... Evolution of Columns, Modules, and Domains in the Neocortex of Primates...

... The specialized regions of neocortex of mammals, called areas, have been divided into smaller functional units called minicolumns, columns, modules, and domains. Here we describe some of these functional subdivisions of areas in primates and suggest when they emerged in mammalian evolution. We ... in all cortical areas. Classic columns are defined by a repeating pattern of two or more types of cortex distinguished by having different inputs and neurons with different response properties. Sensory stimuli that continuously vary along a stimulus dimension may activate groups of neurons that ... neurons are separated by narrow septa of fibers that reflect discontinuities in the receptor sheet. Larger regions of posterior parietal cortex and frontal motor cortex are parts of networks devoted to producing different sequences of movements. We distinguish these larger functionally distinct ... . Some of the columns found in primates likely emerged with the first primates, whereas others likely were present in earlier ancestors. The sizes and shapes of columns seem to depend on the balance of neuron activation patterns and molecular signals during development....

... Department of Psychology, Vanderbilt University, Nashville, TN 37240-7817. E-mail: jon.h.kaas@vanderbilt.edu....

... depend on the cortical areas, the so-called “organs of the brain” (Brodmann, 1909) that are specialized for processing different inputs and providing different outputs. Cortical areas can be hard to define and identify, and their exact number in any species is uncertain. However, it is ... that the number of cortical areas varies across extant taxa, from approximately 20–30 or so to perhaps more than 200 in humans (Kaas and Preuss, 2008). Because the first mammals had little neocortex and likely few cortical areas, interest in the evolution of neocortex across the great ... of mammals has largely focused on the issue of modifying and adding cortical areas. Some of the cortical areas proposed for primates are shown in Fig. 7.1. However, areas are often composed of smaller ... , the cortical columns or modules, and these subdivisions within areas modify and expand the functions of areas. Thus, an understanding of how different types of neocortex evolved depends not only on determining the numbers and types of cortical areas that exist but also on the ... the types of columnar subdivisions of cortical areas that have been proposed (Hendrickson, 1985; Purves et al., 1992; Mountcastle, 1997; da Costa and Martin, 2010) and then consider how and when such modules might have evolved. The phyletic distributions of the types of columns in extant mammals ... one to infer when such columns evolved (Hennig, 1966; Striedter, 2005). Primates, rodents, tree shrews, and lagomorphs are all placed within the superorder Euarchontoglires. Thus, we are especially interested in how types of columns are distributed within ...

... One of the defining features of neocortex is that it consists of layers and various sublayers of neurons specialized for different steps in processing; neurons in radial (vertical) arrays across the layers are more densely ... than neurons along the layers (Casagrande and Kaas, 1994; Nieuwenhuys, 1994b; Kaas, 2010). As a result, neurons in narrow vertical arrays share many response properties, especially the location ... the receptor fields of neurons on the sensory receptor surface. This arrangement has great functional importance, and it is likely responsible for the impressive flexibility and powers of neocortex. Developmentally, minicolumns reflect...

... view of the left cerebral hemisphere. Modular subdivisions of some of these areas are discussed in the text. Visual areas include the first, second, and third areas (V1, V2, V3), dorsomedial (DM or V3a) and dorsolateral visual areas (DL or V4), the middle temporal area (MT), the MT crescent (MTc), and ... medial superior temporal (MST) area. The representation of the zero horizontal meridian (HM) divides the representation of the upper (+) and lower (-) visual hemifields. Motor areas include primary motor cortex (M1), ventral (PMv), and dorsal (PMd) premotor cortex, the supplementary motor ... (SMA), and the frontal eye field (FEF). Somatosensory areas include the four areas of anterior parietal cortex (3a, 3b, 1, 2), with the region representing ... inputs from the hand indicated in area 3b (S1). Modular subdivisions in V1 (dots) and V2 (bands) are shown in black (see text). Ovals mark the locations of proposed reach, defense, and grasp domains in motor and posterior parietal cortex (PPC). ...

