association fiber pathways to the frontal cortex from the superior temporal region in the rhesus...

THE JOURNAL OF COMPARATIVE NEUROLOGY 273~52-66 (1988)

Association Fiber Pathways to the Frontal Cortex From the Superior

Temporal Region in the Rhesus Monkey

M. PETRIDES AND D.N. PANDYA Department of Psychology and the Montreal Neurological Institute, McGill University, Montreal, Canada H3A 1B1 (M.P.); Edith Nourse Rogers Memorial Veterans Hospital,

Bedford, Massachusetts 01730, (D.N.P.); Departments of Anatomy and Neurology, Boston University School of Medicine, Boston, Massachusetts 02118 (D.N.P.); Harvard

Neurological Unit, Beth Israel Hospital, Boston, Massachusetts 02215 (D.N.P.)

ABSTRACT The projections to the frontal cortex that originate from the various

areas of the superior temporal region of the rhesus monkey were investi- gated with the autoradiographic technique. The results demonstrated that the rostra1 part of the superior temporal gyrus (areas Pro, Tsl, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus.

Key words: cerebral cortex, connections

Since the early report of Ferrier (1876) suggesting the existence of a close relationship between the auditory sensory system and the superior temporal gyrus, a great number of anatomical, electrophysiological, and behavioral studies have demonstrated the involvement of the first temporal convolution in various aspects of auditory function. Early electrophysiological mapping studies, using the evoked potential method, demonstrated close topographical relations between the cochlear partition and the cortex on the caudal part of the superior temporal plane which lies hidden within the Sylvian fissure (Ades and Felder '42; Licklider and Kryter, '42; Walzl and Woolsey, '43). More recent studies utilizing microelectrode recording methods

0 1988 ALAN R. LISS, INC.

have extended these early observations and have shown that, in addition to the primary auditory cortex, a number of other auditory fields can be identified within the superior temporal plane (Merzenich and Brugge, '73; Imig et al., '77). These findings are in close agreement with the fact that the primary auditory cortex, which has the koniocortical appearance typical of primary sensory cortex, is sur- rounded, in a beltlike way, by various cytoarchitectonically distinct areas (Merzenich and Brugge, '73; Pandya and Sanides, '73; Jones and Burton, '76). The exposed lateral

Accepted February 17, 1988.

TEMPOROFRONTAL CONNECTIONS 53

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Fig. 1. A Diagrams of the lateral, medial, and orbital surface of the Abbreviations of architectonic areas: Kam, medial koniocortex; Kalt, lat- frontal lobe of the rhesus monkey showing architectonic subdivisions ac- eral koniocortex; OLT, olfactov tubercle; paAc, caudal parakoniocortex; cording to Walker ('40) and Barbas and Pandya ('82). Designations PA11 and paAlt, lateral parakoniocortex; paAr, rostral parakoniocortex; proA, pro- Pro on the medial and orbital surfaces refer to periallocortex and proisocor- koniocortex; paI, parinsular; pros, somatic prokoniocortex @ID; reIpt, re- tex, respectively. B: Architectonic parcellation of the superior temporal troinsular parietal; reIt, retroinsular temporal; Tpt, temporoparietal; Tsl, gyrus and supratemporal plane as described by Pandya and Sanides ('73). Ts2, Ts3, three subdivisions of the rostral superior temporal gyrus.

M. PETRIDES AND D.N. PANDYA

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Fig. 2. Diagrammatic representation of the isotope injection in the rostral part of superior temporal gyrus (STG) involving areas Pro, Tsl, and Ts2 (shown in black) and the distributions of resulting label in the frontal lobe (shown as dots) in case 1. In this and subsequent figures, the coronal sections are taken at the level indicated on the lateral surface of the cerebral hemisphere to show labeled fibers in the white matter and terminal label in the cortex. Abbreviations in this and subsequent figures: AS, arcuate

sulcus; CC, corpus callosum; CF, calcarine fissure; Ci, circular sulcus; CING S, cingulate sulcus; CS, central sulcus; IPS, intraparietal sulcus; IOS, inferior occipital sulcus; LF, lateral (Sylvian) fissure; Li, limen insulae; LS, lunate sulcus; MOS, medial orbital sulcus; OS, orbital sulcus; OTS, occipi. totemporal sulcus; POMS, parieto-occipital medial sulcus; PS, principal sulcus; RhF, rhinal fissure.

