topographic organization of medial pulvinar connections with the prefrontal cortex in the rhesus...

Topographic Organization of MedialPulvinar Connections With the Prefrontal

Cortex in the Rhesus Monkey

L.M. ROMANSKI,* M. GIGUERE, J.F. BATES, AND P.S. GOLDMAN-RAKIC

Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510

ABSTRACTThe medial nucleus of the pulvinar complex (PM) has widespread connections with

association cortex. We investigated the connections of the PMwith the prefrontal cortex (PFC)in macaque monkeys, with tracers placed into the PM and the PFC, respectively.

Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) placed into thePM resulted in widespread anterograde terminal labeling in layers III and IV, and retrogradecellular labeling in layer VI of the PFC. Injections of tracers centered on the central/lateral PMresulted in labeling of dorsolateral and orbital regions, whereas injections centered on caudal,medial PM resulted in labeling of dorsomedial and medial PFC. Since injections of the PMincluded neighboring thalamic nuclei, retrograde tracers were placed into distinct cytoarchi-tectonic regions of the PFC and retrogradely labeled cells in the posterior thalamus werecharted. The results of this series of tracer injections confirmed the results of the thalamicinjections. Injections placed into areas 8a, 12 (lateral and orbital), 45, 46 and 11, retrogradelylabeled neurons in the central/lateral PM, while tracer injections placed into areas 9, 12(lateral), 10 and 24, labeled medial PM. The connections of the PM with temporal, parietal,insular, and cingulate cortices were also examined. The central/lateral PM has reciprocalconnections with posterior parietal areas 7a, 7ip, and 7b, insular cortex, caudal superiortemporal sulcus (STS), caudal superior temporal gyrus (STG), and posterior cingulate,whereas medial PM is connected mainly with the anterior STS and STG, as well as thecingulate cortex and the amygdala. These connectional studies suggest that the central/lateral and medial PM have divergent connections which may be the substrate for distinctfunctional circuits. J. Comp. Neurol. 379:313–332, 1997. r 1997 Wiley-Liss, Inc.

Indexing terms: thalamocortical; frontal lobe; association cortex; primate; thalamus

The medial pulvinar (PM), a subdivision of the pulvinarcomplex, is a thalamic association nucleus that has wide-spread connections with the cerebral cortex (Mauguiereand Baleydier, 1978; Mufson and Mesulam, 1984; Asa-numa et al., 1985; Baleydier and Mauguiere, 1985, 1987).The pulvinar complex expanded during evolution to reachits greatest dimensions in the human brain and is one ofthe few thalamic nuclei present in primates that is notidentifiable in rodents and other small mammals (Rakic,1974; Browne and Simmons, 1984). In man, it is themedial subdivision of the pulvinar complex which appearsto have undergone the greatest expansion (Browne andSimmons, 1984). While anatomical and physiological stud-ies have designated a role in visual processing for thelateral and inferior subdivisions of the pulvinar (Acuna etal., 1983, 1990; Blum, 1985; Petersen et al., 1987; Cudeiroet al., 1989; Robinson, et al., 1991; Robinson and Petersen,1992; Cusick et al., 1993; Gutierrez et al., 1995), thefunction of themedial subdivision, PM, is less clear. Recent

PET and MRI studies have postulated a role for the PM in‘‘directed attention’’ (Anderson, 1987; LaBerge and Buchs-baum, 1990; Mesulam, 1990; Morecraft et al., 1993). It isthis association of PM with executive functions such asattention, that prompted us to examine the connectionsbetween the PM and the prefrontal cortex (PFC), theregionmost notably involved in executive function, such asthe process of working memory (Goldman-Rakic, 1987,1990; Fuster, 1989, 1993).Physiological and anatomical evidence suggests that the

PM is a sensory-motor structure that is intimately associ-

Contract grant sponsor: National Institutes of Mental Health; ContractGrant number: MH-38546; Contract grant sponsor: James S. McDonnellFoundation; Contract grant number: JSMF 93-28.*Correspondence to: Dr. LizabethM. Romanski, Yale University School of

Medicine, Section of Neurobiology, 333 Cedar St., New Haven, CT 06510.E-mail: [email protected] 10 June 1996; Revised 7October 1996;Accepted 15October 1996

THE JOURNAL OF COMPARATIVE NEUROLOGY 379:313–332 (1997)

r 1997 WILEY-LISS, INC.

ated with visual and visuo-spatial cortical associationregions. Physiological studies have demonstrated thatneurons in the PM have visual, auditory, somatosensory,and oculomotor responses (Acuna et al., 1983, 1990;Yirmiyaand Hocherman, 1987; Cudeiro et al., 1989; Robinson etal., 1991; Benevento and Port, 1995). As to its connections,the PM receives its greatest subcortical input from thedeep (nonretinal) layers of the superior colliculus, withminor input from the superficial layers of the superiorcolliculus and brainstem nuclei which include the nucleusof the optic tract and the lateral terminal nucleus (Ben-evento and Fallon, 1975; Harting et al., 1980; Beneventoand Standage, 1983). The cortical targets of the PMinclude the inferior parietal lobe, the superior temporalgyrus, the cortex of the superior temporal sulcus, as well asthe temporal pole (Baleydier and Mauguiere, 1977; Mau-guiere and Baleydier, 1978;Asanuma et al., 1985;Markow-itsch et al., 1985; Moran et al., 1987; Yeterian and Pandya,1989; Schmahmann and Pandya, 1990; Baleydier andMorel, 1992; Hardy and Lynch, 1992; Webster et al., 1993).These thalamocortical projections imply a role for the PMas a visuospatial, somatosensory, or auditory relay (Acunaet al., 1983, 1990; Cudeiro et al., 1989; Robinson et al.,1991; Robinson and Peterson, 1992; Benevento and Port,1995).The PM also has well-documented connections with

several regions of the forebrain that have been linked withmnemonic and/or limbic processing, including the prefron-tal, parahippocampal, cingulate, and insular cortices, aswell as the amygdala (Jones and Burton, 1976a; Mufsonand Mesulam, 1984; Asanuma et al., 1985; Baleydier andMauguiere, 1985). It is these connections with limbicstructures which clouds the classification of PM as solely asensory or sensorimotor relay. Interestingly, some of theseso-called ‘‘limbic’’ cortical regions have been implicated inoculomotor, visuospatial, or somatosensory processes. Forexample, anatomical (Dum and Strick, 1992; Vogt et al.,1992; Bates and Goldman-Rakic, 1993) and physiological(Carlson and Goldman-Rakic, 1993; Olson et al., 1993;Paus et al., 1993) analyses have related the posteriorcingulate cortex to oculomotor, visual, spatial, and motorprocessing. Likewise, neuronal responses to somatosen-sory and vestibular stimuli and connections to somaticrelays in the thalamus, has been demonstrated for theinsular cortex (Robinson and Burton, 1980; Friedman andMurray, 1986; Akbarian et al., 1992) Finally, the largeexpanse of dorsolateral prefrontal cortex, which has knownconnections with the PM, has been physiologically dis-

sected into discrete cortical modules, each of which hasbeen shown to play a critical role in distinct workingmemory domains (Goldman-Rakic, 1990; Funahashi et al.,1993a,b;Wilson et al., 1993). Thus, functional characteriza-tion has revealed cortical organizations which affect ourview of pulvinarcortical connections and the functions ofthese connections in cognitive networks. Furthermore,PET and MRI studies have associated the PM, togetherwith some of its cortical targets, including the prefrontalcortex, with the neuronal circuit of directed attention(Anderson, 1987; LaBerge and Buchsbaum, 1990; Mesu-lam 1990). Hence, a reexamination of PM’s connectionswith cortical areas involved in mnemonic and attentionalprocesses is warranted.There has been some analysis of PM connections with

the PFC (Trojanowski and Jacobson, 1974, 1976; Bos andBenevento, 1975; Kievit and Kuypers, 1977; Kunzle andAkert, 1977; Barbas and Mesulam, 1981; Asanuma et al.,1985; Goldman-Rakic and Porrino, 1985). Many of thesestudies involved the placement of large injections of retro-grade tracers into the cortex. While these studies de-scribed the widespread connectivity of the PM, noneaddressed the selectivity of PM-PFC connections, and/ordeterminedwhether projections to the PFC are topographi-cally constrained within PM.The present study has established the general topo-

graphic organization of the projections of the PM to theprefrontal cortex and to several primary targets outside ofthe prefrontal cortex, and describes the laminar pattern ofthe corticopulvinar cells and thalamocortical terminals.The results of the present study indicate that the central/lateral PM is connected with widespread regions of thefrontal lobes and most impressively with the inferiorconvexity, arcuate, and ventral principal sulcus regions, aswell as temporal, parietal, insular, and cingulate regions.Caudal/medial PM is connected with dorsomedial andorbital prefrontal regions. Outside of the PFC, caudal/medial PM has connections mainly with rostral temporalcortex, cingulate cortex and the amygdala.

MATERIALS AND METHODS

Overview

Anterograde and retrograde tracers were placed in boththe thalamus and the cortex to characterize the connec-tions of themedial pulvinar nucleus (PM) with the prefron-tal cortex and with several other major targets. In the first

Abbreviations

AMYG amygdaloid complexASd arcuate sulcus, dorsal branchASv arcuate sulcus, ventral branchbsc brachium of the superior colliculusCd caudate nucleusCgS cingulate sulcusCS central sulcusHb habenulaINS insular cortexIPS intraparietal sulcusLGN lateral geniculate nucleusLi limitans nucleusLOS lateral orbital sulcusLP lateral posterior nucleusLS lateral or sylvian fissureMD mediodorsal nucleus

MG medial geniculate bodyMOS medial orbital sulcusOFO orbito-frontal operculumPFC prefrontal cortexPI inferior nucleus of the pulvinar complexPL lateral nucleus of the pulvinar complexPM medial nucleus of the pulvinar complexPo posterior nucleus of the thalamusPO nucleus oralis of the pulvinar complexPrCo precentral opercular areaPS principal sulcusSF sylvian fissureSG suprageniculate nucleusSTG superior temporal gyrusSTS superior temporal sulcus

314 L.M. ROMANSKI ET AL.

series of experiments, the PM was injected with eitherwheat germ agglutinin-horseradish peroxidase (WGA-HRP) or tritiated amino acids (3H-AA) and the resultingtransport to the prefrontal and other cortices was ana-lyzed. To verify and extend the findings of these experi-ments we utilized a second series of cases in whichWGA-HRP or fluorescent retrograde tracers had beenplaced into discrete prefrontal cortical regions and theretrograde cell labeling in PM was charted to determinethe topographic nature of PM-prefrontal connections. Somecorticocortical connections from these same cases havebeen reported previously (Bates andGoldman-Rakic, 1993).

