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A cortico-subthalamic circuit rapidly engages and releases inhibition of specific movements depending on the environmental context
Journal article   Open access   Peer reviewed

A cortico-subthalamic circuit rapidly engages and releases inhibition of specific movements depending on the environmental context

Cheol Soh, Mario Hervault, Nathan H Chalkley, Kien Huynh, Qiang Zhang, Ergun Y Uc, Jeremy D W Greenlee and Jan R Wessel
PLoS biology, Vol.24(4), e3003635
04/24/2026
DOI: 10.1371/journal.pbio.3003635
PMCID: PMC13132434
PMID: 42030369
url
https://doi.org/10.1371/journal.pbio.3003635View
Published (Version of record) Open Access

Abstract

Response inhibition is an important cognitive control mechanism that enables flexible behavior by stopping inappropriate actions. Intracranial recordings across species have identified a neural circuit that implements response inhibition via the subthalamic nucleus of the basal ganglia. However, this work has been limited to simple tasks, in which unequivocal, salient "stop"-signals require the inhibition of all ongoing responses. Notably, response inhibition in the real world is substantially different. Real-world response inhibition is selective: it occurs only after specific salient signals ('stimulus-selectivity') and stops only specific movements, while others continue ('response-selectivity'). If and how the fronto-subthalamic system implements selective inhibition is largely unknown. Here, we recorded subthalamic local field potentials and scalp-EEG in humans performing a novel, selective inhibition task. Salient signals either required stopping all initiated responses (global inhibition), stopping only some responses (response-selective inhibition), or continuing all responses-i.e., ignoring the signal (which ensures stimulus-selectivity). All three signals initially triggered a common fronto-subthalamic inhibitory process, signified by a rapid increase in β-burst activity. During global inhibition, subthalamic β-bursting subsequently increased above baseline, persisting for over a second. During response-selective inhibition, this activity was delayed, which enabled a second bout of disinhibition and allowed appropriate responses to continue. Throughout this period, frontal cortical and subthalamic β-band activity were tightly coupled. This shows that selective inhibition is accompanied by rapid, context-dependent engagement and release of fronto-subthalamic inhibition. Moreover, subthalamic activity lasted substantially longer than assumed by classic behavioral-computational models. This supports recent theoretical models that assume protracted response inhibition during action-stopping.

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