Cerebral Cortex Advance Access originally published online on November 23, 2005
Cerebral Cortex 2006 16(10):1389-1417; doi:10.1093/cercor/bhj076
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Cortical Connections of the Inferior Parietal Cortical Convexity of the Macaque Monkey
Dipartimento di Neuroscienze, Sezione di Fisiologia, Università di Parma, I-43100 Parma, Italy, 1 Current address: Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA, 2 Current address: Laboratory of Neuropsychology, NIMH, NIH, Bethesda, MD, USA
Address correspondence to Prof. Giuseppe Luppino, Dipartimento di Neuroscienze, Sezione di Fisiologia, Università di Parma, Via Volturno 39, I-43100 Parma, Italy. Email: luppino{at}unipr.it.
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Abstract |
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We traced the cortical connections of the 4 cytoarchitectonic fields—Opt, PG, PFG, PF—forming the cortical convexity of the macaque inferior parietal lobule (IPL). Each of these fields displayed markedly distinct sets of connections. Although Opt and PG are both targets of dorsal visual stream and temporal visual areas, PG is also target of somatosensory and auditory areas. Primary parietal and frontal connections of Opt include area PGm and eye-related areas. In contrast, major parietal and frontal connections of PG include IPL, caudal superior parietal lobule (SPL), and agranular frontal arm-related areas. PFG is target of somatosensory areas and also of the medial superior temporal area (MST) and temporal visual areas and is connected with IPL, rostral SPL, and ventral premotor arm- and face-related areas. Finally, PF is primarily connected with somatosensory areas and with parietal and frontal face- and arm-related areas. The present data challenge the bipartite subdivision of the IPL convexity into a caudal and a rostral area (7a and 7b, respectively) and provide a new anatomical frame of reference of the macaque IPL convexity that advances our present knowledge on the functional organization of this cortical sector, giving new insight into its possible role in space perception and motor control.
Key Words: area 7a • area 7b • dorsal visual stream • space coding • visuomotor transformations
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Introduction |
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The posterior parietal cortex of the macaque contains a multiplicity of areas involved in the analysis of visual information necessary for motor planning and execution of eye, limb, and body movements (see, e.g., Rizzolatti and others 1997
; Colby 1998).
The rich parietofrontal connections of these areas mediate the transformation of visual information into action, and a series of parietofrontal circuits has been so far identified, linking visually related areas of the caudal superior parietal lobule (SPL) and of the intraparietal sulcus (IPS) with different sectors of the agranular frontal cortex or with the frontal eye fields. These circuits are involved in the visual guidance of reaching, grasping, or eye movements (Colby 1998; Rizzolatti and others 1998).
Within this general framework, there are still several aspects of the anatomical organization of the cortical convexity of the inferior parietal lobule (IPL) and its possible role in visuomotor transformations and/or space coding that need to be elucidated.
This cortical sector is usually subdivided according to the architectonic studies of Vogt O and Vogt C (1919) into a caudal and a rostral area, 7a and 7b, respectively, considered as functional and hodological different entities (see, e.g., Andersen and others 1997; Siegel and Read 1997a). According to this view, 7a is a visually responsive area, located at the vertex of the occipitoparietal visual information flow (dorsal visual stream, Ungerleider and Mishkin 1982), linked with oculomotor area lateral intraparietal area (LIP) and the rostral prearcuate cortex and where retinal and extraretinal signals are combined to construct a representation of space. In contrast, 7b is mostly related to the analysis of somatosensory information, connected with the ventral premotor cortex, and involved in the control of arm and face movements.
Area 7a, however, is also involved in the control of arm-reaching movements (Mountcastle and others 1975; Blum 1985; MacKay 1992; Battaglia-Mayer and others 2005), and according to Hyvärinen (1981) there is a functional segregation in this area between a more rostral, visually and somatosensory responsive, arm field and a more caudal field, in which eye movement signals predominate. Furthermore, in the rostral IPL convexity (area 7b) there is a visual and somatosensory responsive arm/hand and face field (Hyvärinen 1981; Ferrari and others 2003), where visual neurons appear to be involved in higher order visuomotor processings (Gallese and others 2002; Yokochi and others 2003; Fogassi and others 2005). These data, therefore, suggest, first, that area 7a is not homogeneous and, second, that 7b is not exclusively involved in somatomotor functions.
In their architectonic study, Pandya and Seltzer (1982) indeed suggested that the IPL convexity contains at least 3 distinct areas: a rostral, an intermediate, and a caudal one, defined as PF, PG and Opt, respectively, plus a transitional area located between areas PF and PG and named PFG. Accordingly, areas 7a and 7b are both cytoarchitectonically not homogeneous and, in particular, area 7a would consist of at least 2 areas, PG and Opt. This subdivision, however, was never validated by clear connectional and/or functional data, and it is common practice in the literature to refer to areas 7a and PG as synonyms (Siegel and Read 1997a).
In the present study we used cytoarchitectonic data to guide the location of neural tracer injections to study the cortical connections of the IPL convexity. Specific aims were 1) to examine whether patterns of connections validate the subdivision of this sector into more than 2 distinct areas, 2) to identify all the possible sources of sensory information to each of these areas, and 3) to trace their projections to the frontal lobe, where there are multiple representations of different effectors (see, e.g., Rizzolatti and others 1998; Rizzolatti and Luppino 2001) and identify all the several possible parietofrontal circuits involving the IPL convexity and their possible role in space representation and motor control. The results provide strong support for a subdivision of the IPL convexity into 4 distinct areas, referred, in agreement with Pandya and Seltzer (1982), to as PF, PFG, PG, and Opt.
Preliminary data have been presented in abstract form (Luppino, Belmalih, and others 2004).
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Methods |
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The experiments were carried out on 6 macaque monkeys (3 Macaca nemestrina and 3 Macaca fascicularis) in which neural tracers were injected in cytoarchitectonic fields PF, PFG, PG, and Opt. Additional data from 2 M. nemestrina, in which retrograde tracers were injected in the lateral funiculus of the spinal cord, were used for the definition of the corticospinal projections from the IPL. The brains of 5 additional monkeys (4 M. nemestrina and 1 M. fascicularis, 8 hemispheres), 2 of them used in tracing experiments not related to the present one, were used for preliminary cytoarchitectonic analysis of the IPL convexity.
All experimental procedures were approved by the Veterinarian Animal Care and Use Committee of the University of Parma and complied with the European law on the care and use of laboratory animals.
Surgical Procedures and Tracers Injections
Each animal was anasthetized with ketamine hydrochloride (15 mg/kg intramuscularly) and placed in a stereotaxic apparatus.
In all animals in which tracers were injected in the IPL areas, under aseptic conditions, an incision was made in the scalp, the skull was trephined over the target region, and the dura was opened to expose the IPL convexity. Injection sites were chosen by using cytoarchitectonic data as frame of reference, referred in terms of stereotaxic coordinates and location of anatomical landmarks such as the IPS, the lateral fissure (LF), and the superior temporal sulcus (STS).
Once the appropriate site was chosen, fluorescent tracers (Fast Blue [FB] 3% in distilled water, Diamidino Yellow [DY] 2% in 0.2 M phosphate buffer at pH 7.2, True Blue [TB] 5% in distilled water, EMS-POLYLOY GmbH, Gross-Umstadt, Germany), wheat germ agglutinin–horseradish peroxidase conjugated (WGA-HRP, 4% in distilled water, SIGMA, St. Louis, Missouri), biotinilated dextran amine (BDA, 10% phosphate buffer 0.1 M, pH 7.4; Molecular Probes, Eugene, Oregon), and cholera toxin B subunit, gold conjugated (CTB-g, 0.5% in distilled water, LIST, Campbell, California) or conjugated with Alexa 488, Alexa 555, or Alexa 594 (CTB-A, 1% in phosphate-buffered saline, Molecular Probes) were slowly pressure injected at about 1.2–1.5 mm below the cortical surface as described in detail in previous studies (e.g., Luppino and others 2003). Table 1 summarizes the locations of injections, the injected tracers, and their amounts. After the injection, the dural flap was sutured, the bone replaced, and the superficial tissues sutured in layers.
