AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 118:324 –340 (2002)
Brain Size and the Human Cranial Base:
A Prenatal Perspective
Nathan Jeffery* and Fred Spoor
Evolutionary Anatomy Unit, Department of Anatomy and Developmental Biology, University College London,
London WC1E 6JJ, UK
KEY WORDS fetal ontogeny; basicranium; relative encephalization; MRI; human evolution
ABSTRACT Pivotally positioned as the interface be-
tween the neurocranium and the face, the cranial base has
long been recognized as a key area to our understanding of
the origins of modern human skull form. Compared with
other primates, modern humans have more coronally ori-
entated petrous bones and a higher degree of basicranial
flexion, resulting in a deeper and wider posterior cranial
fossa. It has been argued that this derived condition re-
sults from a phylogenetic increase in the size of the brain
and its subcomponents (infra- and supratentorial vol-
umes) relative to corresponding lengths of the cranial base
(posterior and anterior, respectively). The purpose of this
study was to test such evolutionary hypotheses in a pre-
natal ontogenetic context. We measured the degree of
basicranial flexion, petrous reorientation, base lengths,
and endocranial volumes from high-resolution magnetic
The cranial base of modern humans differs mark-
edly from that of other primates (Fig. 1). The petrous
pyramids are more coronally oriented, the foramen
magnum faces more inferiorly, and it shows a higher
degree of midline basicranial flexion, i.e., the basi-
occipital has a more vertically inclined orientation
relative to the anterior cranial base (e.g., Keith,
1910; Duckworth, 1915; Zuckerman, 1955; Cam-
eron, 1930; Ashton, 1957). Consequently, modern
human crania have a deeper and wider posterior
cranial fossa, than other primates, including the
extant African apes (Dean, 1988; Ross and Ravosa,
1993; Spoor, 1997). Analysis of the evolutionary fac-
tors underlying this uniquely derived morphology is
complex, owing to the cranial base’s central position
in the head as the interface between the face, the
neurocranium, and the neck. Based on specific struc-
tural demands that appear to follow from these re-
lations a multitude of hypotheses have been pro-
posed, which phylogenetically link the modern
human morphology with, among others, brain ex-
pansion (i.e., phylogenetic encephalisation), obliga-
tory bipedalism, and facial orthognathism (e.g.,
Biegert, 1963; Du Brul, 1977; Dean, 1988; Ross and
Ravosa, 1993). Most recently, some of these hypo-
thetical associations have been assessed by analyz-
ing interspecific trends among extant and fossil pri-
mates (e.g., Ross and Ravosa, 1993; Ross and
© 2002 WILEY-LISS, INC.
resonance images (hrMRI) of 46 human fetuses ranging
from 10 –29 weeks of gestation. Bivariate comparisons
with age revealed a number of temporal trends during the
period investigated, most notable of which were coronal
rotation of the petrous bones and basicranial retroflexion
(flattening). Importantly, the results reveal significant in-
creases of relative endocranial sizes across the sample,
and the hypotheses therefore predict correlated variations
of cranial base flexion and petrous orientation in accor-
dance with these increases. Statistical analyses did not
yield results as predicted by the hypotheses. Thus, the
propositions that base flexion and petrous reorientation
are due to increases of relative endocranial sizes were not
corroborated by the findings of this study, at least for
the period investigated. Am J Phys Anthropol 118:
324 –340, 2002. © 2002 Wiley-Liss, Inc.
Henneberg, 1995; Spoor, 1997; Strait and Ross,
1999; Lieberman et al., 2000).
Phylogeny can be seen as the product of successive
ontogenies, as the accumulation of developmental
change (Garstang, 1922). Indeed, a number of stud-
ies advanced possible ontogenetic mechanisms un-
derlying the phylogenetic origin of the modern hu-
man cranial base (e.g., Ford, 1956; Moss, 1958;
Scott, 1958; Knowles, 1963; Enlow and Hunter,
1968; Enlow, 1976). Such hypotheses generally take
a mechanistic approach, in which the cranial base
responds during ontogeny to the differential growth
and development of closely related structures, such
as the brain, or aspects of the face. These mechanis-
Grant sponsor: Medical Research Council; Grant sponsor: Wellcome
Trust; Grant sponsor: University of London Intercollegiate NMR Re-
search Service Scheme, Queen Mary and Westfied College.
*Correspondence to: Nathan Jeffery, Evolutionary Anatomy Unit,
Department of Anatomy and Developmental Biology, University Col-
lege London, Rockefeller Building, University St., London WC1E 6JJ,
UK. E-mail ucgansj@ucl.ac.uk
Received 30 April 2001; accepted 11 October 2001.
DOI 10.1002/ajpa.10040
Published online in Wiley InterScience (www.interscience.wiley.
com).
 FETAL ENCEPHALIZATION AND BASE ARCHITECTURE
Fig. 1. Sketches of midline and transverse sections through
the primate skull. a: Loris. b: Chimpanzee. c: Modern human.
Differences of basicranial flexion (top row) and petrous bone
orientation (bottom row) are highlighted in grey. Notice that the
cranial base is flatter and the petrous bones are more sagittally
orientated in the chimpanzee than in the modern human skull.
Not to scale.
tic explanations are often contrasted with evidence
of direct genetic control, emerging from studies of
mutations and knockout gene experiments (reviews
in Herring, 1993; Thorogood, 1993). A broader inter-
pretation is that the ontogenetic basis for phyloge-
netic change contains both genetic and mechanical
elements (e.g., Baker, 1941; Scott, 1954; Thorogood,
1987, 1988). While the genetic contributions to skull
development and evolution were the focus of numer-
ous studies (reviews in Sperber, 1992; Scheuerle,
1995; Thesleff, 1998), the mechanistic determinants
remain largely unexplored by comparison.
This study has two main aims. Firstly, it seeks to
document major changes in basicranial and brain
morphology during human fetal development, focus-
ing on those aspects that uniquely characterize mod-
ern humans. Secondly, using this information it
tests phylogenetic hypotheses describing the inter-
action between the brain and cranial base, in a first
systematic attempt to evaluate possible ontogenetic
mechanisms that may contribute to the derived cra-
nial morphology of modern humans.
PHYLOGENETIC PERSPECTIVE
Now often referred to as spatial-packing hypoth-
eses, phylogenetic scenarios linking the origin of the
modern human cranial base with encephalization
suggest that base flexion and petrous reorientation
are solutions to a “spatial-packing” problem created
by the phylogenetic increase of relative brain size
(e.g., Cameron, 1924; Biegert, 1963; Gould, 1977;
Dean, 1988; Ross and Ravosa, 1993; Lieberman et
al., 2000). This implies that in modern humans, the
basioccipital and foramen magnum were driven an-
teroinferiorly, the anterior cranial base was de-
flected ventrally, and the petrous bones reoriented
coronally to accommodate a relatively larger brain.
Inspired by Gould (1977), Ross and Ravosa (1993)
formulated a specific version of the spatial-packing
hypothesis, which proposes that the derived nature
325
of the modern human basicranium follows from the
combination of a large brain and a short cranial
base. The authors tested the hypothesis and estab-
lished among extant primate species a correlation of
greater cranial base flexion with increases of brain
volume measured relative to midline cranial base
length (i.e., index of relative encephalization 1,
IRE1). Ross and Henneberg (1995) demonstrated
that modern humans deviate from this primate
trend by showing less flexion than expected for their
relative brain sizes. This they interpret as evidence
of a limit to the degree of flexion, perhaps imposed
by structural demands other than relative enceph-
alization (e.g., maintaining airway patency). Spoor
(1997) also found an interspecific association be-
tween cranial base flexion and relative brain size,
but in contrast to Ross and Henneberg (1995),
showed that modern humans do not deviate signifi-
cantly from the primate trend. This discrepancy be-
tween the studies of Spoor (1997) and Ross and
Ravosa (1993) and Ross and Henneberg (1995) prob-
ably reflects differences in the landmarks used to
measure cranial base angle and length (see Mc-
Carthy, 2001). In addition to examining basicranial
flexion, Spoor (1997) also assessed the orientation of
the foramen magnum and the petrous pyramids. He
found that increases of relative brain size across
extant primate species are concurrent with coronal
reorientation of the petrous pyramids and a more
inferior-facing foramen magnum. In his study, mod-
ern humans follow the primate trend for the orien-
tation of the foramen magnum, but their petrous
pyramids are less coronally orientated than pre-
dicted. As with base flexion, this could imply that
petrous reorientation is in some way constrained. A
recent study by Lieberman et al. (2000) adds consid-
erable evidence in support of the hypothesis of Ross
and Ravosa (1993). The authors found significant
correlations between relative brain size and cranial
base angle across extant primates while controlling
for the influence of phylogenetic relationships
among species studied (see Harvey and Pagel, 2000),
using different measures of cranial base angle and
relative brain size, as well as at two taxonomic levels
(primates and haplorhines).
Rather than relating the spatial-packing concept
to entire brain size, Moss (1958) focused on the pos-
terior cranial fossa. He noted that confinement of
the modern human cerebellum to an inadequately
sized posterior fossa, due to skull deformation, is
invariably accompanied by increased flexion of the
cranial base. Later, Dean (1988) proposed that the
derived modern human basicranium follows from an
enlarged cerebellum combined with a short posterior
cranial base. That is, enlargement of the posterior
cranial fossa, through coronal reorientation of the
petrous pyramids and increased basicranial flexion,
is a structural solution to the spatial-packing prob-
lem which followed from disproportionate enlarge-
ment of the cerebellum relative to the posterior fossa
length. Ross and Ravosa (1993) tested this hypoth-
326 N. JEFFERY AND F. SPOOR
esis by comparing absolute cerebellar volume
against cranial base angle for an interspecific sam-
ple of extant primates. They found no correlation,
but this does not refute the hypothesis put forward
by Dean (1988), as the latter pertains to relative
rather than absolute cerebellar size.
A different perspective on the spatial-packing idea
is found in hypotheses which link base morphology
with size increases in one part of the brain relative
to another. Hofer (1969) was among the first to pro-
pose such a hypothesis. He suggested that differen-
tial enlargement of the cerebrum not only maxi-
mizes its sphericity, and thereby provides the
potential adaptive advantages of reduced neural
wiring lengths and better skull balance (see Jerison,
1982; Ross and Henneberg, 1995), but also necessi-
tates a flexion between the cerebrum and brain-stem
that is matched by flexion of the midline basicra-
nium. Similar explanations focusing on brain shape
are posited elsewhere, and broadly speaking suggest
that differential enlargement of the supratentorial
brain (cerebrum and diencephalon) compared with
the infratentorial brain (cerebellum and brain-stem)
creates a “spatial-packing” problem with various
predicted consequences for base architecture (e.g.,
Dean and Wood, 1981; Dean, 1988; Strait, 1999). In
particular, Strait (1999) noted that anatomically dif-
ferent parts of the brain exhibit distinct scaling tra-
jectories across extant primate species, and he hy-
pothesized that phylogenetic increases of neocortical
(cerebral neocortex) relative to noncortical (medulla,
mesencephalon, and diencephalon) parts of the
brain might be responsible for the derived condition
of the modern human basicranium. A recent inter-
specific evaluation of the influence of differential
encephalization revealed a significant correlation
between increases of cerebral volume over brain-
stem volume and cranial base flexion across extant
primates (Lieberman et al., 2000).
ONTOGENETIC PERSPECTIVE
The developmental literature contains several hy-
potheses, ideas, and findings that are congruous
with the evolutionary mechanisms described above.
Perhaps most striking are the similarities between
the hypothesis of Ross and Ravosa (1993), formu-
lated to explain flexion during human evolution, and
a model Enlow (1976) detailed to explain flexion
during human growth. Enlow (1976) proposed that
cranial base flexion during human prenatal and
postnatal ontogeny is due to increased brain growth
relative to slower growth of the midline basicra-
nium. This is consistent with human fetal studies
showing that growth along the cranial base is sig-
nificantly slower than in other parts of the skull
(e.g., Houpt, 1970; Mandarim-de-Lacerda and Alves,
1992; Plavcan and German, 1995) and that fetal
brain growth is markedly rapid at the same time
(e.g., Jenkins, 1921; Koop et al., 1986). Taken to-
gether, these findings imply that relative brain size
increases during human fetal life. Previous investi-
gations also demonstrated simultaneous changes in
fetal base morphology, particularly in base angula-
tion (e.g., Burdi, 1965; Cousin, 1969; Erdoglija,
1989, 1990; Dimitriadis et al., 1995), but these are
difficult to interpret due to inconsistencies in the
morphological landmarks and methods of visualiza-
tion these studies used. For example, Erdoglija
(1989) and Dimitriadis et al. (1995) employed x-ray-
based imaging techniques, i.e., plain film radiogra-
phy and computed tomography, to visualize the fetal
cranial base. These modalities rely on the radioden-
