Abstract

We found that the macaque inferior parietal (PFG and anterior intraparietal [AIP]), ventral premotor (F5p and F5a), and ventrolateral prefrontal (rostral 46vc and intermediate 12r) areas forming a network involved in controlling purposeful hand actions (“lateral grasping network”) are a source of corticotectal projections. Based on injections of anterograde tracers at the cortical level, the results showed that all these areas displayed relatively dense projections to the intermediate and deep gray layers of the ipsilateral superior colliculus (SC) and to the ventrally adjacent mesencephalic reticular formation. In the SC, the labeling tended to be richer in the lateral part along almost the entire rostro-caudal extent, that is, in regions controlling microsaccades and downward gaze shifts and hosting arm-related neurons and neurons modulated by the contact of the hand with the target. These projections could represent a descending motor pathway for controlling proximo-distal arm synergies. Furthermore, they could broadcast to the SC information related to hand action goals and object affordances extraction and selection. This information could be used in the SC for controlling orienting behavior (gaze and reaching movements) to the targets of object-oriented actions and for the eye–hand coordination necessary for appropriate hand-object interactions.

Introduction

Connectional studies (Rozzi et al. 2006; Borra et al. 2008, 2011; Gerbella et al. 2011, 2012) provided evidence for the involvement of a series of hand-related ventral premotor (PMv), inferior parietal lobule (IPL), and ventrolateral prefrontal (VLPF) areas in a cortical network, here designated as “lateral grasping network” (Fig. 1). This network is considered to play a role in selecting and controlling object-oriented hand actions, based on visual and memory-based information and on information on behavioral goals (see, e.g., Grafton 2010; Davare et al. 2011). Furthermore, recent evidence (Borra et al. 2010) showed that the PMv area F5p, which in this network represents the gateway for the access of signals related to the selection of hand motor acts to the primary motor cortex, is a source of projections to the superior colliculus (SC).

Figure 1.

A summary view of the areas of the lateral grasping network object of the present study and of their interconnections. AI, inferior arcuate sulcus; AS, superior arcuate sulcus; C, central sulcus; i12r, intermediate part of area 12r; IO, inferior occipital; IP, intraparietal sulcus; L, lateral fissure; P, principal sulcus; r46vc, rostral part of area 46vc; ST, superior temporal sulcus.

Figure 1.

A summary view of the areas of the lateral grasping network object of the present study and of their interconnections. AI, inferior arcuate sulcus; AS, superior arcuate sulcus; C, central sulcus; i12r, intermediate part of area 12r; IO, inferior occipital; IP, intraparietal sulcus; L, lateral fissure; P, principal sulcus; r46vc, rostral part of area 46vc; ST, superior temporal sulcus.

The SC is a multilayered sensorimotor midbrain structure where sensory, primarily visual, information is used for orienting behavior, that is, the generation of eye, head, and arm movements toward an object of interest (see, e.g., Stein et al. 2009; Wurtz 2009; Gandhi and Katnani 2011). As the SC hosts arm-reaching neurons (Werner 1993; Werner, Dannenberg, et al. 1997; Werner, Hoffmann, et al. 1997; Stuphorn et al. 2000) and neurons modulated by the contact of the hand with the target (Nagy et al. 2006), it is possible that the F5p projections to the SC represent a descending motor pathway for controlling proximo-distal arm synergies.

It is well established that the intermediate and deep layers of the SC are a target of projections originating from the parietal and frontal visuomotor areas involved in a cortical network for initiating and controlling voluntary eye movements (for review, see Lynch and Tian 2006). However, it seems from indirect data (Leichnetz et al. 1981; Fries 1984; Lock et al. 2003) that corticotectal projections originate from a territory extending beyond the location of oculomotor areas and, apparently, involving the location of areas of the lateral grasping network. If this is the case, then it is possible that signals related not only to the execution, but also to the selection of hand motor acts, are broadcasted to the SC for the generation of eye-, head-, and arm-orienting movements (Stuphorn et al. 2000; Krauzlis and Carello 2003; Wurtz 2009).

To assess the possible neural substrate for this hypothesis, in the present study, we examined the projections to the brainstem labeled after injections of anterograde tracers in the PMv, IPL, and VLPF nodes of the lateral grasping network.

Materials and Methods

Subjects, Surgical Procedures, and Selection of the Injection Sites

The present study is based on the results from 9 macaque monkeys (6 Macaca mulatta, 2 M. nemestrina, and 1 M. fascicularis), in which anterograde tracers were injected in the PMv areas F5p and F5a, in the IPL areas anterior intraparietal (AIP) and PFG, and in the VLPF areas 12r and 46v (Table 1). Most of the results described here are from tracer injections (listed in Table 1) that have already been used in previous studies focused on the cortical connectivity of the areas under study (Rozzi et al. 2006; Borra et al. 2008, 2011; Gerbella et al. 2011, 2012). To have data from at least 2 tracer injections in each area, data from 5 not previously published tracer injections were also used. The corticotectal projections observed after a tracer injection in F5p in Case 35r have already been described in a previous study (Borra et al. 2010) and were reanalyzed here for the sake of comparison with those of the other areas of the lateral grasping network.

Table 1

Location of injection sites and the type and amount of injected tracers

Case Species Hemisphere Area Tracer Amount (µL) 
Case 14 M. nemestrina PFGa BDA 10% 4 × 1 
Case 30 M. nemestrina AIPb BDA 10% 4 × 1 
 F5a WGA-HRP 4% 1 × 0.1 
Case 34 M. fascicularis F5ac BDA 10% 2 × 1 
Case 35 M. mulatta F5pc BDA 10% 2 × 1 
Case 43 M. mulatta 46vc LYD 10% 1 × 1 
Case 44 M. mulatta 12rd FR 10%f 1 × 1 
 12rd LYD 10% 1 × 1 
Case 52 M. mulatta 46vce BDA 10% 1 × 2 
Case 54 M. mulatta AIP BDA 10% 4 × 1 
 PFG FR 10% 4 × 1 
Case 55 M. mulatta 12r FR 10% 2 × 1 
Case Species Hemisphere Area Tracer Amount (µL) 
Case 14 M. nemestrina PFGa BDA 10% 4 × 1 
Case 30 M. nemestrina AIPb BDA 10% 4 × 1 
 F5a WGA-HRP 4% 1 × 0.1 
Case 34 M. fascicularis F5ac BDA 10% 2 × 1 
Case 35 M. mulatta F5pc BDA 10% 2 × 1 
Case 43 M. mulatta 46vc LYD 10% 1 × 1 
Case 44 M. mulatta 12rd FR 10%f 1 × 1 
 12rd LYD 10% 1 × 1 
Case 52 M. mulatta 46vce BDA 10% 1 × 2 
Case 54 M. mulatta AIP BDA 10% 4 × 1 
 PFG FR 10% 4 × 1 
Case 55 M. mulatta 12r FR 10% 2 × 1 

fMix 1:1 of the MW 3000/10 000.

