The Secondary Motor Cortex-External Globus Pallidus Pathway Regulates Auditory Feedback of Volitional Control

Effective use of brain-computer interfaces (BCIs) requires the ability to suppress a planned action (volitional inhibition) for adaptable control in real-world scenarios, but their mechanisms are unclear. Here, we used fiber photometry to monitor external globus pallidus (GPe) and subthalamic nucleus (STN) neurons' activity in mice during a volitional stop-signal task (67% GO, 33% NO-GO). GPe/STN neurons (receiving M2 projections) responded to auditory cues, feedback, and rewards in both trials. Importantly, chemogenetic activation of the M2-GPe pathway enhanced volitional inhibition by modulating auditory feedback response, yet inhibited GPe neurons' feedback response. Furthermore, time-locked optogenetic inhibition of M2-projecting GPe neurons at auditory feedback also enhanced volitional inhibition via prolonged GO trial response times. Collectively, these findings identified the M2-GPe pathway for auditory biofeedback to improve volitional control, offering novel avenues for the advancement of neural interfaces for biofeedback and enhancement of BCI efficacy.