sity of tissues to highlight morphologies. While
these techniques are suitable for imaging radio-
dense structures like bone, they are not effective in
imaging the incompletely ossified structures of the
fetal cranial base, where key landmarks are often
defined by less radiodense tissues like cartilage. In
contrast to these x-ray-based modalities, the tech-
nique used in the present study, known as magnetic
resonance imaging (MRI), relies on the quantum
properties of hydrogen nuclei and allows for the
noninvasive visualization and differentiation of
many more soft tissues, as well giving indirect views
of ossified bone (see Spoor et al., 2000a,b).
Several developmental studies allude to an onto-
genetic process of relative cerebellar enlargement,
similar to the process Dean (1988) described as an
evolutionary mechanism. Ford (1956) suggested
that fetal changes of base morphology are a compen-
satory mechanism for slower growth of the posterior
cranial base compared with that of the anterior cra-
nial base and brain. Fetal studies confirm that
growth of the posterior cranial base is slower than
that of the anterior base (Burdi, 1965, 1969; Levihn,
1967; Houpt, 1970). Moreover, following a slow
start, fetal cerebellar growth accelerates with siz-
able increases of surface area, mass, and width at
rates exceeding those of the cerebrum (Noback and
Moss, 1956; Dobbing and Sands, 1973; Rakic and
Sidman, 1970). The likely outcome of this growth
spurt, combined with conservative growth along the
posterior cranial base, is relative infratentorial en-
largement within the confines of the posterior cra-
nial fossa.
Findings from fetal studies are also consistent
with processes of ontogenetic differential enceph-
alization. Marked increases in the supratentorial
portion of the brain occur in relation to the infra-
tentorial portion during fetal development (Guihard-
Costa and Larroche, 1990, 1992). More importantly,
Moss et al. (1956) linked fetal differential enceph-
alisation with changes of posterior fossa morphol-
ogy. The authors noted that critical developmental
phases in growth of the occipital and temporal bones
correlate with changes in overall proportions of the
fetal brain.
HYPOTHESES
Based on the reviewed models of phylogenetic and
ontogenetic interaction between the brain and cra-
nial base, the following hypotheses were tested for
 FETAL ENCEPHALIZATION AND BASE ARCHITECTURE
morphological change during the second and part of
the third trimester of human fetal development.
General spatial-packing
The first hypothesis predicts that increases of fe-
tal brain volume relative to cranial base length cre-
ate a spatial-packing problem that results in base
flexion and coronal petrous reorientation. Three of
the possible outcomes are: 1) variations of cranial
base angle and petrous orientation correlate with
changes of brain volume relative to base length and
thus, the hypothesis is corroborated; 2) cranial base
angle and petrous orientation remain essentially
unchanged if cranial base length scales isometri-
cally with brain volume, i.e., relative brain size re-
mains unchanged and the hypothesis is not applica-
ble; and 3) there are no correlations or isometric
scaling, and the hypotheses is uncorroborated.
The model of spatial-packing following Ross and
Ravosa (1993) (cube root brain volume/base length)
assumes that the midline cranial base is influenced
by expansion of the brain in all directions. However,
it could be that relative brain size increases mostly
due to, for example, lateral expansion of the brain
without impinging on the two-dimensional midline
basicranium. Hence, it should be assessed whether
increases of the midline endocranial area, which is
spatially associated with the midline cranial base,
are equal to or greater than overall increases of
brain volume.
Infratentorial spatial-packing
This hypothesis predicts that increases of infra-
tentorial volume measured against the length of the
posterior cranial base create a “spatial-packing”
problem within the posterior cranial fossa that re-
sults in cranial base flexion and coronal petrous
reorientation. The three possible outcomes are es-
sentially the same as those described for the general
spatial-packing hypothesis.
Differential encephalization
The third hypothesis predicts that prenatal in-
creases of supratentorial volume relative to infra-
tentorial volume impinge on the cerebellum and
brain-stem, creating a spatial-packing problem that
drives coronal reorientation of the petrous bones and
cranial base flexion. Possible outcomes include: 1)
differential encephalization in association with base
flexion and coronal petrous reorientation; 2) no dif-
ferential encephalization, and consequently the hy-
pothesis is not testable; and 3) differential enceph-
alization but no correlation with either base flexion
or coronal petrous reorientation, and hence the hy-
pothesis is uncorroborated.
MATERIALS AND METHODS
Sample
Fifty formalin-fixed human fetuses from museum
collections of therapeutic and natural abortuses
327
housed at the Department of Anatomy and Develop-
mental Biology, University College London, and the
Department of Anatomy, Queen Mary and Westfield
College, London, were imaged with high-resolution
magnetic resonance imaging (hrMRI). Although
specimens were carefully screened for pathologies
before scanning, four individuals were excluded
from the study because of abnormalities shown in
the images. Estimated gestational age (EGA) was
computed to the nearest tenth of a week for each
fetus from measures of biparietal diameter with ref-
erence to the regression equation for exocranial
measures given in Chitty et al. (1994). Ages were
calculated to the nearest tenth of a week to maintain
the distinction between individuals provided by bi-
parietal diameter while presenting the data in a
more readily interpreted format, i.e., that of gesta-
tional time. Other, perhaps more suitable age prox-
ies (see Sherwood et al., 2000) were precluded due to
previous invasive work on the material. The age
range of the specimens thus calculated was 10 –29
weeks of gestation (Table 1). The sample distribu-
tion in respect of biparietal diameter was neither
significantly skewed nor kurtotic (skew ⫽ ⫺0.08, ns;
kurtosis ⫽ ⫺0.25, ns).
The fetuses were imaged using a 4.7T imaging
and spectroscopy unit (Sisco-Varian). The following
parameters and pulse sequences were used: 10
Gcm⫺1 (max) gradient coil; an 8.8-cm (internal di-
ameter) saddle coil; and a 6.2-cm birdcage coil, ac-
cording to the size of the specimen; matrix size,
256 ⫻ 256; number of averages (NEX), 24 with typ-
ical scanning times of 18 –22 hr; and a T2-weighted
spin-echo multislice sequence (TR and TE were ap-
proximately 9,000 msec and 40 msec, respectively).
Fields of view (FOV) were adjusted according to the
size of the specimen, and varied from 30 –115.2 mm,
giving a pixel size of 0.12– 0.45 mm. The T2 weight-
ing was employed in preference to T1 in order to
maximize contrast between the formalin solution
(high water content) surrounding the brain and the
skull base. Images were acquired contiguously along
the transverse (axial) plane, with a slice thickness of
between 0.23– 0.90mm. Coordinates for anatomical
landmarks were taken from the original transverse
images and from resampled sagittal and coronal
images (AVS5, Advanced Visual Systems). Slice
thickness, field of view, biparietal diameter, and
computed age are given in Table 1 for each speci-
men. Pixel sizes for each specimen can be computed
by dividing the field of view (FOV) by the acquisition
matrix size (i.e., 256).
Measurements
The degree of basicranial flexion was measured as
the cranial base angle (CBA) computed from land-
mark coordinates of the foramen caecum (Fc), sella
(S), and basion (Ba), taken in midsagittal images.
Some developmental studies used nasion rather
than foramen caecum to measure CBA (e.g., Ford,
1956; Burdi, 1965). However, the nasion is a facial
328 N. JEFFERY AND F. SPOOR
1
TABLE 1. Sample
EGA FOV Slice thickness
Code BPD (mm) (weeks) (mm) (mm)
UMSCL-163 15.0 10.1 40 0.31
UMSCL-39 15.0 10.1 30 0.23
QMWF49 19.0 11.5 40 0.31
UMSCL-61 21.0 12.1 40 0.31
QMWF7 24.0 13.1 40 0.31
UMSCL-2992 24.0 13.2 40 0.31
QMWF34 25.5 13.5 40 0.31
UMSCL-164 27.0 14.0 50 0.39
UMSCL-962 29.0 14.1 50 0.39
011A2 32.0 15.4 50 0.39
UMSCL-165 32.0 15.4 64 0.50
UMSCL-94 33.0 15.7 50 0.39
Z101 35.0 16.3 64 0.50
UMSCL-63 37.0 16.8 64 0.50
UMSCL-92 37.0 16.8 64 0.50
UMSCL-216 38.5 17.2 64 0.50
QMW35 40.0 17.6 64 0.50
QMW28 40.0 17.6 80 0.63
UMSCL-223 40.0 17.6 64 0.50
UMSCL-86 42.0 18.2 64 0.50
UMSCL-91 42.0 18.2 64 0.50
UMSCL-287 42.0 18.2 80 0.63
Z102 43.0 18.4 64 0.50
UMSCL-220 43.0 18.4 80 0.63
UMSCL-2222 44.0 18.7 64 0.50
UMSCL-221 44.0 18.7 80 0.64
UMSCL-210 45.0 19.0 80 0.63
ZN1 45.0 19.0 80 0.63
UMSCL-166 46.0 19.2 80 0.63
UMSCL-215 46.0 19.2 80 0.63
UMSCL-212 47.0 19.5 80 0.63
UMSCL-207 48.0 19.8 80 0.63 Fig. 2. High-resolution magnetic resonance images (hrMRI)
UMSCL-218 49.0 20.1 80 0.63 of fetal head, and schematic representations of measures taken
UMSCL-214 49.0 20.1 80 0.63 thereon. a: Midline hrMR image of fetal head. b: Sketch showing
UMSCL-211 49.0 20.1 80 0.63
measure of cranial base angle computed from coordinates for
UMSCL-297 50.0 20.3 80 0.63
UMSCL-209 52.0 20.9 80 0.63 foramen caecum (Fc), sella (S), and basion (Ba). c: Transverse
UMSCL-292 52.0 20.9 80 0.63 hrMR image at level of anterior semicircular canals and presphe-
UMSCL-286 54.0 21.5 80 0.63 noid. d: Sketch showing measure of interpetrosal angle computed
UMSCL-281 57.0 22.3 80 0.63 from coordinates for medialmost (Md) and lateralmost (Lt) at-
UMSCL-301 57.5 22.5 80 0.63 tachments of tentorium cerebelli to petrous ridges. Scale bars, 10
UMSCL-284 60.5 23.4 80 0.63 mm.
UMSCL-242 62.0 23.8 102.4 0.80
UMSCL-248 64.0 24.5 85 0.66
UMSCL-232 64.0 24.5 89.6 0.70
UMSCL-229 66.0 25.1 102.4 0.80 the foramen caecum, seen as a pit on the cribriform
UMSCL-238 67.0 25.5 102.4 0.80 plate between the fetal crista galli and the endocra-
UMSCL-275 69.5 26.3 102.4 0.80 nial wall of the frontal bone; S, the centerpoint of the
UMSCL-240 70.0 26.5 102.4 0.80
UMSCL-303 77.0 29.2 115.2 0.90 sella turcica; and Ba, the tip or point of greatest
1
curvature of the basioccipital on the anterior margin
BPD, biparietal diameter; EGA, estimated gestation age; FOV, of the foramen magnum.
imaging field of view. Specimens with codes commencing with
UMSCL are from University College London; codes starting with
A number of studies measured petrous orientation
Z, QMW, or 01 refer to those specimens from Queen Mary and using exocranial landmarks (e.g., Dean and Wood,
Westfield College, London. 1981, 1984) and landmarks on the endocranial
2
Excluded from study. petrosal surface (Putz, 1974; Spoor, 1997; Spoor and
Zonneveld, 1995, 1998), but these cannot be repli-
cated in the developing fetus. Here, petrous orienta-
rather than a basicranial landmark, and its use is tion was approximated with a measure of interpetro-
inappropriate because it introduces variation from sal angle (IPA). This was defined as the angle
facial growth (Enlow and Moyers, 1971). Ideally, between line segments fitted through the lateral-
measures of CBA would attempt to approximate the most to the medialmost attachments of the tento-
primary points of flexion, i.e., the spheno-ethmoidal, rium cerebelli to the petrous ridges (Fig. 2c,d; Table
midsphenoidal, and spheno-occipital synchondroses 2). In practice, landmarks were taken from coronal
(see Lieberman and McCarthy, 1999). However, not images anterior to the cochleae and just anterior to
all of the synchondroses were sufficiently resolved the sigmoid sulci.
with hrMRI throughout the period investigated. The Total, anterior, and posterior cranial base lengths
landmarks used were defined as follows (Fig. 2a,b; were measured as the distances between Fc, S, and
Table 2): Fc, the center of the endocranial opening of Ba (Fig. 2b; Table 2). Thus, unlike the definition in
 FETAL ENCEPHALIZATION AND BASE ARCHITECTURE 329
TABLE 2. Landmarks, angles, and volume measurements
Measure Abbreviation Definition
Landmarks
Basion Ba Midline point on anterior margin of foramen magnum
Foramen caecum Fc Midline point marking pit between fetal crista galli and endocranial wall of
frontal bone
Sella S Center of sella turcica in midline
Medial petrous Md Points marking medialmost tentorial attachments to left and right petrous
ridges
Lateral petrous Lt Points marking lateralmost tentorial attachments to left and right petrous
ridges
Linear measures
Total cranial base length TBL Total linear distance from basion (Ba) to sella (S), and sella to foramen caecum
(Fc)
Anterior cranial base length ABL Linear distance from sella (S) to foramen caecum (Fc)
Posterior cranial base length PBL Linear distance from basion (Ba) to sella (S)
Angles
Cranial base angle CBA Ventral angle between midline anterior cranial base (Fc-S) and posterior
cranial base (S-Ba)
Interpetrosal angle IPA Posterior angle between left and right line segments fitted through medialmost
(Md) and lateralmost (Mt) tentorial attachments to petrous ridges
Volumes and areas
Endocranial volume EV Sum of voxels within endocranial cavity
Supratentorial volume SV Sum of voxels within endocranial cavity above tentorium cerebelli
Infratentorial volume IV Sum of voxels within endocranial cavity below tentorium cerebelli
Midline area MA Sum of pixels representing midline plane of endocranial cavity
Derived measures
Relative endocranial size IRE 1 Cube root of endocranial volume divided by total cranial base length (EV0.33/
TBL)
Relative infratentorial size RIE Cube root of infratentorial volume divided by posterior cranial base length
(IV0.33/PBL)
Index of differential encephalisation IDE Sum of endocranial voxels below tentorium cerebelli, divided by sum of voxels
above tentorium (IV/SV)