Animal handling, as well as surgical and experimental procedures, complied with the European guidelines (86/609/EEC and 2003/65/EC Directives) and Italian laws in force regarding the care and use of laboratory animals, and were approved by the Veterinarian Animal Care and Use Committee of the University of Parma and authorized by the Italian Health Ministry.

Under general anesthesia and aseptic conditions, each animal was placed in a stereotaxic apparatus, and an incision was made in the scalp. The skull was trephined to remove the bone overlying the target region, and the dura was opened to expose the PMv, IPL, and VLPF. The criteria for the selection of the injection sites have been described in detail in previous studies (Table 1). Briefly, in the PMv, the injection sites were chosen using architectonic data as a frame of reference (Belmalih et al. 2009), referred in terms of the location of anatomical landmarks, such as the arcuate sulcus, its spur, and the inferior precentral dimple. In the IPL, the injection sites in AIP were placed in the lateral bank of the intraparietal sulcus (IPS) at antero-posterior (AP) stereotaxic levels between −2 and 6 (Borra et al. 2008), and injection sites in PFG were chosen by using cytoarchitectonic data as a frame of reference (Gregoriou et al. 2006), referred in terms of stereotaxic coordinates and the location of anatomical landmarks such as the IPS and the lateral fissure. In the VLPF, the choice of the injection sites was based on identified anatomical landmarks, that is, the inferior arcuate sulcus, infraprincipal dimple, and principal sulcus (PS), and using an average architectonic map of the caudal VLPF providing an estimate of the average location of the various areas of this region (Gerbella et al. 2007). These data were then used to estimate the AP level of the injection sites within the VLPF.

After the tracer injections were placed, the dural flap was sutured, the bone was replaced, and the superficial tissues were sutured in layers. During surgery, hydration was maintained with saline, and temperature was maintained using 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 cages and closely monitored. Dexamethasone and prophylactic broad-spectrum antibiotics were administered pre- and postoperatively. Furthermore, analgesics were administered intra- and postoperatively.

Tracer Injections and Histological Procedures

Once the appropriate site was chosen, the mostly anterograde tracer biotinylated dextran amine ([BDA] 10 000 molecular weight [MW], 10% 0.1 M phosphate buffer, pH 7.4; Invitrogen) and the retro-anterograde tracers dextran conjugated with tetramethylrhodamine (Fluoro-Ruby [FR], 10 000 MW, or equal mixture of 10 000 and 3000 MW volumes, 10% 0.1 M phosphate buffer, pH 7.4; Invitrogen) or with lucifer yellow (Lucifer Yellow Dextrane [LYD], 10 000 MW, 10% in 0.1 M phosphate buffer, pH 7.4; Invitrogen-Molecular Probes) and wheat germ agglutinin-horseradish peroxidase conjugated (WGA-HRP, 4% in distilled water, Sigma, St. Louis, MO, USA) were slowly pressure injected through a glass micropipette (tip diameter: 50–100 µm) attached to a 1- or 5-µL Hamilton microsyringe (Reno, NV, USA). Table 1 summarizes the locations of the injections, the injected tracers, and their amounts.

After appropriate periods following the injections (28 days for BDA, FR, and LYD and 2 days for WGA-HRP), each animal was deeply anesthetized with an overdose of sodium thiopental, perfused consecutively with saline, 3.5–4% paraformaldehyde, and 5% glycerol, and prepared in 0.1 M phosphate buffer, pH 7.4, through the left cardiac ventricle. 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, each brain was cut frozen into coronal sections of 60-µm thickness. In Case 14r, only sections through the rostral half of the SC were available. In all cases of BDA injections, one series of each fifth section was processed to visualize BDA (incubation 60 h), using a Vectastain ABC kit (Vector Laboratories, Burlingame, CA, USA) and 3,3′-diaminobenzidine (DAB) as a chromogen. The reaction product was intensified with cobalt chloride and nickel ammonium sulfate. In Case 54r and in Cases 43r, as well as 44r, in which BDA was injected in other areas, 2 series of each fifth section were processed to visualize FR and BDA, or LYD and BDA, using the double-labeling protocol described in detail in Gerbella et al. (2010). Briefly, the sections were first processed to visualize BDA, except for a shorter incubation period in the ABC solution (overnight), and then BDA was stained brown using DAB. Then, the sections were incubated overnight in avidin–biotin blocking reagent (Vector SP-2001), for 72 h at 4°C in a primary antibody solution of rabbit anti-FR or rabbit anti-LYD (1:3000; Invitrogen) in 0.3% Triton, 5% normal goat serum in PBS, and for 1 h in biotinylated secondary antibody (1:200, Vector) in 0.3% Triton, 5% normal goat serum in PBS. Finally, FR or LYD labeling was visualized using the Vectastain ABC kit (Vector Laboratories) and the Vector SG peroxidase substrate kit (SK-4700, Vector) as a chromogen. With this procedure, BDA labeling was stained brown, and the FR or the LYD labeling was stained blue in the same tissue sections. To obtain comparable results, the same protocol for FR labeling was used in Case 55r, in which BDA was not injected. In Case 30l, one series of each fifth section was processed for HRP histochemistry following the protocol described by Mesulam (1982). Sections were rinsed in 0.01 M acetate buffer, pH 3.3, and developed at 4°C in an acetate buffer solution, 0.09% sodium ferricyanide, using tetramethylbenzidine as chromogen. In all cases, one series of each fifth section was stained with the Nissl method (0.1% thionin in 0.1 M acetate buffer, pH 3.7).

Data Analysis

The distribution of anterograde labeling in the brainstem was analyzed and plotted in every 300-µm sections, together with the outlines of the section, the aqueduct, and the blood vessels. The attribution of anterograde labeling to the SC and to the other brainstem structures was made by superimposing adjacent Nissl-stained sections on the plots of the labeling, with the aid of a microprojector. Differences in shrinkage between adjacent, differentially processed sections were corrected by slightly changing the magnification of the microprojector. The SC layers were defined according to May (2006), and the brainstem structures were designated mostly according to the nomenclature of the atlas of Paxinos et al. (2000).