surface of the superior temporal gyrus also includes various cytoarchitectonically distinct fields (Pandya and Sanides, '73) that are closely interconnected with the auditory areas of the posterior supratemporal plane (Galaburda and Pan- dya, '83). The involvement of these fields in auditory sensory processing is clearly demonstrated by electrophysiological investigations, as well as by studies of auditory disturbances after damage to these regions (Neff et al., '75).

Previous anatomical investigations have demonstrated significant projections to the frontal cortex from various parts of the superior temporal gyrus (Hurst, '59; Krieg, '63;

Pandya and Kuypers, '69; Pandya et al., '69; Jones and Powell, '70; Chavis and Pandya, '76; Forbes and Moskowitz, '77; Jacobson and Trojanowski, '77; Barbas and Mesulam, '81, '85). These investigations have contributed signifi- cantly to our understanding of the anatomical relationships betwen the superior temporal gyrus and the frontal cortex. Nevertheless, with the exception of the studies by Krieg ('63), which were carried out with the Marchi technique, no attempt has yet been made to examine the course of these fibers. As is well known, many pathways cannot be demonstrated with the Marchi technique. For example, Krieg ('63) reported that there were no connections to the frontal


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CASE 2 Fig. 3. Diagrammatic representation of the isotope injection involving the central parts of areas Tsl and Ts2

of STG and the distribution of labeled fibers and terminations in case 2.

lobe from the anteriormost part of the superior temporal gyrus, yet later studies have left no doubt as to the existence of such projections (e.g., Barbas and Mesulam, '85).

The paucity of information concerning the course of fibers from the superior temporal gyrus to the frontal lobe is particularly noticeable in view of the interest that exists in these pathways in relation to various clinical syndromes. A number of studies have examined the hypothesis that damage to the pathways linking the posterior temporal gyrus with the anterior speech region within the left frontal lobe can give rise to conduction aphasia (e.g., Geschwind, '65; Benson et al., '73; Damasio and Damasio, '80). A better delineation of the temporofrontal fiber pathways will be of considerable value to such attempts at clinicoanatomical correlations.

Recently, Galaburda and Sanides ('80) have examined the cytoarchitecture of the human auditory region in the light of the previous cytoarchitectonic parcellation of this region in the rhesus monkey by Pandya and Sanides ('73). This study demonstrated the existence of a very similar pattern of cytoarchitectonic organization in man and monkey. In

view of the limited information regarding the course of fibers linking the superior temporal gyrus to the frontal lobe, the availability of a comparable cytoarchitectonic parcellation of the auditory regions in the macaque and human brains, and the considerable clinical and theoretical interest that the course of these fibers holds, we have reexam- ined these connections with autoradiographic techniques.

MATERIALS AND METHODS Intracortical injections of radioactively labeled amino

acids (3H-leucine and/or proline; volume range, 0.4-1.0 pl; specific activity range, 40-80 pCi) were made in different parts of the superior temporal gyrus in ten rhesus monkeys following a craniotomy under pentobarbital-induced ane- thesia. An attempt was made to place the various injections into the different cytoarchitectonic areas of the superior temporal gyrus according to the parcellation of Pandya and Sanides ('73). After survival periods ranging from 5 to 7 days, the animals were deeply anesthetized with sodium pentobarbital and perfused transcardially with physiologic saline followed by a 10% formalin solution. The brains were

