Function and localization within rostral prefrontal cortex

Article (PDF Available)inPhilosophical Transactions of The Royal Society B Biological Sciences 362(1481):887-99 · May 2007with44 Reads
DOI: 10.1098/rstb.2007.2095 · Source: PubMed
Abstract
We propose that rostral prefrontal cortex (PFC; approximating area 10) supports a cognitive system that facilitates either stimulus-oriented (SO) or stimulus-independent (SI) attending. SO attending is the behaviour required to concentrate on current sensory input, whereas SI attending is the mental processing that accompanies self-generated or self-maintained thought. Regions of medial area 10 support processes related to the former, whilst areas of lateral area 10 support processes that enable the latter. Three lines of evidence for this 'gateway hypothesis' are presented. First, we demonstrate the predicted patterns of activation in area 10 during the performance of new tests designed to stress the hypothetical function. Second, we demonstrate area 10 activations during the performance of established functions (prospective memory, context memory), which should hypothetically involve the proposed attentional system. Third, we examine predictions about behaviour-activation patterns within rostral PFC that follow from the hypothesis. We show with meta-analysis of neuroimaging investigations that these predictions are supported across a wide variety of tasks, thus establishing a general principle for functional imaging studies of this large brain region. We then show that while the gateway hypothesis accommodates a large range of findings relating to the functional organization of area 10 along a medial-lateral dimension, there are further principles relating to other dimensions and functions. In particular, there is a functional dissociation between the anterior medial area 10, which supports processes required for SO attending, and the caudal medial area 10, which supports processes relating to mentalizing.
Function and localization within rostral prefrontal
cortex (area 10)
Paul W. Burgess
1,
*
, Sam J. Gilbert
1
and Iroise Dumontheil
1,2
1
UCL Institute of Cognitive Neuroscience and Psychology Department, University College London,
17 Queen Square, London WC1E 6BT, UK
2
MRC Cognition and Brain Sciences Unit, Cambridge CB2 7EF, UK
We propose that rostral prefrontal cortex (PFC; approximating area 10) supports a cognitive system
that facilitates either stimulus-oriented (SO) or stimulus-independent (SI ) attending. SO attending
is the behaviour required to concentrate on current sensory input, whereas SI attending is the mental
processing that accompanies self-generated or self-maintained thought. Regions of medial area 10
support processes related to the former, whilst areas of lateral area 10 support processes that enable
the latter. Three lines of evidence for this ‘gateway hypothesis’ are presented. First, we demonstrate
the predicted patterns of activation in area 10 during the performance of new tests designed to
stress the hypothetical function. Second, we demonstrate area 10 activations during the performance
of established functions (prospective memory, context memory), which should hypothetically involve
the proposed attentional system. Third, we examine predictions about behaviour–activation patterns
within rostral PFC that follow from the hypothesis. We show with meta-analysis of neuroimaging
investigations that these predictions are supported across a wide variety of tasks, thus establishing a
general principle for functional imaging studies of this large brain region. We then show that while the
gateway hypothesis accommodates a large range of findings relating to the functional organization of
area 10 along a medial–lateral dimension, there are further principles relating to other dimensions
and functions. In particular, there is a functional dissociation between the anterior medial area 10,
which supports processes required for SO attending, and the caudal medial area 10, which supports
processes relating to mentalizing.
Keywords: frontal lobes; executive function; BA 10; anterior prefrontal cortex; neuroimaging;
neuropsychology
1. INTRODUCTION
Area 10 of the brain (also termed ‘rostral prefrontal
cortex (PFC)’, ‘anterior PFC’ or ‘frontopolar cortex’)
presents one of the most fascinating puzzles in
cognitive neuroscience. There are many good reasons
to suppose that it plays a critical part in the higher
cognitive functions of humans yet, until very recently,
virtually nothing was known about the mental
processes that it might support.
The first reason for supposing that this region is
important for human cognition is simply its size. It is a
very large brain region in humans, covering at least
25–30 cubic cm (Christoff et al. 2001; Semendeferi
et al. 2001). Indeed, it is the largest single architectonic
region of the PFC (Christoff et al. 2001; Ongur et al.
2003). The second reason is that it is relatively larger in
the human brain than in any other animal, including
the great apes (Semendeferi et al. 2001; Holloway
2002). The third reason for supposing that area 10
supports cognition, which is both important and
peculiar to humans, is its structure. It has a lower cell
density in humans than that found in monkeys and
apes. This has been interpreted as meaning that the
supragranular layers of area 10 in humans have more
space available for connections with other higher-order
association areas than in other animals (Semendeferi
et al. 2001). Support from this view comes from
findings that the number of dendritic spines per cell
and the spine density are higher than in comparable
cortical areas (Jacobs et al. 2001; Semendeferi et al.
2001). Furthermore, area 10 is also unusual in that it is
the only PFC region that is almost exclusively
connected to other supramodal areas within PFC and
elsewhere (for a review, see Ramnani & Owen 2004).
The fourth reason for supposing a role for this region in
higher cognitive functions is that rostral PFC shows
remarkably late developmental maturation. It is
probably the last brain region to achieve myelination
(Bonin 1950) and is one of the brain regions with the
highest rates of brain growth between 5 and 11 years
(Sowell et al. 2004). Indeed, reductions in grey matter
density continue from adolescence to young adulthood
(Sowell et al. 1999).
On these grounds, it is a reasonable hope that
gaining an understanding of the role of this region in
human cognition may provide a key to how the brain
affects some of the behaviours peculiar to humans and,
perhaps, thereby the symptoms that accompany its
dysfunction (e.g. certain forms of psychological
disorder).
Phil. Trans. R. Soc. B (2007) 362, 887–899
doi:10.1098/rstb.2007.2095
Published online 2 April 2007
One contribution of 14 to a Discussion Meeting Issue ‘Mental
processes in the human brain’.
* Author for correspondence (p.burgess@psychol.ucl.ac.uk).
887 This journal is q 2007 The Royal Society
However, scientific evidence that might bear on
the issue has only begun to emerge over the last 10
yearsorso.Therearemanyreasonsforthis
situation. For instance, the extreme difference in
size and structure of this region in humans when
compared with other animals limits the degree to
which one might safely generalize from animal data
to human experience. Furthermore, it is difficult to
record from, and lesion, thisregioninnon-human
primates for practical anatomical considerations.
Other cognitive neuroscience methods also face
limitations. For instance, until very recently, the
available electrophysiological methods have not
had the required spatial resolution to collect data
from different sub-regions within the frontal
lobes. Transcranial magnetic stimulation studies of
rostral PFC have also proved difcult for ana-
tomical reasons (although these may not prove
insurmountable).
Moreover, human lesion studies into the functions
of this area have not, until very recently, been
conducted. Partly, this has been due to the length of
time it takes to collect sufficient data for this type of
investigation (typically several years). But it is also
because, traditionally, rostral PFC lesions have been
considered neuropsychologically and neurologically
‘silent’. In other words, they do not cause impairments
easily elicited during the standard neurological or
neuropsychological consultation. Thus, until very
recently, virtually the only available evidence originated
from the relatively new method of functional brain
imaging.
Until the late 1990s, these neuroimaging findings
were, however, largely restricted to the findings of
rostral PFC haemodynamic changes associated with a
particular cognitive function (e.g. episodic memory),
rather than emanating from investigations that had the
specific aim of discovering the functions of the brain
region (but see, in particular, the studies by Kalina
Christoff, Etienne Koechlin, and Raichle et al. 2001).
Unfortunately, these findings did not provide a firm
basis for theorizing, since there seemed to be little
obvious similarity between the paradigms that pro-
voked area 10 activation. Indeed, area 10 activations
could be found during the performance of just about
any kind of task, ranging from the simplest (e.g.
conditioning paradigms; Blaxton et al. 1996) to highly
complex tests, involving memory and judgement (e.g.
Koechlin et al. 1999; Burgess et al. 2001, 2003; Frith &
Frith 2003) or problem solving (e.g. Christoff et al.
2001).
It was in this context that we started our
research programme. It differed from most in that
it had the specific aim of attempting to discover the
cognitive functions of the brain area (BA) 10. This
paper describes the stages that we have followed,
and our conclusions at this early, but we hope
promising, stage. We do not intend to provide an
overview of the important work on this topic by our
colleagues elsewhere. For this, the interested reader
is referred to reviews by Grady (1999), Ramnani &
Owen (2004),Burgesset al.(2005, 2006b)and
Gilbert et al. (2006c).
2. STAGE 1: OBSERVATIONS OF EVERYDAY
MULTITASKING PROBLEMS IN BRAIN-DAMAGED
PATIENTS
The starting point for our investigations was a puzzling
clinical observation that had been noted since the
1930s (e.g. Penfield & Evans 1935; see also Brickner
1936; Ackerly & Benton 1947). This was that some
neurological patients show a marked behavioural
disorganization in everyday life, despite little sign of
impairment in intellect, memory, perception, motor
and language skills—at least according to the evaluative
methods available at the time.
It was not until 50 years later, however, that the full
extent of this pattern became clear. Eslinger & Damasio
(1985) described the case of EVR, who had undergone
surgical removal of a large bilateral frontal menin-
gioma. Premorbidly, EVR had been a trusted financial
officer, a good father and a respected member of his
community. But, following his operation, EVR lost his
job, went bankrupt and divorced his wife. Extensive
psychological evaluations found no deficit, however,
and he was superior or above average on most tests (e.g.
Verbal IQ of 125; Performance IQ of 124; no difficulty
on Wisconsin Card Sorting Test). Notably, Eslinger &
Damasio (1985, p. 1737), however, report prospective
memory (PM) problems in everyday life: .it was as if
he forgot to remember short- and intermediate-term
goals.’.