Subjects and surgical procedures

Fifteen rhesus monkeys (macaca mulatta) weighing 2.5to 7.0 kg were used in this study. All surgical procedurescomplied with policies and procedures proscribed in theGuide for the Care and Use of Laboratory Animals, byNIH. Sterile surgery was conducted by using sodiumpentobarbital (40 mg/kg), as an anesthetic and ketamine(10mg/kg) as a preoperative agent. Heart rate and respira-tion were monitored continuously. The animal was placedin a Kopf stereotaxic apparatus, an incision was made inthe scalp and the skull was trephined to remove the boneoverlying the target region(s). An incision was made in thedura and a sterile Hamilton syringe was lowered to thetarget region. For cortical injections, several small injec-tions of either WGA-HRP or fluorescent dyes were madewhile a single small injection was used for tracer injectionsinto the PM.After the injections, the syringe was removed,the dura was sutured, and the incision was closed inlayers. Upon recovery from anesthesia the animal wasreturned to its home cage and closely monitored.

Stereotaxic localization of thalamus

In cases where WGA-HRP (2.5%) or 3H-AA (equal mix-ture of 3H-proline and leucine, specific activity5 50 µCi/µl)were injected directly into the medial nucleus of thepulvinar (PM), X-ray ventriculography was used to guidethe placement of the injection cannulae. The details of thismethod are given in a previous paper (Giguere and Gold-man-Rakic, 1988), and employ the sagittal atlas of Ilinskyet al. (1978). The coordinates for the thalamic injectionswere within the following range: 11 to 13 mm posterior tothe anterior commissure; 5 to 6 mm lateral to the midline;1.5 to 2.5 mm dorsal to the AC-PC line. Monkeys receivedan injection of either WGA-HRP (n 5 5; total volume 5 0.2µl per case) or 3H-AA (n5 2; total volume5 0.4 µl per case)in PM. Two of the PM injection sites intruded upon thefornix and a third extended too far rostrally and were,therefore, not used in the present study.

Prefrontal cortex injections

Regions of the PFC were injected with either WGA-HRP(1.25%) or fluorescent dyes (Fast Blue, 10% or DiamidinoYellow, 2%). WGA-HRP (0.2 µl) and the fluorescent tracers(total volume 1.0 µl) were pressure-injected via a Hamiltonsyringe. The cortical injections were circumscribed withina single cytoarchitectonic subdivision of the prefrontalcortex, which were identified by surface landmarks, andincluded Walker’s (1940) areas 8a, 9, 10, 11, 12, 13, 24, 45,and 46. Several injections were made into areas 12 and 46which have been functionally defined in previous studies(Wilson et al., 1993; Funahashi et al., 1990, 1993a,b).

Perfusion and histochemistry

WGA-HRP or 3H-AA. Approximately 48 hours afterinjection of WGA-HRP, the animal was given an overdoseof sodium pentobarbital and perfused with saline and thena mixture of 1% paraformaldehyde and 1.25% glutaralde-hyde. The brain was removed, and cryoprotected in su-crose before sectioning. The brain was sectioned coronallyat 40 µm and every tenth section was processed, by usingthe TMBmethod (Mesulam, 1978). Adjacent sections werecounterstained with cresyl violet or thionin. In casesinvolving 3H-AA injections, after perfusion, sections wereprocessed for autoradiography (see Giguere and Goldman-Rakic, 1988) and then were counterstained with thionin.Fluorescent tracers. When fluorescent tracers were

placed into regions of the prefrontal cortex, the animalswere perfused 12–14 days post-surgery with 0.9% saline,followed by 4% paraformaldehyde. The brain was re-moved, blocked in the coronal plane, and incubated for24–48 hours in an increasing gradient of sucrose solutions(10–30%). The blocks were sectioned on the cryostat at 40µm, mounted immediately onto gelatin-subbed slides, andstored refrigerated at 4°C. An adjacent series was counter-stained with cresyl violet.

Data analysis

For WGA-HRP or 3H-AA injections placed into the PM,coronal sections through the prefrontal cortex were exam-ined for labeled cells or terminals under bright and darkfield illumination. Injection sites in the thalamus and theresultant labeling in the prefrontal cortex were recon-structed by using a Leitz Orthoplan. For each thalamicinjection case, anterograde terminals and retrogradelylabeled cells from representative sections from the mostrostral aspect of the frontal pole up to, and including, thearcuate cortex were drawn. Each injection into the PM isshown with the corresponding prefrontal cortical coronalsections (Figs. 2, 4, 5). Representative sections from corti-cal association regions outside of the PFC which werelabeled as a result of the thalamic injections, including thetemporal, parietal, and insular cortices, were plotted byusing the Neurolucida digital plotting system with a LeitzOrthoplan (Fig. 8). The density of terminal labeling (sparseor heavy) was evaluated by eye and conveyed in thecameral lucida drawings as sparse (light grey stippling) orheavy (dark grey stippling).For WGA-HRP or fluorescent injections of the prefrontal

cortex, coronal sections through the thalamus were ana-lyzed. Only the retrogradely labeled cells in the pulvinar orin the mediodorsal nucleus (MD) were plotted. Althoughthe focus of this study is the medial pulvinar we felt itwould complement and clarify cortical connections byplotting retrogradely labeled cells in both the MD and thepulvinar. Coronal sections through the pulvinar, 400 µmapart, were drawn by hand by using a camera lucidaattachment or were constructed using the Neurolucidadigital plotting system. In each cortical injection case,sections through the PM are shown along with a schematicdrawing of the corresponding cortical injection site (Figs.6, 7).

Photographic presentation

Coronal sections were photographed with a Zeiss Ax-iophot by using bright or dark field optics. Photomicro-graphs were prepared by scanning photographic negatives

MEDIAL PULVINAR CONNECTIONS WITH PREFRONTAL CORTEX 315

into Adobe Photoshop where the image was cropped,enlarged, and oriented on the page. Contrast was in-creased in the entire picture to mimic the effect of using ahigh contrast photographic paper. Scanned images wereimported into Adobe Illustrator where they could be as-sembled as a half or full page plate and labeled appropri-ately with letters and numbers. Grey-scale prints weremade on a Tektronics Phaser II.Camera lucida drawings, prepared with the Neurolu-

cida digital plotting system were imported into Canvas3.52 for Windows, labeled appropriately, and printed ingrey-scale on the Tektronics Phaser II. Under no circum-stances were any data altered by using these electronicprocesses.

Cytoarchitecture of PM

Olszewski’s atlas (1952) was used to delimit the subdivi-sions of the pulvinar complex. The pulvinar complex showsconsiderable uniformity throughout its rostrocaudal ex-tent (Fig. 1). Nevertheless, it can be subdivided on thebasis of Nissl stains, the course of fiber tracts, as well asknown connectional topography. The four major subdivi-sions detailed by Olszewski (1952) include the pars oralis(PO), pars inferior (PI), pars lateralis (PL), and the parsmedialis (PM; Fig. 1A). The pars oralis (not shown), ischaracterized mainly by its low cellular density and theabsence of large fiber bundles. It forms the rostral pole ofthe pulvinar and lies adjacent and ventral to the caudalregion of the mediodorsal nucleus. The inferior pulvinar(PI) is the least difficult to delimit because of the majorfiber bundles (external medullary lamina rostrally andbrachium of the superior colliculus caudally) separating itfrom the rest of the pulvinar. The pars lateralis (PL) andpars medialis (PM) are both present at the same rostrocau-dal level and are distinguishable by the large number offiber tracts which course through the PL contrasting withthe higher cell density of PM.Although anatomical criteriahas been used in the present study to delimit the pulvinarcomplex, several investigations of the retinotopic and/orneurochemical organization of PL and PI have revealedthat the classical cytoarchitectonic borders are not, in fact,functional borders of the pulvinar nuclei (Bender, 1981;Ungerleider et al., 1984; Cusick et al., 1993; Gutierrez etal., 1995).

Cytoarchitecture of the prefrontal cortex

In delineating the cytoarchitectonic regions of the dorso-lateral and orbital prefrontal cortex, Walker’s (1940) cyto-architectonic delineation of the prefrontal cortex was usedwith somemodifications according to Preuss andGoldman-Rakic (1991), who have distinguished orbital area 12 (12o)and lateral area 12 (12l) on the inferior convexity. We willalso refer to dorsal and ventral banks of the principalsulcus, areas 46d and 46v, separately. In addition, weemployed Barbas’ description of the medial prefrontal

Fig. 1. Photomicrographs of counterstained, coronal sectionsthrough the macaque pulvinar are shown rostrally (A) to caudally (C).The medial subdivision (PM), which is the focus of the present study isdelimited by a dotted line as are other thalamic nuclei present.Abbreviations: LP, lateral-posterior nucleus; Li, limitans nucleus; MD,mediodorsal nucleus; MG, medial geniculate body; PI, inferior pulvi-nar; PL, lateral pulvinar; PM, medial pulvinar; Po, posterior nucleus;SG, suprageniculate nucleus (SG). The oral pulvinar nucleus is notvisible at these levels. Scale bar 5 800 µm in C.


cortex to partition the prefrontal areas that line themedialwall of the frontal lobes (Barbas, 1992). The areas exam-ined include areas 8, 9, 10, 11, 12l (lateral), 12o (orbital),13, 14, 24, 25, 32, 45, 46d (dorsal bank of the principalsulcus), and 46v (ventral bank of the principal sulcus).

