Opinion
Inhibition and the right inferior frontal cortex: one decade on

https://doi.org/10.1016/j.tics.2013.12.003Get rights and content

Highlights

  • The right inferior frontal cortex (rIFC) implements a brake over response tendencies.

  • This brake can be turned on totally or partially by external signals.

  • It can also be turned on by goals/intentions.

  • Damage to this region and/or its network contributes to impulse control disorders.

In our TICS Review in 2004, we proposed that a sector of the right inferior frontal cortex (rIFC) in humans is critical for inhibiting response tendencies. Here we survey new evidence, discuss ongoing controversies, and provide an updated theory. We propose that the rIFC (along with one or more fronto–basal–ganglia networks) is best characterized as a brake. This brake can be turned on in different modes (totally, to outright suppress a response; or partially, to pause), and in different contexts (externally, by stop or salient signals; or internally, by goals). We affirm inhibition as a central component of executive control that relies upon the rIFC and associated networks, and explain why rIFC disruption could generally underpin response control disorders.

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.).

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