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THE JOURNAL OF COMPARATIVE NEUROLOGY 441:197–222 (2001)
Architectonic Identification of the Core
Region in Auditory Cortex of Macaques,
Chimpanzees, and Humans
TROY A. HACKETT,1,3* TODD M. PREUSS,2 AND JON H. KAAS3
Department of Hearing and Speech Sciences, Vanderbilt University,
Nashville, Tennessee 37203
2
Cognitive Evolution Group, University of Louisiana at Lafayette,
New Iberia, Louisiana 70560
3
Department of Psychology, Vanderbilt University, Nashville, Tennessee 37203
1
ABSTRACT
The goal of the present study was to determine whether the architectonic criteria used to
identify the core region in macaque monkeys (Macaca mulatta, M. nemestrina) could be used to
identify a homologous region in chimpanzees (Pan troglodytes) and humans (Homo sapiens).
Current models of auditory cortical organization in primates describe a centrally located core
region containing two or three subdivisions including the primary auditory area (AI), a surrounding belt of cortex with perhaps seven divisions, and a lateral parabelt region comprised of at least
two fields. In monkeys the core region can be identified on the basis of specific anatomical and
physiological features. In this study, the core was identified from serial sets of adjacent sections
processed for cytoarchitecture, myeloarchitecture, acetylcholinesterase, and cytochrome oxidase.
Qualitative and quantitative criteria were used to identify the borders of the core region in
individual sections. Serial reconstructions of each brain were made showing the location of the
core with respect to gross anatomical landmarks. The position of the core with respect to major
sulci and gyri in the superior temporal region varied most in the chimpanzee and human
specimens. Although the architectonic appearance of the core areas did vary in certain respects
across taxonomic groups, the numerous similarities made it possible to identify unambiguously
a homologous cortical region in macaques, chimpanzees, and humans. J. Comp. Neurol. 441:
197–222, 2001. © 2001 Wiley-Liss, Inc.
Indexing terms: comparative; primate; neuroanatomy; neurolinguistics; language; imaging;
evolution; acetylcholinesterase; myelin
The search for cortical regions that are largely or wholly
devoted to auditory processing has been the subject of
numerous investigations for over 125 years, leading to the
identification of multiple auditory cortical fields in most
mammals studied. The number of fields identified ranges
from 1 (in marsupials) to over 12 (in primates). In cats, a
single primary auditory field (AI) is surrounded by several
nonprimary auditory fields. In monkeys two or three primary fields, including AI, are enveloped by an even
greater number of nonprimary fields (for reviews, see
Woolsey and Walzl, 1982; Brugge and Reale, 1985; Aitkin,
1990; Schreiner, 1992, 1998; Ehret, 1997; de Ribaupierre,
1997; Rouiller, 1997; Kaas et al., 1999; Kaas and Hackett,
2000). Currently, only the homology of AI has been well
established across major taxonomic groups. Thus, the extent to which findings in one species can be generalized to
another is uncertain. Extending findings from research
© 2001 WILEY-LISS, INC.
DOI 10.1002/cne.1407
animals to humans is especially problematic because experimental constraints limit direct comparisons between
species. One consequence is that both bodies of knowledge
expand, but little connection is made between them. As
Grant Sponsor: National Institutes of Health, NIDCD grants DC00249
and DC04318; Grant sponsor: the McDonnell-Pew Program in Cognitive
Neuroscience; Grant number: JSMF 98-45; Grant sponsor: the James S.
McDonnell Foundation; Grant number: JSMF 20002029; Grant sponsor:
NINDS; Grant number: NS16446; Grant sponsor: the National Institute on
Aging; Grant number: NS1P30 AG-13854-01.
*Correspondence to: Troy A. Hackett, Ph.D., Vanderbilt University, 301
Wilson Hall, 111 21st Avenue South, Nashville, TN 37203.
E-mail: [email protected]
Received 9 March 2001; Revised 17 July 2001; Accepted 17 September
2001
Published online the week of November 12, 2001
198
T. HACKETT ET AL
Fig. 1. Schematic view of the macaque left hemisphere showing
the location and intrinsic connections of auditory cortex. The dorsal
bank of the lateral sulcus has been removed (cut) to expose the
superior temporal plane (LS ventral bank). The floor and outer bank
of the circular sulcus (CiS) have been flattened to show the medial
auditory fields. The core region (dark shading) contains three subdivisions (AI, R, RT). In the belt region (light shading) seven subdivisions are proposed (CM, CL, ML, AL, RTL, RTM, RM). The parabelt
Abbreviations
AChE
AI
AL
AS
ASC
CiS
CL
CM
CPB
CS
CSHG
HG1
HG2
HSa
HSp
IPS
LS
LuS
LuSMF
ML
N
PS
R
RM
RMRPB
RT
RTL
RTM
RTLRTMSI
STG
STS
TTG
acetylcholinesterase
auditory area I (core)
anterior lateral auditory belt
arcuate sulcus
caudal
circular sulcus
caudolateral auditory belt
caudomedial auditory belt
caudal parabelt
circular sulcus
Heschl’s gyrus
first (anterior) gyrus of Heschl
second (posterior) gyrus of Heschl
Heschl’s sulcus (anterior)
Heschl’s sulcus (posterior)
intraparietal sulcus
lateral sulcus
lunate sulcus
myelinated fibers
middle lateral auditory belt
Nissl substance
principal sulcus
rostral area (core)
rostromedial auditory belt
rostral parabelt
rostrotemporal area (core)
rostrotemporolateral auditory belt
rostrotemporomedial auditory belt
sulcus intermedius
superior temporal gyrus
superior temporal sulcus
transverse temporal gyrus (of Heschl)
region (RP, CP; no shading) occupies the exposed surface of the
superior temporal gyrus (STG). The core fields project to surrounding
belt areas (arrows). Inputs to the parabelt arise from the lateral and
medial belt subdivisions. Connections between the parabelt and medial belt fields are not illustrated to improve clarity. Tonotopic gradients in the core and lateral belt fields are indicated by the letters H
(high frequency) and L (low frequency). For abbreviations, see list.
this trend continues, the need for studies that attempt to
link these findings also grows. Toward this end, we have
initiated comparative architectonic studies of auditory
cortex in macaque monkeys, chimpanzees, and humans.
Our goal is to identify features of auditory cortical organization that are common, and unique, to each taxonomic
group.
In recent years we have developed a model of auditory
cortical organization in nonhuman primates based on a
wide range of anatomical and physiological findings
(Hackett et al., 1998a; Kaas et al., 1999; Kaas and Hackett, 2000). According to the model, primate auditory cortex
consists of three major regions containing as many as 12
different fields (Fig. 1). Two or three cochleotopically organized primary or primary-like auditory areas (AI, R,
RT) with independent parallel inputs from the ventral
division of the medial geniculate complex (MGv) comprise
the core region at a first level of processing. The core fields
are surrounded by a belt region of possibly seven fields
(CL, CM, RM, RTM, RTL, AL, ML) at a second level of
processing, with major inputs from the core and the dorsal
division of the medial geniculate complex (MGd). Cochleotopic organization is preserved in at least some of the
belt fields (Rauschecker et al., 1995; Kosaki et al., 1997).
The belt region is bordered laterally on the superior temporal gyrus by a parabelt region of two or more divisions
(CP, RP) that are activated by inputs from the belt areas
and the MGd, but not MGv or the core. Neurons in the belt
and parabelt project to auditory-related fields in the temporal, parietal, and frontal lobes. Experimental evidence
IDENTIFICATION OF THE AUDITORY CORE
supporting this model is derived from numerous studies of
monkeys and chimpanzees (Campbell, 1905; Beck, 1929;
Walker, 1937; von Bonin, 1938; Ades and Felder, 1942;
Bailey et al., 1943; Walzl and Woolsey, 1943; Walzl, 1947;
von Bonin and Bailey, 1947; Bailey et al., 1950; Akert et
al., 1959; Merzenich and Brugge, 1973; Jones and Burton,
1976; Imig et al., 1977; Fitzpatrick and Imig, 1980; Galaburda and Pandya, 1983; Aitkin et al., 1988; Luethke et
al., 1989; Morel and Kaas, 1992; Morel et al., 1993; Jones
et al., 1995; Kosaki et al., 1997; Rauschecker et al., 1997;
Hackett et al., 1998a,b; Recanzone et al., 2000).
Extension of this model to human auditory cortex can be
done in a limited way by comparing anatomical features.
Detailed architectonic parcellations of the human auditory cortex have appeared regularly for nearly a century
(Campbell, 1905; Brodmann, 1909; Vogt and Vogt, 1919;
Flechsig, 1920; von Economo and Koskinas, 1925; Beck,
1928; von Economo, 1929; von Economo and Horn, 1930;
Poljak, 1932; Hopf, 1954; Blinkov, 1955; Braak, 1978;
Galaburda and Sanides, 1980; Seldon 1981a,b, 1982; Ong
and Garey, 1990; Rademacher et al., 1993; Rivier and
Clarke, 1997; Clarke and Rivier, 1998; Morosan et al.,
2001). Although these parcellations differ from one another in many respects, including nomenclature, common
features include a centrally located region with anatomical features typical of primary sensory cortex (e.g., koniocortical cytoarchitecture, dense myelination) surrounded
by a variable number of nonprimary fields with distinctive
architectonic features. These findings suggest that the
basic organizational scheme proposed for monkeys (i.e.,
core, belt) may also apply to humans.
