THE JOURNAL OF COMPARATIVE NEUROLOGY 225:31-43 (1984)

Some Observations on the Course and

Composition of the Cingulum Bundle in
the Rhesus Monkey
ELLIOTT J. MUFSON AND DEEPAK N. PANDYA
Bullard and Denny-Brown Laboratories of Harvard Neurology Department and Charles
A. Dana Research Institute of Beth Israel Hospital, Boston, Massachusetts 02215 and
Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts 01730

ABSTRACT
The course and composition of the cingulum bundle was examined by
using the autoradiographic tracer technique in the rhesus monkey. The
cingulum bundle is observed to consist of three major fiber components
originating from thalamus, cingulate gyrus, and cortical association areas.
Following isotope injections in the anterior and lateral dorsal thalamic
nuclei, labelled fibers form an arch in the white matter behind the cingulate
sulcus and occupy the ventral sector of the cingulum bundle. The fibers from
the anterior thalamic nucleus coursing in the cingulum bundle extended
rostrally to the frontal cortex and caudally to area 23 and the retrosplenial
cortex. In contrast, the fibers from lateral dorsal nucleus reached the retro-
splenial cortex as well as the parahippocampal gyrus and presubiculum.
Efferent fibers from the cingulate gyrus occupy a dorsolateral sector of the
cingulum bundle. Those fibers from area 24 of the cingulate gyrus are
directed to the premotor and prefrontal regions as well as area 23 and
retrosplenial cortex. The fibers from area 23 extend rostrally to the prefron-
tal cortex and caudoventrally to the presubiculum and parahippocampal
gyrus. Finally, a n association component originates mainly from prefrontal
cortex and posterior parietal region. These fibers occupy a more dorsal and
lateral periphery in the cingulate white matter. Cingulum bundle fibers
from the prefrontal cortex extend up to the retrosplenial cortex while those
from the posterior parietal cortex extend caudally to the parahippocampal
gyrus and presubiculum, and rostrally up to the prefrontal cortex.

Key words: cingulate, cortex, thalamus, autoradiography,connections

The cingulum bundle has been described traditionally as
the primary association bundle of the cingulate gyrus (Kap-
pers et al., ’36). This white matter fiber system is thought
to consist of relatively short association fibers within the
cingulate gyrus and of longer association fibers connecting
the cingulate gyrus with the cortex of the orbital, frontal,
and juxtahippocampal regions (Bevore, 1891).Early studies
of the cingulum bundle by the Golgi technique in the rat
led Cajal (’55)to conclude that the fibers of the cingulum
proper consisted of short corticocortical fibers as well as
long fibers which traversed parallel to the cingulate gyrus.
Cajal considered fibers within the bundle which coursed
posteriorly as “associational” (i.e., corticocortical) while
those that course anteriorly he regarded as “projectional,”
i.e., reaching subcortical targets (Cajal, ’55).
In Cajal’s description of the composition of the cingulum
bundle, however, there is no mention of how thalamocorti-
cal fibers travel within the cingulum bundle. More recent
studies of the projections of rat thalamus (Domesick, ’70;
Krieg, ’61) have revealed an extensive component of the
cingulum bundle associated with thalamocortical projec-
tions. Moreover, Domesick (’70) demonstrated that cortico-
fugal and corticopetal fibers of the cingulate cortex occupy
different sectors within the white matter of the cingulum
bundle. This latter investigation revealed that the thala-
mocortical fibers were situated in the external portion of
the medullary core which included the cingulum bundle,
while cortical fibers were virtually absent from this sector
of the cingulum bundle. On the other hand, cortical fibers
do traverse the more ventral stratum, corresponding to the
Accepted October 27, 1983.

0 1984 ALAN R. LISS, INC.

