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

22 GREGOR RAINER AND NIKOS K. LOGOTHETIS

Tolhurst, D.J., Movshon, J.A., and Dean, A.F. (1983). The statistical reliability of signals in single neurons in cat and monkey visual cortex. Vision Res. 23 (8), 775–85.

Ungerleider, L.G. and Mishkin, M. (1982). Two cortical visual systems. In Analysis of visual behavior (ed. D.J. Ingle, M.A. Goodale, and R.J.W. Mansfield), Vol. 18, pp. 549–86. MIT Press, Cambridge, Massachusetts.

Werner, G. and Mountcastle, V.B. (1963). The variability of central neural activity in a sensory system, and its implications for the central reflection of sensory events. J. Neurophysiol. 26, 958–77.

Zeki, S.M. (1973). Colour coding in rhesus monkey prestriate cortex. Brain Res. 53 (2), 422–7.

Chapter 2

Cortical connections and functional interactions between visual cortical areas

Jean Bullier

Introduction

Since the late 1980s it has been usual to partition the cortical surface of vertebrates in a number of functional areas. These do not always correspond to the areas discovered by Brodmann and the cytoarchitectonic school of the beginning of the century. In the visual system, functional areas are usually smaller than cytoarchitectonic areas, with the exception of area 17, which corresponds exactly to area V1, and area 18, which, in some species such as the cat and the tree shrew (Kaas 1996), corresponds to area V2. The discovery of functional areas in the human brain is more recent but conforms to this general rule that functional areas are smaller than Brodmann’s areas. The present chapter reviews what is known of the interconnections between visual areas in the two animals that have received the most attention, the macaque monkey and the cat. A simplified version of the visual cortical areas in these two animals is presented in Fig. 2.1.

Functional areas are interconnected by a very dense network of cortico-cortical connections, also called interarea or extrinsic connections. Connections exist between areas of the same cortical hemisphere (intrahemispheric connections), as well as between areas of opposite hemispheres (interhemispheric or callosal connections). Diagrams of the intrahemispheric connections between visual areas of the cat and monkey can be found in earlier reviews (Boussaoud et al. 1990; Bullier et al. 1996; Felleman and Van Essen l991), and are summarized in later sections.

Interarea or extrinsic connections are made by pyramidal neurons, which also send collaterals to neighbouring neurons within a few millimetres. These connections, together with those of inhibitory -aminobutyric acid (GABA)ergic interneurons, are called intraarea, local, horizontal, or intrinsic connections. Although these connections are not the subject of the present review, they share several characteristics with interarea connections and much of the present line of research consists in distinguishing between influences mediated by intrinsic and by extrinsic cortico-cortical connections. All pyramidal neurons that send extrinsic cortico-cortical connections also send local

CORTICAL CONNECTIONS AND FUNCTIONAL INTERACTIONS 25

1

Fig. 2.2 Pyramidal neuron stained by intracellular injection of horseradish peroxidase in cat area 17. Note the dense arborization of the axon collaterals in area 17 and the axon leaving the cortex in the white matter. The local collaterals are the main source of the horizontal connections in the cortex (also called intrinsic connections). They carry the same messages as the axons of extrinsic connections that connect to other cortical areas. (Reproduced from Martin 1984.)

of GABAergic smooth stellate cells send connections between neighbouring cortical areas (McDonald and Burkhalter 1993). Interhemispheric connections have also been found to arise from a few presumably inhibitory interneurons in the rat (Hughes and Peters l992a,b) and in the cat (Peters et al. 1990). Despite this evidence from anatomy, no monosynaptic inhibitory synaptic potential has ever been reported in electrophysiological studies of connections between cortical areas of the same or opposite hemisphere. It can therefore be concluded that interarea and interhemispheric cortico-cortical connections are excitatory. However, intraand interhemispheric connections always contact excitatory pyramidal cells as well as inhibitory interneurons in the target area (see below for the proportions) and the net effect of cortico-cortical connections is therefore a mixture of excitatory and inhibitory influences.

It is known that, within the local intraarea network, the densest connections are with immediate neighbour neurons. This is demonstrated by placing small injections of

26 JEAN BULLIER

anterograde or retrograde tracers in a given site and examining the local distribution of labelled axons and neurons. The higher density of local connections is due to the branching pattern of axons that arborize more profusely near the main axon trunk. The distribution of boutons along axonal branches, on the other hand, appears to be more or less uniform (Braitenberg and Schüz 1991).

