organization of cortical afferents to the frontal ... · cal connections in the monkey (52) and in...

ACTA NEUROBIOL. EXP. 1987, 47: 137-161

ORGANIZATION OF CORTICAL AFFERENTS TO THE FRONTAL ASSOCIATION CORTEX IN DOGS

Grazyna MARKOW-RAJKOWSKA and Anna KOSMAL

Department of Neurophysiology, Nencki Institute of Experimental Biology Pasteura 3, 02-093 Warsaw, Poland

Key words: dog's frontal as,sociation cortex, cortical afferents, HRP method

Abstract. The source of cortical frontal association cortex (FAC) afferents and their terminal distribution in the dog's brain was determined by the HRP tracing method. It was shown that the sources of ipsilateral FAC afferents are limbic and paralimbic areas of allo- and mesocortex and parasensory areas of the neocortex. Most of these areas with the exception of the piriform olfactory cortex could be characterized as cortical association fields. The terminal distribution of FAC afferents gave evidence to distinguish dorsal and ventral FAC zones. The dorsal FAC zone which includes the premotor and dorsal prefrontal regions is supplied by afferents originating in the temporal, parietal, occipital, perirhinal and parahippocampal cortical areas. In contrast, the ventral FAC zone, involving the ventral part of the prefrontal cortex, receives characteristic projections from the subcallosal area and from the anterior parts of the piriform cortex. However, both FAC zones receive intensive projections from the cingular and insular cortices. The organization of FAC afferents in the dog was discussed in comparison with ather species.

INTRODUCTION

Previous research on the dog's frontal association cortex (FAC) based on behavioral effects of lesions (9, 10, 25, 32, 33, 40, 63, 64) as well as cyto- (1, 19, 24, 61) and myeloarchitectonic (34) studies have shown mor-

pho-functional heterogeneity of this cortical region. Recent results show the diversification in afferent projections into particular FAC parts co- ming from thalamic and also from extrathalamic structures (26-30, 51, 65, 67, 68). It is particularly well expressed by the distribution of indi- rect FAC afferents passing via mediodorsalnucleus (MD), which is known to be precisely and topographically connected with this cortex (65). Since MD afferents were determined, it seems justifiable to distinguish within FAC two principal regions, namely the dorsolateral and medioventral. The dorsolateral FAC region is via the lateral MD segment predominantly related to structures involved in the regulation of motor activity, such as motor cortex, nigro-striatal system and cerebellar nuclei (65). In contrast, the medioventral FAC region via the medial MD segment is related to the structures of the limbic system i.e., the cingular and insular cortices, amygdaloid complex, septum, nucleus of diago- nal band, anterior olfactory nucleus and olfactory tubercle (65).

Cortical ipsilateral afferents and their distribution within the FAC region in the dog are unknown, while in other species they are generally less known than the subcortical ones. Previous investigations in various species have shown that they originate in the cortex which can be determined as "nonprimary" or parasensory, as well as in paralimbic (3-8, 11, 12, 15, 16, 21, 22, 41, 43, 44, 50, 52-56, 58-60, 72). Among the mammalian species the cortico-frontal connections are the richest and best organized in primates. The results obtained from Rhesus monkeys sho- wed the existence of abundant projections from the association parasensory areas of the temporal, parietal and occipital neocortex reaching predominantly the dorsolateral fields of the frontal association cortex (3, 4, 15, 21, 22, 41, 52, 54). On the other hand, the frontal orbital surface receives connections mainly from limbic and paralimbic mesocortical areas like the cingular, subcallosal, temporal pole, perirhinal, parahippocampal areas, as well as from the entorhinal, subicular and presubi- cular limbic allocortical areas (2, 52, 53, 72). The authors, studying cortical connections in the monkey (52) and in the cat (60) divide the dorsolateral convexity of the frontal association cortex into prefrontal and premotor regions. This division was made on the basis of differences in the terminal distribution of the connections originating in the first and second order parasensory areas. The first-order (proximal) parasensory areas send afferents to the premotor region, whereas the second-order (distal) areas reach the prefrontal region. Up to now, only the premotor region apart from its characteristic connections, has been distinguished in the monkey from the point of view of its electrophysiological features. As for other features, the presence of the movement-related neurons was defined (71) as active due to the occurrence of some sensory signals.

