Cerebral Cortex August 2007;17:1757--1765
doi:10.1093/cercor/bhl086
Advance Access publication September 29, 2006
The Association between Handedness,
Brain Asymmetries, and Corpus Callosum
Size in Chimpanzees (Pan troglodytes)
William D. Hopkins1,2, Leslie Dunham2, Claudio Cantalupo3 and
Jared Taglialatela2
It has been suggested from studies in human subjects that sex,
handedness, and brain asymmetries influence variation in corpus
callosum (CC) size and these differences reflect the degree of
connectivity between homotopic regions of the left and right
cerebral hemispheres. Here we report that handedness is associated with variation in the size of the CC in chimpanzees. We further
report that variation in brain asymmetries in a cortical region
homologous to Broca’s area is associated with the size of the CC
but differs for right- and left-handed individuals. Collectively, the
results suggest that individual differences in functional and
neuroanatomical asymmetries are associated with CC variation
not just in humans but also in chimpanzees and therefore may
reflect a common neural basis for laterality in these 2 species.
studies and differences may reflect 1) the types of specimens used
(post mortem vs. in vivo imaging), 2) the manner in which the CC
is quantified, and 3) with respect to handedness, the procedure
by which subjects are classified as left- or right-handed.
Less studied in humans has been the association between
neuroanatomical asymmetries and CC size, particularly in relation to handedness or other functional asymmetries (Clarke
et al. 1993; Clarke and Zaidel 1994; Moffatt et al. 1997; Dorion
et al. 2000). Some have reported negative associations between
magnitudes of brain asymmetry in the posterior sylvian fissure
and CC size, particularly in males (Aboitiz et al. 1996). Luders
et al. (2003), in one of the only studies to examine the modulating effect of handedness on the association between brain
asymmetries and CC size, found a significant association
between sylvian fissure length and total and anterior CC size,
particularly among right-handed subjects. In contrast, the
splenium positively correlated with asymmetries in the postcentral sulcus. Clearly more studies are needed in which the
combined effect of handedness and brain asymmetry in relation
to CC size is assessed because handedness may not necessarily
be the best indicator of all neuroanatomical asymmetries. For
example, correlations between handedness and asymmetries in
the planum temporale (PT), inferior frontal lobe, and motorhand area, although significant, seldom account for more than
50% of the variance (Foundas et al. 1995; Beaton 1997;
Hammond 2002). Thus, there is variability in directional biases
in brain asymmetries within defined handedness groups and
therefore the combined rather than the independent effects of
handedness and brain asymmetries might potentially explain
a greater amount of variability in CC size.
When considering data from nonhuman animals, there are
almost no studies on the relation between behavioral or brain
asymmetries and CC size. It has been reported that the size of
the CC in male rats is larger than in females and these effects can
be modified by early handling experiences as well as prenatal
hormone exposure (Denenberg et al. 1991). Furthermore, rats
with more asymmetric brains have smaller CCs compared with
rats with less asymmetric brains (summarized in Rosen 1996).
Several studies on mice with callosal agenesis or surgical
transection of the CC have shown that they are significantly
left-pawed and the incidence of complete agenesis is greater in
females compared with males (Manhães et al. 2002, 2003, 2005).
In dogs, the CC is larger in right- compared with left-pawed
individuals (Aydinlioğlu et al. 2000), a finding similar to those
recently reported by Dunham and Hopkins (in press) in
chimpanzees. Franklin et al. (2000) did find that female rhesus
monkeys have smaller CC compared with males, however, no
correction was made for differences in brain volume.
The paucity of data from nonhuman animals on limb preferences and brain asymmetry in relation to CC size is problematic
given the assumption that associations between CC size and
Keywords: brain asymmetry, chimpanzees, corpus callosum, handedness
Introduction
The corpus callosum (CC) is the major tract of fibers connecting homotopic cortical regions of the left and right cerebral
hemispheres. The role of the CC in interhemispheric transfer of
information and duality of cognitive functions has been demonstrated extensively in studies of split-brain patients and
animals (Gazzaniga 2000) as well as individuals with agenesis
of the CC (Jancke et al. 1997b). It has been hypothesized that
variation in the size of the CC can explain both individual and
evolutionary differences in behavioral and brain asymmetries
(Ringo et al. 1994; Rilling and Insel 1999; Aboitiz et al. 2003).
Specifically, it has been suggested that as brain size increases,
interhemispheric connectivity decreases, resulting in greater
neuroanatomical and behavioral specializations of the left and
right cerebral hemispheres, and increased intrahemispheric
connectivity. From a phylogenetic perspective, there is some
support for this theory. Recent comparative studies in vertebrates, including nonhuman primates, have shown an inverse
relationship between brain size and CC morphology as well as
fiber density (Rilling and Insel 1999; Olivares et al. 2000, 2001).
Moreover, in primates, it has also been reported that species
with smaller CC to brain size ratios have larger brain asymmetries (Hopkins and Rilling 2000) than species with larger ratios.
Less clear from the literature is whether or not individual
differences in brain size and asymmetries are associated with
CC morphology (see Jancke et al. 1997a). In humans, a significant body of research has accumulated examining CC size
differences between sexes and handedness groups (Witelson
1985; Habib et al. 1991; Burke and Yeo 1994; Driesen and Raz
1995; Bishop and Wahlsten 1997). In general, the results
indicate that males have smaller CCs than females, and that
left-handed or inconsistently handed subjects have larger CCs
compared with right- or consistently handed individuals (i.e.,
those with either a left or right hand preference). Notwithstanding, the findings have not always been consistent among
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1
Department of Psychology, Agnes Scott College, Decatur,
GA 30030, USA, 2Division of Psychobiology, Yerkes National
Primate Research Center, Atlanta, GA 30322, USA and
3
Department of Psychology, Clemson University, Clemson,
SC 29634, USA
brain asymmetry underlie the organization of lateralization in
the central nervous system of all vertebrates (see Galaburda et al.
1990; Rosen 1996). The complete absence of data from
chimpanzees is particularly unfortunate because recent studies
have shown that great apes, like humans, exhibit populationlevel handedness for a variety of tasks (Hopkins in press) as
well as leftward neuroanatomical asymmetries in brain regions
homologous to the human language areas including Broca’s and
Werrnicke’s areas (Gannon et al. 1998; Hopkins et al. 1998;
Cantalupo and Hopkins 2001; Cantalupo et al. 2003). In addition,
there is some evidence that variation in hand preferences is
associated with neuroanatomical asymmetries in the primary
motor cortex as well as regions of the inferior frontal gyrus (IFG)
(Hopkins and Cantalupo 2004; Taglialatela et al. 2006).