... the radial migration of clones of excitatory neurons from progenitors in the ventricular and subventricular zones (Rakic, 1995b), as radially arranged sister neurons preferentially develop synapses with each other (Yu et al., 2009). These ... minicolumns (Mountcastle, 1957, 2003). Minicolumns are sometimes visible as vertical arrays of neurons separated somewhat by neuropil (Buxhoeveden and Casanova, 2002; DeFelipe et al., 2002). Minicolumns are thought to be 30–50 μm in diameter, although functional boundaries between them are ... likely to be sharp owing to the spread of apical dendrites of pyramidal cells and the extents of axon arbors of cortical neurons and subcortical activating inputs. Because minicolumns are clearly visible in a number of cortical areas, and across mammalian species, including ...

... somatosensory input. The subsequent evidence for such alternating patches of neurons activated by either deep or superficial receptors of the skin and deeper tissue has been limited, and they do not seem to exist in area 3b (S1 proper) of somatosensory cortex of monkeys. Instead, there is evidence ... receptors of the skin (Sur et al., 1981, 1984). There is also evidence for at least a partial segregation of territories activated by slowly adapting and rapidly adapting receptors in area 1 of somatosensory cortex of monkeys (Friedman et al., 2004). However, given these limited observations, we can ... little about the phyletic distribution of slowly adapting and rapidly adapting cortical columns, or their evolution, even in primates....

... More can be said about the blob and interblob surround organization of primary visual cortex (V1) in primates (Fig. 7.2). All primates seem to have a pattern of cytochrome oxidase (CO)- ... blobs (reflecting high metabolic activity) within interblob surrounds of lower CO levels (Horton, 1984; Horton and Hedley-Whyte, 1984; Preuss and Kaas, 1996). Neurons in the blobs respond to color, are less selective for stimulus orientation, and have higher firing rates than neurons between ... blobs (Livingstone and Hubel, 1984; Hendrickson, 1985; Felleman, 2008; Lu and Roe, 2008; Economides et al., 2011). However, blobs and interblob regions are found not only in primates with trichromatic or dichromatic color systems but also in nocturnal primates with only one ... type of cone in the retina (Wikler and Rakic, 1990). The blobs and interblobs are also distinguished by different patterns of inputs from the visual thalamus, intrinsic connections, and connections with other visual ... (Livingstone and Hubel, 1984; Casagrande and Kaas, 1994). In macaque monkeys, most of these connections are well developed in newborns (Barone et al., 1996; Baldwin et al., 2012). The ... in response characteristics that are mediated by differences in activating inputs fits the classic definition of cortical columns, although the blobs and interblobs do not occupy equal territories, and the interblob territory is continuous. The blob and surround pattern evolved in the immediate...

... FIGURE 7.2 Anatomically defined columns in visual cortex of primates. Sections of primary visual cortex (V1) and the adjoining second visual area (V2) of a macaque monkey have been cut parallel to the brain surface and processed for CO, a marker of neurons with ... metabolic requirements. The brain sections provide a “surface view” of parts of V1 and V2. In V1, there is a pattern of CO-rich “blobs” (also called “puffs” or “patches”) surrounded by cortex that ... less CO, the interblob territory. In V2 an alternating pattern of CO-dark bands, separated by CO-light bands, cross the width of V2. The CO-dark bands are of two types, thick and thin. Thus, there are three types of bank-like structures in V2 that can be anatomically distinguished. Because the CO ... and interblobs, as well as the CO-dense thick, thin, and interbands have neurons that differ in response properties, they can be considered classic columns. A pattern of CO-dense and CO-light bands is also present in ...

... ancestors of primates, or in archaic primates, given that none of the close relatives of primates, tree shrews, rodents, and lagomorphs have blobs in V1....