Ross and Ravosa (1993), the anterior cranial base
length Fc–S includes the cribriform plate. This is
because the ethmoid region is ontogenetically recog-
nized as part of the cartilaginous base plate and
thus of the cranial base (De Beer, 1937; Shapiro and
Robinson, 1980). Moreover, the cribriform plate
forms a substantial portion of the endocranial sur-
face available to the developing brain, and omission
in tests of spatial packing hypotheses would not be
justified (see discussion in McCarthy, 2001).
The midsagittal endocranial area was measured
as the number of pixels in the outlined region of
interest multiplied by pixel area. Endocranial, in-
fratentorial, and supratentorial volumes were mea-
sured by manually outlining regions in all sagittal
images showing the anatomy of interest (typically
70 –90 images), taking care not to include normal
dural structures such as the confluence of sinuses,
falx cerebelli, or tentorium cerebelli. Regions of in-
terest were outlined using the trace function in
AVS5 (Advanced Visual Systems). For each slice,
the number of pixels in the region of interest was
multiplied by pixel area (i.e., 0.014 – 0.203 mm2) and
subsequently by slice thickness (i.e., 0.23– 0.90 mm).
This gave a volume of interest for each slice, and the
sum for all relevant slices provided a measure of
volume. Tests of accuracy indicate that this method
incurs an error of between 1–3% (Jeffery, 1999).
Infratentorial volumes were measured using the
same method by outlining the endocranial region
below the tentorium cerebelli. Supratentorial vol-
umes were calculated by subtracting infratentorial
volume from endocranial volume. All measurements
were taken by the same rater (N.J.) and are avail-
able upon request.
Statistical analyses
Measurements for each individual were computed
to the nearest pixel size rounded to tenths of a mil-
limeter. For example, measures for individuals im-
aged with a 40 ⫻ 40 mm and 50 ⫻ 50 mm FOV were
taken to the nearest two tenths of a millimeter,
because their pixel size was 40/256 ⫽ 0.156 and
50/256 ⫽ 0.195, respectively. Angular measure-
ments were taken to the nearest degree, area mea-
surements were taken to the nearest square milli-
meter, and volume measurements were taken to the
nearest 10 cubic millimeters. Volumes and areas
were reduced for linear comparisons using cube and
square roots, respectively. Relative endocranial size
(IRE 1) was computed as the cube root of endocra-
nial volume over cranial base length. Relative in-
fratentorial size (RIE) was calculated as the cube
root of infratentorial volume over posterior base
length, and the index of differential encephalization
(IDE) was calculated as the ratio of infratentorial
volume over supratentorial volume. Measurement
precision was evaluated by comparison of five repe-
titions for four randomly selected fetuses over 5
consecutive days. One-way analysis of variance
(ANOVA) of repeated measurements (see Table 3)
showed that errors incurred among repeated mea-
surements are negligible in comparison with the
biological variation between individual fetuses. In
330 N. JEFFERY AND F. SPOOR
TABLE 3. Results for one-way ANOVA test of linear, angular, and volume measurements showing mean
square differences between fetuses and repeated measures1
Measurement MS repeated measures
Anterior cranial base length 0.125
Posterior cranial base length 0.022
Total cranial base length 0.105
Cranial base angle 1.851
Interpetrosal angle 24.174
Endocranial volume (⫻10⫺3) 0.608
Supratentorial volume (⫻10⫺3) 0.479
Infratentorial volume (⫻10⫺3) 0.057
Midline area (⫻10⫺2) 4.061
1
MS, mean square.
2
n ⫽ 20, k ⫽ 5; F0.001(3,16) ⫽ 9.0, F0.01(3,16) ⫽ 5.29, F0.05(3,16) ⫽ 3.24.
other words, the null hypothesis that values for re-
peated measures from one individual fetus are the
same was accepted (P ⬍ 0.01).
The relationships between variables were evalu-
ated by nonparametric methods and without loga-
rithmic transformations. Spearman rank correla-
tion coefficients (rrank) and model II reduced major-
axis (RMA) regression equations were employed to
investigate bivariate trends between variables
(Sokal and Rohlf, 1995). Complex trends were de-
scribed with second-order polynomial regressions
and, in one case, a two-step RMA. Partial product-
moment correlations were used to evaluate the ef-
fects of colinearities with age, nee biparietal diame-
ter, on rank correlations used to test the hypotheses.
t-tests were used to test the statistical significance of
correlation and RMA statistics. In all significance
tests, a level of P ⬍ 0.05 was used to reject null
hypotheses.
RESULTS
Temporal changes
Mean values of the linear, angular, and volumet-
ric measures, computed at 2-week intervals of EGA,
are listed in Table 4 to illustrate the magnitude of
their variations during the 10 –29-week period rep-
resented by the sample.
Angular measures. Figure 3a plots CBA and IPA
against EGA. This reveals a significant positive cor-
relation for both variables with age (Table 5). Over
the period investigated, the cranial base is shown to
retroflex, i.e., flatten out, by some 9°, and the pe-
trous bones are shown to reorientate coronally, i.e.,
away from one another, by 10 –15°.
Length measures. Plots of total, posterior, and
anterior cranial base lengths against EGA show no-
table increases (Fig. 3b). The slope of anterior base
length against EGA was almost twice that of the
posterior base (Table 5). This demonstrates that in-
creases of total cranial base length are mostly due to
elongation of the anterior cranial base.
Volumetric measures. Comparisons of absolute
endocranial volume against age yield a second-order
polynomial (i.e., parabola) fit of y ⫽ 664.75x2 ⫺
MS between fetuses F P2
52.167 417.333 ⬍0.001
20.574 924.674 ⬍0.001
160.467 1,531.908 ⬍0.001
49.198 26.579 ⬍0.001
150.300 6.217 ⬍0.01
3,265.894 5,367.342 ⬍0.001
2,669.377 5,571.894 ⬍0.001
30.148 524.501 ⬍0.001
14,458.750 35.606 ⬍0.001
14,686x ⫹ 84,264 (R2 ⫽ 0.966). The enlargement
was markedly rapid, and described a 136-times in-
crease from an initial mean value of 1,625 mm3 at
10.1 weeks EGA to 220,520 mm3 at 29.2 weeks EGA.
The endocranial volume is compartmentalized by
the tentorium cerebelli into infratentorial and su-
pratentorial components. Temporal variations of
these volumes against EGA were described with a
second-order polynomial of y ⫽ 39.877x2 ⫺
757.21x ⫹ 4037.9 (R2 ⫽ 0.930) for infratentorial
volume, and of y ⫽ 625.91x2 ⫺ 13969x ⫹ 80563
(R2 ⫽ 0.966) for supratentorial volume. These rep-
resent 48- and 158-fold increases of their initial
mean values at 10.1 weeks EGA, respectively. In
order to clarify these trends, volumes were linear-
ized using cube roots, i.e., volume1/3 and plotted
against EGA (Fig. 3c). The slope of cube root supra-
tentorial volume against EGA is over twice that of
cube root infratentorial volume against EGA (Table
5). These plots show that increases of overall en-
docranial volume are mostly due to increases of su-
pratentorial volume as opposed to infratentorial vol-
ume. Note that anterior cranial base length is
spatially associated with supratentorial volume, as
is posterior cranial base with infratentorial volume.
Derived ratios. Temporal changes of relative
brain sizes and IDE were evaluated with compari-
sons against EGA. A significant linear increase of
relative endocranial size was observed with EGA
(Table 5). However, no significant change in relative
infratentorial size was revealed in relation to EGA
(rrank ⫽ 0.084, ns). Bivariate comparisons of IDE
with EGA produced a negative polynomial curve
fitting of y ⫽ 0.0008x2 ⫺ 0.0388x ⫹ 0.5488 (R2 ⫽
0.817). This describes an early period of rapid dif-
ferential enlargement in which supratentorial vol-
ume increases in relation to infratentorial volume,
i.e., the ratio of infratentorial volume/supratentorial
volume decreases (Fig. 3d). This trajectory gradually
tapers off towards week 20 of EGA, and from weeks
20 –29 it levels almost to plateau. The variation in
IDE before week 20 of EGA ranges from 0.07– 0.27,
whereas that after week 20 of EGA ranges from
0.06 – 0.11.
 FETAL ENCEPHALIZATION AND BASE ARCHITECTURE 331

