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Towards real-world generalizability of a circuit for action-stopping

Abstract

Two decades of cross-species neuroscience research on rapid action-stopping in the laboratory has provided motivation for an underlying prefrontal–basal ganglia circuit. Here we provide an update of key studies from the past few years. We conclude that this basic neural circuit is on increasingly firm ground, and we move on to consider whether the action-stopping function implemented by this circuit applies beyond the simple laboratory stop signal task. We advance through a series of studies of increasing ‘real-worldness’, starting with laboratory tests of stopping of speech, gait and bodily functions, and then going beyond the laboratory to consider neural recordings and stimulation during moments of control presumably required in everyday activities such as walking and driving. We end by asking whether stopping research has clinical relevance, focusing on movement disorders such as stuttering, tics and freezing of gait. Overall, we conclude there are hints that the prefrontal–basal ganglia action-stopping circuit that is engaged by the basic stop signal task is recruited in myriad scenarios; however, truly proving this for real-world scenarios requires a new generation of studies that will need to overcome substantial technical and inferential challenges.

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Fig. 1: Cortico–basal ganglia–thalamocortical networks for action control in the stop signal task.
Fig. 2: Timing of events in the action-stopping network.
Fig. 3: From the laboratory to the real-world: gait.

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Acknowledgements

The authors gratefully acknowledge funding support from the US National Institutes of Health (NS106822 and DA026452) and comments on the manuscript from J. Rothwell.

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Glossary

Offline transcranial magnetic stimulation

(TMS). Non-invasive brain stimulation eliciting long-lasting after-effects. Typically delivered before a participant undergoes behavioural testing or neuroimaging.

Electrocorticography

(ECoG). Invasive electrophysiological technique that uses electrodes placed directly on the exposed surface of the brain to record electrical activity from the cerebral cortex.

Hyperdirect pathway

Pathway connecting cortical areas directly to the subthalamic nucleus, bypassing the striatum.

Electromyography

(EMG). Electrophysiological technique that uses electrodes placed on the skin over a muscle to record its electrical activity.

Online TMS

Non-invasive brain stimulation eliciting short-lived after-effects. Typically delivered while a participant undergoes behavioural testing or neuroimaging.

Conflict resolution

In the motor domain, the process of resolving competition between competing action plans.

Go–no-go task

A paradigm where the participant is required to perform speeded responses to a go cue and to withhold a response following a no-go cue.

Global motor system suppression

Suppression of motor system excitability detected in task-irrelevant muscle representations when stopping with another effector. Relies on transcranial magnetic stimulation and electromyography methods.

Premanifest Huntington disease

The presymptomatic phase of the disease in an individual carrying the genetic mutation causing it.

Agonist muscle

The muscles that, when activated, are primarily responsible for causing movement about a joint.

Gait

The normal pattern of limb movements underpinning locomotion.

Kohnstamm phenomenon

A long-lasting (10–60-s) involuntary muscle contraction that develops after a sustained, voluntary isometric contraction: after pushing your arm against a wall for a long period, you experience your arm rising.

Antagonist muscles

The muscles that, when activated, oppose the movement caused by the agonist muscles about a joint.

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Hannah, R., Aron, A.R. Towards real-world generalizability of a circuit for action-stopping. Nat Rev Neurosci 22, 538–552 (2021). https://doi.org/10.1038/s41583-021-00485-1

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