Ординатура / Офтальмология / Английские материалы / The Neuropsychology of Vision_Fahle, Greenlee_2003

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areas. Thus, the variability of laminar distribution among feedback connections between areas at different distances on the cortical surface (see the section ‘Definitions’) may correspond to different functional roles played by distant feedback connections (for example TE to V1) compared to those between adjacent areas (like V2 to V1).

Assuming that the patchy and unbranched nature of feedforward connections reflects the necessity to organize inputs according to specific properties, the more diffuse character of the feedback connections to layer 1 suggests that it plays a more general role such as controlling the contrast gain or membrane potential of target neurons. Such a general role cannot be extended to all feedback connections because feedback connections to layers 2 and 3, with their patchy organization, probably play a very specific role in the processing of visual information (see below).

What differentiates neurons with axonal bifurcation to several cortical areas from neurons that project to only one cortical area? This question is particularly interesting for the feedback connections from the infragranular layers that contain a sizeable proportion of axonal bifurcation (Bullier and Kennedy 1987). It is possible that such bifurcation concerns preferentially axons with fast conduction velocity. As shown by modelling studies (Murre and Sturdy 1995), axon size is under strong constraints in the brain of large mammals. Projection of thick axons to several areas by way of bifurcation is one way of limiting their number. Indeed, there are many examples of thick axons that bifurcate. Y cells in the cat lateral geniculate nucleus (LGN) that have the largest axons send bifurcation to areas 17 and 18 (Bullier and Kennedy 1987) and Meynert cells in layer 6 of area V1 send bifurcating axons to at least area MT and the superior colliculus (Fries et al. 1985). In functional terms, the bifurcation of thick axons to several cortical areas is an efficient way to rapidly and simultaneously coactivate several cortical areas.

Synaptic transmission

Reports of electron microscopy (EM) studies on cortico-cortical connections all agree that such connections make excitatory synapses on their target neurons (Anderson et al. 1998; Gonchar and Burkhalter 1999; Johnson and Burkhalter 1996; Lowenstein and Somogyi 1991). Given the laminar and morphological differences between feedforward and feedback connections reviewed above, it is expected that the synaptic organization of these different sets of connections will also show differences. The morphology of feedforward connections from V1 to V5 was recently investigated by Anderson and his collaborators (1998). Terminal boutons formed asymmetric (presumably excitatory) synapses and tended to contact preferentially spiny neurons (excitatory, mostly pyramidal), but also terminated on smooth, presumably inhibitory, cells in 20% of the cases. Very similar proportions were reported by Lowenstein and Somogyi (1991) in their study of the feedforward projection from area 17 to PMLS in the cat, an area that has been considered homologous to area MT of primates (Payne 1993). In a study of feedforward connections between visual cortical areas in the rat, Johnson and Burkhalter (1996) reported a smaller proportion of contacts on to synaptic shafts (10%).

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Less is known concerning the synaptic organization of feedback connections. The early results of Johnson and Burkhalter (1996) suggested that feedback connections contact more specifically spines of pyramidal cells (98% of the cases) and rarely terminate on dendritic shafts. However, a more recent report by the same group found similar proportions of terminals on parvalbumin-rich GABAergic interneurons (10%) in feedforward and in feedback connections in the rat visual system (Gonchar and Burkhalter 1999). Differences were found in the site of termination, with feedback connections terminating on distal parts of the dendrites of GABAergic parvalbuminrich interneurons whereas feedforward connections contact dendritic regions closer to the cell body (Gonchar and Burkhalter 1999). This is in keeping with functional data from the same group showing that feedback connections have mostly an excitatory influence, whereas electrical stimulation of intrinsic and feedforward connections tend to recruit inhibitory circuits at higher stimulus intensities (Shao and Burkhalter 1996). The latter results, however, should be treated with caution since electrical stimulation acts exclusively on axonal branches (Nowak and Bullier 1998a,b) and therefore stimulating in one area stimulates orthodromically the efferent axons as well as the afferent axons antidromically. It is impossible to differentiate the synaptic potentials evoked by direct orthodromic activation from those evoked by recurrent collaterals of antidromically activated axons. This confusion probably explains why the laminar pattern of electrical activation elicited in a given cortical area by electrical stimulation in another does not always fit with that predicted from the laminar distribution of axon terminals (Domenici et al. 1995; Nowak et al. 1997).

The low proportion of terminals on dendritic shafts reported for feedback connections by Burkhalter and his colleagues contrasts with the results of an earlier EM study of the feedback connections between areas 18 and 17 in the cat (Fisken et al. 1975). In that study the authors concluded that more than 30% of the terminals of feedback connections were located on dendritic shafts. Whether this discrepancy is related to a species difference or whether there is indeed a strong feedback projection to dendritic shafts remains to be determined by further studies.