32 E.J. MUFSON AND D.N. PANDYA
internal portion of the white matter of the cingulum bun- -
dle. According to Domesick ('701, these latter fibers do not
A bbreoiations
actually become enclosed within the cingulum bundle, but AC anterior commissure
rather traverse the bundle and aggregate in the deeper AMG amygdala
fiber stratum (the internal stratum) from which they pene- AS arcuate sulcus
trate the callosal fiber system to join the internal capsule. Br. ST. brainstem
Thus, in the rat, the available data suggest that the cin- C claustrum
cc corpus callosum
gulum bundle does in fact contain thalamocortical projec- Cd caudate nucleus
tions. This, however, conflicts with the earlier notion of cdc centralis densocellularis thalamic nucleus
Cajal that the cingulum bundle contains mostly fibers of CF calcarine fissure
cortical origin. A complete understanding of the precise Ci internal capsule
CING BD cingulum bundle
course and configuration of the cingulum bundle in other CING S cingulate sulcus
mammalian species is at best fragmentary. CL centralis lateralis thalamic nucleus
The available information concerning the composition and CM centromedian thalamic nucleus
trajectory of the cingulum bundle in primates has been cs central sulcus
GP giobus pallidus
derived from gross dissections of the human brain (Bevore, H hippocampus
1891), as well as from Marchi (Showers, '59) and myelin m habenula
(Yakovlev and Locke, '61) studies in the monkey. Although 10s inferior occipital sulcus
Showers ('59) described in great detail the afferent and IPS intraparietal sulcus
LD lateral dorsal thalamic nucleus
efferent connections of the cingulate gyrus, she did not LG lateral geniculate nucleus
attempt to ascertain the topographic distribution of the LP lateral posterior thalamic nucleus
different fiber systems traveling within the cingulum bun- LS lunate sulcus
dle. By contrast, Yakovlev and Locke ('61) demonstrated MD mediodorsal thalamic nucleus
MG medial geniculate nucleus
that efferents from the cingulate gyrus occupy specific parts OL lateral orbital sulcus
of the cingulum bundle en route to various cortical and OM medial orbital sulcus
subcortical regions. These investigators also suggested that OTS occipitotemporal sulcus
Pa paraventricular thalamic nucleus
fibers originating from the thalamus reach the cingulate PAR parietal cortex
gyrus via a short route through the "lamina zonalis" and PAR HIPP. parahippocampal gyrus
the internal capsule before entering the cingulum bundle. PF prefrontal sulcus
The technique used by these investigators, namely, retro- POMS parietal occipital medial sulcus
Pre. Sub. presubiculum
grade cell loss and axonal demyelination, however, pre- PS principal sulcus
cluded them from determining the precise course of efferent Pul. pulvinar
and afferent fibers within the cingulum bundle. With the Put. putamen
advent of the autoradiographic technique it is now possible R reticular thalamic nucleus
Re nucleus reuniens
to evaluate cortical association fiber pathways in greater Ret. Sp. retrosplenial cortex
detail. The present study attempts to elucidate the precise RF rhinal sulcus
course and composition of the cingulum bundle using this SF sylvian fissure
tracer technique in the rhesus monkey. More specifically, SN substantia nigra
ST subthalamic nucleus
this study is directed toward the differentiating of the thal- ST. BD. striatal bundle
amocortical from the corticofugal components of the cin- STS superior temporal sulcus
gulum bundle. Sub. Th. subthalamic region
Th thalamus
METHODS V ventricle
VA ventral anterior thalamic nucleus
Sixteen rhesus monkeys with injections of labelled amino VL ventral lateral thalamic nucleus
acids were used in this study. Three received injections of VP ventral posterior thalamic nucleus
radiolabelled amino acids in different thalamic nuclei by VPL ventroposterolateral thalamic nucleus
way of the stereotaxic approach. Eight received direct injec- VPM ventroposteromedial thalamic nucleus
Zi zona incerta
tions into various subdivisions of the cingulate gyrus, the -
remaining five had injections in frontal and parietal corti-
cal association areas. Each injection consisted of a mixture
of labelled amino acids (3H-proline and -leucine) with a RESULTS
volume range of 0.4-1.0 p1 and a specific activity range of The main objective of the present investigation is to out-
40-80 pCi. After a survival period of 6-8 days, animals line the course and composition of the cingulum bundle.
were perfused transcardially with physiological saline fol- Since the precise termination patterns of the cortical and
lowed by 10% formalin and processed for autoradiography subcortical projections of the fibers of the cingulum bundle
according to the protocol of Cowan et al. ('72). Exposure have been previously described (Pandya et al., '81; Baley-
times ranged from 3 to 6 months. Tissue was counter- dier and Mauguiere, '80; Vogt et al., '79; Yetarian and Van
stained through the emulsion with thionin. With bright- Hoesen, '78), they will not be dealt with in detail in this
and darkfield light microscopy the composition and trajec- paper.