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In the 2 animals in which tracers were injected in the spinal cord, under aseptic conditions, following a laminectomy, the dura was opened and the segment of the spinal cord selected for the injection exposed. Retrograde tracers were, then, pressure injected with a 5 µL Hamilton microsyringe in the left lateral funiculus. In 1 animal (Case 10), DY (2%, 8 injections, total amount 12 µL) was injected at the T6 spinal level and 26 days later (HRP, 30% in 2% lysolecithin, SIGMA, 6 injections, total amount 10 µL) at the C4–C5 spinal level. In the second animal (Case 21), HRP was injected at the C3–C5 level. Upon the completion of the injections, the spinal cord was covered with Gelfoam and wounds were closed in layers.
During surgeries, hydration was maintained with saline (about 10 cc/h, intravenously) and temperature with a heating pad. Heart rate, blood pressure, respiratory depth, and body temperature were continuously monitored. Upon recovery from anesthesia, the animals were returned to their home cage and closely monitored.
Histological Procedures
After appropriate survival periods following cortical (28 days for BDA, 12–14 days for fluorescent tracers and CTB-A, 7 days for CTB-g and 2 days for WGA-HRP) or spinal cord (29 days for DY and 3 days for HRP) injections, each animal was anesthetized with ketamine hydrochloride (15 mg/kg intramuscularly) followed by an intravenous lethal injection of sodium thiopental and perfused through the left cardiac ventricle with saline, 3.5–4% paraformaldehyde, and 5% glycerol in this order. All solutions were prepared in phosphate buffer 0.1 M, pH 7.4. Each brain was then blocked coronally on a stereotaxic apparatus, removed from the skull, photographed, and placed in 10% buffered glycerol for 3 days and 20% buffered glycerol for 4 days. Finally, it was cut frozen in coronal sections 60 µm thick. In Cases 10 and 21 (spinal cord injections) the spinal cord was removed and, after cryoprotection, cut transversally at 60 µm.
In Cases 27 and 29, 1 section of 5 was mounted, air-dried, and quickly coverslipped for fluorescence microscopy. In Cases 13, 20, and 23, 1 section of 5 was processed for WGA-HRP histochemistry with tetramethylbenzidine as chromogen (Mesulam 1982). In Case 13, in 1 section of 5, CTB-g was revealed by the silver-intensification protocol described by Kritzer and Goldman-Rakic (1995). In Cases 14 and 29, 1 series of each fifth section was processed for the visualization of BDA, using a Vectastain ABC kit (Vector Laboratories, Burlingame, California) and 3,3'-diaminobenzidine (DAB) as a chromogen. The reaction product was intensified with cobalt chloride and nickel ammonium sulfate. In all cases, 1 series of each fifth section was stained with the Nissl method (thionin, 0.1% in 0.1 M acetate buffer pH 3.7), and in Cases 23, 27, and 29 a further series was stained for myelin (Gallyas 1979).
All the other brains, but Case 1, used for cytoarchitectonic analysis were processed as described above and cut frozen in coronal (5 hemispheres) or parallel to the direction of the IPS (2 hemispheres) sections, 60 µm thick. The 2 hemispheres of Case 1, embedded in celloidin, were cut, one in a plane perpendicular to the direction of the IPS, the other in a plane parallel to the direction of the IPS, both at 40 µm. In all cases, 1 series of each fifth section was stained with the Nissl method.
Data Analysis
Injection Sites and Distribution of Retrogradely Labeled Neurons
Injection sites were defined according to criteria previously described in detail (Luppino and others 2001, 2003) and attributed to the architectonic areas of the IPL convexity with analysis of adjacent Nissl-stained sections. The injection sites presented in this study (listed in Table 1) were all restricted within the limits of a single cytoarchitectonic area. One WGA-HRP injection in Case 27 involved both PG and PFG and was not considered for this study.
FB, DY, TB, WGA-HRP, and CTB-g labeling was identified as described in detail in Luppino and others (2001, 2003). CTB-A labeling was analyzed by using standard fluorescein (for CTB-A 488) or rhodamine (for CTB-A 555 and CTB-A 594) sets of filters. CTB-A 488–labeled neurons were identified for a green granular fluorescence in the cytoplasm and CTB-A 555– and CTB-A 594–labeled neurons for a red–orange and a red granular fluorescence in the cytoplasm, respectively. These 2 last tracers were never used in the same animal.
The distribution of retrograde and anterograde (for WGA-HRP and BDA injections) labeling was analyzed in each section every 300 µm and plotted in each section every 600 µm, together with the outer and inner cortical borders, by using a computer-based charting system. Data from individual sections were then imported into a three-dimensional (3D) reconstruction software (Bettio and others 2001), creating volumetric reconstructions of the hemispheres from individual histological sections containing connectional and/or architectonic data. The results of this processing allowed us to obtain realistic visualizations of the labeling distribution for a more precise comparison of data from different hemispheres. Distribution of labeling on exposed cortical surfaces was visualized in standard mesial, dorsolateral, or bottom views of the hemispheres. Distribution of labeling within sulci was visualized in nonstandard views of the hemispheres in which sulcal banks were exposed with appropriate dissections of the 3D reconstructions (Fig. 1).
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Areal Attribution of the Labeling
Retrograde and anterograde labeling was found in several areas of the parietal, temporal, cingulate, agranular frontal, and prefrontal cortices.
In the parietal cortex, outside the IPL convexity, connections were attributed, when possible, to functional areas that, although in many cases still lack a clear architectonic definition, have been well established in electrophysiological studies. Accordingly, the lateral bank of the IPS was subdivided into a caudal (LIP), a rostral (anterior intraparietal, AIP), and a ventral (ventral intraparietal, VIP) area, according to Blatt and others (1990), Murata and others (2000), and Colby and others (1993), respectively. The SPL and the posterior cingulate cortex were subdivided as in Matelli and others (1998) (see also Marconi and others 2001) where functional areas V6A (Galletti and others 1999) and medial intraparietal (MIP) (Colby and others 1988; Colby and Duhamel 1991) were included in the map of Pandya and Seltzer (1982). Area V6A was subdivided into a dorsal (V6Ad) and a ventral (V6Av) sector according to Luppino and others (2005). For the parietal operculum the functional maps of the SII region and neighboring areas of Robinson and Burton (1980a, 1980b) and Krubitzer and others (1995) were considered, although these areas could not be precisely distinguished one from another. In cases of uncertain functional correspondence, labeling was attributed according to the architectonic maps of Pandya and Seltzer (1982) and Lewis and Van Essen (2000a). Temporal areas of the STS and inferior temporal gyrus were defined according to Boussaoud and others (1990) and Saleem and Tanaka (1996). In the frontal lobe, agranular frontal and cingulate areas were cytoarchitectonically defined according to Matelli and others (1985, 1991) and Geyer and others (2000). The prefrontal cortex was subdivided according to the cytoarchitectonic map of Walker (1940) and the prearcuate cortex also according to Stanton and others (1989) and Petrides and Pandya (2002).
Quantitative Analysis and Laminar Distribution of the Labeling
To obtain more objective information on the relative strength of the connections observed within the same case or across different cases, for each cortical injection, but those of BDA (because of the paucity of retrograde labeling observed with this tracer), we counted the number of labeled neurons plotted in the ipsilateral hemisphere in one section every 600 µm and located beyond the limits of the injected field. Because the absolute number of labeled neurons was largely variable across cases, mainly because of differences in amount, spread, and sensitivity of injected tracers, afferents to the injected field were expressed in terms of percent of labeled neurons found in a given cortical area or sector, with respect to the total number of labeled neurons. The percent distribution of the retrograde labeling observed for each area was then used for guiding the qualitative description of its connections. In this analysis, some sectors (e.g., parietal operculum) in which labeling extended across adjacent areas, which could not be precisely defined, were considered as a whole.