An important observation with relevance to the issue of
homology is that the core, belt, and parabelt regions in
macaques can be reliably identified on the basis of their
structural architectonic features (e.g., cytoarchitecture,
myeloarchitecture). In addition, various molecules (e.g.,
cytochrome oxidase, acetylcholinesterase, parvalbumin)
are expressed at higher levels in the core than in the
surrounding belt areas (Wallace et al., 1991; Morel et al.,
1993; Jones et al., 1995; Hutsler and Gazzaniga, 1996;
Rivier and Clarke, 1997; Hackett et al., 1998a; Clarke and
Rivier,1998). Cytochrome oxidase, involved in the oxidative metabolism of cells, exhibits patterned expression
reflecting the modular organization of primary sensory
cortices (Wong-Riley, 1989) and is also related to the neurovascular events measured in functional imaging studies
(Wobst et al., 2001). Acetylcholinesterase is linked to cholinergic activity in cortex (Mesulam and Geula, 1992) and
is well known to modulate neuronal activity in primary
auditory cortex (Edeline, 1999). The role of the calcium
binding protein parvalbumin is less clear, but it has been
associated with distinct subpopulations of ␥-aminobutyric
acid (GABA)ergic neurons in sensory cortex (van Brederode et al., 1990) and is expressed at high levels in
primary thalamocortical pathways to auditory cortex (Molinari et al., 1995; Hackett et al., 1998b). The coexpression
of these molecules at high levels in the core suggests they
may be used as markers of this region and adds support to
the theory that the core is a functionally distinct region of
auditory cortex. Furthermore, comparative studies of the
architecture could reveal similarities and differences
across taxonomic groups relevant to the organization and
evolution of auditory cortex in primates.
The purpose of the present study was to determine
whether the architectonic criteria currently used to iden-
199
TABLE 1. Histologic Treatment of Macaque, Chimpanzee, and
Human Brain Specimens1
Case
M1–M4
M5–M6
Ch1
Ch2
Ch3
Ch4
Hu1
Hu2
Hu3
Fixation procedure
Postmortem
delay
P 4% PBPF
P 4% PBPF
I 4% PBPF
P 4% PBPF ⫹ 0.1% GA
P 10% formalin
I 10% formalin
I 4% PBPF
I 2% PBPF
I 2% PBPF
0
0
⬍12 hr
0
20 min
12 hr
6 hr
⬍24 hr
23 hr
Plane of
section
Off-coronal
Coronal
Off-coronal
Off-coronal
Off-coronal
Off-coronal
Off-coronal
Off-coronal
Off-coronal
A
A
A
A
A
A
A
B
1
M, macaque; Ch, chimpanzee, Hu, human; P, perfusion; I, immersion; PBPF,
phosphate-buffered paraformaldehyde; GA, glutaraldehyde; off-coronal A, perpendicular to the superior temporal plane and midline; off-coronal B, perpendicular to the
superior temporal plane and long axis of the first transverse temporal gyrus. All cortical
blocks are left hemisphere.
tify the core region in monkeys could be used to identify a
homologous region in chimpanzees and humans. A preliminary report of these findings was previously published in
abstract form (Hackett et al., 1998c).
MATERIALS AND METHODS
Tissue specimens
The brains of six macaque monkeys (three Macaca mulatta and three M. nemestrina), four chimpanzees (Pan
troglodytes), and three humans (Homo sapiens) were obtained post mortem for use in these studies. Of the macaque brains, four were included in previous experiments
of auditory cortex in which the auditory core had been
identified by microelectrode mapping and/or tracer injections (Morel et al., 1993; Hackett et al., 1998a); thus,
nonarchitectonic verification of the boundaries of the core
region was available for these cases only. Chimpanzee
brains were obtained from the New Iberia Research Center (New Iberia, LA) and the Yerkes Regional Primate
Center (Atlanta, GA). All animals died of natural causes
or were euthanized for veterinary reasons. Chimpanzees
were adult males, age range 20 –33 years (estimated), and
presumed wild-caught. One human brain (Hu1) was obtained from the Vanderbilt University Medical Center
Department of Pathology from an adult male (45 years)
who died of non-Hodgkin’s type lymphoma. The other two
human brains were normal controls provided to the University of Louisiana at Lafayette by the Northwestern
Alzheimer’s Disease Center. The present analyses were
limited to the left temporal lobe; thus hemispheric differences were not addressed.
Histological processing
All macaque monkey brains were perfused transcardially immediately after death. Perfusates consisted of the
following solutions delivered in succession: 500 ml
phosphate-buffered saline (pH 7.4, room temperature);
500 ml 4% paraformaldehyde dissolved in 0.1 M phosphate buffer (4°C, pH 7.4); and 500 ml 4% paraformaldehyde ⫹ 10% sucrose in 0.1 M phosphate buffer (4°C, pH
7.4; Table 1). Immediately after perfusion the brains were
removed, separated from the thalamus and brainstem,
and cut into blocks. The blocks containing the temporal
lobe were immersed in 30% sucrose in 0.1 M phosphate
buffer (4°C, pH 7.4) overnight and then cut in a coronal or
semicoronal plane (Off-coronal type A, perpendicular to
200
T. HACKETT ET AL
Fig. 2. Dorsolateral views of the superior temporal plane.
A,B: Macaque cases M1 and M3. C,D: Chimpanzee cases Ch1 and
Ch4. E,F: Human cases Hu1 and Hu2. Single asterisks denote location of HG1 (first gyrus of Heschl). Double asterisk in E denotes HG2
(second gyrus of Heschl). In human case Hu2 (F), only one HG is
present. Solid white lines indicate plane of section. Dashed straight
white lines designate sulcal landmarks. a, anterior; m, medial. For
other abbreviations, see list. Scale bars ⫽ 5 mm.
superior temporal plane and midline) at 40 or 50 ␮m on a
freezing microtome (Fig. 2). Chimpanzee brains were perfused at variable postmortem delays ranging from zero
minutes (Ch2) to 20 minutes (Ch3) or fixed by immersion
after a postmortem delay of up to 12 hours (Table 1).
Human brains were obtained at postmortem delays ranging from 6 to 23 hours and were not perfused. These
specimens were fixed by immersion for 24 – 48 hours (4°C),
as indicated in Table 1 and then cut into blocks. Temporal
lobe blocks were sunk in 30% sucrose (4°C) and then cut
on a freezing microtome. Chimpanzee and two human
cases (Hu1 and Hu2) were cut at 50 ␮m in a plane perpendicular to the superior temporal plane and long axis of
the circular sulcus (Off-coronal A), as indicated in Figure
2. One human case (Hu3) was cut perpendicular to the
superior temporal plane and long axis of the first trans-
verse temporal gyrus of Heschl (Off-coronal B). Series of
adjacent sections were processed for 1) anatomical tracers
(macaque experimental cases only); 2) acetylcholinesterase (Geneser-Jensen and Blackstad, 1971); 3) myelin (Gallyas, 1979); or 4) staining for Nissl substance with thionin.
In most brains, three additional series were reserved for
additional reactions that were not included in the present
analyses. Sections were mounted on glass slides and coverslipped.
Architectonic analyses were conducted in sections
stained for Nissl substance (N), myelinated fibers (MF),
and acetylcholinesterase (AChE). The staining quality of
the N, MF, and AChE was not noticeably degraded by
postmortem delays to fixation of up to 23 hours. An exception was case Hu2, which was immersed in formalin for an
unknown period of less than 24 hours (Table 1). Compared
IDENTIFICATION OF THE AUDITORY CORE
with cases Hu1 and Hu3, which were fixed at 6 and 23
hours postmortem, respectively, Hu2 exhibited weakened
neuropil staining of AChE. AChE staining of cell soma
was comparable in the three cases. The normal appearance of AChE expression in case Hu3 suggests that histological factors account for the weak neuropil staining in
case Hu2.
Data analysis
Individual sections were studied at magnifications
ranging from 1.25 to 200⫻ on three microscopes: Nikon
E800S, Zeiss Axioscope 20, and Olympus BH-2. Borders
between the core and belt were independently identified
and marked on individual slides for matched sets of sections stained for N, MF, and AChE. Sections in which a
border(s) could not be identified were not marked. For
stack reconstructions (Figs. 11–13), grayscale images of
individual AChE sections (1.25⫻, 300 dpi) were obtained
with a Leaf Systems Lumina scanning digital camera
(Southborough, MA) mounted on a Nikon E800M microscope and Adobe Photoshop 5.0 software (Adobe Systems,
San Jose, CA). The images were adjusted uniformly for
brightness (10%) and contrast (5%) and then printed. Borders in adjacent sections were marked on the printed
AChE sections with reference to blood vessels, lesions, and
surface landmarks by using a drawing tube affixed to the
microscope. In most sections, the deviations in border
location assessed independently using N, MF, and AChE
were within 100 to 400 ␮m. Deviations exceeding 400 ␮m
were uncommon, but in some sections ambiguous features
or histological imperfections prohibited precise border
identification. These sections were excluded from the
analysis. The location of final borders represented a visual
average of the three preparations. The marked AChE
images were imported into Adobe Illustrator 7.0 and arranged in stacks, roughly perpendicular to the long axis of
the core region. An outline of the core was made by a
dashed line connecting the border markers (Figs. 11–13).
