differential connections of the temporal pole with the orbital and medial prefrontal networks in...

Differential Connections of theTemporal Pole with the Orbital and

Medial Prefrontal Networks inMacaque Monkeys

HIDEKI KONDO, KADHARBATCHA S. SALEEM, AND JOSEPH L. PRICE*

Department of Anatomy and Neurobiology, Washington University School of Medicine,St. Louis, Missouri 63110

ABSTRACTPrevious studies indicate that the orbital and medial prefrontal cortex (OMPFC) is

organized into “orbital” and “medial” networks, which have distinct connections with cortical,limbic, and subcortical structures. In this study, retrograde and anterograde tracer experi-ments in monkeys demonstrated differential connections between the medial and orbitalnetworks and the dorsal and ventral parts of the temporal pole. The dorsal part, includingdysgranular and granular areas (TGdd and TGdg), is reciprocally connected with the medialnetwork areas on the medial wall and gyrus rectus (areas 10m, 10o, 11m, 13a, 14c, 14r, 25,and 32) and on the lateral orbital surface (areas Iai and 12o). The strongest connections arewith areas 10m (caudal part), 14c, 14r, 25, 32, and Iai. The agranular temporal pole (TGa) isconnected with several areas, but most strongly with medial network area 25. The granulararea around the superior temporal sulcus (TGsts) and the ventral dysgranular and granularareas (TGvd and TGvg) are reciprocally connected with the orbital network (especially areas11l, 13b, 13l, 13m, Ial, Iam, and Iapm). TGsts is strongly connected with the entire orbitalnetwork, whereas areas TGvd and TGvg have lighter and more limited connections. Intrinsicconnections within the temporal pole are also restricted to dorsal or ventral parts. Togetherwith evidence that the dorsal and ventral temporal pole are differentially connected toauditory and visual areas of the superior and inferior temporal cortex, the results indicateseparate connections between these systems and the medial and orbital prefrontal networks.J. Comp. Neurol. 465:499–523, 2003. © 2003 Wiley-Liss, Inc.

Indexing terms: orbital cortex; medial prefrontal cortex; temporal cortex; anterograde axonal

tracers; retrograde axonal tracers; architectonic areas

Recent anatomical studies of the orbital and medialprefrontal cortex (OMPFC) in monkeys defined two dis-tinct prefrontal networks, an “orbital network,” which con-sists of most of the areas on the orbital surface, and a“medial network,” which consists of areas on the medialwall and a few areas on the orbital surface. The twonetworks were defined from an analysis of corticocorticalconnections within the OMPFC (Carmichael and Price,1996), but they also have distinct connections with othercortical, limbic, and subcortical areas (Ray and Price,1993; Carmichael and Price, 1995a,b; An et al., 1998;Ongur et al., 1998; Ferry et al., 2000; Ongur and Price,2000). The orbital network receives several sensory inputsfrom visual, somatosensory, olfactory, and gustatory cor-tical areas (Carmichael et al., 1994; Carmichael and Price,1995b). It appears to be involved in analysis of sensory

stimuli related to food and reward (Rolls, 2000). The me-dial network receives few of these sensory inputs (Car-michael and Price, 1995b) but sends outputs to the hypo-thalamus (Ongur et al., 1998) and the periaqueductal gray(An et al., 1998). It has been considered to be a viscero-motor or emotomotor system (Ongur and Price, 2000). In

Grant sponsor: National Institutes of Health; Grant number: DC000093.*Correspondence to: Joseph L. Price. Department of Anatomy & Neuro-

biology, Campus Box 8108, Washington University School of Medcine, 660S. Euclid Avenue, St. Louis, MO 63110. E-mail: [email protected]

Received 21 March 2003; Revised 19 May 2003; Accepted 20 May 2003DOI 10.1002/cne.10842Published online the week of September 8, 2003 in Wiley InterScience

(www.interscience.wiley.com).

THE JOURNAL OF COMPARATIVE NEUROLOGY 465:499–523 (2003)

© 2003 WILEY-LISS, INC.

addition, the orbital and medial networks have substan-tial and distinct connections with limbic structures includ-ing the amygdala, entorhinal cortex and hippocampus(Amaral and Price, 1984; Barbas and De Olmos, 1990;Barbas and Blatt, 1995; Carmichael and Price, 1995a;Ghashghaei and Barbas, 2002), the striatum (Ferry et al.,2000), and the thalamus (Ray and Price, 1993; Ongur andPrice, 2000).

Previous studies in monkeys have shown that theOMPFC is connected with the temporal pole, althoughthey did not analyze the connection in terms of the twoprefrontal networks or specific regions of the temporalpole (Pandya and Kuypers, 1969; Jones and Powell, 1970;Van Hoesen et al., 1975; Markowitsch et al., 1985; Moranet al., 1987, Barbas, 1988, 1993; Morecraft et al., 1992;Carmichael and Price, 1995a; Barbas et al., 1999; Cavadaet al., 2000; Rempel-Clower and Barbas, 2000). Moran etal. (1987) reported that the dorsal and ventral part of thetemporal pole have distinct sensory cortical inputs andmay be functionally distinct; this is also supported byseveral other studies (Galaburda and Pandya, 1983; Ci-polloni and Pandya, 1989; Webster et al., 1991; Suzukiand Amaral, 1994; Saleem and Tanaka, 1996). That is, theventral part of temporal pole receives visual inputs fromthe inferior temporal cortex, whereas the dorsal part re-ceives auditory inputs from the superior temporal cortex.

In this study, we have examined whether these distinctportions of the temporal pole are differentially connectedwith the two prefrontal networks. The results indicatethat the medial and orbital networks are interconnectedwith dorsal and ventral parts of the temporal pole, respec-tively.

MATERIALS AND METHODS

Animals

Nine macaque monkeys (Macaca fascicularis) were usedin this study. In addition, a number of cases with injec-tions in the OMPFC, which had been prepared and used in

previous studies (Carmichael and Price, 1995a,b, 1996; Anet al., 1998; Ongur et al., 1998; Ferry et al., 2000), werere-examined and analyzed in relation to the temporal pole.All animal protocols were reviewed and approved by theAnimal Studies Committee of Washington University.

Injections

Prior to surgery, each monkey was anesthetized (seebelow) and placed in a magnetic resonance imaging (MRI)-compatible stereotaxic frame. An MRI scan (1.5T or 3Tscanner, T-1 MPRAGE image with 1.0 or 0.7 mm voxels)was then obtained with the animal’s head aligned with thestereotaxic axes. Stereotaxic coordinates for each desiredinjection site that were specific for each animal were mea-sured from the MRI images and coordinated with the atlasof Szabo and Cowan (1984).

For surgery and the MRI scan, anesthesia was inducedby injection of ketamine (10 mg/kg, i.m.) and xylazine(0.67 mg/kg, i.m.). The animals were then placed in astereotaxic apparatus, and surgical anesthesia was con-tinued with a gaseous mixture of oxygen, nitrous oxide,and halothane. After surgery, a long-lasting analgesic (bu-prenorphine, 0.1 mg/kg, i.m.) was given as the animal wasbrought out of anesthesia.