To obtain information on possible hierarchical relationships of the observed cortical connections, labeling attributed to a given area and reliably observed across different sections and cases, was analyzed in each section every 300 µm, in terms of laminar distribution of the anterogradely labeled terminals and in terms of percent of labeled neurons located in the superficial (I–III) versus deep (V–VI) layers. These data were then analyzed according to the criteria reviewed by Felleman and Van Essen (1991) (see also Andersen and others 1990). Based on the laminar distribution of labeled terminals, projections were classified as "feedforward" when mostly concentrated in layer IV and lower III, "feedback" when distributed in superficial and deep layers, but avoiding layer IV, "lateral" when fairly even distributed in all cortical layers, and "mixed" when patches of "feedforward" projections were found together with patches of "feedback" projections. Based on the laminar distribution of labeled neurons, connections were classified as "feedforward" or "feedback" when labeled neurons in the superficial layers were >70% or <30%, respectively. More equal distributions were classified as "bilaminar." This last pattern has been generally used to infer that 2 given areas are located at the same hierarchical level. However, as noted by Felleman and Van Essen (1991) (see also Andersen and others 1990; Boussaoud and others 1990; Lewis and Van Essen 2000b), bilaminar connections, at least at the level of parietal and temporal areas, can be compatible with different types of hierarchical relationship, according to the disposition of the anterograde labeling. Because most of the connections observed in the present study, as already noticed by Andersen and others (1990) and Lewis and Van Essen (2000b) in their connectional studies of different parietal areas, showed a bilaminar projection pattern, where not otherwise specified, possible hierarchical relationships as suggested by Felleman and Van Essen (1991) and following Andersen and others (1990) were established on the basis of the laminar distribution of labeled terminals (data available for Opt, PG, and PFG).
In the agranular frontal and cingulate areas, the lack of layer IV forced us to modify these criteria and connections characterized by retrograde labeling mostly in layers III and VI, and anterograde terminals mostly in layers III and V were considered as "feedforward" connections. In some cases, connections were characterized by retrograde labeling mostly in layers III and VI, and terminal labeling was densest in layers I and II and very weak in layer VI. This pattern only partially fits with the criteria used for the definition of "feedback" connections and was left undefined.
Photographic Presentation
Photomicrographs shown in the present study were obtained by capturing images directly from the sections with a digital camera attached to the macroscope or to the microscope. Individual images were then imported in Adobe Photoshop in which they could be processed, eventually assembled into digital montages, and reduced to the final enlargement. In most of the cases, image processing required lighting, contrast, brightness, and contrast adjustments.
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Cytoarchitecture of the IPL Convexity and Location of Injection Sites
The cytoarchitectonic analysis of the IPL convexity showed, in substantial agreement with Pandya and Seltzer (1982), that in this cortical sector 4 different fields can be defined and located at different rostrocaudal levels. Following the nomenclature of Pandya and Seltzer (1982) these fields will be here referred, from rostral to caudal, to as PF, PFG, PG and Opt. The major cytoarchitectonic criteria used in defining these fields are illustrated in Figure 2, in low-power photomicrographs of 4 Nissl-stained coronal sections taken at different rostrocaudal levels from Case 10 and in Figure 3 (upper part) in higher magnification views of representative fields from the same sections.
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In PF, a radial pattern is recognizable in lower layer III as well as in layers V and VI. Cells in layer III display a size gradient with medium-sized pyramids spread in its lower half. Layer IV is homogeneous and lacks a sharp upper border with layer III. Layer V is relatively poor and thin, with rather small pyramids, and layer VI is broad and subdivided into 2 sublayers.
In PFG a columnar organization is evident only in layer III. In this layer, medium-sized pyramids are mainly concentrated in its lowest part. A well-developed layer V is evident, even in low-power views. This layer is populated mainly not only by medium-sized pyramids but also by scattered larger pyramids, which represent a major distinctive feature of PFG, compared with PF and PG. Layer VI is rather uniform.
In PG, the overall cellular density in layer III appears higher, compared with the more rostral areas. This layer is mainly formed by small pyramids, and the almost complete absence of larger cells gives it a rather uniform appearance. Layer V is well developed and populated by densely packed small pyramids. Layer VI is relatively homogeneous.
Opt displays a clear, broad columnar pattern particularly evident in layer III. A size gradient is present in layer III with many medium-sized pyramids occupying its lowest part. Layer IV is sharply defined, and it is denser than in PG. Cell size is also increased in layer V, compared with that of PG, with many medium-sized pyramids. Layer VI has a clear border with layer V and can be subdivided into 2 sublayers.
All these fields enter medially in the IPS for about 2 mm, whereas laterally PF, PFG, and PG border with opercular areas extending in the dorsal bank of the LF (PFop and PGop of Pandya and Seltzer 1982). In general, architectonic features were found to change gradually from one field to another, in the range of less than 1 mm. For this reason, cytoarchitectonic borders presented in this study represent the intermediate point of the transitions and were found to run roughly in the coronal stereotaxical plane, slightly obliquely in caudoventral direction.
The average location along the IPL convexity of the identified cytoarchitectonic fields was quantitatively estimated in 13 hemispheres of M. nemestrina and 8 hemispheres of M. fascicularis. Cytoarchitectonic borders, set as the intermediate points of the transitional zones, were measured in terms of antero-posterior stereotaxic coordinates (AP), according to the M. nemestrina atlas of Winters and others (1969) (AP values referred to the interaural line), and to the M. fascicularis atlas of BrainInfo (2000) (AP values referred to the anterior commissural line, AC). Average cytoarchitectonic maps, shown in Figure 3 (lower part) were, then, generated separately for the 2 species by plotting the average AP values on a dorsolateral view of a standardized hemisphere. To provide an estimate of the interindividual variability across hemispheres of the same species, standard deviation values of the mean AP position of the borders at the level of the lateral crown of the IPS and at the level of the border with the opercular areas are also shown in the maps. The result of this analysis showed that the location of these fields was quite constant across different cases and similar to that shown by Pandya and Seltzer (1982).
In selecting the location of the injection sites our aim was not only to involve different parts of each IPL field but also the more peripheral transitional zones to avoid spread of tracers across different fields. All the injection sites considered for this study (most of them shown in Fig. 4, in drawings of representative sections through the core and the rostral and caudal part of the halo) were restricted to a single architectonic field, only in few cases marginally involving transitional zones. For this reason, the patterns of connections described in this study mostly concern much more the core of each field rather than the transitional zones. Given the relatively low interindividual variability in the location of cytoarchitectonic borders, only in 1 case a WGA-HRP injection in Case 27 was found to be not restricted to a single field, involving both PG and PFG. The labeling distribution observed of in this case was fully compatible with an almost equal involvement of both these fields and, therefore, not considered in this study.
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The general distribution of the retrograde labeling observed in Cases 23 and 27 DY and TB and drawings of representative coronal sections from Case 23 are presented in Figures 6 and 7, respectively. The percent distribution of the labeled neurons observed in Cases 23 and 27 DY, as well as the mean values of all the 3 Opt injections, are shown in Table 2. Representative patterns of the laminar distribution of retrograde and anterograde labeling observed in Case 23 are illustrated in Figure 8.
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Parietal and Posterior Cingulate Cortices
In the IPL very strong "lateral" connections of Opt were observed with PG (Figs. 6, 7, section f, and 8, PG), whereas PFG was only very marginally labeled. Weak, "lateral" connections were observed in the parietal operculum, only with its outermost and caudalmost part, corresponding to area PGop of Pandya and Seltzer (1982). Caudal to Opt, moderate "feedback" connections were observed with the dorsal aspect of the prelunate gyrys (area DP, Andersen and others 1990). In the lateral bank of the IPS, numerous and dense patches of marked cells were observed in its caudal part in both the dorsal (LIPd) and the ventral (LIPv) subdivisions of area LIP (Blatt and others 1990). In this area, the anterograde labeling showed a "feedback" pattern, and retrograde labeling in layers I–III was >70% (Fig. 8, LIP). In the SPL, connections were limited to the mesial surface of the hemisphere and to the anterior wall of the parietooccipital sulcus (Fig. 6). In particular, these very strong connections extensively involved, with some variability in the relative distribution across cases, area PGm (Fig. 7, sections b–e), extending caudally in V6Av (Luppino and others 2005; Fig. 7, section a) and rostrally, in the caudal part of the cingulate gyrus (posterior cingulate cortex, CGp; Olson and others 1996). In all these areas the anterograde labeling showed a "feedback" pattern, and in PGm the labeled neurons in layers I–III were >70% (Fig. 8, PGm). Some labeling was also found more rostrally, in areas 23a and 23b.
