The cortical visual area V6: brain location and visual topography

Transcription

1 European Journal of Neuroscience, Vol.11, pp.3922±3936, 1999 Ó European Neuroscience Association The cortical visual area V6: brain location and visual topography Claudio Galletti, Patrizia Fattori, Michela Gamberini and Dieter F.Kutz 1 Dipartimento di Fisiologia umana e generale, Universita di Bologna, Piazza di Porta S. Donato 2, Bologna, Italy 1 Department ofzoology and Neurobiology, Ruhr-University Bochum, D Bochum, Germany Keywords: macaque monkey, parieto-occipital cortex, superior parietal lobule, visual topography, visuomotor integration Abstract The brain location and topographical organization of the cortical visual area V6 was studied in ve hemispheres of four awake macaque monkeys.area V6 is located in the caudal aspect of the superior parietal lobule (SPL).It occupies a `C'-shaped belt of cortex whose upper branch is in the depth of the parieto-occipital sulcus (POS) and lower one is in the depth of the medial parieto-occipital sulcus (POM), with the medial surface of the brain as a zone of junction between the two branches.area V6 contains a topographically organized representation of the contralateral visual eld up to an eccentricity of at least 80.The lower visual eld representation is located dorsally, in the ventral part of POS, and the upper eld ventrally, in the dorsal wall of POM.The representation of the horizontal meridian forms the posterior border of V6.It is adjacent to area V3 in POS as well as in the caudal part of POM, on the ventral convexity of the brain.the lower vertical meridian forms the anterior border of V6, adjacent to area V6A.The upper vertical meridian is in the depth of POM.The representation of the central visual eld is not magni ed relative to that of the periphery.the central visual eld (below 20± 30 of eccentricity) is represented in the medial-most aspect of the annectant gyrus, in the lateral part of the posterior bank of POS.The visuotopic organization of area V6 suggests a role in the analysis of the ow eld resulting from self-motion, in selecting targets during visual searching as well as in the control of arm-reaching movements towards non-foveated targets. Introduction The prestriate cortex of primates contains many representations of the visual eld, each one of them considered as a different functional area. Some of these representations show a point-to-point retinotopic organization, while others a cruder visual topography. In the macaque for instance, areas V2and V3 represent a large part of the visual eld in a highly orderly manner (Van Essen & Zeki, 1978; Gattass et al., 1981, 1988; Burkhalter et al., 1986), while areas V3A, V4 and V5 show a coarser topographic organization (Van Essen & Zeki, 1978; Gattass & Gross, 1981; Van Essen et al., 1981; Gattass et al., 1985, 1988). Quite recently, a further representation of the visual eld was discovered in the prestriate cortex located in the precuneate gyrus of the macaque brain. It was called the parieto-occipital area (PO, Covey et al., 1982). Area PO was reported to occupy the anterior bank of the parieto-occipital sulcus (POS), and to extend onto adjacent portions of the medial surface of the hemisphere medially and the medial bank of the intraparietal sulcus (IPS) laterally. It contained a complete representation of the contralateral visual eld, although the visual eld appeared to be discontinuously represented within the area (Gattass et al., 1985). The central 30 of the retina was represented in three different parts of PO, two dorsally and one ventrally, so that Gattass and co-workers advanced the hypothesis that what they had called area PO `may be more than one visual area' (see Gattass et al., 1985, p. 9). Actually, the same authors found that the cells of the dorsal zone of PO gave consistently weaker visual responses with respect to those in the ventral one. In addition, it was reported that the dorsal zone had a set of connections different from that found for the ventral one (Colby et al., 1988). The term PO was then retained to indicate the ventral, visually more responsive region of the originally described area PO, leaving unnamed the visually less-responsive cortical region dorsal to it (see Colby et al., 1988). The functional characteristics of cells in the precuneate cortex of the macaque brain have been recently studied in awake animals (Galletti et al., 1991, 1996, 1999). Two functional areas have been found there: area V6A, containing visual neurons as well as neurons insensitive to visual stimulation; and area V6, whose cells are all responsive to visual stimulations. Area V6A is a horseshoe-like strip of cortex that occupies the dorsal region of the anterior bank of POS, and extends onto adjacent portions of the medial surface of the hemisphere medially and the medial bank of IPS laterally (Galletti et al., 1999). Area V6 is located ventrally and posteriorly with respect to V6A in the deepest part of the anterior bank of POS (Galletti et al., 1996). It is likely that area V6 corresponds to area PO, according to its last de nition (Colby et al., 1988), while area V6A corresponds to the weakly responsive region dorsal to it, though some inconsistencies have been observed (see Galletti et al., 1996). The aim of the present work is to describe the brain location, extent, limits and visual topography of area V6. Preliminary data on this matter have been previously published in abstract form (Galletti et al., 1998). Correspondence: Professor C. Galletti, as above. galletti@alma.unibo.it Received 9 December 1998, revised 7 May 1999, accepted 9 July 1999 Materials and methods Experiments were carried out on four monkeys (Macaca fascicularis; 3.1±7.1 kg) trained to perform a visual xation task. Experimental