RESULTS

A. Injections of WGA-HRP in the PM:Analysis of connectionswith prefrontal cortex

Injection of WGA-HRP into the PM gave rise to projec-tion patterns that varied depending on the extent of theinjection site within PM. Large injections of the PMresulted in labeling of dorsolateral prefrontal cortex, theorbital cortex, as well as medial prefrontal cortical areas.When smaller PM injections were made, their respectiveprojections revealed a difference between the central/lateral and the medial PM. In cases where WGA-HRP wasplaced into the central and lateral portions of the PM,sparing the medial and caudo-medial portions of the PM,labeling was present in the ventral bank of the principalsulcus, the inferior convexity, arcuate cortex, and orbitalcortex. In contrast, injections which were placed moremedially and caudally in the PM resulted in labeling thatwas restricted to the dorso-medial prefrontal cortex and asmall area of lateral orbital cortex. We will describe indetail the prefrontal labeling due to these PM injectionswith attention to both anterograde and retrograde label-ing.Large PM injections. The WGA-HRP injection of PM

in case 1 (Fig. 2A) was quite large in its medio-lateral androstro-caudal spread, covering most of the PM except forit’s caudal-medial tip. There was some spread to PL, PI,and MD with this injection. In the frontal lobe, patches ofanterograde terminals and rows of retrogradely labeledcells extended anteriorly from the frontal pole, caudally, tothe arcuate sulcus. Anterograde terminals were mostconspicuous in the inferior convexity (area 12l), the arcu-ate sulcus (areas 8a, 45), and the principal sulcus (area 46)(Figs. 2B–I, 3). Within the principal sulcus, the ventralbank (area 46v) contained more dense terminal labelingthan the dorsal bank (Figs. 2B–E, 3). Distinct patches ofanterograde terminals were present on the lateral surfaceof the inferior convexity, extending the length of theinferior convexity (area 12 lateral) to the orbital surface toinclude areas 12o, 11, and 13 (Fig. 2C–G). Dorsomedially,there was a light stippling of terminals in area 9 androstrally in area 10. On the medial wall of the PFC, areas24, 32, and 25 were also lightly labeled. Cortex surround-ing the inferior arcuate sulcus (areas 6, 8a, 45) had densepatches of anterograde terminals while the ventral bank ofthe superior arcuate was sparsely labeled with terminals(Fig. 2G–I). More caudally, area PrCo, in the frontaloperculum, was densely labeled. Retrogradely labeled cellbodies were most concentrated in the ventral bank of theprincipal sulcus, area 46v, and in areas 12l, 12o, 11, and 13(Fig. 3B). They were also present in areas 14, 25, 32, andarea 45.Central PM injections. In case 2, the injection ap-

peared to be concentrated in the central and lateral PMand extended from themost caudal pole to the rostral tip ofthe PM (Fig. 4A). This injection also spread ventrallytowards the suprageniculate nucleus. Rostrally, there wassome involvement of the lateral pulvinar (PL) with this

injection. As in case 1, the inferior convexity (area 12 lat),and the ventral bank of the principal sulcus (area 46v),were heavily labeled with patches of anterograde termi-nals (Fig. 4). A patch of anterogradely labeled terminalswas present near the rostral border of area 10 and 46 (Fig.4B). Orbital areas 11, 12, and 13 had light terminallabeling (Fig. 4C-F). The cortex surrounding both theinferior and the superior arcuate sulcus, areas 8a, 45, and6, also contained anterograde terminals. As in case 1,retrogradely labeled cells were prominent in areas 12lateral, 46v, 45, 8a, and 13. Area 24 (anterior cingulatecortex) had both anterograde terminals and retrogradecells (Fig. 4G). The most rostral segment of the frontal polewas devoid of label, as was the dorsal bank of the principalsulcus (area 46d), the dorsal (area 9), and the medial(areas 32, 14, and 25) prefrontal cortex.Similar findings were observed in another case (011786)

with a central-lateral PM injection of H3-AA (not shown).This laterally placed injection was smaller and slightlydorsal to that in Figure 4A and there was some spread tothe adjacent lateral pulvinar. Cortical labeling was dens-est in the ventral bank of the principal sulcus and theinferior convexity (lateral area 12), as in the previous case.In addition, there was terminal labeling in the dorsal andventral banks of the inferior arcuate sulcus (areas 6, 45, 8),and in orbital area 12.Medial PM injections. The injection of WGA-HRP in

case 3 filled the caudal half of the medial part of the PM(Fig. 5A). The injection site intruded on caudal, medialregions of MD. This injection resulted in selective labelingof the medial surface of the frontal lobe. Anterogradeterminal labeling was present on the medial wall of theprefrontal cortex in areas 24, 25, and 32 as well as inorbital area 14 (Fig. 5C–G). There was also some antero-grade labeling rostrally in the frontal pole (area 10) anddorsally in area 9 (Fig. 5B–E). The principal sulcus and thelateral convexity, which were both labeled in central/lateral PM injections (Figs. 3, 4), were not labeled. How-ever, orbital area 12 was very lightly labeled with termi-nals and OFO also received some sparse terminal labeling(Fig. 5E–F). Retrogradely labeled cells could only be foundin areas 9, 14, 25, and 32 (Fig. 5E–G).

B. Injections of retrograde tracers in theprefrontal cortex: Analysis of PM-prefrontal

projections

The findings described above suggest a mediolateraltopographic arrangement of pulvinarcortical projections.Since there was some involvement of MD as well as PL andPI with some of the thalamic injections (see above) weplaced either WGA-HRP or fluorescent retrograde tracersinto cytoarchitectonically distinct regions of the prefrontalcortex and charted the retrogradely labeled cells in the PMand surrounding thalamic nuclei (Figs. 6, 7). By using boththe thalamic and cortical injection connectional informa-tion we could determine more definitively whether theprefrontal labeling seen in the thalamic injection experi-ments was due solely to the PM or to involvement of theMD and other adjacent nuclei. A total of 12 injections weremade into regions of the prefrontal cortex that had beenshown to receive projections from the PM in the experi-ments detailed in section A. Corticocortical projectionsfrom some of these prefrontal injections have been de-scribed previously (Bates andGoldman-Rakic, 1993, 1988).


Fig. 2. A–I: Coronal sections from a large injection of wheat germagglutinin-horseradish peroxidase (WGA-HRP) into the medial pulvi-nar (case 1) which included both the central/lateral and the medialportions of the PM (A, injection site). Labeled cells and terminals aredepicted on coronal sections of the frontal lobe from rostral (B) tocaudal (I). Small black circles depict retrogradely labeled cells andregions of anterogradely labeled terminals are shown as grey patches.

Density of the terminal field is indicated by color; dark grey signifiesdense terminal labeling and lighter grey indicates lighter terminallabeling. Cytoarchitectonic boundaries are labeled by their correspond-ing numbers according to the schemata of Walker (1940) for thedorsolateral and orbital regions, and Barbas (1988) for the medialprefrontal regions. Scale bar 5 800 µm inA.


These cases will be described with respect to the location ofretrogradely labeled cells in the central-lateral vs. caudal-medial regions of the PM.1. Prefrontal injections which labeled central/lateral

PM: Areas 11, 12, 8a, 45, and 46v

Area 12l and 12o. Since injections into the PM de-scribed above, revealed dense projections to area 12 of thePFC, several injections of retrograde tracers were madeinto areas 12 lateral and 12 orbital to decipher theconnections of PM with this region. An injection of WGA-HRP into the ventral portion of the lateral convexity (area12l) labeled both medial and central portions of PM at thecaudal and rostral poles of PM, respectively and is de-scribed below (Fig. 7C). The injection shown in Figure 6A,was restricted to a small portion of area 12 orbital (12o)and resulted in a small cluster of retrogradely labeled cellsin the mediolateral center of PM.Area 11. Injections into area 11, with some minor

spread to area 13 also produced labeling in the center of

PM, with some sparse labeling of the medial PM at caudallevels. In this injection (Fig. 6B), the caudal two-thirds ofthe PM were lightly labeled. Thus it appears that area 11and a portion of 12 orbital have cells of origin in the centralPM while 12 lateral receives projections from both centraland medial PM.Area 46v. In the case where an injection was placed in

the ventral bank of the principal sulcus, area 46v, labeledcells were dispersed across the entire pulvinar complex,including PM, PL, PI, as well as the medial geniculate(MGB) (Fig. 6C). Within the PM, the retrograde cells weredensest in the center of PM but also spread to lateral PMmore rostrally.Area 46v was the only region injected in thePFC which labeled the central/lateral PM from caudal torostral pole and which also labeled PL, PI, and MGB.Area 8a. An injection of area 8a also resulted in

retrogradely labeled cells in PM, PL, PI, and MGB; how-ever, the labeling within PM did not extend to the caudaland rostral poles of PM but was concentrated within thecentral one-third of the PM (Fig. 6D). The retrogradelylabeled cells in this case were arranged in clusters withinthe central portion of PM.Area 45. In contrast to the widespread PM labeling due

to 46v injections, the labeling in the PMwhich resulted from asmall injection of area 45 (Fig. 6E) was quite circumscribedwithin PM. The retrogradely labeled cells were arranged in atight, focal clusterwithin the center of the PM.2. Injections of prefrontal cortex which labeled

medial PM: Areas 9, 10, 12, and 24

Area 9. Injections of area 9 (representative in Fig. 7A)resulted in retrogradely labeled cells in the caudal, medial,and dorsal portion of PM, (i.e., the caudo-medial pole ofPM). Area 9 injections resulted in the most caudal PMlabeling of any PFC injection. The labeled cells werelocated in several, small, focal clusters within PM.MDwasalso labeled with area 9 injections.Area 12l. The injection of the inferior convexity de-

picted in Figure 7B labeled both the central/lateral and themedial aspects of PM. Cells were densest in the medialregion of PM at caudal levels but spread to central regionsof PM rostrally (Fig. 7B).Area 10. WGA-HRP injections into area 10, whether

placed medially (Fig. 7C) or laterally, (not shown), pro-duced a sparse amount of retrograde cell labeling in thePM. Labeled cells were present rostrally in the medialsector of PM and continued anteriorly into theMDnucleus.Area 24. The retrograde labeling of the PM following

the injection of area24wasalso quite sparse (Fig. 7D). The fewretrograde cells that were found in PM were situated in aregion similar to that labeled following area 10 injections, i.e.,rostrally in the medial PM. In both area 10 and area 24 in-jections, theMDwasmuchmore heavily labeled than the PM.To summarize the results from the injections in the PM

in (A) and in the PFC in (B): central/lateral PM projects toareas 8a, 11, 12l, 12o, 13, 45, and 46v while the medial PMmainly projects to areas 9, 12l, and sparsely to areas 10and 24. An injection of the dorsal bank of the principalsulcus, are 46d (not shown) did not result in labeling of thecentral/lateral ormedial PM, but did label theMDnucleus.Moreover, PM injections (in part A) revealed projectionsfrom medial PM to areas 13, 25, and 32 although thesewere not confirmed by further injections into these cortical

Fig. 3. Photomicrographs of anterograde and retrograde labelingin areas 46 and 12 of the prefrontal cortex, as a result of the PMinjection shown in Figure 2E. In A, a low-power photomicrographshows that the lateral aspect of the principal sulcus (PS), the inferiorconvexity and lateral orbital cortex are densely labeled with antero-grade terminals (indicated with arrows). A box is drawn around acluster of retrogradely labeled cells in the ventral bank of the principalsulcus, shown in B at higher power. B, Retrogradely labeled cells inthe ventral bank of the principal sulcus are mostly present in layer VI.Scale bar 5 775 µm inA, 100 µm in B.