BPD, biparietal diameter; ABL, anterior base length; PBL, posterior base length; TBL, total base length; CBA, cranial base angle; IPA, interpetrosal angle; EV, endocranial volume;
General spatial-packing

141
134
19
52
129
117
190
227
212
s.d.
MA (mm2)
In order to test the general model of spatial-pack-
ing (cube root volume/base length), a comparison of

Mean
277
520
886
1,121
1,678
1,998
2,456
3,110
4,328
square root midline endocranial area against cube
root of endocranial volume was made. This demon-
strates that increases of the midline area are larger
1,663
1,931
1,381
2,637
3,815
2,979
4,055
6,008
5,597
s.d.

than the overall increase in brain volume, and that

SV (mm3)

lateral brain expansion is not predominant (Table 5;

slope ⬎1 at P ⬍ 0.001).
2,733
9,333
18,468
29,071
47,431
66,843
92,440
126,523
192,960
Mean

Increases of relative endocranial size across the

sample were examined with a comparison of cube
root endocranial volume against total base length
273
382
221
266
272
435
581
433
416
s.d.

(Table 5). The slope is significantly greater than 1

IV (mm3)

(P ⬍ 0.001). This shows that relative endocranial

558
1,348
2,580
2,898
4,459
5,913
8,050
10,453
15,050

size increases significantly across the sample. The

Mean

general spatial-packing hypothesis predicts that

this increase of relative endocranial size will corre-
TABLE 4. Descriptive statistics for fetal measurements at 2-week intervals1

spond with a decrease of CBA and an increase of

1,933
2,306
1,558
2,860
4,069
3,303
4,555
6,297
5,748

IV, infratentorial volume; SV, supratentorial volume; MA, midline endocranial area; s.d., one standard deviation; wks, weeks.
s.d.

IPA. However, the opposite relationship was found

EV (mm3)

for CBA, which shows a small, statistically signifi-

3,290
10,680
21,048
31,969
56,548
72,757
100,490
136,975
208,010

cant correlation with relative endocranial size that

Mean

is positive rather than negative (Fig. 4a, Table 5). As

predicted, increases of interpetrosal angle are posi-
tively correlated to increases of relative endocranial
s.d.
3.2
5.8
5.9
9.2
8.8
7.1
6.6
3.4
3.7

size, though only weakly (Fig. 4b, Table 5). Partial

IPA (°)

correlation coefficients for CBA and IPA against rel-

Mean

ative endocranial size are insignificant, while hold-

74.3
77.0
76.0
75.8
79.3
87.7
83.3
81.8
91.5

ing biparietal diameter constant (r ⫽ ⫺0.017, ns; r ⫽

⫺0.064, ns).
s.d.
4.1
3.7
2.2
3.1
2.4
3.0
1.9
1.7
2.1
CBA (°)

Infratentorial spatial-packing
Mean
132.0
133.3
136.5
138.0
134.2
134.0
140.3
139.8
141.5

To evaluate variations of relative infratentorial

size across the sample, the cube root of infratento-
rial volume was compared against posterior base
s.d.
2.7
3.0
1.5
2.3
3.1
2.8
2.3
2.0
1.9
TBL (mm)

length. This produces a slope that is significantly

greater than 1 (Table 5) and shows that relative
Mean

infratentorial size increased across the sample. The

14.6
21.8
27.5
30.5
35.8
39.6
41.3
44.2
49.6

hypothesis predicts a correlated decrease of CBA

and increase of IPA, but neither of these correlations
was significant (rrank ⫽ 0.119, ns, and 0.008, ns,
s.d.
1.2
1.2
0.7
1.0
1.0
1.0
0.4
0.6
0.8
PBL (mm)

respectively). Thus, increases of infratentorial vol-

ume relative to posterior base length are not accom-
Mean
6.4
9.3
11.2
12.3
14.1
15.5
16.4
18.1
18.7

modated in the posterior cranial fossa by base flex-

ion or coronal reorientation of the petrous bone.
s.d.
1.5
1.8
0.8
1.3
2.1
1.8
1.9
1.5
1.4
ABL (mm)

Differential encephalization
Comparisons of supratentorial and infratentorial
Mean
8.2
12.5
16.4
18.2
21.7
24.1
24.9
26.1
31.0

volume against EGA, as well as IDE against EGA,

reveal differential enlargement in which the supra-
tentorial volume increases disproportionately (Fig.
15–21
24–32
33–37
38.5–44
43–52
52–57
57.5–64
64–70
69.5–77
BPD (mm)

3c,d). The differential encephalization hypothesis

—

therefore predicts a correlated increase of IPA and a

correlated decrease of CBA. Comparisons of CBA
and IPA against IDE revealed small significant neg-
4
4
4
9
12
3
4
4
2
N

ative correlations (rrank ⫽ ⫺0.297, P ⬍ 0.05, and

⫺0.481, P ⬍ 0.001, respectively). However, as Fig-
wks
wks
wks
wks
wks
wks
wks
wks
wks

ure 5 demonstrates, these trends are clearly bipha-

Age
10–13
13–15
15–17
17–19
19–21
21–23
23–25
25–27
27–29

sic, not linear. In the first phase, there is little vari-

ation of the index of differential encephalization
1
332 N. JEFFERY AND F. SPOOR

Fig. 3. Bivariate plots of measured variables against estimated gestational age (EGA). a: Cranial base angle (CBA) and
interpetrosal angle (IPA) against EGA. b: Total base length (TBL), anterior base length (ABL), and posterior base length (PBL) against
EGA. c: Cube root endocranial volume (EV), supratentorial volume (SV), and infratentorial volume (IV) against EGA, with reduced
major axis (mra) line fittings shown. d: Index of differential encephalisation (IDE) against EGA, with the second-order polynomial line
fitting shown.