Temporal Cortex, Including Area MST and Insula
Opt was connected with different STS and inferotemporal areas. In the caudal part of the STS (Fig. 6) very strong "feedback" connections (retrograde labeling in layers I–III >70%) were found in area MST (Figs. 7, section e, and 8, MST), mostly in its dorsal and caudal part (presumably dorsal MST, MSTd; Komatsu and Wurtz 1988). Weak labeling was observed in the middle temporal area (MT) (Fig. 7, sections d and e) and very sparse labeled cells in the fundal superior temporal area (FST). In the upper bank of the STS robust, "lateral," or "mixed" connections (Fig. 8, superior temporal polysensory area, STP) were observed in restricted sectors lateral and rostral to MST, attributable to both the posterior (STPp; Fig. 7, section e) and anterior (STPa; Fig. 7, sections h, i, and n) subdivisions of the superior temporal polysensory area, respectively. Ventral to STPa, "feedforward" connections were observed with the fundal region of the sulcus (area IPa; Fig. 7, section l; Fig. 8, IPa), extending also in the ventral bank, in the medial part of area TE (TEm) (Fig. 7, sections m and n). Additional labeling in the inferotemporal cortex, showing a "lateral" pattern, was observed in the postero-ventral part of area TE (TEpv) (Figs. 6 and 7, sections g and h), on the lateral lip and the fundus of the occipitotemporal sulcus. With the only exception of a small cluster of marked neurons observed in the postero-dorsal part of area TE (TEpd) in Case 27 (Fig. 6), in both Cases 23 and 27, labeling in TEm and TEpv was observed in very similar locations, suggesting that Opt is target of specific subsectors of these inferotemporal areas. Spots of labeling were also observed at different rostrocaudal levels in the parahippocampal area TF, and few scattered marked neurons were located in the perirhinal cortex (Figs. 6 and 7, sections g, i, l, and m). In Case 23, some purely anterograde labeling was found in the caudal part of the presubiculum. Very poor labeling was inconstantly located in the granular insula (Fig. 7, sections l and n).
Agranular Frontal and Cingulate Cortices
Two agranular frontal sectors, located in the dorsal premotor cortex (PMd) and ventral premotor cortex (PMv), respectively, showed relatively weak connections with Opt (Fig. 6). In PMd (Fig. 7, section o), labeling was consistently observed in the lateral part of the rostral PMd area F7, not including the supplementary eye field (F7 non-SEF [Luppino and others 2003]). In this premotor sector, anterograde labeling was very weak in deep layers, and much denser in layers I and II (Fig. 8, F7). In PMv (Fig. 7, section p), labeling, with some variability across cases, was found in the rostral area F5, in a relatively rostral part of the posterior bank of the arcuate sulcus, the anterograde labeling being mostly focused in layer III ("feedforward" pattern). In the agranular cingulate cortex, sparse labeling was observed in area 24b.
Prefrontal Cortex
Several relatively weakly labeled sectors were observed in the prefrontal cortex (Figs. 6 and 7, sections p–r). In both Cases 23 and 27, some labeling was located relatively caudally in the principal sulcus, mostly in the ventral bank and much weaker labeling was found on the mesial surface of the hemisphere, in medial area 8B. Some labeling was also found in the ventral prearcuate cortex, in area 45 ventral to the frontal eye field (FEF), as defined cytoarchitectonically in adjacent Nissl-stained sections (area 45b of Petrides and Pandya 2002). Part of the labeling was also observed on the dorsal lip of the principal sulcus (dorsal area 46) and in the dorsalmost part of area 8A. Finally, a very weak connection was also observed with the orbitofrontal area 12o (Fig. 6). All prefrontal connections of area Opt showed a "feedforward" pattern (Fig. 8, 45).
Connections of Area PG
Five tracer injections in 3 animals (Case 20, WGA-HRP; Case 27, CTB-A 594; Case 29, TB and CTB-A 488; Case 29, BDA) were placed in different parts of area PG. Figure 5B shows the location of the WGA-HRP injection in Case 20, placed in the middle of the inferior parietal gyrus (see also Fig. 4), in a sector where cytoarchitectonic features typical of area PG, for example, a layer III quite homogeneous in cell size and density, a layer V densely populated by relatively small pyramids, could be observed in the adjacent Nissl-stained section (Fig. 5B1).
The general distribution of retrograde labeling observed in Cases 20 (WGA-HRP) and 27 (CTB-A 594) and drawings of representative coronal sections from Case 20 are presented in Figures 9 and 10, respectively. The percent distribution of the labeled neurons observed in these 2 cases, as well the mean values of all the PG injections, but the BDA one, is shown in Table 2. Representative patterns of laminar distribution of retrograde and anterograde labeling observed in Cases 29, BDA, and 20 are illustrated in Figure 11.
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Parietal and Posterior Cingulate Cortices
In the IPL, strong "lateral" connections were observed with areas PFG, PGop, and the rostral part of area Opt (Figs. 9, 10, sections d–g, and 11, Opt). A few marked neurons were also found in area PF and in area DP. In the parietal operculum, in addition to PGop, very strong connections showing a "feedback" pattern were observed with the retroinsular cortex, but also more rostrally and deeply, with area SII (Figs. 9, 10, sections f–h, and 11, SII). A more rostral, minor labeling can be attributed to area PV. In the lateral bank of the IPS, moderate "lateral" connections were observed with the mid-rostral part of it, mostly involving area AIP and, at a very minor extent, area VIP (Figs. 9 and 10, sections f–h). Area LIP, which was heavily connected with Opt, was virtually devoid of marked neurons. Moderate to rich connections showing a "lateral" pattern (Fig. 11, PEci) were observed in different areas of the caudal part of the SPL, with some variability in their relative distribution across cases. These connections involved the caudal part of the ventral bank of the cingulate sulcus (area PEci), area V6Ad (Figs. 9 and 10, sections a and b) and area PEc. Area PGm and the CGp were virtually devoid of labeling. Dense patches of "lateral" connections (Fig. 11, MIP) were also observed in the medial bank of the IPS, where, although with some variability across cases, most of them were observed in the mid-caudal part of it, attributable mostly to area MIP. In the cingulate area 23, rich "lateral" connections (Fig. 11, 23c) were observed with the ventral bank of the cingulate sulcus (area 23c) and the dorsal part of the cingulate gyrus (area 23b).
Temporal Cortex, Including Area MST and Insula
Very rich labeling was observed in MST (Figs. 9 and 10, sections d and e), which extended also more rostrally (and deeply) with respect to Opt injections, possibly involving also the lateral part of MST (MSTl, Komatsu and Wurtz 1988). Dense, but restricted labeling was also found at different rostrocaudal levels of area STP attributable to both STPp and STPa (Figs. 9 and 10, sections f, i, and o). In particular, the labeling in STPa shown in Figure 10, section i, appears to occupy a location similar to the labeling observed following injections in Opt. In both MST and STP the anterograde labeling showed a "feedback" pattern (Fig. 11, MST and STP). Very weak "feedforward" connections (more evident following BDA injection) were also observed in area IPa (Figs. 10, section m, and 11, IPa). Very sparse labeling was observed in area MT (Fig. 10, section c) and in perirhinal and parahippocampal cortices (Fig. 10, section l). In 2 cases (Case 29 BDA and 29 TB), some labeling was observed in area TEav, close to the anterior medial temporal sulcus. In Case 29 BDA, labeled terminals were also observed in the caudal part of the presubiculum. One additional and distinctive relatively strong connection of PG, showing a "feedback" pattern (retrograde labeling in layers I–III >70%), was located caudally, in the ventral bank of the LF, extending also on the adjacent part of the superior temporal gyrus (Figs. 9, 10, sections f and g, and 11, C), involving areas C of Morel and others (1993) and Tpt of Pandya and Sanides (1973; see also Lewis and Van Essen 2000a). Rich "feedforward" connections (retrograde labeling in layers I–III <70%) were also observed in insular area Ig (Figs. 9 and 10, section l).