To visualize the distribution of the BDA, FR, and LYD anterogradely labeled terminals, similarly to Dancause et al. (2005) and Borra et al. (2010), a grid pattern (100 × 100 µm) was overlaid on the digitalized images of the sections. A marker was placed in a square of the grid when at least 3 labeled terminals were located within the square. After preliminary analysis, we defined 2 types of marked squares, based on the number of terminals located within: squares displaying 3–8 terminals and squares displaying >8 terminals. These 2 types reflected relatively sparser (e.g., en passant varicosities) and relatively richer (e.g., clusters of synaptic endings) labeling observed in 100 × 100 × 60 µm tissue voxels. The WGA-HRP anterograde labeling was plotted qualitatively based on the distribution of the foci of fine granular reaction products considered to reflect the presence of labeled synaptic terminals or axonal arborizations of preterminals.

The distribution of the labeling in the SC was also visualized in 2-dimensional (2-D) reconstructions obtained as follows. As shown in Figure 2, in each plotted section, the SC was flattened at the level of a virtual line running in the mediolateral direction along the middle of SC thickness. The flattened sections were then aligned to correspond with the midline, and the labeling was distributed along the space between the 2 consecutive plotted sections (300 µm).

Figure 2.

Unfolding procedure for obtaining 2D reconstructions of the SC, shown for 3 representative coronal sections taken at a rostral, an intermediate, and a caudal level. In each section, the SC was flattened at the level of a virtual line (dashed line) starting from the midline (a) and running in the mediolateral direction along the middle of SC thickness. The medial and lateral borders of the SC are marked by the dotted lines (b and c). The 2D reconstruction shown in the lower part of the figure was then obtained by aligning the flattened sections to correspond with the midline and by assigning to each section a thickness of 300 µm (gray shading). Arrows mark the levels of the 3 representative sections. APT, anterior pretectal area; BIC, nucleus of the brachium of the inferior colliculus; bsc, brachium of the superior colliculus; IC, inferior colliculus; L, lateral; Lim, limitans nucleus of the thalamus; 5Me, mesencephalic trigeminal nucleus; MG, medial geniculate nucleus of the thalamus; MRF, mesencephalic reticular formation; OPT, olivary pretectal nucleus; PAG, periaqueductal gray; PN, pontine nuclei; R, rostral; SG, suprageniculate nucleus of the thalamus.

Figure 2.

Unfolding procedure for obtaining 2D reconstructions of the SC, shown for 3 representative coronal sections taken at a rostral, an intermediate, and a caudal level. In each section, the SC was flattened at the level of a virtual line (dashed line) starting from the midline (a) and running in the mediolateral direction along the middle of SC thickness. The medial and lateral borders of the SC are marked by the dotted lines (b and c). The 2D reconstruction shown in the lower part of the figure was then obtained by aligning the flattened sections to correspond with the midline and by assigning to each section a thickness of 300 µm (gray shading). Arrows mark the levels of the 3 representative sections. APT, anterior pretectal area; BIC, nucleus of the brachium of the inferior colliculus; bsc, brachium of the superior colliculus; IC, inferior colliculus; L, lateral; Lim, limitans nucleus of the thalamus; 5Me, mesencephalic trigeminal nucleus; MG, medial geniculate nucleus of the thalamus; MRF, mesencephalic reticular formation; OPT, olivary pretectal nucleus; PAG, periaqueductal gray; PN, pontine nuclei; R, rostral; SG, suprageniculate nucleus of the thalamus.

Results

The injection sites used in the present study involved PMv, IPL, and VLPF areas or fields, which, based on their cortical connectivity, appear to form a network involved in selecting and controlling goal-directed hand actions, here designated as the lateral grasping network. Figure 3 shows in the upper part a composite view of the location of all the injection sites and in the lower part the exact location of those injection sites not previously published. In the PMv, 2 tracer injections (Cases 34l BDA and 30l WGA-HRP) were placed in F5a, a visuomotor hand-related field (Theys et al. 2012) tightly connected to F5p and displaying consistent connections with the IPL areas AIP and PFG and with the prefrontal areas 46v and 12r (Gerbella et al. 2011). In the IPL, 2 tracer injections (Cases 14r BDA and 54r FR) involved PFG, a visuomotor hand-related area (Rozzi et al. 2008) consistently connected both to F5p and F5a and to area 46v (Rozzi et al. 2006). Two other tracer injections (Cases 30l BDA and 54r BDA) involved AIP, a visuomotor hand-related area (Murata et al. 2000) consistently connected both to F5p and F5a and to the prefrontal areas 46v and 12r (Borra et al. 2008). In the VLPF, 2 tracer injections (Cases 43r LYD and 52r BDA) were placed in the caudal part of area 46v (46vc), at about 5–6 mm from the caudal border. These injections involved a sector of this area (rostral 46vc), displaying consistent connections with F5a, PFG, and AIP (Gerbella et al. 2012). Three other VLPF tracer injections (Cases 44r LYD and FR, and 55r FR) involved the intermediate part of area 12r (intermediate 12r), that is, the sector consistently connected to F5a and AIP (Borra et al. 2011). Finally, the previously published data from one representative case (Case 35r BDA) of tracer injection in area F5p were reanalyzed here to allow a comparison of the corticotectal projections of this area with those of the other areas of the hand action cortical network.

Figure 3.

Location of injection sites. Upper part: composite view of all the injection sites mapped on a template right hemisphere. Each injection site was numbered and reported, based on anatomical landmarks and stereotaxic coordinates, in the posterior bank of the arcuate sulcus (A) in the IPL (B), and in the VLPF (C). In order to avoid distortions of the template hemisphere, the AP level of the injections sites in anterior intraparietal (AIP) in the ventral bank of the inferior parietal sulcus and in rostral area 46vc in the ventral bank of PS is indicated by arrows. Arrowheads in B indicate the rostro-caudal extent of area AIP, which does not extend on the lateral surface. Lower part: the location of injection sites in Cases 30l WGA-HRP (D), 54r FR and BDA (E), and 55r FR and 43r LYD (F), shown on dorsolateral views of the injected hemispheres and in coronal sections through the core (shown in black) and the halo (shown in lighter gray). The arrows in the dorsolateral views of the hemispheres in D, E, and F indicate the levels of the injection sites within sulci. For the sake of comparison, all the reconstructions in this figure are shown as a right hemisphere. Cg, cingulate sulcus; LO, lateral orbital sulcus; Lu, lunate sulcus; MO, medial orbital sulcus. Other abbreviations as in Figure 1.