The purpose of this study was to examine whether or not
handedness modulates the association between brain asymmetries and CC size in a sample of chimpanzees. Based on
behavioral and brain asymmetries identified previously in
chimpanzees, it was hypothesized that individual differences
in CC morphology would be associated with variation in
laterality within this species. Specifically, our hypothesis was
that if laterality is associated with a reduction in interhemispheric connectivity in chimpanzees, as manifest by smaller CC,
then more lateralized subjects should show significantly smaller
CC than less lateralized apes. Moreover, if handedness represents a functional asymmetry in chimpanzees, then it was
further hypothesized that variation in the association between
CC size and brain asymmetries would differ between left- and
right-handed individuals.
structed to 256 3 256). Ten of the chimpanzees were scanned using
a 3.0-T scanner (Siemens Trio). T1-weighted images were collected
using a 3-dimensional gradient echo sequence (pulse repetition = 2300
ms, echo time = 4.4 ms, number of signals averaged = 3, matrix size =
320 3 320).
After completing MRI procedures, the subjects scanned in vivo were
returned to the YNPRC and temporarily housed in a single cage for 6--12
h to allow the effects of the anesthesia to wear off, after which they
were returned to their home cage. The archived MRI data were
transferred to a PC running Analyze 6.0 (Mayo Clinic, Mayo Foundation,
Rochester, MN) software for postimage processing.
Brain Regions of Interest
Behavioral assessment of handedness and magnetic resonance images
(MRIs) were collected in a sample of 60 captive chimpanzees (Pan
troglodytes) including 32 females and 28 males ranging in age from 6 to
45 years (mean = 22.06, SD = 11.39). All the chimpanzees are or were
members of a captive colony housed at Yerkes National Primate
Research Center (YNPRC) in Atlanta, GA. Twelve of the brains were
scanned post mortem, whereas the other 48 subjects were alive and
healthy at the time of the scan.
CC Measurement
CC area measurements were taken from the midsagittal slice using
a method similar to that described by Witelson (1989). The method
divides the CC into 7 segments, which are roughly associated with
different sets of fiber projections to various cortical regions of the brain
(LaMantia and Rakic 1990; Pandya et al. 1986; Witelson 1989). Witelson’s
(1989) study was conducted on post-mortem brain tissue, therefore the
method was adapted for use with MRI scans and computer analysis (see
Fig. 1). Using the region of interest function (ROI) within ANALYZE, the
CC was first divided into thirds. The anterior third was then subdivided
into 3 regions by inserting a vertical line through the point where the
anterior CC begins to curve back slightly. This delineated regions 1, 2,
and 3, which are congruent to Witelson’s (1989) rostrum, genu, and
rostrum body. The region of the middle third was subdivided into 2
equal sections, creating regions 4 and 5 referred to as the anterior and
posterior midbodies. The posterior third was further subdivided into 2
sections, the isthmus and splenium. Witelson (1989) defined the
splenium as occupying the posterior one-fifth of the total CC length.
To delineate this region, a total CC length measurement, from the most
anterior point to the most posterior point of the CC, was taken. Based on
the length measurement, a vertical line was drawn through the CC to
define the posterior one-fifth as the splenium. The remaining section,
just anterior to the splenium, was congruent to Witelson’s (1989)
isthmus. Using the tracing tool, the area (in mm2) of the CC lying within
each outlined region was measured in each individual.
Consistent with previous studies (Luders et al. 2003), we combined
the area measures for the 3 most anterior regions (rostrum, genu, and
rostrum-midbody) and referred to this as the anterior CC region. Areas
measures of the CC for each region were calculated for each subject.
Brain volumes were also obtained using an automated segmenting
module within ANALYZE and included white and gray matter as well as
the ventricles but not the cerebellum or brain stem structures. L.D.
Image Collection and Procedure
MRIs were obtained from cadaver specimens and in vivo. The cadaver
specimens (n = 12) were stored in a solution of water and 10%
formaldehyde for intervals ranging from 1 week to 5 years and were
scanned with a 4.7-T magnet (Bruker, BioSpec). For the in vivo scans,
subjects were first immobilized by ketamine injection (10 mg/kg) and
subsequently anaesthetized with propofol (40--60 mg/kg/h) following
standard procedures at the YNPRC. Subjects were then transported to
the MRI facility. The subjects remained anaesthetized for the duration of
the scans as well as the time needed to transport them between their
home cage and the imaging facility (total time ~2 h). Subjects were
placed in the scanner chamber in a supine position with their head fitted
inside the human-head coil. Scan duration ranged between 40 and 80
min as a function of brain size. The majority of the subjects (n = 38)
were scanned using a 1.5-T scanner (Phillips, Model 51). The remaining
chimpanzees (n = 10) were scanned using a 3.0-T scanner (Siemens
Trio, Siemens Medical Solutions USA, Inc., Malvern, PA) at the YNPRC.
For all chimpanzees scanned in vivo using the 1.5-T machine, T1weighted images were collected in the transverse plane using a gradient
echo protocol (pulse repetition = 19.0 ms, echo time = 8.5 ms, number
of signals averaged 8, and a 256 3 256 matrix). For the 12 postmortem
scans, T2-weighted images were collected in the transverse plane using
a gradient echo protocol (pulse repetition = 22.0 s, echo time = 78.0 ms,
number of signals averaged = 8--12, and a 256 3 192 matrix recon-
Figure 1. Midsagittal slice of a chimpanzee brain with each measured region of the
CC outlined according to the procedure used by Luders et al. (2003).
Method
Subjects
1758 Corpus Callosum Size in Chimpanzees
d
Hopkins et al.
traced all the CC and was blind to the sex and handedness of the
subjects. To assess reliability, 2 individuals (L.D. and J.T.) blind to the
handedness of the subjects independently measured the entire CC
and each region within the CC in a sample of 10 chimpanzees. For the
entire CC, the correlation was positive and significant (r = 0.81, df = 8,
P < 0.01). The correlation coefficients for each region of the CC
ranged from 0.69 to 0.89, all of which were significant at P < 0.05.
Brain Asymmetry Measurements
Two brains regions considered homologous to the classic language areas
of the human brain were measured in this study including the frontalorbital sulcus (FO) and PT. Population-level leftward asymmetries have
been reported for both of these regions in chimpanzees (Cantalupo and
Hopkins 2001; Cantalupo et al. 2003; Hopkins and Cantalupo 2004) and
therefore they were ideal for characterizing the association between
brain asymmetry and handedness. The procedure used to trace reach
region is described below. All experimenters tracing the MRI scans were
blind to the sex and handedness of the subjects. Two individuals blind to
the handedness of the subjects and orientation of the brain independently traced FO and PT. Interrater correlation coefficients between
2 individuals were positive and significant for FO (r = 0.998, df = 6,
P < 0.001) and PT (r = 0.947, df = 6, P < 0.01).
