Inhibition and the right inferior frontal
cortex
Adam R. Aron
1,2
, Trevor W. Robbins
3
and Russell A. Poldrack
2
1
Department of Psychiatry, University of Cambridge, Cambridge CB2 2QQ, UK
2
Department of Psychology, Franz Hall, Box 951563, University of California, Los Angeles, CA 90095, USA
3
Department of Experimental Psychology, Downing Street, University of Cambridge, Cambridge CB2 3EB, UK
It is controversial whether different cognitive functions
can be mapped to discrete regions of the prefrontal cor-
tex (PFC). The localisationist tradition has associated
one cognitive function – inhibition – by turns with
dorsolateral prefrontal cortex (DLPFC), inferior frontal
cortex (IFC), or orbital frontal cortex (OFC). Inhibition is
postulated to be a mechanism by which PFC exerts its
effects on subcortical and posterior-cortical regions to
implement executive control. We review evidence con-
cerning inhibition of responses and task-sets. Whereas
neuroimaging implicates diverse PFC foci, advances in
human lesion-mapping support the functional localiz-
ation of such inhibition to right IFC alone. Future
research should investigate the generality of this pro-
posed inhibitory function to other task domains, and its
interaction within a wider network.
Many researchers agree that the function of the prefrontal
cortex (PFC) is broadly one of ‘executive control’ (i.e. the
scheduling and optimizing of subsidiary processes imple-
mented by posterior cortical and subcortical regions; see
[1] for a review). There is, however, theoretical controversy
over whether subregions of PFC are functionally differen-
tiated. One influential view is that different areas within
PFC perform the same operation (i.e. ‘working memory’)
but for different sensory inputs [2] (but see [3]). Avariant of
the ‘working memory’ hypothesis is one which regards the
PFC as providing top-down bias of posterior cortical and
subcortical ‘modules’ [4]. Accordingly, the PFC acts like the
signalman at a railway junction; depending on the context,
different incoming traffic gets directed towards different
outcomes [1]. Another, complementary, view of PFC func-
tion is that it integrates events across time [5].
Meta-analysis of neuroimaging results suggests a
localization of function to a network of PFC regions. It
appears that, regardless of the particular contrast of tasks,
there is regularity of (bilateral) activation of dorsolateral
prefrontal cortex (DLPFC), inferior frontal cortex (IFC),
and dorsal anterior cingulate cortex (ACC), but not other
frontal regions [6]. This indicates a surprising sort of
specialization of the PFC: a specific frontal network con-
sistently recruited for solution of diverse cognitive problems.
Although it is not disputed that memory is a funda-
mental function of the PFC, nor that most neuroimaging
task comparisons activate the same set of PFC regions
(often including bilateral DLPFC, IFC and ACC), recent
advances suggest that the IFC, right-lateralized (Figure 1a),
can be identified with a particular function. We review
recent evidence from behavioural studies of patients with
unilateral PFC lesions. Lesion studies, unlike neuroimag-
ing, can establish which brain regions are necessary for
cognition, and advances in lesion-mapping technology,
using structural MRI, allow better lesion resolution. The
evidence supplements classic monkey-lesion work [7,8],by
showing that damage to the right IFC impairs indepen-
dent measures of executive control by disrupting inhi-
bition (specifically of responses and task-sets). This poses a
challenge to alternative views concerning the localization
of such inhibitory functions to DLPFC [9] or orbital frontal
cortex (OFC) [10] (see [11] for a review).
The right IFC and inhibitory control
Historically, an important paradigm for studying execu-
tive control has been the Wisconsin Card Sorting Test
(WCST). The subject sorts a series of cards on different
dimensions such as colour, number and shape. Once the
subject has established the currently appropriate rule
(e.g. ‘sort successive cards by color’), the experimenter
gives negative feedback, and the subject is required to
change classification to another dimension. Patients with
frontal cortical damage are notoriously bad at the change
stage (see [12] for a review) – often explained by
‘perseveration’ of the previously appropriate rule. How-
ever, because the WCST is complex, requiring not just
shifting – but hypothesis generation, memory, and so on –
any component could be affected by lesion damage. Hence,
researchers have used executive control paradigms that
more effectively decompose cognitive components. Two such
influential paradigms are response inhibition (see [13] for
a review), and task-set switching (see [14] for a review).
Damage to right IFC crucially affects performance in these
paradigms, apparently by disrupting inhibition. Addition-
ally, we review studies showing that wider areas of the
right PFC are required for the suppression of memories
and responses to visual or auditory distractors.