Densitometric measurements of
AChE expression
Densitometric analyses were conducted on subgroups of
sections processed for AChE from each brain. Grayscale
images of individual sections were adjusted uniformly for
brightness (10%) and contrast (5%) and then imported
into NIH Image 1.61 for Macintosh for densitometric measurements and subsequent manipulations. Two analyses
were used to support qualitative judgments about border
locations. Both analyses were based on radial density
profiles (Rivier and Clarke, 1997; Schleicher et al., 1999),
obtained by measuring gray level density in rectangular
samples (3 pixels in width) aligned parallel to radial fiber
columns spanning layers I–VI (Fig. 3C). When possible,
the open profiles of blood vessels, lesions, tissue tears, and
other imperfections were circumvented to avoid an artifactual modulation of optical density. The raw gray level
density values (0 –255), averaged across the 3-pixel width,
were converted to relative values by dividing by the mean
gray level density of the white matter underlying the
region of interest (Fig. 3D). Based on these mean density
values, the border between regions was estimated by the
following procedures. The mean of 5 adjacent profiles (e.g.,
1–5) was subtracted from the mean of the next 5 profiles
(e.g., 6 –10). The starting profile was then incremented by
1 so that the mean of profiles 2– 6 was subtracted from the
201
mean of profiles 7–11. This procedure was repeated until
the last profile was reached (e.g., Fig 3D, profile 41). The
two arithmetic differences with the greatest absolute
value were considered to represent the lateral and medial
boundaries of the most intensely stained region, corresponding to the core. In Figure 3D, this simple procedure
identified borders between profiles 12 and 13 (lateral), and
29 and 30 (medial). The data were then imported into a
MATLAB routine (MathWorks, Natick, MA) for subsequent analyses. Relative gray level densities of each profile were plotted as a function of percentage distance from
the pial surface for inspection of laminar trends (Fig.
3E–H). Compared with the actual distance (e.g., pixels or
micron-equivalents), plotting the density values as a function of percentage distance from the surface resulted in
better alignment of laminar peaks between samples because variability in cortical thickness altered absolute
laminar relationships. Individual profiles were detrended
by a linear regression, and then a cross-correlation matrix
was computed from these values among all profiles in the
section. Correlation coefficients were grouped into clusters
of high and low coefficients by an arbitrary criterion (e.g.,
0.65). Groups of profiles were related to predefined architectonic borders (Fig. 3C, arrows).
RESULTS
Gross anatomical features of the superior
temporal plane
In each of our macaque, chimpanzee, and human cases
the auditory core region was confined to the supratemporal plane on the dorsal surface of the temporal lobe, hidden from view by the overlying frontoparietal operculum
(Fig. 2A,B). In macaques there was no transverse temporal gyrus of Heschl (HG), and only gross anatomical features (e.g., vascular patterns, slight elevations or depression) sometimes coincided with the location of the core
region. The core was elongated along the rostrocaudal axis
of the temporal lobe in both species of macaque monkeys
(M. mulatta, M. nemestrina). The core was at its widest
caudally, narrowing rostrally as the supratemporal plane
also diminished in width. One result of this narrowing was
that the rostral portion of the core draped over the medial
edge of the supratemporal plane in some cases to occupy
the outer bank of the ventral circular sulcus. This feature
is not always obvious in flattened sections of cortex (e.g.,
Hackett et al., 1998a). Among the four chimpanzee brains,
three variants were noted. In one chimpanzee (Fig. 2C,
case Ch1), the core region was located on a rudimentary
transverse gyrus elongated rostrocaudally along the medial edge of the supratemporal plane and outer bank of the
circular sulcus, similar to that of M. fuscata (e.g., Jones et
al., 1995). The planum temporale and planum polare were
located posterior and anterior to the core, respectively. In
a second chimpanzee (see Fig. 12A) there was no clear
evidence of a transverse gyrus. Instead, the surface of the
supratemporal plane appeared relatively flat, as it does in
the macaque. In the two other animals there was a single
prominent HG oriented from posteromedial to anterolateral across the supratemporal plane (e.g., Fig. 2D, case
Ch4; Fig. 12B). In these brains, HG was bounded anteromedially by the anterior transverse sulcus of Heschl (HSa)
extending from the circular sulcus, and caudolaterally by
the posterior transverse sulcus of Heschl (HSp). The ar-
Figure 3
IDENTIFICATION OF THE AUDITORY CORE
chitectonic analyses detailed below indicated that the core
region was roughly coextensive with the single HG. Posterior to the HSp was a broad, mostly flat triangular
region corresponding in location to the human planum
temporale. Anterior to the HSa was a large region tentatively defined as the planum polare. In our human specimens, the left hemisphere contained either one or two
HGs, the long axes of which were oriented from posteromedial to anterolateral (Fig. 2E,F). The HG variants were
bounded by the HSa and HSp, as described above and by
previous investigators (von Economo and Horn, 1930;
Campaign and Minkler, 1976; Steinmetz et al., 1989;
Musiek and Reeves, 1990; Rademacher et al., 1993; Penhune et al., 1996; Leonard et al., 1998; Kim et al., 2000).
The double, or bifid, HG variant was bifurcated by the
sulcus intermedius (SI). The anteromedial HG was labeled HG1, and the posterolateral HG was labeled HG2
(Fig. 2E, case Hu1). The core was confined to HG when one
gyrus was present. For the double HG variants, the core
occupied portions of HG1 and HG2.
Note that because there is currently no consensus on the
nomenclature for description of HG variants, we have
adopted a nomenclature for labeling the HG based on
anatomical location (i.e., HG1, most anterior; HG2, posterior to HG1; HG3, posterior to HG2, etc.). The sulci bounding single or multiple gyri of Heschl were named based on
anatomical location relative to the HG complex, regardless of number; thus, HSa is always anterior to HG1,
separating it from the planum polare region, and HSp is
always posterior to the most posterior HG, dividing it from
the planum temporale region.
In several locations throughout the remaining text, we
refer to the parabelt region of auditory cortex. This region
was previously defined in macaque monkeys on the bases
of architectonic features and connections (Hackett et al.,
1998a). In macaques, the parabelt region lies on the exposed surface of the superior temporal gyrus, lateral to the
lateral belt fields bordering the core. In this report, the
term parabelt was used to denote that specific region only
in the macaque preparations.
Cytoarchitecture
We found the cytoarchitecture of the cortex corresponding to core and belt regions to be generally consistent with
earlier descriptions in the literature. A centrally located
core region, with koniocortical cytoarchitecture, was surrounded by a number of belt fields with features typical of
para- or pro-koniocortex. The koniocortical appearance of
203
the core derived from the predominance of small cells in
all layers. The dense concentration of small cells in layers
II through IV and VI contrasted with lower cell density in
layer V (Figs. 4A– 6A). The inner and outer granular layers (IV and II) were prominent and densely populated by
very small cells. Layer III was populated by small to
mid-sized pyramidal cells from IIIa to IIIc. Large pyramidal cells were rare in layer III but were found more often
at the border with the lateral belt region. In sections cut
perpendicular to the radial orientation of the apical dendrites in layer III, the small pyramidal cells were arranged in short radial columns, extending partially into
layers II and IV. This feature appears to correspond to the
“rainshower formation” described by von Economo and
Koskinas (1925).
The core was not homogenous with respect to the cytoarchitectonic features described above. For example, the
granular construction and radial orientation of small pyramidal cells in layer III were more prominent features in
the medial and caudal (posterior) portions of the core. In
the lateral and rostral (anterior) domains of the core,
especially near the core/belt border, pyramidal cells were
slightly larger in IIIc, and the “rainshower formation” was
a less dominant feature. Thus, a range of minor cytoarchitectonic variants was observed within the “koniocortical”
boundaries of the core. These variations were most obvious in the chimpanzee and human specimens.
These structural variants sometimes contributed to ambiguity in border identification, although the cytoarchitecture of the core contrasted with the belt (Figs. 4B– 6B) in
key ways that served as the primary criteria for border
identification. First, cell packing density and columnar
spacing was lower in the belt, a feature most noticeable in
layers II–IV. Second, pyramidal cells in layer III of the
belt areas were clearly larger and more numerous than in
the core. This feature was most obvious in layer IIIc,
where the largest layer III pyramidal cells were concentrated. Such cells were rarely found within the core but
were sometimes found at the border between the core and
lateral belt areas. With respect to columnar organization
in the belt, layer III pyramidal cells in belt areas lateral to
the core were arranged in well-organized vertical columns,
referred to by von Economo and Koskinas (1925) as the
“organ pipe formation.” The thin radial lines formed by
strings of small pyramidal cells in the core were exaggerated in the lateral belt where pyramidal cell size increased
from layer IIIa to IIIc (Figs. 4B– 6B). The columnar arrangement of pyramidal cells in layer III was less orderly
in the belt fields medial and caudal (posterior) to the core.