FO sulcus. A portion of the IFG, where part of Broca’s area is located,
was measured by tracing the length of the FO sulcus, a prominent
landmark of the opercular portion of the IFG (see von Bonin 1949;
Cantalupo and Hopkins 2001; Sherwood et al. 2003). FO could be clearly
seen in para-sagittal (1 mm thick) MRI slices, and its length was traced
from the first lateral slice where it was present up to the slice
immediately preceding the opening of the insula (between 4 and 9
slices). The lengths of FO within each hemisphere were summed across
slices to derive an estimate of the area of this region.
Planum temporale. To measure the surface area of PT, the MRI scans
were aligned in the coronal planes and cut into 1-mm slices using
multiplanar reformatting software (ANALYZE). Coronal rather than
sagittal image sequences were used because, according to some, these
provide the best direct assessment of the full depth of the sylvian fossa of
which the PT is its floor (Larsen et al. 1989; Shapleske et al. 1999). The
anterior border of the PT was defined by the most rostral slice showing
Heschl’s gyrus (HG). The posterior border was defined by the most
caudal slice showing the sylvian fissure. Once the anterior and posterior
borders were delineated, the depth of SF (i.e., width of the PT) on each
slice was measured from the superolateral margin of the superior
temporal gyrus. Depth measures were taken up to the lateral ridge of
HG in all the slices where HG was present (normally, HG was no longer
present in slices proximal to the posterior border of PT). Following
a well-established procedure in the human literature, an estimate of the
PT surface areas (in mm2) was computed as the sum of the cumulative
PT depth measures for each slice within a hemisphere multiplied by the
slice thickness.
Handedness Measurement
Like the previous study by Dunham and Hopkins (in press) in
chimpanzees, a composite measure of handedness was derived from 4
measures of hand use previously described in these subjects including
manual gestures (Hopkins et al. 2005), simple reaching (Hopkins et al.
2002), bimanual feeding (Hopkins 1994), and a task measuring coordinated bimanual actions, referred to as the TUBE task (Hopkins
1995). These 4 measures were selected on which to derive a single
measure of handedness because 1) they were uncorrelated with each
other (see Hopkins in press), 2) they each elicit consistent hand
preferences in the chimpanzees, and 3) these measures were available
in the largest cohort of subjects. A brief description of each measure is
provided below.
Manual Gestures
At the onset of each trial, an experimenter would approach
the chimpanzee’s home cage and center themselves in front of the
chimpanzee at a distance of approximately 1.0--1.5 m. If the chimpanzee
was not already positioned in front of the experimenter at the onset of
the trial, the chimpanzee would immediately move toward the front of
the cage when the experimenter arrived with the food. The experimenter then called the chimpanzee’s name and offered a piece of food
until the chimpanzee produced a manual gesture. Only responses in
which the chimpanzee’s unimanually extended their digit(s) through
the cage mesh to request the food were considered a response. Other
possible manual responses such as cage banging or clapping were not
counted as a gesture. Two-handed gestures, although rare, were not
scored as were gestures that were produced by the chimpanzee prior to
the experimenter arriving in front of the chimpanzee’s home cage.
When the chimpanzees produced a unimanual gesture, the experimenter recorded hand use as left or right.
Simple Reaching
On each trial, a raisin was thrown into the subject’s home cage. The
raisin was thrown by the experimenter to a location at least 3 m from
the focal subject so that the chimpanzees had to locomote to position to
the raisin, pick up the raisin, and bring it to their mouth for
consumption. When the chimpanzee acquired the raisin, the experimenter recorded the hand used as left or right. One, and only one,
reaching response was recorded each trial to assure independence of
data points (see McGrew and Marchant 1997; Hopkins 1999 for
contrasting views). Thus, raisins were not randomly scattered in home
cages but rather an individual raisin was thrown into cages and subjects
retrieved the raisin before another was thrown into the cage. Subjects
were required to locomote at least 3 strides between reaching
responses to maintain postural readjustment between trials.
Bimanual Feeding (FEED)
Each afternoon, the primates housed at the YNPRC receive fruits and
vegetables as part of their daily diet. Each subject usually receives 2
oranges, 1 banana, some celery stalks, and/or carrots. Upon retrieving
the food, the subjects typically move to a seating place and consume the
food. The chimpanzees generally hold the extra pieces of food with one
hand and feed with the opposite hand. Hand use was recorded when the
subjects were feeding with one hand for a minimum duration of 3
seconds and the nonfeeding hand was holding the remaining portions of
food. The dominant hand was recorded as the one feeding.
Coordinated Bimanual Actions (TUBE)
The second handedness measure was a task requiring bimanual coordinated actions, referred to as the TUBE task (Hopkins 1995). For the
TUBE task, peanut butter is smeared on the inside edges of polyvinyl
chloride (PVC) tubes approximately 15 cm in length and 2.5 cm in
diameter. Peanut butter is smeared on both ends of the PVC pipe and is
placed far enough down the tube such that the subjects cannot lick the
contents completely off with their mouths but rather must use one hand
to hold the tube and the other hand to remove the substrate. The PVC
tubes were handed to the subjects in their home cages and a focal
sampling technique was used to collect individual data from each
subject. The hand of the finger used to extract the peanut butter was
recorded as either right or left by the experimenter. Each time the
subjects reached into the tube with their finger, extracted peanut butter
and brought it to their mouth, the hand used was recorded as left or
right.
All the chimpanzees were tested in the outdoor portion of their home
cages. The number of responses obtained from each subject differed
within and between tasks. Notwithstanding, a minimum of 30 responses
were obtained for each individual for each task. Individuals recording
the hand use data were blind to the brain asymmetries of the subjects,
the size of the CC, and the hypothesis of the study.
Data Analysis
Corpus Callosum
The best way to analyze differences in CC morphology is a matter of
some debate (Bermudez and Zatorre 2001; Smith 2005). The principle
issue is the confounding relationship between CC size and overall brain
volume. To address this issue, brain volume was regressed on the total
CC area as well as the area measures for each of the 5 CC regions. The
Cerebral Cortex August 2007, V 17 N 8 1759
individual unstandardized residuals were saved from these analyses and
served as subsequent dependent variables in evaluating the influence of
hand and sex on CC morphology. The residuals represent the degree of
deviation in size of the CC area of each individual as predicted from their
brain size. Thus, positive values represent individuals that have larger CC
areas for an organism of their brain volume, whereas negative values
represent individuals that have smaller CC areas for their individual
brain volume. We opted to use the residual values because they have
been used in previous studies on the association between handedness
and CC size in chimpanzees (Dunham and Hopkins in press) as well as in
comparative studies of the relative size of the CC between different
primate species (Hopkins and Rilling 2000).