Burr holes were made in the skull at the sites indicatedby the stereotaxic analysis. A tungsten electrode was in-serted along the expected injection track for electrophys-iological recording of spontaneous, multiunit activity. Thisallowed the determination of the coordinates of structurallandmarks such as the boundaries between gray andwhite matter, the position of sulci, and the bottom of thebrain. The recordings made it possible to refine the ste-reotaxic coordinates determined from the MRI scans, es-pecially in the vertical axis. Several retrograde tracers(Fast Blue [FB, Sigma, St. Louis, MO], Diamidino Yellow[DY, Sigma], and cholera toxin subunit B [Ctb, List Bio-logical, Inc.]) and anterograde tracers (biotinylated dex-tran amine [BDA, Molecular Probes, Eugene, OR]) andbidirectional tracers (Fluoro Ruby [FR], Lucifer Yellow[LY], and Alexa Fluor 488 [green, FG] coupled to dextranamine [Molecular Probes]) were injected in each animal.The injections were made through micropipettes with anair pressure system that applied 25-msec. air pulses to thepipette. The volume of injection was calculated by moni-toring the meniscus level of the micropipette with a cali-brated reticule in the dissecting microscope. The volume oftracers injected varied between 300 and 1,200 nl, depend-ing on the sensitivity of tracers. To avoid spread of tracerinto areas along the pipette track, the micropipette wasleft in place for 30 minutes after the injection was fin-ished. With this procedure, there was little spread oftracer into the overlying cortex or white matter.

Perfusions and tissue processing

After a survival period of 2 weeks, the animals wereanesthetized with ketamine (10 mg/kg, i.m.), followed bysodium pentobarbital (25–30 mg/kg i.v. or i.m.). When theanimals were deeply anesthetized, they were perfusedtranscardially with phosphate-buffered saline and a se-quence of 4% paraformaldehyde solutions, first at pH 6.5,then at pH 9.5 (Carmichael and Price, 1994), and finally atpH 9.5 with 10% sucrose. The brain was removed andtransferred through 10, 20, and 30% sucrose solutions inphosphate buffer at 4°C.

Abbreviations

BDA biotinylated dextran amineCtb cholera toxin subunit BDY Diamidino yellowFB Fast blueFR Fluoro rubyG gustatory cortexIai intermediate agranular insular areaIal lateral agranular insular areaIam medial agranular insular areaIapm posteromedial agranular insular areaLY Lucifer yellowOMPFC orbital and medial prefrontal cortexPrCO precentral opercular areaSTG superior temporal gyrusSTS superior temporal sulcusTEad dorsal subregion of anterior area TETEav ventral subregion of anterior area TETEpd dorsal subregion of posterior area TETEpv ventral subregion of posterior area TETGa agranular part of the temporal poleTGdd dysgranular part of the dorsal temporal poleTGdg granular part of the dorsal temporal poleTGsts STS part of the temporal poleTGvd dysgranular part of the ventral temporal poleTGvg granular part of the ventral temporal poleWM white matter

500 H. KONDO ET AL.

After 2 days, the brain was frozen in dry ice and isopen-tane, and several alternating series of coronal sectionswere cut at 50 �m thickness on a freezing microtome. Oneseries was processed for each tracer. The fluorescent trac-ers FB, DY, and FG were analyzed from unstainedsections. Tracers Ctb, FR, and LY were processed immu-nohistochemically with an avidin-biotin-horseradish per-oxidase technique; BDA was processed directly with theavidin-biotin-peroxidase method (Carmichael et al., 1994;Haber et al., 2000). Additional series of sections wereprocessed with the Nissl, acetylcholinesterase (AChE),and myelin (Gallyas) stains, or immunohistochemicallyfor parvalbumin and a neurofilament epitope (with anti-body SMI-32).

Method of analysis

The location and the extent of each injection and thedistribution of labeled cells and varicosities were plottedfrom the histological sections with a microscope digitizersystem that has encoders attached to the microscope stageand is interfaced with a personal computer (AccuStage,Shoreview, MN). Cortical boundaries and other land-marks were added to these plots by camera lucida draw-ings of adjacent Nissl-, parvalbumin-, AchE-, and myelin-stained sections. With the retrograde tracers, each labeledcell was plotted as a single point. With the anterogradetracers, varicosities along the labeled axons were plotted.The subdivision of the OMPFC defined by Carmichael andPrice (1994) on the basis of multiple staining methods wasused to define the architectonic areas in the prefrontalcortex (Fig. 1).

Unfolded maps of the prefrontal cortex were prepared ina similar manner as described previously (Carmichael andPrice, 1994). Briefly, lines were drawn through layer IV, orthe boundary between layer III and V, in serial coronalsections. These lines were “cut” at the depth of the prin-cipal sulcus and then “pulled out” to straight lines andaligned to construct unfolded maps. A separate unfoldedmap was constructed for each brain. The distribution anddensity of retrogradely labeled cells or anterogradely la-beled axonal varicosities were plotted directly onto un-folded maps from the plots of coronal sections made withthe microscope digitizer system. For retrograde tracingexperiments, the density of labeled cells was representedby four different circle sizes. The largest circle representsmore than 17 cells in a column 0.83 mm wide through alllayers, the second largest circle between 8 and 16 cells, thethird largest between 3 and 7 cells, and the smallest circleindicates either 1 or 2 cells. For anterograde tracing ex-periments, the largest circle represents more than 100labeled axonal varicosities in a column 0.83 mm wide, thesecond largest circle between 30 and 99 varicosities, thethird circle between 6 and 29 varicosities, and the smallestcircle between 1 and 5 varicosities.

The relative density of labeled cells and varicosities wasquantified with a customized computer program thatcounted points within designated and outlined areas onthe section maps. Because of inherent differences betweencases in factors such as the size and efficacy of the injec-tions, the numbers were used only for analysis of therelative pattern of labeling within each brain. The densityin each area was normalized as a ratio of the highest

Fig. 1. The architectonic subdivisions of the orbital and medial prefrontal cortex in monkeys. Theorbital surface (right) and medial surface (left) of the OMPFC. The medial prefrontal network is shownby dark gray shading, and the areas of the orbital network are unshaded. The light gray areas areconnected with both networks.

501TEMPORAL POLE CONNECTIONS WITH THE OMPFC

density of labeled cells or varicosities for that brain andconverted to a one to three plus system (Tables 2–5).Three plus indicates a density ratio between 0.5 and 1compared with the maximum density in the same case,two plus between 0.2 and 0.5, and one plus between 0.05and 0.2. Very weak labeling (below 0.05) was not repre-sented in the tables. Because cases with very little labelcan be over-represented with this system, the maximumlabels in all cases in each table were compared, and thecases in the lowest quartile were restricted to one and twoplus indications.

RESULTS

Cytoarchitecture

In this study, we used terminology for the temporal polesimilar to that used by Moran et al. (1987) and Carmichaeland Price (1995a), with further modifications to fit theexperimental observations (Table 1). The temporal polewas designated area TG, following the commonly usedterminology of von Bonin and Bailey (1947), and wassubdivided into six regions: granular and dysgranular ar-

eas in the dorsal temporal pole (TGdg and TGdd, respec-tively), granular and dysgranular areas in the ventraltemporal pole (TGvg and TGvd, respectively), a granulararea around the rostral tip of the superior temporal sulcus(TGsts), and an agranular area on the medial side of thetemporal pole (TGa) (Fig. 2).