Fig. 4. Coronal sections depicting anterograde and retrogradelabeling in the prefrontal cortex after an injection of WGA-HRP intothe central/lateral PM (case 2). The injection site into the PM isdelimited by a black dotted line in A. Labeled cells and terminal fields

are depicted on coronal sections from rostral (B) to caudal (G). As inFigure 2, small black circles depict retrogradely labeled cells andregions of anterogradely labeled terminals are shown as grey patches.Scale bar 5 800 µm inA.


Fig. 5. Coronal sections from rostral (B) to caudal (G), depictinganterograde and retrograde labeling in the prefrontal cortex after aninjection of WGA-HRP into the medial region of the PM (case 3). Theinjection site is delimited by a black dotted line in A. Most of the

anterograde and retrograde labeling was present in the medialprefrontal cortex. Conventions for retrograde cellular and anterogradeterminal labeling as in Figures 2 and 4. Scale bar 5 800 µm inA.


Figure6

regions. The regions which were most densely connectedwith the PM were areas 8a, 12, and 46v. In the 8a and 46vinjections, the labeled cells in the PM were orientedmedio-laterally forming bands (Fig. 7C–E), as has beendescribed for PM-parietal projections (Hardy and Lynch,1992; Asanuma et al., 1985).

C. Connections of PM with otherassociation areas

The injections located in the central/lateral part of PM(case 2, Fig. 4A) revealed extensive projections to corticalassociation areas including the insular cortex, the superiortemporal gyrus and sulcus, posterior parietal cortex, andposterior cingulate cortex (Figs. 8, 9). In contrast, the mostmedial PM injection (case 3, Fig. 5A) resulted in denselabeling of only the the temporal pole, rostral STG andSTS, and portions of the anterior and posterior cingulatecortex (Figs. 8, 9).Regions of common innervation. One of the most

densely labeled regions, as a result of central/lateral PMand medial PM injections, was the dorsal bank of the STS.There was an almost unbroken band of retrogradelylabeled cells throughout the dorsal bank and fundus of theSTS in the central/lateral PM injection (Fig. 8, top, A–E).Anterograde terminal fields were also present along therostro-caudal extent of the sulcus but were most intense inthe caudal half of the dorsal bank of the STS (Fig. 8, top,D–E). Since PL is also known to project to the STS, thedensity of this label may have been partly due to inclusionof PL in the injection site. Injection of the medial PM alsoproduced labeling within the dorsal bank and fundus ofthe STS; however, anterograde labeling predominated andthis labeling was most prominent in the rostral half of theSTS (Figs. 8, bottom, A–C, 9). Another cortical regionwhich received anterograde terminal labeling as a result ofinjections in either medial or central/lateral PM is theposterior cingulate cortex, which was consistently, thoughlightly labeled in all cases. Both medial PM injections (Fig.8, bottom) and central/lateral PM injections (Fig. 8, top)resulted in bands of terminals in the middle layers of theposterior cingulate. Moreover, a dense band of retro-gradely labeled cells were located in layer VI of theposterior cingulate in central/lateral PM injections (Fig. 8,top). The anterior cingulate, area 24, also received lightanterograde and retrograde labeling as a result of WGA-HRP injections in either medial or lateral regions of thePM.Injections of either central/lateral or medial PM pro-

duced anterograde and retrograde labeling of the temporalpole (Figs. 4G and 5G), although medial PM injectionsresulted in denser labeling with anterograde terminallabeling exceeding that of the retrograde cellular labeling

in the temporal pole. In the central/lateral PM injectionsthe retrograde cellular labeling was denser than antero-grade terminal labeling in the temporal pole. This was alsotrue of labeling in the superior temporal gyrus. Medial PMinjections produced dense patches of anterograde termi-nals in the middle laminae of the rostral half of the STG(Figs. 9C, 8, bottom, A–C) but only sparse labeling in thecaudal STG (Fig. 8, bottom, D–E). Conversely, injections ofcentral/lateral PM resulted in light anterograde labeling ofthe rostral STG (Figs. 8, top, A–C, 9A) and heavieranterograde terminals and retrograde cellular labeling incaudal regions (Fig. 8, top, D–E).Topographic distinctions betweenmedial and central/

lateral PM. There were several regions of the brainwhich were labeled following central/lateral PM injectionsbut not after medial PM injections, strengthening thenotion of a true topography within the PM. In central/lateral PM injections both the insular cortex and theposterior parietal cortex (area 7) were densely labeled,while these regions were not labeled after medial PMinjections (Figs. 8, 9). The insular cortex had dense patchesof anterograde terminals and retrograde cells throughoutits rostro-caudal extent following central/lateral PM injec-tions (Figs. 8, top, 9A). The labeling included regions of thegranular and dysgranular insular cortex (Mufson andMesulam, 1984), although granular insular cortex wasmore densely labeled with terminals and the dysgranularportion of the insula was labeled more heavily with cells.Posterior parietal area 7 was also densely labeled follow-ing central/lateral PM injections (Fig. 9D) but was barelylabeled as a result of medial PM injections. Terminal andcellular labeling appeared densest in area 7ip (Cavada andGoldman-Rakic, 1989), and was slightly less dense inareas 7a and 7b (Fig. 8, top, D–E, 9D).The only region (besides those in the prefrontal cortex)

that received a projection from themedial PM that was notlabeled following central/lateral PM injections was theamygdala. The terminal labeling in the amygdala (Fig. 8A,bottom) included the lateral and basal nuclei of thiscomplex, confirming previous reports (Jones and Burton,1976a; Aggleton et al., 1980).

D. Laminar distribution of labeled cellsand terminals

As a result of PM injections, the labeled cells in anycytoarchitectonic subdivision of the PFC were locatedprimarily in layer VI, most prominently in its superficialpart (Fig. 3B). Few cells were observed in layer V. Thelaminar arrangement of terminals in the prefrontal cortexwhich originated from the PM was confined to deep layerIII and layer IV (Fig. 3A–B). This pattern is shown inFigure 3 for areas 46V (ventral bank) and 12l (lateral),which received the majority of the PFC afferents. Fewlabeled terminals were found in layer I.In contrast to the prefrontal cortex, which, as mentioned

above, showed very few labeled cells in layer V, some of theother cortical association areas had a bilaminar distribu-tion of labeled cells located superficially in layer V as wellas in VI. In the insular cortex (Fig. 9A–B), although layerVI contained many more labeled cells, the number of cellslabeled in layer V was quite high, compared to the amountof layer V labeling observed in the PFC.The pattern of retrograde and anterograde labeling in

the temporal lobe was more like that of the PFC; mostlabeled cells were present in layer VI and labeled termi-

Fig. 6. Retrograde cell labeling of central/lateral PM after injec-tions of tracers in areas 12o (orbital), 11, 46v (ventral), 8a, and 45. Incases B–E, WGA-HRP was injected into the cortex, whereas in A, FastBlue was injected into area 12o. In each case (A–E) a lateral or orbitalbrain schemata shows the location of the injection site as a blackenedarea within a cytoarchitectonic region of the macaque brain. Retro-grade cellular labeling, depicted as black dots, in the PM is shown onrepresentative coronal sections through the posterior thalamus fromcaudal (left) to rostral (right) levels. The most robust labeling of thecentral/lateral PMwas achieved with injections of areas 46v and 8a. Ineach case (A–E), numbers or letters next to each thalamic drawingrepresent coronal section numbers through the thalamus.


Figure7

nals were located in layers III and IV. The posteriorcingulate cortex had a different pattern of cell labeling.Similar to the PFC, very few labeled cells were found inlayer V; however, the labeled cells in layer VI in theposterior cingulate filled both the superficial and deepparts of this layer.Interestingly, absolute reciprocity of cells and terminals

was not observed in all cortical areas. For example,although terminal labeling in areas 12 and ventral 46, ofthe prefrontal cortex (Figs. 2–5) was coextensive withretrogradely labeled cells, in the inferior arcuate sulcus,areas 8 and 45, dense terminal labeling was accompaniedby only sparse cellular labeling. In parietal and cingulatecortex the locations of cells and terminals were roughlyequal (Figs. 9D, 8, top, D–E).

DISCUSSION

Until the mid-seventies, the prefrontal cortex (PFC) wasthought to receive its thalamic input exclusively from themediodorsal nucleus. However, with the advent of retro-grade tracing methods, it came to be recognized that otherthalamic nuclei, among them the medial pulvinar nucleus(PM), contribute to the innervation of the PFC. While thePM is certainly not the primary source of thalamic input tothe prefrontal cortex it does provide a small but significantsource of afferents. The earliest evidence of medial pulvi-nar connections with the PFC was reported by Tro-janowski and Jacobson (1974, 1976) and Bos and Ben-evento (1975). Both sets of investigators injected thefrontal eye fields and the orbital cortex with retrogradetracers and found labeled cells in the medial pulvinar.Later studies indicated connections of PM with otherprefrontal areas as well (Kievit and Kuypers, 1977; Gold-man-Rakic and Porrino, 1985; Giguere and Goldman-Rakic, 1988; Barbas et al., 1991). However, the full extentof PM projections is best appreciated by the placement ofanterograde tracers into the PM as was accomplished byBaleydier and Mauguiere (1985) and the present study.Baleydier and Mauguiere (1985) described extensive pro-jections to the paralimbic neocortex (presubiculum, parasu-biculum, parahippocampal, posterior cingulate, rhinal sul-cus, and retrosplenial cortex) but little detailed informationwas provided on the connections of the PM with the PFC.The present anterograde and retrograde studies confirmand extend previous work by revealing evidence of topogra-phy in pulvinarprefrontal circuitry.

