Abstract
Controlling action and thought requires the capacity to stop mental processes. Over the past two decades, evidence has grown that a domain-general inhibitory control mechanism supported by the right lateral prefrontal cortex achieves these functions. However, current views of the neural mechanisms of inhibitory control derive largely from research into the stopping of action. Whereas action stopping is a convenient empirical model, it does not invoke thought inhibition and cannot be used to identify the unique features of this process. Here, we review research that addresses how organisms stop a key process that drives thoughts: memory retrieval. This work has shown that retrieval stopping shares right dorsolateral and ventrolateral prefrontal mechanisms with action stopping, consistent with a domain-general inhibitory control mechanism, but also recruits a distinct fronto-temporal pathway that determines the success of mental control. As part of this pathway, GABAergic inhibition within the hippocampus influences the efficacy of prefrontal control over thought. These unique elements of mental control suggest that hippocampal disinhibition is a transdiagnostic factor underlying intrusive thinking, linking the fronto-temporal control pathway to preclinical models of psychiatric disorders and fear extinction. We suggest that retrieval-stopping deficits may underlie the intrusive thinking that is common across many psychiatric disorders.
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Acknowledgements
This work was supported by Medical Research Council grant MC-A060-5PR00 (M.C.A.).
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Glossary
- Default mode network
-
(DMN). A group of functionally connected brain regions (including the hippocampus) that are more active when the brain is in a resting state, not focused on external tasks, and engaged in internally oriented thoughts.
- Effective connectivity
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An estimate of the influence that one brain region exerts over another, often assessed with model-based connectivity approaches such as dynamic causal modelling to determine the direction and strength of causal interactions between brain regions.
- Fear extinction
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A learning process through which a conditioned fear response diminishes after repeated exposure to the conditioned stimulus without the aversive outcome.
- Functional connectivity
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The level of statistical dependence over time (for example, correlations) of the activity of different brain regions, putatively reflecting the degree to which those regions may be communicating and working together in coordinated fashion.
- Inhibitory control
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A core cognitive control function that enables organisms to suppress dominant motor, cognitive or affective responses to stimuli if circumstances or goals require those responses to be stopped.
- Intrusive thoughts
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Involuntarily retrieved ideas, images or memories that interrupt ongoing thought and that are often distressing and repeated.
- Multiple-demand control network
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A group of brain regions, primarily in the frontal and parietal cortex, that are activated across a wide range of cognitively demanding tasks, suggesting a role in flexible cognitive control and integration.
- Pattern completion
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A key mechanism of memory retrieval, supported by the hippocampus, which allows an organism to retrieve a full event, by reinstating the full pattern of activity across neurons representing the event, when a subset of those neurons are activated by cue input.
- Representations
-
A pattern of neural activity that encodes information about stimuli, events, concepts or actions, allowing the brain to interpret, store and manipulate information to guide perception, thought and behaviour.
- Stop-signal action-stopping task
-
A task that quantifies motor response inhibition speed by having participants respond as quickly as possible to ‘go’ stimuli and then, on a small fraction of trials, withhold that response when a ‘stop’ signal tone occurs. By progressively increasing the delay after motor preparation begins at which the stop tone occurs, the challenge of stopping the response increases, and an estimate of the speed of the underlying stopping process can be derived.
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Anderson, M.C., Crespo-Garcia, M. & Subbulakshmi, S. Brain mechanisms underlying the inhibitory control of thought. Nat. Rev. Neurosci. 26, 415–437 (2025). https://doi.org/10.1038/s41583-025-00929-y
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DOI: https://doi.org/10.1038/s41583-025-00929-y