TGsts is the most well-developed cortical area, with adense, well-defined layer IV in Nissl sections (Figs. 2A,3D). There is a prominent layer II, and layer III is subdi-vided, with large pyramidal cells in the deeper portion(Fig. 3D). In parvalbumin sections, staining in layer IV isdenser and more sharply differentiated in TGsts than inother subregions of temporal pole (Fig. 2B). In SMI-32-stained sections, TGsts is characterized by prominentstaining of layer III pyramidal cells, in addition to thestaining in layer V that is seen throughout temporal pole(Fig. 2C). Within TGsts, three regions can be distin-guished in the dorsal bank, the fundus and ventral bank ofthe superior temporal sulcus. The fundal part can be dis-tinguished from the dorsal and ventral parts by its lessdense layer III in Nissl-stained sections.

TGdg is located dorsal to TGsts and in Nissl sections hasa less sharply delimited granular layer IV and a lessclearly subdivided layer III (Figs. 2A, 3A). Parvalbuminstaining in layer IV is also weaker and more diffuse inTGdg than TGsts (Fig. 2B). There is strong staining withSMI-32 of pyramidal cells in layer V and some cells inlayer III, although the layer III staining is less than inTGsts (Fig. 2C).

Medial to TGdg, TGdd has a thin layer IV and a lessprominent layer II (Fig. 3B). Parvalbumin staining isweaker in most of TGdd than TGdg. The caudodorsal partof TGdd is distinguished by a dense band of parvalbumin

Fig. 2. Photographs of coronal sections of temporal pole, stainedwith the Nissl method (A) or immunohistochemically with anti-parvalbumin (B) and SMI-32 (C). The arrows indicate areal bound-aries. The lines at the gray-white matter border indicate borders

between the dorsal, fundal, and ventral subdivisions within TGsts,and the border of the caudodorsal part of TGdd (see text). Scale bar �1 mm.

TABLE 1. Comparison of Terminology Used in Present Study With OtherPrevious Architectonic Descriptions of the Temporal Pole

Architectonicgranularity

Moran et al.,1987

Gower,1989

Carmichael and Price,1995a

Presentstudy

Agranuular TPa-p TPpAll TPag TGaDysgranular TPdg TPproD TPdgd TGdd

TPproV TPdgv TGvdGranular TPg TS TPg TGdg

STS TGstsTE TGvg

502 H. KONDO ET AL.

Fig. 3. Coronal sections of each area within the temporal pole, stained with the Nissl method. Scalebar � 0.25 mm.


staining in layer IV (Fig. 2B), but subdivision of the areadoes not seem warranted at this time.

Like TGdg, TGvg is less granular than TGsts in Nissl-stained sections; layer III is not clearly subdivided (Fig.3E). In parvalbumin-stained sections, layer IV is also lesssharply defined (Fig. 2B). There is very strong stainingwith SMI-32 in layers V and VI and some staining in layerIII (Fig. 2C). In TGvd, layer IV is only slightly granularand only weakly and diffusely stained for parvalbumin(Figs. 2B, 3F).

TGa is located in the medial part of the temporal polebetween TGdd and TGvd, rostral to and slightly overlap-ping the periamygdaloid cortex. Layer IV is absent andparvalbumin staining is very weak (Figs. 2B, 3C). There isno sublamination in layer III, and layer V is poorly differ-entiated from layer VI (Fig. 3C).

The borders between the temporal pole and more caudaltemporal cortical areas are not sharply defined. However,the cortical layers, and parvalbumin staining in layer IV,are generally less differentiated in the temporal pole thanin areas of the superior temporal gyrus (STG), superiortemporal sulcus (STS), or inferior temporal cortex (areaTE). Perhaps the clearest distinction is between areasTGa and TGvd and the immediately caudal perirhinalareas 35 and 36. Area 35 is more obviously laminated thanTGa, with a cell-sparse layer between superficial and deepcellular layers. Compared with TGvd, area 36 also ap-pears to be more laminated, with a denser layer II andbetter developed layer V. Areas 35 and 36 also stand out inparvalbumin-stained sections, due to their more intenseand distinctly laminated patterns of staining. This changeoccurs approximately at the coronal level at which thecortical white matter is continuous between the frontaland temporal lobes, along with the appearance of theentorhinal cortex. As a working distinction, therefore, thislevel was taken as the caudal border of the temporal pole.

In the OMPFC, the architectonic maps of Carmichaeland Price (1994) were used. As in previous studies from

this lab, the areas of the OMPFC were divided into twonetworks (Fig. 1; Carmichael and Price, 1996; Ongur andPrice, 2000). The medial network includes all of the areason the medial wall and gyrus rectus (areas 10m, 10o, 11m,14c, 14r, 24a, 24b, 25, and 32), plus area Iai in the lateralpart of the orbital cortex. Areas 13a and 12o in the orbitalcortex are also generally associated with the medial net-work, although they have connections to both networks.The orbital network includes the other areas on the orbitalsurface and ventrolateral convexity of the frontal lobe(areas 11l, 12l, 12m, 12r, 13b, 13l, 13m, Ial, Iam, Iapm,and Iapl). It should be noted that some areas (e.g., 14c or13b), which are defined as belonging to one network be-cause of their major connections, may also have lesserconnections to the other network.

Projections from the OMPFC to thetemporal pole

Retrograde tracer injections in the temporal pole.

Seven injections of retrograde tracers, including FB, DY,Ctb, and FR, were made into specific areas of the temporalpole (Table 2). Except as noted below, all the injectionsinvolved both supra- and infragranular layers of the cor-tex. Retrogradely labeled cells were observed in theOMPFC, with very little or no labeling in the dorsolateralprefrontal cortex (areas 8, 9, and 46). Injections into thedorsal and ventral parts of the temporal pole produceddistinct patterns of labeled cells into different parts of theOMPFC.

Retrograde tracer injections in TGdg and TGdd. Tworetrograde tracer injections (FB in case OM49 and Ctb inOM51) were made in TGdg and TGdd. In both cases, manylabeled cells were found in the medial network, includingareas 10m, 14c, 14r, 25, and 32 in the medial wall andareas 11m, 13a, and Iai in the orbital surface (Figs. 4, 6A,7A; Table 2). The highest density of labeled cells was inthe more caudal part of the medial network, including thecaudal part of area 10m and areas 25 and Iai in both cases,

TABLE 2. Pattern of Labeled Neurons in the OMPFC After Injections of Retrograde Tracers in the Temporal Pole1

TGdd TGdg TGsts TGsts TGsts TGvg2 TGvd2

OM51 OM49 OM52 OM55 OM58 OM54 OM55Ctb FB FB FR DY FB FB

Medial Network10o � �10m �� 11m � ��14c � �� 14r �� 24a/b �32 �� 25 �� Iai ��

Medial/Orbital Network12o � �� 13a � ��

Orbital Network111 �� 121 �� 12m �� 12r �� 13b �� 131 � �� 13m �� Ial �� Iam � �� Iapm ��

1See Materials and Methods for an explanation of the � to �� rating system. The three lines in the heading are the area, the case number and the tracer used. For abbreviations,see list.2These brains had low absolute density of retrogradely labeled cells and were restricted to a � to �� scale (see Materials and Methods).