In a similar fashion, interarea connections tend to be densest with neighbouring cortical areas. For example, the strongest connections of area V2 are with neighbouring areas V1 and V4 in the monkey. Similarly, in the cat, the strongest connections of area 17 are with adjacent areas 18 and 19. There are, however, a few examples of adjacent areas that are not interconnected, such as the retrosplenial visual area in the monkey that has no connections with area V1 although it is surrounded by it on its caudal and lateral borders. The major exception to the rule of preferential connections with neighbour areas is observed in the relationship between visual areas of the occipital, parietal, and temporal lobes with the frontal eye field area (FEF in Fig. 2.1). This probably corresponds to the different functional roles played by parietal, temporal, and frontal cortical regions in visual processing.

It has been argued that the organization of connectivity in the mammalian brain is under the constraint of minimizing the volume of cortical white matter and that this governs both the local organization of terminal arbors (patchy or diffuse) and the network of interarea connections (Murre and Sturdy 1995). It has also been proposed that the folding of cortex in gyri and deep sulci (Fig. 2.1) in most brains is due to the mechanical tensions created during development by the numerous axons that link together adjacent cortical areas (Van Essen 1997). Minimizing axon tension and volume probably explains the typical folded pattern of most mammalian brains (Fig. 2.1).

Feedforward, feedback, lateral connections

Definitions

Intrahemispheric cortico-cortical connections are often subdivided into three classes: feedforward; feedback; and lateral connections. The difference between feedforward and feedback originated in the distinction made by Rockland and Pandya (1979) who noted that some connections (forward-going) tended to originate in neurons located in supragranular layers (layers 2 and 3) and terminate around layer 4, whereas reciprocal connections (backward-directed) were predominantly made by neurons in infragranular layers (layers 5 and 6) and project outside layer 4. This was later formalized by Maunsell and Van Essen (1983) and Felleman and Van Essen (1991) who defined feedforward, feedback, and lateral connections and used this classification to construct the hierarchy of cortical areas (see the section ‘Hierarchical organization of cortical areas’). Lateral connections do not fit into either feedforward or feedback classes. Their neurons of origin belong to infraand supragranular layers and their terminals arborize in all layers (Fig. 2.3).

These three groups of cortico-cortical connections are not as homogeneous as implied by the synthetic presentation of Van Essen and his colleagues. Quantitative estimates of the proportions of source neurons in infragranular (layers 5 and 6) versus

CORTICAL CONNECTIONS AND FUNCTIONAL INTERACTIONS 27

Feedforward

Feedback

supragranular layers (layers 2 and 3) reveal that there is a continuum in the organization of feedback and feedforward connections instead of two homogeneous populations (Barone et al. 2000). Although this has not been quantified, it appears that a similar continuum is found when the depth level of axonal arborization is considered. As argued earlier (Salin and Bullier 1995), the archetypal organization of feedback connection (neurons in infragranular layers providing input into layers 1 and 2) is only found for connections between areas that are distant on the cortical surface and in the hierarchy of cortical areas. In contrast, feedback connections between neighbouring areas, which are extremely numerous, do not follow the archetypal model and originate from neurons in supraas well as infragranular layers and terminate in all layers except the lower portion of layer 4. Such is the case for the very dense feedback connections from area V2 to V1 in the monkey (Kennedy and Bullier 1985; Kennedy et al. 1989).

28 JEAN BULLIER

Interhemispheric connections have morphological characteristics that class them in the feedforward group for the laminar position of the source neurons (in layers 2 and 3) and in the feedforward or feedback connections for the distributions of the axon terminals. In fact, the organization of axon terminals in interhemispheric connections tends to follow that of intrahemispheric connections. In general, a given area connects to the same areas in the same and in the opposite cortical hemipheres and the laminar distributions of the terminals are similar for interand intrahemispheric connections (Kennedy et al. 1991).

Retinotopic organization

All anatomical studies show an important degree of convergence and divergence in cortico-cortical connections. Typically, a cortical zone a few hundred microns wide projects to and receives from a region that is usually of the order of a few millimetres wide, but can cover up to 15 mm on the cortical surface of a connected area (see review in Salin and Bullier 1995). This important degree of convergence and divergence has consequences for the retinotopic organization of cortico-cortical connections.