tory of the labelled fibers were traced from the injection
site through the cingulum bundle to their point of termi- Thalamic injections
nation. The results were then reconstructed onto enlarged Of the three thalamic cases, two animals (cases 1 and 2)
tracings of coronal sections. The cortical cytoarchitectonic had isotope injections placed in the anterior thalamic nu-
regions are according to the parcellations of Brodmann clei, while in the other animal (case 31, the thalamic target
('05), Walker ('40),and Bonin and Bailey. ('47). was the lateral dorsal nucleus. Although the injection in
CINGULUM BUNDLE
Fig. 1. Diagrammatic representation of the trajectory of the labelled
fibers (indicated as broken lines) shown on tracings of coronal sections (1-9)
following an isotope injection in the anterior thalamus (case 1).Terminal
case 1was aimed at the anterior nucleus of the thalamus,
there was some spread of the isotope, rostrally into the
reticular nucleus, and medially into the paraventricular
and centralis densocellularis nuclei. Caudally, isotope ex-
tended into the medial part of the mediodorsal and centralis
superior thalamic nuclei. Within the anterior nucleus, the
main portion of the injection was concentrated in the ante-
rior medial and the medial part of the anterior ventral
nucleus (Fig. 1). In case 2, the bulk of the injection re-
mained in the posterior sector of the anterior ventral nu-
cleus with some additional involvement of the mediodorsal
thalamic nucleus. The basic fiber trajectory in these two
cases was similar. Fibers emerging from the thalamic injec-
tion travelled in a rostra1 direction beneath the caudate
nucleus and then continued as far as the anterior limb of
33
label is shown as black dots. The extent of the isotope injection is shown in
black on the medial surface of the cerebral hemisphere (upper left1 as well
as in coronal sections 4 and 5.
the internal capsule (Fig. 1, sections 3-5). From the dorsal
aspect of the internal capsule, fibers ascended within the
white matter of the superior frontal gyrus before proceed-
ing ventromedially to the ventralmost portion of the cin-
gulum bundle. This pattern of outflow from the internal
capsule continued rostrally beyond the genu of the corpus
callosum. Labelled fibers remained deep to the fundus of
the cingulate sulcus spreading into the dorsal part of the
cingulum bundle to terminate in areas 24 and 25 (Fig. 1,
sections 1,2).
Within the frontal lobe, another contingent of labelled
fibers from the ventral portion of the internal capsule was
observed to follow a lateral course in the white matter lying
deep to the fundus of the principal sulcus. As shown in
Figure 1 (sections 1,2), this fiber system appeared to course
34
Fig. 2. Diagrammatic representation of the trajectory of the labelled fibers i n the cingulum bundle (sections 1-81 following an isotope injection in
the lateral dorsal thalamic nucleus (case 3).
in the lateral and ventral sectors of the frontal white mat-
ter (along the lateral and ventral surface of the frontal lobe)
before terminating in the orbital cortex and in the principal
sulcus. Since the injections in these cases involved that
portion of the mediodorsal thalamic nucleus which is known
to project through the internal capsule to these lateral and
ventral frontal cortical regions (Tobias, '751, it is quite pos-
sible that fibers observed leading to the orbital surface and
the principal sulcus may not be a part of the cingulum
bundle. At the level of the isotope injection, labelled fiber
fascicles looped around the lateral border of the caudate
nucleus to ascend into the white matter and reached the
cingulum bundle where fibers aggregated in the ventral
sector of the bundle (Fig. 1, sections 4,5 and Fig. 8B,D). At
this level, some of the fibers were found to leave the cin-
gulum bundle to terminate in area 24. Caudal to the injec-
tion site, fibers were also observed to continue to course
laterally around the caudate nucleus en route to the mid-
portion of the cingulum bundle. These fibers followed a
trajectory similar to that described for the more rostral
E.J. MUFSON AND D.N. PANDYA
component of the cingulum bundle. Thus, the fibers were
seen arching in the white matter behind the cingulate
sulcus up to the level of the pulvinar and subsequently
occupied the central core of the cingulum bundle (Fig. 1,
sections 6,7). These fibers appeared to terminate, in part,
in area 23. More caudally, labelled fibers of the cingulum
bundle extended mainly to the level of the retrosplenial
cortex. Only a minor fiber contingent reached beyond this
region (Fig. 1,sections 8,9). These fibers appeared to termi-
nate in discrete clusters in both caudal area 23 and in the
retrosplenial cortex.
In case 3, the isotope injection occupied the rostral portion
of the lateral dorsal thalamic nucleus (Fig. 2, section 4).
Fibers arising from this injection were observed to travel
in the superior thalamic fiber capsule beneath the caudate
nucleus (Fig. 2). Rostrally, these fibers travelled in the most
superior and medial portion of the anterior limb of the
internal capsule as far as the level of the genu of the corpus
callosum. From this position, labelled fibers left the inter-
nal capsule and coursed toward the cingulum bundle. These
CINGULUM BUNDLE
fibers arched dorsally in the white matter behind the cin-
gulate sulcus and then descended ventromedially before
actually reaching the cingulum bundle (Fig. 8A). Once they
entered the cingulum bundle, the fibers occupied its most
lateral and ventral sectors (Fig, 2, sections 1-3). Labelled
fibers at the level of the lateral dorsal thalamic nucleus
first travelled below the caudate nucleus and then ascended
in the white matter following a course similar to that ob-
served for the more rostral fibers (Fig. 2, sections 43).
