The human brainstem's red nucleus was upgraded to support goal-directed action.

The red nucleus, a large brainstem structure, coordinates limb movement for locomotion in quadrupedal animals. In humans, its pattern of anatomical connectivity differs from that of quadrupeds, suggesting a different purpose. Here, we apply our most advanced resting-state functional connectivity based precision functional mapping in highly sampled individuals (n = 5), resting-state functional connectivity in large group-averaged datasets (combined n ~ 45,000), and task based analysis of reward, motor, and action related contrasts from group-averaged datasets (n > 1000) and meta-analyses (n > 14,000 studies) to precisely examine red nucleus function. Notably, red nucleus functional connectivity with motor-effector networks (somatomotor hand, foot, and mouth) is minimal. Instead, connectivity is strongest to the action-mode and salience networks, which are important for action/cognitive control and reward/motivated behavior. Consistent with this, the red nucleus responds to motor planning more than to actual movement, while also responding to rewards. Our results suggest the human red nucleus implements goal-directed behavior by integrating behavioral valence and action plans instead of serving a pure motor-effector function.