To be assured that the residual measures were comparable with other
measures, we calculated ratio measures for the entire CC and each
region by dividing the area measures by the total brain volume. The
resulting ratios were then correlated with the residual CC values for the
entire CC as well as the anterior region, anterior-midbody, posteriormidbody, isthmus, and splenium. The resulting correlation coefficients
were 0.650, 0.755, 0.688, 0.684, 0.801, and 0.789, respectively. Each of
these correlation coefficients was significant at P < 0.01.
Brain Asymmetries
For both the FO sulcus and PT, asymmetry quotients (AQ) were derived
following a commonly used formula AQ = [(R – L)/R + L) 3 0.5] in which
positive values reflect rightward asymmetries and negative values
reflected leftward biases. Based on the sign of the AQ values, we
classified any chimpanzees having a negative AQ value as being left
hemisphere biased and any subjects with a positive AQ as right
hemisphere biased.
Hand Preference Classification
For each measure, a handedness index (HI) was determined following
the formula HI = (R – L)/R + L), where R and L reflect the frequency of
left and right hand use. HI values varied from –1.0 to 1.0 with negative
values reflecting left hand biases and positive values reflecting right
hand biases. Rather than consider each handedness measure separately
in the analyses, we derived a single composite handedness value by
averaging the HI values for the 4 tasks. Based on the sign of the averaged
HI values, we classified subjects as right (HI > 0) or left handed (HI < 0).
Using this criterion, there were 39 right-handed and 21 left-handed
chimpanzees in our sample.
Results
Descriptive Statistics
Few studies have examined different aspects of CC size in
chimpanzees. Therefore, for the sake of providing descriptive
data for this species, we have provided the mean area for the
overall CC as well as the specific ROIs for males and females in
our sample (see Table 1). In rhesus monkeys and rats, early
rearing experiences have been shown to influence CC size
(Denenberg et al. 1991; Sánchez et al. 1998). Thus, to assess
whether rearing had a significant effect on CC size in our
subjects, a multiple analysis of variance (MANOVA) was per-
formed with the raw CC area measures serving as the dependent
variables. Sex and rearing history (mother, nursery, wild) served
as between group variables. The MANOVA was performed with
and without brain volume serving as a covariate. For both
analyses, no significant main effects or interactions were found.
Thus, neither rearing history nor sex had a significant influence
on the raw or adjusted CC size. We also examined the potential
effect of sex and rearing history on the AQ values for FO and PT as
well as the average handedness index. No significant main effects
or interactions were found. Lastly, one sample t-tests on the AQ
values for the PT, t(59) = –5.19, P < 0.001, and FO, t(59) = 2.34, P <
0.01, revealed significant population-level leftward asymmetries,
whereas a population-level rightward bias was found for the
average HI value, t(59) = 3.11, P < 0.01. These findings are
consistent with previous reports in our laboratory (Cantalupo
and Hopkins 2001; Cantalupo et al. 2003; Hopkins in press).
Handedness and Sex Differences in Brain Asymmetry
We next examined the influence of sex and handedness on
brain asymmetries. For this analysis, the AQ values for the PT and
FO served as repeated measures in a mixed model analysis of
variance. Sex (male, female) and handedness (left, right) served
as between-group factors. No significant main effects or interaction were found. The mean AQ values for left- and righthanded males and females are shown in Table 2.
Because we were interested in the potential modulating
effect of CC size in relation to handedness and brain asymmetry,
we reran the same analysis as described above but included the
overall CC residual as a covariate. The subsequent results
indicated a significant 2-way interaction between handedness
and brain asymmetry, F1,52 = 4.08, P < 0.04 (see Table 2). Post
hoc analysis indicated that right-handed males were more
leftward in their AQ values compared with left-handed males.
In contrast, no significant difference was found between leftand right-handed females.
Handedness, Brain Asymmetry and Residual CC Size
(ADD FOOTNOTE)
For this analysis, the total and regional residual CC values served
as dependent variables in a MANOVA. Handedness (left, right),
brain asymmetry (left, right), and sex (male, female) served as
between-group factors. Separate analyses were performed for
the FO and PT measures of brain asymmetry. For FO, the
MANOVA revealed a significant 2-way interaction between
handedness and brain asymmetry, F6,47 = 2.45, P < 0.04. The
subsequent univariate F-tests revealed significant 2-way interactions between handedness and brain asymmetry for the total
CC F1,52 = 11.92, P < 0.01, anterior F1,52 = 6.43, P < 0.02,
Table 2
Mean AQ values for FO in left- and right-handed male and female chimpanzees
Table 1
Descriptive statistics for corpus area measures and brain volume
Total CC mm2
Anterior third mm2
Anterior-midbody mm2
Posterior-midbody mm2
Isthmus mm2
Splenium mm2
Brain volume cc
Females
Males
309.33
125.59
39.25
33.47
28.78
84.53
353.77
304.61
125.41
38.44
31.61
29.95
80.17
386.13
(6.35)
(3.12)
(1.21)
(0.85)
(1.18)
(2.29)
(6.95)
Values in parentheses indicate standard errors.
1760 Corpus Callosum Size in Chimpanzees
d
Hopkins et al.
(8.36)
(4.20)
(1.63)
(1.14)
(1.59)
(3.08)
(9.35)
Left handed
Right handed
Raw AQ
Males
SE
Females
SE
0.021
(0.06)
0.202
(0.07)
0.131
(0.05)
0.101
(0.05)
AQ adjusted for total CC size
Males
SE
Females
SE
0.005
(0.06)
0.193
(0.07)
0.150
(0.05)
0.106
(0.05)
anterior-midbody F1,52 = 12.48, P < 0.01, posterior-midbody
F1,52 = 3.88, P < 0.05, and isthmus F1,52 = 4.23, P < 0.05. The
mean residual CC value for the total CC and each region is
shown in Figure 2. Post hoc analysis was performed using
Tukey’s honestly significant difference test. Despite relative
large differences in the residual CC values, among left-handed
chimpanzees, post hoc analyses indicated no significant differences between chimpanzees considered left or right hemisphere biased based on the sign of their AQ value. In contrast,
among right-handed chimpanzees, individuals who had positive
AQ values for FO had significantly higher residual CC values
than individuals with negative AQ values. Moreover, among
individuals with positive AQ values for FO, left-handed chimpanzees had significantly lower residual values for each CC
region compared with right-handed chimpanzees. For the PT,
the same analysis was performed and no significant main effects
or interactions were found. Thus, there was no justification to
consider the univariate F-tests for each individual CC region. For
50
Right-Handed
Left Hemisphere
Right Hemisphere
Mean CC Residual ( + / - s.e.)