2 Visuotopic organization of area V FIG. 1. Microelectrode penetrations through the cortex of POS. (A and B) Two parasagittal sections of the brain of case 16R, taken at the level shown on the dorsal view of the brain reported at the centre of the gure. Letters `a', `b', `c' and `d' on the sections indicate the reconstructions of four microelectrode penetrations passing through the occipital pole and reaching the cortex of POS in the depth. Dashed lines on the grey matter mark the limits between different cortical visual areas. In the bottom part of the gure, the reconstructions of RF sequences encountered along these penetrations are reported. In some cases, a continuous line joins the RF centres of cells recorded from the same area. The numbers along these lines indicate the rst and last RF encountered along each cortical area. V1, V2, V3, V6, V6A, areas V1, V2, V3, V6 and V6A; CAL, calcarine ssure; CIN, cingulate sulcus; IPL, inferior parietal lobule; IPS, intraparietal sulcus; LS, lunate sulcus; POM, medial parieto-occipital sulcus; POS, parieto-occipital sulcus; SPL, superior parietal lobule. protocols were approved by the Bioethical Committee of the University of Bologna, and were complied with the National and European laws on the care and use of laboratory animals. Detailed descriptions of training, surgical and recording procedures, as well as visual stimulation, anatomical reconstruction of recording sites and animal care are reported elsewhere (Galletti et al., 1995). The following is a brief description of them. Animals sat in a primate chair facing a large ( ) tangent screen. They performed a xation task with the head restrained while single neurons from the cortex of the precuneate gyrus were extracellularly recorded by glass-coated Elgiloy microelectrodes (Suzuki & Azuma, 1976). Eye positions were recorded using an infrared oculometer (Dr Bouis, Germany; Bach et al., 1983). The sample rate for action potentials was 1 khz and that for eye position 100 Hz. Once a single cell was isolated, its visual receptive eld (RF) was mapped by using visual stimuli of different form, colour, size, orientation, direction and speed of movement, rear-projected on the screen facing the animal. Occasionally, also the RFs of small clusters of cells were mapped. RF mapping started by oscillating the optimal stimulus at successive points away from the centre of the visually responsive region until the cell no longer responded. The screen locations where the response was lost were marked as RF edges. The locations of these edges were then con rmed, and if the case modi ed, by entering with the appropriate visual stimulus into the RF from outside, with the correct orientation, direction and speed of movement (many V6 neurons were direction and orientation selective and were sensitive to particular speeds of movement; see Galletti et al., 1996). RFs were drawn as squares or rectangles parallel to the axis of best orientation. RF sizes and locations were then transferred to a database together with the other functional characteristics of the studied cells. At the end of the recording sessions, the electrode tracks and the approximate location of each recording site were reconstructed on parasagittal sections of the brain on the basis of marking lesions and several other cues, e.g. the coordinates of penetrations within the recording chamber, the kind of cortical areas passed through, the location of boundaries between white and grey matter, and the distance of recording site from the surface of the hemisphere. Because our penetrations often reached very deep and convoluted

3 3924 C. Galletti et al. FIG. 3. RF size versus eccentricity in prestriate areas. Regression plots of RF size (square root of area) against eccentricity in degrees ( e) for cells recorded in areas V2(n = 485), V3 (n = 353), V6 (n = 466) and V6A (n = 408). The regression equations are as follows. Area V2: size = e; r 2 = Area V3: size = e; r 2 = Area V6: size = e; r 2 = Area V6A: size = e; r 2 = FIG. 2. RF size versus eccentricity in area V6. (A) Regression plot of RF size (square root of area) against eccentricity in degrees ( e) for 466 cells recorded in area V6. The regression equation is: size = e; r 2 = (B) Dual regression plot of RF size against eccentricity for V6 cells with RF in the upper ( lled circles) and lower (empty circles) visual eld (VF), respectively. The regression equations are as follows. Upper VF (n = 91): size = e; r 2 = Lower VF (n = 375): size = e; r 2 = ANCOVA analysis established that the two regression lines were not signi cantly different in slope (F 1,462 = ; P > 0.6), but they were signi cantly different in elevation (mean difference in RF size = 6.8 ; F 1,463 = 93.6; P < ). cortical regions, straight and sturdy electrodes were used to minimize electrode bending during penetrations, and particular attention was paid in reconstructing penetrations lacking in marking lesions. Several cross-controls were carried out between the above-mentioned criteria, so that the nal position of penetrations on brain sections was that which matched the highest number of these criteria. Results General remarks A total of 226 microelectrode penetrations were carried out in ve hemispheres of four awake, behaving animals. Penetrations were usually made in each hemisphere in a grid pattern with spacing of 1 mm. In some cortical regions a ner grid was used. Microelectrodes entered through the dura mater and the cortex of the dorso-medial part of the occipital pole along a parasagittal plane; they were tilted 30±40 with respect to a coronal plane. As shown in Fig. 1, penetrations could reach deep into both banks of POS. All cells encountered in the posterior bank of POS were responsive to visual stimulation. They were assigned to areas V2, V3 or V6 on the basis of the pattern of RF location sequences observed FIG. 4. Visual eld representation in V6. The lled circles indicate the retinotopic distribution of RF centres of the same cell population shown in Fig. 2. An outline of the most peripheral RF borders is also reported. along the penetration. Cells were assigned to areas V2or V3 when their RF locations and sequences agreed with the well-known visual topography of these cortical areas (see Gattass et al., 1981, 1988). They were assigned to area V6 when the sequence of RF locations followed the typical pattern of V6, that will be described later on in this section. Cells recorded from the anterior bank of POS were either visual or non-visual in nature, and were assigned to areas V6 or V6A according to the functional criteria described in Galletti et al. (1996). Note that one of these criteria was the different pattern in the sequence of RF locations observed along a penetration. This different pattern between V6 and V6A is visible in penetrations `a' and `c' in Fig. 1. While in