... columns are also found in the second visual area, V2, of most primates, where V2 is characterized by a repeating series of CO-dense thick stripes and CO-dense thin stripes separated by CO-pale interstripes. These band-like stripes cross the narrow width of V2, and they seem to exist in all ... primates (Kaas, 2003). The three types of stripes differ in anatomical connections and have neurons with different response properties. The stripes and differences in connections are apparent in newborn macaques (Barone et al., 1996; Baldwin et al., 2012). Although the CO-dense stripes are not ... as thick or thin, they can be identified by functional differences, with neurons in the thick stripes sensitive to binocular disparities and stimulus orientation, the neurons in the thin stripes sensitive to luminance and color, and neurons...

... in pale stripes sensitive to stimulus orientation (Hubel and Livingstone, 1987; Livingstone and Hubel, 1988; Lu and Roe, 2007; Felleman, 2008; Kaskan et al., 2009). The thick stripes project to visual area MT, whereas the other bands project to DL (V4). In ... primates, CO stripes in V2 are only weakly apparent, and such stripes are not present in V2 of tree shrews and rodents (Kaas, 2003). Thus, aspects of the stripe pattern may have evolved in early primates, whereas such stripes became fully developed as ...

... Although the V1 blob and interblob regions, as well as the V2 stripes, do not look like cylindrical pillars, they otherwise conform to the expectations of classic cortical ... poorly understood visual area is composed of a series of CO-dense puffs in a single row, like beads on a string in a belt of CO-pale tissue (Kaas and Morel, 1993). The significance of these puffs and surrounds in MTc, which have different connections with other visual areas, remains to be ...

... Several cortical areas have repeating representations of stimulus orientations for different portions of the visual field (Hubel and Wiesel, 1963). Most notably, primary visual cortex of primates, carnivores, and tree shrews have repeating “pinwheel” patterns of cortex, ... which stimulus orientation is systematically represented from vertical to horizontal lines and edges and back again (Bonhoeffer and Grinvald, 1991; Fitzpatrick, 1996; Kaschube et al., 2010). Groups of neurons most sensitive to one stimulus orientation or another can be selectively ... , the activity pattern optically imaged, and regions of cortex sensitive to different orientations color coded to produce colorful illustrations of arrays of orientation “columns.” ... ” between orientation columns are arbitrary. In addition, all “orientation columns” are selective for the same stimulus features, and thus these columns are not of the classic type, which are segregated by different classes of activating inputs. However, each entire array of ... -selective neurons, the pinwheel for a given location in the visual field, can be considered as a larger domain or hypercolumn (Hubel and Wiesel, 1972, 1977). Orientation hypercolumns are widespread in visual cortex of primates: they also have been identified in V2 stripes, V3, V4 (DL), ...

... grouping of neurons by their preferences for stimulus orientation seems to be a trait that emerged first in V1 in the common ancestors of tree shrews and primates, because tree shrews also have orientation hypercolumns. However, the more distant relatives, rodents and rabbits, have orientation-...

... These hue-selective subregions are not classic columns because they are not separated by columns that are most sensitive to another stimulus feature, and they have arbitrary boundaries....

... on one end, to high-frequency sounds on the other (Kaas, 2011). Thus, there are no modular divisions based on sound frequency, although isofrequency bands with arbitrary borders have been described. However, bands of primary auditory cortex where neurons that are excited from both ears (EE bands) ... with bands of cortex with neurons that are excited by the contralateral ear and inhibited by the ipsilateral ear (EI bands) have been reported for cats (Merzenich and Kaas, 1980). The EE and EI bands extend across the isofrequency contours. Because EE and EI bands have ... of differing functional properties, they qualify as classic columns (although shaped like bands). Such bands have not been identified in auditory cortex of primates....

... of neurons in somatotopic maps of the body surface, or retinotopic maps of the two eyes, in areas of cortex. The best-known example is the rows and columns of “barrels” in primary...

... somatosensory cortex of rats and mice, where a barrel-like structure represents each of the large sensory whiskers on the side of the face (Woolsey et al., 1975). The digits and pads ... the feet also relate to separated groups of neurons (Dawson and Killackey, 1987)....