However, similar neurons were also found in the caudal region of the dorsolateral prefrontal cortex (13, 14). Such results could suggest the lack of a sharp border between the prefrontal and premotor regions. In other species, like the bush baby (56), cat (6-8, 20, 43, 44, 59, 60), guinea pig (55), hamster (58) and rat (5, 11, 50), the FAC connections originating in most of the above mentioned cortical regions were detected, although the patterns of their organization differ to some extent. Among subprimates the dog's brain is characterized by the relatively well developed frontal association cortex which occupies about 7O/o of the entire neocortex (12).

Up to now, little has been known about the morphology of the cortex in the dog's brain, particularly about the localization of association areas. According to the results obtained from monkeys and other species, most of the association cortical areas can be defined by their relation to the frontal association cortex. Thus, in the present study $we intend do determine the sources of cortical FAC afferents and their terminal differentiation. We would like to find out whether the distribution of particular cortical projections provides additional arguments for a division of the FAC area in the dog into dorsal and ventral zones, as was suggested by the analysis of subcortical afferents topography. Mo- reover, we would like t~ discuss the extent to which the division of FAC into prefrontal and premotor regions is justified from the point of view of their afferent connections.

METHODS

Twenty-two young dogs were used to determine the distal intrahemispheric cortical FAC connections. Each animal was under nembutal anesthesia 35 mglkg of body weight and received unilateral injections of HRP (Sigma, Type VI or Boehringer Grade I). Particular FAC fields were multiply injected in 8-12 points with 30-50°/o HRP solution with total amount about 2 pl at a depth of 2-3 mm from the cortical surface. The dogs survived for 48-72 h, then they were deeply anesthetized and perfused with Mc Evans saline followed by fixative solution at pH = 7.4. The removed brains were kept for 48 h in the fixative mixture with 30°/o sucrose and then frozen 40 pm sections were cut.

In order to reveal the reactive HRP in accordance with the procedu- res of Mesulam every 10th section was incubated in a medium containing benzidine dihydrochloride or tetramethyl benzidine (46, 47). The sections were brightly counterstained with cresyl violet or neutral red. Microscopic observations of HRP labeled cells were made with light and

2 - Acta Neurobiol. Exp. 4i87

dark field illumination. To determine the cortical regions in which labeled neurons were found, Kreiner's division of the dog's cortex (37) was used.

RESULTS

The localization of injections. To investigate cortical intrahemispheric FAC afferents, particular HRP injections covered the entire surface of the cortex. The injection sites, together with zones of their diffusion are schematically shown in Figs. 1 and 2. The results are presented in two groups, following the characteristic distribution of the frontal afferents.

GROUP I

Fig. 1. Diagramatic illustration of HRP injections in Group I (dorsal FAC cases) presented on the schemes of the lateral ( A ) and medial (B) surfaces of the frontal lobe. The black area indicate the site of injections; broken lines show the extent

of enzyme diffusion. For the names used, see Abbreviations.

GROUP I1

Fig. 2. Diagramatic illustration of HRP injections in Group I1 (ventral FAC cases). Denotations as in Fig. 1.

Group I involved dorsal injections made in dogs 1-12 (Fig. 1) and covering dorsal, dorsolateral and dorsomedial fields of the FAC. Three injections were placed in the premotor cortex (dogs D 1-3), whereas nine others were injected in various fields of the prefrontal cortex (dogs D 4-12). Particular injections were arranged on the basis of their localization - namely, from posterior to anterior as well as from dorsal to ventral directions. Group I1 included ventral injections made in dogs D 13-21 (Fig. 2), which were placed in the ventral, ventrolateral or ventromedial fields of the FAC involving the prefrontal cortex. only.

Sources of cortical afferents to FAC. The results presented in this paper refer to the distribution of the retrograde labeled cells situated in cortical fields of the entire ipsilateral hemisphere. The cortical projections from the contralateral hemisphere as well as the intrinsic FAC connections wiil be described in separate papers.

Distribution of labeled cells after dorsal injections (Group I ) . The most representative distribution of labeled cells was found in dog 7 (Fig.

3). In this case, a large injection was placed in the dorsal FAC zone, involving mainly the caudal prefrontal and partly the premotor cortices. A high concentration of reaction product was found on the dorsolateral surface of the caudal proreal gyrus (PR), the central precruciate area (XC) and a part of the dorsal paraorbital area (PORd), which is situated on the medial wall of the presylvian fissure (Figs. 1 and 3A). However, on the medial surface of the hemisphere its noticeable concentrations were also found predominantly in the dorsal parts of the medial precruciate (XM) and dorsal pregenual (PGd) areas (Figs. 1 and 3B). A stri- king aggregation of labeled cells was observed in the two vast cortical areas, on the medial surface in the cingular gyrus, while on the lateral surface it was observed in the regions of sylvian (sS), ectosylvian (sEs) and rhinal (sRh) sulci (Fig. 3A, B and C).