Six years later, Shallice & Burgess (1991a) reported
three cases with a similar profile in everyday life. None
of them showed any significant impairment on formal
tests of perception, language or intelligence. Moreover,
two performed well on a variety of traditional tests of
executive function. Shallice & Burgess (1991a,b)
measured everyday life problems by inventing a real-
life multitasking test carried out in a shopping precinct
(the ‘Multiple Errands Test’). Participants were
required to complete a number of tasks, principally
involving shopping in an unfamiliar shopping precinct,
while following a set of rules (e.g. no shop should be
entered other than to buy something). The tasks varied
in terms of complexity (e.g. buy a small brown loaf
versus discover the exchange rate of the Euro yester-
day), and there were a number of ‘hidden’ problems in
the tasks that had to be appreciated and the possible
course of action evaluated (e.g. one item asked that
participants write and send a postcard, yet they were
given no pen and, although they could not use anything
not bought on the street to help them, they were also
told that they needed to spend as little money as
possible). In this way, the task is quite ‘open-ended’ or
‘ill-structured’ (i.e. there are many possible courses of
action, and it is up to the individual to determine for
themselves which one they will choose). All three of
Shallice and Burgess’s patients were significantly
poorer than a group of age- and IQ-matched healthy
controls on this test. The patients made a range of types
of error, many of which could be interpreted as PM
failures. For instance, they would find themselves
having to go into the same shop more than once to
buy items that could all have been bought at one visit;
they did not complete the tasks that they had previously
learnt that they needed to do; and they tended to forget
to come over to the experimenter and tell them what
888 P. W. Burgess et al. Rostral PFC and cognition
Phil. Trans. R. Soc. B (2007)
they had bought when leaving a shop, which was a pre-
learnt task rule. They also made a range of social
behaviour errors (e.g. leaving a shop without paying,
offering sexual favours in lieu of payment).
3. STAGE 2: DEVELOP ‘MODELS’ OF THE REAL
WORLD WITH SIMPLER LABORATORY TASKS
Shallice & Burgess (1991a) also developed a laboratory
task that aimed to mimic some of the critical demands of
the multiple errands test, and thus serve as a ‘model of
the world’ for experimental and assessment purposes.
Termed the ‘Six Element Test’ (SET), this task required
subjects to swap efficiently between three simple
subtasks, each divided into two sections, while following
some arbitrary rules (e.g. ‘you cannot do part A of a
subtask followed immediately by part B of the same
subtask’; figure 1). Participants were given 15 minutes
to perform the test, which was insufficient for all
subtasks to be completed. There were no cues as to
when to switch tasks, and although a clock was present it
was covered so that checking it had to be a deliberate
action. Despite their excellent general cognitive skills, all
three cases reported by Shallice and Burgess performed
these tasks below the 5% level when compared with the
age- and IQ-matched controls.
However, it was not possible from these single case
studies to determine the precise location of the lesion
that caused this pattern of clinical impairment.
Although all these people (and others with similar
symptoms) were suffering from lesions affecting PFC,
the lesions in each case were large, and invaded a
number of prefrontal sub-regions (for brain scan results
on these cases, see Shallice 2004; Burgess et al. 2005).
It was not possible therefore with this small sample to
ascertain the critical locus of damage. However, we
now had a criterion laboratory measure that we could
use for this purpose.
4. STAGE 3: ESTABLISH THE BRAIN REGIONS
INVOLVED USING THE HUMAN GROUP LESION
METHOD
Accordingly, Burgess et al. (2000) examined the
performance of a series of 60 acute neurological
patients (approx. three quarters of whom were suffering
from brain tumours) and 60 age- and IQ-matched
healthy controls on a multitasking test that shared
similar principles with the SET. Called the ‘Greenwich
Test’ this presented participants with three different
simple tasks. They were told that they had to attempt at
least some of each of the tasks in 10 minutes, while
following a set of rules. One of these rules relates to all
subtests (‘in all three tasks, completing a red item will
gain you more points than completing an item of any
other colour’) and there were four task-specific rules
(e.g. ‘in the ‘Tangled Lines Test’ you must not mark the
paper other than to write your answers down’).
It may be important to note that multitasking tests of
this kind differ from most dual-task or task-switching
paradigms in that: (i) only one subtask is attempted at
any one time (unlike most dual-task paradigms) and (ii)
switches of task have to be voluntarily initiated without
the appearance of a cue (unlike most task-switching
paradigms). In this way, tasks like the SET make strong
demands upon PM abilities (i.e. the ability to remember
to carry out an intended action after a delay).
The Greenwich Test was administered in a form that
allowed consideration of the relative contributions of
task-rule learning and remembering, planning, plan-
following and remembering one’s actions to overall
multitasking performance. Specifically, before the
participants began the test, their ability to learn the
task rules (by both spontaneous and cued recall) was
measured. They were then asked how they intended to
do the test, and a measure of the complexity and
appropriateness of their plans was gained. This enabled
us to look at whether their failures could be due to poor
planning (e.g. Kliegel et al.2000, 2005). The
participants then performed the task itself and by
comparing what they did with what they had planned to
do, a measure of ‘plan-following’ was made. Multi-
tasking performance itself was calculated as the
number of task switches minus the number of rule-
breaks committed. After these stages were finished,
subjects were asked to recollect their own actions by
describing in detail what they had done and, finally,
delayed memory for the task rules was examined.
audio
recorder
timer
instruction
sheet
paper
pencil and
eraser
pictures
A
booklet
pictures
B
booklet
arithmetic
A booklet
2+4 = 9–3 =
arithmetic
B booklet
(a)(b)
Figure 1. (a) Materials for the Modified Six Element Test (Burgess et al. 1996). Participants are given 10 minutes to complete at
least some of each of the three subtasks, each divided into two parts (i.e. verbal dictation A and B, picture naming A and B,
arithmetic A and B), but are not permitted to perform two subtasks of the same type straight after each other (e.g. arithmetic A
then arithmetic B). (b) Lesion overlap figure from Burgess et al. (submitted b) for a group of right rostral PFC-damaged
participants who made fewer task switches than other patients or healthy controls on a new version of the Six Element Test (right
rostrals: mean voluntary task switches 3.0 (s.d. 2.1), other patients mean 6.3 (s.d. 4.0), p!0.005).
Rostral PFC and cognition P. W. Burgess et al. 889
Phil. Trans. R. Soc. B (2007)
We found that lesions in different brain regions were
associated with impairment at these different stages in
the multitasking procedure. Lesions in posterior medial
brain regions, including the left posterior cingulate and
forceps major, gave deficits on all measures except
planning. Remembering task contingencies after a
delay was also affected by lesions in the region of the
anterior cingulate. Critically, however, Burgess et al.
(2000) found that patients with left hemisphere rostral
PFC lesions, when compared with patients with lesions
elsewhere, showed a significant multitasking impair-
ment, despite no significant impairment on remember-
ing task rules. Indeed, the left rostral prefrontal cases
showed no significant impairment on any variable
except the one reflecting multitasking performance. In
other words, despite being able to learn the task rules,
form a plan, remember their actions and say what they
should have done, they nevertheless did not do what
they said that they intended to do.
A subsequent study using a slightly modified form of
the SET also showed that it is rostral PFC lesions that
can lead to multitasking and PM problems in the context
of preserved intellect and retrospective memory (Burgess
et al.submittedb; reported in Burgess et al. 2005). In this
study, a new version of the Burgess et al.(1996)SET was
administered to 69 acute neurological patients with
circumscribed focal lesions and to 60 healthy controls,
using the administration framework of Burgess et al.
(2000;seealsoBurgess 2000). Compared with other
patients, those whose lesions involved the rostral
prefrontal regions of the right hemisphere made
significantly fewer voluntary task switches, attempted
fewer subtasks and spent far longer on individual
subtasks (figure 1). They did not, however, make a
larger number of rule-breaks (in contrast to the left
rostral patients in the Burgess et al.2000study). As with
the study of Burgess et al. (2000), these multitasking
deficits could not be attributed to deficits in general
intellectual functioning, rule knowledge, planning or
retrospective memory. Burgess et al. (in press a) argue
that the hemispheric difference between these studies
may reflect the differences between these two multi-
tasking tests: the SET differs from the Greenwich Test in
that the multitasking score reflects mainly voluntary
time-based switching rather than rule-following. (For
further discussion of this issue, see Burgess et al. in press
a,b; Okuda et al.inpress; for other relevant human lesion
evidence, e.g. Goldstein et al.1993; Burgess et al.2000;
Goel & Grafman 2000; Alexander et al. 2003; Bird et al.
2004; Picton et al. 2006.) Looking back from these group
study results to previous case studies of patients with
similar symptoms, revealed that all of them had rostral
PFC involvement (e.g. Shallice & Burgess 1991a,b;
Goldstein et al.1993; Goel & Grafman 2000;see
Burgess 2000 for details, and further cases).
5. STAGE 4: ESTABLISH THE RELATION
BETWEEN ROSTRAL PFC AND THE
HYPOTHETICAL SUB -FUNCTION USING
NEUROIMAGING
Since the patients’ problems on the multitasking tests
could not be attributed to deficits in memory or
planning, we hypothesized that deficits in PM were the
core impairment in these people with rostral PFC
lesions. If this were the case, then we might expect to see
haemodynamic changes in this region when healthy
people are performing PM tasks. And indeed, this seems
to be the case. Burgess et al. (2001) showed, using
positron emission tomography (PET), that regional
cerebral blood flow (rCBF) increases in lateral BA 10
occur when people are performing a PM task, relative to
when they are performing the ongoing task alone (see
also Okuda et al. 1998). Importantly, these increases
were just as large when participants were told that a PM
cue might appear, but none actually did. Thus, we could
conclude that at least some regions of lateral BA 10 are
more involved with the maintenance of an intention
rather than cue recognition or intention execution.
