BiologyMedicine

Atsushi Yoshida, Richard J. Krauzlis, O. Hikosaka

2026.4.24PROGRESS IN NEUROBIOLOGY

DOI: 10.1016/j.pneurobio.2026.102921

Abstract

The subthalamic nucleus (STN) is a core component of the basal ganglia circuitry, traditionally viewed as a “brake” that suppresses motor output via the indirect and hyperdirect pathways. While this model explains certain aspects of motor control, it fails to account for the complex involvement of the STN in dynamic, value-based behaviors. Movement-related increases in STN neuronal activity have been well documented across species, but the functional organization of these responses during value-based decisions has remained unclear. Here, we recorded 187 STN neurons from macaque monkeys performing a value-based sequential choice task. Data-driven clustering identified three functionally distinct populations. Two populations (comprising approximately 89% of task-responsive neurons) exhibited facilitative activity modulated by learned object value. Temporal alignment analysis revealed that the majority of these neurons were target-locked, suggesting a predominantly stimulus-driven evaluation signal rather than a strictly movement-locked command. A third, smaller population encoded a negative value signal upon presentation of unrewarded objects, independent of subsequent motor strategy. Response latencies of the facilitative STN populations systematically preceded those of functionally analogous populations in the GPe recorded during the same task paradigm, supporting an STN-GPe facilitative pathway for value-based action selection. These findings reveal a functional organization within the ventral STN in which evaluation of stimulus target value, beyond the traditional motor suppressive model, is the predominant mode of processing.

Citation format

YOSHIDA, Atsushi; KRAUZLIS, Richard J.; HIKOSAKA, O. Beyond the brake: The subthalamic nucleus predominantly facilitates action in non-human primates. PROGRESS IN NEUROBIOLOGY, 2026, 262: 102921–102921.