In the cingular gyrus, labeled cells were distributed through the entire length: frontally from the area around the callosal genu (G), and caudally to the area of callosal splenium (RSPL) (Fig. 3B and C1-6). La- beled cells were found in the cortex of the surface of this gyrus, as well as in the depth of the splenial sulcus (sSpl), which borders dorsally with the cingular gyrus. The most extensive aggregation seemed to involve the medial part of this gyrus (CN), whereas in its anterior part above the corpus callosum labeled cells were fairly less numerous. In the area frontal to the genu as well as in retrosplenial and parahippocampal areas lying behind the spleniurp of the corpus callosum only single cells were found (G, RSPL, PH in Fig. 3B, C1 and C6).

The cortex of the cingular region in which the labeled cells were found correspond to fields: 32, 24, 23, 31, 30, 29 of Klempin's (24) and Gurewitsch's (19) cytoarchitectonic maps of the dog's cerebral cortex, and to area limbica prima (L,) and secunda (Lz) according to Adrianov's division (1). The same cortical fields were named as follows according to the myeloarchitectonic division of Kreiner (35): area genualis - G, area limbica anterior - LA, media - LM and posterior - LP. Thus, the main projection to FAC originates from fields 23 and 24 of Klempin's and Gurewitsch's division, based on the Brodman's nomenclature. ,The ventral edge of the splenial sulcus, where labeled cells were also present is usually regarded as a part of the cingular cortex (19, 24, 35), whereas the dorsal edge and the bottom of the same sulcus belong to different cortical regions (19, 24, 38, 39). Its anterior part is considered to be parietal cytoarchitectonic fields 5 and 7, while the caudal part belongs to fields 18 and 19 of the occipital cortex.

On the lateral surface, labeled cells were found in a vast region of the cortex, and they covered a few cortical areas (Fig. 3A). Anteriorly, labeled cells were situated along the rhinal sulcus (sRh), (Fig. 3A and

Fig. 3. Distribution of labeled neurons in different regions of the cerebral cortex after injection into the dorsal prefrontal and premotor FAC fields in the case of Dog. D7; A, lateral surface of the hemisphere; B, medial surface; C , frontal sections from anterior (1) to the posterior (7). Black color is used for the places with the highest enzyme concentration; broken lines, a region of enzyme diffusion; crosses, localization of labeled neurons of the surface of gyri; dots, in the depth of the sulci. Due to a large number of the labeled cells found in this case, each symbol (cross or dat) represents three la- -

beled cells. For names used, see Abbreviations. P W

C1-6). It should be emphasized that they also occuppied the most caudal part of the orbital gyrus (ORB), between the presylvian (fPs) and the anterior rhinal (sRha) sulci. This aggregation of labeled cell was continued more caudally around the sylvian sulcus (sS). But in the depth of sylvian sulcus, as well as on the surface of the anterior part of sylvian gyrus (S), the cells were most densely packed. The cortical region situated close to the rhinal and sylvian sulci is believed to belong to the insular cortex, but is named differently by the above mentioned authors. According to the investigators of cytoarchitectonic, these are fields 13, 14 (18) or area insularis prima - I (I), while it is named area orbitalis tertia (ORB 111) and area sylvia interna (SI) according the myeloarchitectonic division (34, 36). However, the cortex of the anterior sylvian gyms is regarded as the insular (1) or temporal area (36).

The projection area described above continued dorsocaudally in the medial and posterior parts of the sylvian gyrus, as well as in the depth of the ectosylvian sulcus (S, sEs; Fig. 3A and C4-6). On the surface of the ectosylvian gyrus (ES), labeled cells were less numerous (Fig. 3A and C2-6). The terminology of the cortex of the medial and posterior sylvian gyms is also inconsistent. Some authors include this cortex in the para- insular (I), but the others include it in the temporal region (36, 45). According to Gurewitsch and Klempin, it corresponds to cytoarchitectonic field 52 (19, 24). The depth of the ectosylvian sulcus and ectosylvian gyrus, however, has consistently been considered as temporal cortex (19, 24, 36). The cortex of the anterior and posterior ectosylvian sulci and of the ectosylvian gyrus has been defined as fields 50, 22 and 20 respecti- vely (19, 24). It should be stressed that the places in which labeled cells appeared were localized outside the primary auditory cortex (66, 69, 70), so they belong to its association area. The main projection group of cells in the insulo-temporal region was surrounded by scattered labeled cells (Fig. 3A). They were localized in the depth of medial and posterior suprasylvian sulci (sSs), caudal suprasylvian gyrus (SS) and posterior rhinal sulcus (sRhp), often named the perirhinal cortex (Fig. 3A and C 4-6). In the medial part of the suprasylvian sulcus, cytoarchitectonic fields 5 and 7 are localized, while in its posterior part, field 21 is localized (19, 24). The caudal suprasylvian gyrus corresponds to field 20 (19, 24) or area TE (1) and area composita lateralis - CPL (36) of the above cited divisions. In this case described labeled cells in parietal and occipital cortices form separate groups on the lateral or medial surface of the hemisphere. The groups are a continuation of main projection zones, but they do not overlap one another.