4 Visuotopic organization of area V FIG. 5. Brain location, extent and limits of area V6 in case 16R. (A±E) Parasagittal sections of the brain taken at the levels shown on the brain silhouette reported on the top left of the gure. Shaded areas on each section indicate the extent of V6 at that parasagittal level. Arrowheads in (D,E) indicate the two branches of POS. Other details and abbreviations as in Fig. 1. area V6 the RFs `move' coherently along the penetration, in a certain direction and with a physiological scatter (penetration `a'), in area V6A they often jump in different directions, so that cells near one another in the cortex can have RFs in completely different locations in the visual eld (penetration `c'; see also Galletti et al., 1999). Another distinctive feature among the cells of areas V2, V3, V6 and the visual cells of V6A was the size of their RFs. We have constantly observed that in area V6 the RFs were larger than in areas V2and V3, and smaller than in area V6A (see Fig. 1). The RF size in area V6 increases with eccentricity (Fig. 2), as in all other prestriate areas, but they remain on average smaller than in V6A and larger than in V2and V3 at any value of eccentricity (Fig. 3). Note that the data reported in Fig. 3 were all collected by the same laboratory, hence their comparison should be quite reliable. The differences in RF size indicated by the regression lines of Fig. 3 turned out to be statistically highly signi cant for all comparisons (ANCOVA, P < ) and were used as a further criterion to assign recorded cells to the different prestriate areas. Besides being correlated to the eccentricity, the size of RFs in V6 turned out to also be correlated to the eld representation, as shown in Fig. 2B. We divided V6 RFs into two populations according to the location of their centre in the upper or lower visual eld. The regression lines of the two populations showed about the same slope but signi cantly different values of intercept. This means that RFs located in the upper visual eld were on average larger than those in the lower visual eld, at any value of eccentricity (ANCOVA, P < ). Figure 4 shows the retinotopic distribution of the RF centres and the outline of the most peripheral RF borders of the same group of V6 cells reported in Fig. 2. It is evident that the whole contralateral hemi eld is represented in V6. Both the central part of the visual eld and the periphery, up to ~ 80 of eccentricity, are well represented. There is a prevailing representation of the lower visual eld with respect to the upper one. The reasons for the under-representation of the upper visual eld, particularly for its central part, will be discussed later on in this paper. Brain location of area V6 Figure 5 shows the cortical regions where V6 cells were recorded from a typical case (16R). V6 cells were found in the medial surface of the hemisphere (Fig. 5A), in the anterior bank and fundus of POS (Fig. 5B±D), in the lateral part of the posterior bank of POS (Fig. 5D and E), and in the dorsal wall of the medial parieto-occipital sulcus (POM; Fig. 5B±D). Thus, area V6 occupies a `C'-shaped belt of cortex orientated in the brain in a coronal plane. The upper branch of this `C'-shaped belt of cortex is located in the POS and the lower one in the POM, with the medial surface of the brain as a zone of junction between the two. Laterally, the upper branch of V6 moves down from the anterior bank to the fundus of POS (Fig. 5C and D), and then up along the posterior bank of POS (Fig. 5D and E) where it merges into the cortex of area V3. Dorsally and anteriorly, area V6 borders continuously on area V6A, from the medial surface of the hemisphere (Fig. 5A), through the anterior bank (Fig. 5B and C), and fundus (Fig. 5D and E) of POS (see also Galletti et al., 1999). Ventrally and posteriorly, area V6 borders on area V3: along the border between cuneate and precuneate gyri, medially (Fig. 5B), along the caudal end of POM in the ventral convexity of the brain (Fig. 5C), and along the fundus and posterior bank of POS laterally (Fig. 5C±E). In all our cases, the fundus of POS splits into two branches a few millimetres laterally to the interhemispheric midline (see arrowheads