Agranular Frontal and Cingulate Cortices
Minor connections were observed with several agranular frontal areas. In PMv, clusters of marked cells, with labeled terminals densest in layer III ("feedforward" pattern; Fig. 11, F5), were located along the entire extent of the posterior bank of the inferior arcuate sulcus (area F5; Figs. 9 and 10, sections n and o). In PMd, labeling was consistently observed in the ventrorostral part of area F2 (F2vr; Luppino and others 2003), close to the spur of the arcuate sulcus (Figs. 9 and 10, sections m–o), and additional, sparse labeling was located in area F6/pre-supplementary motor area (pre-SMA) (Fig. 9). Finally, clusters of labeled cells were also found in the cingulate motor area 24d (Fig. 10, section n), mainly in the ventral bank of the cingulate sulcus and in area 24b (Fig. 9). In F2vr, F6 and area 24, labeled terminals were mostly confined to layers I and II (Fig. 11, F2vr).
Prefrontal Cortex
The only prefrontal sector consistently labeled following PG injections was the ventral part of area 46 (Figs. 9 and 10, sections p and q). In particular, "lateral" connections (Fig. 11, 46v) were found mostly in the ventral bank of the principal sulcus, partially overlapping with the sector connected with Opt, but also extending more dorsally to include the ventral lip of the sulcus and the adjacent cortical convexity.
Connections of Area PFG
Five tracer injections were placed in 4 animals in different parts of area PFG (Case 13, WGA-HRP; Case 14, BDA; Case 27, CTB-A 488; Case 29, FB and CTB-A555). Figure 5C shows the location of the WGA-HRP injection site in Case 13, placed in the mid-ventral part of the inferior parietal gyrus (see also Fig. 4), where cytoarchitectonic features typical of area PFG, for example, medium-sized pyramids in the lowest part of layer III and a well-developed layer V, with occasional relatively large pyramids, could be observed in the adjacent Nissl-stained section (Fig. 5C1).
The distribution of the retrograde labeling observed in Cases 13, WGA-HRP, and 29, FB (shown in light blue), is illustrated in Figure 12. The percent distribution of the labeled neurons observed in these 2 cases, as well as the mean values of all the PFG injections, but the BDA one, is shown in Table 2. Three-dimensional reconstructions of Case 29 in Figure 12 also show in red the distribution of the neurons marked following TB injection in PG to provide direct comparison between the differential patterns of cortical connectivity of PFG and PG found in the present study. Drawings of representative coronal sections from Case 13 are presented in Figure 13, and representative patterns of the laminar distribution of retrograde and anterograde labeling observed in Cases 14, BDA, and 13 are illustrated in Figure 14.
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Parietal and Posterior Cingulate Cortices
Following PFG injections, the labeled territory extended to the adjacent caudal and rostral areas PG and PF, respectively (Figs. 12 and 13, sections b, c, and f). The strong, "lateral" connections between PFG and PG (Fig. 14, PG) were very evident in Case 29, where retrograde tracers were injected in both these areas (Fig. 12). In the parietal operculum, similarly to PG, very dense labeling ("lateral" connections) was found more caudally in correspondence of PGop (Fig. 13, sections c and d) and retroinsular cortex, and more rostrally ("feedback" connection; Fig. 14, SII) in correspondence of SII (Fig. 12, sections e–h) and PV. In the lateral bank of IPS, strong "lateral" connections were observed in areas AIP and VIP (Figs. 12, 13, sections d–g, and 14, VIP). The dense labeling in VIP extended also in the rostral part of the medial bank of the IPS, in the rostral part of area PEa, rostral to MIP, corresponding to the medial IPS sector source of corticospinal projections (area PEip of Matelli and others 1998; Figs. 12, 13, sections d, e, and h, and 14, PEa). In contrast, in areas MIP and V6Ad, source of rich afferents to PG (Fig. 12, Case 29, TB, red labeling) marked neurons were poor. Weak connections ("lateral" pattern) were observed with areas PEci and 23.
Temporal Cortex, Including Area MST and Insula
"Feedback" connections (retrograde labeling in layers I–III >70%), weaker than those observed following PG injections, were observed in area MST in all cases of injections in PFG (Figs. 12, 13, section b, and 14, MST). In STP restricted but relatively robust labeling showing a "mixed" type of connections (Fig. 14, STP) was found in both STPp and STPa (Figs. 12 and 13, sections c, g, and h). In particular, the labeled STPa sector in Figure 13, section g, appeared to largely overlap with the STPa sector connected with PG and Opt. In the ventral bank of the STS, in addition to few marked neurons found in area MT (Fig. 13, section a), some labeling was also located in area FST (Fig. 13, section d). More rostrally, some clusters of marked neurons were consistently observed, in all cases, in areas IPa and TEm, where labeled terminals showed a "feedforward" pattern (Figs. 12, 13, sections e and f, and 14, TEm). Robust "feedforward" connections (retrograde labeling in layers I–III <70%) were observed in the insular area Ig.
Agranular Frontal and Cingulate Cortices
Connections of PFG with the agranular frontal cortex were rich and by far densest in PMv. (Figs. 12 and 13, sections i–m). In F4, which is virtually not connected with PG, relatively weak labeling was almost completely confined to the dorsal part of it, whereas in F5 a rich labeling involved the whole posterior bank of the arcuate sulcus, extending also on the cortical convexity. Labeled terminals in both these areas tended to be relatively evenly distributed across all layers ("lateral" connections, Fig. 14, F5). Weak labeling (with high degree of variability among cases) was observed, especially in Case 14, BDA, in F2vr, where terminals were mostly concentrated in the superficial layers (Fig. 14, F2vr) and even sparser labeling could also be observed in F6/pre-SMA, F3 and F1. In area 24 labeling showing a "lateral" pattern was observed in areas 24d and 24b.
Prefrontal Cortex
Substantial connections, with some variability across cases, were observed with ventral area 46 in a location similar to that labeled following injections in PG (Figs. 12 and 13, sections o and p). Additional and distinctive connections of area PFG, with respect to PG (although with some variability in their strength among cases), were observed in the caudal and lateral part of the orbitofrontal cortex (area 12o of Carmichael and Price 1994) and in the disgranular, precentral opercular area (PrCO) ventral to F5. All these connections could be classified as "lateral" (Fig. 14, 46v).
Corticospinal Projections from the IPL Convexity
Figure 15 shows the distribution of the labeled corticospinal neurons observed in the hemispheres of Cases 10 and 21 contralateral to large HRP injections in the lateral funiculus of the spinal cord at upper cervical levels. Considering the size and the level of the injections, the distribution of labeled neurons can be considered, in both cases, quite representative of the origin of projections to all spinal levels caudal to C4–C5. In the IPL convexity a cortical sector, very well corresponding to area PFG, was found to be a source of corticospinal projections. These projections represent a distinctive connectional feature of this area with respect to the other IPL convexity areas. In Case 10, DY was also injected in the same lateral funiculus at the upper thoracic level to identify the origin of projections to the thoracic and lumbar spinal levels. The results (not shown in the figure) showed that DY-labeled neurons were virtually absent in PFG, thus suggesting that this area is a source of corticospinal projections mostly directed to the cervical levels of the spinal cord.
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Connections of Area PF
Three tracer injections were placed in area PF in 3 different monkeys (Case 13 CTB-g, Case 27 FB, and Case 29 DY), which produced remarkably similar distributions of retrograde labeling. Figure 5D shows the location of the DY injection site in Case 29, placed in the middle of the inferior parietal gyrus (see also Fig. 4), in a cortical sector showing a dense layer III with medium-sized pyramids in the lower half, a well-developed layer IV, and a relatively poor layer V (area PF, Fig. 5D1). Figure 16 shows the results observed in Case 29 DY in 3D reconstructions of the injected hemisphere and in drawings of representative coronal sections. The percent distribution of the labeled neurons observed in Case 29 DY and 27 FB, as well as the mean values of all the PF injections, is shown in Table 2. In general, PF displayed connections with a much more limited set of cortical areas, with respect to the other IPL convexity fields, virtually all confined to the parietal and frontal cortices.
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Parietal Cortex
The major feature of the cortical connections of PF was the very strong connection with the postcentral gyrys (Fig. 16, dorsolateral view and sections d and e). In this sector, retrograde labeling was very dense and almost completely confined to area 2, in its ventral part. In the IPL convexity, the connections with area PFG were very strong, extending also more caudally to involve, at a minor extent, area PG (Fig. 16, dorsolateral view and sections a and b). In the parietal operculum (Fig. 16, upper bank of the LF and sections d–f), very dense labeling was found in the SII region, with substantial labeling involving, presumably, also area PV. In the IPS, connections were quite strong with areas AIP and VIP (Fig. 16, sections a–c) but weak with rostral PEa. Weak labeling was observed in the insular cortex (Fig. 16, section f).