Hierarchical organization of cortical areas

The classification of cortico-cortical connections in feedforward, feedback, and lateral connections led Maunsell and Van Essen (1983) to define a hierarchy of cortical areas on the basis of a simple rule: the areas are arranged in a series of levels defined by their connections with each other. At the lowest level is found the area that receives only feedback connections and sends only feedforward connections to other areas (area V1 in the monkey, area 17 in the cat). At the next level is found V2 which receives feedforward connections from V1 but receives only feedback connections from other areas. Above V2 is found V3 which receives feedforward connections from V1 and V2 and feedback connections from other areas. In addition, it is possible for two areas to belong to the same level if they exchange lateral connections.

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It is remarkable that this simple set of rules is in most cases internally consistent. If area A sends feedforward connections to area B, then area B sends feedback connections to area A; if area A sends lateral connections to B, B sends lateral connections to A. A small number of exceptions have been noted (Felleman and Van Essen 1991). Applying these rules to the areas of the macaque monkey initially generated the pattern shown in Fig. 2.5(a). More recent versions (Fig. 2.5(b)) have a similar organization but become more complicated as more connections have been discovered (DeYoe et al. 1994; Felleman and Van Essen 1991).

This method helps in organizing the large number of cortical areas of the monkey visual system in a small number of distinct levels but it has two disadvantages: (1) it is an anatomical classification that says little about the functional interactions between the areas (we will come back to this question below); (2) it is largely underdetermined as pointed out by Malcolm Young and his associates (Hilgetag et al. 1996). This means that the set of rules used to construct the hierarchy leads to many different ways of classifying cortical areas in different levels. Optimal solutions lead to smaller numbers of rule violations, but it is impossible to claim that one configuration is optimal because of the lack of knowledge concerning many connections. As shown in Fig. 2.5(c), the consequence of the underdetermined character of the hierarchical scheme is that a given cortical area such as area MT can occupy levels 5–10. As a consequence, for most pairs of cortical areas beyond V1, V2, and V3, it is difficult to determine whether one area is at a lower or at a higher level, or whether they belong to the same level in the hierarchy.

An attempt has been made recently to reduce this underdetermined character by quantifying the proportions of source neurons in supragranular versus infragranular layers (Barone et al. 2000). When this is done, a reasonably good match to the original hierarchy of Felleman and Van Essen is obtained and, provided a few adjustments are made, the proportion of labelled neurons in supragranular layers is a good predictor of the hierarchical level (Fig. 2.6). However, when Figs 2.5 and 2.6 are compared, there are discrepancies between the levels at which a given area belongs. Note, for example, how the FEF belongs to the highest level in the original map (Fig. 2.5(a)), to the eighth level in the 1991 version (Fig. 2.5(b)), and is brought down to the fourth level when attention is paid to the proportions of supragranular layer neurons (Fig. 2.6).

The underdetermined character and the variability of classification of different schemes shown in Figs 2.5 and 2.6 suggest that caution should be applied when attempts are made at deriving functional interpretations from the hierarchical classification. Furthermore, as mentioned below (see section on timing), the latencies of neurons in different cortical areas cannot be predicted from the hierarchy of cortical areas, as would be expected if the hierarchical organization corresponded to a functional model with a succession of processing stages along the hierarchy.

Another interpretation of the laminar organization of neurons and axon terminals of different cortico-cortical connections has been proposed by Barbas (Barbas 1986; Barbas and Rempel-Clower 1997) for the connections in the monkey frontal cortex.

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differences between feedforward and feedback connections in occipital, parietal, and temporal cortex may simply reflect differences in organization between sensory cortices of the occipital cortex with well differentiated structures (areas V1 and V2) and areas with less differentiated structures in the parietal and temporal cortices. One advantage of this model is that it predicts the observed progressive shift toward projections from infragranular layers terminating at higher levels in the target area with increasing distance (in terms of levels of organization that reflect distance on the cortical surface). The interpretation of laminar organization of cortico-cortical connections in terms of the phylogenetic evolution of cortex is supported by the results from development studies that show major reorganizations of this organization during preand postnatal development (see the section ‘Development of cortico-cortical connections’).

Functional streams and channels in feedforward cortico-cortical connections

The extensive array of connections between cortical areas shown in Fig. 2.5(b) contains a number of streams or channels that group some connections together. The idea of functional streams goes back to the classification of retinal ganglion cells and thalamocortical neurons. In the 1970s, the population of cat retinal ganglion cells was subdivided into X and Y and W cells. Each of these classes was found to be connected to different neuronal subgroups in the LGN and cortex (Stone 1983). Subsequently, a similar division was found in the retinogeniculostriate system of monkeys with the characterization of magnocellular, parvocellular, and koniocellular streams in the retinogeniculate system (Hendry and Reid 2000; Hendry and Yoshioka 1994; Merigan and Maunsell 1991).

