Combining noninvasive brain stimulation and neuroimaging to study human brain biology

关于大脑是如何工作的，有一些理论。这些理论可以用工具来测试，这些工具可以改变大脑功能，并确定这如何影响行为。这类工具在动物模型(例如光遗传学)中很常见，但在人脑中还没有这样的工具。我们的长期NSERC支持计划需要开发这样的工具。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可以成为这一主要手段。 以前的研究观察到，TCS在体内调节人类的行为，而其他研究发现没有影响。这些不一致在很大程度上反映了TCS的非侵入性质量。事实上，仅靠TCS并不能说明它在调节行为时是如何影响大脑的。这是塔塔咨询公司调查中缺失的一个基本步骤：塔塔咨询公司调节什么，从而影响行为？ 这项为期5年的计划的主要目标是通过同时进行TCS和MRI的基础研究来表征TDC如何调节人脑活动。多亏了之前的发现资助，我们开发了一种同时结合TCS和静息状态MRI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，在静息状态下，健康成年人背外侧前额叶皮质上的TCS增强了额顶网络的连通性，并提高了前额叶NAA和纹状体谷氨酸的水平。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。我们最近还观察到，脑形态计量学，特别是体积，影响TCS诱导的神经递质水平的变化。值得注意的是，关于形态测量和示踪成像如何影响TCS对大脑活动的影响的研究很少。然而，形态测量学和脑束成像是电流通过的主要途径(我们可以在人脑中进行活体评估)来调节大脑活动，从而调节行为。 在本计划中，我们建议具体测试： 1.如果假tDCS是一个良好的控制条件，作为最常用的假tdcs方案之一，还有待MRI结果的检验； 2.刺激过程中和刺激后tdcs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(形态计量学、脑束成像)对这些影响的影响； 3.在刺激过程中和刺激后，tDCs对神经递质水平的影响的个体内可靠性，并表征了脑解剖(形态计量学、脑束成像)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。这些工具将具有通过建立大脑-行为因果关系来测试人类大脑功能的质量。

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.