, 1991 and Falchier et al., 2002); in primary motor cortex, the head and leg regions are connected with different areas ( Tokuno et al., 1997 and Hatanaka et al., 2001). In human cortex, internal heterogeneity Dactolisib ic50 within a single area can exceed the connectivity differences between corresponding topographic locations in neighboring areas; as illustrated below, this can result in marked differences in boundaries revealed by connectivity versus architectonic methods. (3) Topographic complexity. Topographic organization is precise and orderly in early sensory areas (e.g., visual

area V1). It becomes coarser and more disorderly for areas that are progressively farther from the primary area; some areas also have an incomplete or biased representation of the contralateral sensory space, e.g., the visual field or body surface ( Maunsell and Van Essen, 1987, Hansen et al., 2007, Kolster et al., 2009 and Kolster et al., 2010). Genuine irregularities in topographic organization make it difficult to delineate areal boundaries, and this can buy GSK1120212 be compounded by methodological noise or bias. (4) Individual variability. Comparisons across individuals are vital for crossmodal validation and for assessing the

consistency of any given parcellation scheme. However, such comparisons must cope with individual variability in the size (surface area) of each cortical area and in its location relative to cortical folds. Well-defined

cortical areas such as V1 vary in areal size by 2-fold or more in humans and nonhuman primates ( Andrews et al., 1997, Amunts et al., 1999 and Amunts et al., 2000). MTMR9 The relationship of areal boundaries to gyral and sulcal folds is reasonably consistent in the moderately gyrencephalic macaque ( Van Essen et al., 2012a) but is much more variable in humans, especially in regions of high folding variability ( Amunts et al., 1999 and Van Essen et al., 2012b). A corollary of this observation is that perfect alignment of cortical areas (and hence cortical function) cannot be achieved using any registration method that relies exclusively on folding patterns or other shape features. Fortunately, novel approaches now enable registration based on function and other areal features (see below). The next three subsections provide an update on cortical parcellations in the mouse, macaque, and human, along with reference to key historical milestones in order to provide perspective. Visual cortex warrants special consideration owing to the recent identification of many more visual areas than envisioned in classical schemes. Early studies of rodent visual cortex suggested that area V1 was surrounded by only one or two neighboring retinotopically organized visual areas (E. Wagor et al., 1977, SfN, abstract).