A second PET study confirmed this role for lateral
BA 10 in PM conditions, and also showed that medial
BA 10 is more active in ongoing conditions than PM
ones (Burgess et al. 2003), i.e. the opposite pattern of
results to that observed in lateral BA 10. Furthermore,
medial BA 10 was also more active (compared with PM
conditions) in a simple attentional baseline condition
where the subject (S) just responded as fast as possible
to any change in the display. These results raised the
possibility that lateral and medial rostral PFC regions
supportasystemthatworksinconcertinPM
situations, with a cost to environmental attending
(one signature of which is anterior medial area 10
haemodynamic change) that accompanies the need to
‘bear the PM intention in mind’ (the signature of which
is lateral area 10 activation.) (See e.g. Smith & Bayen
(2004) for related views from experimental
psychology.)
The two PET studies of Burgess et al.(2001, 2003)
had used a ‘multiple task averaging’ experimental
design. This is where one investigates haemodynamic
changes across two or more tasks that putatively stress
the process of interest (Shallice 1988), but where the
other demands of the tasks are made quite different, for
example, using spatial material for one and verbal for
the other. Accordingly, Burgess et al. (2003) inter-
preted their results as suggesting that the functions
supported by area 10 in PM are ‘central’ in the respect
that they are material non-specific, and unrelated to the
precise intention retrieval or cue recognition demands.
Instead, Burgess and colleagues favoured an expla-
nation in terms of one of the possibilities raised by
Okuda et al. (1998), that the rostral PFC rCBF changes
were related to the attentional demands made by
having to ‘bear in mind’ an intention while performing
an ongoing task.
We subsequently tested this hypothesis. Simons et al.
(2006b) measured brain activity (using functional
magnetic resonance imaging (fMRI) and a conjunction
of two different PM tasks: ‘words’ and ‘shapes’) while
manipulating the demands on either recognizing the
appropriate context to act (‘cue identification’) or
remembering the action to be performed (‘intention
retrieval’). A consistent pattern of haemodynamic
changes was found in rostral PFC (BA 10) across
both types of task and across both PM conditions
(compared with the ongoing task alone). There was
increased blood oxygen level-dependent (BOLD)
signal in lateral BA 10, which was accompanied by
890 P. W. Burgess et al. Rostral PFC and cognition
Phil. Trans. R. Soc. B (2007)
decreased BOLD signal in medial BA 10. Direct
comparison of the ‘high intention retrieval demand’
with the ‘high cue recognition demand’ PM conditions
also revealed greater BOLD signal in lateral area 10
regions bilaterally in the intention retrieval condition.
These regions were somewhat more medial and caudal
to those that showed activation common to both
conditions. (For further investigations of the role of
BA 10 in PM, see Burgess et al. in press b.)
6. STAGE 5: FORMULATE A HYPOTHESIS OF THE
CRITICAL PROCESSING COMPONENT USING
CONSTRAINTS FROM BOTH LESION AND
NEUROIMAGING DATA
The studies described earlier suggested that the
processes supported by rostral PFC are involved in
PM and therefore multitasking. This is useful in
understanding how the brain supports these ‘functions’
(i.e. behaviours understood in context of (i) a goal and
(ii) a task analysis; see Burgess et al. 2006a,b for
explanation). However, area 10 has been implicated as
important in supporting many other functions, such as
recollection or reflecting on mental states (see Grady
1999; Ramnani & Owen 2004; Gilbert et al. 2006ac
for review). It therefore seemed plausible that different
subsections of area 10 support quite different func-
tions. However, an account of this type raises two
problems. The first is the possibility of infinite
explanatory regress. Most functions will have sub-
functions (or sub-operations) and the localization of
each is likely at some level to be different. Moreover,
one would be unlikely to discover processing common
to many functions with this approach. The second
problem is that starting with an assumption of strong
modular functional specialization may leave the
discovery of the relevant functions essentially to
chance. Accordingly, in order to provoke new
hypotheses, we proceeded on the basis of the
simplifying assumption that BA 10 may support some
critical processing component (or ‘construct’) which is
shared by all the implicated functions (for definition of
the terms function and construct in this context, see
Burgess et al. 2006a).
The challenge was to find a function that fitted the
myriad of observations from functional imaging and
also those from the human lesion data. This was not
straightforward, in particular because the findings from
the two methods seemed to present a conundrum. This
was that, based on the functional imaging findings of
BA 10 activation in a wide range of tasks, an obvious
suggestionmightbethatBA10supportssome
cognitive processing that is important to the per-
formance of all of them. But if this were the case,
then one would expect to see performance deficits
across a correspondingly wide variety of tasks when this
region is damaged in humans. However, this is not the
case. As we have seen, neurological patients with rostral
PFC lesions need not show impairments on tests of
intelligence, clinical (retrospective) memory tests,
language, perception and even tests of executive
function such as the Wisconsin Card Sorting Test,
FAS fluency, etc.
An appropriate account had to accommodate this
apparent conundrum and also to be compatible with
the other sets of constraints for theorizing presented by
these different methods. Burgess et al. (2005) list the
constraints we took as a starting position. There were
seven constraints from human lesion studies and 17
from the functional imaging literature. Examples of the
former were: ‘rostral PFC lesions disproportionately
impair performance in ‘ill-structured’ situations, in
other words where the optimal way of behaving is not
precisely signalled by the situation’; and ‘rostral PFC
lesions need not markedly impair performance on
standard tests of intelligence, especially those that
measure ‘crystallized’ intelligence, or those involving
the use of over-learned procedures (e.g. arithmetic)’.
Examples of the constraints for theorizing presented by
the functional imaging literature were, for example,
‘rostral PFC activation is not sensitive to the precise
nature of stimuli, the nature of the intended action (in
PM tasks) nor the precise response method, but is
consistently implicated in tasks where one has to ‘bear
something in mind’ while doing something else’.
The account that emerged as a potential solution
was termed the ‘gateway hypothesis’ (Burgess et al.
2003, 2005, 2006b). This theory of the role of BA 10 in
human cognition rests upon a distinction between
stimulus-oriented (SO) and stimulus-independent (SI)
attending (McGuire et al. 1996). SO attending refers to
the attending behaviour that is required to concentrate
on current sensory input. (Here, we make a distinction
between ‘attention’ as a construct (i.e. a hypothetical
processing resource that may operate across a range of
operations or functions), and attending behaviour as a
function or operation ( function, directly observable
behaviour; operation, mental experience) that may be
indirectly inferred from observation; e.g. if presented
with the sum 2C4 and a person responds ‘6’, one might
infer that they have performed a calculation operation;
see Burgess et al. 2006a,b for explanation.)
Examples of SO attending range from performance
of vigilance tasks, to reading, watching the television,
listening to a conversation and so forth. By contrast, SI
attending is the attending behaviour required to effect
either self-generated or self-maintained thought. Self-
generated thought is cognition that goes beyond the
overlearned associations or semantic memories pro-
voked by currently available stimuli. In this respect, the
concept shares similarities with that of N-order (i.e.
second order, third order, etc.) representations used in
experimental and developmental psychology and
artificial intelligence. By contrast, self-maintained
thought is where one deliberately maintains a represen-
tation in the absence of the stimuli that provoked it. It is
the absence of the stimulus that provoked the
representation that defines this operation as belonging
to the class of ‘SI’ cognition. Examples of SI cognition
therefore range from task-irrelevant thoughts such as
mind-wandering or daydreaming, to goal-directed
cognition such as that involved in making up a novel
story, or maintaining a representation over a delay
period, and so forth.
We assume that many mental experiences which
occur over all but the briefest of durations will consist of
combinations of SO and SI attending. Accordingly, for
Rostral PFC and cognition P. W. Burgess et al. 891
Phil. Trans. R. Soc. B (2007)
empirical purposes, data relating to an SO or SI
distinction might be thought of as existing along a
continuum of relative proportions of variance.
However, at the extremes at least, the distinction may
be robust enough for empirical purposes. For instance,
we describe four characteristics with which one can
imbue a task that would increase the relative demand
for SO attending, compared with a task that did not
have these characteristics (Burgess et al. submitted a):
(i) Requires vigilance (e.g. attending in absence of
stimulus or attentional capture).
(ii) Requires stimulus processing, i.e. awareness of
stimulus characteristics (e.g. as required for
conditional responding of the form ‘if charac-
teristic X, then respond Y’).
(iii) The information required to respond appro-
priately is currently available. For instance, the
task that presents subjects with maths problems
of the form ‘4C2Z will be a purer measure of
SO attending than one that requires comparing
the sum of the currently presented numbers
with the sum of two previously (but not
currently) seen.
(iv) The operations involved prior to responding are
automatic, well learnt or involve retrieval from
semantic memory only (i.e. they are not novel).
Similarly, one might describe characteristics with
which one might imbue a task which would increase the
relative demand for SI attending, thus:
(i) The task encourages mind-wandering, for
example, by being easy, monotonous, non-novel
and repetitive.
(ii) All the information required to respond appro-
priately is not currently being presented, and:
(a) The information that is required in order to
respond appropriately is not well learnt or
from semantic memory, but comes from a
previously witnessed episode (e.g. as in a
delay task).
(b) The task requires the use of self-generated
representations (e.g. novel problem solving,
imagination).
(c) The task requires working with represen-
tations that were self-generated on a
previous occasion and have not been
rehearsed in the meantime.
It is important to note that these are not the only
characteristics one might outline. An everyday example
to demonstrate the contrast between SO and SI modes
of attending might be where one is trying to concentrate
on a rather dull lecture (SO attending) versus imagining
what one might do that evening after the lecture (SI
attending). The gateway hypothesis proposes that
rostral PFC in part supports a system which operates
when one is required to maintain either mode of
attending to an unusual degree or switch between
them. More specifically, it proposes that medial rostral
PFC plays a role in supporting SO attending, and lateral
rostral PFC facilitates switching to, maintaining and
voluntarily switching away from, SI cognition (figure 2).
