Correspondingly, hominid VEN-containing brain regions show enhanced connectivity with frontotemporal regions including prefrontal see more cortex, amygdala, and septum (Allman et al., 2011) and contribute to functional networks implicated in salience detection, attention, and sensorimotor control (Cauda et al., 2012). Interestingly, Evrard et al. (2012) draw attention to circumstantial evidence and preliminary tract-tracing data suggesting that the projection targets of VENs may be distinct from

those of other neurons within anterior insula (and anterior cingulate). Rather, VENs may have longer projections: Evrard et al. (2012) give evidence for sparse connectivity to anterior cingulate and contralateral insula, yet speculate a greater concentration of projections to brainstem targets including periaqueductal gray (PAG) and parabrachial nucleus (PBN). These structures are proximally involved in the efferent control of the internal state of the body through the autonomic nervous system and in its afferent visceral sensory mapping, i.e., interoception (the sense of internal physiological state). Interoceptive pathways can be distinguished from those of other sensory TGF-beta inhibitor modalities and have a primary cortical mapping within insula. Interoceptive information is further integrated with other representations within anterior insula (perhaps particularly in the right hemisphere), resulting in an enriched encoding of motivational

salience. Importantly, human anterior insula cortex appears to support conscious access to both the interoceptive information and associated integrated representations of how encoded

objects and concepts relate to the (biological) self (Singer et al., 2009 and Craig, 2011). In von Economo’s description of VENs as rod or corkscrew cells, he recognized the association between the VEN-containing regions (anterior insular and cingulate cortices) and autonomic function, speculating “a cerebral representation of the autonomic or sympathetic nervous systems in particular areas of the insula” (Seeley et al., 2012). A link to the control of internal state and associated motivations is also indicated by biochemical study of human VENs demonstrating the presence of proteins linked to control of digestion, “stress,” pain, and immune reactions (Allman et al., 2011). The lateralized Adenylyl cyclase preponderance of VENs within right insula (Allman et al., 2011 and Evrard et al., 2012) is also arguably suggestive of a role in interoceptive representation (Craig, 2011). Evrard et al. (2012) propose that VENs may contribute to interoception by providing inhibitory feedback from insula presumably to earlier (brainstem) levels of interoceptive representation. This notion is not dissimilar from our hypothesis that “interoceptive predictive coding” underpins integrative processing necessary for self-representation that ultimately supports conscious awareness (Seth et al., 2011).