with either CBA or IPA. This is followed by a second
phase in which the index of differential encephaliza-
tion increases, but there is little change in either
CBA or IPA. Indeed, the phases are so distinct that
neither complete trend was successfully resolved
with second-order polynomial fittings (R2 ⬍ 0.2).
Note from Figure 3d that the first phase revealed in
Figure 5 corresponds to later fetal life, and that the
second phase corresponds to early fetal life. To ex-
plore these phases pragmatically, these data were
subdivided for each ordinate variable according to
mean abscissa value (Fig. 5). Each of the four sub-
sets, two for both IPA and CBA, reflected their re-
spective phases well and were analyzed separately.
These analyses revealed that CBA is not signifi-
cantly correlated to IDE for either phase one (IDE
values ⬍ IDEmean; rrank ⫽ 0.055, ns) or two (IDE
values ⬎ IDEmean; rrank ⫽ 0.113, ns). Furthermore,
interpetrosal angle was not significantly correlated
to IDE for the second phase (rrank ⫽ 0.393, ns).
However, analysis of IPA against IDE for the first
phase yields a significant negative correlation (Fig.
5; Table 5). These subanalyses show that CBA is
independent of differential encephalization. It is
also suggested that coronal reorientation of the pe-
trous bones is associated with disproportionate su-
pratentorial enlargement, but only as the process of
differential encephalization tapers off to a state of
equilibrium later in fetal life. However, the partial
correlation coefficient for IPA against IDE for the
first phase is insignificant when biparietal diameter
is held constant (r ⫽ ⫺0.196, ns). In addition, partial
correlation coefficients for both IPA and CBA
against IDE are insignificant for the whole sample
when biparietal diameter is held constant (r ⫽
0.178, ns; r ⫽ 0.154, ns).
 FETAL ENCEPHALIZATION AND BASE ARCHITECTURE 333
1
TABLE 5. Reduced major axes and rank correlation statistics
Plot rrank P Slope 95% confidence interval of slope Intercept
CBA ⫻ EGA 0.431 ** 0.98 0.72 ⬎ 1.24 117.49
IPA ⫻ EGA 0.504 *** 1.60 1.18 ⬎ 2.02 48.75
TBL ⫻ EGA 0.976 *** 2.10 1.96 ⬎ 2.37 ⫺7.03
ABL ⫻ EGA 0.975 *** 1.33 1.23 ⬎ 1.43 ⫺5.61
PBL ⫻ EGA 0.960 *** 0.78 0.72 ⬎ 0.84 ⫺1.72
EV1/3 ⫻ EGA 0.982 *** 2.65 2.53 ⬎ 2.78 ⫺15.15
SV1/3 ⫻ EGA 0.983 *** 2.62 2.50 ⬎ 2.75 ⫺15.69
IV1/3 ⫻ EGA 0.965 *** 0.98 0.91 ⬎ 1.04 ⫺2.73
IRE ⫻ EGA 0.813 *** 0.02 0.01 ⬎ 0.02 0.75
MA1/2 ⫻ EV1/3 0.987 *** 1.10 1.06 ⬎ 1.14 ⫺0.99
EV1/3 ⫻ TBL 0.987 *** 1.26 1.20 ⬎ 1.33 ⫺6.23
CBA ⫻ IRE 0.425 ** 60.79 43.80 ⬎ 77.78 71.63
IPA ⫻ IRE 0.356 * 99.43 71.57 ⬎ 127.28 ⫺26.26
IV1/3 ⫻ PBL 0.952 *** 1.25 1.16 ⬎ 1.34 ⫺0.60
IPA ⫻ IDE, first phase ⫺0.349 * ⫺557.51 ⫺749.64 ⬎ 365.39 131.97
1
CBA, cranial base angle; EGA, estimated gestational age; IPA, interpetrosal angle; TBL, total base length; ABL, anterior base length;
PBL, posterior base length; EV, endocranial volume; SV, supratentorial volume; IV, infratentorial volume; IRE, relative endocranial
size; MA, midline endocranial area; IDE, index of differential encephalisation.
* P ⬍ 0.05.
** P ⬍ 0.01.
*** P ⬍ 0.001.