In this way, the cognitive system supported by rostral
PFC was characterized as a ‘gateway’ between mental
life and the external world. (For related accounts from
neuroimaging, see McGuire et al. 1996; Christoff &
Gabrieli 2000; Christoff et al. 2001, 2003, 2004;
Pollmann 2001, 2004; Mason et al. 2007.) Within the
information processing framework of Shallice & Burgess
(1996), it is assumed that this attentional system lies
between the contention scheduling (routine schema
selection) and the other supervisory system modules
(controlled processing), effecting bias between them
(see also Shallice & Burgess 1991b, 1993)
This potential account, if true, might solve the
apparent conflict between the imaging and lesion
evidence since (i) the attentional ‘gate’ would operate in
a wide variety of tasks, but not be critical to the
performance of tasks that involve routine, information-
ally encapsulated processing resources or where attend-
ing is strongly driven by the environment, (ii) the
difficulties that patients with rostral PFC damage
experience (e.g. with multitasking and PM) are those
that are particularly likely to require the operation of the
attentional gate. This is because both multitasking tasks
of the type investigated here (i.e. where one task is carried
out while bearing in mind that one has to voluntarily
switch to another soon) and also typical PM paradigms,
both require active intention maintenance (SI cognition)
while also engaging with external stimuli (SO attending)
in performance of the ongoing task, or current subtask.
7. STAGE 6: TEST THE GATEWAY HYPOTHESIS
The gateway hypothesis was then tested directly in
three ways:
position A
p
osition B
central
representations
to
output
systems
from
input
systems
gate 1
gate 2
pos B
pos B
Figure 2. Stylized representation of the ‘gateway hypothesis’
of rostral prefrontal function. Rostral PFC regions are
hypothesized to support a system that biases the flow of
information between basic systems and central represen-
tations (i.e. equivalent to the adjustment of the position of the
‘gates’). The gates are shown in the neutral position (equal to
bias freely determined by context). If both gates are at
position A, SI cognition is favoured. If both gates are at
position B, full engagement with (external) stimuli is effected.
Other combinations have further experiential correlates,
especially when one considers dynamic, moment-by-moment
switching. The operation of processes supported by lateral
rostral PFC would correspond to the effecting of both gates to
position A, with the operation of anterior medial rostral PFC
regions effecting movement towards position B. However,
this cartoon should not be taken too literally. The main
purpose of the diagram is to emphasize how even a very
simple switch system could effect a range of mental activity.
Many other types of analogy could be used.
892 P. W. Burgess et al. Rostral PFC and cognition
Phil. Trans. R. Soc. B (2007)
Stage 6(i). Development of direct indicators (i.e.
tests) of the proposed function, and investigation of the
involvement of area 10 in the performance of the tests
using fMRI.
Stage 6(ii). Investigation with neuroimaging and
lesion studies of specific functions (e.g. context
memory), which should in theory make heavy demands
upon this system.
Stage 6(iii). Meta-analyses of functional imaging
studies to test the predictions that the theory would
make about activation–behaviour associations.
We will consider these in turn.
(a) Stage 6(i)
Gilbert et al. (2005) invented three tasks that could be
performed either using stimuli that were presented by
visual display (i.e. requiring SO attending) or by
performing the same tasks ‘in one’s head’ only (i.e. SI
attending). In the first task, subjects either tapped a
response button in time with a visually presented clock
or ignored the visual display (which now presented
distracting information) and continued to tap at the
same rate. The second task required subjects either to
navigate around the edge of a visually presented shape,
or, when the shape was replaced by a ‘thought bubble’,
to imagine the same shape and continue navigating as
before. In the third task, in the SO condition,
participants performed a classification task on sequen-
tial letters of the alphabet that were presented on a
display. In the SI condition, they mentally continued
the sequence and performed the same classification on
each self-generated letter. Thus, all three tasks
alternated between phases where subjects attended to
externally presented information, and phases where
they ignored this information and attended to
internally represented information instead. We investi-
gated both the sustained neural activity that differed
between two phases, and transient activity at the point
of a switch between these two phases. Consistently,
across all three tasks, medial rostral PFC exhibited
sustained increased activity when participants attended
to externally presented information. By contrast, right
lateral rostral PFC exhibited transient activity when
subjects switched between these phases, regardless of
the direction of the switch. This dissociation between
medial and lateral rostral PFC regions was confirmed
statistically in all three tasks. Thus, the results of the
study strongly supported the hypothesis that rostral
PFC is involved in selection between SO and SI
attending, and suggested dissociable roles of medial
and lateral rostral PFC in this selection process. It also
showed that lateral BA 10 is activated at the point when
one switches from performing a task in one’s head to
using displayed stimuli and vice versa.
A further fMRI study (Gilbert et al.2006a)
demonstrated performance-related activation (i.e.
increased activation was associated with faster reaction
times) in medial area 10 in simple reaction time
conditions that did not require substantial stimulus
processing (figure 3b). Thus, the characterization of
medial rostral PFC as most active when an unusual
degree of attention to external stimuli is required was
supported. Moreover, unpublished data from this
second experiment also showed that lateral rostral PFC
is activated bilaterally during periods of extended SI
cognition, and not only at the SI/SO switch points (SI–
SO contrast: left hemisphere, K40, 36, 24, BA 9/46/10,
zZ4.28, cluster sizeZ403 voxels; right hemisphere, 38,
0
(b)
(a)
0.1
0.2
0.3
0.0
0.1
0.1
0.2
0.2
0.3
0.05
0.50
0.35
0.20
0.3
SO
SO
simple
RT
fastest
RT quartile
slowest
SO+SI
SI
condition
voxel
33, 60, 15
–39, 51, 15
–3, 63, 3
percentage of signal change
Figure 3. (a) Results from Burgess et al. (submitted a). Tasks requiring SO attending only are contrasted with tasks requiring SO
attending plus SI attending (see text for details of the tasks). There is increased BOLD signal bilaterally in lateral area 10 in
conditions requiring SI attending. Rostral medial area 10 shows the opposite pattern. The regions rendered on the brain (left)
are colour coordinated to the graph (right). Coordinates are MNI. Bars are s.e.m. (b) Results from Gilbert et al. (2006a).
Regions of activation revealed in the comparison of SO against SI conditions are shown in yellow. Regions where the BOLD
signal correlated with reaction time in a separate simple-reaction time baseline condition are shown in red. This shows that
BOLD signal in medial rostral PFC was greater on trials with relatively fast reaction times, ruling out an account of the role of
this region in terms of task-unrelated thought during low-demand conditions (since this would be expected to compromise
reaction time). (RT, reaction time.)
Rostral PFC and cognition P. W. Burgess et al. 893
Phil. Trans. R. Soc. B (2007)
44, 32, BA 9/46/10, zZ4.43, cluster sizeZ643 voxels;
both p!0.001 uncorrected; S. J. Gilbert 2006, personal
communication).
However, there are different forms of both SO and
SI attending. Therefore, we next considered whether
we could see common BA 10 activations across the
different forms, or whether rostral PFC seems to show
regional specialization for the different types. Burgess
et al. (submitted a) administered two quite different
tasks, each of which consisted of four conditions, in an
fMRI conjunction design. The conditions varied in the
degree to which they made demands upon five
attentional constructs, two of which were stimulus
oriented (vigilance and stimulus attending) and three
of which were stimulus independent in nature (mind-
wandering, use of self-generated representations and
maintenance over a delay). Regardless of task, con-
ditions stressing both of the SO attentional forms
activated similar regions of rostral medial area 10, and
all three that stressed SI cognition activated similar
regions of caudal lateral area 10. There was little
evidence for further functional specialization within
these regions. Figure 3a gives an example of these
results, and shows the BOLD signal changes revealed
by a contrast between tasks that required stimulus
attending (e.g. deciding which of two numbers is the
largest) and those that additionally required the use of
self-generated representations (e.g. comparing the sum
of two currently displayed numbers with the sum of two
numbers seen on a previous trial).
(b) Stage 6(ii)
Another way to measure the utility of the gateway
hypothesis using neuroimaging is to use it to predict
which functions should activate area 10. Clearly, if the
investigated function does not involve area 10, then the
hypothesis is challenged. We chose a specific form of
context memory as a prototype function. Context
memory is, prima facie, a good candidate for the
involvement of a mechanism that plays a role in
the control of SI versus SO attending because the
recollection of context requires the retrieval of infor-
mation that goes beyond the associations immediately
provoked by the current stimulus. We assume that
when a trace is encoded, the strength of the links
between elements will be indexed at least in part by
what one was attending to at the time, which in turn is
influenced by the nature of the task (see Burgess &
Shallice 1996 for theoretical background). Thus, being
required to recollect details that were part of the event
but which were not central to it (or at least to what was
attended, i.e. context details) will require the voluntary
establishing of a partially new representation, i.e. SI
cognition, and integration with the current perceived
stimulus (requiring SO attending). Context memory
paradigms should therefore be good examples of
memory tasks that require switching between represen-
tations directly provoked by current stimuli (i.e.
requiring SO attending) and those that are not
currently perceived (i.e. SI attending).
Simons et al. (2005a) asked participants to make two
different types of decision about words or famous faces
that were presented either on the right or left of a display.
They were then shown the words and faces again, while
lying in an fMRI scanner, and were asked either which
decision they had been required to make about the
stimulus (‘task memory’), or on which side of the screen
the stimulus had appeared (‘position memory’). Across
both words and faces, activation in lateral rostral PFC
regions occurred during both task and position memory
conditions compared with a semantic classification
baseline task. By contrast, medial BA 10 regions showed
significantly increased BOLD signal during the task
memory conditions compared with during the position
memory ones. In a second study with a similar design
(Simons et al. 2005b), we contrasted position memory
with judging which of two previously presented and
temporally distinct lists the stimuli belonged to (‘list
memory’). As with the previous experiment, both
experimental conditions activated lateral rostral PFC
relative to baseline. However, the aspects of left rostral
PFC in both medial and lateral sub-regions additionally
showed increased activation during the recollection of
task compared with list. Furthermore, the time-courses
of the activations in medial and lateral BA 10 were
different, with lateral regions more active at the early
stages, and medial regions more active at the later stages.