The second case of the FAC of dorsal injections group is represented by dog D2 in which the injection was restricted to the premotor cortex

Fig. 4. Distribution of labeled neurons in different regions of the cerebral cortex after injection into the FAC premotor region in the case of Dog D2. One symbol (cross or dot) stands for two cells. Other denotations as in Fig. 3. -

P V1

and placed in the anterior composite area (CA) of the lateral presylvian wall (Fig. 4), thus more caudally than in the previous dog. Such a small injection caused the labeling of a much smaller amount of cells: Their distribution, however, seems to be very significant. The cells appeared in the same cortical areas as in the previous subject, but their accumu- lation was observed in the upper parts of the projection zones.

On the medial surface the main aggregation of labeled cells was observed in the dorsal part of the cingular gyrus and in the dephh of splenial sulcus (CN, sSpl; Fig. 4B and C 1-5). They were significantly less numerous in the ventral and caudal parts of this gyrus. In contrast to the previous subject, labeled cells appeared additionally on the dorsally neighboring cortex of the splenial gyrus (SPL), in the depth of supras- plenial sulcus (sSspl) and some single cells, in the marginal gyrus (MA; Fig. 4B and ;C2-4). Thus, they occupied the upper parts of the cytoarchitectonic fields 5 and 7 of the parietal cortex (19, 24).

On the lateral surface of the hemisphere, labeled cells were mainly aggregated in the anterior and medial parts of the ectosylvian sulcus, predominantly in its depth, but also in thq neighboring dorsal part of the ectosylvian gyrus (sES Es; Fig. 4A and C1-5). So, the main projection to the premotor cortex originates from the anterior part of the temporal cortex, i.e. from the region constituting the dorsal part of the projection zone in the previous case.

Labeled cells in the insular cortex prevailed in the depth of the sylvian sulcus, whereas on the surface of the same gyrus as well as along the rhinal sulcus such cells were less numerous (sS, S, sRhp; Fig. 4 A and C2-4).

In the cortex of the lateral surface, similar to the cortex of the medial one, labeled cells also appeared more dorsally to the main projection area. Fairly numerous cells were found in the depth of the suprasylvian sulcus (sSs), as well as on the surface of the suprasylvian gyrus (SS) and in the depth of the lateral sulcus (sL; Fig 4A and C3-5). According to cytoarchitectonic maps these newly appeared cells could be localized in fields 5 and 7 of the parietal cortex and the most anterior parts of the occipital cortex (19, 24, 39).

Distribution of labeled cells after ventral injections (Group 11). This group is represented by two subjects D20 (Fig. 5) and Dl3 (Fig. 6). Injec- tion in D20 covered the medioventral prefrontal fields: the ventral pregenual area (PGv), the subgenual area (SG) and a small part of the subproreal gyrus (SPR; Figs. 2 and 5). Following injection, labeled cells were found mainly in two cortical areas: the cingular cortex of the medial surface and the insular cortex of the lateral one. In the cingular cortex, labeled cells were situated in the anterior and middle parts of this gyrus (G,

20

ORB

A 1 1 I 1 1 1 6 6 4 8 2 1

Fig. 5. Distribution of labeled neurons in different regions of the cerebral cortex after injection into the ventromedial prefrontal FAC fields in the case of dog. D20. Denotations as in Fig. 3,

CN; Fig. 5B and C). Anteriorly, they were localized around the callosal genu, while caudally they extended to the medial part of gyms, occu- pying approximately 2/3 of its length. The most caudal (retrosplenial) part of the cingular gyrus was free of labeled cells. It is interesting to mention that the main aggregationof cells was found only In the ventral part of this gyms. Thus, in comparison with the distribution of labeled cells in those cases with dorsal injections, the source of projection to the ventral FAC covers exclusively the ventral part of the previous projection zone.