Myeloarchitecture
Fig. 3. Densitometric measurements of auditory cortex. A: Coronal section from macaque monkey stained for AChE. Arrows indicate
lateral (left) and medial (right) borders of the auditory core. B: Same
image as in A after filtering and thresholding (see text). The dense
band in layer IIIc/IV corresponds to dense AChE staining in the core.
C: Same image as A showing placement of rectangular radial density
samples used to obtain profiles in E–H. D: Mean relative gray level
density values for each radial profile in C. The white horizontal line at
4.25 represents the grand mean. Arrows indicate lateral (left) and
medial (right) borders of the core region. E–H: Radial density profiles
sorted by cortical region. Within a panel, each curve represents the
gray level density of a single rectangular sample plotted as a function
of the percentage distance from the pial surface. Profiles were grouped
into core, lateral belt, medial belt, and parabelt regions on the basis of
architectonic criteria, as denoted by the arrows in A–C. For abbreviations, see list. Scale bar ⫽ 1 mm in A–C.
In coronal sections stained for myelin, the auditory cortex of all three primates had a densely stained central core
(Figs. 4E– 6E), flanked laterally and medially by belt regions of less dense myelination (Figs. 4F– 6F) in which
prominent radial fiber bundles could be followed from the
white matter to low/mid layer III. Following the typology
of Pandya and Sanides (1973), the characteristic pattern
of myelination in the core was astriate (i.e., no horizontal
stria visible in layers IV or Vb due to uniformly dense
fibrillarity from IV through VIb) to unistriate (i.e., only the
outer stria in layer IV was visible due to relatively weaker
myelination in layer Va). The density of myelination in the
core was highest caudally, in presumptive AI, with a gradual reduction rostrally. In all three primates, it was pos-
Fig. 4. Architecture of macaque monkey core and lateral belt regions. A,B: Thionin stain for Nissl
substance. C,D: Acetylcholinesterase histochemistry. E,F: Myelin stain. A,C,E are from the primary
auditory core region. B,D,F are from the lateral belt. Scale bar ⫽ 250 ␮m.
IDENTIFICATION OF THE AUDITORY CORE
Fig. 5. Architecture of chimpanzee core and lateral belt regions. A,B: Thionin stain for Nissl substance. C,D: Acetylcholinesterase histochemistry. E,F: Myelin stain. A,C,E are from the primary auditory core region. B,D,F are from the lateral belt. Scale bar ⫽ 250 ␮m.
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Fig. 6. Architecture of human core and lateral belt regions. A,B: Thionin stain for Nissl substance.
C,D: Acetylcholinesterase histochemistry. E,F: Myelin stain. A,C,E are from the primary auditory core
region. B,D,F are from the lateral belt. Scale bar ⫽ 250 ␮m.
IDENTIFICATION OF THE AUDITORY CORE
sible to distinguish between medial and lateral domains
within the core on the basis of subtle differences in myelination. The medial domain tended to be astriate, whereas
fibrillar density was weaker in layer Va of the lateral
domain, which was, therefore, unistriate. This distinction
between medial and lateral domains of the core was maintained through most of the length of the core and was
more apparent in sections stained for myelin than those
stained for Nissl substance. In the belt areas myelin density was lower compared with the core, but particularly in
the interstriate layers, VIa and Va. The resulting bistriate
pattern of myelination resulted from prominent horizontal
fiber bands in layers Vb and IV. The transition to this
pattern was the principal criterion for identification of the
core/belt border in myelin preparations.
Acetylcholinesterase expression
Throughout most of the superior temporal cortex, AChE
was distributed in laminar-specific bands that varied in
density between and within architectonic areas. AChEreactive elements included subpopulations of cell soma,
proximal dendrites, and axons. The expression of AChE
was greatest in layers I–IV and weaker in layers V and VI,
except for minor bands in Vb and VIb (Figs. 4C,D– 6C,D).
Reactivity in layer I was consistently high across architectonic subdivisions, whereas AChE expression in other
layers varied by region. These areal differences served as
the primary criteria for the localization of borders between
fields. The borders identified in adjacent sections stained
for myelin and Nissl substance matched closely those determined independently on the basis of AChE expression.
Reactivity for AChE was higher in the core than in
surrounding cortex (Figs. 4C– 6C). AChE expression increased markedly from layer IIIa to IIIc, reaching peak
density in a band involving layers IIIc and IV. The density
and radial extent (thickness) of the IIIc/IV band diminished abruptly at the borders with most of the belt areas.
This rapid transition was one of the primary criteria for
localization of the borders between auditory cortical regions in AChE preparations. In layers V and VI, AChE
expression was much lower than in layer IV. A modest
increase in the concentration of AChE⫹ elements formed a
minor band in layer Vb. A second criterion for border
identification was based on the significant increase in the
number of moderate and large AChE⫹ pyramidal cells in
layer IIIc in the belt (Figs. 4D– 6D). In the medial belt
areas, these cells were loosely arranged, often in clusters.
In the lateral belt areas, cellular arrangement was more
orderly, as columns of AChE⫹ cells could be found extending from IIIc into IIIb. Recall that the increase in the
number of moderate and large pyramidal cells in the belt
was also observed in thionin-stained sections, but our
present observations suggest that only a subpopulation of
these cells were AChE⫹ in the lower part of layer III.
One notable exception to the typical patterns of AChE
expression described above was found in an adjacent belt
field situated caudal (posterior) and medial to the core. In
macaques this field is known as the caudomedial area
(CM; Fig. 1). For convenience, we will use the term CM to
denote the homologous field in chimpanzees and humans.
In all three species the density of AChE expression in the
IIIc/IV band of this field was high, comparable to that
found in the core (Fig. 7A). Based on that criterion alone,
CM could be considered part of the core. However, layers
IIIb and IIIc were also populated by numerous AChE⫹
207
pyramidal cells, medium to large in size (Fig. 7C). This
feature was found only in fields outside of the core. Thus,
with respect to the expression of AChE, CM shares features of core and belt cortex. In contrast, the cytoarchitecture and myeloarchitecture of CM were more typical of the
belt. Thionin staining revealed that CM was highly granular, but layers IIIb and IIIc were populated by numerous
medium and large pyramidal cells (Fig. 7B), and columnar
organization in layer IV was somewhat irregular. In myelin, the staining pattern was bistriate, with a denser
inner stria (layer Vb) and visible Kaes-Bechterew strip in
layer IIIa (Fig. 7D). The combined architectonic picture,
therefore, places CM outside of the core in the caudal
(posterior) and medial domain of the belt region. This
conclusion is consistent with connection patterns and electrophysiological recordings in macaque monkeys (see Discussion).
Density measurements
In most sections, the location of the core in AChE preparations could be estimated with great precision by
thresholding the Gaussian smoothed grayscale image at
one standard deviation above the mean density of the
white matter (see Materials and Methods). Thresholding
at this level preserved prominent suprathreshold regions
corresponding to the dense bands of AChE expression in
layers I and IIIc/IV of the core (Fig. 3A,B). In this example,
only thin interrupted bands in layer IV extended from the
borders of the core (arrows) into lateral and medial belt
fields. Except for layer I, AChE expression outside of the
core was strongly reduced or eliminated by the thresholding procedure, revealing the position of the core. Thresholding was of limited usefulness for border estimation in
two conditions. First, in weakly stained sections, even
mild thresholding degraded AChE-dense laminae in layers I and IIIc/IV (i.e., human case 2). Second, in the CM
belt area, the layer IIIc/IV band was not degraded by
thresholding; thus, the border between the core and CM
was not revealed. Higher thresholds (e.g., 1.5 or 2 standard deviations above the mean) tended to erode even the
dense bands corresponding to layers I and the IIIc/IV band
in the core.
The border between the core and most belt fields could
be objectively identified by the two analyses based on
radial density profiles (see Materials and Methods). In the
example illustrated in Figure 3C,D, the lateral and medial
borders of the core (arrows) were identified as profiles 13
and 29 by the sliding window analysis of mean profile
densities. Post hoc comparisons supported these findings,
indicating that mean relative gray level densities for profiles judged to be in the core (13–29) were significantly
greater than profiles judged to be in the parabelt (1–7),
lateral belt (8 –12), or medial belt (30 – 41), as determined
by a two-tailed t-test (P ⬍ 0.001). Mean densities of parabelt and lateral belt profiles were not significantly different (P ⫽ 0.33).
In Figure 3E–H, radial density profiles were plotted as
a function of the percentage distance from the pial surface.
Profiles in this example, and the majority of other cases,
were typically characterized by two prominent peaks corresponding to dense AChE expression in layers I and
IIIc/IV, respectively (Figs. 3E–H). Across cortical regions,
layer I density was constant, whereas the density of the
IIIc/IV band was weaker in the belt regions outside of the
core. The reduction of the second peak in the belt and
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parabelt contributed to lower mean relative gray level
densities in these regions, as described above (Fig. 3D).
Across cases, cross-correlation coefficients among profiles
within a region tended to be high (range 0.70 – 0.96),
whereas between regions (e.g., core vs. belt), they were
much lower (range 0.1– 0.55). These results indicate that
profiles within an architectonic field were comparable,
whereas profiles between regions were dissimilar. Border
identification, achieved by grouping of correlation coefficients according to an arbitrary fixed criterion (e.g., 0.65)
was generally in good agreement with borders identified
by qualitative criteria.