It is usually assumed that all connections in the visual system are retinotopically organized, meaning that the receptive field (RF) centres of the afferent neurons are included in the RF centre of the recipient cell. This appears to be the case for a number of connections such as the thalamocortical connections (Reid and Alonso 1995; Tanaka 1983), but cannot be true for all types of cortico-cortical connections because of the large difference in RF sizes between the neurons in some interconnected areas. Mapping studies in the cat (Price et al. 1994; Sherk and Ombrellaro 1988) and inactivation studies in the monkey (Girard and Bullier 1989; Girard et al. 1991a,b) have revealed that feedforward connections are retinotopically organized, i.e. the RF centre of the recipient cell corresponds to the sum of the RF centres of the afferent feedforward connections (Fig. 2.4).

Because the RF centres of neurons tend to increase in size as one moves away from area V1, it is clear that the feedback connections cannot be organized in a similar fashion. Earlier mapping studies showed that the organization of feedback connections is compatible with the rule that neurons tend to interconnect if their RF centres overlap at least partially (Salin et al. 1992). As a consequence, the extent of visual field represented by the feedback connections corresponds to the sum of twice the average diameter of the RF centre in the source area and the average RF centre in the recipient area (Fig. 2.4). Given that some projections to area V1 in the macaque come from inferotemporal cortex neurons (Kennedy and Bullier 1985; Rockland et al. 1994), which have very large receptive fields, it is evident that such connections enable V1 neurons to be influenced by information coming from the highest stages of processing and concerning very large portions of the visual field.

In a similar way, but to a much smaller scale, the horizontal connections link together neurons with neighbouring and partially overlapping receptive fields. The region of the visual field covered by the horizontal connection array approximately corresponds to the point image (the average scatter of RF centres plus the average RF

CORTICAL CONNECTIONS AND FUNCTIONAL INTERACTIONS 29

HM

HM

HM

V1

VM

Fig. 2.4 Retinotopic organization of feedforward, feedback, and horizontal connections. The left part of the figure represents schematically areas V1 and V2 seen from above. Triangles correspond to neuron cell bodies. The direction of the connection is indicated by the arrows on the simplified axons. On the right is represented the right lower visual field of the animal (FP, fixation point; HM, horizontal meridian; VM, vertical meridian). For the feedforward connections, the large square represents the receptive field (RF) centre of the V2 neuron receiving convergent information from the V1 neurons that have the small black squares as RF centres. The combination of RF centres of the afferent V1 neurons make up the RF centre of the target V2 neuron: feedforward connections are visuotopically organized. For the feedback connections, the small black square represents the RF centre of the V1 neuron receiving convergent information from V2 neurons with the large open squares as RF centres. The RF centres of V2 neurons cover a larger region of visual field than that covered by the RF centre of their target neuron in area V1. The feedback connections are only loosely retinotopic and can be used to mix information from distant regions of the visual field. For the horizontal connection, the grey square represents the RF centre of the V1 neuron receiving convergent horizontal connections from neighbouring neurons with RF centres indicated by the black square. The combination of the horizontal afferents covers a larger part of the visual field than the RF centre of the target neuron. Horizontal connections are loosely retinotopic.

30 JEAN BULLIER

centre diameter; Angeluci et al. 2002). Thus, the extent of visual field concerned with the local connections is much smaller than that corresponding to the feedback connections from some of the most distant source areas (Fig. 2.4).

Interhemispheric connections, like horizontal connections, also interconnect neurons with overlapping and partially overlapping receptive fields, particularly around the vertical meridian. In addition, some interhemispheric connections appear to link together neurons with separate receptive fields that sometimes correspond to mirror images in both visual hemifields (Houzel and Milleret 1999; Innocenti 1986; Kennedy et al. 1991).

Patchy organization and axonal bifurcation

Following the discovery of patchy organization in horizontal connections (Rockland and Lund 1982), it was found that extrinsic cortico-cortical connections also tend to be similarly organized in most species, with the possible exception of the mouse (Braitenberg and Schüz 1991). This is demonstrated in neuroanatomical tracing studies that show that neurons retrogradely filled by a small deposit of retrograde tracer tend to be grouped in small patches a few hundred microns wide and separated by 500–1000 microns depending on the connection and the species. Results of anterograde tracer studies also demonstrate that terminals of axons labelled by a small amount of tracer placed in a given cortical area are grouped together in small patches.

