Development of decision-making paradigms using noninvasive brain stimulation and neuroimaging

我们在日常生活中不断面临决策：糟糕的决策可能是由于对选择的分析不足或过于冒险（或过于谨慎）的方法，并可能对健康，安全和财务状况产生有害后果。我们在研究计划中追求的长期问题是，为什么有些人吃得好，适度饮酒，与其他人相比，运动？ 该研究计划的主要目标是开发一种同时结合非侵入性脑刺激和神经成像的新方法。具体来说，我们将在基于任务的功能性磁共振成像（fMRI）过程中提供经颅直流电刺激（tDCS），以研究人类的决策机制。这将使我们能够测试因果关系的大脑行为相互作用。 tDCS可以在体内调节人类认知功能。然而，当tDCS调节认知功能时，我们对大脑如何刺激知之甚少。多亏了我们之前的发现基金，我们开发了真实的时间捕获tDCS调节大脑的因果证据的协议。作为一个例子，我们提供了tDCS的背外侧前额叶皮层在健康受试者在静息状态的功能磁共振成像以及在磁共振波谱。静息状态的功能连通性由tDCS调节，在健康受试者中对比真实的和假tDCS条件时，加强右前额叶皮层和后扣带皮层之间的连通性。此外，与假tDCS相比，真实的tDCS在刺激健康成年人期间升高了纹状体谷氨酸和前额叶NAA水平。这项工作是第一次证明tDCS在MR采集过程中真正调节人脑基质。 我们建议通过将tDCS与基于任务的fMRI相结合来进行这一工作，以表征决策的认知和神经根源。在认知过程方面，我们建议专注于奖励寻求，冲动和抑制控制，以保持我们以前和正在进行的工作的可行性。我们还包括真实的奖励，例如在各种情况下的金钱和食物（食物限制，实验诱导的压力和注意力训练）。 这项研究计划背后的驱动力是决策能力及其相关的神经基质是我们日常生活中健康，健康，安全，财务和社会选择的重要方面的基础。决策已被广泛研究的背景下，经济学和从群体的角度来看，以及在临床人群中，很少有人知道的基本过程中涉及的生活方式决策的背景下，代表真实的生活。

We are continuously faced with decisions in our daily life: Poor decision-making may be due to inadequate analysis of choices or an excessively risky (or overly cautious) approach and can have deleterious consequences for health, safety, and financial well-being. The long-term question that we are pursuing in our research program is Why do some individuals eat well, drink moderately, and exercise compared to others? The main goal of the proposed research program is to develop a novel method that combines simultaneously noninvasive brain stimulation and neuroimaging. Specifically, we will deliver transcranial direct current stimulation (tDCS) during task-based functional magnetic resonance imaging (fMRI) to study decision-making mechanisms in humans. This will allow us to test for causal brain-behavior interactions. tDCS can modulate human cognitive functions in vivo. However we know little on how the brain is stimulated when tDCS modulates cognitive functions. Thanks to our previous Discovery grant, we developed protocols that capture, in real time, the cause and effect evidence of tDCS modulating the brain. As an example, we delivered tDCS over the dorsolateral prefrontal cortices in healthy subjects during resting-state fMRI as well as during MR spectroscopy. Resting state functional connectivity was modulated by tDCS, strengthening connectivity between the right prefrontal cortex and posterior cingulate cortex when contrasting real and sham tDCS conditions in healthy subjects. Also, real as compared to sham tDCS elevated striatal glutamate and prefrontal NAA levels during stimulation in healthy adults. This work is among the first demonstrations that tDCS truly modulates human brain substrates during MR acquisition. We propose to pursue this line of work by combining tDCS with task-based fMRI in order to characterize the cognitive and neural roots of decision-making. In terms of cognitive processes, we propose to focus on reward seeking, impulsivity, and inhibitory control in order to maintain feasibility following our previous and ongoing work. We also include real rewards such as money and food in various contexts (food restrictions, experimentally-induced stress and attentional biais training). The drive behind this research program is that decision-making abilities and its associated neural substrates underlie important aspects of wellness, health, security, financial and social choices in our daily life. Decision-making has been extensively studied in the context of economics and from a group perspective, as well as in clinical populations, and little is known on the fundamental processes involved in lifestyle decision-making in contexts representative of real life.