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

Samuel R. Krimmel (), Timothy O. Laumann, Roselyne J. Chauvin, Tamara Hershey, Jarod L. Roland, Joshua S. Shimony, Jon T. Willie, Scott A. Norris, Scott Marek, Andrew N. Van, Anxu Wang, Julia Monk, Kristen M. Scheidter, Forrest I. Whiting, Nadeshka Ramirez-Perez, Athanasia Metoki, Noah J. Baden, Benjamin P. Kay, Joshua S. Siegel, Hadas Nahman-Averbuch, Abraham Z. Snyder, Damien A. Fair, Charles J. Lynch, Marcus E. Raichle, Evan M. Gordon and Nico U. F. Dosenbach ()
Additional contact information
Samuel R. Krimmel: Washington University School of Medicine
Timothy O. Laumann: Washington University School of Medicine
Roselyne J. Chauvin: Washington University School of Medicine
Tamara Hershey: Washington University School of Medicine
Jarod L. Roland: Washington University School of Medicine
Joshua S. Shimony: Washington University School of Medicine
Jon T. Willie: Washington University School of Medicine
Scott A. Norris: Washington University School of Medicine
Scott Marek: Washington University School of Medicine
Andrew N. Van: Washington University School of Medicine
Anxu Wang: Washington University School of Medicine
Julia Monk: Washington University School of Medicine
Kristen M. Scheidter: Washington University School of Medicine
Forrest I. Whiting: Washington University School of Medicine
Nadeshka Ramirez-Perez: Washington University School of Medicine
Athanasia Metoki: Washington University School of Medicine
Noah J. Baden: Washington University School of Medicine
Benjamin P. Kay: Washington University School of Medicine
Joshua S. Siegel: New York
Hadas Nahman-Averbuch: Washington University School of Medicine
Abraham Z. Snyder: Washington University School of Medicine
Damien A. Fair: University of Minnesota
Charles J. Lynch: New York
Marcus E. Raichle: Washington University School of Medicine
Evan M. Gordon: Washington University School of Medicine
Nico U. F. Dosenbach: Washington University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-58172-z

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