Trends in Cognitive Sciences
OpinionInhibition and the right inferior frontal cortex: one decade on
Introduction
Since Ferrier in the 19th century [1], it has been posited that one of the functions of the prefrontal cortex (PFC) is to inhibit behavior. In our previous review [2], we defined inhibition psychologically as ‘the suppression of inappropriate responses, stimulus–response mappings or task-sets when the context changes, and suppression of interfering memories during retrieval.’ We claimed that such inhibition depends on the rIFC (uniquely among PFC regions) and that, neurally, one-way rIFC could implement its function is via a subcortical projection to the subthalamic nucleus (STN). Here we reappraise these claims based on 10 years of evidence and in light of several challenges (e.g., 3, 4, 5, 6, 7). We focus on a narrower psychological definition of inhibition, that is, of response tendencies. This is an exemplary case in which there is (i) the largest amount of evidence, (ii) a clear operationalization at the behavioral level via stopping or slowing, and (iii) a relation to one or more prefrontal–basal–ganglia circuits with the requisite features for suppression of motor responses.
We start by reviewing the evidence that the rIFC is critical for stopping action outright. We then address two major branches of criticism: whether the rIFC is the critical PFC node for inhibition and whether the rIFC implements a function other than inhibition. We then show that the rIFC is also important for pausing and braking responses, in addition to outright stopping. This broader role for the rIFC could explain why rIFC dysfunction occurs in neuropsychiatric disorders – a weakness in this system will affect many types of inhibitory response control. Finally, we discuss the reverse inference problem – under what circumstances can researchers interpret rIFC activation as indicating inhibition in their task?
Section snippets
The role of the rIFC within a network for outright action stopping
To properly engage a neurocognitive response inhibition process, a task must require the stopping of a response that is already initiated. The stop signal task [8] does this, as do some versions of the Go/NoGo task, and some other response-overriding tasks 9, 10, 11, 12. Much research now shows that the rIFC is activated by, and is critical for, outright stopping (reviewed in 1, 13, 14, 15, 16, 17). Other studies, using high spatio-temporal resolution electrocorticography (ECoG), show that rIFC
Criticisms of the rIFC/inhibition hypothesis
Our theory that the rIFC implements inhibitory control during the stopping of actions has been challenged from two directions: whether the rIFC is the critical locus for inhibition, and whether the function of the rIFC is best characterized as inhibition or some other function.
Is the rIFC the locus of inhibitory control?
We argued, based on lesion data in left and right hemispheres 43, 44, 45 (also see [46]) that right-lateralized IFC is critical for inhibitory control. Swick et al. [17] challenged this by showing that patients with left IFC/insula damage more often responded on NoGo trials than controls. However, there was a deficit even in a 50% Go/NoGo condition. When only 50% of trials require NoGo it is unlikely that subjects have to stop an initiated response; instead they are probably making a decision
Is inhibitory control the function of the rIFC?
Some authors propose that the rIFC implements attentional monitoring or attentional detection rather than inhibition. We discuss these in turn.
Following an extensive analysis of frontal lesion results, Stuss and Alexander [4] commented that ‘The interpretation of our data, including the classic “inhibitory” tasks such as the Stroop, did not have to rely on inhibition as an explanatory phenomenon. Apparent inhibitory processes can be explained by our triad of frontal processes: energization;
Braking: when stopping is partial
If the putative rIFC-mediated inhibition function is to extend into everyday life then it should be recruited endogenously 70, 71 as well as by external signals – for example, when a dieter resists reaching for a box of chocolates. Endogenously triggered inhibition can be studied using a paradigm in which people anticipate they might have to stop (Figure 1A). Subjects respond more slowly on Go trials where stopping is anticipated (Maybe Stop) compared to Go trials in which it is not (No Stop).
The rIFC in impulse control disorders
Many studies have shown slower stopping and functional or structural changes in the rIFC for patients versus controls (reviewed in 1, 13). To take two recent examples: a large fMRI study in 1896 adolescent volunteers [51] showed that functional activation in right frontal cortex (i) was greater for those with faster than slower SSRT, (ii) discriminated those who had taken illicit drugs from those who had not, and (iii) was related to a polymorphism in a noradrenaline transporter gene
Reverse inference, but with more precision?
Activation of the rIFC is often taken to mean that inhibition is an underlying function of a task – a ‘reverse inference’ [84]. Indeed, we made reverse inferences in the above sections on unconscious, automatic, and tonic inhibition. Yet the reverse inference is only valid if rIFC activation is selective to inhibition. However, the rIFC receives input from auditory and visual streams [85], connects to many brain regions, and doubtless has many functions, including prosody [86], imitation [87],
Concluding remarks
The evidence over the last 10 years corroborates our proposal that a sector of the rIFC implements inhibitory control via a wider prefrontal–basal ganglia network when actions are stopped outright. Moreover, recent evidence extends the role of the rIFC by showing that it can also be triggered (i) by an external (infrequent or unexpected) signal to pause action, (ii) by an internal goal to slow action, (iii) by a subliminal stimulus or a stimulus with a learned association with stopping, and
Acknowledgments
Thanks to Nicole Swann, Scott Freeman, and four reviewers (including Chris Chambers and Hugh Garavan) for constructive comments on the manuscript. We appreciate funding from National Institutes of Health (NIH) National Institute on Drug Abuse (NIDA) Grant DA026452 (to A.R.A.); the Wellcome Trust Grant 089589/Z/09/Z and a joint award from the Medical Research Council and Wellcome Trust, G00001354 (to T.W.R.); and the James S. McDonnell Foundation (to R.A.P.).