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Fig. 4. The distribution of cells in the OMPFC that were retro-gradely labeled from an injection of FB into TGdg (OM49). Each dotrepresents one retrogradely labeled cell. The lines on the lateral viewof the brain illustrate the levels of the coronal sections. The dashedlines show layer IV or the border between layers III and V. Note that

most cells projecting to TGdg are located in the medial network areas,including areas 10m, 11m, 13a, 14c/14r, 25, 32, and Iai. There are veryfew labeled cells in the orbital network areas. A dense cluster of cellsis found in Iai, part of medial network, but not in surrounding orbitalnetwork areas. Scale bar � 5 mm.


and areas 14c and 14r in OM49. There were almost nolabeled cells in the orbital network. The restricted labelingin Iai in OM49, with little or no labeling in the surround-ing orbital network areas, is particularly striking (Fig. 4,sections 9–11). In case OM51, labeled cells were alsofound in areas 12o and Iapm.

Retrograde tracer injections in TGsts. Two retrogradetracers and one bidirectional tracer were injected in TGsts(cases OM52, OM55, and OM58). In all three cases, manylabeled cells were found in areas of the orbital networkand in areas associated with both networks. In caseOM58, a DY injection was made into the supragranularlayers of TGsts (Figs. 5, 6B). The injection was centered inthe fundal and ventral parts of TGsts, with a slight spreadinto the dorsal part. Retrogradely labeled cells were con-centrated in orbital network areas 11l, 12l, 12r, 13b, 13l,13m, Ial, Iam, and Iapm. In addition, there were labeledcells in ventromedial areas 13a, 14c, and the lateral area12o, which have connections with both networks (Fig. 5,Table 2). There were few if any labeled cells in core medialnetwork areas 10m, 11m, 25, 32, and Iai.

Another injection of the bidirectional tracer FR into theventral and fundal parts of TGsts in OM55 produced asimilar pattern of retrogradely labeled cells (Table 2). Aninjection of FB that also involved the dorsal part of TGstsin OM52, however, labeled more cells in areas of themedial network (Table 2).

Retrograde tracer injections in TGvg and TGvd. Incase OM55, FB was injected into the superficial layers ofTGvd (Fig. 7B). The injection was relatively small, andthere were fewer labeled cells in the OMPFC than in thecases described above. On the other hand, substantialnumbers of labeled cells were present in more caudaltemporal cortical areas and in the pulvinar, indicatingthat the light labeling in the OMPFC is not due to failureof transport. Labeled cells were found mainly in areas ofthe orbital network, including areas 12m, 13b, 13l, 13m,Ial, Iam, and, Iapm, whereas there were almost no labeledcells in areas of the medial network, except in area 14c(Figs. 6C, 7B; Table 2). The greatest number of labeledcells was found in areas 13m, Ial, and Iapm in the caudalpart of the orbital network. In case OM54, an injection ofFB was made in TGvg. This produced a very comparablenumber and distribution of labeled cells in the OMPFC(Table 2).

Anterograde tracer injections in the OMPFC. An-terograde tracers were injected into restricted areas of theOMPFC in 17 cases, involving both supra- and infra-granular layers (Table 3). In all but one case, antero-gradely labeled axons and axonal varicosities were ob-served in the temporal pole. Because most axonalvaricosities, at least, represent synaptic boutons, the dis-tribution of varicosities provides an excellent representa-tion of the synaptic component of each projection. Tracerinjections into the orbital and medial networks produceddistinct patterns of distribution of anterogradely labeledterminals in the ventral and dorsal part of the temporalpole.

Anterograde tracer injections in the medial networkareas. Eleven injections of anterograde tracers weremade into the medial network, plus one injection thatoverlapped areas 12o and 13l (Table 3). Of these, eightinjections were made in areas 10m, 10o, 11m, 14r, 25, and32 on the medial wall and frontal pole. Injections in area25 (OM32 and OM49) and the caudal part of area 10m

(OM39) produced a dense plexus of labeled axons andaxonal varicosities in TGdd, as well as in TGdg and TGa(Figs. 8A, 9C; Table 3). There were also some labeledaxons in the dorsal part of TGsts. More rostral injectionsproduced a smaller absolute number of labeled varicosi-ties in TGdg and TGdd and none in TGa. In all these cases,there was almost no axonal label in TGvg and TGvd.Axonal label was not found in the temporal pole after aninjection in area 24b (not illustrated).

Three BDA injections were made in the medial networkareas Iai and 12o in the lateral orbital cortex; two of theseoverlapped slightly into area 13l and 13m. These injec-tions produced moderate numbers of labeled axon varicos-ities in TGdg and TGdd and a few labeled axons andvaricosities in TGa and the dorsal part of TGsts (Fig. 8B;Table 3). The injection in area 12o produced a denserconcentration of labeled terminals in TGsts, especially inits dorsal part. In all cases, there was little or no label inTGvg and TGvd.

Anterograde tracer injections in the orbital networkareas. Three anterograde tracer injections were made inareas 11l, 13l, and 13m of the orbital network (Table 3). Inthese cases (OM27, OM42, and OM53), there were sub-stantial numbers of labeled axons and axonal varicositiesin the fundal and ventral parts of TGsts (Figs. 8C,D; 9D;Table 3). A smaller number of labeled axons were alsofound in areas TGvg and TGvd. The relatively low densityof axonal label in these areas fits well with the smallnumber of retrogradely labeled cells seen after injectionsof retrograde axonal tracers into TGvd (see OM55, FBinjection, Figs. 6C, 7B) and TGvg (Table 2). A similarpattern was seen in two other experiments with injectionsin areas 12m and 12r (not illustrated), at the lateral edgeof the orbital cortex, although the absolute number oflabeled axons in these cases was very low. In all casesthere were virtually no labeled axons in TGdg and TGdd.

Projections from the temporal poleto the OMPFC

Anterograde tracer injections in the temporal pole.

Five injections of anterograde tracers (BDA and FR) weremade into restricted areas of the temporal pole in fourmonkeys (Table 4). The injections all involved both supra-and infragranular layers. In all cases, anterogradely la-beled axons and axonal varicosities were observed in theOMPFC, but very few in the dorsolateral prefrontal cor-tex. After injections in the ventral and dorsal parts of thetemporal pole, distinct patterns of label were found in theorbital and medial prefrontal networks, respectively.

Anterograde tracer injections in TGdg and TGdd. Incase OM53, BDA and FR injections were made into TGddand TGdg, respectively (Figs. 7C, 9A, 10, 12A). The injec-tions were located close to each other, on either side of theboundary between TGdd and TGdg. The distribution oflabeled axons in the OMPFC was similar in both cases.Many labeled axons and axonal varicosities were observedin the medial network, including areas 10m, 14c, 14r, 25,and 32 on the medial wall and frontal pole, and 13a andIai on the orbital surface (Fig. 10; Table 4). Few if anylabeled axons were present in the areas of the orbitalnetwork, with the exception of area Iapm. In both casesthere was a striking plexus of labeled axons in area Iai,but not in surrounding areas (Figs. 9A, 10, sections 8–10),similar to the pattern of labeled cells seen with retrogradetracers injected into the dorsal part of the temporal pole.