56 M. PETRIDES AM) D.N. PANDYA

Fig. 4. Diagrammatic representation of the isotope injections involving the dorsal parts of areas Ts2 of STG and adjacent supratemporal plane (STP) and the distribution of label in the frontal lobe in case 3

and Ts3

subsequently processed for autoradiography according to the technique described by Cowan et al. (‘72). The exposure times varied between 3 and 6 months. A series of coronal sections of the hemispheres in which an injection had been placed were examined microscopically with darkfield illu- mination. The labeled fibers in the white matter and the terminal labeling in the frontal cortex were recorded with the aid of an X-Y plotter that was electronically coupled to the stage of the microscope. This information was then used to reconstruct the injection and termination sites, as well as the path of the labeled fibers, on drawings of the surface of the brain. These drawings were made from photographs of each brain taken before sectioning. The cytoarchitectonic boundaries of the projection areas within the frontal lobe and the sites of origin of the pathways within the superior temporal gyrus were also established in the experimental material which had been counterstained with thionine.

RESULTS In this investigation, the cytoarchitectonic parcellation of

the superior temporal gyrus was made according to the criteria of Pandya and Sanides (’73). The parcellation of the frontal cortex follows that of Brodmann (‘09) and of Walker (‘40) as modified by Barbas and Pandya (‘82). See Figure 1 for an illustration of these cytoarchitectonic subdivisions.

Rostra1 superior temporal gyrus In two cases, the isotope injections were placed in the

rostral part of the superior temporal gyrus. In case 1, the iniection involved Dortions of areas Pro and Tsl. as well as

and Ts2 (see Fig. 3). In both cases, the fibers that were directed toward the frontal lobe emerged from their point of origin within the temporal pole and made a sharp turn at the level of the limen insulae to occupy the ventralmost portion of the extreme capsule in the form of a dense fasciculus. Further forward these fibers began to fan out and travel just above the orbitofrontal cortex (Figs. 11G-I, 12). A number of these fibers terminated in the orbitofrontal proisocortex as well as in orbital areas 13, 14, 12, and 10. The distribution of terminal label within the orbitofrontal proisocortical area was more marked in case 1 than in case 2. On the medial surface of the frontal lobe, terminal label was observed in areas 9, 14, 24, 32, and 25. In case 2, terminal label was also observed in medial area 10 and, in both cases, terminal label was observed in area 12 on the lateral surface of the frontal lobe.

Middle part of the superior temporal gyrus There were three cases (Figs. 4-6) in which the injection

sites involved the middle part of the superior temporal gyrus, i.e., areas Ts3 and paAlt. In case 3, the isotope injection involved the dorsal part of area Ts2 as well as area Ts3 (Fig. 4). In case 4, the isotope occupied the rostral portion of area Ts3 (Fig. 5), and, in case 5 , the dorsal portion of Ts3 together with the adjoining part of paAlt (Fig. 6).

The distribution of terminal label observed within the frontal cortex in case 3 resembled that of cases 1 and 2, but with two notable differences: in case 3, in contrast to cases 1 and 2. terminal label was observed in area 46 on the t i e rostralmost pokion of area Ts2 (Fig. 2). In case 2, the

injection was confined to the ventral portion of areas Tsl lateral aspect of the frontal lobe and there was no label in


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Fig. 5. Diagrammatic representation of the isotope injection involving area Ts3 of STG and the distribution of labeled fibers and terminations in the frontal lobe in case 4.

the orbitofrontal proisocortex and nearby area 13 (compare Fig. 4 with Figs. 2 and 3).

Cases 4 and 5 were very similar in terms of the pattern of terminal label observed within the frontal cortex. In both of these cases considerable label was found in the dorsal part of area 10, in the dorsal part of area 46 within and around the rostra1 part of the principal sulcus, as well as in areas 9 and 12. Only a small amount of label could be identified in dorsal area 8. On the medial surface of the frontal lobe, fibers terminated in areas 24, 25, 32, and 10, in both cases. Terminal label in the orbitofrontal cortex was very limited. In case 4, it was observed in areas 10 and 14, and in case 5 in area 12.