Figure 3.

Location of injection sites. Upper part: composite view of all the injection sites mapped on a template right hemisphere. Each injection site was numbered and reported, based on anatomical landmarks and stereotaxic coordinates, in the posterior bank of the arcuate sulcus (A) in the IPL (B), and in the VLPF (C). In order to avoid distortions of the template hemisphere, the AP level of the injections sites in anterior intraparietal (AIP) in the ventral bank of the inferior parietal sulcus and in rostral area 46vc in the ventral bank of PS is indicated by arrows. Arrowheads in B indicate the rostro-caudal extent of area AIP, which does not extend on the lateral surface. Lower part: the location of injection sites in Cases 30l WGA-HRP (D), 54r FR and BDA (E), and 55r FR and 43r LYD (F), shown on dorsolateral views of the injected hemispheres and in coronal sections through the core (shown in black) and the halo (shown in lighter gray). The arrows in the dorsolateral views of the hemispheres in D, E, and F indicate the levels of the injection sites within sulci. For the sake of comparison, all the reconstructions in this figure are shown as a right hemisphere. Cg, cingulate sulcus; LO, lateral orbital sulcus; Lu, lunate sulcus; MO, medial orbital sulcus. Other abbreviations as in Figure 1.

The results showed that all the areas of the lateral grasping network are a source of projections to the mesencephalon, mostly involving the SC and the adjacent mesencephalic reticular formation (MRF). Additional dense spots of labeled terminals were observed in the pontine nuclei after tracer injections in areas F5a, PFG, and AIP. Furthermore, after tracer injections in area F5a, some anterograde labeling was observed in the pontine reticular formation. Thus, the brainstem projections of F5a were similar to those of F5p, which, however, also projects to the bulbar reticular formation (Borra et al. 2010).

Cortico-Mesencephalic Projections From the Lateral Grasping Network

The distribution of anterograde labeling observed in the mesencephalon after injections in the various areas of the lateral grasping network is shown in Figures 4–7 in drawings of selected coronal sections through the brainstem and in 2D reconstructions of the ipsilateral SC.

Figure 4.

Drawings of coronal sections through the ipsilateral SC showing the distribution of anterograde labeling observed following tracer injections in the PMv areas F5p (Case 35r BDA) and F5a (Cases 34l BDA and 30l WGA-HRP). For each case, the sections are shown in a rostral to caudal order. In Cases 35r BDA and 34l BDA, each square corresponds to a 100 × 100 × 60 µm voxel containing: 3–8 labeled terminals (gray) and >8 labeled terminals (black). In Case 30l WGA-HRP, dot density is proportional to the density of the fine grain chromogen precipitate. For the sake of comparison, anterograde labeling in this and in the subsequent figures is shown as in a right SC. ECIC, external cortex of the inferior colliculus; HB, habenula; pc, posterior commissure; SGI, stratum griseum intermediale; SGP, stratum griseum profundum; SGS, stratum griseum superficiale; SO, stratum opticum. Other abbreviations as in Figure 2.

Figure 4.

Drawings of coronal sections through the ipsilateral SC showing the distribution of anterograde labeling observed following tracer injections in the PMv areas F5p (Case 35r BDA) and F5a (Cases 34l BDA and 30l WGA-HRP). For each case, the sections are shown in a rostral to caudal order. In Cases 35r BDA and 34l BDA, each square corresponds to a 100 × 100 × 60 µm voxel containing: 3–8 labeled terminals (gray) and >8 labeled terminals (black). In Case 30l WGA-HRP, dot density is proportional to the density of the fine grain chromogen precipitate. For the sake of comparison, anterograde labeling in this and in the subsequent figures is shown as in a right SC. ECIC, external cortex of the inferior colliculus; HB, habenula; pc, posterior commissure; SGI, stratum griseum intermediale; SGP, stratum griseum profundum; SGS, stratum griseum superficiale; SO, stratum opticum. Other abbreviations as in Figure 2.

Figure 5.

Drawings of coronal sections through the ipsilateral SC showing the distribution of anterograde labeling observed following tracer injections in the parietal areas AIP (Cases 30l BDA and 54r BDA) and PFG (Cases 54r FR and 14r BDA). In Case 14r BDA, sections through the caudal SC were not available. Conventions and abbreviations as in Figures 2 and 4.

Figure 5.

Drawings of coronal sections through the ipsilateral SC showing the distribution of anterograde labeling observed following tracer injections in the parietal areas AIP (Cases 30l BDA and 54r BDA) and PFG (Cases 54r FR and 14r BDA). In Case 14r BDA, sections through the caudal SC were not available. Conventions and abbreviations as in Figures 2 and 4.

Figure 6.

Drawings of coronal sections through the ipsilateral SC showing the distribution of anterograde labeling observed following tracer injections in the prefrontal fields intermediate 12r (Cases 44r LYD and FR, and 55r FR) and rostral 46vc (Cases 43r LYD and 52r BDA). Conventions and abbreviations as in Figures 2 and 4.

Figure 6.

Drawings of coronal sections through the ipsilateral SC showing the distribution of anterograde labeling observed following tracer injections in the prefrontal fields intermediate 12r (Cases 44r LYD and FR, and 55r FR) and rostral 46vc (Cases 43r LYD and 52r BDA). Conventions and abbreviations as in Figures 2 and 4.

Figure 7.

Distribution of anterograde labeling observed following injections in F5p, F5a, AIP, PFG, rostral 46vc, and intermediate 12r shown in 2D reconstructions of the ipsilateral SC, aligned to the midline, and indicated by a solid straight line. Arrows pointing to the midline indicate AP stereotaxic levels. Arrowheads pointing to the lateral part of the SC indicate the levels of the sections shown in Figures 4–6. AP = 0 corresponds to the posterior commissure. Conventions and abbreviations as in Figures 2 and 4.

Figure 7.

Distribution of anterograde labeling observed following injections in F5p, F5a, AIP, PFG, rostral 46vc, and intermediate 12r shown in 2D reconstructions of the ipsilateral SC, aligned to the midline, and indicated by a solid straight line. Arrows pointing to the midline indicate AP stereotaxic levels. Arrowheads pointing to the lateral part of the SC indicate the levels of the sections shown in Figures 4–6. AP = 0 corresponds to the posterior commissure. Conventions and abbreviations as in Figures 2 and 4.