506 H. KONDO ET AL.

Fig. 5. The distribution of retrogradely labeled cells in the OMPFC following an injection of DY intoTGsts (OM58). Conventions as in Figure 4. Note that most cells projecting to TGsts are located in areasof orbital network, which is in contrast with the labeling in Figure 4. In contrast to Figure 4, there arevery few cells in Iai, but many cells in surrounding orbital network areas. Scale bar � 5 mm.


Fig. 6. Unfolded map illustrating the distribution of retrogradelylabeled cells in the OMPFC following injections of FB into TGdg(OM49), DY into TGsts (OM58), and FB into TGvd (OM55) (comparewith Figs. 4 and 5). The circles represent the number of cells in acolumn 0.83 mm wide across all layers of the cortex. The largestcircles represent more than 17 cells/column, the second largest circlesbetween 8 and 16 cells, the third largest circles between 3 and 7 cells,

and the smallest circles 1 or 2 cells. Note the complementary distri-bution of labeled cells following the injection in TGdg (A) comparedwith that following the injections in TGsts and TGvd (B,C). Thedashed lines represent the ventrolateral and dorsomedial convexitiesof the frontal lobe. The coronal sections that were used to constructthe unfolded map are shown on the left (see Materials and Methods).Scale bar � 5 mm.

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Fig. 7. Additional cases showing the distribution of retrogradelylabeled cells or anterograde labeled axonal varicosities in the OMPFCfollowing injections into the dorsal or ventral parts of the temporalpole. Note that the label is located in the medial network areas 10m,

25, 32, and Iai following the dorsal injections (A,C), whereas orbitalnetwork areas 13m, Ial, Iam, and Iapm are labeled following theventral injections (B,D). Scale bar � 5 mm.

Anterograde tracer injections in TGsts. The patterns oflabel observed in cases with injections into the ventralpart of the temporal pole were complementary to those inthe cases with dorsal temporal pole injections. In caseOM55 the injection of FR in the fundal and ventral partsof TGsts labeled axons and varicosities in areas of theorbital network, including areas 11l, 13b, 13l, 13m, Ial,Iam, and Iapm and also in areas 12o and 14c (Figs. 9B, 11,12B; Table 4). There were very few if any labeled axons inother areas of the medial network.

Anterograde tracer injections in TGvg. In case OM58,an injection of BDA was made in TGvg (Fig. 7D). CaseOM56 had a similar but slightly more caudal injection inTGvg. Although the density of labeled axons and axonalvaricosities was smaller than with the TGsts injection, inboth cases the label was distributed primarily in the or-bital network, especially to areas 13l, 13m (in OM58), Ial,and Iapm (Figs. 7D, 12C; Table 4).

Retrograde tracer injections in the OMPFC. Retro-grade tracers, including FB, DY, and Ctb, were injectedinto restricted areas of the OMPFC in 20 cases (Table 5),almost always involving both supra- and infragranularlayers. Tracer injections into subregions in the orbital andmedial network produced distinct patterns of distributionof retrogradely labeled cells in the ventral and dorsal partof the temporal pole.

Retrograde tracer injections in the medial networkareas. Nine injections were made in the medial networkareas 10m, 10o, 11m, 14r, 24b, 25, and 32 on the medialwall, gyrus rectus, and frontal pole, and two injectionswere made in the medial/orbital area 12o in the orbitalcortex (Table 5). Substantial numbers of cells were labeledin the dorsal part of the temporal pole, including TGdgand TGdd, from all these injections (Figs. 13A,B; Table 5).Cells were also labeled in TGa, especially in cases withinjections in area 25 and the caudal part of area 10m (OM6 and OM53). In almost all the cases, there were no morethan scattered labeled cells in the ventral temporal poleareas TGsts, TGvg, and TGvd. The main exceptions werethe injections in the rostral areas 10o and 11m, whichlabeled some cells in the dorsal part of TGsts. Almost nolabeled cells were found in the temporal pole after aninjection in area 24b (not illustrated).

Retrograde tracer injections in the orbital network areas.Nine injections of retrograde tracers were made in theorbital network areas, three in the agranular insular ar-

eas Iam, Iapm, and Ial, four in the central areas 13b and13m, and two in the more rostral area 11l, (Table 5). Thepattern of distribution of labeled cells was similar in al-most all these cases. Many labeled cells were distributedin the fundal and ventral parts of TGsts and in TGvd, withmoderate numbers of cells in TGvg (Fig. 13C,D; Table 5).Few if any cells were labeled in the dorsal areas TGdg andTGdd except in one of the two cases with an injection inarea 11l. This pattern was not seen with the other area 11linjection, and it may have been due to slight involvementof area 11m in the injection. A few cells were also labeledin TGa in many of the cases, especially OM8, with aninjection in area Iam (Fig. 13D, Table 5).

Intrinsic and other connections of thetemporal pole

Although this paper is focused on the connections be-tween the two networks of the OMPFC and the temporalpole, distinct patterns of connections were also foundwithin the temporal pole, and between the temporal poleand more caudal temporal cortical or subcortical areas.These are relevant to the interpretation of the connectionswith the OMPFC and will be described briefly.

Tracer injections in the dorsal or ventral parts of thetemporal pole produce label primarily within the sameregion of the temporal pole and avoid the other. For ex-ample, injections of FB and Ctb into TGdg and TGdd(cases OM49 and OM51, respectively) labeled cells in ar-eas TGdg, TGdd, TGa, and dorsal TGsts but not in TGvgand TGvd (Fig. 14A,B). Similarly, after the BDA injectioninto TGdd in case OM53, anterogradely labeled axonalvaricosities were largely restricted to TGdd, TGdg, andTGa, with a few varicosities in dorsal TGsts (Fig. 15A). Incontrast, an injection of FB in TGvd (case OM55) labeledcells only in TGvd, TGvg, and the ventral parts of TGa andTGsts (Fig. 14D). Anterogradely labeled axons with ap-proximately the same distribution were found in the ven-tral temporal pole areas after a BDA injection in TGvg(case OM58; Fig. 15B). Injections into TGsts (e.g., casesOM55 or OM58) labeled cells or axons primarily in theventral part of the temporal pole, but some label was alsofound in dorsal areas (Fig. 14C).

Temporal and insular cortical inputs also showed adorsal-ventral distinction in the temporal pole. Followingdorsal injections in TGdg and TGdd, many labeled cellswere observed in the rostral part of the superior temporal

TABLE 3. Pattern of Labeled Axonal Varicosities in the Temporal Pole After Injections of Anterograde Tracers in the OMPFC

Areas Case # Tracer TGdd TGdg TGa TGsts TGvd TGvg

Medial Network10m(r)1 OM36 BDA � ��10m(c) OM39 BDA �� 10o1 OM38 BDA �� 11m OM40 BDA � ��14r OM18 FR �� 25 OM49 BDA �� 25 OM32 BDA �� 32/10m OM35 BDA �� Iai1 MN12 BDA � ��Iai OM28 BDA ��

Medial/Orbital Network12o/131 OM31 BDA � � ��

Orbital Network111 OM27 BDA �� 131 OM42 BDA �� 13b OM53 FG � ��

1These brains had low absolute density of retrogradely labeled varicosities and were restricted to a � to �� scale (see Materials and Methods). r, rostral; c, caudal.