DISCUSSION of soft tissues as well as cartilage and bone. The

Insight into the way morphological differences be-
tween closely related species emerge during ontoge-
netic development can make a major contribution to
our understanding of the phylogenetic origins of the
modern human cranium. The unique morphology
among primates of the human cranial base has long
been seen as the direct evolutionary consequence of
encephalization (e.g., Virchow, 1857; Cameron,
1924; Dabelow, 1931; Biegert, 1957; Ross and Ra-
vosa, 1993; Ross and Henneberg, 1995; Spoor, 1997;
Lieberman et al., 2000; McCarthy, 2001). This study
set out to assess possible ontogenetic mechanisms
underlying this phylogenetic relationship by testing
a number of specific hypotheses describing the in-
teraction between the brain and cranial base.
Temporal trends
Cranial base angle. Findings reported here
show cranial base retroflexion of about 9° in total
during the second and early third trimesters. This is
in agreement with a number of studies documenting
basicranial retroflexion (e.g., Kvinnsland, 1971;
Dimitriadis et al., 1995), and contrasts with studies
suggesting stasis (e.g., Burdi, 1965, 1969) or basi-
cranial flexion (e.g., Levihn, 1967; Erdoglija, 1989;
van den Eynde et al., 1992) during development.
These past studies often used small sample sizes
(e.g., N⫽ 24: Burdi, 1965), inappropriate basicranial
landmarks (e.g., nasion: van den Eynde et al., 1992),
and/or x-ray-based methods of visualization with
which radiotranslucent soft tissues are not clearly
discerned (e.g., film radiography: Erdoglija, 1989).
In contrast, the present study used a comparatively
large sample (N ⫽ 46), carefully selected landmarks
that were both spatially and temporally homologous
(i.e., can be clearly defined in all individuals of the
sample irrespective of developmental stage), and a
method of visualization (MRI) that provided details
findings of the present study are therefore more
likely to be correct.
Lieberman and McCarthy (1999) showed that the
base flexes from 143° at 1 postnatal month to 134° at
age 17 years, with the majority of flexion occurring
within the first postnatal year. The authors used the
same measure of cranial base angle as used in the
present study. Together with the findings detailed in
this study, the report of postnatal flexion contradicts
the “fetalization” concept which proposes that the
degree of base flexion is established during early
fetal life and is subsequently retained into adult-
hood (see Zuckerman, 1955; Schultz, 1955). The ag-
gregate of findings suggests that cranial base angu-
lation is temporally dynamic, i.e., polyphasic, not
fixed. Studies reveal phases of embryonic flexion
(e.g., Müller and O’Rahilly, 1980; Diewert, 1983,
1985; Sperber, 2001), fetal retroflexion (e.g., Kvinns-
land, 1971; Dimitriadis et al., 1995), and postnatal
flexion (e.g., Lieberman and McCarthy, 1999). Inter-
estingly, Lieberman and McCarthy (1999) reported
an adult mean cranial base angle that is similar to
the mean values reported here for fetal periods
10 –12 weeks and 13–15 weeks. It has already been
shown that these similarities are not due to reten-
tion of the fetal condition. This suggests that tem-
porally isolated, perhaps different, ontogenetic
mechanisms or controls can independently afford
resemblances, or convergence, between fetal and
adult morphologies.
The pattern of base angulation seen during late
prenatal and early postnatal human development is
distinct from that observed for macaques during
equivalent periods (see Sirianni and Van Ness,
1978; Sirianni and Newell-Morris, 1980). Studies
show that the cranial base angle of Macaca nemes-
trina remains essentially unchanged during most of
the fetal period (Sirianni and Newell-Morris, 1980)
334 N. JEFFERY AND F. SPOOR
Fig. 4. Bivariate plots of (a) cranial base angle (CBA) against
relative endocranial size (IRE), and (b) interpetrosal angle (IPA)
against IRE. Reduced major axes regression line fittings are
shown for each plot.
and subsequently retroflexes by some 10° after birth
(Sirianni and Van Ness, 1978). In contrast, the hu-
man base retroflexes before birth and subsequently
flexes postnatally. It is plausible that the process of
human fetal retroflexion is a precocious variant of
the retroflexion seen in postnatal nonhuman pri-
mates.
A possible explanation for such precocity may be
found in comparisons between the order in which
the basicranial synchondroses fuse in modern hu-
mans and macaques. The synchondroses are major
centers for growth of the midline primate basicra-
nium and major determinants of its architecture
(see Scott, 1958; Lieberman and McCarthy, 1999).
In macaques, the spheno-ethmoidal synchondrosis
(MES) fuses at birth (Michejda and Lamey, 1971).
The midsphenoidal synchondrosis (MSS) becomes
inactive during the first few months of postnatal life
(Melsen, 1971; Giles et al., 1981) and fuses at
around 2 years (Michejda, 1971, 1972; Sirianni,
Fig. 5. Bivariate plots of interpetrosal angle (IPA) and cranial
base angle (CBA) against index of differential encephalisation
(IDE). Two distinct phases are shown for both variables in rela-
tion to IDE, and are separated by mean abscissa value (vertical
line). Analysis of IPA against IDE for the first phase realized a
significant association, for which the reduced major axes regres-
sion line fitting is given (diagonal line).
1985). The spheno-occipital synchondrosis (SOS)
only normally fuses in adult macaques (Melsen,
1969; Sirianni, 1985). In modern humans, the MSS
is the first to fuse and does so late in fetal life (Ford,
1958; Hoyte, 1971, 1975; Kodama, 1976a,b; Shapiro
and Robinson, 1980). This is followed by fusion of
the SES, which normally remains patent for up to 6
postnatal years (Scott, 1958). Like macaques, the
modern human SOS fuses during adulthood (Brash,
1953; Scott, 1958). These observations demonstrate
that the temporal sequence of fusion in the macaque
moves posteriorly along the basicranium, starting
with the SES and ending with the SOS. By contrast,
the timing of SES and MSS fusion is reversed during
human development. Perhaps it is the earlier fusion
of the MSS that pushes retroflexion into the human
fetal period, allowing for postnatal flexion up and
until SES fusion (Jeffery, 1999). This explanation
remains to be evaluated.
Interpetrosal angle. The findings of the present
study show that the petrous bones gradually reori-
ent coronally by some 15° over the period investi-
gated. Ford (1956) noted that the angle between the
long axes of the otic capsules, which surround the
fetal inner ear apparatus, is about 90°. This is close
to the mean interpetrosal angle computed in the
present study for the interval 27–29 weeks. Ford
(1956) also described an increase in distance be-
tween the medial margins of the internal auditory
meatuses in accordance with overall fetal skull
growth. However, he added that after ossification of
the otic capsules, at around 18 weeks of gestation,
the petrous bones are more sagittally aligned than
before. This is consistent with the findings of Lee et
al. (1996), who recorded that the angle between the
otic capsules rapidly decreases during the period
 FETAL ENCEPHALIZATION AND BASE ARCHITECTURE
22–30 weeks of gestation. The authors showed that
this sagittal reorientation slows, almost to a pla-
teau, later in fetal life. This and the latter finding of
Ford (1956) are incongruous with that reported in
the present study, which showed a coronal reorien-
tation of the petrous bones beyond 18 weeks and
during the period 22–29 weeks. It is worth noting,
however, that Lee et al. (1996) measured their angle
between line-segments that pass through the otic
capsules and an intercept that is fixed at the center
of the pituitary fossa in the ventral radiographic
view. By forcing an intercept at this point, the au-
thors assumed that its position remains stable rel-
ative to the axes of the otic capsules. It is plausible
that shifts in the relative position of the pituitary
fossa (e.g., Latham, 1972) draw the line segments
together and reduces the angle defined by Lee et al.
(1996) without regard to petrous orientation. This
would appear to be the case. Bossy and Gaillard de
Collogny (1965) showed that without a fixed inter-
cept, the angle between the long axes of the otic
capsules, each defined by a line segment passing
through the cochlea and center of the anterior semi-
circular canal, increases by some 30°, or 15° relative
to the midline, from 10 weeks until birth. This dem-
onstrates coronal as opposed to sagittal reorienta-
tion of the otic capsules, and as such is in agreement
with the findings of this study.
Cranial base lengths. The results of the present
study confirm a previous observation that increases
in length of the anterior cranial base exceed those of
the posterior cranial base by as much as twofold
(e.g., Mestre, 1959; Burdi, 1965, 1969; Levihn, 1967;
Houpt, 1970; Johnston, 1974; Anagnostopoulou et
al., 1988; Eriksen et al., 1995). A similar difference
is also seen in macaque fetuses (Sirianni and New-
ell-Morris, 1980). According to Ford (1956, 1958),
the human fetal anterior cranial base has a faster
rate of elongation because its direction of midline
extension closely matches the anteroposterior vector
of brain enlargement, whereas the midline posterior
cranial base is inclined to the brain vector and has a
slower, skeletal rate of extension. The extension of
the midline anterior cranial base in macaques is
said to correspond with growth of the face rather
than the brain (Sirianni and Swindler, 1979). Two
factors that may also underlie differences in the rate
of extension between the anterior and posterior
parts of the primate cranial base are the positions of
growth loci and ossification. The midline anterior
cranial base has three major sites for anteroposte-
rior extension, the fronto-ethmoidal suture, spheno-
ethmoidal synchondrosis, and midsphenoidal syn-
chondrosis. The midline posterior cranial base, on
the other hand, only has two, the midsphenoidal and
spheno-occipital synchondroses (see Lieberman et
al., 2000). Furthermore, the greater part of the pos-
terior cranial base, the basioccipital, ossifies earlier
than parts of the anterior cranial base. This reduces
the amount of interstitial cartilage growth, which
335
Johnston (1974) suggested is more prodigious than
that of bone.
Brain volumes and differential encephaliza-
tion. The scale of endocranial, supratentorial, and
infratentorial enlargement reported in the present
study is consistent with the findings of Jenkins
(1921) and Koop et al. (1986). However, note that
technical differences between these studies and the
present investigation mean that detailed compari-
sons of absolute volumes are of little value (see Jef-
fery, 1999). Notwithstanding this, the findings of
Jenkins (1921) and Koop et al. (1986) also demon-
strate that the rate of supratentorial expansion
exceeds that of the infratentorial brain. This is com-
mensurate with the process of differential enceph-
alization noted in this study. Further corroboration
comes from studies showing that regions of the fetal
brain anterior to the sella have a greater rate of
enlargement than regions posterior to the sella
(Blechschmidt, 1977; Friede, 1981). More in partic-
ular, Guihard-Costa and Larroche (1990) detailed a
trend of decreasing infratentorial mass relative to
supratentorial mass with age. This trend has an
early period of rapid change followed by a gradual
decrease of change, almost to a plateau, and is thus
similar to the temporal trajectory of differential en-
cephalization noted in the present study. Guihard-
Costa and Larroche (1990) also showed that the rate
of change begins to increase again later in fetal life,
as the infratentorial mass increases relative to the
supratentorial mass. Adult modern human values of
IDE, computed with volumes from Stephan et al.
(1981) and Filipek et al. (1989), range from 0.130 –
0.137. These values are larger than the values re-
ported in this study for late fetal life. This confirms
the suggestion that differential infratentorial, as op-
posed to supratentorial, enlargement occurs at some
point during the intervening period of the late third
fetal trimester to adulthood, since infratentorial vol-
ume must increase relative to supratentorial volume
for there to be an increase of IDE (infra/supra vol-
ume). Indeed, studies show that the cerebellum,
which makes up most of the infratentorial volume,
starts to develop later than other parts of the fetal
brain but finishes its growth earlier, by way of a late
fetal to early postnatal period of rapid expansion
(Noback and Moss, 1956; Rakic and Sidman, 1970;
Dobbing and Sands, 1973). Relative infratentorial
enlargement at this time may be augmented by a
contemporaneous deceleration of supratentorial
growth (Guihard-Costa and Larroche, 1990), which
perhaps evolved in modern humans as a safeguard
against difficult births of large-headed neonates (see
