Effects of deep non-invasive brain stimulation on emotion, motivation and decision making

人类不断调整自己的决定，以适应内部和外部环境的变化。这种灵活性通常与前额叶皮层（PFC）有关，这是人类大脑中最独特的部分。然而，PFC与大脑深处的遗传学上较老的皮质下区域高度相互关联。这些区域在健康人类中更难研究，但动物研究表明它们对决策至关重要。目前，我们还不知道下皮层和PFC如何相互作用。DeepStim将使用尖端工具来测试一个总体假设，即PFC导致的人类决策过程严重依赖于与深层皮层下区域的相互作用。DeepStim将克服研究人类皮层下的两个主要障碍。首先，缺乏非侵入性的工具来调节大脑深处的活动：通过使用经颅超声刺激（TUS），我最近在猕猴身上开创了一项技术，我将非侵入性地改变人类皮层下区域，首次研究它们的因果作用。其次，缺乏可靠的空间分辨皮层下神经成像信号：通过将最先进的超高场神经成像与我最近开发的新皮层下图谱相结合，我将以前所未有的分辨率研究人类皮层下。DeepStim有三个关键目标：（1）在不同任务阶段应用TUS，以确定皮层下对决策的因果贡献;（2）结合联合收割机和7 T-fMRI研究皮质下与PFC的相互作用;（3）使用新的图谱和选择性TUS刺激分离单个皮质下核团的贡献。DeepStim将揭示皮质下区域在人类决策中的因果作用。这种超越相关性工作并考虑决策回路的分布式性质的能力将为人类神经科学开辟一个新的视野，因为这里刺激的皮层下回路在精神疾病中经常功能失调，因此具有相当大的翻译潜力。

Humans constantly adapt their decisions to changes in their internal and external circumstances. This flexibility is typically associated with prefrontal cortex (PFC), the most uniquely human part of the brain. However, PFC is highly interconnected with phylogenetically older subcortical regions deep within the brain. These regions are more difficult to study in healthy humans, yet animal work suggests they are vital for decision-making. Currently, we do not understand how subcortex and PFC interact. DeepStim will use cutting-edge tools to test the overarching hypothesis that human decision processes attributed to PFC critically rely on interactions with deep subcortical regions. DeepStim will overcome two major barriers for studying human subcortex. First, the lack of non-invasive tools to modulate activity deep within the brain: by using transcranial ultrasonic stimulation (TUS), a technique I recently pioneered in macaques, I will non-invasively alter human subcortical areas to study their causal role for the first time. Second, the lack of reliable spatially resolved subcortical neuroimaging signals: by combining state-of-the-art ultra-high field neuroimaging with new subcortical atlases I recently developed, I will study human subcortex at unprecedented resolution.DeepStim has three key aims: (1) apply TUS at different task stages to determine the causal contribution of subcortex to decision-making; (2) combine TUS and 7T-fMRI to study subcortical interactions with PFC; (3) dissociate the contribution of individual subcortical nuclei using new atlases and selective TUS stimulation.DeepStim will reveal the causal role of subcortical regions in human decision-making. This ability to move beyond correlational work and consider the distributed nature of decision circuits will open a new horizon for human neuroscience that holds considerable potential for translation because the subcortical circuits stimulated here are frequently dysfunctional in mental illness.