510 H. KONDO ET AL.

Fig. 8. The distribution of anterograde labeled axonal varicosities in the temporal pole following BDAinjections into the medial (A,B) or orbital (C,D) prefrontal networks. Note that the label is located inTGdg, TGdd, and TGa with injections into the medial network, whereas the label is located in TGsts,TGvg, and TGvd with injections into the orbital network. Scale bar � 5 mm.

Fig. 9. Photomicrographs of anterograde axonal labeling in theOMPFC and the temporal pole. A: BDA injection into TGdd in caseOM53, with anterograde label in area Iai. B: FR injection into TGstsin case OM55, with anterograde label in areas Iapm and Ial. Note the

complementary pattern of labeling between these cases. C: BDA in-jection into area 25 in case OM32, showing label in TGdd, TGdg, andTGa. D: BDA injection into area 13l in case OM42 with label in TGsts.Scale bar � 1 mm in B (also applies to A); 2 mm in D (also applies to C).

gyrus and the adjacent dorsal bank of the superior tem-poral sulcus. Cells were also labeled in the parainsularcortex and caudal agranular insular cortex, as well as inthe entorhinal cortex (area 28) and in the parahippocam-pal cortex (areas TF and TH; Fig. 14A,B). Almost nolabeled cells were observed, however, in the inferior tem-poral cortex (area TE), or in the perirhinal cortex (areas 35and 36). In contrast, a ventral injection into TGvd (caseOM55) produced many labeled cells in the anterior part ofthe inferior temporal cortex, especially the ventral part ofanterior TE (area TEav), the ventral bank of STS, and theperirhinal cortex (Fig. 14D). In case OM58, an injection ofDY into TGsts produced a somewhat intermediate pat-tern, with many labeled cells in the deep parts of therostral STS (including dorsal and ventral banks), TEav,and the perirhinal cortex (Fig. 14C). There were also manylabeled cells in the dysgranular and caudal agranularinsular areas. With both of these more ventral injections,there were relatively few labeled cells in areas TF and TH.

Anterograde tracer experiments with injections into thetemporal pole demonstrated reciprocal projections. Fol-lowing a BDA injection in TGdd (OM53), many labeledaxons and axonal varicosities were found in the rostralpart of the superior temporal gyrus (Fig. 15A). Moderateaxonal labeling was also found in the caudal agranularinsula and parahippocampal areas TF and TH. A BDAinjection in TGvg (case OM58) labeled axonal varicositiesin the anterior part of the TE, the ventral bank and fundusof STS, and the perirhinal cortex (Fig. 15B).

We also observed both retrograde and anterograde la-beling in the amygdala, claustrum (Figs. 14, 15), andpulvinar and anterograde labeling in the striatum (Figs.10, 11) following temporal pole injections. These projec-tions are beyond the scope of the current study and areconsistent with previous reports (Herzog and Van Hoesen,1976; Van Hoesen et al., 1981; Amaral and Price, 1984;

Markowitsch et al., 1985; Moran et al., 1987; Stefanacci etal., 1996).

DISCUSSION

The main finding is that the orbital and medial prefron-tal networks have distinct connections with the ventraland dorsal parts of the temporal pole (Fig. 16). The dorsalareas TGdg and TGdd have strong bidirectional connec-tions with the medial network, including medial areas10m, 13a, 14r, 14c, 25, and 32, and the lateral orbitalareas Iai and 12o. The heaviest projections are from thecaudal part of this network. The connections with area Iaiare particularly striking, because they are not shared byadjacent orbital network areas Ial and Iam. In the ventraltemporal pole, area TGsts has strong bidirectional connec-tions with the areas of the orbital network, includingareas 11l, 13b, 13l, 13m, Ial, Iam, and Iapm. The moreventral areas TGvd and TGvg are also reciprocally con-nected with the orbital network, although these connec-tions are less strong than those from TGsts. Area TGa, atthe junction of the dorsal and ventral regions, has connec-tions with areas of both networks, although the strongestconnections are with the medial prefrontal area 25. Inaddition, the intrinsic connections of the dorsal and ven-tral regions of the temporal pole are largely restricted toeach region.

Architectonic subdivision of thetemporal pole

Brodmann (1909) labeled the temporal pole area 38,whereas von Economo and Koskinas (1925) and later vonBonin and Bailey (1947) referred to it as area TG. Webased our analysis on the more recent descriptions byMoran et al. (1987) and Carmichael and Price (1995a)(Table 1). Moran et al. (1987) defined agranular, dys-granular, and granular portions of the temporal pole. Car-michael and Price (1995a) used a similar subdivision, butthey added the additional distinction of dorsal and ventralparts of the dysgranular temporal pole, divided by theagranular part. Because the region around the rostral tipof the STS was found to have structural and connectionaldistinctions from the granular cortex dorsal and ventral toit, we recognized it here as an addition area, TGsts. Thisseparated TGdg from TGvg, and this separation was con-firmed by the distinct connections of the dorsal and ven-tral regions of the temporal pole. The subdivisions used inthis study are also very consistent with those of Gower(1989).

Although we believe that the areas defined in this studyare justified on both architectonic and connectionalgrounds, it is important to note that other studies have notalways recognized the temporal pole as a distinct archi-tectonic region. Pandya and his coworkers (Galaburda andPandya, 1983; Cipolloni and Pandya, 1989) extended theirtemporal areas TS1 and TS2 into the temporal pole, in-cluding areas TGdg and TGdd, as described here. Otherparts of the temporal pole are included in their areas pAll(periallocortex) and Pro (proisocortex), although these alsoextend into the posterior orbital cortex. Area pAll includesarea TGa, whereas area Pro includes areas TGdd andTGvd, as well as most of area TGsts. In another scheme,Amaral and his colleagues included the temporal polewithin the perirhinal cortex (areas 35 and 36; Insausti et

TABLE 4. Pattern of Labeled Axonal Varicosities in the OMPFC AfterInjections of Anterograde Tracers in the Temporal Pole1

TGdd TGdg TGsts TGvg TGvg2

OM53 OM53 OM55 OM56 OM58BDA FR FR BDA BDA

Medial Network10m �� 10o11m �14c �� 14r �� 24a/b �25 �� 32 �� Iai ��

Medial/Orbital Network12o � �� 13a ��

Orbital Network111 ��121 � �12m �12r13b � �131 � �� 13m �� Ial �� Iam �Iapm ��

1The three lines in the headings are the area, the case number, and the tracer used. Forabbreviations, see list.2This brain had low absolute density of anterogradely labeled varicosities, and wererestricted to a � to �� scale (see Materials and Methods).


Fig. 10. The distribution of anterogradely labeled axonal varicosities in the OMPFC following aninjection of BDA into TGdd (OM53). Note the dense labeling in the medial network, including areas 10m,14c, 14r, 25, 32, and Iai. Scale bar � 5 mm.