5 3926 C. Galletti et al. FIG. 6. Brain location, extent and limits of area V6 in case 15L. Details and abbreviations as in Fig. 5. in Fig. 5D and E). The anterior branch of POS (see arrowhead on the left in Fig. 5D and E) is the result of a sharp bending, anteriorly, of the POS fundus (Fig. 5C and D), that then continues into the fundus of the lunate sulcus (LS) more laterally (Fig. 5E). The posterior branch of POS (see arrowhead on the right in Fig. 5D and E) is the original POS fundus that continues medio-laterally at about the same anteroposterior level (Fig. 5C and D), and then dies 6±8 mm away from the interhemispheric midline (Fig. 5E). As shown in Fig. 5D and E, area V3 occupies most of the cortex around the posterior branch of the POS, while area V6 occupies the large fundus of POS, between its two branches, as well as the posterior wall of the anterior branch of POS, just in front of area V3. The lateral edge of area V6 in the POS is often recognizable even macroscopically. It is located more or less at the level where the posterior branch of POS collapses and the anterior branch continues in the LS, in a cortical region that represents the most medial appendix of the annectant gyrus (Fig. 5E). This region appears as a tongue of cortex arising from the fundus of the POS and merging into the cortex of the posterior wall of the POS (Fig. 5D and E). Case 16R is representative of two out of the ve hemispheres we studied (14L and 16R). In two other cases (13L and 15L), the cortex of cuneate and precuneate gyri remained separated from each other as far as 5±6 mm away from the interhemispheric midline (Fig. 6A±C). Accordingly, the upper and lower branches of the `C'-shaped V6 cortex remained in continuity through the cortex of the ventro-caudal tip of the precuneate gyrus as far as 5±6 mm laterally to the interhemispheric midline. Also, due to the separation between cuneate and precuneate cortices, area V6 contacted V3 only at the lateral end of POS, where the occipital cortex nally merged into the parietal one (Fig. 6D and E). When cuneate and precuneate cortices merged together, the posterior branch of POS became recognizable (see left arrowheads in Fig. 6D and E), and it also became evident that V3 occupied the posterior branch of POS as in the other cases. Laterally, area V6 occupied the fundus and the posterior bank of the anterior branch of POS (see right arrowheads in Fig. 6B±E), as in the other cases. Again as in all other cases, area V6 was bordered anteriorly by V6A and posteriorly by V3. The fth hemisphere we studied (case 16L) showed a signi cantly different gyral morphology. In this case (Fig. 7), the caudo-ventral tip of the precuneate gyrus was absent while an additional amount of cortex was present in the corresponding region of the cuneate gyrus, in the occipital pole (Fig. 7A). According to these morphological differences, area V6 occupied the additional amount of cortex in the cuneate gyrus (Fig. 7A and B). Apart from this peculiarity, and in spite of the different gyral morphology, area V6 occupied a `C'- shaped belt of cortex as in the case shown in Fig. 5, with the dorsal branch in the POS and the ventral one in the POM (Fig. 7B±D). Again, similarly to the case shown in Fig. 5, area V6 bordered anteriorly with area V6A and posteriorly with area V3. In the case shown in Fig. 7 the anterior and posterior branches of POS were dif cult to recognize (see their probable positions indicated by arrowheads in Fig. 7C and D). Anyhow, as in the cases of Figs 5 and 6, the anterior branch was occupied by V6 and the posterior one by V3. Visual topography of area V6 In order to study the visuotopic organization of area V6, we analysed the RF sequences of V6 cells recorded along the same penetration, as well as along nearby penetrations reconstructed on the same or nearby brain sections. Figures 8±16 are examples of this study. Figure 8 describes in detail the visual topography of V6 in case 16R. As illustrated by penetrations reported on section A, the region of V6 located on the medial surface of the hemisphere showed a wellde ned retinotopic organization. In this region of V6, RFs occupied the peripheral part of the visual eld. They moved from the lower to the upper visual eld along each penetration, constantly crossing the horizontal meridian along the way (see RFs number 6 in penetration `a' and number 10 in `b'). The eccentricity of RFs progressively decreased along the penetration, so that they were more eccentric in the lower than upper eld representation.

6 Visuotopic organization of area V FIG. 7. Brain location, extent and limits of area V6 in case 16L. Details and abbreviations as in Fig. 5. As reported above and illustrated in Fig. 5, the part of area V6 located on the medial surface of the brain continues into the anterior bank of POS dorsally and the upper bank of POM ventrally. The RF sequences of penetrations `a', `b' and `c' in Fig. 8 show that the lower visual eld is represented in the upper branch of this `C'-shaped belt of cortex, while the upper visual eld is represented in the lower branch of V6. Accordingly, the horizontal meridian representation is located in-between, running rostro-caudally on the medial surface of the brain, more or less parallel to the lip of POM (sites 6 and 10 in penetrations `a' and `b', respectively, and 8 in `d'). Figure 8 also shows that moving medio-laterally in the upper branch of V6, RFs move from the periphery towards more central representations. The central-most RFs (less than 20±30 in eccentricity) were found in the posterior bank of POS, where the V6 cortex merges into the cortex of V3 (penetration `e', and sites 1 and 2in penetration `f'). Penetrations through this cortical region showed RFs that moved from the horizontal meridian posteriorly, at the border with area V3, to the vertical meridian anteriorly. Note that laterally to section C of Fig. 8, the cortex of the posterior wall of POS merges into that of the fundus of this sulcus (see Fig. 5E). Thus, the vertical and horizontal meridian representations of the posterior wall of POS continue with the same representations in the fundus of this sulcus (sites 3±6 in penetration `f' and sites 1±8 in penetration `g'). The lower vertical meridian represents the anterior limit of area V6. It runs medio-laterally along the anterior bank of POS, at the border between areas V6 and V6A (sites 1±4 in penetration `c' in Fig. 8). Laterally, it bends downwards and reaches the fundus of POS, again at the border with V6A (sites 3±6 in penetration `f'). Then, following the above-described course of the upper branch of V6, it rises along the posterior bank of POS in its lateral end (site 6 in penetration `e') reaching the central-most representation of V6. The horizontal meridian representation is at the ventral, posterior limit of area V6, at the border with area V3. The V6±V3 border represents the central 40 degrees of the horizontal meridian (more peripheral representations being on the medial surface of the hemisphere, as described above) and runs medio-laterally along the fundus of POS (site 1 in penetration `d', sites 1±8 in penetration `g'). Then, it rises along the posterior bank of this sulcus to reach the central-most representation of V6 at the lateral end of POS (site 1 in penetration `e'). Figure 9 summarizes the visual topography of area V6 in case 16R. The gure shows aggregate eld outlines obtained by grouping cells from separate microelectrode penetrations carried out in different parts of area V6. It con rms the retinotopic organization of V6, and in particular: (i) the lower visual eld representation is located in POS and the upper one in POM; (ii) the central representation is located in the most lateral part of the posterior bank of POS; (iii) the vertical meridian representation is located at the border with area V6A and the horizontal one at the border with area V3. The fact that on the medial surface of the hemisphere area V6 abuts V3 was an unexpected nding, as in the literature it has been repeatedly reported that the dorsal aspect of V3 does not reach the medial surface of the hemisphere, but terminates into the parietooccipital cleft (Van Essen et al., 1986; Gattass et al., 1988). In our cases, the V3 belt surrounded anteriorly area V2in the LS and POS, in agreement with the literature, as well as in the ventral convexity of the brain, a nding previously not reported. Figure 10 illustrates this aspect in case 16R. Medially (section 6), V2occupied almost the entire posterior bank of POS, and V3 the ventral-most part of the cuneate cortex. The V2±V3 border was in the fundus of POS and represented the horizontal meridian (sites 6±7). This cortical region, at the junction between cuneate and precuneate cortices, also represented the border between areas V3 and V6 (sites 7±8 versus 14±15). Area V2extended from the POS to the medial surface of the hemisphere and reached the stem of calcarine ssure (CAL), where it was sandwiched between V3 ventrally and V1 dorsally (sites 11±13). The V2±V1 border, within the CAL, represented the vertical meridian (sites 12±13). The V2±V3 border, around the rim of CAL, probably