Response inhibition
Response inhibition is the cognitive process required to
cancel an intended movement. It is tested using Go/No-Go
and stop-signal tasks [13]. The subject is required toCorresponding author: Adam R. Aron (adamaron@psych.ucla.edu).
Review TRENDS in Cognitive Sciences Vol.8 No.4 April 2004
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perform speeded responses on Go trials (e.g. pressing a
button in response to the letters Q, P, T) and to inhibit
responding on (i) No-Go trials (e.g. to the letter X) or (ii)
Stop trials (when a beep is sounded). For Go/No-Go tasks
the index of inhibitory control is the number of errors a
subjectmakes onNo-Go trials (i.e. Goingwhen they should
not). For stop-signal tasks, the index of inhibitory control
is the duration of the stopping process, called the stop-
signal reaction time (SSRT) [13]. In neuroimaging studies
response inhibition consistently and especially activates
a right-lateralized inferior frontal cortex (IFC) region
(e.g. [15,16–21]), and this region (but not other regions of
right or left PFC) was shown to be crucial by a neuro-
psychological study of patients with unilateral right-PFC
damage [22]. The greater the damage to this region alone,
the worse the response inhibition, as indexed by SSRT
(Figure 1b,c). Lesions to a homologue of this region (the
inferior prefrontal convexity; see Box 1) also impaired
No-Go performance in monkeys [8], and it is note-
worthy that problems with response inhibition have
been widely documented in children and adults with
a diagnosis of attention-deficit hyperactivity disorder
(ADHD) (e.g. [23,24,25]). Structural MRI (e.g. [26,27]),
functional MRI [28,29] and EEG (e.g. [30]) evidence
strongly suggests that a right-frontal (especially inferior
frontal) deficit underlies impaired response inhibition
in this group.
Task-set switching
Changing from performing one task to another exercises
executive control. A precise measure is given by the task-
set switching paradigm (for a review see [14]), which
measures switching in terms of the time taken to switch
compared with repeating a task (the ‘switch cost’). In brief,
subjects perform a series of trials of task A and then switch
to performing a series of task B. For each subject, the
switch cost is computed by subtracting the average
reaction time (RT) of non-switch trials from the average
RT of switch trials. Intuitively, it is clear that having to
switch task requires configuring a new attentional and
response set (e.g. getting ready to take up your cup once
you have finished pouring the coffee). Apart from taking
time to load new stimulus–response (S–R) mappings and
choosing which attributes to attend to, changing tasks
might require the inhibition of competing S–R links
specified by the now inappropriate task, or even the
inhibition of the entire task [31].
Converging evidence suggests the right frontal
cortex might subserve inhibitory processes underlying
switching. Neuroimaging studies of the WCST [32–34],
reversal learning (e.g. [32,35]) and task-set switching
(e.g. [36,37–39]) have especially reported activation of
DLPFC and right IFC (although sometimes there is
co-activation of left frontal cortex). A direct neuroimaging
comparison of a form of switching (the WCST) and
response inhibition demonstrated a common locus in the
right IFC [18]. A combined EEG/fMRI study investigating
Go/No-Go and Switch/Repeat factors suggested that the
right IFCwas responsible for ‘switching into a suppression
mode’ [40]. Most persuasively of all, a study of patients
with unilateral PFC damage demonstrated that the greater
the damage to the right IFC, the greater the switch cost
[41] (Figure 2a,b). This was not true for damage to any
other region of right or left PFC. The switch deficit of these
patients with right frontal damage appeared most consis-
tent with impaired ability to suppress irrelevant responses
or irrelevant task-sets on the switch trial relative to non-
switch trials. In addition to being reliably correlated with
the amount of damage to the right IFC, the switch cost was
also reliably correlatedwith the SSRTmeasure of response
inhibition (Figure 2c). This suggests disruption to a
common mechanism underlying performance of the two
independent tasks.
Inhibition during memory retrieval
In the course of daily life we often try to ‘push out of mind’
unpleasant events or memories. Such blocking of memory
retrieval could be like overriding a pre-potent motor
Figure 1. Disruption of response inhibition by right inferior frontal cortex (IFC) damage. (a) A single coronal slice through a structural template of the human brain. The
thick white line demarcates the IFC in the right hemisphere. For each patient, the volume of lesion damage to this region was computed from a structural MRI scan (see [22]
for methods). (b) Extent of damage to right IFC, but not other regions, correlated with a response-inhibition measure (indexed by stop-signal reaction time, SSRT): greater
damage leads to slower inhibition ðr ¼ 0:83; P , 0:0001Þ [22]. (c) There was also a reliable correlation between SSRT and damage to a more specific region of IFC, the pars
opercularis (a posterior-ventral region; see Box 1).
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