514 H. KONDO ET AL.

Fig. 11. The distribution of anterogradely labeled axonal varicosities in the OMPFC by an injectionof FR into TGsts (OM55). Note the dense labeling located in the orbital network, including areas 11l,13m, Ial, and Iapm. Some labeled axons are also present in areas 12o and 14c that also have connectionswith both medial and orbital networks. Scale bar � 5 mm.


Fig. 12. Unfolded map illustrating the distribution of antero-gradely labeled axonal varicosities in the OMPFC following injectionof BDA into TGdd (OM53), FR into TGsts (OM55), and BDA into TGvg(OM58) (compare with Figs. 10 and 11). The largest circles representmore than 100 axonal varicosities in a column 0.83 mm wide through

all layers, the second largest circles between 30 and 99 axonal vari-cosities, the third largest circles 6 to 29 varicosities, and the smallestcircles 1 to 5 varicosities. Note the complementary distribution oflabel between the TGdd case (A) and the TGsts and TGvg cases (B,C).Scale bar � 5 mm.

516 H. KONDO ET AL.

al., 1987; Suzuki and Amaral, 1994). In their description,the temporal pole is largely divided between area 36d(dorsally), and the rostral part of their area 36r (ventrally).

Temporal polar connections withthe OMPFC

Although previous studies have not related the tempo-ral pole to the orbital and medial prefrontal networks,several studies have demonstrated connections betweenthe temporal pole and the OMPFC that are in agreementwith the current results (Pandya and Kuypers, 1969;Jones and Powell, 1970; Van Hoesen et al., 1975; Moran etal., 1987; Barbas, 1988, 1993; Petrides and Pandya, 1988;Seltzer and Pandya, 1989; Morecraft et al., 1992; Suzukiand Amaral, 1994; Bachevalier et al., 1997; Barbas et al.,1999; Cavada,et al., 2000; Rempel-Clower and Barbas,2000). Moran et al. (1987) illustrated retrograde tracerinjections in the dorsal temporal pole that labeled cells inareas apparently corresponding to the medial network. Inan earlier paper from this lab, Carmichael and Price(1995a) reported differential connections between the dor-sal and ventral temporal pole and several areas of theOMPFC. These connections were not analyzed in terms ofthe orbital and medial networks at that time, but they arein good agreement with the results reported here. Simi-larly, Barbas and her colleagues have reported severalexperiments with injections in the medial prefrontal cor-tex that preferentially labeled cells in the dorsal temporalpole (Barbas et al., 1999), as well as other experimentswith injections in the orbital cortex that labeled cells inthe ventral temporal pole (Barbas, 1988). Romanski et al.(1999a) also described projections from the dorsal tempo-ral pole to the medial prefrontal cortex.

In addition to these connections with the temporal pole,connections have been demonstrated between the prefron-tal cortex and more caudal temporal areas. Carmichaeland Price (1995b) identified connections from the superiortemporal cortex to the medial network and from the infe-rior temporal cortex to the orbital network. The studies byBarbas et al. (1999) and Romanski et al. (1999a) alsodescribed projections from the superior temporal cortex tothe medial prefrontal cortex. Several papers have pro-posed a rostral-caudal organization in the projection to the

prefrontal cortex as a whole, such that more caudal tem-poral areas project preferentially to dorsolateral prefron-tal areas, whereas the projections from more rostral tem-poral areas are shifted progressively to more ventral andmedial prefrontal areas (Pandya and Yeterian, 1985; Pet-rides and Pandya, 1988; Seltzer and Pandya, 1989; Web-ster et al., 1994; Hackett et al., 1999; Romanski et al.,1999a). Within this general organization, the temporalpole areas represent the most rostral part of the temporalcortex, which projects to the most ventromedial part of thefrontal cortex. Thus, as shown here, the temporal pole isconnected exclusively to the OMPFC, with few if any pro-jections to the dorsolateral prefrontal cortex.

Functional considerations

The function of the temporal pole has usually beenconsidered in relation to the sensory inputs it receivesfrom more caudal parts of the temporal cortex. The dorsaltemporal pole receives inputs from auditory associationareas in the rostral part of the superior temporal cortex(Galaburda and Pandya, 1983, Moran et al., 1987; Cipol-loni and Pandya, 1989; present results). In contrast, theventral temporal pole receives inputs from visual associ-ation areas in the rostral part of the inferior temporalcortex (Moran et al., 1987; Webster et al., 1991; Suzukiand Amaral, 1994; Saleem and Tanaka, 1996; presentresults). The present finding that intrinsic connectionswithin the temporal pole are largely restricted to the dor-sal or ventral parts, with little interaction between them,suggests that the auditory and visual inputs remain seg-regated within the temporal pole and are continued in theseparate connections with the medial and orbital prefron-tal networks.

Although functional studies on the temporal pole havebeen limited, there are several indications that sensoryresponses in the temporal pole are related to specific,complex sensory stimuli. Nakamura et al. (1994) foundvisual responsive neurons in the ventral part of the tem-poral pole (especially in TGsts), but not in the dorsal part.Complex stimuli were more effective than simple stimuli,and the responses were relatively selective for a limitednumber of distinct images. In a subsequent paper theyreported that neurons in the same region appeared to code

TABLE 5. Pattern of Labeled Neurons in the Temporal Pole After Retrograde Tracer Injections in the OMPFC

Areas Case # Tracer TGdd TGdg TGa TGsts TGvd TGvg

Medial Network10m(c) OM53 FB �� 10m(c)/14r OM6 FB �� 10o1 OM19 FB � �� 11m1 OM13 FB � ��11m1 OM13 DY �� 14r OM19 DY �� 25/10m OM53 Ctb �� 321 OM7 DY ��

Medial/Orbital Network12o OM14 FB �� 12o OM7 FB ��

Orbital Network111 OM5 FB �� 111 OM21 DY � � ��13b OM8 FB � �� 13b OM53 DY �� 13m OM5 DY ��13m OM21 FB � �� Ial OM22 FB � �� Iam OM8 DY �� Iapm OM18 DY � ��

1These brains had low absolute density of retrogradely labeled cells and were restricted to a � to �� scale (see Materials and Methods).


Fig. 13. The distribution of retrogradely labeled cells in the temporal pole following injections ofretrograde tracers into medial network areas (A,B) or orbital network areas (C,D). Note that labeled cellsare located in the dorsal temporal pole following injections into the medial network, whereas cells arelocated in the ventral temporal pole with injections into the orbital network. Scale bar � 5 mm.

Fig. 14. Coronal sections illustrating the intrinsic and temporallobe inputs into the temporal pole, labeled by retrograde tracer injec-tions into the dorsal (A,B) or ventral (C,D) temporal pole. In A, C, andD, the injection sites are indicated by solid black areas; the surround-ing blank region and dashed line indicates an area of very densetransported label. See Figure 7A for injection site in OM51 (B). Notethat the intrinsic connections within the temporal pole are largelyrestricted to dorsal or ventral regions. Subregions of the temporal pole

also receive inputs from different temporal cortical areas. Injectionsin TGdg and TGdd labeled cells in the STG, whereas the injection inTGvd labeled cells in anterior TE, the ventral bank of the STS, andthe perirhinal cortex. The injection in TGsts produced label in thedeep part of STS, TEav, and the perirhinal cortex. All the injectionsalso labeled cells in the entorhinal cortex and amygdala. Scale bar �5 mm.


for mnemonic information during a visual recognitionmemory task (Nakamura and Kubota, 1995). Lesions ofthe temporal pole in humans cause deficits in the ability torecognize specific entities, particularly persons (Damasioet al., 1996; Tranel et al., 1997). Positron emission tomog-raphy (PET) studies also indicate that the right temporalpole is activated during discrimination of familiar facesand scenes, suggesting a high degree of sensory specificity(Nakamura et al., 2000; Grabowski et al., 2001).