In spite of some variability observed across the cases, all the injected areas displayed several common connectional features in their projections to the mesencephalic structures. First, relatively dense anterograde labeling was observed in the ipsilateral SC, in the intermediate and the deep gray layers (stratum griseum intermediale [SGI] and stratum griseum profundum [SGP], respectively), but not in the superficial layers. Secondly, the labeling in the ipsilateral SC tended to be richer in the lateral part along almost the entire rostro-caudal extent. Thirdly, though with some variability, anterograde labeling extended from the lateral part of the SGP to the ventrally adjacent MRF. All these connectional features also characterized the corticotectal projections from F5p.

Besides these common connectional features, some differences were observed across the cases, mostly in the distribution of anterograde labeling in the ipsilateral SC. Specifically, after tracer injections in the IPL and VLPF areas, in most of the cases, the labeling tended to be more extensive and was relatively rich also more medially. Furthermore, some labeled terminals were observed in the SGI of the contralateral SC (not shown) in all cases, but those of VLPF tracer injections. This contralateral labeling showed a distribution similar to that observed in the ipsilateral SC, but was considerably less rich and extensive. Finally, in those cases in which the labeling in the MRF appeared to be more extensive (e.g., Cases 30l WGA-HRP and 52r BDA, Figs 4 and 6), some anterograde labeling was also observed in the periaqueductal gray. The relatively limited number of tracer injections on which the present study is based does not allow us to draw any firm conclusion about whether these differences are due to true interareal connectional differences or due to some unavoidable variability intrinsic to the tract-tracing experimental approach used in the present study.

In all cases, anterograde labeling in the SC, particularly in the lateral part, tended to be organized into 2 distinct zones, located in the SGI and SGP, respectively (Fig. 8A,D,E). Specifically, preterminal arborizations, varicosities, and synaptic endings tended to be relatively more packed in the SGI and more loosely arranged in the SGP as well as in the adjacent MRF (Fig. 8B,C). Furthermore, labeled axons within and in the proximity of the labeled zones were, typically, relatively thin (about 1–2 µm diameter), although some larger ones (about 4–5 µm diameter) were observed, particularly after injections in F5p.

Figure 8.

(A, D, and E) Low-power photomicrographs showing the distribution of anterograde labeling observed in the SC after tracer injections in F5a (A), AIP (D), and intermediate12r (E). (B and C) Higher magnification views, taken from the section shown in A, of anterograde labeling observed in SGI (B) and SGP (C). Scale bar in A applies also to D and E. Scale bar in B applies also to C. Abbreviations as in Figures 2 and 4.

Figure 8.

(A, D, and E) Low-power photomicrographs showing the distribution of anterograde labeling observed in the SC after tracer injections in F5a (A), AIP (D), and intermediate12r (E). (B and C) Higher magnification views, taken from the section shown in A, of anterograde labeling observed in SGI (B) and SGP (C). Scale bar in A applies also to D and E. Scale bar in B applies also to C. Abbreviations as in Figures 2 and 4.

Discussion

The present study shows that the IPL (PFG and AIP), PMv (F5p and F5a), and VLPF (rostral 46vc and intermediate 12r) areas forming a network involved in controlling purposeful hand actions (lateral grasping network) are a source of corticotectal projections.

Previous studies based on tracer injections in the SC have shown that several cortical areas are a source of corticotectal projections, which can be grouped into 2 components (Leichnetz et al. 1981; Fries 1984; Lock et al. 2003). One component targets primarily the SC superficial layers and originates from V1 and V1 recipient areas. The other component targets primarily the SC intermediate and deep layers and originates from 1) visual and polysensory temporal areas; 2) dorsal visual stream areas; and 3) visuomotor parietal and frontal areas generally assumed to correspond to the areas forming a cortical network controlling voluntary eye movements (see, e.g., Lynch and Tian 2006).

In these studies, labeled corticotectal cells have been also observed in the postarcuate cortex, in the rostral IPL, and relatively rostrally in the VLPF (Leichnetz et al. 1981; Fries 1984, 1985; Lock et al. 2003). These regions, which appear to likely involve the location of hand- and hand/mouth-related areas, at that time were not identified as anatomically and functionally independent areas. After a large tracer injection in the SC, Fries (1985) also observed some labeling extending caudal to the postarcuate cortex toward the lateral part of the central sulcus. As the arm/hand field of the primary motor area M1 does not project to the SC (Hartmann-von Monakow et al. 1979; Shook et al. 1990; Tokuno et al. 1995), it is possible that this labeling mostly involved the M1 face and neck representation.

As the SC has been traditionally viewed as an oculomotor structure, several studies have already examined in details the corticotectal projections from the various fields of the oculomotor network. Specifically, the frontal eye field (FEF; Huerta et al. 1986; Stanton et al. 1988; Shook et al. 1990), the supplementary eye field (SEF; Huerta and Kaas 1990; Shook et al. 1990), areas LIP (Asanuma et al. 1985; Lynch et al. 1985; Lui et al. 1995) and 7m (Leichnetz 2001) all tend to project to the entire extent of the SC, primarily to the intermediate layers. In addition, less dense projections from the FEF, SEF, and LIP to the superficial and deep layers have been observed, though with some variability across different studies. The present data showed a different corticotectal projection pattern for the areas of the lateral grasping network. Indeed, though with some variability across the cases, all these cortical sectors tended to project more richly to the lateral SC involving both the intermediate and deep layers and the adjacent MRF.

It is largely agreed that corticotectal projections from oculomotor fields exert an excitatory drive mostly to the SC intermediate layers where neurons are activated prior to saccadic eye movements and project directly to premotor regions in the brainstem oculomotor system. These projections are deemed to play an important role in the control of voluntary gaze shifts (see, e.g., Lynch and Tian 2006; Wurtz 2009; Gandhi and Katnani 2011).

The present data showing that the SC is also a target of projections from hand-related and, to some extent, also mouth-related areas provide evidence for additional, not previously hypothesized possible roles of the corticotectal projections. Future studies may clarify the possible contribution of these projections to the SC role in orienting behavior. Based on our actual knowledge, it seems plausible to put forward the following working hypotheses.