Caudal to the lateral dorsal nucleus fibers coursed over the
pulvinar nucleus and looped around the caudate nucleus to
join the cingulum bundle (Fig.2, sections 5,6). At this level,
some of the labelled fascicles left the main bundle to enter
the white matter of the posterior parietal lobule (Fig. 2,
sections 6-8). In terms of topography, the fibers appeared
to occupy a more ventral location within the cingulum
bundle as compared to those from the anterior thalamic
nuclei which were primarily concentrated more dorsally
(Fig. 1, sections 6-8). Far caudally, a contingent of these
thalamic fibers was observed to arch around the caudate
nucleus en route to the cingulum bundle (Fig. 2, sections
7,8). From this point, fibers continued around the rostral
portion of the calcarine fissure medial to the posterior horn
of the lateral ventricle, and were joined by another fiber
component which travelled around the lateral wall of the
lateral ventricle (Fig. 2, sections 7,8). Both fiber systems
coursed rostrally and ventrally in the white matter of the
parahippocampal gyrus (perforating sphenocornual fibers;
Cajal, '55) and terminated in the adjoining presubiculum
(Fig. 2, sections 5,6).
Cingulate gyrus injections
Of the eight animals with isotope injections in various
subsectors of the cingulate gyrus, two (cases 4 and 5) had
injections in area 24. In both cases, heavy concentration of
labelled fibers were observed in the lateral portion of cin-
gulate white matter at the site of injection (Fig. 3, sections
2,3). From this position in the cingulum bundle several
labelled fiber fascicles could be traced radially through the
corona radiata (Fig. 3, sections 2,3). One group of fibers
coursed ventrally to occupy a position dorsal to the caudate
nucleus, within which it eventually terminated (Fig. 3,
sections 2,3). Some of these fibers also entered the anterior
limb of the internal capsule to reach the thalamus and the
brainstem while others continued ventrally around the pu-
tamen to become part of the external capsule and termi-
nated, in part, in the claustrum and the putamen (Fig. 3,
sections 2,3). A second group of fibers emanating from the
cingulum bundle arched dorsally in the white matter of the
superior frontal gyrus where they terminated in the medial
portion of the gyrus (Fig. 3, sections 2,3). A third component
coursed through the lateral portion of the white matter of
the cingulum bundle. Some of these latter fibers continued
caudally as well as ventrally to become part of the extreme
capsule and terminated in the amygdala, the perirhinal
cortex, the insula, and the superior temporal cortex (Fig. 3,
sections 4-8). Other labelled fibers extended into the parie-
tal lobe (Fig. 3, sections 6-8). Rostra1 to the injection site,
fibers in the cingulum bundle continued within the white
matter of the prefrontal cortex to terminate in the lateral,
medial, and ventral portions of this cortex. Caudal to the
injection site labelled fibers were observed in a distinct,
comma-shaped bundle in the lateral part of the cingulate
white matter extending into area 23 (Fig. 3, sections 4-8).
Some of these fibers appeared to terminate in adjoining
areas 24 and 23.
35
In cases 8 and 9, the isotope was injected into area 23.
Following these injections, several fiber bundles can be
traced in diverse directions from the injection sites. As in
the previous case, a heavy concentration of fibers was ob-
served in the white matter lateral to the cingulum bundle
near the injection site (Fig. 4, sections 5-7 and Fig. 8E).
From this confluence of fibers several radially directed fas-
cicles can be followed. One group of fibers travelled ven-
trally over the lateral ventricle to take a position dorsal to
the caudate nucleus. These fibers could then be traced
throughout the dorsal periphery of the caudate nucleus
giving off terminations to that nucleus as well as to the
putamen (Fig. 4, sections 3-7). A second group of fibers
continued further ventrally within the internal capsule.
This contingent could be subdivided into thalamic and
brainstem components based on their sites of termination
of fibers (Fig. 4,section 5). Caudal to the injection site, in
area 23, labelled fibers were observed in the corona radiata
coursing toward their termination in the inferior parietal
lobule. At this level, an additional fiber component could
be traced ventrolaterally through the white matter as far
as the cortex of the superior temporal sulcus (Fig. 4, sec-
tions 5-8). Another distinct fiber bundle, occupying the
lateral and dorsal portion of the cingulate gyrus white
matter could be followed both rostrally and caudally (Fig.
8F). In its caudal course, fibers gathered to take a position
behind the splenium of the corpus callosum (Fig. 4, section
8). From here they divided into two components. A medial
component coursed behind the calcarine sulcus while the
lateral coursed laterally around the posterior horn of the
lateral ventricle. These two components joined ventrally
and travelled in the white matter of the parahippocampal
gyrus and terminated in areas TH and TF of the parahip-
pocampal gyrus (Bonin and Bailey, '47) and the presubicu-
lum. At the site of injection, as well as rostral to it, these
fibers were found to occupy the entire periphery of the
cingulum bundle including the white matter behind the
cingulate sulcus (Fig. 4, sections 2-7). Further rostrally in
the prefrontal white matter, these fibers trifurcated to ter-
minate in the dorsal and orbital prefrontal cortex as well
as the cortex of the principal sulcus.