It would probably be premature to take a firm view of
the significance of the finer points of these results; this
awaits progress in our understanding both of the
abilities that area 10 structures support, and of the
processing demands made by context memory para-
digms. However, it is quite clear from these two studies
that: (i) recalling the contextual details is associated with
very substantial haemodynamic changes in rostral PFC
and (ii) there are lateral BA 10 regions that seem to be
involved in context memory functions in a surprisingly
non-specific way. In this way, the gateway hypothesis
intersects with views of BA 10 involvement in memory
retrieval (e.g. Lepage et al. 2000; Reynolds et al. 2006),
which is one exemplar of operations whose signature is
SI attending.
Remaining within the memory domain, a further
prediction we made was that area 10 should be involved
with distinguishing between perceived and imagined
stimuli (Simons et al.2006a). This is because
imagining a stimulus is a cardinal form of SI thought,
and therefore must be recalling that memory. However,
processing a perceived stimulus in an experimental
situation will of course be most effective if one is
attending closely to the presented stimuli. Thus, the
task will require considerable switching between SI and
SO attending states. Accordingly, we showed partici-
pants well-known pair phrases (e.g. Romeo and Juliet;
Laurel and Hardy) and they were asked to count the
number of letters in the third word. This was called the
‘perceive condition’. But on some trials the third word
was replaced by a question mark (e.g. Romeo and ?),
and on these trials, the subjects were required to
imagine the word that completed the phrase and count
its number of letters ‘in their head’. Subsequently, the
participants were presented with the first word from
these phrases (e.g. ‘Romeo’) and required either to
recall whether (i) the accompanying word had
originally been perceived or imagined or (ii) the
word-pair had been presented on the left or right side
of the screen. We replicated our previous findings of
lateral BA 10 activation in recalling which side of the
894 P. W. Burgess et al. Rostral PFC and cognition
Phil. Trans. R. Soc. B (2007)
display the stimuli had appeared (versus baseline).
However, we also found that on a subject-by-subject
basis, people who showed least BOLD signal increase
in a particular region of medial rostral PFC (MNI
coordinates: xZ18, yZ54, zZ6) tended to be those
who made more errors in saying that they had actually
witnessed a stimulus that they had in fact imagined (but
not vice versa). It is probably too early to attempt a full
explanation of these findings in information processing
terms, since models of how people decide that they
have imagined or perceived items are not sufficiently
advanced. Moreover, there is always the possibility that
the region of area 10 we identified in this study is not
the same as those discussed earlier (it is, for instance,
neither quite as medial nor as lateral as those discussed
earlier). However, it does seem probable from these
results that area 10 supports processing relevant to
determining whether one has perceived or imagined an
event. If this is the case, understanding the role this
brain region is playing may help us to understand the
genesis of disorders where mistaking imaginings for
perceived stimuli is a key feature; for example, the
hallucinations of schizophrenia. Indeed, when we
examined the activation during this experiment in all
three brain regions that Whalley et al. (2004) have
argued show abnormalities in schizophrenia (sections
of thalamus, cerebellum as well as the medial rostral
PFC region examined here), we found significant
BOLD signal increases in all three of these regions
when people were engaged in discriminating between
perceived and imagined items (relative to position
memory).
(c) Stage 6(iii)
The third way in which we have tested the plausibility
of the gateway hypothesis is to test a prediction that the
theory would make about activation–behaviour associ-
ations using meta-analysis of functional imaging
studies. If lateral area 10 plays some part in effecting
tasks that require the various forms of SI cognition, as
the gateway hypothesis proposes, then RTs to tasks that
require attending to stimuli plus some form of
stimulus-independent thought will be longer, typically,
than to tasks that only require the stimulus attending
component.
More specifically, we assume that the anterior
medial rostral PFC is involved in simple attending to
the outside world, and this can occur under even very
low demand conditions (cf. Gilbert et al. 2006a). By
‘low demand conditions’, we mean those conditions
that make few demands upon systems other than those
involved in attending to the environment. In practice,
this means that stimuli will tend to be familiar (and thus
easily perceived and understood), conditional respond-
ing is either not required (e.g. simple RT paradigms) or
taps an established S–R correspondence, and adequate
performance of the task is within the capabilities of the
individual. We also assume that lateral PFC is involved
in SI cognition (e.g. attending to ‘the thoughts in our
head’; cf. Burgess et al. submitted a,b) as described
earlier. If this is the case, then medial rostral PFC
activations should tend to be associated with paradigms
where RTs to the experimental condition are as fast, or
faster than, whatever comparison task was used, while
lateral rostral activations should be associated with
conditions where RTs were slower than in the
comparison task. Perhaps the most obvious example
comes from the field of PM. Performing an ongoing
task while maintaining an intention, and checking for
PM cues, is likely to result in slower RTs to stimuli than
when one is performing the ongoing task alone. In this
case, one would expect where the anterior medial area
10 activations were found, that they would be provoked
mainly by the ongoing task alone, and where lateral
activations are found they would be principally
associated with the PM conditions. This is in fact the
case (Burgess et al. 2001, 2003).
Accordingly, Gilbert et al. (2006b) analysed the RTs
to paradigms from 104 PET/fMRI studies that had
reported significant haemodynamic change in area 10.
This yielded 133 independent contrasts. The tasks that
had provoked these BA 10 activations came from a
wide range of functions, e.g. memory, mentalizing,
perception as well as tasks that involved multitask
coordination (e.g. PM, task-switching, dual-task para-
digms, etc.). Similarly, the tasks that had been used for
comparison took many forms, and of course differed
from study-to-study. But, if the gateway hypothesis
holds, the precise form of neither the task under
examination (e.g. memory, perception, etc.) that
provoked the area 10 activation nor the comparison
task (i.e. the task that had been used as a ‘baseline’ for
the task that provoked the area 10 activation) should
matter for these purposes. This is because all cognition
consists of varying degrees of SO and SI cognition, so
all tasks can be classified according to, for example, the
proportion of variance (in BOLD signal change) one
might attribute to one attending form or another. We
assume that experiments where tasks have been
compared that make similar demands upon SO or SI
attending will have tended not to have yielded BA 10
activations. Hence, if we examine studies where BA 10
changes have been detected, and where the logic in the
paragraph holds, there should be a medial–lateral BA
10 difference by RT.
As predicted by the gateway hypothesis, Gilbert et al.
(2006a,b) did indeed find that RTs to tasks that had
provoked lateral area 10 activations tended to be slower
than RTs in whatever control task had been used.
Furthermore, RTs to tasks that had provoked medial
area 10 activations were as fast, or faster, than in the
comparison task (figure 4a). This pattern occurred
regardless of the type of task under study, and thus
seems to be a general principle of area 10 neuroimaging
findings.
8. FURTHER FUNCTIONAL SPECIALIZATION
WITHIN AREA 10
Our studies strongly suggest that lateral and medial
regions within BA 10 are differentially sensitive to the
demands that tasks make upon SO and SI attending,
and that this might provide a dimension along which
the functional organization of rostral PFC might be
understood (Koechlin et al. 2000). However, it does
not provide, nor does it seek to be, a complete account
of the relation between structure and function within
rostral PFC.
Rostral PFC and cognition P. W. Burgess et al. 895
Phil. Trans. R. Soc. B (2007)
Most importantly, the account presented here does
not preclude others. BA 10 is a very large brain region,
with many connections to different brain regions. It is
certainly possible that while we may have identified a
particular function (e.g. attenuating SI versus SO
attending), other sub-regions of rostral PFC may
perform other unrelated functions. It might even be
the case that the same brain regions as we have
identified may perform different functions (e.g. by
virtue of interactions with other brain regions).
Then, the gateway hypothesis as it currently stands
deals only with the functional organization of BA 10 in
respect of one spatial dimension: lateral versus medial.
Yet, there is strong evidence from our own work and
others that principles may emerge for functional
organization along other dimensions (i.e. rostral–
caudal, dorsal–ventral).
For instance, Gilbert et al. (2006c) investigated the
location of activations within area 10 according to the
type of task being used, with the neuroimaging
database already described (see §7c earlier). The
location in X and Y dimensions of area 10 activations
were analysed across 133 contrasts found in the
neuroimaging literature according to the type of task
which provoked them. A classification algorithm was
trained on half of the data and then tested on the other
half to see if it could predict the task from the location
of each activation peak. This algorithm is represented
visually in figure 4b. Accuracy in the three main
categories of task was 71% (chance: 33%; p!10
K39
).
As shown in figure 4, episodic memory tasks were
associated with lateral area 10 activations. More
importantly, however, we found that mentalizing
tasks tending to provoke activations within caudal
medial aspects of BA 10 (see also Frith & Frith 1999;
Gusnard et al. 2001), but paradigms that required the
coordination of two or more activities (dual task, PM,
etc.) were associated with very rostral activations within
area 10 (figure 4b).
In order to investigate this possible rostral–caudal
localization distinction further, we conducted an fMRI
study that crossed the factors of attentional focus (SO
versus SI attending) and mentalizing (mentalizing
versus non-mentalizing). Participants performed two
of the three tasks investigated by Gilbert et al. (2005),
whichswitchedbetweenSOandSIphasesat
unpredictable times. In ‘mentalizing blocks’, the
participants were instructed that the experimenter
was in control of the timing of these switches, and
that they had to judge whether he had tried to be
helpful or unhelpful in that block. In ‘non-mentalizing
blocks’, the participants were instructed that the
switches occurred at times randomly selected by a
computer, and they were asked to judge whether these
switches occurred more or less rapidly than average. In
actuality, there was no difference between mentalizing
and non-mentalizing blocks, but in post-experiment
debriefing participants unanimously described inter-
preting the timing of switches in the mentalizing blocks
in terms of the mental state of the experimenter. For
instance, one subject said ‘I was thinking about
whether you could see if I was stuck.and what was
coming up on your screen so I did imagine what you
were seeing sometimes during the experiment.I was
more aware of the human element entering into the
equation’ (Gilbert et al. submitted).