Patchy arborization is usually observed in horizontal connections (Gilbert and Wiesel 1983; Rockland and Lund 1982), as well as in feedforward connections (Bullier 1984; DeYoe and Van Essen 1985; Shipp and Zeki 1985; Symmonds and Rosenquist 1984). Coupled injections of different retrograde tracers in different cortical areas produce mostly non-overlapping patches of labelled cells (Bullier 1984; DeYoe and Van Essen 1985; Shipp and Zeki 1985), with very few double labelled cells in the regions of overlap. This suggests that a given cortical area sends feedforward connections to several other areas through a system of interdigitating neuronal patches that probably share common functional properties and are interconnected by patchy horizontal connections. Although less frequently demonstrated because of the small number of studies using coupled anterograde tracers, patches of terminal axons also appear to segregate at least partially in the target area for feedforward and interhemispheric connections (Goldman-Rakic and Schwartz 1982; Morel and Bullier 1990).

It is likely that the patchy organization and lack of axonal bifurcation in feedforward connections is the mark of the functional specificity of such connections. This is suggested by the results of Movshon and Newsome (1996) who demonstrated that the V1 neurons projecting to area MT (middle temporal) belong to a specific type with homogeneous properties. This result is comparable to that of an earlier work by Henry and his collaborators (1978) that also demonstrated the specific functional properties of neurons projecting from area 17 to the posterior mediolateral suprasylvian sulcus (PMLS) in the cat. The patchy distribution of feedforward terminals presumably

CORTICAL CONNECTIONS AND FUNCTIONAL INTERACTIONS 31

results from the convergence of axon terminals coming from neurons with some common functional properties. This is suggested by the elegant experiments of Sherk in the lateral suprasylvian sulcus (LS) area (slightly larger area than area PMLS in Fig. 2.1; Sherk 1990). Using a neurotoxin, she killed the neurons in a small region of that area and recorded from what presumably corresponds to the terminals of afferent axons. She found that axons tend to group together according to the direction selectivity, thus suggesting that neurons with the same optimal direction tend to terminate in common patches. The neurons innervated by this axon group presumably inherit the property of direction selectivity transmitted by the converging feedforward axons.

The prevalence of patchy organization is more variable for feedback connections. In general, when relatively extensive injections of retrograde tracers are placed in a given area, neurons in extrastriate areas do not group themselves in well-defined patches as in the case of feedforward connections (Kennedy and Bullier 1985; Perkel et al. 1986). On the other hand, more localized injections in the supragranular layers produce patchy distributions of retrogradely labelled cells in supragranular layers (Salin et al. 1994; Shipp and Grant 1991). Similarly, injections of anterograde tracers produce patchy distributions of terminals, particularly in the supragranular layers (Henry et al. 1991; Salin et al. 1994; Wong-Riley 1979b), whereas a continuous distribution of anterograde labelling has been reported on other occasions (Maunsell and Van Essen 1983; Ungerleider and Desimone 1986).

The major reason for the larger variability of the results concerning the patchy distribution of feedback compared to feedforward connections may be that there is more variability in the laminar distribution of axon terminals in feedback than in feedforward connections. Indeed, direct comparisons of labelled cells or axon terminals distributions in different layers for feedback connections show that patchy distributions exist in the connections between supragranular layers, whereas connections from infragranular layers appear to be less segregated, and afferent terminals in the lamina 1 always arborize in a diffuse manner (Henry et al. 1991; Salin et al. 1992; Shipp and Grant l991). Similar differences between the topographic organizations of terminals in different laminae are also observed when individual axonal arbors are traced in the target area, as demonstrated by the work of Rockland and colleagues (Rockland and Drash 1996; Rockland et al. 1994).

It is interesting that the laminar differences observed for the patchy character of feedback connections are echoed by similar differences in the pattern of axonal bifurcation. Thus, in feedback connections, the proportion of neurons sending bifurcating axons to two cortical areas is higher in infragranular than in the supragranular layers (Bullier and Kennedy 1987). Also, the results of Rockland and her associates (1994) demonstrate that some feedback axons have long axonal collaterals in layer 1 that arborize extensively over at least two cortical areas, whereas terminals in supragranular layers are restricted to one cortical area.

This difference in organization across layers suggests that, for a given set of feedback connections between two areas, different roles are played by different subsets of connections corresponding to different laminar distributions in the source and target