PM projections to the prefrontal cortex

Our results suggest that central/lateral and medial PMhave distinctly different projections to the prefrontal cor-tex with the exception of area 12 l which was connectedwith both central and medial portions of the PM (Fig. 7B).In the present study, injections of WGA-HRP into the

central/lateral PM preferentially labeled the principalsulcus region, the inferior convexity, the cortical regionssurrounding the arcuate sulcus, as well as orbital prefron-tal regions. When the injection was displaced caudally andmedially in PM, the labeling shifted to dorsomedial, andsome medial prefrontal regions as well as some portions ofarea 12 lateral. Injections of retrograde tracers into theprefrontal cortex confirmed and clarified this topography.Thus, the central/lateral PM is most densely connectedwith areas 46v, 12l, 8a, 45, and with orbital cortex (areas11, 12o) whereas the medial PM is connected with areas 9,and 12l and sparsely with areas 10 and 24, according to thepresent study.The findings of the present study are consistent with

those of Barbas et al. (1991), who showed via retrogradetracers placed into the prefrontal cortex, that medial andcaudal portions of the PM send afferents to medial PFCarea 32 and 12l and orbital areas 13 and 14, while centralportions of PM project to area 12 orbital, 46 ventral andarea 8a. Other studies have also noted the connection ofthe orbital surface of the frontal lobe with PM (Kievit andKuypers 1977; Morecraft et al., 1992; Cavada et al., 1995).Our findings are also in agreement with Kievit andKuypers (1977) who reported connections between area 10and caudomedial PM and between the dorso-lateral sur-face of the frontal lobe and central/lateral portions of PM.In contrast, the present results and those of Barbas et al.(1991) and Kievit and Kuypers (1977) differ from those ofTrojanowski and Jacobson (1976), who reported that thedorso-lateral PFC was most densely connected with themedial PM, and not the central/lateral PM, as shownpresently. The disparity in the results may be accountedfor by the large injections which spanned several cytoarchi-tectonic regions of the dorsolateral PFC in the study byTrojanowski and Jacobson (1976).Several anatomical studies have focused on the connec-

tion of the PM with the frontal eye fields (FEF) with thesuggestion that the FEF is the primary prefrontal corticaltarget of the PM (Stanton et al., 1988; Barbas and Mesu-lam, 1981; Morecraft et al., 1993). In the present study wehave documented dense connections between the PM andtwo other prefrontal regions, areas 46 and 12, and connec-tions with areas 45 and 9 as well. In previous retrogradetracer studies, tracer deposits which were aimed at theFEF included variable amounts of areas 46 and 12, as wellas the cortex surrounding the arcuate sulcus (the FEF).These tracing studies demonstrated labeling in the PM,some of which was restricted to the central sector andsome of which spread to more medial regions of the PM(Trojanowski and Jacobson, 1974; Barbas and Mesulam,1981; Morecraft et al., 1993). Evidence from the presentstudy suggests that the inclusion of areas 46 and 12 inthese injection sites greatly contributed to the amount oflabeling of the PM (Trojanowski and Jacobson, 1974;Asanuma et al., 1985) compared with those which werefocused solely on area 8a, the FEF. Thus, areas 46 and 12receive a substantial innervation from the PM and no lessthan that of area 8a.

Connections of the mediodorsal nucleuswith the prefrontal cortex

Anatomical studies have shown that PM and MD haveseveral PFC targets in common including regions locatedon the dorsolateral surface of the frontal lobe and regionson the medial wall of the prefrontal cortex. For example,

Fig. 7. Retrograde cell labeling of medial PM after injections ofWGA-HRP into areas 9, 12l (lateral), 10, and 24. In each case (A–D), alateral or medial brain schemata shows the location of the injectionsite as a blackened area within a cytoarchitectonic region of themacaque brain. Retrograde cellular labeling, depicted as black dots, inthe PM is shown on representative coronal sections through theposterior thalamus from caudal (left) to rostral (right) levels. Theinjection of area 12l (A) resulted in medial PM as well as central PMlabeling. Most injections which labeled medial PM also labeled themediodorsal nucleus (MD).


Figure8

both the central/lateral PM and theMDhave projections toorbital prefrontal cortex and the principal sulcus region. Inthe MD, pars magnocellularis and pars fibrosa (Ray andPrice, 1993) are reciprocally connected with orbital cortex,while MD pars parvocellularis is connected with theprincipal sulcus region (Goldman-Rakic and Porrino, 1985;Ray and Price, 1993) In addition, MD pars caudodorsalis isreciprocally associated with areas 14, 24, and 32 (Ray andPrice, 1993) as was found for the medial PM in the presentand previous studies (Barbas et al., 1991). Due to thepossible spread of the tracer to the MD in the present andin previous studies, our use of retrograde tracers in theprefrontal cortex was necessary to verify PM-PFC afferentconnections and allowed us to dissect MD and PM connec-tions. For example, injections of WGA-HRP into areas 10(Fig. 7) and 46 dorsal (not shown) involved significantlymore retrograde cellular labeling in MD than PM; whileinjections into areas 9, 24 and 8a resulted in roughlyequivalent labeling of both the PM and the caudal MD.Our findings confirm previous results showing that medialMD projects to the medial wall of the prefrontal cortexincluding Walker’s areas 24, 25, and 14 (Goldman-Rakicand Porrino, 1985; Giguere and Goldman-Rakic, 1988) butalso define a minor projection to these same areas from thecaudal, dorso-medial portion of the PM. In several cases(Fig. 6) the medial PM labeling was continuous withlabeling in the caudal pole of the MD, suggesting somedegree of continuity and overlap between rostromedial PMand caudomedial MD.

Laminar distribution of the labeled cellsand terminals in the cortex

We compared the laminar distribution of thalamo-cortical PM terminals and corticopulvinar neurons in thecerebral cortex. Within the PFC and in most other associa-tion areas, labeled terminals were invariably locatedwithinlayer IV and deep layer III (Figs. 3, 9). This result differswith the description of Baleydier and Mauguiere (1985)who, following WGA-HRP injections in the medial pulvi-nar, observed labeling in layer I in addition to the middlelayers in most cortical areas described. This discrepancymay be due to species differences since Baleydier andMauguiere (1985) used baboons and Macaca irus in theirstudies while the present results rely exclusively on Ma-caca mulatta. Alternatively, leakage of the tracer beyondthe bounds of the PM into other thalamic nuclei or into thecortex along the injection track may have also contributedto labeling of layer I in previous studies.

The uniform, laminar distribution of labeled terminalsand labeled cells in the PFC seen presently, contrastedwith the regional variations in the laminae of origin of thecortico-thalamic cells in other regions. In the prefrontalcortex, the retrogradely labeled corticopulvinar cells wereexclusively confined to layer VI (Fig. 3A–B), whereas in theinsula, and in parietal and temporal cortices, corticopulvi-nar projections originated from both layers V and VI (Fig.9A–B). Overall, corticopulvinar projections were leastdense in the PFC. Similar regional differences in the originof corticothalamic projections have been observed byGiguere and Goldman-Rakic (1985).Almost all areas of the cortex that received afferents

from the PM also demonstrated a reciprocal projectionback to the PM. However, cytoarchitectonic areas differedwith respect to the relative density of corticopetal andcorticofugal connections with the PM. For example, medialPM projections to the temporal pole, were denser thancorticopulvinar efferents, while central/lateral PM affer-ents to the temporal pole were less dense than temporalpole efferents to the PM. Although the insula demon-strated reciprocal connections with the PM, the granularinsula received more dense terminal labeling whereas thedysgranular insula had more retrogradely labeled cells.The caudal STS and STG, the posterior cingulate cortexand parietal areas 7a and 7ip all appeared to havereciprocal afferent and efferent projections to the PM byvirtue of the overlapping regions of cellular and terminallabeling. Subcortically, the lateral nucleus of the amygdalareceives an afferent input from the PM but does not projectback to the PM (Jones and Burton, 1976a, Aggleton et al.,1980; the present study).

Topography of efferent PM projectionsto other cortical targets

As discussed, the connections of the PM are quitewidespread and include areas within parietal cortex, tem-poral cortex, and limbic regions in addition to the prefron-tal projections discussed (see above). Moreover, our studysuggests that the central/lateral portion of PM has connec-tions with prefrontal and other association regions whichare distinct from those of the more medial portions of PM(Fig. 10). The central/lateral PM’s efferent targets includethe dorso-lateral and orbital PFC, as well as the granularand dysgranular insula, posterior parietal areas 7a, 7b,and 7ip, the dorsal bank of the STS, the posterior cingulatecortex, and the rostral and caudal STG. The connections ofthe medial portion of the PM are strikingly different. Themedial PM has a much sparser projection to the PFC.Medial PM does not project strongly to the insula, orposterior parietal regions 7a, 7b, or 7ip. Its primaryefferent projections are to the temporal pole, the rostralSTG, the rostral half of the dorsal bank of the STS,posterior cingulate cortex, and the amygdala. Therefore,the projections of the central/lateral and medial subre-gions of the PM seem to define two largely separatecircuits.The regions which were most densely labeled after

central/lateral PM injections include the posterior parietallobe, the superior temporal sulcus, and insular cortex. Theposterior parietal lobe, and in particular areas 7a and 7ip,receive such a prominent innervation from the PM that thePM is viewed as the inferior parietal lobe’s primarythalamic relay (LeGros Clark and Northfield, 1937; Baley-dier and Mauguiere, 1987; Schmahmann and Pandya,

Fig. 8. Coronal sections through the macaque brain illustratingretrograde and anterograde labeling of temporal, insular, cingulate,and parietal cortex due to tracer injections of central/lateral PM (toprow) or medial PM (bottom row). These cases are the same aspresented in Figures 4 (lateral PM injection) and 5 (medial PMinjection). Small black circles depict retrogradely labeled cells andregions of anterogradely labeled terminals are shown as grey patches.Density of the terminal field is indicated by color; dark grey signifiesdense terminal labeling and lighter grey indicates lighter terminallabeling. The sections are ordered rostrally (A) to caudally (E). In thetop row, the superior temporal gyrus, dorsal bank of the superiortemporal sulcus, insula, posterior cingulate, and posterior parietalregions 7a, 7b, and 7ip were labeled as a result of a WGA-HRPinjection into central/lateral PM. In contrast, medial PM injections,(depicted in the bottom row), resulted in mainly anterograde labelingof the rostral superior temporal gyrus, dorsal bank of the superiortemporal sulcus, posterior cingulate, and the amygdala.


