Subspecialization in the human posterior medial cortex
Introduction
The human posterior medial cortex (PMC) has been functionally implicated in tasks as diverse as attention, memory, spatial navigation, emotion, self-relevance detection, and reward evaluation. The PMC relates to the ventral and dorsal posterior cingulate cortex (vPCC and dPCC; areas 23 and 31), retrosplenial cortex (RSC; areas 29 and 30), and precuneus (PrC; area 7 M, Scheperjans et al., 2008b). While the PCC and RSC belong to the cingulate cortex, the PrC belongs to the parietal lobe (Vogt et al., 2006). The RSC is located ventrocaudal to the splenium of the ventral bank of the corpus callosum. This brain region forms a belt in the callosal sulcus around the splenium. That is, the RSC is located on the ventral bank of the cingulate gyrus and only emerges slightly onto the cortical surface, mostly at ventrocaudal portions (Vogt et al., 2001). The PrC is the continuation of the superior parietal lobule on the medial hemispheric surface and abuts the dorsocaudal PCC. The PCC is located between RSC and PrC, caudal to the midcingulate cortex as well as dorsal, caudal, and ventral to the splenium. Although the RSC, PrC, and PCC have different cytoarchitectures and task-related functions, they have each been implicated in the default mode network; hence the notion of an overarching PMC supraregion. Fig. 1 shows these four regions in a neuroanatomical scheme, while Fig. 2 shows them as a combined supraregion.
The organization of the PMC was recently addressed using resting-state-correlation-based parcellation in monkeys and humans (Margulies et al., 2009). The regional functional connectivity patterns converged across species to a sensorimotor role for the anterior precuneus (i.e., dorsal PMC along the marginal ramus), a cognitive/associative role for the central precuneus (i.e., dorsocaudal PMC), a more visual role for the posterior precuneus (dorsal to the parieto-occipital sulcus), and a limbic role for the PCC/RSC (i.e., rostroventral PMC). Importantly, Margulies et al. also provided evidence that the PCC, but not precuneus, is an integral part of the so-called default mode network. Furthermore, all portions of the PMC were strongly interconnected (local interconnections being relatively strongest) as investigated using different antero- and retrograd tracers in monkeys (Parvizi et al., 2006). Yet, PCC and precuneus regions within the PMC were, for instance, distinguishable by the strength of (para-)hippocampal connections. The retrosplenial PCC concurrently dominated in connectivity to limbic networks for emotion processing, whereas the precuneal area 7 m concurrently featured specific connectivity to cingulo-frontal networks for action execution. The particularly diverse connectivity targets of the dorsocaudal PCC could speak in favor of either a distinctive property or a transitory area (by its location between areas 31 and 23). Parvizi et al. concluded that globally strong intra-PMC connectivity together with locally distinct extra-PMC connectivity might indicate realization of supraregional computational goals emerging from collaboration between PMC components. More specifically, neuroanatomists (Vogt, 2005, Vogt et al., 2006) advocated duality in the PCC with a dorsal component (including dorsal areas 23a/b/c and adjacent rostral area 31), frequently related to body-in-space cognition, and a ventral component (including ventral areas 23a/b and adjacent caudal area 31), frequently related to self/emotional relevance cognition vis-à-vis objects. Moreover, resting-state-derived (Zhang and Li, 2012) and DTI-derived (Zhang et al., 2014) parcellations of the PMC provided evidence for a possible functional subspecialization within the precuneus of the PMC.
Perhaps due to the PMC's mosaic organization, attempts of global functional accounts range from covert reallocation of spatial attention (Gitelman et al., 1999), mediation between internal and external focus (Leech and Sharp, 2014), computation of environmental statistics (Pearson et al., 2009), and self-referential visuospatial imagery (Cavanna and Trimble, 2006) to modality-independent integration between emotional states and memories (Maddock, 1999). These proposed domain-spanning roles potentially explain its various domain-specific functional involvements, such as visual rotation, deductive reasoning, autobiographical memory retrieval, and mental navigation in space. As a consequence of overarching functions, the PMC is consistently implicated in a variety of major psychiatric disorders, including schizophrenia, depression, autism, and ADHD (Leech and Sharp, 2014, Whitfield-Gabrieli and Ford, 2012).
