Resolving mesoscale brainstem-prefrontal-striatal pathways underlying decisions upon salient events using...

Value-based decision-making engages brain-wide motivational, cognitive, and motor processes. Yet, information integration and gating that culminate in immediate decisions upon salient events likely occur within small neural nuclei and cortical layers at the mesoscale not resolved with conventional human neuroimaging. Using submillimeter-resolution 7 T functional MRI with acquisition-matched anatomical references and a lottery choice task incorporating salient superhigh stakes, we dissociated mesoscale operations spanning a brainstem-prefrontal-striatal pathway during choice and outcome processing. The locus coeruleus, caudate, and prefrontal cortex showed enhanced activity during superhigh-stake choices, while the substantia nigra/ventral tegmental area and nucleus accumbens additionally distinguished gains from losses. In contrast, gray-matter bridges between caudate and putamen were associated with faster responses. Laminar analyses revealed deeper prefrontal layers predominating during choice selection and superficial layers during outcome evaluation. Here, we show a mesoscale framework integrating brainstem modulation, striatal gating, and laminar cortical computation in human decision-making upon salient events.