... The many studies of the “barrel field” of mice and rats have revealed that differences in neural activity are important in the formation of barrels, such that the number of barrels varies with the ... of facial whiskers. Molecular factors also alter the formation of barrels, as revealed in mutant mice (Erzurumlu and Kind, 2001). Such segregations of cortical neurons by body part are found in primary somatosensory cortex of many species, but are perhaps most ... star-nosed mole, where the highly innervated tactile rays of the nose are each separately represented in three areas of somatosensory cortex (Catania and Kaas, 1996). In primary somatosensory cortex of New World and Old World monkeys (Jain et al., 1998; Qi and Kaas, 2004), and possibly other anthropoid ... separating the representation of digit 1 (thumb) from that of the face. Such separated representations of digits in area 3b of primates are variable and have not been described in prosimian primates. Septa that separate representations of digits are more apparent in macaque monkeys than in New World ... monkeys and squirrel monkeys....

... It could be argued that the narrow septal regions that separate the cortical barrels, bands, and other modules related to body parts do have neurons that differ in connections, such as having corpus callosum connections, and thus there is an ...

... The retina of each eye is a continuous sensory surface, except for the nerve head and a narrow septum corresponding to the nerve head, which disrupts layers of the lateral geniculate nucleus that receive projections from the ... . Thus, the afferents from the hemiretina of each eye terminate in separate layers in the lateral geniculate nucleus of the visual thalamus, and then these layers project in retinotopically matched patterns to primary visual...

... cortex to either congruently overlap or to separate locally in variable patchy-to-banding patterns in layer IV while maintaining some level of retinotopy, depending on species (Florence and Kaas, 1992; Horton and Adams, 2005). Ocular ... columns, first revealed in microelectrode recordings (Hubel and Wiesel, 1968), and axon termination patterns from layers of the lateral geniculate nucleus (Wiesel et al., 1974) can also be demonstrated by differences in activity ... (Horton, 1984; Takahata et al., 2009a). The segregation of eye-related afferents is very weak in some primates, such as nocturnal prosimian galagos and owl monkeys (Kaskan et al., 2007; Takahata et al., 2011), and highly variable patterns exist in New World monkeys, even across individuals within a ... (Horton and Adams, 2005). Ocular dominance patterns may reflect a high degree of segregation of thalamic afferents in layer 4 of primary visual cortex, as in Old ... monkeys (Fig. 7.3), apes, and humans, or reflect such a low level of separation that they are anatomically cryptic and only revealed by relative differences in...

... FIGURE 7.3 Ocular dominance columns (bands) in a flat surface view of primary visual cortex (V1) of an Old World macaque monkey as reflected by distribution of terminations of lateral ... segment (MS) of V1 is activated by the monocular segment of the contralateral visual hemifield that is seen only by the contralateral eye. Foveal and central vision is represented to the left, and the extreme of peripheral vision is represented to the right. The ocular dominance bands break up into ... dot-and-surround pattern in the part of V1 that represents peripheral vision as the inputs from the contralateral eye (white) become proportionately greater, ... form the larger surrounds. Modified from Florence and Kaas (1992)....

... genes (Takahata et al., 2009b). Ocular dominance “columns” are absent in the closest relatives of primates, tree shrews, rodents, and rabbits, and thus are a feature of visual cortex that evolved in early primates but became more pronounced in Old World monkeys, apes, and humans. ... ocular dominance columns have evolved independently in carnivores (Anderson et al., 1988), and they likely exist in other taxa....

... Primary motor cortex and dorsal and ventral premotor areas are widely recognized as valid cortical areas, and each of these areas has a somatotopic representation of small movements of body parts that are revealed by brief trains of near-threshold pulses of ... body parts, such as the forelimb, have a locally fractured somatotopy so that different movement zones, roughly the size of minicolumns, are mixed and repeated (Fig. 7.4). Thus, the forelimb region mixes zones for digit, wrist, elbow, and shoulder movements in a puzzling arrangement (Gould, 1986; ...