As with the thresholding approach to border estimation,
the radial profile analyses yielded variable results under two
conditions: 1) at borders located in or near deep sulci; and 2)
at the border of the core and CM, which exhibited dense
AChE expression in the IIIc/IV band. The density-based
analyses were not sensitive to subtle differences between
fields under these conditions. In the present study, most of
the errors involved the medial portion of the lateral sulcus.
Oblique planes of section and complex cortical folding were
frequent there, resulting in distortions of cortical thickness
and laminar relationships. The morphology of radial density
profiles reflected these distortions. The most common error
was that the border between the core and medial belt was
not identified. By comparison, the border between the core
and lateral belt was usually located on the surface of the
superior temporal plane or HG. Here, the border was rarely
misidentified.
Identification of borders between core
and belt regions
Ambiguity in border identification was reduced when
adjacent sets of sections (i.e., Nissl, myelin, AChE) were
studied and compared; thus, the use of multiple architectonic techniques enabled greater precision in border determination compared with reliance on a single approach.
The images in Figures 8 –10 are centered on the core/belt
border (arrowheads) identified independently in thionin,
AChE, and myelin stains. The panels in the top row are
centered on the border between the medial belt and core.
The panels in the bottom row are centered on the border
between the lateral belt and core. In all panels the core is
on the left. The borders between the core and adjacent belt
fields were most easily identified in AChE preparations,
but the architectonic details visible in the thionin- and
myelin-stained sections are also sufficient to define the
borders at this magnification. The transition from the core
to the belt was abrupt in many sections but sometimes
appeared to occur more gradually (over 300 –500 ␮m),
confounding identification of a precise border on this basis. Gradual transitions were observed more often at the
border of the core and lateral belt than at the border of the
core and medial belt.
Fig. 7. Acetylcholinesterase (AchE) expression in the human caudomedial belt area (CM). A: Off-coronal section (perpendicular to
HG1) caudal and medial to the core. Note the dense AChE expression
in the layer IIIc/IV band in CM compared with the adjacent lateral
field. Arrowheads indicate medial (left) and lateral (right) borders of
CM. B–D: Architecture of CM. A: Thionin stain for Nissl substance. B:
Acetylcholinesterase histochemistry. C: Myelin stain. Note the presence of AchE⫹ pyramidal cells in the IIIc/IV band. Scale bar ⫽ 1 mm
in A, 250 ␮m in B–D.
IDENTIFICATION OF THE AUDITORY CORE
209
Fig. 8. Architecture of macaque auditory cortex showing borders (arrowheads) between the core and
belt regions. Top row: Core is to the left of the arrowhead, and medial belt is to the right. Bottom row:
Core is to the left of the arrowhead, and lateral belt is to the right. A,D: Thionin stain for Nissl substance.
B,E: Acetylcholinesterase histochemistry. C,F: Myelin stain. Scale bar ⫽ 1 mm.
Species differences
In the cytoarchitecture and myeloarchitecture, laminar
divisions and structural variants were easiest to resolve in
the human tissue and most difficult in macaques. These
observations may be related to differences in the relative
concentration of the structural elements. In macaques,
cellular and fibrillar density was relatively high, making
laminar relationships more difficult to resolve. In the
chimpanzee and human specimens, more generous spacing improved the resolution of such details (see also Buxhoeveden et al., 1996). Consequently, differences between
the medial and lateral domains of the core were more
obvious in humans and chimpanzees than in macaques
(compare top and bottom panels in Figs. 8 –10). This may
explain why subdivision of the core into lateral and medial
zones is reported more often in studies of human tissue
than monkeys, and why published parcellations of the
auditory cortex in humans tend to be more variable (see
Discussion). A second observation concerns myelination in
layer III. As Figures 4 – 6 and 8 –10 reveal, the density and
complexity of fibrillar organization in layer III differed
between primates. The network of small-diameter horizontal and tangential fibers was most elaborate (or highly
developed) in humans, intermediate in chimpanzees, and
the least intricate in macaques. Similar differences may
also characterize layers IV–VI, but these could not be
resolved consistently due to heavy myelination in these
layers.
AChE⫹ pyramidal cells in layers III and V of the belt
region were present in greater numbers in the chimpanzee
and human than in the macaque material (refer to Figs.
4 – 6). Cell somata in the human specimens were darkly
stained, and profiles were sharp. In the chimpanzee tissue, cell staining was not quite as intense, and somatic
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Fig. 9. Architecture of chimpanzee auditory cortex showing borders (arrowheads) between the core
and belt regions. Top row: Core is to the left of the arrowhead, and and medial belt is to the right.
Bottom row: Core is to the left of the arrowhead, and lateral belt is to the right. A,D: Thionin stain for
Nissl substance. B,E: Acetylcholinesterase histochemistry. C,F: Myelin stain. Scale bar ⫽ 1 mm.
profiles were somewhat less sharp, but were clearly more
distinct than in macaques. In macaques, AChE⫹ somatic
profiles were typically indistinct or absent. In contrast,
the staining of fibers and dendritic processes did not seem
to vary between species. Inspection of adjacent sections
stained with thionin indicated that an increase in the
number of middle- and large-size pyramidal cells characterized the belt in all three taxa; thus the disparity appeared to be related to a phyletic difference in AChE
expression by a particular class of cells. This issue awaits
further investigation.
Reconstruction of serial sections and
localization of the core
The identification of the borders between the core and
surrounding belt regions in individual sections allowed a
fairly precise outline of the core region to be made in serial
reconstructions. In Figures 11–13 we show reconstructions
for two cases of each species. Stacks of sections stained for
AChE were aligned approximately along the long axis of the
core. Spacing between sections was somewhat arbitrary to
allow better visualization of architectonic details. Sections
were 50 ␮m thick, and every 12th section was illustrated, on
average (i.e., approximate distance of 600 ␮m between sections); thus, the shape of the core (black dashed outlines) was
slightly elongated compared with its shape in the whole
brain (Fig. 14). Some borders were not visible due to complex
folding of the cortex. The overlying parietal cortex was
graphically deleted.
Macaque
There were few cues in the gross anatomy that would
contribute to postmortem localization of the core. The
superior temporal plane was relatively flat, and elevations
IDENTIFICATION OF THE AUDITORY CORE
211
Fig. 10. Architecture of human auditory cortex showing borders (arrowheads) between the core and
belt regions. Top row: Core is to the left of the arrowhead, and medial belt is to the right. Bottom row:
Core is to the left of the arrowhead, and lateral belt is to the right. A,D: Thionin stain for Nissl substance.
B,E: Acetylcholinesterase histochemistry. C,F: Myelin stain. Scale bar ⫽ 1 mm.
or depressions were not consistent markers of architectonic boundaries. The position of the auditory fields in
macaque monkeys (Fig. 11) varied only slightly across
individual macaques. The core was positioned between the
lateral and medial banks of the supratemporal plane;
thus, it was completely contained within the lower bank of
the lateral sulcus. In rare instances, the core region was
shifted medially so that even the medial edge of AI
dropped over the steep bank of the circular sulcus. In
other cases, the width of the core relative to the width of
the superior temporal plane was either greater or extended further laterally, shifting part of the lateral belt
field over the edge of the lateral sulcus onto the exposed
surface of the superior temporal gyrus. The magnitude of
this variability in the mediolateral dimension was on the
order of 1–2 mm. The shape of the core approximated an
elongated oval, widest caudally in AI, and narrowing ros-
trally in R. The boundaries of the core encompass the
region of most intense AChE expression in layer IIIc/IV,
except in CM, where density remained high in that band
(e.g., Fig. 11A). Rostral to the core was a smaller region
with core-like architecture that we tentatively identified
as RT. This small field exhibited higher density AChE and
myelin staining than adjacent fields; however, these features were less robust than in AI and R. Furthermore, this
field had cytoarchitectonic properties of belt cortex (e.g.,
reduced cell packing density, larger pyramidal cells in
layer III). At present, RT remains the least certain member of the core in macaques.
Chimpanzee
Among the four chimpanzee cases, substantial differences were found in the position of the core with respect to
the gross anatomy of the superior temporal plane. In case
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Fig. 11. Reconstructions of AChE sections showing location of the
core region (black dashed ovoid) on the dorsal surface of the superior
temporal plane for two macaque monkeys (A, case M1; B, case M3).
Small white dashed ovoid shows putative location of the CM and RT
fields. The images were aligned on the long axis of the elongated core
region and lateral edge of the lateral sulcus. C, caudal; L, lateral.
Scale bar ⫽ 4 mm.
Ch3 (Fig, 12A; not shown in Fig. 2), the planar surface was
relatively flat and the bulk of the core region was found
medially on the surface of the lateral sulcus. Rostrally, the
medial edge of the core was shifted ventrally as a small
rudimentary gyrus began to form. The medial border of
the rostral core region was positioned in the depths of the
inferior limiting (circular) sulcus. Note also that the position of the core was at a greater distance from the lateral
edge of the superior temporal plane than in macaques. In
case Ch1 (Figs. 2C, 12B), a transverse gyrus was more
IDENTIFICATION OF THE AUDITORY CORE
Fig. 12. Reconstructions of AChE sections showing location of the
core region (black dashed ovoid) on the dorsal surface of the superior
temporal plane for two chimpanzees (A, case Ch3; B, case Ch1). White
dashed ovoid in A marks the estimated position of the caudomedial
belt region (CM). The small white ovoid in B indicates location of
213
putative RT. The images were aligned on the long axis of the elongated core region and lateral edge of the lateral sulcus. PM, posteromedial; AM, anteromedial. For other abbreviations, see list. Scale
bar ⫽ 4 mm.