1990; Baleydier and Morel, 1992; Hardy and Lynch, 1992;Morecraft et al., 1993). The connection of posterior parietalarea 7 with central/lateral PM found in the present studyis supported by many previous studies which have exam-ined PM-parietal connections by placing anterograde orretrograde tracers into these same posterior parietal corti-cal regions (Baizer et al., 1993; Baleydier and Morel, 1992;Selemon and Goldman-Rakic, 1988).Interestingly, the central/lateral PM also gives rise to

projections to inferotemporal (IT) cortex. IT cortex was notdensely labeled in the present study since the PM injectionsites did not include the ventral/lateral edge of PM. This

ventrolateral edge has been designated part of the ‘‘P3’’retinotopic field of PM (Bender, 1981; Ungerleider et al.,1984), where there exists a coarse visual topography. Theregions of IT cortex which have been shown, in previousstudies to be reciprocally connected with lateral PM in-clude TEO, TE, MT, MST, and FST ( Rockland, 1996;Yeterian and Pandya, 1989; Ungerleider et al., 1984;Baizer et al., 1993; Baleydier and Morel, 1992; Boussaoudet al., 1992; Webster et al., 1993). Some studies suggestthat PM is more heavily connected with area TE while PLis associated more with area TEO (Webster et al., 1993).Results from the present study also confirm previous

Fig. 9. Darkfield and brightfield photomicrographs of anterogradeand retrograde labeling in cortical targets outside of the prefrontalcortex after injections of WGA-HRP into the PM. A: Anterograde andretrograde labeling in the insular cortex (delimited by arrowheads)which resulted from an injection into central/lateral PM. Note theabsence of labeling in the rostral superior temporal gyrus in thiscentral/lateral PM injection. A black dotted line is drawn around acluster of retrogradely labeled cells shown at higher magnification inB.B:Higher power image of retrogradely labeled cells from the section

depicted inA, showing large pyramidal neurons in layer V and smallerpyramidal neurons in layer VI. C:Anterograde labeling (marked witharrows) in the rostral superior temporal gyrus after an injection ofWGA-HRP into the medial PM. There was no labeling in the insularcortex (asterisk), in contrast to that observed with central/lateral PMinjections (shown in A). D: Anterograde and retrograde labeling(delimited by arrows) in the parietal cortex in areas 7a and 7ip after aninjection into the central/lateral PM. Scale bar5 800 µm inA,C, 50 µmin B, 900 µm in D.


findings of widespread connections between the PM andthe STS, whether injections are placed dorsally, ventrally,laterally, or medially in the PM (Trojanowski and Jacob-son, 1976; Jones and Burton, 1976b; Streitfield, 1980). Inthe present study, the projection of the PM to the STS wasgreatest to the dorsal bank of the STS, (with some involve-ment of the fundus), in areas corresponding to regions thatare polysensory in nature, areas TPO, TAa, and PGa(Seltzer and Pandya, 1989). Detailed tracing studies re-veal that rostral portions of the dorsal bank receiveprojections from caudal, medial portions of the PM whilecaudal STS, receives afferents from central/lateral regionsof the PM (Mauguiere and Baleydier, 1978; Trojanowskiand Jacobson, 1976; Markowitsch et al., 1985; Moran etal., 1987; Yeterian and Pandya, 1989; Baleydier andMorel,1992; Boussaoud et al., 1992; Webster et al., 1993; Pandyaet al., 1994).Central/lateral PM is also reciprocally connected with

insular and posterior cingulate cortices. For both of theseregions, dorsal PM is the source of connections (Baleydierand Mauguiere, 1985; Mufson and Mesulam, 1984; Yete-rian and Pandya, 1988 ). Topographic studies indicate thatgranular and dysgranular fields of the insula are con-nected with the central or dorsal PM region (Trojanowskiand Jacobson, 1976; Mufson and Mesulam, 1984; Fried-man andMurray, 1986) as was shown in the present study.As for cingulate cortex, our results show that both central/lateral and medial PM injections (which included thedorsal PM) projected to the posterior cingulate while theanterior cingulate was only sparsely labeled by medial PMinjections. Although both anterior cingulate and the PMhave been included as part of directed attention networks,the PM is actually associated more with the posteriorcingulate, while the mediodorsal nucleus is densely con-nected with the anterior cingulate cortex (Yeterian andPandya, 1989; the present study).Whereas most of the previously mentioned PM cortical

targets can be linked with visual/spatial, attention or

oculomotor processes, the connection of the PM with theSTG suggests a possible role in auditory function. Bothcentral and medial regions of the PM project reciprocallyto the STG and to the temporal pole. Medial PM sends andreceives projections from the rostral STG and the temporalpole, while the caudal portions of the STG are connectedwith central/lateral regions of the PM (Locke, 1960; Jonesand Burton, 1976b; Trojanowski and Jacobson, 1976;Mauguiere and Baleydier, 1978; Markowitsch et al., 1985;Pandya et al., 1994; and the present study). In the STG,the PM-recipient zones overlap with physiologically de-fined regions which have been shown to be responsive toauditory stimuli (Rauschecker et al., 1995). In addition,the labeling within the dorsal bank of the STS from bothcentral/lateral and medial PM injections, includes TPO, apolysensory region which has been shown to be responsiveto visual, somatosensory, and auditory stimuli (Bruce etal., 1981). Moreover, both central/lateral PM and medialPM project to area 12 lateral, on the inferior convexity.This region may also be polysensory in nature since visual(Wilson et al., 1993) as well as auditory responses (L.M.Romanski and S. O’Scalaidhe, unpublished observations)have been physiologically recorded from this region.One region which received projections from the medial

PM but not from central/lateral PM is the amygdala. In thepresent study, a caudomedial PM injection resulted interminal labeling of the lateral and basal amygdaloidnuclei, which has been demonstrated previously (Jonesand Burton, 1976a; Aggleton et al., 1980).

Functional implications

The present results highlight the connections of the PMwith the prefrontal cortex and suggest a topography whichlinks central/lateral PM with prefrontal areas 46, 12, 8a,and 45 and orbital prefrontal regions and medial PM withprefrontal areas 9 and 12 lateral as well as medialprefrontal regions. Consideration of the cortical and subcor-

Fig. 10. Summary of PM connections. A schematic diagram of thetopographic organization of PM connections based on this and previ-ous reports, showing that connections for the central/lateral PM aredifferent from those of the medial PM. The connections with theprefrontal cortex are shaded in grey. The central/lateral PM ispreferentially connected with prefrontal areas 8a, 12 (lateral andorbital), 45, and the ventral bank of the principal sulcus, area 46v andto a lesser extent, orbital regions 11 and 13 (shown in lighter print). Incontrast, the medial PM has connections with areas 9 and 12 lateral,

and sparse connections (shown in lighter print) with the medialprefrontal cortex (areas 24, 25, 32), and area 10. The projections fromthe central/lateral and medial PM to other association regions is alsoshown with the area receiving the strongest projections at the top. Thecentral/lateral PM projects to the posterior parietal, insular, STS,STG, inferotemporal, and the posterior cingulate cortices as well asthe temporal pole while themedial PM projects mainly to the temporalpole, the rostral STG and STS, both anterior and posterior cingulatecortices as well as to the amygdala.


tical connectivity of the PM as well as the functions of thecortical targets of the PM, suggests that central/lateral PMis well positioned to relay visual, somatosensory, oculomo-tor, and visuospatial information to and from the cortex.First, the prefrontal regions which receive input from

central/lateral PM have been implicated in visuospatial oroculomotor processing. Area 8a (the frontal eye fields) isinvolved with the execution and control of eye movements(Bruce and Goldberg, 1985) while several studies havedefined an essential role in visuospatial working memoryfor the principal sulcus region, area 46 (Goldman-Rakic1987, 1990; Funahashi et al., 1990, 1993a,b). In addition,previous lesion studies have implied a role for orbitalfrontal regions in other aspects of visual processing includ-ing feature and object memory (Mishkin and Manning,1978). A recent study by Wilson et al. (1993), has impli-cated regions of the inferior convexity (including areas 12and 45), which received projections from the PM in thepresent study, in feature and object processing. Theseinferior convexity neurons showed preferences for particu-lar visual objects and patterns. Moreover, a recent study(Benevento and Port, 1995) has shown that neurons in thelateral PM and PL also display preferences to pattern andcolor stimuli. In fact, these neurons appear to encode bothform/color and saccade related information.As for other connections, the central/lateral PM receives

its greatest subcortical input from the deep layers of thesuperior colliculus (Harting et al., 1980; Benevento andFallon, 1975) and sends dense projections to areas 7a, 7ip,insular cortex, posterior cingulate cortex, as well as rostraland caudal portions of the temporal lobe. Most of theseregions can be related to either visual, visuospatial, oroculomotor processing. Areas 7a and 7ip have been closelylinked with oculomotor and visuospatial processing as wellas visual integration and attention (Anderson, 1987;Brotchie et al., 1995). The posterior cingulate has alsobeen linked with oculomotor processing via functionalimaging studies in humans and electrophysiological record-ings in monkeys (Vogt et al., 1992; Carlson and Goldman-Rakic, 1993; Olson et al., 1993; Paus et al., 1993). A thirdtarget, the insular cortex, may also play a role in oculomo-tor or vestibular functioning. Historically, the insula hasbeen implicated in limbic, and gustatory functions (Muf-son and Mesulam, 1984; Yeterian and Pandya, 1988).However, neurons in the insular cortex respond to somato-sensory stimulation (Robinson and Burton, 1980) andfunctional imaging studies have shown the insula to beactive during vestibular (Akbarian et al., 1992; Bottini etal., 1994), and proprioceptive (Bonda et al., 1995) stimula-tion. Visually responsive neurons also predominate ininferotemporal regions TE and TEOwhile the cortex of thesuperior temporal sulcus, which receives inputs fromextrastriate visual areas and from dorsal stream parietalregions, may play an integrative role in visual/oculomotorfunctions (Bruce et al., 1981; Seltzer and Pandya, 1989).Several studies have shown that when multiple retro-

gradely transported tracers are injected into prefrontaland parietal or parietal and temporal cortex, separateneuronal populations within the PM are labeled but allthese projections appear to overlap within the central/lateral PM (Asanuma et al., 1985; Selemon and Goldman-Rakic, 1988; Baizer et al., 1993; Webster et al., 1993;Yeterian and Pandya, 1985; Baleydier and Morel, 1992),suggesting that these interconnected regions may be partof a common functional circuit. In addition, the PM and itscortical targets share some common features including

large receptive fields and a coarse visual topography(Benevento and Port, 1995; Ungerleider et al., 1984;Bender, 1981), further suggesting a network of connectionssubserving directed visual attention or visual workingmemory. It is especially interesting that both the PM andthe anterior superior temporal polysensory area, to whichcentral/lateral PM projects, share a unique feature in thatthey are both sensitive to form and motion (Benevento andPort, 1995; Oram and Perrett, 1996). The convergence ofboth ‘‘what’’ and ‘‘where’’ information in the PM and in thecortex of the STS suggests a role in visual integration andcomplex computational processes.The function of circuits involving the medial PM are less

obvious. Certainly, it is possible that the medial regions ofthe PM, which have afferent and efferent connections withdorsomedial PFC, auditory cortical regions of the STG,polymodal processing areas of the STS and the amygdala,might play a role in auditory, auditory-spatial, or otherattentional processes, in the same way that the central/lateral PM may do for visuospatial and somatosensoryprocessing. In fact, electrophysiological studies have shownthat the PM, itself, responds to auditory stimuli (Yirmiyaand Hocherman, 1987; Gattass et al., 1979). If the medialpulvinar, as a whole, is essential in attention or memoryprocesses then it would be crucial to relay auditory, as wellas visual information to cortical association areas.Together with its cortical targets, the lateral and medial

PM could orient the body, head and eyes, towards salientvisual and auditory stimuli, as has been suggested for thesuperior colliculus (Allon and Wollberg, 1978) and theposterior parietal cortex (Andersen, 1987). This orientingwould involve an integration between the location ofrelevant stimuli external to the organism and the locationof the organism itself in relationship to relevant stimuli.These notions are consistent with the purported role of thePM, together with the cingulate, posterior parietal, supe-rior temporal, and frontal cortices, in directed attentionand visual salience (Mesulam, 1990; Posner and Driver,1992; Morecraft et al., 1993; Robinson, 1993).