First, it is well-known that the SC hosts arm-related neurons firing during reaching movements (Werner 1993; Werner, Dannenberg, et al. 1997; Werner, Hoffmann, et al. 1997; Stuphorn et al. 2000) and neurons modulated by the contact of the hand with the target (Nagy et al. 2006). These neurons are located in the intermediate layers, intermingled with eye-related neurons, in the deep layers, and in the underlying MRF (Werner, Hoffmann, et al. 1997). Furthermore, they tend to be more concentrated in the lateral SC, showing a distribution similar to that of the corticotectal projections traced in the present study. It is, thus, possible that these projections modulate the SC arm-related neurons during the execution of reaching–grasping movements. Indeed, area F5p is a source of corticospinal projections (Borra et al. 2010), and both areas F5p and F5a project to the pontine and bulbar reticular formation (Borra et al. 2010; present data), which might relay to the spinal cord neural activity for the control of proximo-distal arm synergies (Baker 2011). Accordingly, the corticotectal projections traced in the present study, or at least those originating from F5p and F5a, could represent an additional descending motor pathway.

It is also possible that the corticotectal projections from the lateral grasping network provide the SC with information related to the action goal and to the extraction and the selection of object affordances. Indeed, the parietofrontal circuits linking areas PFG and AIP with area F5 are at the core of a network involved in selecting and organizing purposeful object-oriented hand actions, rather than in their mere execution (Jeannerod et al. 1995; Rizzolatti and Luppino 2001; Grafton 2010). Specifically, the PFG-F5 circuit appears to play a role in organizing hand actions based on their final goal, and the AIP-F5 circuit is crucially involved in visuomotor transformations for grasping, based on the extraction and selection of object affordances. Recent connectional data suggested that intermediate area 12r and rostral area 46vc also take part in these circuits (Borra et al. 2011; Gerbella et al. 2012). These 2 VLPF areas possibly contribute to exploiting memory-related information about object properties or identity and information on behavioral goals or behavioral guiding rules for selecting and organizing hand and, to some extent, also mouth actions.

Information on action goals and object affordances could be used in the SC for representing the behavioral goals of object-oriented actions and for the eye–hand coordination necessary for transporting the hand toward the object. Indeed, it has been proposed that the SC combines sensorimotor and cognitive information for selecting and localizing behavioral goals, independently from the movement (eye, head, and arm) used to achieve it (see, e.g., Krauzlis et al. 2004). In line with this proposal, it has been shown in macaques that, when competing stimuli are presented, the inactivation of the SC causes a strong bias, not explained by motor impairment, in the selection of targets for smooth pursuit, saccadic, or reaching movements placed in the ipsilateral visual field (Lovejoy and Krauzlis 2010; Nummela and Krauzlis 2010; Song et al. 2011). Furthermore, the SC appears to play a critical role in eye–hand coordination for object-oriented actions (e.g., Reyes-Puerta et al. 2011). Indeed, in the SC intermediate layers, arm-related neuron activity modulated by gaze orientation could reflect the representation of the spatial goal for arm movements in a gaze-centered reference frame (Stuphorn et al. 2000). Furthermore, in the rostral SC, most fixation neurons increase their activity during reaching and could be involved in anchoring the gaze to the hand target (Reyes-Puerta et al. 2010). The denser projections observed in the present study in the lateral SC, where the lower visual field and downward gaze shifts are represented (see, e.g., Wurtz 2009), could reflect the more frequent localization of the targets of hand actions and of hand trajectories in this part of the visual field.

In the context of this hypothesis, it is interesting to note the following. First, the inactivation of F5 or PFG produces extinction within the contralateral peripersonal space (Schieber 2000; Fogassi et al. 2001, Bonini et al. 2008), which could be accounted for by a deficit in broadcasting to the SC information on targets and goals for hand actions. Secondly, there is evidence for differences in the oculomotor behavior when objects are examined for perception or for hand-object interactions (Melcher and Kowler 1999; Johansson et al. 2001; Bowman et al. 2009). Specifically, during object grasping and manipulation, proactive eye movements, guided by motor representations of manual actions, orient the gaze to the parts of the object to which the fingertips are directed, likely reflecting affordances extraction and selection. Finally, as the parietofrontal circuits of the hand action network are also involved in action and intention understanding (mirror system; Rizzolatti and Craighero 2004), it is possible that corticotectal projections from this network carry information related to goals of other's actions, which could be used to proactively direct the gaze to the target of the agent's action (Flanagan and Johansson 2003).

Funding

The work was supported by Ministero dell'Istruzione, dell'Università e della Ricerca (grant no: PRIN 2008, 2008J7YFNR_002) and European Commission Grant Cogsystems FP7-250013.

Notes

Conflict of Interest: None declared.

References

Asanuma
C
Andersen
RA
Cowan
WM
The thalamic relations of the caudal inferior parietal lobule and the lateral prefrontal cortex in monkeys: divergent cortical projections from cell clusters in the medial pulvinar nucleus
J Comp Neurol
 , 
1985
, vol. 
241
 (pg. 
357
-
381
)
Baker
SN
The primate reticulospinal tract, hand function and functional recovery
J Physiol
 , 
2011
, vol. 
589
 (pg. 
5603
-
5612
)
Belmalih
A
Borra
E
Contini
M
Gerbella
M
Rozzi
S
Luppino
G
Multimodal architectonic subdivision of the rostral part (area F5) of the macaque ventral premotor cortex
J Comp Neurol
 , 
2009
, vol. 
512
 (pg. 
183
-
217
)
Bonini
L
Rozzi
S
Simone
L
Ugolotti
F
Bastoni
E
Macellini
S
Ferrari
PF
Fogassi
L
Reversible inactivation of inferior parietal lobule but not of ventral premotor cortex impairs organization of goal directed actions
2008
FENS Forum 2008
Geneva
 