Besides the uncertainty associated with its alleged functional roles (cf. Cavanna and Trimble, 2006), the human and non-human primate PMC stands out in a number of studies of brain metabolism, electrophysiologically recorded activity, and myelogenesis. Metabolically, the PMC has the highest level of basal glucose energy consumption in humans (Gusnard and Raichle, 2001) and other species (Harley and Bielajew, 1992, Matsunami et al., 1989). (Patho-)Physiologically, metabolic fluctuations in the human PMC have been closely related to various instances of altered conscious awareness, including anesthesia (Fiset et al., 1999), sleep (Maquet, 2000), and restoration from vegetative states (Laureys et al., 1999). Electrophysiologically, gamma band recordings in humans (Dastjerdi et al., 2011) and single-cell recordings in monkeys (Hayden et al., 2009) revealed activity reductions in the PMC during attentionally demanding tasks compared to rest. Functionally, such activity patterns in the absence of a defined task have long been speculated to reflect constant contemplation of (external) environment and (internal) memory (cf. Berger, 1931, Ingvar, 1979, Vogt et al., 1992). It is noteworthy that the PMC has, however, no direct connections with primary sensory regions (Cavanna and Trimble, 2006, Leech and Sharp, 2014, Parvizi et al., 2006), but has been described as a network “hub” exhibiting high centrality in graphanalytical examination (Hagmann et al., 2008). Finally, axons in parts of the PMC myelinate comparatively late during postnatal development in monkeys (Goldman-Rakic, 1987). Such late postnatal myelination is generally believed to occur in the phylogenetically most developed associations regions (Flechsig, 1920), thus mimicking the phylogenetic brain development during ontogeny (Couch et al., 2007). Taken together, we know that the PMC has numerous exceptional neurobiological properties. Nevertheless, the precise nature of neural processes realized in that part of the brain remains as elusive as its neurobiological organization.
We here aimed at a multi-modal characterization of the organization, connectivity, and function of the PMC supraregion. To this end, we used a data-driven approach that extracts structured knowledge emerging from several hundreds of neuroimaging studies (Hastie et al., 2011). First, we performed connectivity-based parcellation (Eickhoff et al., 2011, Johansen-Berg et al., 2004) of a volume of interest (VOI) comprising those portions of PCC, RSC, and PrC that are located within the PMC. This analysis tested whether local differences in whole-brain meta-analytic connectivity-modeling (MACM) enable identification of distinct regions within the PMC (cf. Cauda et al., 2010, Leech and Sharp, 2014, Margulies et al., 2009, Zhang et al., 2014). Second, the ensuing connectivity-derived regions were characterized by two measures of functional connectivity (cf. Cauda et al., 2011, Chang et al., 2013): the identical MACM approach, capturing brain activity in experimental settings, but also resting-state functional connectivity (RSFC), capturing brain activity in the absence of an experimental paradigm. This analysis thus tested what remote parts of the brain interact with the connectivity-derived regions congruently in the presence and absence of defined psychological tasks. Third, we delineated the derived regions' functional profiles by reference to the extensive meta-data in the BrainMap database (Fox and Lancaster, 2002) using quantitative forward and reverse inference. This last analysis tested whether regions in the PMC are more robustly associated with any taxonomic task descriptions than would be expected by chance. These investigations provided a statistically defensible characterization of subdivisions, connectivity, and function of the PMC supraregion making a minimum of a priori assumptions.
Section snippets
Defining the volume of interest
The volume of interest (VOI) comprising the PMC was defined using neuroanatomical landmarks. Cytoarchitectonic information provided the superior borders, while macroanatomical structures of the MNI (Montreal Neurological Institute) standard brain guided the delineation of most other borders as described below.
Regarding the superior borders of the VOI, topographical information was provided by histological probability maps from the Jülich brain atlas (Zilles and Amunts, 2010). Based on
Parcellation stability
Several metrics were applied to weigh the various cluster solutions for the PMC VOI against each other (Fig. 3). First, the information-theoretic criterion ‘variation of information’ slightly decreased from three to four clusters and steeply increased from four to five clusters. This indicated that each cluster of the k-means clusterings became increasingly chaotic starting from five clusters. Second, the cluster-separation criterion ‘silhouette coefficient’ showed a positive bump at four
Discussion
In this study, we used the data resources provided by BrainMap (Fox and Lancaster, 2002) to delineate the connectional and functional segregation of the posterior medial cortex (PMC). Regional differences in whole-brain coactivation patterns suggested a subdifferentiation of the PMC into four distinct functional modules. The coactivation-derived clusters corresponded to the PrC, ventral and dorsal posterior cingulate cortex (vPCC/dPCC), as well as retrosplenial cortex (RSC). These four clusters
Acknowledgments
This study was supported by the Deutsche Forschungsgemeinschaft (DFG, EI 816/4-1 to S.B.E. and L.A. 3071/3-1 to R.L. and S.B.E.; EI 816/6-1 to S.B.E. and D.B.), the National Institute of Mental Health (R01-MH074457 to A.R.L., P.T.F., and S.B.E.), the Helmholtz Initiative on Systems Biology (Human Brain Model to K.Z. and S.B.E.), and the German National Academic Foundation (D.B.).
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