medial region (Gilbert et al., 2006c, 2007a; Simons et al., 2008). The
present results suggest that mentalizing studies may promote
interactions between medial RoPFC and a variety of other brain
regions, even those that typically co-activate with lateral rather than
medial RoPFC. This would be consistent with the idea that mentalizing
is not supported by a strictly modular system (Fodor, 1983) but
instead involves gathering information from a variety of domains; in
other words mentalizing is not “informationally encapsulated”
(Goldman, 2006, pp. 104–106).
It should be noted that the relationship between functional con-
nectivity and task category was tested in analyses in which extra-
RoPFC activations within a 15 mm sphere were denoted as a single
region. This was important to ensure sufﬁcient statistical power for
these analyses. However, it is possible that at a ﬁner level of analysis
the extra-RoPFC co-activations associated with different categories of
task might be s patially distinct. Indeed, s tudies of functional
specialization within RoPFC indicate considerable ﬁne-grained segre-
gation of function (Gilbert et al., 2006c, 2010). Thus, although the
present results are valid at a relatively coarse level of analysis, it
remains to be seen whether they would also hold at a more detailed
level. In order to address this question, a larger database of studies
would be required, or additional neuroimaging experiments crossing
multiple task demands within the same study. For further discussion
of the question of functional specialization at multiple levels of
analysis, see Henson (2005) and Gilbert et al. (2010).
Although the present study revealed clear differences in functional
connectivity between lateral and medial RoPFC, there were no
signiﬁcant hemispheric effects, or effects of rostral versus caudal or
inferior versus superior RoPFC. This is perhaps surprising because
functional differences have been reported both between rostral and
caudal RoPFC (Gilbert et al., 2006c, 2007a; Simons et al., 2008) and
between inferior and superior RoPFC (Mitchell et al., 2006; Van
Overwalle, 2009). One possibility is that the present database
(containing 200 activations in RoPFC and 1712 co-activations) was
too small, or the voxel size of 5 mm
too coarse, for sufﬁcient statis-
tical power to detect differences in connectivity along these axes.
There may be less variance in connectivity along these axes than the
medial/lateral axis, or the types of study that would reveal this
variance may have been under-represented in the literature to date.
For example, recent studies have suggested a relationship between
activation along the rostro-caudal axis of the RoPFC and the level of
abstraction of task materials and/or complexity of task demands
(Christoff et al., 2009b). However, many studies do not systematically
manipulate (or control for) the abstractness of task materials and
therefore may potentially yield activations in both rostral and caudal
sections of RoPFC, obscuring the ability to discern unique connectivity
patterns. In addition, the present approach, using a database simply
indicating the presence or absence of a signiﬁcant signal change based
on a single RoPFC activation peak from each contrast, may have
missed differences in functional connectivity expressed as differences
in the strength of co-activations (e.g. bilateral activation in a par-
ticular region, more signiﬁcant in the hemisphere ipsilateral to the
activated area of RoPFC). Alternatively, it may be the case that
functional differences between RoPFC subregions along these axes
exist in the absence of systematic differences in functional connec-
tivity, i.e. that different RoPFC subregions perform distinct intrinsic
computations with equivalent input and output representations.
In summary, the present study established clear evidence for
differences in functional connectivity between lateral and medial
RoPFC. Furthermore, we found that these differences in connectivity
were in some cases modulated by task category. These results
underline the importance of delineating 1) particular subregions
within RoPFC, and 2) the speciﬁc roles of brain regions that tend to co-
activate, rather than treating them as functionally homogenous. In
addition, the relationship between functional and anatomical con-
nectivity of RoPFC remains to be explored. The present results may
provide a starting point for investigations of anatomical connectivity
of RoPFC in the human brain using tractography.
SJG was supported by a Royal Societ y University R esearch
Fellowship; EV was supported by the Fondation Bettencourt Schueller.
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Please cite this article as: Gilbert, S.J., et al., Distinct functional connectivity associated with lateral versus medial rostral prefrontal cortex: A
meta-analysis, NeuroImage (2010), doi:10.1016/j.neuroimage.2010.07.032