The course of the fibers traveling to the frontal lobe in case 3 was very similar to that of cases 1 and 2. The fibers

occupied the ventralmost part of the extreme capsule, and further forward within the frontal lobe, they spread out in the white matter just above the orbitofrontal cortex and terminated into their target areas (see Fig. 4).

In cases 4 and 5, the fibers arising from the injection site gathered in the extreme capsule. Further forward, these fibers continued their course toward the frontal cortex occupying a position just dorsal to that of the uncinate fasciculus. In the more anterior parts of the frontal lobe, these fibers lay between the lenticular nucleus and the lateral frontal cortex. Beyond the rostralmost tip of the caudate nucleus, these fibers assumed a central position within the white matter of the frontal lobe and then began terminat- ing in their target zones within the lateral and medial frontal cortex, as described above (Figs. 11D-F, 12). In

58 M. PETRIDES AND D.N. PANDYA

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Fig. 6. Diagrammatic representation of the isotope injection involving areas Ts3 and paAlt and the distribution of labeled fibers and terminations in the frontal lobe in case 5.

agreement with the limited extent of terminal label within the orbitofrontal cortex observed in these cases, only a very small contingent of fibers could be traced into the white matter overlying the orbitofrontal cortex.

Caudal superior temporal gyrus There were three cases (Figs. 7-9) with injections limited

to the caudal part of the superior temporal gyrus. In case 6, the isotope injection involved the caudal part of area paAlt and area Tpt (Fig. 7). In case 7, the injection involved most of area Tpt (Fig. 81, whereas in case 8 it was confined to the caudalmost part of Tpt (Fig. 9).

In all three cases terminal label was found mainly in the lateral prefrontal cortex. In each case terminal label was found in the dorsal part of area 8 within the concavity of the arcuate sulcus. In case 6, with the injection involving both Tpt and paAlt, additional label was seen in dorsal area

46, rostra1 area 6, and area 12. In case 7, in which the injection site did not extend outside Tpt, terminal label was observed in dorsalmost area 6 and in the supplementary motor region, in addition to the strong projection to dorsal area 8. In case 8, with involvement of only the caudalmost part of Tpt, terminal label was strictly confined to dorsal area 8.

In these cases, a fiber pathway originating from the injection site was observed to course around the caudalmost part of the Sylvian fissure and then to direct itself toward the frontal lobe occupying a position very deep within the parietal operculum, just above the upper branch of the circular sulcus. Further forward, these fibers ran under the arcuate sulcus and terminated within their target areas (Figs. 11A- C, 12). A second contingent of fibers directed to the frontal lobe was also observed in these cases. These fibers ran first through the extreme capsule and then moved forward in an


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Fig. 7. Diagrammatic representation of the isotope injection involving areas paAlt and Tpt of STG and the distribution labeled fibers and terminations in the frontal lobe in case 6 .

anterodorsal direction coursing through the claustrum. In case 6, they continued forward past the arcuate sulcus and terminated in area 46. In case 7, only a very small number of these fibers was oberved in the white matter beyond the arcuate sulcus and their termination could not be clearly identified. In case 8, these fibers could not be observed rostral to the arcuate sulcus. In all three cases, however, a number of these fibers terminated within the claustrum.

Supratemporal plane There were two cases with injections confined primarily

within the supratemporal plane. In case 9, the injection

occupied the rostral part of the primary auditory area and extended medially into the circular sulcus, involving area proA. Laterally, the isotope spread into a portion of area paAlt (Fig. 10A). In case 10, the isotope injection was restricted to the rostral portion of the primary auditory area, i.e., area KA (Fig. 10B).

In case 9, some of the labeled fibers originating from the injection site first coursed through the extreme capsule, whereas others entered the white matter above the upper branch of the circular sulcus. Within the frontal lobe, three fascicles could be distinguished. One was seen to run into the white matter above the orbitofrontal cortex and to terminate in small patches within orbital areas 13 and 12. A


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Fig. 8. Diagrammatic representation of the isotope injection involving area Tpt in STG and STP and the distribution of labeled fibers and terminations in the frontal lobe in case 7.

few fibers terminated also in medial areas 14 and 32. A second group of fibers occupied a position under the depth of the sulcus principalis and was seen to terminate in areas 12,46, and 9 within the lateral frontal cortex. A third group of fibers extended rostrally from its position above the upper branch of the circular sulcus into the white matter underlying the arcuate sulcus. These fibers terminated in the sulcal portion of area 8, as well as in area 6.