On the lateral surface of the hemisphere, labeled cells were distributed from the caudal part of the orbital gyrus, along the whole length the anterior rhinal sulcus and both walls of the sylvian gyms [ORB, sRha, S; Fig. 5A and C). They were mainly localized in the depths of these sulci and only single cells - in the convexity of the orbital and sylvian gyri. Single cells that appeared in, this case, slightly dorsal, above the ectosylvian sulcus, seem to be caused by some spreading of the injection into the dorsal FAC zone. In the case of other medioventral injections, labeled cells above the close vicinity of sylvian pulcus cortex were never found. So unlike the cases of dorsal injections, labeled cells were not found outside the restricted region of the insular cortex.

Apart from the above mentioned cortical areas, labeled cells were also observed in the subcallosal area (SC; Fig. 5B, and ,C1). The labeled cells in this cortical field were never observed after any dorsal injection. Thus, SC seems a specific source of projection to the ventral FAC zone. This cortex is defined as field 25 of Klempin's cytoarchitectonic map (24) and area subcallosa I (sCI) and I1 (SC 11) of the limbic cortex according to Kreiner's myeloarchitectonic division (35).

In the second case of the ventral group (dog D13), a small injection involved the anterior part of the subproreal gyrus (SPR), predominantly its lateral surface (Figs. 2 and 6 ) . Generally, less numerous labeled cells were present in the same parts of the cingular, subcallosal and insular cortices. However, some differences in the distribution of these cells were observed. On the lateral surface of the hemi$phere, the main aggregation of labeled cells was found in the most anterior part of the insular cortex involving the caudal orbital and anterior sylvian gyri (ORB, S; Fig. 6A). This group uf cells was continued ventrally in the anterior piriform cortex (Ppir., Pamg; Fig. 6A, B and C1-4). The piriform cortex seems to be specific source of projection into the most antero-ventral prefrontal cortex. This cortex in various cytoarchitectonic maps of the dog's brain is generally considered part of the limbic allocortex (1, 19, 24). Additionally, in the cases of ventrolateral injections, single labeled

R s p l

Fig. 6. Distribution of labeled neurons in different regions of the cerebral cortex after injection into the antero-ventral prefrontal FAC fields in the case of Dog D13. Denotations as in Fig. 3.

cells appeared neighboring the insular parts of the temporal cortex (Fig. 6A - pluses in S).

In all cases of injections labeled neurons were mainly localized in cortical layer I11 while fewer were found in layers 11, V, VI (Figs. 7 and 8). Most often they were pyramidal cells of medium size, although some oval and stellate small neurons were also observed. Often they had a tendency to aggregate into small groups.

Organization of cortico-frontal projections. Table I summarises the results of all injections into FAC which caused the labeling of cells in the following cortical areas: the piriform, cingular, subcallosal, parahippocampal, perirhinal, insular, temporal, parietal and occipital. In the cingular and insular cortices, numerous labeled cells were observed in all cases of injections. Both mesocortical areas gave rise to the most abundant and significant projections to the entire FAC. However, we would like to stress some differentiation of cingular afferents. The medial part of the cingular gyrus (CN) sends more abundant connections to the dorsal FAC, whereas its anterior part (G) sends more to the ventral FAC. In the remaining cortical areas, labeled cells appeared following either dorsal or ventral injections (Table I).

The dorsal FAC is provided with afferents originating in the parahippocampal and perirhinal mesocortical areas, as well as the temporal, parietal and occipital neocortical regions. In contrast, the ventral FAC receives afferents from the subcallosal area of the mesocortex and the piriform area of the allocortex. The only exception is the temporal cortex which, apart from the main projection to the dorsal, also sends some afferents to the ventrolateral FAC.

The arrangement of particular cortical areas giving rise to frontal projections and their terminal distribution is graphically presented in Fig. 9. The cortical areas of the insular cortex (INS) and the cingular gyrus (G, CN, RSPL), (dense vertical lines in Fig. 9A), which give rise to strong projections into the entire FAC (sparse vertical lines in Fig. $4 occupy) the central position of both lateral and medial surfaces of the hemisphere. The cortical areas such as parahippocampal (PH), perirhinal (PRH), temporal (TE), parietal (PA), occipital (OC) which are the sources of projections into the dorsal FAC (sparse slanting lines in Fig. 9B) constitute an outer ring of the cerebral cortex (dense slanting lines in Fig. 9B). The areas which send specific projection to the premotor cortex of the dorsal FAC (sparse lines slanting to the right in Fig. 9B) occupy the most dorsal position in the same outer ring of the cortex (dense lines slanting to the right in Fig. 9B). However, the subcallosal (SC) and piriform (PIR) cortices, supplying the ventral FAC zone (sparse horizontal lines in Fig. 9C) are localized most ventrally in the inner ring of the

Fig. 7. Microphotograph of HRP labeled neurons in the central part of the cingular gyrus following dorsal FAC injection dog D5; A, in a light field; B, in a dark field. Arrows indicate groups of labeled cells.