Frontal Cortex
In the agranular frontal cortex the labeling was quite dense in both PMv areas F4 and F5. In F4, labeling was densest in the dorsal part of this area, close to the spur of the arcuate sulcus (Fig. 16, dorsolateral view and sections f and g). In F5 (Fig. 16, postarcuate cortex and sections f–i), it included the whole extent of the posterior bank of the inferior arcuate sulcus and the cortical convexity, where labeled neurons appeared to extend also more ventrally with respect to those observed following injections in PFG. Relatively weak labeling was also found ventral to F5 in area PrCO and in ventral area 46 (Fig. 16, dorsolateral view and section m). In all cortical areas, but the granular insula, the distribution of the retrograde labeling was bilaminar. In the granular insula, marked cells showed a "feedback" pattern.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
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In this study we traced the cortical connections of the 4 architectonic fields—PF, PFG, PG, and Opt—forming the macaque IPL cortical convexity by placing tracer injections aimed to involve different parts of each field, but the more peripheral, transitional ones. The results showed that each of these fields is robustly connected with the neighboring ones and displays markedly different patterns of connections with visual-, somatosensory-, auditory-, and limbic-related areas and with parietal and frontal areas related to the control of different effectors. Figure 17 summarizes the main results of this study.
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It is largely accepted in neuroscience that the cerebral cortex contains many functionally distinct domains, usually referred to as "areas," although there is no consensus on what precisely constitutes a cortical area and what the best criteria are for their definition (see, e.g., Van Essen 1985
). In general, 3 main experimental approaches, the architectural, the connectional, and the functional, are considered most useful for the definition of a cortical area. Converging evidence from these 3 approaches is generally considered a strong argument for a reliable identification and delineation of a cortical area (see, e.g., Van Essen 1985; Felleman and Van Essen 1991; Lewis and Van Essen 2000a).
In this respect, connectivity patterns undoubtedly provide an important basis for identifying cortical areas and determining whether neighboring regions belong to the same or different areas (see, e.g. Lewis and Van Essen 2000b). Indeed, the present data, although not able to establish how sharp changes in connectivity patterns from one field to another are, clearly indicate that Opt, PG, PFG, and PF are not only cytoarchitectonically, but also connectionally distinct. This proposed subdivision of the IPL convexity in 4 areas still needs to be warranted by detailed functional studies aimed to map the distribution of properties along the IPL convexity. The current proposal, however, appears to seriously challenge the widely used bipartite subdivision of this cortical sector into a caudal and a rostral area (7a and 7b, respectively), confirming, but also extending, the scheme proposed by Pandya and Seltzer (1982). Moreover, the present results provide new insight into the possible role of the IPL convexity in different aspects of space coding and motor control.
Comparison with Previous Studies
Several previous investigations have already aimed to study the pattern of connections of different parts of the IPL convexity (Stanton and others 1977; Pandya and Seltzer 1982; Petrides and Pandya 1984; Neal and others 1987, 1988a, 1988b, 1990; Cavada and Goldman-Rakic 1989a, 1989b; Andersen and others 1990; Lewis and Van Essen 2000b).
All these studies, but those of Pandya and colleagues (see later), were based on the bipartite subdivision of the IPL convexity into a caudal and a rostral area (7a and 7b, respectively) and altogether presented data showing that 7a and 7b have markedly different cortical connections, the former being primarily connected with visual areas, the latter with somatosensory areas.
According to the 2 most comprehensive studies of the cortical connections of 7a and 7b (Cavada and Goldman-Rakic 1989a, 1989b; Andersen and others 1990), 7a is extensively connected with visual areas of both the dorsal (e.g., MST) and the ventral (inferotemporal cortex) visual stream, with the higher order polysensory area STP and with limbic areas of the parahippocampal and posterior cingulate cortices. In the parietal cortex, connections of 7a include primarily those with the adjacent oculomotor area LIP, the mesial area PGm, and visual areas of the caudal SPL (PO and MDP in the nomenclature of these authors). Frontal connections are mainly directed to prefrontal area 46 and also to the prearcuate cortex. In contrast, most prominent connections of area 7b include those with somatosensory areas SI, SII, and area 5 to the granular insular cortex and the rostral cingulate area 24 and in the frontal lobe to PMv and prefrontal areas 46 and 45. Some connections with visual areas of the STS and of the caudal SPL were also described.
Pandya and colleagues (Pandya and Seltzer 1982; Petrides and Pandya 1984; Seltzer and Pandya 1984) relied on a parcellation scheme similar to the one used in our study but placed injections that nevertheless were relatively large and involved, in the mid-caudal part of the IPL, both PG and Opt or both PFG and PG. These studies, therefore, did not distinguish among possible differential patterns of connections of PFG, PG, and Opt. In particular, data from caudal (PG and Opt) IPL injections are in substantial agreement with reports on 7a connections, whereas data from injections in the middle part of the IPL (PFG and PG) are difficult to interpret, the injection sites involving also part of the parietal operculum or of the lateral bank of the IPS.
The present data, based on injections restricted to areas PF, PFG, PG, and Opt provide a new, more detailed view of the connectivity of the IPL convexity, which only partially fits with the general scheme proposed by the abovementioned studies.
Our data on Opt and PG (altogether roughly corresponding to 7a) injections indicate that these areas are strongly interconnected with each other and are both connected with areas MST, DP, and with temporal areas of the STS, including different rostrocaudal sectors of area STP and area IPa. The distribution of the labeling observed in the STS is in line with previous connectional studies of the caudal IPL convexity (Seltzer and Pandya 1984; Neal and others 1988b; Cavada and Goldman-Rakic 1989a; Andersen and others 1990; Cusick and others 1995; Seltzer and others 1996; Lewis and Van Essen 2000b). Furthermore, our data on Opt injections are in full agreement with the study of Andersen and others (1990; see later) in showing that connections with STP appear to be "mixed." It should be mentioned, however, that following large injections in the caudalmost part of the IPL, Cusick and others (1995) defined the connections with the intermediate and rostral sectors of the dorsal bank of the STS (TPOi and TPOr in their nomenclature) as "feedforward." The reason for this discrepancy is not clear.
As summarized in Figure 17, the present data, however, clearly show that Opt and PG, have markedly different connections with parietal, frontal, limbic, and temporal areas other that STP and IPa, clearly supporting the notion that area 7a, at least as originally defined by Vogt O and Vogt C (1919) and usually delineated in the anatomical and functional literature, is not homogeneous.
In particular, a major finding of our study is that the major connections of Opt, summarized in Figure 17, nearly all coincide with those previously attributed to area 7a (Neal and others 1988a; Cavada and Goldman-Rakic 1989a; 1989b; Andersen and others 1990; Neal and others 1990) or to PG and Opt (Pandya and Seltzer 1982; Petrides and Pandya 1984; Seltzer and Pandya 1984).
In contrast, although PG is clearly located within the limits of Vogts' area 7a, most of its connections described here and summarized in Figure 17 have never been attributed to area 7a in previous reports. This is especially true for the observed robust connections of PG with parietal areas V6Ad, MIP, and PEc and the minor connections with agranular frontal and cingulate areas F5, F2vr, F6/pre-SMA, and 24d, all areas related to the control of arm movements (see, e.g., Colby 1998; Rizzolatti and others 1998). This discrepancy can be explained on the basis of the location of the injection sites. Cavada and Goldman-Rakic (1989a, 1989b) placed an injection site in area 7a (their Case 2) relatively caudally, very likely mostly in Opt. Furthermore, in the study of Andersen and others (1990), area 7a is considerably smaller than the Vogts' area 7a (see also Andersen and others 1997), corresponding mostly to Opt, plus only a small part of PG. Accordingly, it is not surprising that also in this study, 7a injections reproduced, to a large extent, the connectivity observed in our study following Opt injections. Finally, Pandya and Seltzer (1982) and Petrides and Pandya (1984) following a large tracer injection involving both PG and Opt (their Case 16) also showed a labeling distribution basically very similar to those of Opt of the present study. Only some connections, for example, with area Tpt, with AIP, or with caudal and dorsal sectors of the SPL according to our data can be attributed to area PG. Connections of the rostral part of area 7a with arm-related premotor fields were, however, noticed by Hedreen and Yin (1981), and labeling in rostral 7a (PG) was also reported following tracer injections in F6/pre-SMA (Luppino and others 1993), F2/caudal PMd (Tanne-Gariepy and others 2002), and PMv (Godschalk and others 1984). It is possible, therefore, that the distinctive pattern of connections of PG versus Opt, consistently observed in our study, was previously missed, mainly because of the location of the injection sites in most of the studies on 7a connections.