40
30
20
10
0
Correlations between AQ Measures,
Handedness, and Sex
In the previous analyses, brain asymmetries were considered as
a categorical variable (leftward or rightward) based on the sign
of the AQ values. Because AQ values lie on a continuous scale of
measurement, we used an alternative approach to assessing the
association between brain asymmetry and CC size within each
handedness group. Specifically, in the next analyses, the FO and
PT AQ values were correlated with the residual CC values
and separate correlation coefficients were performed for leftand right-handed chimpanzees as well as between males and
females (see Table 3). For right-handed chimpanzees, significant
associations were found between the FO AQ values and the
entire CC, anterior-midbody, posterior-midbody, and isthmus.
For left-handed chimpanzees, none of the correlations reached
conventional levels of statistical significance. For the PT, none of
the correlations were significant. For FO, a comparison between
the correlation coefficients of left- and right-handed chimpanzees revealed significant differences for the overall CC as well as
the anterior-midbody, posterior-midbody, and isthmus (see
Table 3). Thus, right- and left-handed chimpanzees showed
significant opposite associations between asymmetries in FO
and regions of the CC. Among right-handed chimpanzees, more
rightward lateralized subjects for FO had larger CC values. In
contrast, in left-handed chimpanzees, more rightward FO values
were associated with smaller CC values.
-10
-20
-30
-40
-50
Total
Anterior- Anterior- Posterior- Isthmus Splenium
Midbody Midbody
Third
Corpus Callosum Region
50
Correlations between Absolute AQ Values,
Handedness, and Sex
Rather than the direction of bias, in the next analyses we
examined the association between strength of brain asymmetry,
handedness, and sex. For these analyses, the absolute value of
the AQ scores was calculated and used in the analyses. Separate
correlation analyses between the absolute FO and PT AQ values
and the CC residual values for males and females as well as leftand right-handed chimpanzees were carried out (see Table 4).
Left-Handed
Left Hemisphere
Right Hemisphere
40
Mean CC Residual ( + / - s.e.)
both regions, no significant main effects or interactions were
found for the sex of the subjects.
30
20
Table 3
Correlation coefficents between FO and PT AQ values and CC size for each sex and
handedness group
CC region
10
Handedness
Left
0
z
Right
Sex
Males
z
Females
FO
-10
-20
-30
Total
Anterior third
Anterior-midbody
Posterior midbody
Isthmus
Splenium
0.306
0.245
0.384
0.220
0.079
0.176
0.525
0.245
0.334
0.422
0.489
0.281
3.11þ
1.73*
2.61þ
2.33þ
2.13þ
1.62
0.189
0.207
0.132
0.107
0.162
0.049
0.086
0.202
0.143
0.147
0.265
0.140
0.38
1.52
1.01
0.15
0.39
0.18
Total
Anterior third
Anterior-midbody
Posterior midbody
Isthmus
Splenium
0.319
0.361
0.097
0.184
0.131
0.269
0.070
0.003
0.056
0.093
0.018
0.062
1.78*
1.29
0.14
0.96
0.39
0.74
0.089
0.143
0.019
0.075
0.068
0.091
0.095
0.040
0.161
0.048
0.083
0.053
0.67
0.38
0.66
0.09
0.05
0.14
PT
-40
-50
Total
Anterior- Anterior- Posterior- Isthmus Splenium
Third
Midbody Midbody
Corpus Callosum Region
Figure 2. Mean residual values for the total CC and each region of the CC for left- and
right-handed chimpanzees. Left hemisphere (in blue) indicates those subjects that had
negative AQ values for FO, whereas right hemisphere (in red) indicates those
individuals with AQ values for FO that were positive.
Bolded values indicate significant correlation coefficients at P \ 0.05. Values underlined are
significant at P \ 0.10. Between hand and between sex differences in correlation coefficients
were statistically compared and are indicated by the corresponding z-scores. þP \ 0.05,
*P \ 0.10.
Cerebral Cortex August 2007, V 17 N 8 1761
Table 4
Correlation coefficients between FO and PT abs-AQ values and cc size for each sex and
handedness group
CC region
Handedness
z
Left
Right
Total
Anterior third
Anterior-midbody
Posterior midbody
Isthmus
Splenium
0.087
0.003
0.078
0.135
0.242
0.021
0.281
0.075
0.067
20.355
0.206
0.137
Total
Anterior third
Anterior-midbody
Posterior midbody
Isthmus
Splenium
0.404
0.451
0.075
0.215
0.201
0.301
0.132
0.079
0.007
0.141
0.046
0.163
Sex
z
Males
Females
0.69
0.24
0.03
0.37
0.13
0.40
20.400
0.326
0.294
0.355
20.518
0.097
0.044
0.212
0.114
0.226
0.092
0.110
1.38
2.03þ
1.53
0.51
2.44þ
0.04
1.94*
1.41
0.24
1.25
0.54
1.65*
0.177
0.303
0.152
0.056
0.058
0.053
0.094
0.094
0.126
0.004
0.091
0.002
0.98
0.80
1.02
0.04
0.12
0.20
FO
PT
Bolded values indicate significant correlation coefficients at P \ 0.05. Values underlined are
significant at P \ 0.10. Between hand and between sex differences in correlation coefficients
were statistically compared and are indicated by the corresponding z-scores. þP \ 0.05,
*P \ 0.10.
Overall, there were few significant associations. With regard to
hand use, among left-handed chimpanzees, more lateralized
asymmetries in the PT were associated with relatively smaller
CC for the total and anterior-third region. Regarding the sex of
the subjects, for FO, males with larger asymmetries had smaller
residual values for the total CC and isthmus.
Discussion
Three significant findings emerged from this study. First,
handedness modulates the association between CC size and
brain asymmetries in the FO sulcus but not the PT in
chimpanzees. Second, after adjusting for the relative size of
the CC, a significant hand by sex interaction was found for the
brain asymmetries. Lastly, correlational analyses between
strength of brain asymmetries and relative CC size revealed
some significant associations, particularly for the FO sulcus in
males.
One of the main findings of this study was that the association
between CC size and brain asymmetries, particularly for FO, the
sulcus comprising part of the frontal operculum varies depending on the handedness of the subjects. In particular, righthanded chimpanzees that had asymmetries in FO that were
ipsilateral to their preferred hand had larger CC residual values
than chimpanzees that had asymmetries that were consistent
with their preferred hand. To our knowledge, this is the first
evidence indicating that an association between brain asymmetries and CC size is altered by their limb preference, in
a nonhuman animal. It is somewhat difficult to interpret these
results comparatively with findings in humans because different
brain regions have been assessed between the 2 species (e.g.,
Luders et al. 2003). Structure--function associations in relation
to CC size have largely focused on the PT in humans and our
results for FO are consistent with at least some of those reports
(Moffatt et al. 1997; Sequeira et al. 2006). That is, for righthanded individuals, greater rightward brain asymmetries were
associated with a larger CC (Moffatt et al. 1997); however, it
should be stated that the results we obtained for the PT in the
chimpanzees are not entirely consistent with those in humans,
in light of the fact that none of the MANOVA results reached
1762 Corpus Callosum Size in Chimpanzees
d
Hopkins et al.
significance. Thus, attempting to compare the findings may not
be entirely legitimate given the procedural differences and
kinds of tasks used to assess asymmetries between the 2 species.