7 3928 C. Galletti et al. a contralateral visual field b c 7 d g e f FIG. 8. RF sequences in penetrations through area V6. (A±C) Parasagittal sections of the brain taken at the levels shown on the brain silhouette reported on the bottom left of the gure. Letters `a' to `g' on the sections indicate the reconstructions of microelectrode penetrations passing through the occipital pole and reaching the cortex of POS and POM in the depth. On the right, the reconstructions of the V6 RF sequences encountered along these penetrations are reported. Thick lines join RF centres. The numbers along these lines, and along the reconstructed penetrations on the left, indicate the RFs and brain locations, respectively, of some V6 cells. The RFs of `numbered' neurons are shown in grey. Other details and abbreviations as in Fig. 1. represented the horizontal meridian, although we have no recordings from this cortical region. We hypothesize that the horizontal meridian representation (V2±V3 border) runs from the fundus of POS anteriorly to the stem of CAL posteriorly, passing on the medial surface of the hemisphere along the margin of the ventral convexity. About 1 mm laterally to section 6 in Fig. 10 (section 9), the V2±V3 border rose up along the posterior bank of POS, still representing the horizontal meridian (sites 4±5). At this parasagittal level, area V3 was partly within the POS (sites 5±8) and partly in the ventral convexity of the brain, at the posterior end of POM (sites 9±12). The orderly and complementary visuotopic organization of these two parts of V3 support the idea that around the medial surface of the hemisphere V3 moves from the POS, dorsally, to the POM, ventrally, remaining sandwiched between V2and V6 in both the POS and the ventral convexity of the brain. Figure 11 shows the visuotopic organization of the part of V3 located in POS in the ventral convexity of the brain, in case 16R. In the POS, V3 represented the central 30 of the contralateral lower visual quadrant. In the ventral convexity of the brain, V3 represented most of the remaining periphery. The central representation of V3, in the POS, was lacking in the representation of the central 5±10 of the visual eld that is well known to

8 Visuotopic organization of area V FIG. 9. Visual topography of area V6 in case 16R. (Left) Parasagittal sections of the brain taken at the levels shown on the brain silhouette reported on the bottom right of the gure. The numbers on the sections within the limits of area V6 indicate the cortical regions whose cells had RFs in the corresponding numbered parts of the visual eld shown in the right part of the gure. Sections 6, 12, 16 are the same as (B±D) in Fig. 5 and (A±C) in Fig. 8. (Right) Outlines of the most peripheral RF borders of groups of V6 cells recorded from the cortical regions indicated by the same numbers in the brain sections, in the left part of the gure. Other details and abbreviations as in Fig. 1. be present in the part of V3 located in the posterior bank of LS (Van Essen & Zeki, 1978; Burkhalter et al., 1986; Gattass et al., 1988). Present data, together with those from literature, suggest that the dorsal aspect of V3 is a topographically organized belt of cortex that represents ~ 50 of the contralateral lower visual eld. Area V3 is located in the depth of LS and POS as well as in the ventral convexity of the brain, and surrounds V2along all its extent. The same type of analysis described in Figs 8±11 for case 16R was carried out in all the other cases we studied. Although some differences were observed among the cases, the basic visuotopic organization of area V6 remained that described above. Figure 12shows some penetrations in two different cases (13L and 14L). Penetrations `a' and `b', carried out in the medial region of brain 13L, show that: (i) the vertical meridian was represented at the border between areas V6 and V6A; (ii) the RF progression in V6 was from the vertical to horizontal meridian; and (iii) the RFs in V6A jumped from one part to another of the visual eld. Penetrations `c' and `d', carried out in the lateral part of the POS in brain 14L, show that: (i) area V6 merged into V3 in the ventral part of the posterior bank of POS; (ii) the anterior border of V6 represented the vertical meridian and abutted area V6A; and (iii) RFs in V6A jumped from one part to another of the visual eld. All these results are in agreement with those showed in case 16R. Figure 13 illustrates the visual topography of V6, and of neighbouring areas V2and V3, in the most lateral part of POS in case 14L. When moving dorso-ventrally along V2, in the posterior bank of POS, RFs moved from the vertical to a more peripheral horizontal meridian representation ( elds 1±3). At the V2±V3 border, RF size suddenly increased and the progression of RFs reversed, moving this time from the horizontal to vertical meridian ( elds 4±7). V3 occupied the cortex around the posterior branch of POS, in the deepest part of the sulcus. V6 occupied the posterior wall of the anterior branch of POS. The locations of both areas are in agreement with those shown in case 16R. Moving caudo-rostrally within area V6, the RFs moved from horizontal to vertical meridian ( elds 8 versus 10; 9 versus 11 and 12). Moving dorso-ventrally, RFs moved from central to peripheral parts of the visual eld ( elds from 8 to 13). The RFs of V6 neurons located along the border with area V3 re ected the topography of V3 itself. As a matter of fact, in both areas they were located near the horizontal meridian dorsally ( elds 8 and 9 in V6 versus 4 in V3) and near the vertical meridian ventrally ( eld 13 in V6 versus 7 in V3). On the whole, in the posterior bank of POS area V6 covered the central 20±30 of the lower contralateral visual quadrant, about the same region of visual eld represented in the lateral part of POS in case 16R. Figure 14 shows some penetrations carried out in case 15L. Also in this case the vertical meridian was represented along the border

