Combining noninvasive brain stimulation and neuroimaging to study human brain biology

结合无创脑刺激和神经影像学研究人脑生物学

• 批准号: RGPIN-2019-06514
• 负责人: Fecteau, Shirley
• 金额: $ 2.4万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=760658
• 关键词: Combining; noninvasive; brain; stimulation; neuroimaging

There are theories about how the brain works. Those theories can be tested with tools that can change brain function and identify how that affects behaviours. Such tools are common in animal models (e.g., optogenetics), but there are no such tools for the human brain. Our long-term NSERC supported program entails developing such tools. A method that could test theories, noninvasively, on human causal brain-behaviour relationships would have a transformative impact in neuroscience. Transcranial current stimulation (tCS) combined with MRI can become such cardinal tool. Previous studies observed that tCS modulated human behaviours in vivo, whereas others found not effects. These inconsistencies reflect in large part the noninvasive quality of tCS. Indeed, tCS alone does not show how it influences the brain when it modulates behaviours. This is a fundamental step missing in tCS investigations: What does tCS modulate to, consequently, influence behaviours? The main goal of this 5-year program is to characterize how tDCS modulates human brain activity by conducting basic investigations concurrently combining tCS and MRI. Thanks to previous Discovery grants, we developed a method concurrently combining tCS with resting state MRI. This method can thus to test whether tCS can truly modulate brain activity, without confounding behavioural influence. We found that tCS over the dorsolateral prefrontal cortex of healthy adults during resting state functional MRI and MR spectroscopy strengthened connectivity in the frontoparietal network and elevated prefrontal NAA and striatal glutamate levels. Our studies provide evidence that tCS can impact human brain activity during stimulation. We also recently observed that brain morphometry, especially the volume, influences tCS-induced changes on neurotransmitter levels. Strikingly, there are scarce studies on how morphometry and tractography influence tCS effects on brain activity. Yet, morphometry and tractography are the main roads that the current travels through (and that we can assess in vivo in the human brain) to modulate brain activity and consequently behaviours. In this program, we propose to specifically test: 1. If sham tDCS is a good control condition, as one of the most used sham tDCS protocol has yet to be tested with MRI outcomes; 2. Intra-individual reliability of tDCS effects on resting state functional connectivity during and after stimulation and characterize the impact of brain anatomy (morphometry, tractography) on these effects; and 3.Intra-individual reliability of tDCS effects on neurotransmitter levels during and after stimulation and characterize the impact of brain anatomy (morphometry, tractography) on these effects. The development of concurrently combining tCS and MRI methods will contribute at providing tools that will reliably modulate specific brain networks. Such tools will have the quality to test human brain functions by establishing brain-behavioural causal relationships.

有关于大脑如何工作的理论。这些理论可以用可以改变大脑功能的工具来测试，并确定它是如何影响行为的。这样的工具在动物模型中很常见（例如，光遗传学），但在人脑中没有这样的工具。我们NSERC长期支持的项目需要开发这样的工具。一种可以无创地测试人类大脑-行为因果关系理论的方法，将对神经科学产生革命性的影响。经颅电流刺激（tCS）结合MRI可以成为这样的主要工具。先前的研究观察到tCS在体内调节人类行为，而其他研究则没有发现效果。这些不一致在很大程度上反映了tCS的非侵入性。事实上，tCS本身并不能说明它在调节行为时是如何影响大脑的。这是tCS研究中缺失的一个基本步骤：tCS调节什么，从而影响行为？这个为期5年的项目的主要目标是通过同时结合tCS和MRI进行基础研究来表征tDCS如何调节人类大脑活动。感谢先前的Discovery资助，我们开发了一种将tCS与静息状态MRI同时结合的方法。因此，这种方法可以测试tCS是否真的可以调节大脑活动，而不会混淆行为影响。我们发现，在静息状态功能MRI和磁共振波谱中，健康成人前额叶背外侧皮层的tCS增强了额顶叶网络的连通性，并提高了前额叶NAA和纹状体谷氨酸水平。我们的研究提供了证据，证明tCS可以在刺激过程中影响人类的大脑活动。我们最近也观察到脑形态测量，特别是体积，影响tcs诱导的神经递质水平的变化。引人注目的是，形态学和神经束造影如何影响tCS对大脑活动的影响的研究很少。然而，形态测量学和神经束造影是电流通过的主要途径（我们可以在人体大脑中评估）来调节大脑活动和行为。在这个项目中，我们建议具体测试：1。如果假手术tDCS是一个很好的对照条件，作为目前最常用的假手术tDCS方案之一，还有待于MRI结果的检验；2. tDCS在刺激期间和刺激后对静息状态功能连通性影响的个体内可靠性，并表征脑解剖（形态学、神经束造影）对这些影响的影响；和3。tDCS在刺激期间和刺激后对神经递质水平影响的个体内部可靠性，并表征脑解剖（形态测量学、神经束造影）对这些影响的影响。同时结合tCS和MRI方法的发展将有助于提供可靠地调节特定大脑网络的工具。这些工具将具备通过建立大脑-行为因果关系来测试人脑功能的能力。