There have been relatively few physiological studies ofauditory function in the dorsal temporal pole and rostralSTG, but a recent study that used 14C-deoxyglucose im-aging to map areas activated by auditory stimuli identi-fied the dorsal temporal pole and parts of the orbitalcortex as areas where activity could be increased by audi-tory stimuli (Poremba et al., 2003). Based on anatomicalstudies, and physiological recordings in more caudal partsof the STG, it has been proposed that the rostral STG ispart of a “what” auditory pathway, comparable to theinferior temporal visual processing stream (Mishkin et al.,1983; Hackett et al., 1999; Romanski et al., 1999b; Raus-checker and Tian, 2000). The dorsal temporal pole wouldbe involved in this stream at the rostral end of the STGand would presumably represent highly processed infor-mation related to specific auditory stimuli. This idea issupported by a recent PET study by Nakamura et al.(2001) that found activation of the right temporal poleduring discrimination of familiar voices.

In addition to the sensory inputs, the temporal pole hassubstantial interconnections with many limbic structures

in the medial temporal lobe, including the amygdala andthe entorhinal, perirhinal, and parahippocampal cortex(Van Hoesen and Pandya, 1975; Herzog and Van Hoesen,1976; Amaral and Price, 1984; Markowitsch et al., 1985;Moran et al., 1987; Insausti et al., 1987; Suzuki and Ama-ral, 1994; Stefanacci et al., 1996; present results). To-gether with the strong and distinct connections with theorbital and medial networks, these imply that the tempo-ral pole is involved in emotional processing and possiblymemory, as well as sensory mechanisms.

The two prefrontal networks were initially defined onthe basis of preferential corticocortical connections withinthe OMPFC (Carmichael and Price, 1996), but the twonetworks have since been found to have distinct connec-tions to other parts of the brain. The orbital networkreceives inputs from several sensory systems, includingolfactory, taste/visceral, somatosensory, and visual sys-tems (Carmichael et al., 1994; Carmichael and Price,1995b). That constellation of sensory inputs suggests thatfood-related stimuli are especially represented (Ongurand Price, 2000). This is supported by physiological re-cordings in the orbital cortex, which indicate responses tomultimodal stimuli, especially related to food (e.g., Rollsand Baylis, 1994). In addition, however, the orbital cortexappears to code for the rewarding or affective qualities ofstimuli, including expectation of reward (Hikosaka andWatanabe, 2000; Rolls, 2000; Schultz et al., 2000). If, asdiscussed above, the neurons of the ventral temporal poleprocess highly specific visual object information, they

Fig. 15. Coronal sections illustrating intrinsic and temporal cor-tical axonal labeling after injections in the dorsal (A) or ventral (B)temporal pole. As in Figure 14, note that the intrinsic connections arelargely restricted to the dorsal or ventral temporal pole. The dorsal

temporal pole also projects to the STG and area TH, whereas theventral temporal pole projects to anterior TE, the ventral bank of theSTS, and the perirhinal cortex. Both parts of the temporal pole projectto the amygdala. Scale bar � 5 mm.

520 H. KONDO ET AL.

Fig. 16. Summary of connections of the temporal pole with theorbital and medial networks within the OMPFC. The dorsal parts ofthe temporal pole (TGdd and TGdg) are strongly connected withmedial network areas (shown in the dark gray shading) that arelocated in the medial wall and part of the orbital surface. TGsts isstrongly connected with the orbital network areas (shown in white).Other ventral parts of the temporal pole (TGvd and TGvg) have

weak-to-moderate connections with the orbital network areas. Theareas related to both the orbital and medial networks (shown in thelight gray shading) are connected with both the dorsal temporal poleand TGsts. The connections shown here are mostly reciprocal. Thethickness of the lines and the size of the arrowheads indicate thestrength of connections.

would presumably transfer that information to the orbitalnetwork.

The medial network does not receive the same, seem-ingly food-related sensory inputs as the orbital network(Carmichael and Price, 1995b; 1996), but it does havesubstantial outputs to visceral control regions in the hy-pothalamus and periaqueductal gray (An et al., 1998; On-gur et al., 1998; Rempel-Clower and Barbas, 1998). Theorbital network, in comparison, has very few such outputsto visceral control areas. Because of this, it has beensuggested that the medial network is a visceromotor sys-tem (Ongur and Price, 2000).

The functions of the medial network extend beyondsimple visceral control, however. Damasio and his col-leagues have provided evidence that visceral activationevoked from the ventromedial frontal cortex is a criticalfactor in decision making (Bechara et al., 2000). In addi-tion, several functional imaging studies have implicatedthe medial prefrontal cortex in emotion and mood disor-ders (Lane et al., 1997; Blood et al., 1999; Damasio et al.,2000; Drevets, 2000; Mayberg et al., 2000; Royet et al.,2000; Simpson et al., 2001). It may be more appropriate,therefore, to consider the medial network as an emotomo-tor system, which modulates visceral function in relationto emotional stimuli. Because auditory stimuli, includinganimal calls, language, and music, can have strong emo-tional significance, it may not be surprising that the me-dial network receives specific auditory-related informa-tion from the dorsal temporal pole.

The heaviest projections to the hypothalamus and peri-aqueductal gray arise from the same caudal parts of themedial network that project most strongly to the dorsaltemporal pole. In addition, the dorsal temporal pole itself,like the medial network, projects to the hypothalamus andperiaqueductal gray (An et al., 1998; Ongur et al., 1998),suggesting that it is directly involved in visceral modula-tion. Earlier experiments by Kaada et al. (1949) indicatedthat electrical stimulation of both the medial prefrontalcortex and the temporal pole can produce changes in heartrate, respiration, and other visceral functions. A recentPET study of responses to emotive (pleasant and unpleas-ant) olfactory, visual, and auditory stimuli demonstratedselective activation of the temporal pole, together with theorbital cortex, the medial prefrontal cortex, the amygdala,and the hypothalamus (Royet et al., 2000). These andother observations imply that both the medial networkand the dorsal temporal pole are part of a system thatsupports cortical modulation of visceral function in re-sponse to emotional stimuli. It is likely that the dorsaltemporal pole is involved in both the auditory processingpathway and the cortical emotomotor system.

In summary, the dorsal and ventral parts of the tempo-ral pole, which receive higher auditory and visual inputs,are associated respectively with the medial and orbitalnetworks of the OMPFC. All together, these can be con-sidered to constitute distinct frontotemporal networksthat provide segregated links between systems processingspecific sensory information and systems related to re-ward and emotion.

ACKNOWLEDGMENTS

We thank Mr. Hieu Luu and Mrs. Van Nguyen for theirexcellent technical assistance.

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