References (109)
- et al.
Inhibition and impulsivity: behavioral and neural basis of response control
Prog. Neurobiol.
(2013) Inhibition and the right inferior frontal cortex
Trends Cogn. Sci.
(2004)The role of the right inferior frontal gyrus: inhibition and attentional control
Neuroimage
(2010)- et al.
Models of response inhibition in the stop-signal and stop-change paradigms
Neurosci. Biobehav. Rev.
(2009) Insights into the neural basis of response inhibition from cognitive and clinical neuroscience
Neurosci. Biobehav. Rev.
(2009)Common and unique components of response inhibition revealed by fMRI
Neuroimage
(2005)Roles for the pre-supplementary motor area and the right inferior frontal gyrus in stopping action: electrophysiological responses and functional and structural connectivity
Neuroimage
(2012)The role of the subthalamic nucleus in response inhibition: evidence from local field potential recordings in the human subthalamic nucleus
Neuroimage
(2012)The role of the pre-supplementary motor area in the control of action
Neuroimage
(2007)Cortico-subthalamic white matter tract strength predicts interindividual efficacy in stopping a motor response
Neuroimage
(2012)
Response inhibition is associated with white matter microstructure in children
Neuropsychologia
Network modelling methods for FMRI
Neuroimage
Primary motor cortex and movement prevention: where Stop meets Go
Neurosci. Biobehav. Rev.
Functional significance of the cortico-subthalamo-pallidal ‘hyperdirect’ pathway
Neurosci. Res.
Association between response inhibition and working memory in adult ADHD: a link to right frontal cortex pathology?
Biol. Psychiatry
Time-course of “off-line” prefrontal rTMS effects – a PET study
Neuroimage
In opposition to inhibition
The Psychology of Learning and Motivation
Current advances and pressing problems in studies of stopping
Curr. Opin. Neurobiol.
Prefrontal neurons coding suppression of specific saccades
Neuron
Neural correlates of blink suppression and the buildup of a natural bodily urge
Neuroimage
Can cognitive processes be inferred from neuroimaging data?
Trends Cogn. Sci.
Functional role of the ventrolateral prefrontal cortex in decision making
Curr. Opin. Neurobiol.
Reorganization of functional and effective connectivity during real-time fMRI-BCI modulation of prosody processing
Brain Lang.
Learning arbitrary visuomotor associations: temporal dynamic of brain activity
Neuroimage
Sub-centimeter scale functional organization in human inferior frontal gyrus
Neuroimage
Opposing mechanisms support the voluntary forgetting of unwanted memories
Neuron
A neuroanatomical model of prefrontal inhibitory modulation of memory retrieval
Neurosci. Biobehav. Rev.
Inhibition of action, thought, and emotion: a selective neurobiological review
Appl. Prev. Psychol.
A unified framework for inhibitory control
Trends Cogn. Sci.
Cognitive control reflects context monitoring, not motoric stopping, in response inhibition
PLoS ONE
Is there a dysexecutive syndrome?
Philos. Trans. R. Soc. Lond. B: Biol. Sci.
The Neurobiology of the Prefrontal Cortex: Anatomy, Evolution, and the Origin of Insight
Disinhibition: more than a misnomer
Soc. Neurosci.
Function and structure of the right inferior frontal cortex predict individual differences in response inhibition: a model-based approach
J. Neurosci.
The role of the ventrolateral frontal cortex in inhibitory oculomotor control
Brain
Cortical and subcortical interactions during action reprogramming and their related white matter pathways
Proc. Natl. Acad. Sci. U.S.A.
A computational model of inhibitory control in frontal cortex and basal ganglia
Psychol. Rev.
Localizing performance of go/no-go tasks to prefrontal cortical subregions
Curr. Opin. Psychiatry
Cognitive control and right ventrolateral prefrontal cortex: reflexive reorienting, motor inhibition, and action updating
Ann. N. Y. Acad. Sci.
Left inferior frontal gyrus is critical for response inhibition
BMC Neurosci.
Intracranial EEG reveals a time- and frequency-specific role for the right inferior frontal gyrus and primary motor cortex in stopping initiated responses
J. Neurosci.
Chronometric electrical stimulation of right inferior frontal cortex increases motor braking
J. Neurosci.
The subthalamic nucleus is involved in successful inhibition in the stop-signal task: a local field potential study in Parkinson's disease
Exp. Neurol.
Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus
J. Neurosci.
Subcortical processes of motor response inhibition during a stop signal task
Neuroimage
Role for subthalamic nucleus neurons in switching from automatic to controlled eye movement
J. Neurosci.
Canceling actions involves a race between basal ganglia pathways
Nat. Neurosci.
The role of the right pre-supplementary motor area in stopping action: two studies with event-related transcranial magnetic stimulation
J. Neurophysiol.
Aging and inhibitory control of action: cortico-subthalamic connection strength predicts stopping performance
J. Neurosci.
Functional connectivity delineates distinct roles of the inferior frontal cortex and presupplementary motor area in stop signal inhibition
J. Neurosci.
Cited by (1417)
Impulsivity and neural correlates of response inhibition in bipolar disorder and their unaffected relatives: A MEG study
2024, Journal of Affective Disorders