In point of fact, we could find no studies that have examined the
association between CC size and asymmetries in the frontal
operculum in human subjects.
One of the main limitations of our study with respect to the
PT was the lack of subjects with a rightward asymmetry. Of the
60 subjects, 48 were classified as leftward biased (80%) and 12
were rightward biased (20%). For right-handed chimpanzees,
9 showed a rightward PT bias, whereas only 3 left-handed
chimpanzees showed a rightward PT bias. Thus, there simply
was not enough variability in PT asymmetry between left- and
right-handed chimpanzees to make this a particularly useful
comparison in our study, despite the obvious heuristic interest
in this brain region. The relatively large distribution of leftward
biased subjects is somewhat higher than the values reported for
human brains (Beaton 1997) but is consistent with one other
report of PT asymmetries in chimpanzee cadaver specimens
(Gannon et al. 1998).
When one considers the correlation between the total CC
size and FO for left- and right-handed chimpanzees, the pattern
of results largely reflects the findings when using the MANOVA
statistics. For right-handed subjects, subjects with more leftward AQ values had smaller CC sizes. In left-handed chimpanzees, the opposite pattern occurs; subjects with more leftward
asymmetries had larger CC residual values. When considered
collectively, the following pattern of results is evident. Left- and
right-handed chimpanzees with FO asymmetries that are larger
in the contralateral hemisphere have CC sizes that do not differ
substantially from what would be predicted for an animal of
their brain size. In contrast, right-handed chimpanzees with FO
asymmetries that are larger in the ipsilateral hemisphere have
large CC values for animals of their brain size. Left-handed
chimpanzees with larger brain asymmetries in the hemisphere
ipsilateral to their preferred hand have smaller CC values for
animals of their brain size. Thus, quite different patterns in
relation to FO asymmetry and CC size are found in these 2
handedness cohorts.
What explains the differential pattern of results between
right- and left-handed chimpanzees in relation to FO brain
asymmetries is not clear. Witelson and Nowakowski (1991) and
others (Galaburda et al. 1990) have suggested that differences in
CC size in right- and left-handed subjects may reflect excessive
or a lack of pruning of interhemispheric cortical cells during
development. These theoretical models have largely attempted
to explain hand and sex difference in CC size in humans and
have not necessarily considered both brain asymmetry and
handedness together. Notwithstanding, if one adopts the
theoretical position of Witelson and Nowakowski (1991), our
results would suggest that the association between brain
asymmetries and the CC in left- and right-handed chimpanzees
may reflect differences in axonal pruning between hemispheres. The origin of these potential neurodevelopmental
effects is not clear but post-mortem studies on CC morphology
and cellular organization in chimpanzee corpus callosi would be
most useful for interpreting the morphology data (see Broadfield 2001).
We found almost no evidence of sex differences in relative CC
size. Specifically, for all of the MANOVA analyses, sex was
a never a significant main effect nor interacted significantly with
either handedness or brain asymmetry. When considering the
Mean Ratio CC Value (+ / - s.e.)
1.2
Right-Handed
1.0
0.8
0.6
0.4
0.2
0.0
Overall Anterior- Anterior Posterior Isthmus Splenium
Third Midbody Midbody
Corpus Callosum Region
1.2
Mean Ratio CC Value (+ / - s.e.)
correlation analyses, there were some significant associations
found between strength of asymmetry and CC size in males but
there were many correlations performed and we cannot rule
out type I error as a potential explanation for this finding.
Notwithstanding these limitations, it is of note that the inverse
relation between brain asymmetry and CC size was in males
only, a finding consistent with 2 other reports in humans
(Aboitiz et al. 1996; Luders et al. 2003) and at least one report
in rats (Berrebi et al. 1998). Thus, where significant associations
were found, our results are consistent with the extant literature.
It could be argued that inclusion of post-mortem images may
have skewed the results in someway due to shrinkage factors. If
the same analyses as described above are performed only on the
in vivo scans, no differences in the results are found. Thus,
inclusion of the cadaver scans is appropriate and does not skew
the results. Moreover, we used the residual CC values and
presumably shrinkage would influence all brain regions in
a similar manner. Thus, relatively speaking, the CC size as well
as overall brain volume were both smaller in post mortem brains
due to the same influence of the fixative agents.
It should also be noted that different approaches have been
employed to statistically control for individual differences in
brain size in relation to CC size (i.e., Smith 2005). We opted to
use residual values but if other measures are used in our sample,
comparable results are found. Specifically, if ratio measures in
the size of the CC relative to brain volume are used (CC values/
brain volume) are used as the dependent measures, significant
intereactions are found between handedness and brain asymmetry for the entire CC, F1,56 = 12.58, P < 0.001, as well as the
anterior region, F1,56 = 9.05, P < 0.01, anterior-midbody, F1,56 =
11.68, P < 0.001, posterior-midody, F1,56 = 7.08, P < 0.01,
isthmus, F1,56 = 6.89, P < 0.01, and splenium, F1,56 = 4.99, P <
0.05. For comparison to the findings using the residual values
depicted in Figure 3 are the mean ratio values for left- and righthanded chimpanzees that had either positive or negative AQ
values for FO (labeled left or right hemisphere biased). As can be
seen, the results for the ratio values are quite comparable with
the results using residual CC values. Thus, our results are
consistent across different methods used in controlling for the
relative difference in CC size in relation to brain volume.
In sum, the results reported here indicate that associations
between the size of the CC and brain asymmetry are modulated
by the handedness of the chimpanzees but not their sex.
Specifically, chimpanzees with brain asymmetries in the FO
sulcus consistent with their preferred hand have significantly
smaller CC residual values than chimpanzees with asymmetries
ipsilateral to their preferred hand and these effects are more
robust for the anterior regions of the CC. Some have questioned
the validity of handedness as a marker of hemispheric specialization in nonhuman primates (Warren 1980; Ettlinger 1988)
and our results contradict this view. Rather, our results suggest
that handedness in chimpanzees when considered alone or in
conjunction with a measure of brain asymmetry explains
a significant proportion of variation in CC size and therefore is
a significant predictor of hemispheric specialization. Lastly, we
found no compelling evidence of sex differences in the relative
size of the CC in chimpanzees, a finding at odds with common
lore in the human literature on CC morphology; however,
reports of sex differences in CC morphology in humans are not
consistent across studies and therefore should be interpreted
with some caution. If sex differences in CC morphology are
evident in humans and not in chimpanzees, this might represent
Left-Handed
1.0
0.8
0.6
0.4
0.2
0.0
Overall Anterior- Anterior Posterior Isthmus Splenium
Third Midbody Midbody
Corpus Callosum Region
Figure 3. Mean ratio values for the total CC and each region of the CC for left- and
right-handed chimpanzees. Left hemisphere (in blue) indicated those subjects that had
negative AQ values for FO, whereas right hemisphere (in red) indicates those
individuals with AQ values for FO that were positive.
a neurological trait unique to hominid evolution, as has been
suggested by some (Holloway et al. 1993).