Frontal and parietal injections
Both posterior parietal and anterior frontal regions have
been shown to project to cingulate gyrus via the cingulum
bundle (Jones and Powell, '70; Nauta '64; Pandya and Kuy-
pers, '69; Petras, '71). Since the aim of this investigation is
to elucidate some of the components of the cingulum bun-
dle, only two representative cases, one with a frontal lobe
(case 15) and one with a parietal lobe (case 16) isotope
injection, are described.
Following an injection situated between the caudal por-
tion of the principal sulcus and the upper limb of the ar-
cuate sulcus, labelled fibers were observed to course through
the white matter at the level of the injection site en route
to the cingulum bundle. Upon joining the cingulum bundle
these fibers occupied its outer sector while coursing cau-
dally (Fig. 5A, sections 1-41. At the level of the splenium of
the corpus callosum, these fibers were observed to move to
a more medial sector within the cingulum bundle and then
to terminate in the caudal portion of medial area 7 (Fig.
5A, sections 5,6). Fibers leading to the cingulum bundle
from more rostral portions of the frontal lobe occupy a
position within the cingulum bundle similar to that de-
scribed for case 15. In these cases, however, the fibers ter-
minate in area 23 and retrosplenial cortex as well as the
36
4 5 6 7
Fig. 3. Diagrammatic representation of an isotope injection in area 24 as shown on the medial surface of the hemisphere (upper left), and in
transverse sections 2 and 3. The resulting labelled fibers in the cingulum bundle and in other cortical and subcortical structures are shown on
transverse sections (case 4).
medial parietal cortex, as has been described previously by
Nauta (‘64) and Pandya et al. (‘71).
In case 16, the injection of isotope involved the caudal
aspect of the inferior parietal lobule (area 7, Fig. 5B). Adja-
cent to the injection site, fibers leading to the cingulate
white matter occupied the dorsalmost sector of the cin-
gulum bundle (Fig. 5B, sections 4 and 8C).Rostrally, how-
ever, these fibers concentrated at the dorsal and ventral
periphery of the cingulum bundle. Along their course, these
fibers gave off terminations in the cingulate gyrus (areas
23 and 24; Fig. 5B).
DISCUSSION
The white matter underlying the cingulate gyrus has
been previously considered to be composed of a heteroge-
neous group of complgx fiber systems. As shown in the
present study, this white matter appears to contain three
E.J. MUFSON AND D.N. PANDYA
principal fiber components: one arising from the thalamus,
a second from the cingulate gyrus, and a third from associ-
ation cortices. Although these fiber systems intermingle
within the cingulum bundle, each also exhibits a distinct
topography. Moreover, each fiber system contributes to the
cingulum bundle in a specific manner.
Thalamic fibers from the anterior and lateral dorsal tha-
lamic nuclei follow a complex pathway before gathering
within the cingulum bundle (Fig. 6A,B). Fibers emanating
from both of these thalamic nuclei travel first anteriorly
via the internal capsule and laterally, as well as posteriorly
through the superior thalamic peduncle. These thalamic
fibers then arch dorsally in the white matter behind the
cingulate sulcus before eventually coming to occupy the
ventral sector of the cingulum bundle. Those fibers origi-
nating in the anterior thalamic nuclei travel anteriorly to
the cingulum bundle to reach the white matter of the fron-
CINGULUM BUNDLE 37

Fig. 4. Diagrammatic representation of an isotope injection in area 23 as shown on the medial surface of the hemisphere (upper left) and i n trans-
verse sections 5-7. The resulting labelled fibers in the cingulum bundle and other cortical and subcortical structures are shown on transverse sections
(case 8).

tal lobe and terminate in the prefrontal cortex (Fig. 6A).
From the anterior thalamic nuclei caudally directed fibers
extend as far as the level of the retrosplenial cortex and
terminate in .ea 23 and retrosplenial cortex. By contrast
fibers from tile lateral dorsal nucleus, upon entering the
cingulum bundle, course posteriorly as far as the level of
the splenium of the corpus callosum and terminate in the
parietal lobe and in the retrosplenial region (Fig. 6B). From
this position, fibers travel ventrally on either side of the
posterior horn of the lateral ventricle to reach the white
matter of the parahippocampal gyrus and terminate in the
cortex of the parahippocampal gyrus and the presubiculum.