abstract number 022.2
Borra
E
Belmalih
A
Calzavara
R
Gerbella
M
Murata
A
Rozzi
S
Luppino
G
Cortical connections of the macaque anterior intraparietal (AIP) area
Cereb Cortex
 , 
2008
, vol. 
18
 (pg. 
1094
-
1111
)
Borra
E
Belmalih
A
Gerbella
M
Rozzi
S
Luppino
G
Projections of the hand field of the macaque ventral premotor area F5 to the brainstem and spinal cord
J Comp Neurol
 , 
2010
, vol. 
518
 (pg. 
2570
-
2591
)
Borra
E
Gerbella
M
Rozzi
S
Luppino
G
Anatomical evidence for the involvement of the macaque ventrolateral prefrontal area 12r in controlling goal-directed actions
J Neurosci
 , 
2011
, vol. 
31
 (pg. 
12351
-
12363
)
Bowman
MC
Johansson
RS
Flanagan
JR
Eye-hand coordination in a sequential target contact task
Exp Brain Res
 , 
2009
, vol. 
195
 (pg. 
273
-
283
)
Dancause
N
Barbay
S
Frost
SB
Plautz
EJ
Chen
D
Zoubina
EV
Stowe
AM
Nudo
RJ
Extensive cortical rewiring after brain injury
J Neurosci
 , 
2005
, vol. 
25
 (pg. 
10167
-
10179
)
Davare
M
Kraskov
A
Rothwell
JC
Lemon
RN
Interactions between areas of the cortical grasping network
Curr Opin Neurobiol
 , 
2011
, vol. 
21
 (pg. 
565
-
570
)
Flanagan
JR
Johansson
RS
Action plans used in action observation
Nature
 , 
2003
, vol. 
424
 (pg. 
769
-
771
)
Fogassi
L
Gallese
V
Buccino
G
Craighero
L
Fadiga
L
Rizzolatti
G
Cortical mechanism for the visual guidance of hand grasping movements in the monkey: a reversible inactivation study
Brain
 , 
2001
, vol. 
124
 (pg. 
571
-
586
)
Fries
W
Cortical projections to the superior colliculus in the macaque monkey: a retrograde study using horseradish peroxidase
J Comp Neurol
 , 
1984
, vol. 
230
 (pg. 
55
-
76
)
Fries
W
Inputs from motor and premotor cortex to the superior colliculus of the macaque monkey
Behav Brain Res
 , 
1985
, vol. 
18
 (pg. 
95
-
105
)
Gandhi
NJ
Katnani
HA
Motor functions of the superior colliculus
Annu Rev Neurosci
 , 
2011
, vol. 
34
 (pg. 
205
-
231
)
Gerbella
M
Belmalih
A
Borra
E
Rozzi
S
Luppino
G
Cortical connections of the anterior (F5a) subdivision of the macaque ventral premotor area F5
Brain Struct Funct
 , 
2011
, vol. 
216
 (pg. 
43
-
65
)
Gerbella
M
Belmalih
A
Borra
E
Rozzi
S
Luppino
G
Cortical connections of the macaque caudal ventrolateral prefrontal areas 45A and 45B
Cereb Cortex
 , 
2010
, vol. 
20
 (pg. 
141
-
168
)
Gerbella
M
Belmalih
A
Borra
E
Rozzi
S
Luppino
G
Multimodal architectonic subdivision of the caudal ventrolateral prefrontal cortex of the macaque monkey
Brain Struct Funct
 , 
2007
, vol. 
212
 (pg. 
269
-
301
)
Gerbella
M
Borra
E
Tonelli
S
Rozzi
S
Luppino
G
Connectional heterogeneity of the ventral part of the macaque area. 46
Cereb Cortex
 , 
2012
, vol. 
23
 (pg. 
967
-
987
)
Grafton
ST
The cognitive neuroscience of prehension: recent developments
Exp Brain Res
 , 
2010
, vol. 
204
 (pg. 
475
-
491
)
Gregoriou
GG
Borra
E
Matelli
M
Luppino
G
Architectonic organization of the inferior parietal convexity of the macaque monkey
J Comp Neurol
 , 
2006
, vol. 
496
 (pg. 
422
-
451
)
Hartmann-von Monakow
K
Akert
K
Künzle
H
Projections of precentral and premotor cortex to the red nucleus and other midbrain areas in Macaca fascicularis
Exp Brain Res
 , 
1979
, vol. 
34
 (pg. 
91
-
105
)
Huerta
MF
Kaas
JH
Supplementary eye field as defined by intracortical microstimulation: connections in macaques
J Comp Neurol
 , 
1990
, vol. 
293
 (pg. 
299
-
330
)
Huerta
MF
Krubitzer
LA
Kaas
JH
Frontal eye field as defined by intracortical microstimulation in squirrel monkeys, owl monkeys, and macaque monkeys: I. Subcortical connections
J Comp Neurol
 , 
1986
, vol. 
253
 (pg. 
415
-
439
)
Jeannerod
M
Arbib
MA
Rizzolatti
G
Sakata
H
Grasping objects: the cortical mechanisms of visuomotor transformation
Trends Neurosci
 , 
1995
, vol. 
18
 (pg. 
314
-
320
)
Johansson
RS
Westling
G
Bäckström
A
Flanagan
JR
Eye-hand coordination in object manipulation
J Neurosci
 , 
2001
, vol. 
21
 (pg. 
6917
-
6932
)
Krauzlis
RJ
Carello
CD
Going for the goal
Nat Neurosci
 , 
2003
, vol. 
6
 (pg. 
332
-
333
)
Krauzlis
RJ
Liston
D
Carello
CD
Target selection and the superior colliculus: goals, choices and hypotheses
Vision Res
 , 
2004
, vol. 
44
 (pg. 
1445
-
1451
)
Leichnetz
GR
Connections of the medial posterior parietal cortex (area 7m) in the monkey
Anat Rec
 , 
2001
, vol. 
263
 (pg. 
215
-
236
)
Leichnetz
GR
Spencer
RF
Hardy
SG
Astruc
J
The prefrontal corticotectal projection in the monkey: an anterograde and retrograde horseradish peroxidase study
Neuroscience
 , 
1981
, vol. 
6
 (pg. 
1023
-
1041
)
Lock
TM
Baizer
JS
Bender
DB
Distribution of corticotectal cells in macaque
Exp Brain Res
 , 
2003
, vol. 
151
 (pg. 
455
-
470
)
Lovejoy
LP
Krauzlis
RJ
Inactivation of primate superior colliculus impairs covert selection of signals for perceptual judgments
Nat Neurosci
 , 
2010
, vol. 
13
 (pg. 
261
-
266
)
Lui
F
Gregory
KM
Blanks
RH
Giolli
RA
Projections from visual areas of the cerebral cortex to pretectal nuclear complex, terminal accessory optic nuclei, and superior colliculus in macaque monkey
J Comp Neurol
 , 
1995
, vol. 
363
 (pg. 
439
-