Leutenegger, 1987). Results from the present study
showed temporally related increases of relative en-
docranial size, but relative infratentorial size was
not temporally correlated. There are no previous
developmental studies with which to compare these
findings. However, it is interesting to note that the
fetal range of relative endocranial size closely
336 N. JEFFERY AND F. SPOOR
matches the range of relative brain sizes observed
across extant primates at the hominoid taxonomic
level (Spoor, 1997; McCarthy, 2001). Assuming that
interspecific analyses provide insights into changes
with phylogenetic time, this would suggest that the
scale of relative brain enlargement seen during fetal
development is similar to that which occurred dur-
ing human evolution. As a corollary point, it is also
worth noting that McCarthy (2001) detailed an
adult modern human value for relative brain size of
1.22. This closely matches the value of relative en-
docranial size observed here in the last few weeks of
the period investigated. It may be that the fetal
value of relative size is retained into adulthood, or
that temporally distinct and possibly different pro-
cesses afford this likeness, as appears the case with
regard to cranial base angle.
Hypotheses
General spatial-packing. This hypothesis sug-
gests that increases of brain size (volume) relative to
length of the midline cranial base create a spatial-
packing problem that drives cranial base flexion and
coronal reorientation of the petrous bones. The find-
ings from this study appear to support one aspect of
the hypothesis while refuting the other. The result
for cranial base angle is the antithesis of the pre-
dicted outcome. The fetal cranial base retroflexed
rather than flexed in relation to increases of relative
brain size. This raised the suspicion that the indi-
vidual trends of these variables with age, nee head
size, were superimposed in the computation of the
simple rank correlation, which showed an associa-
tion between relative encephalization and retroflex-
ion. Indeed, the partial correlation, computed with
biparietal diameter held constant, suggested that
cranial base angle is not directly associated with
relative endocranial size. This suggests that relative
increases of endocranial size were accommodated
elsewhere in the fetal skull, perhaps by enlargement
of the calvaria, to allow for a shallower posterior
cranial fossa.
On first impression, the findings of this study ap-
pear to corroborate the idea that spatial packing is
the driving force behind petrous reorientation. How-
ever, the correlation between relative endocranial
size and interpetrosal angle is small. Moreover, both
these measures also covaried with age. Given the
compounding of variations seen in relation to age in
the case of cranial base angle, it also seemed perti-
nent to question the robusticity of the rank correla-
tion here. This misgiving is justified. The partial
correlation shows that interpetrosal angle is not
associated with relative endocranial size while con-
trolling for biparietal diameter. Thus, the partial
correlation coefficients indicate that cranial base an-
gulation and petrous reorientation were correlated
to increases in vault size rather than directly to
relative endocranial size. As such, the general
spatial-packing hypothesis is not corroborated by
the findings of this study.
Infratentorial spatial-packing. This hypothe-
sis predicts that increases of infratentorial volume,
i.e., cerebellum and brain-stem volume, relative to
the length of the posterior cranial base create a
spatial-packing problem within the posterior cranial
fossa that is alleviated by cranial base flexion and
coronal reorientation of the petrous bones. This
study corroborated that increases in relative infra-
tentorial size are associated with slower growth of
the posterior cranial base (Moss, 1958; Dean, 1988),
but these were not correlated to changes in cranial
base angle and petrous orientation. Thus, the infra-
tentorial spatial-packing hypothesis is not corrobo-
rated for the period studied. This is not to say that
the hypothesis will be invalidated for all of ontogeny.
As previously noted, the human cerebellum under-
goes a relative increase in rate of enlargement dur-
ing a later period of development than that investi-
gated here. This latent and more pronounced
cerebellar expansion may create a spatial-packing
problem that affects a change of basicranial mor-
phology, as per the hypothesis. More work is needed
in this area to evaluate the temporal scope of mech-
anisms for change.
Differential encephalization. Marked changes
of proportions of the brain were observed in the
present study. Supratentorial volume was shown to
increase in relation to infratentorial volume. The
hypothesis predicts that cranial base angle de-
creases and interpetrosal angle increases with the
process of differential encephalization. However,
testing this concept proved complex because of the
biphasic trajectories of the plots. This problem was
circumvented by subdividing the analyses according
to the phases observed. While not objective, this
approach is straightforward, and more importantly
is effective in describing the individual phases
shown. Subsequent analysis of individual phases
showed that changes of cranial base angle are not
associated with differential encephalization during
the period investigated. It was also shown that
changes of interpetrosal angle are not associated
with differential encephalization in early fetal life
(i.e., 10 –20 weeks). These findings do not corrobo-
rate the hypothesis. However, the hypothesis was
seemingly corroborated by the small correlation ob-
served between changes of interpetrosal angle and
differential encephalization later in fetal life (i.e.,
20 –29 weeks). Again, such a small correlation and
the covariation of these measures with age raised
the suspicion that temporal colinearities were com-
pounded in the analysis. This was confirmed by the
partial correlations while holding for biparietal di-
ameter. Thus, the findings are not consistent with
the hypothesis that differential encephalization
drives cranial base flexion or petrous reorientation
during human fetal life, at least during the period
investigated.
 FETAL ENCEPHALIZATION AND BASE ARCHITECTURE
Interpretations
The major finding of this study is that changes of
cranial base angle and interpetrosal angle are inde-
pendent of increases of absolute and relative en-
docranial sizes. Even if we disregard the partial
correlations, there is little support for any of the
hypotheses put forward at the beginning of this
study. Rather, the evidence suggests that the ob-
served changes arise from temporally related factors
that at present remain undetermined. The obvious
question is: what are these factors?
Before considering answers to this question, we
must point out the major limitations of this study.
Results from this study, as well as those from other
prenatal studies, only cover part of the gestational
period and an even smaller part of the overall period
of human development. Mechanistic hypotheses re-
main to be tested over time spans such as the late
fetal or perinatal periods. This caveat, combined
with the finding that many of the trends shown here
are polyphasic (e.g., cranial base angulation and
differential encephalization), raises the possibility
that the hypotheses may prove valid explanations
for one period of development but not for another. In
other words, the findings and conclusions of this
study can only be related with any certainty to hu-
man fetal material from the same period. Any ex-
trapolation from this is useful in guiding further
study and formulating ideas, both developmental
and evolutionary, but such interpretations remain
tenuous until a study of wider scope can be under-
taken. In addition, the aims of the present study
were strictly focused on the effects of brain enlarge-
ment, in its various forms. Other potential mecha-
nistic processes were not considered. For example,
the size of the pharynx has been linked with changes
of cranial base angle during human development
and with the degree of flexion seen in adult modern
humans compared with that of other primates (see
Ross and Henneberg, 1995; Lieberman et al., 2001).
Such mechanisms may work against or in tandem
with the effects of brain enlargement, or even in
opposing phases over ontogenetic time. There is still
some way to go before all possible mechanistic ex-
planations for changes of the human fetal cranial
base, and their permutations, are exhausted.
The fetal basicranium appears to remain unper-
turbed by considerable changes in both brain size
and shape, suggesting that the pattern of variation
taken by the fetal cranial base is partially a conse-
quence of variables other than structural demands.
Notwithstanding those mechanisms not yet tested,
the demonstration of independence implies that fe-
tal basicranial morphology is regulated at some level
by internal, i.e., intrinsic, factors in preference to
external influences. It is unclear from this study
whether “intrinsic” regulation corresponds to direct
gene control or the knock-on effects of gene control
separated from the initial expression by intervening
levels of increasing biological complexity (i.e., from
337
gene expression, through signalling, cellular activ-
ity, and tissue morphogenesis, to architectural vari-
ations). For example, it is plausible that base flexion
and petrous reorientation are directly regulated by
genes that represent a modern human adaptation,
selected for over subsequent ancestral ontogenies in
response to a mechanical force like brain enlarge-
ment but which are now exapted for some other
purpose and are largely independent of brain size.
Perhaps more plausible is that there is no direct
association, and that genetic control is mediated
through processes like the position and activity of
growth loci within the cranial base. That way, sim-
ilar genotypes are gradually overlaid with the struc-
tural demands of growth during ontogeny to produce
different phenotypes.
Some insight can be gained by exploring the dis-
parity between results from the interspecific studies
cited and the ontogenetic findings reported here. In
nearly every case, the findings of this study contra-
dict those obtained from interspecific analyses of
extant primates (e.g., Ross and Ravosa, 1993; Spoor,
1997; McCarthy, 2001). This apparent dichotomy
may be an artifact of the comparative method used
in these interspecific studies. Like the compounding
of variables by their relationship with age seen in
this study, interspecific trends can be compounded
with the phylogenetic relationships among the often
closely related primate species investigated (see
Harvey and Pagel, 2000). Indeed, Lieberman et al.
(2000) noted that with degrees of freedom adjusted
for phylogeny across extant anthropoids, the corre-
lation between differential encephalization (telen-
cephalon/brain-stem) and cranial base angle is
insignificant. The authors indicated that the unad-
justed correlation was significant. Their modified
result is consistent with the finding reported here,
showing that cranial base angle is not significantly
correlated with differential encephalization (infra/
supratentorial). However, this does not resolve all
differences. Many interspecific results remain at
odds with those reported here, even after adjust-
ment. For example, Lieberman et al. (2000) also
showed that while the adjusted correlation between
relative brain size (IRE) and cranial base angle is
less significant than that reported by Ross and Ra-
vosa (1993), it is still robust enough to support the
spatial-packing hypothesis. Such seemingly irrecon-
cilable differences point to a more fundamental in-
congruity, whereby ontogenetic and interspecific
studies produce results pertaining to different
processes (e.g., Zuckerman, 1955; Sirianni and
Swindler, 1979).
Ontogeny and phylogeny are clearly intercon-
nected, but to what extent and is this link constant?
Clearly, the interchange occurs at the adult in-
traspecific level, where variations during ontogeny
provide a suite of variations in the sexually mature
which, if selected for and heritable, can evolve into
new morphologies (see Gould and Lewontin, 1979).
This implies that developmental findings differ in
338 N. JEFFERY AND F. SPOOR
that they pertain to a dynamic process of reversal
between phylogeny and the changes responsible for
intraspecific variation. To put it another way, ontog-
eny is the stochastic accumulation of somatic varia-
tions against the backdrop of decreasing inherited
control of morphology. The core of this idea is well-
established in the literature (e.g., Baker, 1941;
Scott, 1954; Manson, 1968; Dorenbos, 1972; Tuckett
and Morriss-Kay, 1985). According to this concept,
the fetal basicranium is subject to more intrinsic
control and less mechanistic control than the post-