In case 10, which was limited to the primary auditory cortex, labeled fibers originating from the injection site remained strictly within the underlying white matter pro- jecting locally within the superior temporal gyrus. No labeled fibers could be identified within the frontal lobe.

DISCUSSION The present study examined the long association path-

ways that originate from various areas of the lateral surface of the superior temporal gyrus, as well as the supratemporal plane, and terminate within the frontal cortex. Particular emphasis was placed on the reconstruction of the course of these fibers and on the delineation of the cytoarchitectonic areas of the frontal cortex within which

they terminate. The findings can best be summarized in terms of three relatively distinct bundles of fibers (see Figs. 11, 12): (1) a bundle of fibers that links the rostralmost part of the superior temporal gyrus with the orbital and medial frontal cortex and which constitutes a part of the classical pathway known as the uncinate bundle (Un Bd); (2) a second bundle of fibers that links various areas of the middle sector of the superior temporal gyrus predominantly with areas lying on the lateral surface of the frontal lobe; this fasciculus occupies a position in the ventralmost part of the extreme capsule (Extm Cap) just above the fasciculus uncinatus; and (3) a bundle of fibers that connects the posteriormost part of the superior temporal gyrus with the posterior part of the dorsolateral frontal cortex and which forms part of the arcuate fasciculus (Arc F); further forward, these fibers become part of the superior longitudinal fasciculus (SLF). In addition to the above findings, the present investigation has confirmed an earlier observation (Pandya et al., '69) that the primary auditory koniocortical area (KA) does not project to the frontal lobe directly and that its corticocortical connections are restricted to the nearby auditory cortical areas that surround it. It is clear, however,


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Fig. 9. Diagrammatic representation of the isotope 1nJcctlon involving area Tpt of STG and the distribution of thr: labeled fibers in the frontal lobe in case 8.

from the results of the present investigation, that the cortical areas surrounding the auditory koniocortex on the supratemporal plane do project to the frontal cortex, al- though these projections are not extensive (see Fig. 10).

The rostral part of the superior temporal gyrus includes the temporopolar proisocortical area and the isocortical areas Tsl and Ts2 (see Fig. 1). In the proisocortical area, one observes the beginning of a distinct but narrow layer IV, a characteristic that constitutes the first step of differentiation from the primitive periallocortex. The adjacent area Tsl, on the other hand, is true isocortex. It has a well- defined layer IV, but it shares with proisocortex the characteristic of near-fusion of layers V and VI. In material stained for myelin, only the outer stripe of Baillarger can be distinguished. In area Ts2, however, which lies just posterior to Tsl, the inner stripe of Baillarger can be clearly identified and, in material stained with thionine, a clear differentiation between layers V and VI can be observed. The findings of the present investigation have shown that these three areas give rise to a major bundle of fibers that travels to the orbital and medial frontal cortex as part of the fasciculus uncinatus. These fibers curve sharply at about the level of the limen insulae and continue forward into the frontal lobe occupying the ventralmost part of the extreme capsule. In the frontal lobe, they form a flat lamina of fibers running just above the orbital cortex and terminat-

ing within the proisocortical areas on the orbital and medial aspects of the frontal lobe, as well as within the nearby orbital areas 13, 12, 11 and within the medial areas 9, 10, 14.