9 3930 C. Galletti et al. FIG. 10. Visual topography of areas V2and V3 in the medial region of the brain in case 16R. Two parasagittal sections are shown on the left, taken at the levels indicated on the brain silhouette reported at the top of the gure. Triangles, open and full circles and crosses on the sections indicate recording sites in V1, V2, V3 and V6, respectively; the RFs mapped at these recording sites are shown with the same numbers on the right. V6 RFs are indicated with dashed lines. Large, open circles on the sections indicate locations of electrolytic lesions carried out at particular recording sites. Dashed lines on the sections mark the limits between different cortical visual areas. Ipsi 50 Contra V3 POS V3 ventral convexity FIG. 11. Visual eld representation of V3 in POS and the ventral convexity of the brain. The shaded areas were obtained by delineating the external borders of superimposed RFs of V3 neurons recorded in POS and in the ventral convexity of the brain, respectively, in case 16R. 60 between areas V6 and V6A (penetrations `b', `c', `d'). Medially (section 59; penetration `b'), while the electrode advanced into the grey matter V6 RFs moved away from the vertical meridian. Moving medio-laterally along the fundus of POS, the RFs of V6 moved from the periphery towards more central parts of the visual eld (penetrations `b', `c', `d'). The more central RFs were again found where a tongue of cortex arised from the fundus of POS and reached the posterior bank of the sulcus, to merge into the cortex of V3 in the most lateral part of POS (penetration `d'). Areas V3 and V6 at this level showed a similar visuotopic organization (penetration `d'). All these data are in agreement with those of the other cases. Figure 15 shows some penetrations in a case (16L) with a completely different gyral morphology with respect to those described in Figs 8±14. Many similarities and some differences have been observed. In the lateral part of POS (section 19), area V6 was in the fundus of the sulcus, as usual, but in this case V6 continued a few millimetres along the fundus of LS, together with area V6A that

10 Visuotopic organization of area V FIG. 12. Microelectrode penetrations through the cortex of POS in cases 13L and 14L. All details as in Fig. 1. FIG. 13. Visual topography of areas V2, V3 and V6 in the lateral part of POS. All details as in Fig. 10. rostrally abutted V6 (sections 23, 27). The V6±V6A border represented the vertical meridian (penetrations `a' and `e'), as usual. Again as usual, the lower visual eld of V6 was represented in the POS and the upper one in the POM (penetration `b'). Posteriorly, V6 bordered with V3, in POS as well as in POM. In the posterior end of POM, the V3±V6 border represented the horizontal meridian (penetration `d'), as in the most medial part of the brains of the other cases. In the posterior branch of POS and in the fundus of this sulcus, the V3±V6 border represented the vertical meridian (penetrations `b', `c' and `f'), contrary to that observed in the other cases. However, more laterally, at the end of POS and the medial-most part of LS, in the region where V3 and V6 cortices merged together, the visuotopic organization of these two areas was similar: both V3 and V6 showed RFs near the horizontal meridian dorsally and the vertical meridian ventrally (penetrations `e' and `f'). This is the same visuotopic organization observed in the other cases in the lateral-most part of POS. Penetration `e' also shows that RFs increased in eccentricity moving dorso-ventrally along the central representation of V6, as in the other cases. The fact that in case 16L area V3 merges into V6 in the medial part of LS, instead of in the lateral part of POS, is probably due to the lateral extension of the posterior branch of POS into the LS in this case. Anyhow, even in case 16L area V6 merges into V3 more or less where the posterior branch of POS dies, and even in this case this part of V6 contains the representation of the central 30 of the contralateral lower visual quadrant.

