Combining noninvasive brain stimulation and neuroimaging to study human brain biology

有关于大脑如何工作的理论，但由于没有办法改变大脑活动，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，并观察它对行为的影响，以检验这些理论。这样的工具在动物模型(例如光遗传学)中很常见，但在人类神经科学中并不常见。一种可以非侵入性地测试人类因果大脑-行为关系理论的方法将成为神经科学的基础。经颅电流刺激(TCS)结合神经成像可以成为这种主要的工具。以往的研究报道，天花粉蛋白可以在体内调节人类的行为。然而，由于其非侵入性的性质，TCS本身并不能显示它在调节行为时如何刺激大脑。因此，我们需要将TCS与磁共振成像(MRI)等神经成像技术相结合，以开发可靠地调节特定大脑网络的方法。*我们的长期NSERC支持计划需要实现这样的大脑工具的开发，该工具将允许测试关于大脑功能的理论，建立大脑-行为关系。*感谢之前的发现资助，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了TCS调节大脑的因果证据。作为一个例子，我们在健康成年人的背外侧前额叶皮质上进行了静息功能磁共振成像(FMRI)和磁共振波谱检查。TCS调节静息状态的功能连接，加强额顶网络的连接。此外，在刺激过程中，天花粉蛋白提高了纹状体谷氨酸和前额叶NAA的水平。这项工作是TCS在MR获取过程中调制人脑底物的首批演示之一，该演示发表在脑生物学领域的顶级杂志和新闻稿(Hone-Blanchet，Edden，Fecteau，2016生物精神病学)上。*该提案的目的是开发NSERC支持的大脑工具。我们将开发可靠地调节特定网络(例如，额顶、额纹状体网络)的方法。为了实现这一点，我们将开发同时结合TCS和MRI的方法。我们将研究TCS的主要类型(直流电，tCDS；交流电，TACS，随机噪声，TRNS)和MRI方法(fMRI，MRS，Structure，Tracogy)。

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).