The fMRI results were clear. Contrasting SO with SI
phases revealed strong activity in the most rostral part of
meta-analysis 1
relatively
fast RTs
multiple tasks
mentalizing
episodic memory
SO>SI
mentalizing >
non-metalizing
meta-analysis 2
mentalizing study
relatively
slow RTs
(a)
(b)
(c)
Figure 4. (a) Smoothed RT data from a meta-analysis of 104 functional neuroimaging studies reporting activation peaks in
rostral PFC (Gilbert et al. 2006b). On average, contrasts producing activation peaks in regions coloured blue involved faster RTs
in the experimental task than the control task against which it was compared. By contrast, those contrasts where the RTs in the
experimental condition were slower than in the control condition tended to produce activation peaks in the regions marked in
red. This pattern occurred regardless of the type of paradigm under use (e.g. episodic memory, mentalizing, etc.). (b) Results of
a second meta-analysis of these 104 studies, which investigated the association between different types of task and the location of
activation peaks within rostral PFC (Gilbert et al. 2006c). Note that the studies involving multiple-task coordination tended to
yield activation peaks rostral to those involving mentalizing. (c) Results of an fMRI study that crossed the factors of attentional
focus (SO versus SI ) with mentalizing (mentalizing versus non-mentalizing judgments; Gilbert et al. submitted). The regions of
activation in rostral PFC produced by the SO versus SI contrast were rostral to those produced by the mentalizing versus non-
mentalizing contrast. In both (b) and (c), the results are plotted on an axial slice (zZ24) of the participants’ mean normalized
structural scan.
896 P. W. Burgess et al. Rostral PFC and cognition
Phil. Trans. R. Soc. B (2007)
medial PFC. This replicates the earlier finding
of Gilbert et al. (2005). Moreover, the contrast of
mentalizing with non-mentalizing blocks yielded
activity in an adjacent caudal region of medial PFC, as
predicted by the meta-analysis (Gilbert et al. 2006c).
Most importantly, however, there was virtually no
overlap between the brain regions activated in these
two contrasts, and nor were there any regions showing a
significant interaction between the mentalizing and
attention factors (figure 4c). Thus, this study confirmed
that dissociable, adjacent regions of medial rostral PFC
are involved in (i) focusing attention on perceptual
versus self-generated information or (ii) mentalizing.
Taken with the result of the meta-analysis (figure 4b),
these results suggest that it might be possible to establish
a further principle of the functional organization of area
10 based around the rostral–caudal dimension.
9. CONCLUSION
This is an exciting time for scientists involved in trying
to discover the functions of rostral PFC (BA 10). For
many years, there was essentially little or no evidence
that might speak to this issue. Then, the advent of
functional neuroimaging placed the functions of this
region at the heart of human cognition by demonstrat-
ing rostral PFC haemodynamic changes in a very wide
range of tasks. However, the sheer volume and variety
of these findings provided few constraints for theoriz-
ing. But, very recently, some principles have begun to
emerge which suggest that achieving an understanding
of the functional organization of this large, and
uniquely human, brain region may not be an unrealistic
aim. For instance, tasks that, in lay terms, require
participants to ‘bear something in mind while doing
something else’ very consistently provoke area 10
haemodynamic changes (e.g. Okuda et al. 1998, in
press; Koechlin et al. 1999; Burgess et al. 2001, 2003),
and these tasks also seem to be performed poorly by
patients with damage to this brain region (e.g. Burgess
et al. 2000). Yet, the functions of this region cannot be
reduced to this function alone, since other consistent
findings go far beyond this class of task. For instance,
tasks that involve episodic recollection, ‘mentalizing’
and those that provoke mind-wandering are also
accompanied by rostral PFC haemodynamic changes
in a predictable fashion, as are simple tasks that involve
making over-learned responses to environmental
stimuli (e.g. Gilbert et al. 2005, 2006a. For review
see Grady 1999; Ramnani & Owen 2004; Gilbert et al.
2006b,c). We have provided a framework that seeks to
explain the multiplicity of these findings in a simple
way, by invoking a construct that relies on the
distinction between SO and SI attending. The
experimental predictions that follow have been broadly
confirmed in a series of experiments in our own
laboratory, and we have also shown with meta-analysis
that the hypothesis can explain important aspects of the
findings from other laboratories, cutting across gross
task characterizations. However, this gateway
hypothesis, as it currently stands, seeks only to outline
a principle for the functional organization of area 10
along a lateral–medial dimension. The most obvious
next candidate discovery at this stage might be a
principle that relates to functional organization along a
rostral–caudal dimension. Additionally, while we may
have discovered one superordinate function of rostral
PFC, this precludes neither the discovery of other
functions that will provide conceptual challenge nor the
possibility of functional specialization within sub-
regions of area 10 that do not conform to the principle.
In other words, in concentrating on discovering regions
of area 10 which provide results that conform to the
gateway hypothesis, we have not largely sought to
discover those that might not. Nevertheless, we hope
that the hypothesis we advance will prove a useful tool
for investigation. Currently, it has three advantages
over most other current accounts of the functions of
this brain region. First, it is predicated on the results of
both neuroimaging and human lesion data. This is
particularly important, since the remarkably specific
nature of the deficits shown by people with rostral PFC
lesions provides a severe test of many other accounts
that have emerged from neuroimaging data alone.
Second, it provides a principle by which apparently
similar activations (and their behavioural correlates)
across tasks of different forms might be investigated.
Third, it has received direct empirical examination.
Clearly, however, we still have a great deal to learn. But,
the special structure of rostral PFC in humans, its size,
late development and links to the highest levels of
human cognition, give hope that understanding how
this fascinating brain region works may reveal key
insights into the mental experiences and disorders that
are peculiar to humans.
This work was supported by the Wellcome Trust grant
number 061171 to P.W.B.
REFERENCES
Ackerly, S. S. & Benton, A. L. 1947 Report of a case of
bilateral frontal lobe defect. Res. Publ. : Assoc. Res. Nerv.
Mental Dis. 27, 479–504.
Alexander, M. P., Stuss, D. T. & Fansabedian, N. 2003
California Verbal Learning Test: performance by patients
with focal frontal and non-frontal lesions. Brain 126,
1493–1503. (doi:10.1093/brain/awg128)
Bird, C. M., Castelli, F., Malik, O., Frith, U. & Husain, M.
2004 The impact of extensive medial frontal lobe damage
on “Theory of Mind” and cognition. Brain 127 , 914–928.
(doi:10.1093/brain/awh108)
Blaxton, T. A., Zeffiro, T. A., Gabrieli, J. D. E., Bookheimer,
S. Y., Carrillo, M. C., Theodore, W. H. & Disterhoft, J. F.
1996 Functional mapping of human learning: a positron
emission tomography activation study of eyeblink con-
ditioning. J. Neurosci. 16, 4032–4040.
Bonin, G. von. 1950 Essay on the cerebral cortex. Springfield,
IL: Charles C. Thomas.
Brickner, R. M. 1936 The intellectual functions of the frontal
lobes: a study based upon observation of a man after partial
bilateral frontal lobectomy. New York, NY: Macmillan.
Burgess, P. W. 2000 Strategy application disorder: the role of
the frontal lobes in human multitasking. Psychol. Res. 63,
279–288. (doi:10.1007/s004269900006)
Burgess, P. W. & Shallice, T. 1996 Confabulation and the
control of recollection. Memory 4, 359–411. (doi:10.1080/
096582196388906)
Burgess, P. W., Alderman, N., Emslie, H., Evans, J. J.,
Wilson, B. A. & Shallice, T. 1996 The simplified six
element test. In Behavioural assessment of the dysexecutive
Rostral PFC and cognition P. W. Burgess et al. 897
Phil. Trans. R. Soc. B (2007)
syndrome (eds B. A. Wilson, N. Alderman, P. W. Burgess,
H. Emslie & J. J. Evans). Bury St Edmunds, UK: Thames
Valley Test Company.
Burgess, P. W., Veitch, E., Costello, A. & Shallice, T. 2000
The cognitive and neuroanatomical correlates of multi-
tasking. Neuropsychologia 38, 848–863. (doi:10.1016/
S0028-3932(99)00134-7)
Burgess, P. W., Quayle, A. & Frith, C. D. 2001 Brain regions
involved in prospective memory as determined by positron
emission tomography. Neuropsychologia 39, 545–555.
(doi:10.1016/S0028-3932(00)00149-4)
Burgess, P. W., Scott, S. K. & Frith, C. D. 2003 The role of
the rostral frontal cortex (area 10) in prospective memory:
a lateral versus medial dissociation. Neuropsychologia 41,
906–918. (doi:10.1016/S0028-3932(02)00327-5)
Burgess, P. W., Simons, J. S., Dumontheil, I. & Gilbert, S. J.
2005 The gateway hypothesis of rostral PFC function. In
Measuring the mind: speed, control and age (eds J. Duncan,
L. Phillips & P. McLeod), pp. 215–246. Oxford, UK:
Oxford University Press.
Burgess, P. W. et al. 2006a The case for the development and
use of “ecologically valid” measures of executive function
in experimental and clinical neuropsychology. J. Int.
Neuropsychol. Soc. 12, 1–16.
Burgess, P. W., Gilbert, S. J., Okuda, J. & Simons, J. S. 2006b
Rostral prefrontal brain regions (area 10): a gateway
between inner thought and the external world? In Disorders
of volition (eds W. Prinz & N. Sebanz), pp. 373–396.
Cambridge, MA: MIT Press.
Burgess, P. W., Gilbert, S. J. & Dumontheil, I. In press a.A
gateway between mental life and the external world: role of
the rostral prefrontal cortex (area 10). Jpn J. Neuropsychol.
Burgess, P. W., Dumontheil, I., Gilbert, S. J., Okuda, J.,
Scho¨lvinck, M. L. & Simons, J. S. In press b. On the role of
rostral prefrontal cortex (area 10) in prospective memory.
In Prospective memory: cognitive, neuroscience, develop-
mental, and applied perspectives (eds M. Kliegel, M. A.
McDaniel & G. O. Einstein). Mahwah, NJ: Erlbaum.