Fig. 13. Reconstructions of AChE sections showing location of the
core region (black dashed ovoid) on the dorsal surface of the superior
temporal plane for two human cases (A, case Hu1; B, case Hu2).
White dashes indicate estimated position of the caudomedial belt
region. The images were aligned on the long axis of the elongated core
region and lateral edge of the lateral sulcus. PM, posteromedial; AM,
anteromedial. For other abbreviations, see list. Scale bar ⫽ 4 mm.
IDENTIFICATION OF THE AUDITORY CORE
215
Fig. 14. Dorsolateral views of the left superior temporal plane.
A,B: Macaque cases M1 and M3. C,D: Chimpanzee cases Ch1 and
Ch4. E,F: Human cases Hu1 and Hu2. Larger white dashed ovoids in
all panels indicate approximate boundaries of the core. Smaller ovoids
in A–D denote location of putative RT. Dashed straight white lines
designate sulcal landmarks. a, anterior, m, medial. For other abbreviations, see list. Scale bars ⫽ 5 mm.
evident but was still rudimentary compared with the
prominent HG in case Ch4 (Fig. 2D). Except for its caudal
portion, the core region was confined to this transverse
gyrus. In all four cases the general shape of the core region
was similar to that found in macaques, but variability
between the chimpanzee cases was higher. The patchy
staining in some sections (e.g., rostral to the core region in
case 2) was histological.
In case Ch3 (Fig. 12A), the approximate location of
putative CM is outlined in white, as described above for
macaques. The medial border of the field extended slightly
onto the dorsal bank of the lateral sulcus, but in both cases
the remaining portion of the field was removed during
dissection of the tissue into blocks; thus the size and
extent of this field could not be determined. Note also the
outline of a field resembling RT in case Ch1 (Fig. 12B).
This field was not obvious in case Ch3, but it may be
included in the narrow anteromedial extension of the outlined core region in Figure 12A.
Human
Similar variations in gross anatomy complicate descriptions of the core in humans (Fig 13). In case Hu1 (Fig.
13A), there was a double/bifid HG, separated by an intermediate sulcus of Heschl. Along most of its length, the
elongated core region straddles the intermediate sulcus,
while its borders lie laterally and medially near the dorsal
surface of each gyrus (HG1, HG2). The lateral border of
the core shifted medially in more rostral sections, and
eventually the entire core became confined to HG1 rostrally. Caudally, the intermediate sulcus became shallow,
and then ended, but the core continued for a few sections.
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T. HACKETT ET AL
The darkly stained CM region was most evident in this
case. In case 2 (Fig. 13B), a single HG was present. In this
case, the core region was confined to the single HG along
most of its length. In a third case (Hu3, not illustrated), a
double HG was also present. Here, the core also straddled
the intermediate sulcus, but the bulk of the core was
shifted medially, compared with case Hu1, so that the
lateral border of the core was often in the depths of the
intermediate sulcus instead of on the dorsal surface of the
gyrus. Thus, in addition to variability in the gross anatomy of the superior temporal region, there was some variability in the relative position of the core with respect to
these landmarks.
AChE neuropil staining in case Hu2 was less intense
compared with case Hu1, so that the borders of the core
region at low magnification were less obvious. It appears
that the longer postmortem period in this case may have
contributed to a reduction in the intensity of AChE neuropil staining. Interestingly, AChE expression in cells was
not affected, nor was staining for myelin or Nissl. Accordingly, density-based measurements of AChE neuropil expression were not reliable for border identification for case
Hu2.
DISCUSSION
The core region of auditory cortex was identified in
macaque monkeys, chimpanzees, and humans by a combined analysis of cytoarchitecture, myeloarchitecture, and
expression of acetylcholinesterase (AChE). In all three
primates, the core was found to occupy an elongated region of cortex on the superior temporal plane, hidden from
view by the overlying parietal cortex (Fig. 14). In macaques, the long axis of the core was oriented in the rostrocaudal plane. In chimpanzees and humans, the core
was largely coextensive with the first transverse temporal
gyrus, although notable variants were found. The core
exhibited primary-like architectonic features that distinguished it from the adjacent belt fields flanking it on all
sides. Systematic architectonic variations were also noted
within the core itself and appear to be present in all three
species. The combined architectonic approach using multiple markers was found to be more useful in border identification than reliance on a single method. The results
indicate that the core region can be identified in humans
and non-human primates by using the same anatomical
criteria, suggesting that these criteria delineate homologous cortical regions in the taxa we examined.
What is the auditory core?
Most descriptions of the auditory cortex in mammals
identify a single primary field known as AI. In the auditory cortex of monkeys more than one primary or primarylike field can be identified, and the local aggregation of
these fields is referred to as the core. Current models (e.g.,
Fig. 1) include two or three distinct fields (AI, R, RT)
arranged from caudal to rostral along the long axis of the
core region at the initial stage of auditory cortical processing (Kaas and Hackett, 1998, 2000; Rauschecker, 1998,
Rauschecker and Tian, 2000). The identity of a core field
depends on a profile derived from its architecture, connections, and neuron response properties. Architectonic features include koniocortical cytoarchitecture, dense
astriate/unistriate myelination, and dense expression of
AChE, cytochrome oxidase (CO), and parvalbumin in the
neuropil of layer IV. Major subcortical connections favor
the ventral (principal) division of the medial geniculate
complex (MGv), and cortical projections are primarily directed to the belt fields surrounding the core (Akert et al.,
1959; Mesulam and Pandya, 1973; Pandya and Sanides,
1973; Forbes and Moskowitz, 1974; Burton and Jones,
1976; Casseday et al., 1976; Fitzpatrick and Imig, 1978;
Oliver and Hall, 1978; Galaburda and Pandya, 1983; Aitkin et al., 1988; Cipolloni and Pandya, 1989; Luethke et
al., 1989; Morel and Kaas, 1992; Morel et al., 1993; Pandya et al., 1994; Jones et al., 1995; Molinari et al., 1995;
Rauschecker et al., 1997).
Connections with the parabelt region and more distant
cortical fields are at most minor (Hackett et al., 1998a),
and subdivisions within the core are thought to process
information in parallel (Rauschecker et al., 1997). Neurons in the core respond to a variable range of frequencies
centered around a single characteristic frequency (CF).
Neurons with a similar CF are arranged in rows, known
as isofrequency contours. The organization of isofrequency
contours is cochleotopic (e.g., high CF caudomedial, low
CF rostrolateral) and roughly orthogonal to the isofrequency dimension (Licklider and Kryter, 1942; Walzl,
1947; Merzenich and Brugge, 1973; Imig et al., 1977;
Pfingst and O’Connor, 1981; Aitkin et al., 1986; Luethke et
al., 1989; Morel and Kaas, 1992; Morel et al., 1993; Kosaki
et al., 1997; Rauschecker et al., 1997; Recanzone et al.,
1999, 2000). The topography of CF maps in adjacent core
fields (e.g., AI/R; R/RT) appears to be reversed in that AI
and R share a common low-CF border. R and RT may
share a high-CF border, but physiological evidence of a
reversal in the CF gradient in RT is inconclusive. Consequently, of the areas considered, the status of RT as a
member of the core is least certain (Morel et al., 1993;
Hackett et al., 1998a).
In apes and humans, anatomical identification of the
core region primarily depends on the analysis of architectonic features in postmortem tissue. Most of the parcellations of auditory cortex were derived from analyses of
cytoarchitecture and/or myeloarchitecture (chimpanzee:
Beck, 1929; human: Campbell, 1905; Brodmann, 1909;
Vogt and Vogt, 1919; Flechsig, 1920; von Economo and
Koskinas, 1925; Beck, 1928; von Economo, 1929; von
Economo and Horn, 1930; Poljak, 1932; Hopf, 1954; Pandya and Sanides, 1973; Galaburda and Sanides, 1980;
Seldon 1981a,b, 1982; Morosan et al., 2001). A few studies
in humans have also included additional markers (e.g.,
AChE, CO, NADPH-diaphorase) to identify or characterize auditory related cortical fields (Ong and Garey, 1991;
Hutsler and Gazzaniga, 1996; Rivier and Clarke, 1997;
Clarke and Rivier, 1998). Despite substantial variations
in conclusions and nomenclature across studies, a common finding has been the identification of a central region
with primary, or primary-like, architectonic features surrounded by several nonprimary fields.