Fig. 8. Microphotograph of HRP labeled neurons; A, in the dorsal wall of the ectosylvian sulcus following dorsal FAC injection in the case of dog D 7. The labeled neurons are set in a smallgroups, often in vertical rows (arrows); B, the labeled neurons in the upper bank of the splenial sulcus following dorsal FAC injection in case of dog D5.

Cortical regions containing the labeled neurons following FAC injection - --- . -. -

Localization j Allocortex 1 Mesocortex Neocortex of injection 1

The number of plus sigus (+) indicates a relative number of labeled cells in one section; +, 1-5 cells; + I - , 5-10 cells; +++, more than 10 cells; -, indicate of labeled cell.

Gyrus cinguli Area 1 cortex cortex G CN RSPL subcallosa parahipo- perirhinalis

-- I I I campalis

1 - + / ++ + I 2

+

I + + '

+ + -

11 - ++ -

1 2 - 1 - 1 + ++ + 1 13 ++ , + ++ - -

++ I + - -

1 + - -

I1 16 + + - - - - - 17 - + + - 1 - I - -

18 +++ +i-+ + + + ++ - I - 19 - + ++ + + 1 ++

Cortex insularis

++ ++ + +++ ++ ++ +++ ++ + +++ +++ + ++ +++ ++ ++ ++ ++

Cortex temporalis

Cortex 1 Cortex parietalis I occipitalis

20 21

+ ++ -

- -

I + -

+ + + + -

I + + - -

- - - - - - - -

+++ +++ +++ + +++ +++ ++ +++ +++ +++ + + + + -t + + -

++ ++ ++ + ++ ++ ++ + - - - - - - - - - - -

- - - l - ++ +++

+++ ++

- I - ++ + I ++ + ' +

cortex (dense horizontal lines in Fig. 9C). Thus the main differences of connectivity pattern could be attributed to the dorsal and ventral FAC zones. The dorsal FAC is more abundantly supplied by afferents from various fields of meso- and neocortex, while the ventral FAC is supplied

Fig. 9. General schemes of the topography of the distal intrahemispheric FAC cortico-cortical connections shown on the lateral (1) and medial (2) surfaces of the hemisphere. The cortical areas which are the source of afferent connections to the FAC are illustrated by differently arranged dense lines, while the sites of termination of these projections are indicated by the same, but sparsely arranged lines; A, the areas that are the source of strong connections to the entire FAC are marked with vertical lines; B, cortical areas giving rise to differentiated projection to the dorsal zone of FAC are indicated by slanting lines. Lines slanting to the right, areas projecting to the premotor cortex; lines slanting to the left, areas projecting to the prefrontal cortex; C, cortical areas sending differentiated projection to the ventral zone of FAC are Indicated by horizontal lines. For the

names used see Abbreviatlons.

by afferents originating in meso- and allocortex. However, it should be mentioned that the mesocortical areas related to dorsal or ventral FAC zones are localized differently.

DISCUSSION

The results reported here allow recognition for the first time the association cortical areas in the dog's brain on the basis of their relation to the FAC area. The organization of the cortico-frontal connections is considered from the point of view of the localizations of sources of cortical projections and their terminal distribution in the FAC area.

The insular and cingular regions of the mesocortex form a strong ipsilateral projection reaching the entire FAC. The insular cortex, named by some authors limbic (17, 62) and by others paralimbic (48) area, was identified in various species as a cortex situated in the depth of sylvian sulcus as well as in the anterior sylvian gyrus (1, 17, 18, 36, 42, 57). In accordance with the data as well as with the present results it seems justifiable to include into the insular area the cortex localized in the anterior part of the rhinal sulcus and in the most caudal part of the orbital gyrus. Such a point of view is consistent with the previous cytoarchitectonic and myeloarchitectonic results (1, 19, 24, 34, 36) as well as with the distribution of the cortical MD afferents (65) in the dog. However, the projection from these cortices seems to be differentiated to some extent. In the dorsocaudal insular cortex originate afferents which terminate more densely in the dorsal part of FAC zone, whereas, the antero-ventral insular cortex is a source of connections which predominantly supply the ventral FAC zone. The studies of connectivity of the insular cortex in other species provide further evidence for its morp- ho-functional heterogeneity (17, 18, 48, 49, 58). Definite differentiation of this cortical region in the dog needs further morphological and functional examination.