The second major bundle of fibers originates from the middle part of the superior temporal gyrus, which includes cytoarchitectonic areas Ts3 and paAlt. A number of distinct cytoarchitectonic features form the basis of demarcation between these two areas. For instance, paAlt is character- ized by the presence of very large pyramidal cells in the deeper portion of layer 111 and by a relative paucity of cells in layer V, which gives rise to a striking appearance of separation between this latter layer and layer VI. Area Ts3, on the other hand, has a very dense layer V and a layer I11 that is rich in pyramidal cells, but without the very large cells typical of paAlt. The present investigation has shown that fibers originating from these two areas of the superior temporal gyrus travel initially within the med- ullary core of the superior temporal gyrus and, upon reach- ing the inferior circular sulcus, turn upward to occupy the lower portion of the extreme capsule. Further forward, these fibers continue their course, occupying a position just dorsal to that of the uncinate fibers that were described above. Within the frontal lobe, rostral to the level of the temporal pole and where the claustrum has assumed a virtually horizontal position, a relatively small number of these fi-

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CASE 9


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B Fig. 10. Diagrammatic representation of the isotope injections involving

the primary (KA) and secondary auditory (proA) areas and area paAlt in case 9, and the primary auditory area (KA) in case 10, as well as the

distribution of label within the frontal lobes. Note that no label was found in the frontal lobe in case 10.

bers spread out under the rostral putamen to terminate in orbital and medial parts of the frontal lobe. Another stronger contingent of these fibers turns upward over the dorsolateral part of the caudate nucleus to terminate within areas of the dorsolateral frontal cortex (areas 12, upper 46, and 9) and of the dorsal aspect of the medial frontal lobe (medial areas 9 and 10).

The posterior part of the superior temporal gyrus (caudal area paAlt and Tpt) projects to the middle and posterior regions of the dorsolateral frontal cortex, i.e., upper and lower area 46, dorsal area 8, and the rostralmost part of area 6, which lies within the superior bank of the upper limb of the arcuate sulcus. At first, these fibers travel in a medial direction and curve around the caudalmost part of the Sylvian fissure. They then turn in a rostral direction

and run forward, occupying a position lateral to the upper margin of the putamen and medial to the superior branch of the circular sulcus that defines the upper limit of the insula. Within the frontal lobe, these fibers run under the angle formed by the superior and inferior limbs of the arcuate sulcus and, at this point, begin to divide into various fascicles that are directed toward their respective target areas within the dorsolateral frontal cortex.

A general observation regarding the pattern of temporofrontal connections can be made on the basis of the present investigation. The various areas on the lateral surface of the superior temporal gyrus and the supratemporal plane are connected with areas of the frontal cortex that exhibit similar architectonic characteristics. Thus, the rostralmost sector of the superior temporal gyrus, which exhibits rela-


Fig. 11. Darkfield photomicrographs to show the isotope injection sites as well as the location of labeled frontotemporal fiber tracts and terminations in three cases. The upper panel shows an isotope injection of the caudal STG (0, the location of the fiber tract, arcuate (ARC F) and superior longitudinal fasciculi (SLF) (R), and the terminal label in area 8 (A) of the frontal lobe in case 6. The middle panel shows an isotope injection of the

middle STG (F), the location ofthe fiber tract in the extreme capsule (Extm Cap) (El, and the terminal label in area 46 (D) in case 4. The lower panel shows the isotope injection of the rostra1 STG (I); H and G show the location of fiber tracts, uncinate bundle (Un Bd), and terminations in areas 13 and 25 of the frontal lobe in case 2.


Fig. 12. Artist's schematic rendition of the trajectories of the temporo-frontal fibers originating from the rostral (Un Bd: 1) middle (Extm Cap: 2), and caudal (ARC F and SLF: 3) parts of the superior temporal gyrus.

tively primitive architectonic characteristics, is linked with areas of the orbital and medial frontal cortex that are at a comparable stage of architectonic differentiation. Similarly, the midtemporal sector is preferentially connected with the rostral part of the lateral and medial frontal cortex, i.e., areas with comparable architectonic features. Finally, the posteriormost part of the superior temporal gyrus, which shows the most specialized architectonic characteristics, is predominantly linked to frontal areas exhibiting comparable features. These observations suggest that different parts of the superior temporal gyrus may have evolved in parallel with particular sectors of the frontal cortex and that their interconnectivity may reflect subsystems within the cerebral cortex that serve particular functional requirements.

