Shengtao Luo1,2,3 · Yuchen Fan1,2 · Feiyang Yu1,2 · Xiaopeng Zhou1,2 · Ke Hu1,2 · Hang Yi1,2 · Hui Zhou1,2 · Tao Li1,2 · Jiang‑Fan Chen1,2  · Liping Zhang1,2

1 The Molecular Neuropharmacology Laboratory and the Eye‑Brain Research Center, State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China 

2 Oujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health), School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China 

3 The Second People’s Hospital of Lishui, Lishui 323000, China

Abstract

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.

Keywords

Auditory feedback; Biofeedback; Volitional control; Volitional inhibition; BCI; Secondary motor cortex (M2); External globus pallidus (GPe)

[SpringerLink]