The limbic cingular cortex, involving the entire region situated in front of and above the corpus callosum, is not homogeneous in the dog brain. On the basis of the connections presented the cingular cortex could be divided into three parts: (i) The anterior part predominantly supplies the ventral FAC zone which is identified as the prefrontal cortex. (ii) The medial part of the cingular cortex sends abundant 'projection mainly to the dorsal FAC zone in which the dorsal prefrontal region receives more intensive connections than the premotor one. (iii) A weak projection of the posterior cingular part often named the "retrosplenial cortex" also reaches mainly the dorsal FAC zone. The diversity between the anterior part and the rest of the cingular cortex was presented in

previous electrophysiological studies (23) and justified by subcortical connections (65). In previous studies of other species (8, 11, 21, 43, 55-57), the projection from the cingular cortex was detected mainly to the prefrontal cortex with the monkey only having projection to both the prefrontal and premotor regions (2, 52, 53). Usually, the projection was described as strong, but the terminal areas were differently determined. Thus, in spite of the interpretation of the above results in the dog and the conclusion that the both insular and cingular cortices supply the entire FAC zone, it should be emphasized that some of their parts are closely related to the ventral, while others are related to the dorsal FAC zone.

The cortical areas forming differentiated frontal projections terminate in either the dorsal or ventral FAC zone. The dorsal FAC zone receives afferents from the temporal, parietal and occipital neocortical areas, as well as from the perirhinal and parahippocampal areas of the mesocortex. On the contrary, afferents to the ventral FAC zone come from the subcallosal field of the mesocortex and from the anteromedial parts of the piriform lobe which belong to the allocortex.

Among the structures which supply the dorsal FAC zone, the most plentiful connections originate in the temporal cortex related to the depth of the ectosylvian sulcus. Moreover, temporal afferents that supply the premotor cortex originate from a more dorsally situated area of the projection than those supplying the prefrontal cortex. This cortex was identified with morphological (45, 66) and electrophysiological (69, 70) methods as an association auditory area. Additionally, a weak projection originated in the posteromedial part of the suprasylvian sulcus. A cor- responding source of frontal afferents was determined in the cat as an auditory-visual association cortical area (6, 60). In the primates, like carnivores, association fields of the temporal cortex are to source of a strong projection to the dorsolateral prefrontal cortex (21, 22, 52).

Other neocortical areas of the parietal and occipital lobes give rise to weaker projections that terminate exclusively in the dorsal FAC zone. Afferents to the premotor region originate in the more dorsal part of the outer projective ring of both cortical surfaces than to the prefrontal one. These regions correspond to the somatosensory association cortex (1, 19, 24, 38). Occipital afferents originate in the posterior parts of the same projection zone and are regarded as the visual association cortex (1, 19, 24, 39). Comparable projection8 from the association parieto-occi- pita1 fields are described in the cat (44, 60) and monkey (15, 22, 52, 54) as terminating predominantly in the premotor cortex. In our material, an additional weak projection to the dorsal FAC 'zone may come from the perirhinal and parahippocampal fields of the mesocortex. The perir-

hinal mesocortical field, situated between the outer neocortical and inner allocortical ring in cat, is identified as visual association cortex (6, 18, 60). The projection from the hippocampal formation and parahippocampal cortex was identified in the cat (6, 8, 20) and the monkey (16, 52); in the dog, however, it seems to be very weak.

The ventral FAC zone, unlike the dorsal zone, receives characteristic projections from the limbic areas. They originate in the mesocortical subcallosal field, as well as in the anterior and medial parts of the piriform cortex (allocortex). It should be stressed that the piriform cortex, as an olfactory projective zone, is an exception in general pattern of FAC connections. This is the only primary sensory cortex which supplies the FAC area and can be explained by the peculiarity of the dog's behavior. Such results agree with previous data obtained on the dog, which sho- wed that these structures supply the ventral FAC zone indirectly also, through the medial MD segment (65). These MD afferents also originate from the anterior piriform cortex. Afferents from the piriform cortex to the same FAC part were found in the rat (57) and cat (6, 7). In the monkey, however, this projection origin also involved the most caudal part of the piriform lobe, the entorhinal cortex (16, 72). Recently it has been shown that in the monkey, the entorhinal afferents terminate in a vast area of the frontal cortex (16), which may correspond to both the ventral and dorsal FAC zones in the dog.

