Sub-second Dopamine and Serotonin Signaling in Human Striatum during Perceptual Decision-Making

Recent animal research indicates that dopamine and serotonin, neuromodulators traditionally linked to appetitive and aversive processes, are also involved in sensory inference and decisions based on such inference. We tested this hypothesis in humans by monitoring sub-second striatal dopamine and serotonin signaling during a visual motion discrimination task that separates sensory uncertainty from decision difficulty in a factorial design. Caudate nucleus recordings (n = 4) revealed multi-scale encoding: in three participants, serotonin tracked sensory uncertainty, and, in one participant, both dopamine and serotonin tracked deviations from expected trial transitions within our factorial design. Putamen recordings (n = 1) supported a cognition-action separation between caudate nucleus and putamen—a striatal sub-division unique to primates—with both dopamine and serotonin tracking decision times. These first-of-their-kind observations in the human brain reveal a role for sub-second dopamine and serotonin signaling in non-reward-based aspects of cognition and action. •Dopamine and serotonin are measured in human striatum during awake decision-making•Serotonin tracks sensory uncertainty in caudate nucleus•Dopamine and serotonin track sensory statistics in caudate nucleus•Dopamine and serotonin track decision times in putamen Dopamine and serotonin have traditionally been linked to reward processing. Bang, Kishida et al. show in the human brain that these neuromodulators also play a role in non-reward-based aspects of cognition and behavior, including rapid perceptual decision processes and action.