Combining noninvasive brain stimulation and neuroimaging to study human brain biology

有关于大脑如何工作的理论，但没有办法改变大脑的活动，我们真的不知道如何测试这些理论。我们需要工具来改变大脑的功能，看看它是如何影响行为来测试这些理论。这类工具在动物模型（如光遗传学）中很常见，但在人类神经科学中并不常见。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成为神经科学的基础。经颅电流刺激（tCS）结合神经成像可能成为这一重要工具。以前的研究报道，tCS可以在体内调节人类的行为。然而，由于它的非侵入性，tCS本身并不能显示它在调节行为时是如何刺激大脑的。因此，我们需要将tCS与磁共振成像（MRI）等神经成像技术结合起来，开发出能够可靠地调节特定大脑网络的方法。******我们的长期NSERC支持的项目需要实现这样的大脑工具的发展，将允许测试大脑功能的理论，建立大脑行为的关系。******感谢先前的Discovery资助，我们开发了一种同时结合tCS/静息状态MRI的方法。这种方法实时捕捉到tCS调节大脑的因果证据。作为一个例子，我们在静息状态功能磁共振成像（fMRI）和磁共振光谱期间对健康成人的背外侧前额皮质进行了tCS。tCS调节静息状态功能连通性，加强额顶叶网络的连通性。此外，在刺激期间，tCS升高纹状体谷氨酸和前额叶NAA水平。这项工作是首次证明tCS在MR采集过程中调节人脑底物的研究之一，该研究发表在脑生物学领域的顶级期刊和新闻稿上（Hone-Blanchet, Edden, Fecteau， 2016年生物精神病学）。******本提案的目的是追求这个NSERC支持的大脑工具的发展。我们将开发方法，将可靠地调节特定的网络（例如，额-顶叶，额-纹状体网络）。为了实现这一目标，我们将开发同时和随后结合tCS和MRI的方法。我们将研究主要的tCS类型（直流电，tCDS；交流电，tACS，随机噪声，tRNS）和MRI方法（fMRI， MRS，结构，束状图）。

There are theories about how the brain works, but without having a way to change brain activity, we do not really know how to test those theories. We need tools for changing the function of the brain and seeing how that affects the behaviours to test those theories. Such tools are common in animal models (e.g., optogenetics), but not in human neuroscience. An approach that could test theories, noninvasively, on human causal brain-behaviour relationships would become fundamental in neuroscience. Transcranial current stimulation (tCS) combined with neuroimaging could become such cardinal tool. Previous studies reported that tCS can modulate human behaviours in vivo. However, due to its noninvasive quality, tCS alone does not show how it stimulates the brain when it modulates behaviours. We thus need to combine tCS with neuroimaging, such as magnetic resonance imaging (MRI), to develop methods that will reliably modulate specific brain networks. ******Our long-term NSERC supported program entails achieving the development of such brain tool that will permit testing theories on brain function, establishing brain-behavioural relationships. ******Thanks to previous Discovery grant, we developed an approach combining simultaneously tCS/resting state MRI. This method captures, in real time, the cause and effect evidence of tCS modulating the brain. As an example, we delivered tCS over the dorsolateral prefrontal cortex in healthy adults during resting state functional MRI (fMRI) as well as during MR spectroscopy. tCS modulated resting state functional connectivity, strengthening connectivity in the fronto-parietal network. Also, tCS elevated striatal glutamate and prefrontal NAA levels during stimulation. This work is among the first demonstrations that tCS modulates human brain substrates during MR acquisition which was published in a top journal in the field of brain biology and a Press Release (Hone-Blanchet, Edden, Fecteau, 2016 Biological Psychiatry).******The aim of this proposal is to pursue the development of this NSERC supported brain tool. We will develop methods that will reliably modulate specific networks (e.g., fronto-parietal, fronto-striatal network). In order to achieve this, we will develop methods combining simultaneously and subsequently tCS and MRI. We will investigate the main tCS types (direct current, tCDS; alternating current, tACS, random noise, tRNS) and MRI methods (fMRI, MRS, structural, tractography).