Early studies of the primate auditory cortex established its location within the caudal aspect of the superior temporal plane, defined its input from the medial geniculate body, and indicated the existence of an orderly representation of the cochlear partition within it (Poliak, '32; Walker, '38; Licklider and Kryter, '42; Walzl and Woolsey, '43). More recent studies have further demonstrated that the auditory cortex on the supratemporal plane is organized in terms of a core koniocortical area, consisting of a complete and orderly representation of the cochlear partition, sur- rounded by several other fields that can be distinguished on the basis of both anatomical and physiological criteria (Merzenich and Brugge, '73; Pandya and Sanides, '73; Jones and Burton, '76). The lateral surface of the superior temporal gyrus can also be subdivided into a number of cytoarchitectonically distinct fields that are closely linked with the auditory areas of the supratemporal plane (Pandya and Sanides, '73; Fitzpatrick and Imig, '80; Galaburda and Pan- dya, '83).

Evidence for the involvement of the lateral surface of the first temporal convolution in auditory functions comes from a variety of observations. Recordings of auditory evoked potentials from the human temporal cortex during opera- tions have shown that such potentials can be obtained from the lateral surface of the posterior two-thirds of the first temporal convolution, as well as from the cortex of the supratemporal plane (Celesia et al., '68; Celesia, '76). Pa- tients undergoing surgery for the treatment of pharmaco- logically intractable epilepsy report complex auditory experiences, such as hearing a voice, music, or some other meaningful sound when the exposed lateral surface of the first temporal convolution is electrically stimulated. By contrast, when the stimulation is confined to the anterior transverse gyrus of Heschl, buried in the Sylvian fossa, only crude auditory sensations are reported (Penfield and Jasper, '54; Penfield and Perot, '63).

Fui-ther evidence with regard t o the role of the lateral surface of the superior temporal gyrus in auditory function has been provided by studies of patients who had sustained damage to this region of the brain. For example, Milner ('62) has shown that unilateral excisions from the right anterior temporal lobe that included variable amounts of the first temporal convolution resulted in significant impairments on auditory tasks that required comparison between two sequences of tones in order to detect a change in the sequence, as well as on tasks that required judgement of tone quality. It should be noted that these impairments could be demonstrated whether or not Heschel's gyrus was removed. Shankweiler ('66) has subsequently reported a deficit. after right anterior temporal lobectomy in the recognition of melodies that were presented dichotically. More recently, Zatorre ('85) has shown that right anterior tem-

TEMPOROFRONTAL, CONNECTIONS 65

poral lobectomy impairs melodic discrimination and, fur- thermore, that in cases where the excision extends posteriorly to include the primary auditory cortex, an additional deficit can be detected which seems to be indepen- dent of the impairment caused by right temporal lobectomies sparing this region. There is now evidence that the primary auditory cortex and surrounding areas in the right temporal lobe play a major role in extracting the pitch corresponding to the fundamental frequency from a complex auditory stimulus (Zatorre, '86).

In work with nonhuman primates, it has been shown that ablations of the lateral surface of the superior temporal gyrus sparing the primary auditory cortex cause enduring defects in the performance of auditory sequence discrimination tasks (Dewson et al., '70; Cowey and Dewson, '72). Similar defects in auditory sequence discrimination can also be observed in monkeys with lesions restricted to the anterior part of the superior temporal gyrus (Strominger et al., '80). These findings are in agreement with those obtained in investigations with patients and suggest that the cortex of the superior temporal gyrus that lies outside the supratemporal plane is one of the critical regions for processing auditory pattern information.