Notes
This work was supported in part by National Institutes of Health grants
RR-00165, NS-42867, NS-36605, and HD-38051. The Yerkes Center is
fully accredited by the American Association for Accreditation of
Laboratory Animal Care, and American Psychological Association guidelines for the ethical treatment of animals were adhered to during all
aspects of this study. Special thanks to the veterinary staff for assisting
in the care of the animals during scanning. Conflict of Interest : None
declared.
Address correspondence to Dr William Hopkins, Division of Psychobiology, Yerkes National Primate Research Center, 954 Gatewood Road,
Atlanta, GA 30322, USA. Email: [email protected] or Whopkins@
agnesscott.edu.
References
Aboitiz F, Lopez J, Montiel J. 2003. Long distance communication in the
human brain: timing constraints for inter-hemispheric synchrony
and the origin of brain lateralization. Biol Res. 36:89--99.
Cerebral Cortex August 2007, V 17 N 8 1763
Aboitiz F, Rodriguez E, Olivares R, Zaidel E. 1996. Age-related changes in
fiber composition of the human corpus callosum: sex differences.
Neuroreport. 7:1761--1764.
Aydinlioğlu A, Arslan K, Erdoğan AR, Rağbetli Ç, Kelesx P, Diyarbakirli S.
2000. The relationship of callosal anatomy to paw preference in
dogs. Eur J Morphol. 38:128--133.
Beaton AA. 1997. The relation of planum temporale asymmetry and
morphology of the corpus callosum to handedness, gender, and
dyslexia: a review of the evidence. Brain Lang. 15:255--322.
Bermudez P, Zatorre RJ. 2001. Sexual dimorphism in the corpus
callosum: methodological considerations in MRI morphometry.
Neuroimage. 13:1121--1130.
Berrebi A, Fitch R, Ralphe D, Denenberg J, Friedrich V Jr, Denenberg V.
1988. Corpus callosum: region-specific effects of sex, early experience, and age. Brain Res. 438:216--224.
Bishop KM, Wahlsten D. 1997. Sex differences in the human
corpus callosum: myth or reality? Neurosci Biobehav Rev. 21:
581--601.
Burke HL, Yeo RA. 1994. Systematic variations in callosal morphology:
the effects of age, gender, hand preference, and anatomic asymmetry. Neuropsychology. 8:563--571.
Broadfield DC. 2001. Sex differences in the corpus callosum of Macaca
fascicularis and Pan troglodytes [unpublished doctoral dissertation].
New York: Columbia University. 337 p.
Cantalupo C, Hopkins WD. 2001. Asymmetric Broca’s area in great apes.
Nature. 414:505.
Cantalupo C, Pilcher DL, Hopkins WD. 2003. Are planum temporale and
sylvian fissure asymmetries directly related? A MRI study in great
apes. Neuropsychologia. 41:1975--1981.
Clarke JM, Lufkin RB, Zaidel E. 1993. Corpus callosum morphometry and
dichotic listening performance: individual differences in functional
interhemispheric inhibition? Neuropsychologia. 31:547--557.
Clarke JM, Zaidel E. 1994. Anatomical-behavioral relationships: corpus
callosum morphometry and hemispheric specialization. Behav Brain
Res. 64:185--202.
Denenberg VH, Fitch RH, Schrott LM, Cowell PE, Waters NS. 1991.
Corpus callosum: interactive effects of infantile handling and
testosterone in the rat. Behav Neurosci. 105:562--566.
Dorion AA, Chantome M, Hasboun D, Zouaoui A, Marsault C, Capron C,
Duyme M. 2000. Hemispheric asymmetry and corpus callosum
morphometry: a magnetic resonance imaging study. Neurosci Res.
36:9--13.
Driesen NR, Raz N. 1995. The influence of sex, age, and handedness on
corpus callosal morphology: a meta-analysis. Psychobiology. 23:
240--247.
Dunham LD, Hopkins WD. Sex and handedness effects on corpus
callosum morphology in chimpanzees (Pan troglodytes). Behav
Neurosci. Forthcoming.
Ettlinger G. 1988. Hand preference, ability, and hemispheric specialization: in how far are these factors related to the monkey? Cortex.
24:389--398.
Franklin MS, Kraemer GW, Shelton SE, Baker E, Kalin NH, Uno H. 2000.
Gender differences in brain volume and size of corpus callosum and
amygdale of rhesus monkey measured from MRI images. Brain Res.
852:263--267.
Foundas A, Leonard C, Heilman K. 1995. Morphological cerebral
asymmetries and handedness: the pars triangularis and planum
temporale. Arch Neurol. 52:501--508.
Galaburda AM, Rosen GD, Sherman GF. 1990. Individual variability in
cortical organization: its relationship to brain laterality and implications to function. Neuropsychologia. 28:529--546.
Gannon PJ, Holloway RL, Broadfield DC, Braun AR. 1998. Asymmetry of
chimpanzee planum temporale: humanlike pattern of Wernicke’s
language area homolog. Science. 279:220--222.
Gazzaniga M. 2000. Cerebral specialization and interhemispheric
communication: does the corpus callosum enable the human
condition? Brain. 123:1293--1326.
Habib M, Gayraud D, Olivia A, Regis J, Salamon G, Khalil R. 1991. Effects
of handedness and sex on the morphology of the corpus callosum:
a study with brain magnetic resonance imaging. Brain Cogn.
16:41--61.
1764 Corpus Callosum Size in Chimpanzees
d
Hopkins et al.
Hammond G. 2002. Correlates of human handedness in primary motor
cortex: a review and hypothesis. Neurosci Biobehav Rev. 26:
285--292.
Holloway RL, Anderson PJ, Defendini R, Harper C. 1993. Sexual
dimorphism of the human corpus callosum from three independent
samples: relative size of the corpus callosum. Am J Phys Anthropol.
92:481--498.
Hopkins WD. 1994. Hand preference for bimanual feeding in 140
captive chimpanzees: rearing and ontogenetic determinants. Dev
Psychol. 27:395--407.
Hopkins WD. 1995. Hand preferences for a coordinated bimanual task in
110 chimpanzees: cross-sectional analysis. J Comp Psychol.
109:291--297.
Hopkins WD. 1999. On the other hand: Statistical issues in the
assessment and interpretation of hand preference data in nonhuman
primates. Int J Primatol. 20:851--866.
