A new ultrasound technique will let researchers temporarily alter activity in deep brain regions of healthy volunteers, revealing for the first time how these hidden areas shape everyday decisions. The brain’s prefrontal cortex, responsible for flexible decision-making, is known to connect with older subcortical structures buried deep inside the brain. But because these deeper regions are hard to reach with non-invasive tools, scientists have only been able to study them in animals or infer their role from brain scans. This leaves a fundamental gap: we do not know whether the subcortex actively drives decision-making or merely relays signals. DeepStim will close that gap by using transcranial ultrasonic stimulation (TUS) to temporarily change activity in specific subcortical areas while volunteers perform decision tasks, combined with ultra-high-field 7T-fMRI to watch how the prefrontal cortex responds. This is fundamental science with no immediate practical application. But the subcortical circuits being studied are the same ones that malfunction in depression, addiction, and obsessive-compulsive disorder. Understanding their causal role in healthy decision-making could eventually point toward more targeted treatments for these conditions, replacing broad brain stimulation with precise, circuit-specific interventions.
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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.
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