Our data on PF and PFG injections (altogether roughly corresponding to area 7b) indicate that the rostral part of the IPL convexity is not homogeneous either. The present data on PF connections, summarized in Figure 17, are in full agreement with reports of Pandya and colleagues (Pandya and Seltzer 1982; Petrides and Pandya 1984) in which the location of their area PF is very similar to that of the present study. In other studies this rostralmost part of the IPL convexity was clearly avoided or only partially involved by tracer injections, possibly because it was partially included by Vogt O and Vogt C (1919) within area 2. The present data, as well as those of Pandya and colleagues, showing connections of PF with PMv and area 46, clearly support the notion that this rostralmost part of the IPL convexity should be considered as part of the posterior parietal cortex.
One major finding of this study is that cytoarchitectonic area PFG displays a distinctive connectivity pattern. As summarized in Figure 17, connections with MST, STP, and parietal areas PEci and PEa and the lack of connections with SI are major connectional features that clearly characterize PFG with respect to PF. Connections with rostral intraparietal areas PEa and VIP and with F4 and the lack of connections with caudal intraparietal and parietooccipital areas and area Tpt, very well characterize PFG, with respect to PG. Finally, PFG is the only IPL convexity area that is a source of corticospinal projections, apparently mostly directed to the cervical levels.
Pandya and colleagues (Pandya and Seltzer 1982; Petrides and Pandya 1984; Seltzer and Pandya 1984) placed injections in the middle of the IPL convexity involving both PFG and PG and, in some cases, also the IPS or the opercular cortex. Their data, therefore, cannot be compared with the present ones. This is true also for the study of Andersen and others (1990), which set the 7a/7b border more caudally, with respect to that of Vogt O and Vogt C (1919). Accordingly, 7b injections in this study clearly involved also area PG. However, on the basis of its location and extent, the 7b injection in the studies of Cavada and Goldman-Rakic (1989a, 1989b) and Lewis and Van Essen (2000b), appear to involve mostly PFG. In both these studies, connections attributed to 7b, appear to correspond, to a large extent, to the connections described here for PFG. Finally, the finding that PFG is a source of corticospinal projections finds support in the study of Galea and Darian-Smith (1994), which described corticospinal projections from a cortical sector defined as 7b but very likely coincident with PFG.
Functional Considerations
Caudal IPL Convexity
The functional organization of the caudal part of the IPL convexity, usually referred to as area 7a, is an issue that still presents some controversial aspects, mostly due to differences in the criteria used for its anatomical and/or functional definition and the resulting differences in its extent compared with area 7a, as originally defined by Vogt O and Vogt C (1919). Area 7a is generally considered as a visually responsive area, placed at the apex of the dorsal visual stream, where retinal and extraretinal signals contribute to the construction of representations of surrounding space, according to head-, body- or world-centered coordinates, for space perception and guidance of motor behavior (see, e.g., Andersen and others 1997; Siegel and Read 1997a). This view is supported by data showing that 7a neurons have large visual receptive fields, usually bilateral, modulated by the orbital position of the eye or by the position of the head (see, e.g., Andersen and others 1997; Siegel and Read 1997a) and are active during execution of saccadic (Barash and others 1991) or pursuit eye movements (Bremmer and others 1997). Furthermore, 7a, although lacking a reproducible retinotopic organization (Heider and others 2005), displays topography in terms of eye position gain fields (Siegel and others 2003), and neurons in this area appear to be involved in the analysis of different types of optic flow (Siegel and Read 1997b; Phinney and Siegel 2000).
These studies, however, appear to be mostly focused on the caudal part of the Vogts' area 7a, that is, where the inferior parietal gyrus narrows because of the upward bending of the STS, present in virtually all macaque brains. This sector to a large extent coincides with Opt. Indeed, the connectivity pattern reported here for Opt suggests that this is the caudal IPL area in which representations of surrounding space according to head-, body-, or world-centered coordinates are constructed for space perception and the guidance of motor behavior. The Opt connections with corticotectal projecting areas dorsal 8A and 8B (Fries 1985), where intracortical microstimulation evokes eye and/or ear movements (Mitz and Godschalk 1989; Schall and others 1995) and neurons have visual and/or acoustic responses (Azuma and Suzuki 1984; Vaadia and others 1986) also suggest a role of Opt in the control of orienting movements in space. In this context, it appears of interest to note is that recent optical imaging data have suggested a role of caudal 7a (largely corresponding to Opt) in the neural mechanisms underlying shifts of attention in space (Raffi and Siegel 2005).
Recent data suggested a novel role of caudal 7a in the guidance of motor behavior. In particular, Battaglia-Mayer and others (2005) showed that in caudal 7a (likely Opt, cfr. their Fig. 2), neurons are influenced by signals concerning planning and execution of both eye and arm movements and encode eye- and arm-directional visuomotor signals related to the contralateral space. The presence of arm reaching–related activity in this sector has also been reported by Heider and others (2004). Indeed, Opt is connected strongly with PGm and weakly with F7, that is, areas where combined arm and eye movement–related activity was recorded (Ferraina and others 1997; Fujii and others 2000). F7 is, in turn, a target of major projections from PGm (Matelli and others 1998) and from dorsal area 46 (Luppino and others 2003) a prefrontal sector, target of Opt, included into the so-called space memory domain by Wilson and others (1993). Furthermore, Opt is tightly connected with PG, which, as discussed below, may represent a major source of the arm-related signals recorded in this area. Accordingly, Opt would represent a site of convergence of different types of sensory and eye- and arm-related motor signals used, as suggested by Battaglia-Mayer and others (2005), to construct an integrated representation of the contralateral eye and arm motor space.
Functional evidence, however, also indicates that the rostral part of the Vogts' 7a (likely PG), unlike Opt, is mostly involved in the control of arm movements (Mountcastle and others 1975; Lynch and others 1977; Hyvärinen 1981; Blum 1985; Andersen and others 1990; MacKay 1992). All these last studies did not specifically aim to unequivocally dissociate arm-related from possible eye-related signals and the possibility that in PG neurons may be influenced by other types of motor signals cannot be at present completely ruled out. However, our data on PG connections strongly support the view that this area is primarily an arm-related field. Indeed, virtually all the most important parietal connections of PG are with areas involved in visual or visual and somatosensory guidance of distal or proximal arm movements, that is, the hand-related area AIP (Murata and others 2000) and the arm-related areas MIP (Colby and Duhamel 1991; Johnson and others 1996), PEc (Battaglia-Mayer and others 2001), and dorsal V6A (Galletti and others 1997; Battaglia-Mayer and others 2001). Moreover, the relatively weak but consistent connections of PG with agranular frontal and cingulate areas where distal (F5) or proximal and distal (F2, 24d) arm movements are represented (see, e.g., Luppino and others 1991; Rizzolatti and Luppino 2001; Raos and others 2004) may well represent possible pathways, not previously described, mediating a more direct role of PG in the control of arm movements.