ACKNOWLEDGMENTS

We thank J. Coburn, M. Pappy, and K. Szigeti for theirassistance with histology, J. Musco for photography, andDrs. D.R. Kornack and L. Naz-Hazrati for their helpfulcomments on the manuscript. This research was sup-ported by National Institutes of Health Grant MH-38546to P.S.G.-R. and James S. McDonnell Foundation GrantJSMF 93-28 to L.M.R.

LITERATURE CITED

Acuna, C., J. Cudeiro, F. Gonzalez, J.M. Alonso, and R. Perez (1990)Lateral-posterior and pulvinar reaching cells—-comparison with pari-etal area 5a: A study in behaving Macaca nemestrina monkeys. Exp.Brain Res. 82:158–166.

Acuna, C., F. Gonzalez, and R. Dominguez (1983) Sensorimotor unit activityrelated to intention in the pulvinar of behaving Cebus Apellamonkeys.Exp. Brain Res. 52:411–422.

Aggleton, J.P., M.J. Burton, and R.E. Passingham (1980) Cortical andsubcortical afferents to the amygdala of the rhesus monkey (Macacamulatta). Brain Res. 190:347–368.

Akbarian, S., O.J. Grusser, andW.O. Guldin (1992) Thalamic connections ofthe vestibular cortical fields in the squirrel monkey (Saimiri sciureus).J. Comp. Neurol. 326:423–441.

Allon, N., and Z. Wollberg (1978) Responses of cells in the superiorcolliculus of the squirrel monkey to auditory stimuli. Brain Res.159:321–330.


Andersen, R.A. (1987) The role of the inferior parietal lobule in spatialperception and visual-motor integration. In F. Plum, V.B. Mountcastel,and S.R. Geiger (eds): The Handbook of Physiology, Sec. 1, The NervousSystem, Vol. V, Higher Functions of the Brain, Part 2. Bethesda:American Physiological Society, pp. 483–518.

Asanuma, C., R.A. Andersen, and W.M. Cowan (1985) The thalamicrelations of the caudal inferior parietal lobule and the lateral prefrontalcortex in monkeys: Divergent cortical projections from cell clusters inthe medial pulvinar nucleus. J. Comp. Neurol. 241:357–381.

Baizer, J.S., R. Desimone, and L.G. Ungerleider (1993) Comparison ofsubcortical connections of inferior temporal and posterior parietalcortex in monkeys. Vis. Neurosci. 10:59–72.

Baleydier, C., and F. Mauguiere (1977) Pulvinar-latero posterior afferentsto cortical area 7 in monkeys demonstrated by horseradish peroxidasetracing technique. Exp. Brain Res. 27:501–507.

Baleydier, C., and F. Mauguiere (1985) Anatomical evidence for medialpulvinar connections with the posterior cingulate cortex, the retrosple-nial area, and the posterior parahippocampal gyrus in monkeys. J.Comp. Neurol. 232:219–228.

Baleydier, C., and F. Mauguiere (1987) Network organization of theconnectivity between parietal area 7, posterior cingulate cortex andmedial pulvinar nucleus: A double fluorescent tracer study in monkey.Exp. Brain Res. 66:385–393.

Baleydier, C., and A. Morel (1992) Segregated thalamocortical pathways toinferior parietal and inferotemporal cortex in macaque monkey. Vis.Neurosci. 8:391–405.

Barbas, H. (1992) Architecture and cortical connections of the prefrontalcortex in the rhesus monkey. [Review]. Adv. Neurol. 57:91–115.

Barbas, H., T.H. Henion, and C.R. Dermon (1991) Diverse thalamicprojections to the prefrontal cortex in the rhesus monkey. J. Comp.Neurol. 313:65–94.

Barbas, H., and M.M. Mesulam (1981) Organization of afferent input tosubdivisions of area 8 in the rhesus monkey. J. Comp. Neurol. 200:407–431.

Bates, J.F., and P.S. Goldman-Rakic (1993) Prefrontal connections ofmedial motor areas in the rhesus monkey. J. Comp. Neurol. 336:211–228.

Bender, D.B. (1981) Retinotopic organization of macaque pulvinar. J.Neurophysiol. 46:672–293.

Bender, D.B., and J.S. Baizer (1990) Saccadic eye movements followingkainic acid lesions of the pulvinar in monkeys. Exp. Brain Res.79:467–478.

Benevento, L.A., and J.H. Fallon (1975) The ascending projections of thesuperior colliculus in the rhesus monkey (Macaca mulatta). J. Comp.Neurol. 160:339–362.

Benevento, L.A., and G.P. Standage (1983) The organization of projectionsof the retinorecipient and nonretinorecipient nuclei of the pretectalcomplex and layers of the superior colliculus to the lateral pulvinar andmedial pulvinar in the macaque monkey. J. Comp. Neurol. 217:307–336.

Benevento, L.A. and J.D. Port (1995) Single neurons with both form/colordifferential responses and saccade-related responses in the nonretino-topic pulvinar of the behaving macaque monkey. Vis. Neurosci. 12:523–544.

Blum, B. (1985) Manipulation reach and visual reach neurons in theinferior parietal lobule of the rhesus monkey. Behav. Brain Res.18:167–173.

Bonda, E., M. Petrides, M. Frey, and A. Evans (1995) Neural correlates ofmental transformations of the body-in-space. Proc. Natl. Acad. Sci. USA92:11180–11184.

Bos, J., and L.A. Benevento (1975) Projections of the medial pulvinar toorbital cortex and frontal eye fields in the rhesus monkey (Macacamulatta). Exp. Neurol. 49:487–496.

Bottini, G., R. Sterzi, U.E. Paules, G. Vallar, S.F. Cappa, F. Erminio, R.E.Passingham, C.D. Frith, and R.S. Frackowiak (1994) Identification ofthe central vestibular projections in man: A positron emission tomagra-phy study. Exp. Brain Res. 99:164–169.

Boussaoud, D., R. Desimone, and L.G. Ungerleider (1992) Subcorticalconnections of visual areas MST and FST in macaques. Vis. Neurosci.9:291–302.

Brotchie, P.R., R.A. Andersen, L.H. Snyder, and S.J. Goodman (1995) Headposition signals used by parietal neurons to encode locations of visualstimuli. Nature 375:232–235.

Browne, B., and R.M. Simmons (1984) Quantitative studies of the evolutionof the thalamus in primates. J. Hirn. 25:261–274.

Bruce, C.J., R. Desimone, and C.G. Gross (1981) Visual properties ofneurons in a polysensory in the superior temporal sulcus of macaquemonkey. J. Neurophysiol. 46:369–384.

Bruce, C.J., and M.E. Goldberg (1985) Primate frontal eyefields. I. Singleneurons discharging before saccades. J. Neurophysiol. 53:603–635.

Carlson, S., A. Mikami, and P. Goldman-Rakic (1993) Omnidirectionaldelay activity in the monkey posterior cingulate cortex during theperformance of an oculomotor delayed response task. Soc. Neurosci.Abstr. 19:326.7.

Cavada, C., and P.S. Goldman-Rakic (1989) Posterior parietal cortex inrhesus monkey: I. Parcellation of areas based on distinctive limbic andsensory corticocortical connections. J. Comp. Neurol. 287:393–421.

Cavada C., Company T., Hernandez-Gonzalez A., and F. Reinoso-Suarez(1995) Acetylcholinesterase histochemistry in the macaque thalamusreveals territories selectively connected to frontal, parietal and tempo-ral association cortices. J. Chem. Neuroanat. 8:245–257.

Cudeiro, J., F. Gonzalez, R. Perez, J.M. Alonso, and C. Acuna (1989) Doesthe pulvinar-LP complex contribute to motor programming? Brain Res.484:367–370.

Cusick, C.G., J.L. Scripter, J.G. Darensbourg, and J.T. Weber (1993)Chemoarchitectonic subdivisions of the visual pulvinar in monkeys andtheir connectional relations with the middle temporal and rostraldorsolateral visual areas, MT and DLr. J. Comp. Neurol. 336:1–30.

Dum, R.P., and P.L. Strick (1992) Medial wall motor areas and skeletomotorcontrol. Curr. Opin. Neurobiol. 2:836–839.

Friedman, D.P., and E.A. Murray (1986) Thalamic connectivity of thesecond somatosensory area and neighboring somatosensory fields of thelateral sulcus of the macaque. J. Comp. Neurol. 252:348–373.

Funahashi, S., C.J. Bruce, and P.S. Goldman-Rakic (1990) Visuospatialcoding in primate prefrontal neurons revealed by oculomotor para-digms. J. Neurophysiol. 63:814–831.

Funahashi, S., C.J. Bruce, and P.S. Goldman-Rakic (1993a) Dorsolateralprefrontal lesions and oculomotor delayed-responsee performance: evi-dence for mnemonic ‘‘scotomas.’’ J. Neurosci. 13:1479–1497.

Funahashi, S., M.V. Chafee, and P.S. Goldman-Rakic (1993b) Prefrontalneuronal activity in rhesus monkeys performing a delayedd anti-saccade task. Nature 365:753–756.

Fuster, J.M. (1989) The Prefrontal Cortex: Anatomy, Physiology andNeurophysiology of the Frontal Lobe. NewYork: Raven Press.

Fuster, J.M. (1993) Frontal lobes. [Review]. Curr. Opinion Neurobiol.3:160–165.

Gattass, R., E. Oswaldo-Cruz, andA.P.B. Sousa (1979) Single unit responsetypes in the pulvinar of cebus monkey. Brain Res. 158:75–87.

Giguere, M., and P.S. Goldman-Rakic (1988) Mediodorsal nucleus: Areal,laminar, and tangential distribution of afferents and efferents in thefrontal lobe of rhesus monkeys. J. Comp. Neurol. 277:195–213.

Goldman-Rakic, P. (1987) Circuitry of primate prefrontal cortex andregulation of behavior by representational memory. In F. Plum (ed):Handbook of Physiology. Section 1: The Nervous System. Vol. V, HigherFunctions of the Brain. Bethesda: American Physiological Society, pp373–418.

