Combining noninvasive brain stimulation and neuroimaging to study human brain biology

有一些关于大脑如何工作的理论，但如果没有改变大脑活动的方法，我们就不知道如何验证这些理论。我们需要工具来改变大脑的功能，看看它如何影响行为，以测试这些理论。这种工具在动物模型中很常见（例如，光遗传学），但不是在人类神经科学。一种可以非侵入性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）结合神经影像学可能成为这样的基本工具。先前的研究报道，TCS可以调节人体内的行为。然而，由于其非侵入性的性质，单独的TCS并不能显示它在调节行为时是如何刺激大脑的。因此，我们需要将联合收割机与神经成像（如磁共振成像（MRI））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种大脑工具的开发，这将允许测试大脑功能的理论，建立大脑行为关系。** 由于之前的发现基金，我们开发了一种同时结合tCS/静息状态MRI的方法。该方法以真实的时间捕获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性MRI（fMRI）以及MR波谱检查期间，在健康成年人的背外侧前额叶皮层上提供了TCS。TCS调节静息状态功能连接，加强额顶叶网络的连接。此外，TCS升高纹状体谷氨酸和前额叶NAA水平在刺激。这项工作是首次证明tCS在MR采集期间调节人脑基质的研究之一，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 Biological Psychiatry）。该提案的目的是继续开发NSERC支持的大脑工具。我们将开发可靠地调制特定网络的方法（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，tCDS;交流电，tACS，随机噪声，tRNS）和MRI方法（fMRI，MRS，结构，纤维束成像）。

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).