A basic pattern of the distribution of cortico-frontal connections in various mammalian species is generally similar. Slight differences between the phylogenetically less developed rodents and more developed primates could refer to the intensity of this projection and the extent of the cortical regions giving rise to this projection. It seems that in carnivores and rodents, FAC connections with limbic and paralimbic areas of the allo- and mesocortex are stronger and more scattered than with the neocortical areas. On the contrary, in primates the connections with neocortical parasensory areas prevail and they are more focused. Among subprimates, the extent of the cortical regions giving rise to the frontal projection in the dog (present results) is most similar to that observed in the cat's brain (8). It is difficult to compare the pattern of terminal distributions of particular projection system in lower mammals because of significant differences in the extent of FAC. In the monkey, however, the pattern of termination of afferents originating from the primary and secondary parasensory areas enabled the division of the frontal lobe association cortex into the prefrontal and premotor regions (52). In our opinion, the present results show that in the dog the primary and secondary parasensory areas could not be clearly determined on the same basis. The areas of termination of particular projections seem to be wider

3 - Acta Neurobiol. Exp. 4187

than i n the monkey and to a greater extent they overlap with projections from the limbic and paralimbic cortices. The premotor cortex sha- res the features of connectivity with the dorsal prefrontal cortex. There- fore, it would be more justified to divide the entire frontal lobe association cortex in the dog into the dorsal and ventral zones. According to such a division, the ventral FAC zqne could be characterized by strong connections with the limbic and paralimbic areas of the meso- and allocortex which occupy the central and inner ring of the projection zone, whereas the dorsal FAC zone would be characterized by its relations to the mesocortical limbic and paralimbic areas of the central projection area, as well as to the neocortical parasensory areas that constitute the outer projection ring.

Apart from receiving the cortical afferents from parasensory neocortical fields, the most characteristic feature of the dog's dorsal FAC zone is its relation to the motor system. Morphological evidence supporting such a point of view consists, on the one hand, in the existence of a chain of short cortico-cortical connections linking the primary motor cortex with the dorsal prefrontal fields (30) and, on the other hand, in the connectivity with subcortical structures involved in the regulation of motor activity (65). The most significant evidence seem to be the connections between the dorsal FAC zone and the lateral MD segment and via it, with the primary motor cortex, as well as with the structures of the nigrostriatal system and cerebellar nuclei (65). Moreover, the projection from the ventral anterior thalamic nucleus, which is usually considered as a characteristic for the premotor cortex, in the dog involves both the premotor and dorsal prefrontal cortici, thus comprising the entire dorsal FAC zone (28).

This investigation was supported by Project CPBP 0401 of the Polish Aca- demy of Sciences.

ABBREVIATIONS

area area composita anterior area cingularis area composita posterior gyrus ectosylvius firjsura fissura presylvia frontal association cortex gYvs area genualis I

horseradish peroxidase

INS MA MD OC ORB ORBd ORBv Pamg PA F'G PGd PGv PH PIR POL PORd PORv Ppir PR PRH PRL RSPL s s s A sCor sCr sEs sG SL spg sRc sRha sRhp sRspl SS ssp1 sss sssp SC SG S J SPL SPR SPRL SS TE XC XM XP

cortex insularis gyrus marginalis nucleus medlaLis dorsalis cortex occlpitalis gyrus orbitalis gyrus orbltalls pars dorsalis gyrus orbitalis pars ventralis cortex plriformis pars periamygdaloidea cortex parietalis area pregenualis area pregenualis pars dorsalis area pregenualls pars ventralis area parahippocampalis cortex piriformis area polaris area paraorbitalis dorsalis area paraorbitalis ventralis cortex piriformis pass prepisifarmis gyrus proreus cortex perirhinalis area prorea lateralis cortex retrosplenialis sulcus gyrus Sylvius sulcus ansatus sulcus coronalis sulcus cruciatus sulcus ectosylvius sulcus genualis sulcus lateralis sulcus pregenualis sulcus recurens sulcus rhinalis anterior sulcus rhinalis posterior sulcus retrosplenialis sulcus sylvius sulcus splenialis sulcus suprasylvius sulcus suprasplenialis area subcallosa area subgenualis area sylvia insularis gyrus splenialis gyrus subproreus gyrus subproreus lateralis gyrus suprasylvius cortex temporalis area precruciata centralis area precruciata medialis area precruciata posterior

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Accepted 9 March 1987

organization of cortical afferents to the frontal ... · cal connections in the monkey (52) and in...

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