11 3932C. Galletti et al. FIG. 14. Microelectrode penetrations through the cortex of POS in case 15L. All details as in Fig. 1. Figure 16 shows the overall visual topography of V6 in the `anomalous' case 16L. The lower visual eld is located in POS and the upper one in POM as in all other cases. The lower vertical meridian is at the border with area V6A as usual. The horizontal meridian is at the border with area V3 in the medial part of the brain. Laterally, the topography is more complex (see comments on Fig. 15). The most lateral part of area V6 enters into the medial end of the LS (section 27). Here, V6 topography matches that of V3, with the horizontal meridian representation dorsally (1A) and the vertical one ventrally (1B). Note that laterally to section 27, the V6 cortex labelled 1A (representing the horizontal meridian) merges into the V3 cortex located just above it, representing the horizontal meridian too (see penetration `e' in Fig. 15). The central-most representation of V6 is located in the most lateral part of this area, as in all other cases. On the basis of the data collected during microelectrode penetrations, we have tried to reconstruct the brain location and visuotopic organization of area V6 on three-dimensional models of the brain. Figure 17 shows the result of this work on the most typical and studied case 16R. Figure 17A shows the parieto-occipital cleft open. The upper branch of V6 occupies the ventral part of the anterior bank of POS, the fundus and the most lateral part of the posterior bank of POS. Note that in the gure the most lateral part of V6 covers a part of area V3, that remains beneath the V6 cortex. Figure 17B shows the cortex between the two branches of V6 (on the medial surface of the hemisphere), as well as part of the lower branch of this area (in the dorsal wall of POM). Note that the locations of the lower and upper visual eld representations, the vertical and horizontal meridians, and the centralmost representation of the visual eld reported in Fig. 17 are according to the above-described retinotopic organization of area V6 (see Figs 8±16). The small emphasis of central eld representation with respect to the periphery is evident, although the whole visual eld turns out to be represented. Note also that the isoeccentricity lines of the lower visual eld run obliquely along the anterior bank of POS. This explains why penetrations in parasagittal planes through this cortical region show RF sequences that progressively decrease in eccentricity (see Fig. 8, sites 1±5 in penetration `a' and 1±10 in penetration `b'). On the other hand, the oblique running of isoeccentricity lines allows the V6 RFs to remain topographically in register with the RFs of V6A dorsally and those of V3 ventrally, along the common borders of these two areas with area V6. In fact,

12 Visuotopic organization of area V FIG. 15. Microelectrode penetrations through the cortex of POS, POM and LS in case 16L. All details as in Fig. 1. Sections 19, 23, 27 are the same as C±E in Fig. 7. the visual cells of the ventral-most parts of area V6A have RFs in the far periphery (Galletti et al., 1999), while those in the region of V3 abutting area V6 in the POS are much more central (see Fig. 11). Discussion Area V6 is a cortical visual area interposed between areas V3 and V6A in the macaque brain. Previous studies reported the existence of V6 in the anterior bank of POS (Galletti et al., 1996). Present results indicate that this area is located in the depth of POS and POM, as well as in the caudo-ventral tip of the precuneate gyrus, on the medial surface of the hemisphere. The cortical extent of V6 on the medial surface of the hemisphere is strictly dependent on gyral morphology, changing largely from one case to another. Completely new is the nding that part of V6 is located in the posterior bank of POS. Area V6 is retinotopically organized. It contains a topographic representation of almost the entire contralateral visual eld, with the lower visual eld in the POS and the upper one in the POM, the periphery represented medially in the brain and the centre laterally. Although both central and peripheral parts of the retina are represented in V6, the central representation is not magni ed, as is on the contrary usual in all other cortical visual areas. Comparison of areas V6 and PO As suggested in a previous paper (Galletti et al., 1996), area V6 might correspond to the area PO that Colby and co-workers described in anaesthetized and paralysed macaque monkeys (Colby et al., 1988). Like area PO, V6 occupies the ventral aspect of precuneate gyrus, represents the lower visual eld in the anterior bank of POS and does not have an expanded representation of central vision. However, present results show that a number of differences are evident between the two areas. For instance, the upper eld representation of area V6 involves most of the dorsal wall of POM, going into the depth of the sulcus up to several millimetres away from the interhemispheric midline. In contrast, the upper visual eld in PO has been reported to be entirely represented on the medial surface of the hemisphere (see g. 1 of Colby et al., 1988). Accordingly, the representation of the

13 3934 C. Galletti et al. FIG. 16. Visual topography of area V6 in case 16L. Details and abbreviations as in Fig. 9. Sections 14, 19, 27 are the same as B, C and E in Fig. 7. horizontal meridian in PO runs dorso-ventrally along the anterior bank of POS, while in V6 it runs medio-laterally along the fundus of POS. Another example of differences between PO and V6 is the location of central eld representation. In PO, the central-most RFs (below 30 of eccentricity) were found in two separate sites in ventral and lateral parts of the anterior bank of POS, respectively (Gattass et al., 1985). In V6, the central representation is unique and RF centres below 20 of eccentricity were exclusively found at the lateral end of the posterior bank of POS. Because the central-most RFs in V6 were more central than those found in PO, it could be that the disagreement is at least partially due to differences in the extent of recording regions. In other words, the regions of central representation in PO could actually be part of area V6, but the central-most representation of V6 was probably outside the recording site of Gattass et al. (1985). In support of this view is the fact that we too found RF centres with eccentricity of 30 or less in the lateral part of the fundus of POS (see Fig. 8, penetrations `f' and `g'; Fig. 12penetration `d'; Fig. 14 penetration `c'; Fig. 15 penetration `c'; Fig. 17), that is in the region where Gattass and co-workers found their central representations. A third difference between PO and V6 regards the overall topographical organization of the two areas. PO is reported to have a complex visual topography in that it does not conform to the retinal surface (Gattass et al., 1985). In contrast, the visual topography of V6 is quite orderly, as summarized in Fig. 17. The RFs of cells recorded along single penetrations through V6 moved on average in a coherent direction, according to the orderly visuotopic organization of this area. This behaviour was in strong contrast not only with that reported for area PO, but also with that observed in area V6A, a cortical region that completely surrounds area V6 dorsally and anteriorly (see g. 9 of Galletti et al., 1999). The RF locations of V6A visual neurons showed very large scattering in parasagittal penetrations through this area, jumping repeatedly in completely different parts of the visual eld (see penetrations `c' in Fig. 1; `a' and `c' in Fig. 12; `a' in Fig. 14; see also Galletti et al., 1999). This behaviour of V6A cells might help in explaining the differences observed between the visual topography of areas V6 and PO. As fully discussed in a previous paper (Galletti et al., 1996), the antero-dorsal border of area PO, as de ned by myeloarchitecture, might include the caudo-ventral part of area V6A. If this was the case, the complex topography of area PO could be the result of V6A contamination, that would add a non-topographic representation of the retina to the topographic one of area V6. The representation of the central upper eld in area V6 Area V6 contains an almost complete representation of the contralateral visual eld. However, while the central representation of the lower visual eld was unequivocally found at the lateral end of the posterior wall of POS, that of the central upper visual eld was substantially missed (see Fig. 4). The reason for this is not clear. Given that it is unlikely that this sector of the visual eld is not represented in V6, a possible explanation is that we have missed recording from there. Actually, it was not easy to reach the cortical region where the upper visual eld was represented. V6 cells with RFs located in the upper visual eld were found in a relatively small