460
)
Lynch
JC
Graybiel
AM
Lobeck
LJ
The differential projection of two cytoarchitectonic subregions of the inferior parietal lobule of macaque upon the deep layers of the superior colliculus
J Comp Neurol
 , 
1985
, vol. 
235
 (pg. 
241
-
254
)
Lynch
JC
Tian
JR
Cortico-cortical networks and cortico-subcortical loops for the higher control of eye movements
Prog Brain Res
 , 
2006
, vol. 
151
 (pg. 
461
-
501
)
May
PJ
The mammalian superior colliculus: laminar structure and connections
Prog Brain Res
 , 
2006
, vol. 
151
 (pg. 
321
-
378
)
Melcher
D
Kowler
E
Shapes, surfaces and saccades
Vision Res
 , 
1999
, vol. 
39
 (pg. 
2929
-
2946
)
Mesulam
M-M
Mesulam
M-M
Principles of horseradish peroxidase neurohistochemistry and their applications for tracing neural pathways
Tracing neural connections with horseradish peroxidase
 , 
1982
Chichester, UK
Wiley
(pg. 
1
-
152
)
Murata
A
Gallese
V
Luppino
G
Kaseda
M
Sakata
H
Selectivity for the shape, size, and orientation of objects for grasping in neurons of monkey parietal area AIP
J Neurophysiol
 , 
2000
, vol. 
83
 (pg. 
2580
-
2601
)
Nagy
A
Kruse
W
Rottmann
S
Dannenberg
S
Hoffmann
KP
Somatosensory-motor neuronal activity in the superior colliculus of the primate
Neuron
 , 
2006
, vol. 
52
 (pg. 
525
-
534
)
Nummela
SU
Krauzlis
RJ
Inactivation of primate superior colliculus biases target choice for smooth pursuit, saccades, and button press responses
J Neurophysiol
 , 
2010
, vol. 
104
 (pg. 
1538
-
1548
)
Paxinos
G
Huang
X
Toga
AW
The rhesus monkey brain in stereotaxic coordinates
 , 
2000
San Diego
Academic Press
Reyes-Puerta
V
Philipp
R
Lindner
W
Hoffmann
KP
Neuronal activity in the superior colliculus related to saccade initiation during coordinated gaze-reach movements
Eur J Neurosci
 , 
2011
, vol. 
34
 (pg. 
1966
-
1982
)
Reyes-Puerta
V
Philipp
R
Lindner
W
Hoffmann
KP
Role of the rostral superior colliculus in gaze anchoring during reach movements
J Neurophysiol
 , 
2010
, vol. 
103
 (pg. 
3153
-
3166
)
Rizzolatti
G
Craighero
L
The mirror-neuron system
Annu Rev Neurosci
 , 
2004
, vol. 
27
 (pg. 
169
-
192
)
Rizzolatti
G
Luppino
G
The cortical motor system
Neuron
 , 
2001
, vol. 
31
 (pg. 
889
-
901
)
Rozzi
S
Calzavara
R
Belmalih
A
Borra
E
Gregoriou
GG
Matelli
M
Luppino
G
Cortical connections of the inferior parietal cortical convexity of the macaque monkey
Cereb Cortex
 , 
2006
, vol. 
16
 (pg. 
1389
-
1417
)
Rozzi
S
Ferrari
PF
Bonini
L
Rizzolatti
G
Fogassi
L
Functional organization of inferior parietal lobule convexity in the macaque monkey: electrophysiological characterization of motor, sensory and mirror responses and their correlation with cytoarchitectonic areas
Eur J Neurosci
 , 
2008
, vol. 
28
 (pg. 
1569
-
1588
)
Schieber
MH
Inactivation of the ventral premotor cortex biases the laterality of motoric choices
Exp Brain Res
 , 
2000
, vol. 
130
 (pg. 
497
-
507
)
Shook
BL
Schlag-Rey
M
Schlag
J
Primate supplementary eye field: I. Comparative aspects of mesencephalic and pontine connections
J Comp Neurol
 , 
1990
, vol. 
301
 (pg. 
618
-
642
)
Song
JH
Rafal
RD
McPeek
RM
Deficits in reach target selection during inactivation of the midbrain superior colliculus
Proc Natl Acad Sci USA
 , 
2011
, vol. 
108
 (pg. 
1433
-
1440
)
Stanton
GB
Goldberg
ME
Bruce
CJ
Frontal eye field efferents in the macaque monkey: II. Topography of terminal fields in midbrain and pons
J Comp Neurol
 , 
1988
, vol. 
271
 (pg. 
493
-
506
)
Stein
BE
Stanford
TR
Rowland
BA
The neural basis of multisensory integration in the midbrain: its organization and maturation
Hear Res
 , 
2009
, vol. 
258
 (pg. 
4
-
15
)
Stuphorn
V
Bauswein
E
Hoffmann
KP
Neurons in the primate superior colliculus coding for arm movements in gaze-related coordinates
J Neurophysiol
 , 
2000
, vol. 
83
 (pg. 
1283
-
1299
)
Theys
T
Pani
P
van Loon
J
Goffin
J
Janssen
P
Selectivity for three-dimensional shape and grasping-related activity in the macaque ventral premotor cortex
J Neurosci
 , 
2012
, vol. 
32
 (pg. 
12038
-
12050
)
Tokuno
H
Takada
M
Nambu
A
Inase
M
Direct projections from the orofacial region of the primary motor cortex to the superior colliculus in the macaque monkey
Brain Res
 , 
1995
, vol. 
703
 (pg. 
217
-
222
)
Werner
W
Neurons in the primate superior colliculus are active before and during arm movements to visual targets
Eur J Neurosci
 , 
1993
, vol. 
5
 (pg. 
335
-
340
)
Werner
W
Dannenberg
S
Hoffmann
KP
Arm-movement-related neurons in the primate superior colliculus and underlying reticular formation: comparison of neuronal activity with EMGs of muscles of the shoulder, arm and trunk during reaching
Exp Brain Res
 , 
1997
, vol. 
115
 (pg. 
191
-
205
)
Werner
W
Hoffmann
KP
Dannenberg
S
Anatomical distribution of arm-movement-related neurons in the primate superior colliculus and underlying reticular formation in comparison with visual and saccadic cells
Exp Brain Res
 , 
1997
, vol. 
115
 (pg. 
206
-
216
)
Wurtz
RH
Squire
LR
Superior colliculus
Encyclopedia of neuroscience
 , 
2009
, vol. 
Vol. 9
 
Oxford
Academic Press
(pg. 
627
-
634
)