Functional evidence of a core-like region in apes and
humans can be derived from a number of studies. Surface
recordings in the chimpanzee have revealed the presence
of an acoustically responsive region on the superior temporal plane with an orderly representation of stimulus
frequency similar to that found in monkeys (Bailey et al.,
1943; Woolsey, 1971). In humans, patterns of cochleotopic
organization resembling those found in macaques and
chimpanzees have been found along the HG by using a
variety of techniques (electrophysiology/evoked potentials:
IDENTIFICATION OF THE AUDITORY CORE
217
Gross anatomical relationships of the core
often confined to the most anterior gyrus (HG1). In one
case, area 41 “continued for a short distance onto the
intrasulcal portion of the second, more caudal transverse
gyrus” (HG2). In the present study, the two cases presenting with a bifid HG were similar to this in that core
extended posterolaterally across the intermediate transverse sulcus and toward the crown of HG2. However, the
anteromedial boundary of the core was near the crown of
HG1; thus, the core did not encompass HG1 and extend
onto HG2, but was shifted posterolaterally to involve
about two-thirds of HG1 and one-third of HG2. The findings of both studies illustrate the variable relationship of
the primary auditory fields to the surface landmarks. The
diversity in the morphology and location of the HG in
humans (Leonard et al., 1998) is especially problematic for
functional studies in which the location of the auditory
core is in question. Although a small number of brains
have been sampled across studies, the best estimate of the
position and areal extent of the core appears to be related
to the boundaries of HG1, particularly when there is only
one HG. For other configurations of HG, the position of
HG1 is a less reliable guide to the location of the core.
One of the most impressive findings in this study was
the high level of variability in the gross anatomical features of the auditory cortical region between individuals.
The greatest differences were found in chimpanzee and
human brains, where the number, size, shape, and extent
of the transverse temporal gyri varied between individuals. In all three species, the position of the core relative to
sulcal and gyral landmarks was also variable; thus, these
gross anatomical features were used only to approximate
the location of the field. Precise localization depended on
the architectonic analyses.
In macaques, we found that the shape and orientation of
the core (Fig. 14A,B) was consistent with previous anatomical and/or physiological descriptions of this region (for
reviews, see Morel et al., 1993; Hackett et al., 1998a).
Robust surface features marking the location of the core
were generally lacking in macaques, although a slight
elevation on the cortical surface seemed to correspond to
the location of the core in some species (Poljak, 1932;
Jones et al., 1995). In chimpanzees lacking a definitive HG
(Figs. 12A, 14C), the orientation of the core on the superior
temporal plane was situated deep in the lateral sulcus and
elongated along the medial edge of the superior temporal
plane. In chimpanzees with a prominent HG (Fig. 14D),
the orientation and appearance of the core was more similar to that found in humans. The core in these cases was
confined to the HG regardless of its orientation. In humans, the elongated shape of the core resembled that
found in macaques and chimpanzees. The location of the
core with respect to gross anatomical features, however,
was more variable (Fig. 14E,F). When a single HG was
present, the core occupied most of its surface and was
constrained by its sulcal boundaries. When the HG was
divided by an intermediate transverse sulcus (bifid HG,
posterior duplication), the core region was found to occupy
variable portions of both (i.e., HG1 and HG2), spanning
the intermediate sulcus of Heschl.
In their evaluation of the relationship between topographic landmarks and cytoarchitectonic fields, Rademacher et al. (1993) compared the areal extent of area 41
(auditory koniocortex) with variations in the topography
of the HG. When the HG was bifurcated by an intermediate transverse sulcus, they found that area 41 was most
Architectonic variations within a region commonly referred to as primary auditory cortex are well known (e.g.,
Beck, 1928, 1929; von Economo and Horn, 1930; Pandya
and Sanides, 1973; Galaburda and Sanides, 1980; Morosan et al., 2001). In the cytoarchitectonic studies of von
Economo and Horn (1930), for example, up to 11 distinct
“types” of granular cortex were identified within a region
(TC) that corresponds closely to our conception of the core.
However, there is a relative uniformity with respect to the
most consistent features that contributes to the profile of
the core as a distinct region (Brodmann, 1909; Vogt and
Vogt, 1919). Similarly, the fields comprising the belt region surrounding the core are architectonically distinct
from those within the core, but within the belt region,
individual areas share a number of features typical of the
belt. To the extent that these sets of architectonic features
are unique to the core and belt, they can provide the basis
for identification of the borders between regions.
In the present study, the architectonic features within
the region defined as the core were not uniform. Subtle
and sometimes systematic variations were observed, particularly in sections stained for Nissl substance and myelin. One of the more robust divided the core into medial
and lateral domains along the long axis of the region.
Myelination in the medial domain was more often astriate, whereas in the lateral portion, a reduction in fiber
density allowed better delineation of layer IV, contributing to a unistriate profile. This particular feature was
matched by trends in the cytoarchitecture. Granularity
and columnar organization in layer III were more prominent in the medial domain. The identification of two koniocortical domains, splitting the region lengthwise, has
been suggested previously for humans (Hopf, 1954;
Sarkissow et al., 1955; Galaburda and Sanides, 1980).
This feature was also identified in macaque monkeys by
Pandya and Sanides (1973); however, it was not preserved
in subsequent adaptations of their schema (e.g., Galaburda and Pandya, 1983). Pandya and Sanides (1973)
concluded that the denser myelination in Kam was related
to a proposed greater concentration of callosal fibers medially. As yet, additional support for a distinction between
Verkindt et al., 1995; Howard et al., 1996; magnetoencephalography: Elberling et al., 1982; Pantev et al., 1988,
1995; Bertrand et al., 1991; Yamamoto et al., 1992; Romani et al., 1992; Tiitinen et al., 1993; Huotilainen et al.,
1995; Langner et al., 1997; Hoke et al., 1998; Lutkenhoner
and Steinstrater, 1998; Rosburg et al., 1998; positron
emission tomography: Lauter et al., 1985; de Rossi et al.,
1996; Ottaviani et al., 1997; Lockwood et al., 1999; functional magnetic resonance imaging: Strainer et al., 1997;
Wessinger et al., 1997; Bilecen et al., 1998; Talavage et al.,
2000; Di Salle et al., 2001).
The anatomical and physiological findings reviewed
above, coupled with those of the present study, strongly
support the existence of a core-like region in chimpanzees
and humans that should be considered homologous to the
auditory core identified in monkeys (Walker, 1937). Detailed anatomical studies and the refinement of noninvasive functional assays will allow us to evaluate this hypothesis further and extend our inquiries to fields
surrounding the core, such as CM.
Architectonic variation within the core
218
T. HACKETT ET AL
the medial and lateral domains has not been reported in
either the connections or physiological profiles of neurons
in the core.
Architectonic variations also distinguished the caudal
(posteromedial) and rostral (anterolateral) domains
within the core. Myelination and AChE expression gradually increased caudally, where the cytoarchitecture was
more typical of koniocortex. Previous architectonic studies
in chimpanzees and humans have also identified regional
variations along this dimension of granular cortex (Beck,
1928, 1929; von Economo and Horn, 1930; Morosan et al.,
2001). The transverse prima interna and externa of Beck
(1928, 1929), for example, mirror the relative positions of
AI and R in the macaque. Most recently, Morosan et al.
(2001) identified three adjacent zones (Te1.1, Te1.0, Te1.2)
distributed along the long axis of HG in humans. These
anatomical gradients may relate to functional gradients
(e.g., cochleotopy), as identified within the core region of
macaques (e.g., AI, R).
Based on comparison of the findings in the present
study with qualitative and quantitative descriptions of
temporal cortex in previous studies, we conclude that the
core corresponds most closely to the following fields: area
41 (Brodmann, 1909); TC (von Economo and Koskinas,
1925); ttrIi/e (Beck, 1928, 1929); koniosus supratemporalis (Bailey and von Bonin, 1951); Kam/Kalt (Pandya and
Sanides, 1973; Galaburda and Sanides, 1980; Galaburda
and Pandya, 1983); temporal granulous core (Braak,
1978); AI (Rivier and Clarke, 1997); and Te1.0 (Morosan et
al., 2001).
Architectonic variation within the belt
Although we made no attempt to define subdivisions
within the belt region in this study, our results indicate
that the belt is not anatomically homogeneous in monkeys, chimpanzees, or humans. Systematic differences
were evident within and between the medial, lateral, and
caudal domains of the belt. However, these fields also
share a basic architectonic profile that distinguishes them
from the core and more distant regions, such as the parabelt in macaques (Hackett et al., 1998a). Additional support for these differences can be found in microelectrode
studies of macaque monkeys. Functional subdivisions of
the belt correlate well with those identified anatomically
(e.g., Rauschecker et al., 1995, 1997; Kosaki et al., 1997;
Romanski et al., 2000; Tian et al., 2001).
In the present study, we briefly described the architectonic features of the belt field, CM, compared with the
adjacent part of the core (i.e., AI). In macaque monkeys
CM is considered to be a belt field on the basis of its
architecture, connections, and neuron response properties. Major inputs to CM originate in the dorsal (MGd) and
magnocellular (MGm) divisions of the medial geniculate
complex (Rauschecker et al., 1997), and AI in the core
(Galaburda and Pandya, 1983; Morel et al., 1993). Cortical
projections of CM include the parabelt auditory cortex
(Hackett et al., 1998a) and posterior parietal cortex (Lewis
and van Essen, 2000). Many neurons in CM are broadly
tuned, are more responsive to temporally and spectrally
complex acoustic stimuli, and appear to be dependent on
intact inputs from AI for responses to pure tones (Merzenich and Brugge, 1973; Rauschecker et al., 1997; Recanzone et al., 2000). The results of the present study indicate
that the architectonic profile of CM is most consistent with
its inclusion in the caudal portion of the belt region of
macaques. The present findings also emphasize architectonic similarities between macaque CM and a field caudal
(posterior) and medial to the core in chimpanzees and
humans. Based on architectonic descriptions in previous
studies, the CM field in humans appears to correspond
most closely to the following areas: the medial portion of
the koniocortical TD sector of the Regio acustica (von
Economo and Koskinas, 1925; von Economo and Horn,
1930); ttrIin2 of the Pars intima of chimpanzees and humans (Beck, 1928, 1929); medial PaAc (Galaburda and
Sanides, 1980); and medial Te1.1 (Morosan et al., 2001).