The massive input from the superior temporal region to the frontal cortex that has been demonstrated in the present as well as in previous anatomical investigations raises the question of the significance of these projections. The frontal cortex is a large region of the brain that is hetero- geneous in terms of both structure and function. It has major reciprocal connections with a variety of cortical association areas, some of which provide modality-specific and others multimodal input (see Pandya and Barnes, '87). Investigations of the behavioral deficits resulting from damage to the frontal cortex in man and monkey suggest that this part of the cortex subserves complex regulatory processes (see Luria, '66; Fuster, '80; Milner and Petrides, '84; Stuss and Benson, '86). For example, damage to the frontal cortex impairs the ability to organize and monitor sequences of responses (Pinto-Hamuy and Linck, '65; Brody and Pribram, '78; Petrides and Milner, '821, to adapt behavior to changes in environmental circumstances (Milner, '64; Mishkin, '64; Luria, '66), and to learn the appropriate responses to various stimuli in situations requiring selection from a set of alternative responses (Petrides, '85). It is therefore to be expected that, under certain circumstances, damage to the frontal cortex will result in impairments on tasks involving auditory stimuli (e.g., Blum, '52; Weis- krantz and Mishkin, '58; Gross and Weiskrantz, '62; Symmes, '67; Goldman and Rosvold, '70; Stamm, '73; We- gener, '73). Such impairments, however, should not be taken to imply that lesions to the frontal cortex cause primary defects in the perception of acoustic signals, but rather that the regulatory mechanisms subserved by the frontal cortex can find expression in tasks involving stimuli from any sensory modality, including audition. For instance, some of the impairments on auditory tasks following large frontal lesions or lesions restricted to the inferior frontal convexity of the monkey can be attributed to perseveration of inappro- priate response patterns (Iversen and Mishkin, '70, '73). Similarly, it has been shown that certain impairments on auditory tasks after lesions to the periarcuate region of the dorsolateral frontal cortex can be ascribed to a failure in conditional learning, i.e., in learning to produce the correct responses when particular auditory stimuli are presented (Petrides, '86).

In addition, there is no strong evidence that lesions of the human frontal cortex can cause auditory perceptual impair-

ments. Using signal detection methods, Zatorre ('85) was able to show that whereas patients with right temporal excisions exhibited significant impairments in melodic discrimination, patients with right frontal lesions did not differ from the normal control subjects on the discrimination measure. The patients with frontal cortical excisions, however, had significant response biases which might have resulted in impaired performance in melodic discrimination had the appropriate methods not been used to separate these biases from discrimination performance. The few studies that had previously reported impairments on auditory tasks after frontal-lobe lesions had not used methods appropriate for separating perceptual impairments from response biases (Grossman et al., '81; Shapiro et al., '81).

Thus, there is no convincing evidence, either in man or in the monkey, to indicate that the frontal cortex plays an important role in the perception of auditory stimuli as distinct from its role in the regulation of behavior on the basis of information provided by the various sensory modal- ities, including the auditory system. This should not be taken to imply that there is no specialization within the frontal cortex with reference to particular sensory systems. On the contrary, the demonstration in the present investigation of "preferred' sites within the frontal cortex for auditory input originating from different parts of the superior temporal gyrus together with the findings of previous anatomical investigations concerning auditory, visual, and somatosensory inputs (e.g., Jones and Powell, '70; Chavis and Pandya, '76; Jacobson and Trojanowski, '76; Barbas and Mesulam, '81, '85; Petrides and Pandya, '84) suggests the existence of some degree of functional organization within the frontal lobe along modality-specific lines (Pe- trides, '87). Indeed, the challenge for the future lies not only in specifying the particular contribution(s1 of different areas of the frontal cortex to the control of behavior, but also in determining to what extent this control is effected along modality-specific lines and at what point complex multimodal interactions occur. In this endeavor, further anatomical studies of the frontal cortex in association with behavioral and electrophysiological investigations will play a pivotal role.

ACKNOWLEDGMENTS This work was supported by E.N.R.M. Veterans Hospital,

Bedford, MA, by NIH grant NS16841 to D.N. Pandya, and by NSERC grant A7466 to M. Petrides. We are thankful to Dr. E. Yeterian for his comments on the mansucript and to Mr. Michael Schorr for technical assistance.

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