Another source of fibers of the cingulum bundle is from
the cingulate cortex itself (areas 23 and 24; Fig. 7A,B). In
contrast to the fiber contingent originating in the thalamus
which is situated in the ventral sector of the cingulum
bundle, fibers derived from the cingulate cortex occupy the
dorsolateral sector of the cingulum bundle, including the
fiber fascicle arching around the cingulate sulcus. Those
cingulum bundle fibers originating from area 24 of the
cingulate gyrus which course within the cingulum bundle
terminate in the premotor and prefrontal regions, rostrally,
and in area 23 and retrosplenial cortex, caudally. Cingulum
fibers derived from area 23 travel rostrally to the white
38

Fig. 5. Diagrammatic representations of isotope injections in the prefrontal and inferior parietal lobule shown on the lateral surface of cerebral
hemisphere (upper right). The resulting trajectories of labelled fibers in the cingulum bundle are shown in transverse sections in cases 15 and 16,
respectively.
CINGULUM BUNDLE
matter of the frontal lobe where they terminate in prefron-
tal cortex. Caudally directed fibers from area 23, by con-
trast, arch around the splenium of the corpus callosum and
course ventrally around the posterior horn of the lateral
ventricle to join the perforating sphenocornual fibers of
Cajal('55). These fibers then terminate in the presubiculum
and parahippocampal gyrus. Laterally directed fibers orig-
inating from the cingulate cortex radiate into several differ-
ent fiber bundles in the white matter taking the shape of
an "Indian war bonnet" (Fig. 8E) as described by Yakovlev
and Locke ('61). These fascicles are further directed to the
corpus callosum, thalamus, lateral parieto-temporal re-
gions, and the corpus striatum. The cingulostriatal fiber
system courses parallel to the cingulum bundle and encom-
passes the entire circumference of the medial striatum from
the anterior to the inferior horn of the lateral ventricle as
has been described by other investigators (Mettler '35;
Showers '59; Yakovlev and Locke, '61). Unlike earlier ob-
servations, which showed the origin of these fibers to be
mainly the anterior cingulate gyrus (Yakovlev and Locke,
'611, the present findings indicate that the anterior and
posterior cingulate gyrus contribute fibers to this cortico-
striate fascicle, which from its location, would appear to
correspond to the subcallosal fascicle of Muratoff (1893). It
should be noted, however, that some of the fibers from area
24 to the striatum also travel via the external capsule in
the frontal lobe.
An additional component of the cingulum bundle consists
of fibers arising from cortical association areas. These in-
clude frontal and parietal areas. Other cortical regions such
as insula (Mufson, unpublished observations) and certain
inferior temporal areas (Rosene and Pandya, unpublished
observations) also contribute to the cingulum bundle. In
comparison to the thalamic component of the cingulum
bundle, which occupies a more ventral position, the associ-
ation fibers from the parietal and frontal areas are situated
in the more dorsal and lateral periphery of the cingulate
white matter. In this sense the location of these association
fibers resembles that of the cingulate gyrus fibers.
Thus, the cingulum bundle comprises thalamic, cingu-
late, and association fiber components. Each component has
a characteristic distribution and topography within this
bundle. The thalamic contingent forms an arch in the white
matter and then crystalizes in the ventral core of the cin-
gulum bundle while the fibers from the cingulate gyrus
remain in the lateral periphery of the cingulate white mat-
ter extending dorsally around the cingulate sulcus and then
diverge laterally into several fascicles. The contingent of
the cingulum bundle fibers originating in association cor-
tex, like the cingulate gyrus fibers, remains in the lateral
and ventral periphery of the bundle.
It should be noted that there are certain similarities
among the termination patterns of the subcomponents of
the cingulum bundle, Fibers arising in the anterior tha-
lamic nuclei, the anterior cingulate gyrus, and frontal lobe
have similar sites of termination. Similarly, the cingulum
bundle fibers from the lateral dorsal thalamic nucleus, the
posterior cingulate gyrus, and the parietal lobe have com-
mon fiber termination patterns. Fibers from the anterior
thalamic nuclear group course within the cingulum bundle
to reach the cingulate gyrus and the retrosplenial cortex.
Likewise, fibers from area 24 travel rostrally to the medial
ventral prefrontal cortex, insula, amygdala, and perirhinal
region as well as caudally to area 23 and retrosplenial
cortex. Frontal lobe fibers coursing within the cingulum
39
bundle terminate in the posterior cingulate region (area
231, medial parietal cortex (area 7), and retrosplenial cortex.
By contrast, the cingulum bundle fibers coming from the
lateral dorsal thalamic nucleus are directed caudally around
the splenium of the corpus callosum to terminate in the
presubiculum. In the same manner, fibers from area 23
follow a similar trajectory around the splenium of corpus
callosum before terminating in the presubiculum and para-
hippocampal gyrus. Parietal lobe-derived cingulum bundle
fibers terminate, rostrally, in area 24 and caudally, in area
23. These caudally directed fibers assume a course similar
to that described for fibers emanating from the lateral
dorsal nucleus and area 23 (see cases 3, 8, 16, sections 8, 8,
and 5, respectively) and terminate in the parahippocampal
gyrus as well as presubiculum (Seltzer and Pandya, '83).