The possible functional role of PG appears to rely on the analysis of a large variety of sensory information. The strong afferents from MSTd could explain the visual responses in 7a (Mountcastle and others 1975; Hyvärinen 1981) and their selectivity for different types of optic flow (Siegel and Read 1997b; Phinney and Siegel 2000), suggesting a role of this area also in the control of arm movement, in agreement with previous data showing direct projections from MSTd to F2vr (Luppino and others 2001). Moreover, PG appears to be a target also of MSTl, where there are neurons that appear to code object motion in world-centered coordinates (Ilg and others 2004) and are supposed to be involved in the guidance of eye or arm movements (Ilg and Schumann 2004). Finally, the strong connections with Opt may represent a further major source of visual input possibly related to space coding according to several different frames of reference. PG is also a target of projections from SII, retroinsular cortex, and PEci, potential sources of somatosensory information (Robinson and Burton 1980a, 1980b; Murray and Coulter 1981), in line with reports of somatosensory responses in the rostral part of the Vogts' area 7a (Hyvärinen 1981; Andersen and others 1990). Finally, PG is strongly connected with areas C and Tpt, potential sources of auditory information (Pandya and Sanides 1973; Leinonen and others 1980; Morel and others 1993). Although auditory responses have never been observed in the IPL convexity, it is possible that, as shown in LIP (Mazzoni and others 1996), this information is used only when crucial for planning motor activity. It is then possible that in PG there is a multimodal integration of visual, somatosensory, and auditory information, in which extrapersonal space coded on the basis of different frames of reference, is coregistered with arm-position signals for the control of arm movements.
Altogether, our data strongly suggest that the rostral and the caudal part of 7a correspond to different cortical areas, Opt and PG, respectively. This distinction is based not only on cytoarchitectural data, as previously also suggested by Pandya and Seltzer (1982), but also by the markedly different connectivity patterns of these 2 areas, which cannot be simply explained in terms of any type of topographic organization. This proposed subdivision is not in contrast with the possibility that PG and Opt, though primarily related to different aspects of motor control, cooperate in the mechanisms giving rise to representations of motor space through their strong reciprocal connections. Future electrophysiological or optical imaging experiments focused on both these areas are highly desirable to clarify this issue.
In this respect, quite interesting are the substantial, "lateral" connections of PG and Opt (but also PFG) with the superior temporal polysensory area (STP; Bruce and others 1981) and site of convergent projections from somatosensory, auditory, and visual areas (for reviews, see Felleman and Van Essen 1991; Cusick 1997). STP has been subdivided into a caudal sector (STPp), target of parietal areas of the dorsal visual stream, and a rostral sector (STPa), where inputs from dorsal and ventral visual stream areas converge (Boussaoud and others 1990; Baizer and others 1991; see also Felleman and Van Essen 1991; Cusick 1997). Almost all the neurons studied in STP are visually responsive, but over half of them also have somatosensory and/or auditory responses (Bruce and others 1981). It has been then suggested an that there is an involvement of this area in integration of information within and across modalities, subserving orienting behavior to novel stimuli (Bruce and others 1981; Bayliss and others 1987). Furthermore, visually responsive neurons may have complex functional properties, extensively studied by Perrett and others (1989) (for review, see, e.g., Carey and others 1997). In particular, STP visual neurons (mostly in STPa) may code whole-body or body-parts postures, particular types of body motion, may differentiate between self-produced actions and actions made by others, and may code movements in terms of goal-directed actions. Finally, STPa neurons appear to code biological motion also implied from static postures and intentionality of actions (Jellema and others 2000; Jellema and Perrett 2003). Thus, the possible functional role of PG and Opt (but also PFG, as discussed later) may also rely on these higher order perceptual processes of crucial importance in the social behavior of primates.
One final point that deserves some comments is the finding that both Opt and PG (but also PFG) project in a differential way to their target premotor areas, in some of them displaying a "feedforward" pattern of projections and in others displaying projections primarily to the superficial layers. These observations open the possibility that Opt and PG (but also PFG) may have a more specific effect on some premotor areas and a possible modulatory role on others.
Rostral IPL Convexity
According to Hyvärinen (1981), 7b contains a rostral, mostly somatosensory, mouth and face field and a caudal hand, arm and face field, in which neurons are responsive to visual or to visual and somatosensory stimuli (see also Robinson and Burton 1980b). Recent data suggested a role of this caudal field in higher order aspects of visuomotor transformations and organization of goal-directed arm/hand and face movements. First, the caudal part of 7b, likely PFG (L. Fogassi, personal communication), contains visually responsive neurons active during the observation of arm, hand, and mouth goal-directed movements made by the experimenter (parietal mirror neurons, Gallese and others 2002), suggesting a role of this area in action recognition. Second, Fogassi and others (2005) recently showed that a class of these parietal mirror neurons appears to be engaged in understanding intentions of others. Finally, in this same sector there are neurons active during the execution of combined face/hand movements (Ferrari and others 2003; Yokochi and others 2003) or coding the final goal of a complex action (Fogassi and others 2005).
The present data are fully in line with the apparent functional segregation in 7b. Connections of PF with the ventral part of area 2 and with SII and PV suggest a major role for this area mostly in somatomotor transformations for the guidance of face and mouth movements. Furthermore, PF could be a source of somatosensory information to the visual and somatosensory face-related area VIP (Colby and others 1993). Frontal projections of PF are directed to F4, where many neurons have somatosensory and visual receptive fields around the face (Fogassi and others 1996), and also to ventral and dorsal sectors of F5, where the mouth and the hand are mostly represented, respectively (Gentilucci and others 1988). These data, as well as the connections with PFG and AIP, suggest a role for PF also in somatomotor transformations related to the control of hand movements.
PFG is a newly defined cortical area with a distinctive pattern of connections. Connections with SII, parietal (e.g., PG, AIP), and temporal visual areas, as well with areas VIP and PEa, where peripersonal space around the face or the arm is coded, respectively (Colby and others 1993; Iriki and others 1996; Duhamel and others 1998), could explain the somatosensory and visual responses described in caudal 7b (Robinson and Burton 1980b; Hyvärinen 1981). Connections with the ventral premotor areas F4 and F5, where premotor mirror neurons are located (Gallese and others 1996), suggest a role for PFG in visuo- and somatomotor transformation for the guidance of arm/hand and face movements and a joint involvement of PFG and F5 in a cortical system engaged in high order motor functions related to the organization of complex actions, action understanding, and intention understanding (Rizzolatti and others 2001; Fogassi and others 2005).
In this respect, particularly interesting are the connections with temporal areas (mostly STPa), where neurons appear to code actual or implied biological motion and intentionality of actions or appear to code goal-directed hand actions (Perrett and others 1989; see also Carey and others 1997). These connections provide a strong anatomical support to the hypothesis that PFG represents a step in a pathway linking STP with PMv, mediating the matching between the visual description of an observed action, coded in STPa, with corresponding motor representations, coded in F5 (cortical mirror system, Rizzolatti and others 2001).
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Conclusions |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
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The primate posterior parietal cortex consists of several areas, involved in parallel in the analysis of specific aspects of visual information, alone or in combination with the somatosensory one. These areas are distributed over both the SPL and the IPL, in contrast to the classical notion that the dorsal visual stream involves only the IPL (for reviews, see Caminiti and others 1996
; Galletti and others 2003; Rizzolatti and Matelli 2003). A major result of this processing is the construction of multiple representations of space based on different frames of references used for the control of specific classes of actions (Andersen and others 1997; Rizzolatti and others 1997; Colby 1998). Our data, showing that the IPL convexity is formed by several distinct areas, potential sites of convergence of multimodal sensory information and connected with parietal and frontal areas involved in motor control of different effectors, are congruent with such an organizational view. The present data also show that 3 of these IPL areas—Opt, PG, and PFG—in addition to areas LIP (Blatt and others 1990) and AIP (Luppino, Murata, and others 2004) are target not only of areas of the so-called magnocellular cortical pathway but also of high order visual areas of the temporal cortex. Thus, the macaque IPL appears to be a site where visual information from both the dorsal and the ventral visual stream is integrated with information about motor programs. This view is in line with the possible homology of this region with the corresponding sector of the human brain, which, in the evolutionary processes leading to lateralization of functions, developed areas involved, in the right hemisphere, to perception of spatial relationships and, in the left hemisphere, to the storage of complex representations of actions. |
Acknowledgments |
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Professor Massimo Matelli died on August 2003. The authors are profoundly indebted to him for his contribution to this study and agreed that his name had to be included as a coauthor in this manuscript. We wish to remember him not only as a scientist but also as a person contagious in his enthusiasm for research and as an example for all of us. The authors are also grateful to Leonardo Fogassi and Claudio Galletti for their suggestions and comments on a preliminary version of the manuscript. The 3D reconstruction software was developed by CRS4, Pula, Cagliari, Italy. This study was supported by EU (Contract QLRT-2001-00746) and MIUR.
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