Our preliminary results suggest that this field may be
homologous in macaques, chimpanzees, and humans.
Sources of variability in border
identification
Borders between adjacent cortical fields are not always
characterized by an abrupt transition in the architecture.
There is no a priori reason why margins must be sharp,
but this is commonly reported in studies of sensory cortex.
Indeed, conclusions sometimes depend on the identification of clean boundaries between fields. Transitional architecture may, in fact, separate some fields in cortex, but
the blurring of clean borders is often related to technical
variables. One important factor is the plane of section.
Distortion results from cutting across and/or between the
radial axes of cell columns, thereby altering the threedimensional relationships between the neural structures.
An oblique plane of section alters the point of view, altering the appearance of the architecture. Depending on the
nature of the distortion, the distinction between the two
fields may be obvious only at some variable distance from
the border. In brains with greater gyrification, the cortex
exhibits complex folding in several directions (e.g., the HG
in chimpanzees and humans). Thus, a coronal plane of
section results in radially aligned sections through some
areas and oblique sections through others. In the present
study, we found no single plane of section to be ideal for all
fields of interest. For macaques, a modified coronal plane,
perpendicular to the surface of the superior temporal
plane, resulted in minimal distortion and was roughly in
line with the long axis of the elongated core. For chimpanzees and humans with a HG, a modified parasagittal
plane, perpendicular to the long axis of the transverse
gyrus (gyri) and its dorsal surface, resulted in minimal
distortion of fields on and immediately adjacent to the HG.
A second variant is the relationship of borders to the
gross anatomy. The presence of deep sulci at and between
architectonic borders substantially alters anatomical features, particularly laminar relationships. In our macaque,
chimpanzee, and human specimens, for example, the border between the core and the medial belt was frequently
located at or near the sharp turn of the inferior limiting
(circular) sulcus. Another troublesome location was the
intermediate sulcus of Heschl in those human specimens
with a double, or bifid, HG. The compression of cortex in
these sulci distorted laminar relationships, compromising
the integrity of calculations based on radial density profiles. In severely distorted sections, even the identity of
the fields at a distance from the estimated border were in
question, so that judgements were based on modified criteria using identifiable features, as well as comparisons of
the intact architecture on either side of the sulcus.
A third source of variability is histological. Aberrant
staining patterns can result from variations in postmor-
IDENTIFICATION OF THE AUDITORY CORE
tem delay, fixation, sectioning, buffer solutions, or minor
details in the histological protocol. Although severe distortions are obvious and easily excluded from analysis,
subtle variations may not be detected. A gradual dissipation of AChE expression at a border, for example, may be
an inherent property of the architecture, but this does not
explain why abrupt transitions are found in some sections,
but not others. In this study, staining quality for Nissl
substance and myelinated fibers was highly consistent
across cases, regardless of species, perfusion, fixation, or
postmortem delay. Staining for AChE was more variable
(see Materials and Methods) but was not consistently
related to any identifiable histological factor. As a partial
control, densitometric analyses in the present study were
limited to measurements within individual sections. No
attempt was made to compare density measurements between cases or between sections.
Given the many factors that contribute to histological
variability, one of the merits of the multifaceted architectonic analysis is that the redundancy increases confidence
in border identification. The intense expression of AChE
in the core, for example, was an invaluable clue in approximating the position of the core, but the identification of
borders was most precise when direct comparisons were
made with adjacent thionin- and myelin-stained sections.
When the borders were near or within sulci or when fields
were sectioned tangential to the cortical surface (e.g., medial belt region), important features of the cytoarchitecture and myeloarchitecture were severely distorted, limiting border identification to differences in the density of
cellular or fibrillar elements. In such cases, the rapid
change in layer IIIc/IV expression of AChE was often
visible and served as the most valid estimate of the border.
The combined architectonic approach was also useful in
case Hu2, in which AChE neuropil expression was relatively weak. In this case, border identification was reinforced by cytoarchitecture, myeloarchitecture, and AChE⫹
cell distribution.
Observer-independent border identification
One limitation of most architectonic studies is that decisions rely on the qualitative judgments of the observer.
As discussed above, the use of multiple architectonic
markers greatly improves the consistency and precision of
border identification. The quantitative analyses employed
herein were accurate under certain conditions (e.g., wellstained tissue, mild structural distortions imposed by cortical folding). The analyses did not, however, produce reliable border identification when radial density profiles
were distorted by cortical folding, an oblique plane of
section, low contrast staining, or gradual architectonic
transitions. Similar problems have been reported by others using different techniques (Schleicher et al., 1999;
Morosan et al., 2001). To account for such architectonic
variability, the ideal reliable observer-independent
method must be sensitive only to relevant features. Otherwise, actual borders may be missed or false borders
identified, depending on the criteria chosen. We are evaluating ways of improving the sensitivity of such methods
to key criteria, without introducing a bias toward the
identification of false borders. The present findings suggest that the concurrent use of multiple histological markers could be used to reduce qualitative and quantitative
errors in border identification. A combined approach may
219
be particularly useful in the validation of borders identified by a strictly quantitative approach.
Directions for future research
Functional studies in humans suggest that certain elements of the monkey model may be applicable to humans.
In addition to evidence of tonotopic organization in the
putative core region along the HG (see above), there is also
evidence of hierarchical processing in human auditory
cortex involving the core and surrounding regions. Numerous studies in humans indicate that auditory related
activity in cortical fields outside of the core region can be
dissociated from activity within by using stimuli of varied
acoustic complexity or linguistic significance (Petersen et
al., 1988; Liegeois-Chauvel et al., 1991, 1994; Price et al.,
1992; Demonet et al., 1992; Zatorre et al., 1992; Binder et
al., 1994, 2000; Berry et al., 1995; Hickock et al., 1997;
Scheich et al., 1998; Nishimura et al., 1999; Belin et al.,
1999, 2000; Celsis et al., 1999; Jancke et al., 1999; Howard
et al., 2000; Scott et al., 2000; Talavage et al., 2000; Di
Salle et al., 2001). These results are consistent with findings in monkeys that describe serial and parallel processing among subdivisions of the core and belt regions (e.g.,
Rauschecker et al., 1997). Because the homology of the
core in monkeys and humans appears to be well established, and homologies among belt areas such as CM seem
likely, further comparative studies will be needed to identify other similarities and differences in the organization
of auditory cortex across taxonomic groups. For architectonic studies, progress will depend on the establishment of
anatomical profiles to distinguish cortical fields. The sensitivity of observer-independent techniques could be improved by incorporating these features into the analyses.
CONCLUSIONS
In macaque monkeys the auditory core region represents the first stage of processing in auditory cortex. A
homologous region can be identified in chimpanzees and
humans by using architectonic criteria combining cytoarchitecture, myeloarchitecture, and acetylcholinesterase
histochemistry. The combined architectonic approach using multiple markers provides a more reliable estimate of
the boundaries of the core region than detailed analysis of
a single preparation. In all three species, the core region is
surrounded by a belt of areas with distinctive architectonic features that vary by location. The position of the
core with respect to surface landmarks is most variable in
humans and chimpanzees, but it appears to be largely
confined to the first transverse temporal gyrus of Heschl,
even when more than one such gyrus is present. Although
we consider the region identified as the core to be homologous in macaques, chimpanzees, and humans, species
differences were noted in patterns of myelination and
acetylcholinesterase expression. These data establish a
foundation for subsequent anatomical studies of auditory
fields outside of the core and for functional studies of
auditory cortex in these species.
ACKNOWLEDGMENTS
The authors thank the veterinary staff of the New Iberia Research Center for their assistance in obtaining
chimpanzee material. We also thank Dr. William O. Whet-
220
T. HACKETT ET AL
sell of the Vanderbilt University School of Medicine, Dr.
Bruce Quinn and Dr. John Smiley of the Northwestern
University Alzheimer’s Disease Center, and the Clinical
Core of the Northwestern University Alzheimer’s Disease
Center, Chicago for assistance in obtaining human material. The authors also recognize Thomas Dinsenbacher for
assistance with data analysis, as well as Judy Ives and
Laura Trice for histological assistance. T.A.H. was the
recipient of grants DC00249 and DC04318 from the National Institutes of Health. T.M.P. was the recipient of
grant JSMF 98-45 from the McDonnell-Pew Program in
Cognitive Neuroscience and grant JSMF 20002029 from
the James S. McDonnell Foundation. J.H.K. was the recipient of grant NS16446 from NINDS. Northwestern
University was the recipient of grant NS1P30 AG13854-01 from the National Institute on Aging.
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