Despite the different sources of input to the cingulum bun-
dle, there appear then to be certain commonalities in terms
of limbic and paralimbic terminations between the anterior
thalamic nuclear group, area 24, and frontal lobe, on the
one hand, and the lateral dorsal thalamic nucleus, area 23,
and posterior parietal cortex, on the other.
Although this study has not completely identified the
source of all fibers going into the making of the cingulum
bundle, it has demonstrated its heterogeneous composition;
i.e., fibers within the bundle are derived from the thalamus,
cingulate gyrus, and association cortices as previously sug-
gested to by Showers ('59) and Yakovlev and Locke ('61). It
may be useful then to conceptualize the white matter of the
cingulate gyrus as similar to that of any other white matter
system underlying a given cortical region. The fiber bundle
underlying a cortical area includes an association compo-
nent, consisting of those fibers connecting it with other
ipsilateral zones (associational fibers) and contralateral
(commissural fibers) areas. Another component would be
destined toward subcortical structures such as the thala-
mus, the brainstem, and the striatum. The third component
would consist of thalamic radiation fibers. As has been
shown, the white matter of cingulum bundle contains an
association fascicle from parietal-temporal and frontal re-
gions, a subcortical fascicle to the thalamus, brainstem, and
striatum; and a thalamic component from anterior and
lateral dorsal thalamic nuclei. The white matter of the
cingulate gyrus also conveys substantial fibers destined for
limbic and paralimbic structures, such as the insula, retro-
splenial area, parahippocampal gyrus, presubiculum, and
the perirhinal region. In this respect the cingulum bundle
bears close resemblance to the white matter underlying
prefrontal, posterior parietal, and ventral temporal cortical
regions since all of these cortical areas have been shown to
have a fiber component leading to limbic and paralimbic
regions (Jones and Powell, '70; Nauta, '64; Pandya et al.,
'71; Pandya and Kuypers, '69; Seltzer and Pandya, '78, '76;
Seltzer and Van Hoesen, '79).
The present findings underscore the complexity of the
different fiber components making up the cingulum bundle.
Because of the heterogeneity of the cingulum bundle any
procedure disrupting the cingulum bundle, whether for
clinical or experimental purposes, must necessarily involve
extensive disconnections among various cortical, subcorti-
cal, and limbic structures.
ACKNOWLEDGMENTS
We wish to thank Drs. G.W. Van Hoesen and B. Seltzer
for their helpful comments on the manuscript. We are also
grateful to Brian Buttler, Lydia Kenton, and Leah Christie
 Fig. 6. Artist’s rendition of the trajectory of the thalamic component of the cingulum bundle originating from the anterior thalamus (A) and lateral
dorsal thalamic nucleus (B).
Fig. 7. Artist’s rendition of the trajectory of cingulum bundle fibers originating from areas 24 (A) and area 23 (B).
42 E.J. MUFSON AND D.N. PANDYA

Figure 8
CINGULUM BUNDLE
for technical and secretarial assistance. This study is sup-
ported by the Veterans Administration, Edith Nourse Rog-
ers Memorial Veterans Hospital, Bedford, Massachusetts
and NIH grants NS 09211, NS 16841, and NS 07211.
We would like to dedicate this paper to Dr. Paul Yakovlev,
whose original thinking and outstanding contribution to
the limbic system has prompted us to conduct the present
investigation.
LITERATURE CITED
Baleydier, C., and F. Mauguiere (1980) The duality of the cingulate gyrus
in monkey. Brain 103:525-554.
Bevore, C.E. (1891) On the course of the fibers of the cingulum and posterior
parts of the corpus callosum and fornix in the Marmoset monkey. Philos.
Trans. 182135-200.
Bonin, G.V., and P. Bailey (1947)The Neocortex of Macaca mulatta. Urbana:
The University of Illinois Press.
Brodmann, K. (1905) Beitrage zur histologischen Localisation der Gros-
shirnrinde. 111. Dritte Mitteilung. Die Rindenfelder der niederen Affen.
J. Psychol. Neurol. (Lpz.)4:177-226.
Cajal, S. Ramon y (1955) Studies on the cerebral cortex (Lisbeth Kraft,
Transl.). Chicago: Year Book Publishers, pp. 101-118.
Cowan, W.M., D.I. Gottlieb, A.E. Hendrickson, J.L. Price, and T.A. Woolsey
(1972) Autoradiographic demonstration of axonal connections in the
central nervous system. Brain Res. 3731-51.