Burgess, P. W., Dumontheil, I., Gilbert, S. J. & Frith, C. D.
Submitted a. Similar regions of area 10 (rostral PFC) are
involved in various forms of stimulus-oriented or stimulus-
independent attending.
Burgess, P. W., Veitch, E. J. & Costello, A. Submitted b.
Multitasking deficits in humans following rostral pre-
frontal lesions: the Six Element Test.
Christoff, K. & Gabrieli, J. D. E. 2000 The frontopolar cortex
and human cognition: evidence for a rostrocaudal
hierarchical organization within the human prefrontal
cortex. Psychobiology 28, 168–186.
Christoff, K., Prabhakaran, V., Dorfman, J., Zhao, Z.,
Kroger, J. K., Holyoak, K. J. & Gabrieli, J. D. E. 2001
Rostrolateral prefrontal cortex involvement in relational
integration during reasoning. Neuroimage 14, 1136–1149.
(doi:10.1006/nimg.2001.0922)
Christoff, K., Ream, J. M., Geddes, L. P. T. & Gabrieli,
J. D. E. 2003 Evaluating self-generated information:
anterior prefrontal contributions to human cognition.
Behav. Neurosci. 117, 1161–1168. (doi:10.1037/0735-
7044.117.6.1161)
Christoff, K., Ream, J. M. & Gabrieli, J. D. E. 2004 Neural
basis of spontaneous thought processes. Cortex 40, 1–9.
Eslinger, P. J. & Damasio, A. R. 1985 Severe disturbance of
higher cognition after bilateral frontal lobe ablation:
patient E. V. R. Neurology 35, 1731–1741.
Frith, U. & Frith, C. D. 1999 Interacting minds—a biological
basis. Science 286, 1692–1695. (doi:10.1126/science.286.
5445.1692)
Frith, U. & Frith, C. D. 2003 Development and neurophy-
siology of mentalizing. Phil. Trans. R. Soc. B 358, 459–473.
(doi:10.1098/rstb.2002.1218)
Gilbert, S. J., Frith, C. D. & Burgess, P. W. 2005 Involvement
of rostral prefrontal cortex in selection between stimulus-
oriented and stimulus-independent thought. Euro.
J. Neurosci. 21, 1423–1431. (doi:10.1111/j.1460-9568.
2005.03981.x)
Gilbert, S. J., Simons, J. S., Frith, C. D. & Burgess, P. W.
2006a Performance-related activity in medial rostral
prefrontal cortex (area 10) during low demand tasks.
J. Exp. Psychol. Hum. Percept. Perform. 32, 45–58. (doi:10.
1037/0096-1523.32.1.45)
Gilbert, S. J., Spengler, S., Simons, J. S., Frith, C. D. &
Burgess, P. W. 2006b Differential functions of lateral and
medial rostral prefrontal cortex (area 10) revealed by
brain-behavior correlations. Cereb. Cortex Jan 18 [Epub
ahead of print].
Gilbert, S. J., Spengler, S., Simons, J. S. S., Steele, J. D.,
Lawrie, S. M., Frith, C. D. & Burgess, P. W. 2006c
Functional specialisation within rostral prefrontal cortex
(area 10): a meta-analysis. J. Cogn. Neurosci. 18, 932–948.
(doi:10.1162/jocn.2006.18.6.932)
Gilbert, S. J., Williamson, I., Dumontheil, I., Simons, J. S.,
Frith, C. D. & Burgess, P. W. Submitted. Distinct regions
of rostral prefrontal cortex supporting social and nonsocial
functions.
Goel, V. & Grafman, J. 2000 The role of the right prefrontal
cortex in Ill-structured problem solving. Cogn. Neuropsychol.
17,415436.(doi:10.1080/026432900410775)
Goldstein, L. H., Bernard, S., Fenwick, P. B. C., Burgess,
P. W. & McNeil, J. 1993 Unilateral frontal lobectomy can
produce strategy application disorder. J. Neurol. Neurosurg.
Psych. 56, 274–276.
Grady, C. L. 1999 Neuroimaging and activation of the frontal
lobes. In The human frontal lobes: function and disorders (eds
B. L. Miller & J. L. Cummings), pp. 196–230. New York,
NY: Guilford Press.
Gusnard, D. A., Akbudak, E., Shulman, G. L. & Raichle,
M. E. 2001 Medial prefrontal cortex and self-referential
mental activity: relation to a default mode of brain
function. Proc. Natl Acad. Sci. USA 98, 4259–4264.
(doi:10.1073/pnas.071043098)
Holloway, R. L. 2002 Brief communication: how much larger
is the relative volume of area 10 of the prefrontal cortex in
humans? Am. J. Phys. Anthropol. 118, 399–401. (doi:10.
1002/ajpa.10090)
Jacobs, B. et al. 2001 Regional dendritic and spine variation in
human cerebral cortex: a quantitative golgi study. Cereb.
Cortex 11, 558–571. (doi:10.1093/cercor/11.6.558)
Kliegel, M., McDaniel, M. A. & Einstein, G. O. 2000 Plan
formation, retention, and execution in prospective
memory: a new approach and age-related effects. Mem.
Cogn. 28, 1041–1049.
Kliegel, M., Phillips, L. H., Lemke, U. & Kopp, U. A. 2005
Planning and realisation of complex intentions in patients
with Parkinson’s disease. J. Neurol. Neurosurg. Psych. 76,
1501–1505. (doi:10.1136/jnnp.2004.051268)
Koechlin, E., Basso, G., Pietrini, P., Panzer, S. & Grafman, J.
1999 The role of the anterior prefrontal cortex in human
cognition. Nature 399, 148–151. (doi:10.1038/20178)
Koechlin, E., Corrado, G., Pietrini, P. & Grafman, J. 2000
Dissociating the role of the medial and lateral anterior
prefrontal cortex in planning. Proc. Natl Acad. Sci. USA
97, 7651–7656. (doi:10.1073/pnas.130177397)
Lepage, M., Ghaffar, O., Nyberg, L. & Tulving, E. 2000
Prefrontal cortex and episodic memory retrieval mode.
Proc. Natl Acad. Sci. USA 97, 506–511. (doi:10.1073/
pnas.97.1.506)
Mason, M. F., Norton, M. I., Van Horn, J. D., Wegner,
D. M., Grafton, S. T. & Macrae, C. M. 2007 Wandering
898 P. W. Burgess et al. Rostral PFC and cognition
Phil. Trans. R. Soc. B (2007)
minds: the default network and stimulus-independent
thought. Science 315, 393–395. (doi:10.1126/science.
1131295)
McGuire, P. K., Paulesu, E., Frackowiak, R. S. J. & Frith,
C. D. 1996 Brain activity during stimulus independent
thought. Neuroreport 7, 2095–2099.
Okuda, J., Fujii, T., Yamadori, A., Kawashima, R.,
Tsukkiura, T., Fukatsu, R., Suzuki, K., Ito, M. &
Fukuda, H. 1998 Participation of the prefrontal cortices
in prospective memory: evidence from a PET study in
humans. Neurosci. Lett. 253, 127–130. (doi:10.1016/
S0304-3940(98)00628-4)
Okuda, J., Fujii, T., Ohtake, H., Tsukiura, T., Yamadori, A.,
Frith, C. D. & Burgess, P. W. 2006 Differential
involvement of regions of rostral prefrontal cortex
(Brodmann area 10) in time- and event-based prospective
memory. Int. J. Psychophysiol. Nov 23. [Epub ahead of
print.]
Ongur, D., Ferry, A. T. & Price, J. L. 2003 Architectonic
subdivision of the human orbital and medial prefrontal
cortex. J. Comp. Neurol. 460, 425–449.
Penfield, W. & Evans, J. 1935 The frontal lobe in man: a
clinical study of maximum removals. Brain 58, 115–133.
(doi:10.1093/brain/58.1.115)
Picton, T. W., Stuss, D. T., Shallice, T., Alexander, M. P. &
Gillingham, S. 2006 Keeping time: effects of focal frontal
lesions. Neuropsychologia 44, 1195–1209. (doi:10.1016/
j.neuropsychologia.2005.10.002)
Pollmann, S. 2001 Switching between dimensions, locations,
and responses: the role of the left frontopolar cortex.
Neuroimage 14, S118–S124. (doi:10.1006/nimg.2001.
0837)
Pollmann, S. 2004 Anterior prefrontal cortex contributions
to attention control. Exp. Psychol. 51, 270–278.
Raichle, M. E., MacLeod, A.-M., Snyder, A. Z., Powers,
W. J., Gusnard, D. A. & Shulman, G. L. 2001 A default
mode of brain function. Proc. Natl Acad. Sci. USA 98,
676–682. (doi:10.1073/pnas.98.2.676)
Ramnani, N. & Owen, A. M. 2004 Anterior prefrontal cortex:
insights into function from anatomy and neuroimaging.
Nat. Rev. Neurosci. 5, 184–194. (doi:10.1038/nrn1343)
Reynolds, J. R., McDermott, K. B. & Braver, T. S. 2006 A
direct comparison of anterior prefrontal cortex involve-
ment in episodic retrieval and integration. Cereb. Cortex 16,
519–528. (doi:10.1093/cercor/bhi131)
Semendeferi, K., Armstrong, E., Schleicher, A., Zilles, K. &
Van Hoesen, G. W. 2001 Prefrontal cortex in humans and
apes: a comparative study of area 10. Am. J. Phys. Anthropol.
114,224241.(doi:10.1002/1096-8644(200103)114:3!
224::AID-AJPA1022O3.0.CO;2-I)
Shallice, T. 1988 From neuropsychology to mental structure.
Cambridge, UK: Cambridge University Press.
Shallice, T. 2004 The fractionation of supervisory control. In
The cognitive neurosciences III (ed. M. S. Gazzananiga),
pp. 943–956. Cambridge, MA: MIT Press.