Another functional subdivision of the visual system was proposed at the same period— that between structures subserving form and space vision. The separation between space and form vision was already present in the early models of the visual system based on the study of non-primate species, with the superior colliculus involved in space vision and the visual cortex dealing with form vision (Schneider 1969). A similar distinction was made between structures dealing with focal and ambient vision (Trevarthen 1968). Since the beginning of the twentieth century, it was known that, in humans, lesions in the parietal and temporal cortex lead to deficits in space and form vision, respectively. All these ideas were synthesized in the concept of two functional streams in the primate visual cortex, with the ventral occipitotemporal stream dealing with form vision and the dorsal occipitoparietal stream involved in space vision. The success of this subdivision was established by the demonstration in the monkey of a double dissociation of the effects of lesions in the parietal and inferotemporal cortex (Pohl 1973) that mirrored the clinical observations in humans, and by the tracing of anatomical connections between striate cortex and parietal and inferotemporal cortex (Ungerleider and Mishkin 1982). The segregation of cortical connections into dorsal and ventral streams was confirmed by the results of mathematical models grouping together the densest connections between different cortical areas of the monkey (Jouve et al. 1998; Young 1992).

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Since then, questions have been raised concerning the roles of the two cortical streams. The initial idea was that the dorsal stream is involved in processing where an object is located in the visual field, whereas the ventral stream is engaged in the recognition of objects (the ‘where/what’ of Ungerleider and Mishkin 1982). More recently, the emphasis has shifted to the visuomotor aspects of processing in the dorsal stream. In addition to dealing with where an object is located, the dorsal stream is important for grasping and manipulating an object (Goodale and Milner 1992; Jeannerod et al. 1995). Despite these evolutions, the basic idea that parietal and inferotemporal cortices deal with different aspects of vision has stood the test of time. More recent work showed that the two streams remain partially separate in the frontal cortex and that there are regions of convergence in frontal cortex and in the depths of the superior temporal sulcus (Baizer et al. 1991; Bullier et al. 1996; Morel and Bullier 1990). Various diagrams of the two visual streams are presented in Fig. 2.7.

The two visual streams have been integrated in the hierarchical organization of cortical areas: in the diagrams of Van Essen and his colleagues, the ventral stream is to the right and the dorsal stream to the left (Fig. 2.5(b)), whereas they are located above each other in the Ungerleider and Desimone’s version of the hierarchy (Fig. 2.7(b)).

In 1984, in a sweeping synthesis, Livingstone and Hubel attempted to combine together the magno/parvo subdivision in retino-thalamo-cortical pathways and the two cortical visual streams in primates. The impetus behind this new synthesis was the discovery of the subdivisions in V1 and V2 revealed by reacting the tissue for cytochrome oxidase, a metabolic enzyme sensitive to neural activity (Wong-Riley 1979a). This showed the presence of cytochrome oxidase-rich blobs in V1 (Horton and Hubel 1981) and the thin, thick, and pale cytochrome oxidase bands in V2 (Livingstone and Hubel 1984, 1987a). Cytochrome oxidase bands in V2 became particularly important when it was demonstrated that they mark the territories providing inputs to the dorsal and ventral streams (Fig. 2.8). The thick cytochrome oxidase bands in V2 were found to project to area MT and from there to the dorsal stream. The thin and pale bands project to V4 (DeYoe and Van Essen 1985; Shipp and Zeki 1985) that constitutes the entry to the ventral stream (Fig. 2.8). The interconnections between these different territories were thought to be minimal, suggesting the presence of two (or three) parallel and independent cortical channels beginning in V2. The story became even more interesting when Hubel and Livingstone showed that the blobs in V1 project to the thin bands in V2, whereas the interblob regions in layers 2–3 of V1 project to the pale bands of V2. Finally, layer 4B in V1 projects to the thick bands in V2 that relay information to area MT (Fig. 2.8). Although connections between them have since been demonstrated (Levitt et al. 1994; Yoshioka et al. 1994), these channels are usually considered as transferring information in parallel from V1 to areas V4 and MT, in a manner similar to that of the parallel channels through the LGN.

Because it was thought at the time that blobs and interblobs receive exclusively parvocellular inputs, Livingstone and Hubel proposed that the parvo/magno division in the LGN continues in the cortex, with the parvocellular neurons driving the ventral

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Fig. 2.8 The magno-, parvo-, and koniocellular streams. For simplicity, only feedforward connections have been illustrated. P and M, parvocellular and magnocellular layers of the LGN. K, koniocellular layers of the LGN, also called interlaminar. C-O band, cytochrome-oxidase band. Note that beyond the first stages in V1 (layer 4C and ), the magno, parvo, and konio streams are no longer segregated as they are in the LGN. Note also that the parietal cortex is mostly under the influence of the magno stream with direct connections from layer 4B to MT and indirect connections through the thick cytochrome oxidase bands.