Hopkins WD. Hemispheric specialization in chimpanzees: evolution
of hand and brain. In: Shackelford T, Keenan JP, Platek, SM,
editors. Evolutionary cognitive neuroscience. Boston: MIT Press.
Forthcoming.
Hopkins WD, Cantalupo C. 2004. Handedness in chimpanzees (Pan
troglodytes) is associated with asymmetries of the primary motor
cortex but not with homologous language areas. Behav Neurosci.
118:1176--1183.
Hopkins WD, Cantalupo C Wesley MJ, Hostetter AB, Pilcher DL. 2002.
Grip morphology and hand use in chimpanzees (Pan troglodytes):
evidence of left hemispheric specialization of motor skills. J Exp
Psychol Gen. 131:412--423.
Hopkins WD, Marino L, Rilling J, MacGregor L. 1998. Planum temporale
asymmetries in great apes as revealed by magnetic resonance
imaging (MRI). Neuroreport. 9:2913--2918.
Hopkins WD, Rilling JK. 2000. A comparative MRI study of the relationship between neuroanatomical asymmetry and interhemispheric
connectivity in primates: implication for the evolution of functional
asymmetries. Behav Neurosci. 114(4):739--748.
Hopkins WD, Russell J, Freeman H, Buehler N, Reynolds E, Schapiro SJ.
2005. The distribution and development of handedness for manual
gestures in captive chimpanzees. Psychol Sci. 16:487--493.
Jancke L, Staiger JF, Schlaug G, Huang Y, Steinmetz H. 1997a. The
relationship between corpus callosum size and forebrain volume.
Cereb Cortex. 7:48--56.
Jancke L, Wunderlich G, Schlaug G, Steinmetz H. 1997b. A case of
callosal agenesis with strong anatomical and functional asymmetries.
Neurosychologia. 35:1389--1394.
LaMantia AS, Rakic P. 1990. Cytological and quantitative characteristics
of four cerebral commissures in the rhesus monkey. J Comp Neurol.
291:520--537.
Larsen JP, Ødegaard H, Grude TH, Høien T. 1989. Magnetic resonance
imaging—a method of studying the size and asymmetry of the
planum temporale. Acta Neurol Scand. 80:438--443.
Luders E, Rex DE, Narr KL, Woods RP, Jancke L, Thompson PM,
Mazziotta JC, Toga AW. 2003. Relationships between sulcal asymmetries and corpus callosum size: gender and handedness effects. Cereb
Cortex. 13:1084--1093.
Manhães AC, Krahe TE, Caparelli-Dáquer E, Ribeiro-Carvalho A, Schmidt
SL, Filgueiras CC. 2003. Neonatal transaction of the corpus callosum
affects paw preference lateralization of adult Swiss mice. Neurosci
Lett. 348:69--72.
Manhães AC, Medina AE, Schmidt SL, Filgueiras CC. 2002. Sex differences in the incidence of total callosal agenesis in BALB/cCF mice.
Neurosci Lett. 325:159--162.
Manhães AC, Schmidt SL, Filgueiras CC. 2005. Callosal agenesis affects
consistency of laterality in a paw preference task in BALB/cCF mice.
Behav Brain Res. 159:43--49.
McGrew WC, Marchant LF. 1997. On the other hand: current issues in
and meta-analysis of the behavioral laterality of hand function in non
human primates. Am J Phys Anthropol. 104:201--232.
Moffatt SD, Hampson E, Lee DH. 1997. Morphology of the planum
temporale and corpus callosum in left-handers with evidence of
left and right hemisphere speech lateralization. Brain. 121:
2369--2379.
Olivares R, Michalland S, Aboitiz F. 2000. Cross-species and intra-species
morphometric analysis of the corpus callosum. Brain Behav Evol.
55:37--43.
Olivares R, Montiel J, Aboitiz F. 2001. Species differences and similarities
in the fine structure of the mammalian corpus callosum. Brain Behav
Evol. 57:98--105.
Pandya DN, Seltzer B. 1986. The topography of the commissural
fibers. In: Lepore F, Ptito M, Jasper HH, editors. Two hemispheresonebrain: Functions of the corpus callosum. New York: Alan R.
Liss. p. 47--73.
Rilling J, Insel T. 1999. Differential expansion of neural projection
systems in primate brain evolution. Neuroreport. 10:1453--1459.
Ringo J, Doty R, Demeter S, Simard P. 1994. Timing is of essence:
a conjecture that hemispheric specialization arises from interhemispheric conduction delay. Cereb Cortex. 4:331--343.
Rosen GD. 1996. Cellular, morphometric, ontogenetic and connectional
substrates of anatomical asymmetry. Neurosci Biobehav Rev.
20:607--615.
Sánchez MM, Hearn EF, Do D, Rilling JK, Herndon JG. 1998. Differential
rearing affects corpus callosum size and cognitive function of rhesus
monkeys. Brain Res. 812:38--49.
Sequeria SS, Woerner W, Walter C, Kreider F, Lueken U, Westerhausen R,
Wittling RA, Wittling W. 2006. Handedness, dichotic-listening, and
gender effects on planum temporale asymmetry—a volumetric
investigation using structural magnetic resonance imaging. Neuropsychologia. 44:622--636.
Shapleske J, Rossell SL, Woodruff PWR, David AS. 1999. The planum
temporale: a systematic, quantitative review of its structural,
functional and clinical significance. Brain Res Rev. 29:26--49.
Sherwood CC, Broadfield DC, Holloway RL, Gannon PJ, Hof PR. 2003.
Variability of Broca’s area homologue in African great apes: implications for language evolution. Anat Rec A Discov Mol Cell Evol Biol.
271A:276--285.
Smith RJ. 2005. Relative size versus controlling for size: interpretation of
ratios in research on sexual dimorphism in the human corpus
callosum. Curr Anthropol. 46:249--273.
Taglialatela J, Cantalupo C, Hopkins WD. 2006. Gesture handedness
predicts asymmetry in the chimpanzee inferior frontal gyrus. Neuroreport. 17:923--927.
von Bonin G. 1949. Architecture of the precentral motor cortex and
some adjacent areas. In: Bucy PC, editor. The precentral motor
cortex. Urbana, IL: University of Illinois Press. p. 7--82.
Warren JM. 1980. Handedness and laterality in humans and other
animals. Physiol Psychol. 15:349--360.
Witelson S. 1989. Hand and sex differences in the isthmus and genu of
the human corpus callosum: a postmortem morphological study.
Brain. 112:799--835.
Witelson SF. 1985. The brain connection: the corpus callosum is larger in
left-handers. Science. 229:665--668.
Witelson SF, Nowakowski RS. 1991. Left out axons make men right:
a hypothesis for the origin of handedness and functional asymmetry.
Neuropsychologia. 29:327--333.
Cerebral Cortex August 2007, V 17 N 8 1765