14 Visuotopic organization of area V FIG. 17. Retinotopic organization of area V6. (Left) Dorsal view of the brain in the region of POS. In the enlargement shown in A, the POS, LS and IPS are shown opened to reveal the cortex buried within them (dark grey area). Area V6 in the parieto-occipital cleft is shown in a lighter grey. Filled and empty circles indicate the representation of the horizontal (HM) and vertical (VM) meridians of area V6, respectively; the star, the centre of gaze (F). The dashed lines are isoeccentricity lines. The `minus' sign indicates the lower visual eld representation. The dotted lines are the borders between different cortical areas, according to the present as well as previous results (see Galletti et al., 1999). V2, V3, V6, V6A, areas V2, V3, V6 and V6A. (Right) Medial view of the hemisphere in the region of POM. In the enlargement shown in B, the cortex of the cuneate gyrus is pulled back and down to show part of the dorsal wall of POM. The `plus' sign indicates the upper visual eld representation. Other details as in A. strip of cortex in the upper wall of POM, located more than 10 mm away from the entry point of the electrode into the brain. Not all of our penetrations reached the POM, thus data on this cortical region were less numerous with respect to those from other regions of V6. For these reasons, we cannot exclude having missed recording from the cortical region representing the central part of the upper visual eld. An alternative explanation is that the central upper- eld representation of V6 is not located in the POM, but in another region of the brain not explored in our experiments. To this regard, some data from the literature suggest an intriguing hypothesis. Van Essen & Zeki (1978) originally described area V3A as a strip of cortex located in the LS, containing both lower and upper eld representations of the central 20±25 of the visual eld. They also reported the nding of an anomalous `second' central eld representation of V3A medially, in the lateral end of POS, in a location where they would have expected to nd the representation of the far periphery of V3A. This secondary representation of V3A (medial V3A) encompasses the central 20±25 of the retina, both in the lower and upper contralateral quadrants. The authors questioned whether this secondary central representation could form part of an unidenti ed additional visual area. As a support to this hypothesis, the same authors found that the V3A in the LS had RFs `reasonably small', while the medial V3A had RFs `large even when they overlap the fovea' (Van Essen & Zeki, 1978, p. 214). It seems reasonable to suppose that the medial V3A is actually the central representation of area V6. As far as the lower quadrant representation is concerned, the brain location of the medial V3A and that of the central V6 is the same, in the posterior wall of the lateral end of POS; in addition, the sector of the visual eld they represent is more or less the same (central 20±25 ) and the RF size is of the same order of magnitude. As far as the upper quadrant representation is concerned, it is located anteriorly to the lower one, between the lateral end of the POS and the caudal end of the IPS (see gs 9 and 10 from Van Essen & Zeki, 1978), in a cortical region not explored in our experiments; the sector of the upper visual eld the medial V3A represents (central 20±25 ) is complementary to that represented in the upper- eld representation of V6 located in the POM; nally, the RF size is of the same order of magnitude as the central eld representation in V6. For all these reasons, we believe it likely that the medial V3A is actually the central eld representation of V6. We also suggest that the posterior intraparietal area (PIP), that has been described as occupying the same cortical region of the medial V3A and is reported to contain both upper- and lower- eld representations (Colby et al., 1988), is actually the central representation of area V6. Functional considerations The present results show that area V6 contains an orderly, retinotopic map of the visual eld, with an emphasis for the periphery representation and a more detailed representation of the lower visual eld with respect to the upper one. V6 cells respond briskly to visual stimulations, are very sensitive to orientation, direction and speed of movement of visual stimuli, and many of them are sensitive to oculomotor activity (Galletti et al., 1991, 1995, 1996). The visuotopic organization and cells' characteristics of V6 suggest a number of possible functional roles for this area. For instance, it could be engaged in the analysis of the ow eld resulting from self-motion, and/or play a role in selecting peripheral targets in visual searching. It could also be engaged in the control of arm-reaching movements towards non-foveated targets. The strong anatomical connection of V6 with area V6A (Matelli et al., 1995; Shipp & Zeki, 1995; Shipp et al., 1998) seems to support this view. V6A contains cells able to directly encode visual space (Galletti et al., 1993, 1996) as well as