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

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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.