Goldman-Rakic, P.S. (1990) Cellular and circuit basis of workingmemory inprefrontal cortex of nonhuman primates. Prog. Brain Res. 85:325–435.

Goldman-Rakic, P.S., and L.J. Porrino (1985) The primate mediodorsal(MD) nucleus and its projection to the frontal lobe. J. Comp. Neurol.242:535–560.

Gutierrez, C., A. Yaun, and C.G. Cusick (1995) Neurochemical subdivisionsof the inferior pulvinar in Macaque monkeys. J. Comp. Neurol. 363:545–562.

Hardy, S.G., and J.C. Lynch (1992) The spatial distribution of pulvinarneurons that project to two subregions of the inferior parietal lobule inthe macaque. Cerebral Cortex 2:217–230.

Harting, J.K., M.F. Huerta, A.J. Frankfurter, N.L. Strominger, and G.J.Royce (1980) Ascending pathways from the monkey superior colliculus:An autoradiographic analysis. J. Comp. Neurol. 192:853–882.

Ilinsky, I.A., K. Kultas-Ilinsky, and K.R. Smith (1978) A stereotaxic methodbased on ventricular radiography in the cat (with special reference tothe stereotaxic topography of the substantia nigra). Exp. Brain Res.33:469–480.

Jones, E.G., and H. Burton (1976a)Aprojection from the medial pulvinar tothe amygdala in primates. Brain Res. 104:142–147.

Jones, E.G., andH.Burton (1976b)Areal differences in the laminar distributionof thalamic afferents in cortical fields of the insular, parietal and temporalregions of primates. J. Comp.Neurol. 168:197–248.


Kievit, J., and H.G. Kuypers (1977) Organization of the thalamo-corticalconnexions to the frontal lobe in the rhesus monkey. Exp. Brain Res.29:299–322.

Kunzle, H., and K. Akert (1977) Efferent connections of cortical, area 8(frontal eye field) in Macaca fascicularis. A reinvestigation using theautoradiographic technique. J. Comp. Neurol. 173:147–164.

LaBerge, D., and M.S. Buchsbaum (1990) Positron emission tomographicmeasurements of pulvinar activity during an attention task. J. Neuro-sci. 10:613–619.

LeGros Clark, W.E., and D.W.C. Northfield (1937) The cortical projection ofthe pulvinar in the macaque monkey. Brain 60:126–142.

Locke, S. (1960) The projection of the medial pulvinar of the macaque. J.Comp. Neurol. 115:155–168.

Markowitsch, H.J., D. Emmans, E. Irle, M. Streicher, and B. Preilowski(1985) Cortical and subcortical afferent connections of the primate’stemporal pole: a study of rhesus monkeys, squirrel monkeys, andmarmosets. J. Comp. Neurol. 242:425–458.

Mauguiere, F., and C. Baleydier (1978) Topographical organization ofmedial pulvinar neurons sending fibres to Brodman’s areas 7, 21 and 22in the monkey. Exp. Brain Res. 31:605–607.

Mesulam, M.M. (1978) Tetramethylbenzidine for horseradish peroxidaseneurohistochemistry: A non-carcinogenic blue reaction product withsuperior sensitivity for visualizing neural afferents and efferents.Cytochemistry 26:106–117.

Mesulam, M.M. (1990) Large-scale neurocognitive networks and distrib-uted processing for attention, language, and memory. Ann. Neurol.28:597–613.

Mishkin, M., and F.J. Manning (1978) Non-spatial memory after selectiveprefrontal lesions in monkeys. Brain Res. 143:313–323.

Moran, M.A., E.J. Mufson, and M.M. Mesulam (1987) Neural inputs intothe temporopolar cortex of the rhesus monkey. J. Comp. Neurol.256:88–103.

Morecraft, R.J., C. Geula, and M.M. Mesulam (1992) Cytoarchitecture andneural afferents of orbitofrontal cortex in the brain of the monkey. J.Comp. Neurol. 323:341–358.

Morecraft, R.J., C. Geula, and M.M. Mesulam (1993) Architecture ofconnectivity within a cingulo-fronto-parietal neurocognitive networkfor directed attention. Arch. Neurol. 50:279–284.

Mufson, E.J., andM.M.Mesulam (1984) Thalamic connections of the insulain the rhesus monkey and comments on the paralimbic connectivity ofthe medial pulvinar nucleus. J. Comp. Neurol. 227:109–120.

Olson, C.R., S.Y. Musil, and M.E. Goldberg (1993) Neurophysiology ofposterior cingulate cortex in the behaving monkey. In B.A. Vogt and M.Gabriel (eds): The neurobiology of cingulate cortex. Boston: Birkhauser.

Olszewski, J. (1952) The Thalamus of theMacacaMulatta: AnAtlas for UseWith the Stereotaxic Instrument. Basel: Karger.

Oram, M.W., and D.I. Perrett (1996) Integration of form and motion in theanterior superior temporal polysensory area (STPa) or the macaquemonkey. J. Neurophys. 76:109–129.

Pandya, D.N., D.L. Rosene, and A.M. Doolittle (1994) Corticothalamicconnections of auditory-related areas of the temporal lobe in the rhesusmonkey. J. Comp. Neurol. 345:447–471.

Paus, T., M. Petrides, A.C. Evans, and E. Meyer (1993) Role of the humananterior cingulate cortex in the control of oculomotor, manual, andspeech responses: a positron emission tomography study. J. Neurophys.70:453–469.

Petersen, S.E., D.L. Robinson, and J.D. Morris (1987) Contributions of thepulvinar to visual spatial attention. Neuropsychologia 25:97–105.

Posner, M.I. and J. Driver (1992) The neurobiology of selective attention.Curr. Opinion Neurobiol. 2:165–169.

Preuss, T.M., and P.S. Goldman-Rakic (1991) Myelo- and cytoarchitectureof the granular frontal cortex and surrounding regions in the strepsi-rhine primate Galago and the anthropoid primate Macaca. J. Comp.Neurol. 310:429–474.

Rakic, P. (1974) Embryonic development of the pulvinar-LP complex inman. In M. Riklan, I.S. Cooper, and P. Rakic (eds): The Pulvinar-LPComplex. Springfield: Charles C. Thomas Publishers, pp 3–30.

Ray, J.P., and J.L. Price (1993) The organization of projections from themediodorsal nucleus of the thalamus to orbital and medial prefrontalcortex in macaque monkeys. J. Comp. Neurol. 337:1–31.

Rauschecker, J.P., B. Tian, and M. Hauser (1995) Processing of complexsounds in the macaque nonprimary auditory cortex. Science 268:111–114.

Robinson, C.J., and H. Burton (1980) Somatic submodality distributionwithin the second somatosensory (SII), 7b, retroinsular, postauditory,and granular insular cortical areas of M. fascicularis. J. Comp. Neurol.192:93–108.

Robinson, D.L. (1993) Functional contributions of the primate pulvinar.Prog Brain Res. 95:371–380.

Robinson, D.L., J.W. McClurkin, C. Kertzman, and S.E. Petersen (1991)Visual Responses of pulvinar and collicular neurons during eye move-ments of awake, trained macaques. J. Neurophys. 66:485–496.

Robinson, D.L., and S.E. Petersen (1992) The pulvinar and visual salience.Tr. Neurosci. 15:127–132.

Rockland, K.S. (1996) Two types of cortico-pulvinar terminations: Round(type 2) and elongate (type 1). J.Comp.Neurol. 368:57–87.

Schmahmann, J.D., and D.N. Pandya (1990) Anatomical investigation ofprojections from thalamus to posterior parietal cortex in the rhesusmonkey: a WGA-HRP and fluorescent tracer study. J. Comp. Neurol.295:299–326.

Selemon, L.D., and P.S. Goldman-Rakic (1988) Common cortical andsubcortical targets of the dorsolateral prefrontal and posterior parietalcortices in the rhesus monkey: Evidence for a distributed neural networksubserving spatially guided behavior. J. Neurosci. 8:4049–4068.

Seltzer, B., and D.N. Pandya (1989) Intrinsic connections and architecton-ics of the superior temporal sulcus in the rhesus monkey. J. Comp.Neurol. 290:451–471.

Stanton, G.B., M.E. Goldberg, and C.J. Bruce (1988) Frontal eye fieldefferents in the macaue monkey: I. Subcortical pathways and topogra-phy of striatal and thalamic terminal fields. J. Comp. Neurol. 271:473–492.

Streitfeld, B.D. (1980) The fiber connections of the temporal lobe withemphasis on the rhesus monkey. Intl. J. Neurosci. 11:51–71.

Trojanowski, J.Q., and S. Jacobson (1974) Medial pulvinar afferents tofrontal eye field in rhesus monkey demonstrated by horseradishperoxidase. Brain Res. 80:395–411.

Trojanowski, J.Q., and S. Jacobson (1976)Areal and laminar distribution ofsome pulvinar cortical efferents in rhesus monkey. J. Comp. Neurol.169:371–392.

Trojanowski, J.Q., and S. Jacobson (1977) The morphology and laminardistribution of cortico-pulvinar neurons in the rhesus monkey. Exp.Brain Res. 28:51–62.

Ungerleider, L.G., R. Desimone, T.W. Galkin, and M. Mishkin (1984)Subcortical projections of area MT in the macaque. J. Comp. Neurol.223:368–386.

Vogt, B.A., D.M. Finch, and C.R. Olson (1992) Functional heterogeneity incingulate cortex: the anterior executive and posterior evaluative re-gions. Cerebral Cortex 2:435–443.

Walker, A.E. (1940) A cytoarchitectural study of the prefrontal area of themacaque monkey. J. Comp. Neurol. 73:59–86.

Webster, M.J., J. Bachevalier, and L.G. Ungerleider (1993) Subcorticalconnections of inferior temporal areas TE and TEO in macaquemonkeys. J. Comp. Neurol. 335:73–91.

Wilson, F.A., S.P. Scalaidhe, and P.S. Goldman-Rakic (1993) Dissociation ofobject and spatial processing domains in primatee prefrontal cortex.Science 260:1955–1958.

Yeterian, E.H., and D.N. Pandya (1988) Corticothalamic connections ofparalimbic regions in the rhesusmonkey. J. Comp.Neurol. 269:130–146.

Yeterian, E.H., and D.N. Pandya (1989) Thalamic connections of the cortexof the superior temporal sulcus in the rhesus monkey. J. Comp. Neurol.282:80–97.

Yirmiya, R., and S. Hocherman (1987) Auditory- and movement-relatedneural activity interact in the pulvinar of the behaving rhesus monkey.Brain Res. 402:93–102.


topographic organization of medial pulvinar connections with the prefrontal cortex in the rhesus...

Documents