... electrical pulses at higher current levels evoke more complex movement sequences from motor cortex than do short trains at threshold levels (Leyton and Sherrington, 1917). More recently, Graziano et al. (2002) have used longer (0.5 s) trains of electrical pulses to define different regions or domains ... (Fig. 7.1) in motor cortex where different ethologically relevant movement can be evoked (climbing, reaching, grasping, defense of the head, hand-to-mouth). Matching movement domains have been identified in posterior parietal cortex (Cooke et al., 2003; Stepniewska et al., 2005; Gharbawie et al. ... parts of the forelimb representation, perhaps offering some explanation for the mosaic of minicolumns for different but related small movements and muscle twitches that are revealed by short trains of pulses at threshold levels of stimulating current (Fig. 7.4). Thus, circuits within a domain may ...

... FIGURE 7.4 Proposed functional organization of the hand–forearm segment of primary motor cortex (M1) in monkeys and other primates. Although M1 has an overall somatotopy, the local somatotopy is fractured to form a mosaic of radial rows of neurons that evoke small, ... relevant movement sequences, such as grasping, reaching, or defending the head against a blow. We refer to these larger divisions of motor, premotor, and posterior parietal cortex (Fig. 7.1) as domains (Gharbawie et al., 2011a)....

... Functionally matched domains for at least some of the complex movement patterns of primary motor cortex also exist in premotor cortex and in posterior parietal cortex. The domains in posterior parietal cortex may be parts of larger cortical areas. The domains in frontal and posterior ... cortex have similar spatial arrangements in prosimian galagos, two species of New World monkeys, and Old World macaque monkeys, and there is indirect evidence for them in humans (Kaas et al., 2011). Thus, they likely exist in all primates. Such domains for complex movements may ... exist in motor cortex of the relatives of primates, tree shrews and rodents, where M1 also has a fractured somatotopy (Remple et al., 2007; Cooke et al., 2011). However, posterior parietal cortex is no more than a ... strip of cortex in tree shrews and rodents and is unlikely to contain a series of primate-like domains....

... Other areas of cortex may also have larger functionally distinct regions within cortical areas. For example, some of the face-selective and object-...

... selective regions of temporal cortex in macaque monkeys and humans resemble domains (Tsao et al., 2003, 2008a; Pinsk et al., 2005; Rajimehr et al., 2009). Likewise, the large visual area termed V4 or DL has ... selective or orientation selective (Tanigawa et al., 2010), although these large regions might also be considered separate cortical areas (Cusick and Kaas, 1988; Stepniewska and Kaas, 1996)....

... How Do Columns and Modules Emerge in Development?...

... of coactive afferents together with cellular signals that are position dependent probably are two of the most important variables (Erzurumlu and Kind, 2001; Sur and Leamey, 2001; Kaas and Catania, 2002). There is considerable evidence to support this conclusion, but some of the most impressive ... comes from studies that created three-eyed frogs (Constantine-Paton and Law, 1978; Katz and Constantine-Paton, 1988). In frogs, each optic tectum normally receives inputs from only the contralateral eye, but when a third eye is added ... , but local groups of tectal neurons favor inputs from one eye or the other. The result is that the afferents from the two eyes form alternating bands or stripes that resemble the ocular dominance bands in cats and anthropoid primates. The borders between these bands in the optic tectum and visual ... correspond to locations where abrupt differences in activity patterns occur, and they do not develop or they degrade when activity is blocked (Cline et al., 1987). Obviously, the ability to form ocular dominance bands did not ... that produced these columns were present for other reasons that are not clear but apparently are widely important in nervous system development (Katz and Constantine-Paton, 1988). The capacity for module formation seems to be inherent in all cortical tissue, as well as in other tissue such as the optic ... or superior colliculus, where inputs of different activation patterns compete for location with an overall global map. Thus, ocular dominance bands and other configurations, as well as orientation modules and other types of columns, including those based on discontinuities of the receptor sheet, have ... independently in several lines of mammalian evolution. For some of these types of modules, asking what they do (Horton and Adams, 2005) may be the wrong...

... question. Instead, we might ask, what else is achieved in neural tissue by the mix of activity-dependent and position-dependent factors that select and group synaptic contacts when these factors coexist at particular developmental times? Purves et al. (1992) have suggested that some of the columns ...