of non-invasive focused ultrasound can be assessed in real time in awake behaving monkeys by recording discharge activity from a brain region reciprocally connected with the stimulated region. The study opens the door for further parametric studies for fine-tuning the ultrasonic parameters. The ultrasonic effect could indeed be quantified based on the direct measurement of the intensity of the modulation induced on a single neuron in a freely performing animal. The technique should be readily reproducible in other primate laboratories studying brain function, both for exploratory and therapeutic purposes and to facilitate the development of future clinical TUS devices.

摘要

背景

低强度经颅超声刺激(TUS)已被证明能够非侵入性地短暂刺激神经系统。尽管 US 神经调节在啮齿动物研究中表现出很强的效果,但在大型哺乳动物和人类中的效果最多只是适度的。此外,对于 US 刺激神经元的反应,缺乏直接记录。我们的研究调查了 US 对清醒行为猴子神经元放电的影响程度,从而填补了这两个方面的空白。

目的/假设:在这项研究中,我们证明了在猕猴执行反扫视任务时,同时将 TUS 应用于额眼区(FEF),记录补充眼区(SEF)中的动作电位是可行的。

结果

我们表明,与视觉皮层的对照刺激相比,SEF 活动在 TUS 开始后不久就会发生明显的调制。在所有细胞类型中,有 40%的神经元在 TUS 后其活动发生了显著变化。一半的神经元显示出 TUS 诱导的短暂活动增加。

结论

我们的研究表明,通过记录与刺激区域反向连接的脑区的放电活动,可以在清醒行为猴子中实时评估非侵入性聚焦超声的神经调节效应。该研究为进一步进行参数研究以微调超声参数开辟了道路。该超声效应确实可以基于对自由行为动物中单个人工神经元调制强度的直接测量来定量。该技术应该可以在其他研究大脑功能的灵长类动物实验室中重现,无论是用于探索性还是治疗性目的,都有助于开发未来的临床 TUS 设备。

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