Domesick, V.B. (1970) The fasciculus cinguli in the rat. Brain Res. 20:19-
32.
Jones, E.G., and T.P.S. Powell (1970) An anatomical study of converging
sensory pathways within the cerebral cortex of the monkey. Brain
93:793-820.
Kappers, C.V.A., C.G. Huber, and E.C. Crosby (1936) The Comparative
Anatomy of the Nervous System of Vertebrates, Including Man. New
York: The Macmillan Company.
Krieg, W.J. (1961) Connections of the cerebral cortex. I. The albino rat. C.
Extrinsic connections. J. Comp. Neurol. 86367-394.
Mettler, F.A. (1935) Corticofugal fiber connections of the cortex of Macaca
mulatta: The Frontal Region. J. Comp. Neurol. 61509-542.
Muratoff, W. (1893) Secundare Degeneration nach Durchschneiden des Cor-
Fig. 8. Darkfield photomicrographs showing isotope injections in the
thalamus and cingulate gyrus and resulting labelled fibers in the cingulum
bundle. Magnification, x9. In A and B isotope injections are in lateral
dorsal thalamic nucleus (case 3)and anterior thalamus (case 11,respectively.
Note the arching fibers (white arrows) leading to the cingulum bundle. In C
and D the location of labelled fibers in cingulum bundle from the parietal
lobe (case 16) and anterior thalamus (case 2) injections are shown, respec-
tively. Note the dorsal location (white arrow) of the fibers from the parietal
lobe and the ventral location of fibers (white arrow) from the thalamus in
the cingulum bundle. In E the isotope injection in area 23 (case 8 ) and
resulting trajectory of adjacent labelled fibers portraying the appearance of
an Indian Warbonnet are shown. In F the location of rostrally directed
labelled fibers (white arrow) in cingulum bundle from area 23 (case 8 )
injection to occupy the midportion of cingulum bundIe is shown.
43
pus Callosum. Neurol. Zbl. 12316, 714-729.
Nauta, W.J.H. (1964) Some efferent connections of the prefrontal cortex in
the monkey. In J.M. Warren and K. Akert (eds): The Frontal Granular
Cortex and Behavior. New York: McGraw-Hill, pp. 397-409.
Pandya, D.N., P. Dye, and N. Butters (1971) Efferent cortico-cortical projec-
tions of the prefrontal cortex in the rhesus monkey. Brain Res. 31:35-
46.
Pandya, D.N., and H.G.J.M. Kuypers (1969) Cortico-cortical connections in
the rhesus monkey. Brain Res. 14:49-65.
Pandya, D.N., G.W. Van Hoesen, and M.-M. Mesulam (1981) Efferent con-
nections of the cingulate gyrus in the rhesus monkey. Exp. Brain Res.
42319-330.
Petras, J.M. (1971)Connections of the parietal lobe. J. Psychiatr. Res. 8:189-
201.
Seltzer, B., and D.N. Pandya (1976)Some cortical projections to the parahip-
pocampal area in the rhesus monkey. Exp. Neurol. 50:146-160.
Seltzer, B., and D.N. Pandya (1978) Afferent cortical connections and archi-
tectonics of the superior temporal sulcus and surrounding cortex in the
rhesus monkey. Brain Res. 149:l-24.
Seltzer, B., and D.N. Pandya (1983) Parieto-temporal connections in the
rhesus monkey. Anat. Rec. 205:180A.
Seltzer, B., and G.W. Van Hoesen (1979) A direct inferior parietal lobe
projection to the presubiculum in the rhesus monkey. Brain Res.
179:157-161.
Showers, M.J.C. (1959) The cingulate gyrus: Additional motor area and
cortical autonomic regulator. J. Comp. Neurol. 12231-301.
Tobias, T.J. (1975) Afferents to prefrontal cortex from the thalamic medio-
dorsal nucleus in the rhesus monkey. Brain Res. 83:191-212.
Vogt, B.A., D.L. Rosene, and D.N. Pandya (1979) Thalamic and cortical
afferents differentiate anterior from posterior cingulate cortex in the
monkey. Science 204:205-207.
Walker, A.E. (1940) A cytoarchitectural study of the prefrontal area of the
Macaque monkey. J. Comp. Neurol. 73:59-86.
Yakovlev, P.I., and S. Locke (1961) Limbic nuclei of thalamus and connec-
tions of limbic cortex. 111. Corticocortical connections of the anterior
cingulate gyrus, the cingulum, and the subcallosal bundle in monkey.
Arch. Neurol. 5364-400.
Yetarian, E.H., and G.W. Van Hoesen (1978) Cortico-striate projections in
the rhesus monkey: The organization of certain cortico-caudate connec-
tions. Brain Res. 139r43-63.