Shallice, T. & Burgess, P. W. 1991a Deficits in strategy
application following frontal lobe damage in man. Brain
114, 727–741. (doi:10.1093/brain/114.2.727)
Shallice, T. & Burgess, P. W. 1991b Higher-order cognitive
impairments and frontal lobe lesions in man. In Frontal
lobe function and dysfunction (eds H. S. Levin, H. M.
Eisenberg & A. L. Benton), pp. 125–138. New York, NY:
Oxford University Press.
Shallice, T. & Burgess, P. W. 1993 Supervisory control of
action and thought selection. In Attention: selection,
awareness and control: a tribute to Donald Broadbent (eds
A. Baddeley & L. Weiskrantz), pp. 171–187. Oxford, UK:
Clarendon Press.
Shallice, T. & Burgess, P. W. 1996 The domain of supervisory
processes and temporal organisation of behaviour. Phil.
Trans. R. Soc. B 351, 1405–1412. (doi:10.1098/rstb.1996.
0124) Reprinted in The prefrontal cortex: executive and
cognitive functions (eds A C. Roberts, Robbins, T. W. &
Weiskrantz, L.), pp. 22–35. Oxford, UK: Oxford
University Press, 1998, 2000.
Simons, J. S., Gilbert, S. J., Owen, A. M., Fletcher, P. C. &
Burgess, P. W. 2005a Distinct roles for lateral and medial
anterior prefrontal cortex in contextual recollection.
J. Neurophysiol. 94,813820.(doi:10.1152/jn.01200.2004)
Simons, J. S., Owen, A. M., Fletcher, P. C. & Burgess, P. W.
2005b Anterior prefrontal cortex and the recollection of
contextual information. Neuropsychologia 43, 1774–1783.
(doi:10.1016/j.neuropsychologia.2005.02.004)
Simons, J. S., Davis, S. W., Gilbert, S. J., Frith, C. D. &
Burgess, P. W. 2006a Discriminating imagined from
perceived information engages brain areas implicated in
schizophrenia. Neuroimage 32, 696–703. (doi:10.1016/
j.neuroimage.2006.04.209)
Simons,J.S.,Scho¨ lvinck, M., Gilbert, S. J., Frith, C. D. &
Burgess, P. W. 2006b Differential components of prospective
memory? Evidence from fMRI. Neuropsychologia 44,
1388–1397. (doi:10.1016/j.neuropsychologia.2006.01.005)
Smith, R. E. & Bayen, U. J. 2004 A multinomial model of event-
based prospective memory. J. Exp. Psychol. Learn. Mem.
Cogn. 30,756777.(doi:10.1037/0278-7393.30.4.756)
Sowell, E. R., Thompson, P. M., Holmes, C. J., Jernigan,
T. L. & Toga, A. W. 1999 In vivo evidence for post-
adolescent brain maturation in frontal and striatal regions.
Nat. Neurosci. 2, 859–861. (doi:10.1038/13154)
Sowell, E. R., Thompson, P. M., Leonard, C. M., Welcome,
S. E., Kan, E. & Toga, A. W. 2004 Longitudinal mapping
of cortical thickness and brain growth in normal children.
J. Neurosci. 24, 8223–8231. (doi:10.1523/JNEUROSCI.
1798-04.2004)
Whalley, H. C., Simonotto, E., Flett, S., Marshall, I.,
Ebmeier, K. P., Owens, D. G., Goddard, N. H.,
Johnstone, E. C. & Lawrie, S. M. 2004 fMRI correlates
of state and trait effects in subjects at genetically enhanced
risk of schizophrenia. Brain 127, 457–459.
Rostral PFC and cognition P. W. Burgess et al. 899
Phil. Trans. R. Soc. B (2007)
    • "During win anticipation, participants expect to gain money, which, in turn, may induce such positive feelings as happiness, joy, increase in interest and motivation to continue task performance, etc. During this condition, connectivity density in the fronto-parietal-temporo-striatal subnetwork in healthy control subjects was the lowest compared with other groups, and lateral frontal regions involved in prospective (Burgess et al., 2007) and working Brain connectivity for anticipation in depression BRAIN 2016: Page 9 of 13 | 9 (Owen et al., 2005) memory were disconnected from VS and medial PFC, potentially because no emotion regulation was required during win anticipation. MDD had the same connectivity density and a 'bottomup' connectivity pattern originating in LVS for win and loss anticipation. "
    [Show abstract] [Hide abstract] ABSTRACT: Bipolar disorder is often misdiagnosed as major depressive disorder, which leads to inadequate treatment. Depressed individuals versus healthy control subjects, show increased expectation of negative outcomes. Due to increased impulsivity and risk for mania, however, depressed individuals with bipolar disorder may differ from those with major depressive disorder in neural mechanisms underlying anticipation processes. Graph theory methods for neuroimaging data analysis allow the identification of connectivity between multiple brain regions without prior model specification, and may help to identify neurobiological markers differentiating these disorders, thereby facilitating development of better therapeutic interventions. This study aimed to compare brain connectivity among regions involved in win/loss anticipation in depressed individuals with bipolar disorder (BDD) versus depressed individuals with major depressive disorder (MDD) versus healthy control subjects using graph theory methods. The study was conducted at the University of Pittsburgh Medical Center and included 31 BDD, 39 MDD, and 36 healthy control subjects. Participants were scanned while performing a number guessing reward task that included the periods of win and loss anticipation. We first identified the anticipatory network across all 106 participants by contrasting brain activation during all anticipation periods (win anticipation + loss anticipation) versus baseline, and win anticipation versus loss anticipation. Brain connectivity within the identified network was determined using the Independent Multiple sample Greedy Equivalence Search (IMaGES) and Linear non-Gaussian Orientation, Fixed Structure (LOFS) algorithms. Density of connections (the number of connections in the network), path length, and the global connectivity direction (‘top-down’ versus ‘bottom-up’) were compared across groups (BDD/MDD/healthy control subjects) and conditions (win/loss anticipation). These analyses showed that loss anticipation was characterized by denser top-down fronto-striatal and fronto-parietal connectivity in healthy control subjects, by bottom-up striatal-frontal connectivity in MDD, and by sparse connectivity lacking fronto-striatal connections in BDD. Win anticipation was characterized by dense connectivity of medial frontal with striatal and lateral frontal cortical regions in BDD, by sparser bottom-up striatum-medial frontal cortex connectivity in MDD, and by sparse connectivity in healthy control subjects. In summary, this is the first study to demonstrate that BDD and MDD with comparable levels of current depression differed from each other and healthy control subjects in density of connections, connectivity path length, and connectivity direction as a function of win or loss anticipation. These findings suggest that different neurobiological mechanisms may underlie aberrant anticipation processes in BDD and MDD, and that distinct therapeutic strategies may be required for these individuals to improve coping strategies during expectation of positive and negative outcomes.
    Article · Jun 2016
    • "MPFC has been argued to have a role in directing ongoing thought processes (Moran et al., 2013), and its frontopolar aspect, in particular, has been proposed to perform a 'gateway' function (Burgess et al., 2007a). It is said to be active when a person must choose to attend to one among competing sensory representations – from internal and external sources – and particularly in unstructured settings where the correct response is not readily known (Burgess et al., 2007a; Burgess et al., 2007b). Its transitional location between ventral MPFC, which regulates processes in the homeostatic-motivational domain, and dorsal MPFC, which represents higher cognitive 'reflective' thinking about oneself in relation to others (Moran et al., 2006; Northoff et al., 2006), suggests it integrates these information sources in performing this gateway role. "
    [Show abstract] [Hide abstract] ABSTRACT: The brain's default mode network (DMN) has become closely associated with self-referential mental activity, particularly in the resting-state. While the DMN is important for such processes, it has functions other than self-reference, and self-referential processes are supported by regions outside of the DMN. In our study of 88 participants we examined self-referential and resting-state processes to clarify the extent to which DMN activity was common and distinct between the conditions. Within areas commonly activated by self-reference and rest we sought to identify those that showed additional functional specialization for self-referential processes: these being not only activated by self-reference and rest, but also showing increased activity in self-reference versus rest. We examined the neural network properties of the identified ‘core-self’ DMN regions — in medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and inferior parietal lobule — using dynamic causal modeling. The optimal model identified was one in which self-related processes were driven via PCC activity, and moderated by the regulatory influences of MPFC. We thus confirm the significance of these regions for self-related processes, and extend our understanding of their functionally specialized roles.
    Full-text · Article · Feb 2016
    • "595). Burgess and colleagues [7,8] put forward a theoretical explanation of rostral PFC function, which they termed the 'gateway hypothesis'. Central to this hypothesis is the assertion that rostral PFC supports mechanisms that enable humans to attend to either environmental stimuli or to internally self-generated/maintained representations, as required. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Goal neglect is a significant problem following brain injury, and is a target for rehabilitation. It is not yet known how neural activation might change to reflect rehabilitation gains. We developed a computerised multiple elements test (CMET), suitable for use in neuroimaging paradigms. Design: Pilot correlational study and event-related fMRI study. Methods: In Study 1, 18 adults with acquired brain injury were assessed using the CMET, other tests of goal neglect (Hotel Test; Modified Six Elements Test) and tests of reasoning. In Study 2, 12 healthy adults underwent fMRI, during which the CMET was administered under two conditions: self-generated switching and experimenter-prompted switching. Results: Among the clinical sample, CMET performance was positively correlated with both the Hotel Test (r = 0.675, p = 0.003) and the Modified Six Elements Test (r = 0.568, p = 0.014), but not with other clinical or demographic measures. In the healthy sample, fMRI demonstrated significant activation in rostro-lateral prefrontal cortex in the self-generated condition compared with the prompted condition (peak 40, 44, 4; ZE = 4.25, p(FWEcorr) = 0.026). Conclusions: These pilot studies provide preliminary evidence towards the validation of the CMET as a measure of goal neglect. Future studies will aim to further establish its psychometric properties, and determine optimum pre- and post-rehabilitation fMRI paradigms.
    Full-text · Article · Jan 2016
Show more