natal basicranium. Thus, the period of ontogeny ex-
amined determines the findings of the study with
regard to the testing of mechanistic hypotheses.
This can explain the adult interspecific/human fetal
inconsistencies at two levels. First, it can be pro-
posed that inconsistency results from generally
tighter regulation of primate fetal development com-
pared with the adult primate form. In other words,
the adult interspecific studies, by comparison, high-
light biomechanistic-driven changes across taxa,
while the results presented here indicate that in-
trinsic controls are not yet sufficiently relaxed in the
early fetus to allow for such marked relationships.
This predicts that intraspecific studies of fetal de-
velopment particularly at the earliest stages in
other primate taxa, will yield similar inconsistencies
with the adult interspecific evidence. Second, it can
also be proposed that within this general scheme of
primate fetal development, different temporal pat-
terns in the relaxation of control exist between spe-
cies, thereby contributing to interspecific differences
later in life, and that modern humans exhibit a
comparatively extended period of tighter morpholog-
ical control. This predicts that developmental stud-
ies across primate taxa will demonstrate that cer-
tain species group trends are consistent with adult
interspecific trends owing to the comparatively ear-
lier relaxation of control, perhaps even at the fetal
stage of life.
Despite such insights, a number of questions re-
main unanswered. In particular, the essential prob-
lem remains of distinguishing adaptations incorpo-
rated into the genome by successive ontogenies from
those morphologies that do not require assimilation
into the genome, because the ubiquitous nature of
mechanical laws can be relied on to deliver a suffi-
cient phenotype, and from morphologies produced
by the mechanistic knock-on effects of adaptive
change. Only by combining ontogenetic and inter-
specific analyses, tempered with evidence from the
fossil record, can we hope to obtain a clearer picture
of the processes underlying human evolution, and in
particular the factors underlying the derived condi-
tion of the modern human skull.
CONCLUSIONS
Data were collected from a sample of human fe-
tuses ranging from 10 –29 weeks of gestation in or-
der to test hypotheses that cranial base angle and
petrous orientation follow from increases of relative
endocranial size, increases of relative infratentorial
size, or differential encephalization. We found that:
1) The cranial base retroflexes during the human
fetal period investigated. Considering findings
from previous studies, it was determined that the
process of basicranial angulation is polyphasic,
and that fetal values of cranial base angle are not
retained into adulthood.
2) It was also revealed that the petrous bones coro-
nally reorientate, relative brain size increases,
and supratentorial volume differentially enlarges
over the period investigated.
3) Results show distinct growth rates on either side
on the tentorium cerebelli for both cranial base
lengths and endocranial volumes. Those compo-
nents superoanterior to the tentorium cerebelli
increase at rates exceeding those of inferoposte-
rior components.
4) Lastly and most importantly, the findings of this
study show that cranial base angulation and pe-
trous reorientation are associated with increases
of vault size, which represent age, rather than
increases of relative brain sizes. Given the nota-
ble increases of relative sizes observed, this sug-
gests that fetal basicranial morphology is regu-
lated more intrinsically than proposed by the
hypotheses tested, though many other mechanis-
tic explanations remain to be discounted.
ACKNOWLEDGMENTS
We thank B. Berkovitz, W. Birch, M. Bird, P.
Kinchesh, and P. O’Higgins for permission and help
with imaging the material. We also thank four anon-
ymous referees for their comments and suggestions.
LITERATURE CITED
Anagnostopoulou S, Karamaliki DD, Spyropoulos MN. 1988. Ob-
servations on the growth and orientation of the anterior cranial
base in the human foetus. Eur J Orthod 10:143–148.
Ashton EH. 1957. Age changes in the basicranial axis of the
anthropoidea. Proc Zool Soc Lond 129:61–74.
Baker LW. 1941. The influence of the formative dental organs on
the growth of bones and the face. Am J Orthod 27:489 –506.
Biegert J. 1957. Der Formwandel des Primatenschädels und
seine Beziehungen zur ontogenetischen Entwicklung und den
phylogenetischen Spezialisationen der Kopforgane. Gegen-
bauers Morphol Jahrb 98:77–199.
Biegert J. 1963. The evaluation of characteristics of the skull,
hands, and feet for primate taxonomy. In: Washburn SL, editor.
Classification and human evolution. London: Methuen. p 116 –
145.
Blechschmidt E. 1977. The beginnings of human life. Translated
by Transemantics, Inc. New York: Spinger-Verlag.
Bossy J, Gaillard de Collogny L. 1965. Orientation comparée de la
cochlée et du canal semi-circulaire anterieur chez le foetus. J Fr
Otorhinolaryngol 14:727–735.
Brash JC. 1953. Cunningham’s text-book of anatomy. London:
Oxford University Press.
Burdi AR. 1965. Sagittal growth of the nasomaxillary complex
during the second trimester of human prenatal development. J
Dent Res 44:112–125.
Burdi AR. 1969. Cephalometric growth analyses of the human
upper face region during the last two trimesters of gestation.
Am J Anat 125:113–122.
 FETAL ENCEPHALIZATION AND BASE ARCHITECTURE
Cameron J. 1924. The cranio-facial axis of Huxley. Part I. Em-
bryological considerations. Trans R Soc Can 18:115–123.
Cameron J. 1930. The human and comparative anatomy of Cam-
eron’s craniofacial axis. J Anat 64:324 –336.
Chitty LS, Altman DG, Henderson A, Campbell S. 1994. Charts of
fetal size: 2. Head measurements. Br J Obstet Gynaecol 101:
35– 43.
Cousin RP. 1969. Étude en projection sagittale de crânes
d’enfants orientés dans les axes vestibulaires. Ph.D. disserta-
tion, University of Paris.
Dabelow A. 1931. Über Korrelationenin der phylogenetischen
Entwicklung der Schädelform II. Die Beziehungen zwischen
Gehirn und Schädelbasisform bei den Mammalien. Gegen-
bauers Morphol Jahrb 67:84 –133.
Dean MC. 1988. Growth processes in the cranial base of homi-
noids and their bearing on morphological similarities that exist
in the cranial base of Homo and Paranthropus. In: Grine FE,
editor. Evolutionary history of the “robust” australopithecines.
New York: Aldine de Gruyter. p 107–112.
Dean MC, Wood BA. 1981. Metrical analysis of the basicranium
of extant hominoids and Australopithecus. Am J Phys An-
thropol 54:63–71.
Dean MC, Wood BA. 1984. Phylogeny, neoteny and growth of the
cranial base in Hominoids. Folia Primatol (Basel) 43:157–180.
De Beer GR. 1937. The development of the vertebrate skull.
Oxford: Clarendon Press.
Diewert VM. 1983. A morphometric analysis of craniofacial
growth and changes in spatial relations during secondary pal-
atal development in human embryos and fetuses. Am J Anat
167:495–522.
Diewert VM. 1985. Development of human craniofacial morphol-
ogy during the late embryonic and early fetal periods. Am J
Orthod 88:64 –76.
Dimitriadis AS, Haritanti-Kouridou A, Antoniadis K, Ekonon-
mou L. 1995. The human skull base angle during the second
trimester of gestation. Neuroradiology 37:68 –71.
Dobbing J, Sands J. 1973. Quantitative growth and development
of human brain. Arch Dis Child 48:757–767.
Dorenbos J. 1972. In vivo cerebral implantation of the anterior
and posterior halves of the spheno-occipital synchondrosis in
rats. Arch Oral Biol 17:1067–1072.
Du Brul EL. 1977. Early hominid feeding mechanisms. Am J
Phys Anthropol 47:305–320.
Duckworth WLH. 1915. Morphology and anthropology. Cam-
bridge: Cambridge University Press.
Enlow DH. 1976. The prenatal and postnatal growth of the hu-
man basicranium. In: Bosma JF, editor. Symposium on devel-
opment of the basicranium. Bethesda: US Government DHEW.
Publication no. NIH 76-989. p 192–205.
Enlow DH, Hunter WS. 1968. The growth of the face in relation
to the cranial base. Rep Congr Eur Orthod Soc 44:321–335.
Enlow DH, Moyers RE. 1971. Growth and architecture of the face.
J Am Dent Assoc 82:763–774.
Erdoglija LJ. 1989. Dynamics of the cranial base angle changes
during the second trimester of the normal intrauterine growth
and development. Bilt Udruz Ortod Jugosl 22:7–14.
Erdoglija LJ. 1990. Dynamics of changes of anteroposterior jaw
positions relative to the cranial base during the second trimes-
ter of normal intrauterine growth. Bilt Udruz Ortod Jugosl
23:59 – 68.
Eriksen E, Bach-Petersen S, van den Eynde B, Solow B, Kjaer I.
1995. Midsagittal dimensions of the prenatal human cranium.
J Craniofac Genet Dev Biol 15:44 –50.
Filipek PA, Kennedy DN, Caviness VS Jr, Rossnick SL, Sprag-
gins TA, Starewicz PM. 1989. Magnetic resonance imaging
based brain morphometry: development and application to nor-
mal subjects. Ann Neurol 25:61– 67.
Ford EHR. 1956. The growth of the foetal skull. J Anat 90:63–72.
Ford EHR. 1958. Growth of the human cranial base. Am J Orthod
44:498 –506.
Friede H. 1981. Normal development and growth of the human
neurocranium and cranial base. Scand J Plast Reconstr Surg
15:163–169.
339
Garstang W. 1922. The theory of recapitulation: a critical restate-
ment of the biogenetic law. Zool J Linn 35:81–101.
Giles WB, Philips CL, Joondeph DR. 1981. Growth in the basi-
cranial synchondroses of the adolescent Macaca mulatta. Anat
Rec 199:259 –266.
Gould SJ. 1977. Ontogeny and phylogeny. London: Harvard Uni-
versity Press.
Gould SJ, Lewontin RC. 1979. The spandrels of San Marco and
the Panglossian paradigm: a critque of the adaptationist pro-
gramme. Proc R Soc Lond [Biol] 205:581–598.
Guihard-Costa AM, Larroche JC. 1990. Differential growth be-
tween the fetal brain and its infratentorial part. Early Hum
Dev 23:27– 40.
Guihard-Costa AM, Larroche JC. 1992. Growth velocity of some
fetal parameters. I. Brain weight and brain dimensions. Biol
Neonate 62:309 –316.
Harvey P, Pagel M. 2000. The comparative method in evolution-
ary biology. Oxford: Oxford University Press.
Herring SW. 1993. Epigenetic and functional influences on skull
growth. In: Hanken J, Hall BK, editors. The skull: develop-
ment. Chicago: Chicago University Press. p 153–207.
Hofer HO. 1969. On the evolution of the craniocerebral topogra-
phy in primates. Ann NY Acad Sci 162:15–24.
Hoyte DA. 1971. Mechanisms of growth in the cranial vault and
base. J Dent Res 50:1447–1461.
Hoyte DA. 1975. A critical analysis of the growth in length of the
cranial base. Birth Defects 11:255–282.
Houpt MI. 1970. Growth of the craniofacial complex of the human
fetus. Am J Orthod 58:373–383.
Jeffery N. 1999. Fetal development and evolution of the human
cranial base. Ph.D. dissertation, University College, London.
Jenkins GB. 1921. Relative weight and volume of the component
parts of the brain of the human embryo at different stages of
development. Contrib Embryol 29:41– 60.
Jerison HJ. 1982. Allometry, brain size and convolutedness. In:
Armstrong E, Falk D, editors. Primate brain evolution: meth-
ods and concepts. New York: Plenum Press. p 77– 84.
Johnston LE. 1974. A cephalometric investigation of the sagittal
growth of the second trimester fetal face. Anat Rec 178:623–
630.
Keith A. 1910. Description of a new craniometer and of certain
age changes in the anthropoid skull. J Anat 44:251–270.
Knowles CC. 1963. The influence of cranial base structure on the
orientation of the middle third of the face. Dent Pract Dent Rec
13:531–542.
Kodama G. 1976a. Developmental studies on the presphenoid of
the human sphenoid bone. In: Bosma JF, editor. Symposium on
development of the basicranium. Bethesda: US Government
DHEW. Publication no. NIH 76-989. p 141–155.
Kodama G. 1976b. Developmental studies on the body of the
human sphenoid bone. In: Bosma JF, editor. Symposium on
development of the basicranium. Bethesda: US Government
DHEW. Publication no. NIH 76-989. p 156 –165.
Koop M, Rilling G, Herrmann A, Kretschmann HJ. 1986. Volu-
metric development of the fetal telencephalon, cerebral cortex,
diencephalon, and rhombencephalon including the cerebellum
in man. Bibl Anat 28:53–78.
Kvinnsland S. 1971. The sagittal growth of the foetal cranial
base. Acta Odontol Scand 29:699 –715.
Latham RA. 1972. The sella point and postnatal growth of the
human cranial base. Am J Orthod 61:156 –162.
Lee SK, Kim YS, Jo YA, Seo JW, Chi JG. 1996. Prenatal devel-
opment of cranial base in normal Korean fetuses. Anat Rec
246:524 –534.
Leutenegger W. 1987. Neonatal brain size and neurocranial di-
mensions in Pliocene hominids: implications for obstetrics. J
Hum Evol 16:291–296.
Levihn WC. 1967. A cephalometric roentgenographic cross-sec-
tional study of the craniofacial complex in fetuses from 12
weeks to birth. Am J Orthod 53:822– 848.
Lieberman DE, McCarthy RC. 1999. The ontogeny of cranial base
angulation in humans and chimpanzees and its implications for
reconstructing pharyngeal dimensions. J Hum Evol 36:487–
517.
340 N. JEFFERY AND F. SPOOR
Lieberman DE, Ross CF, Ravosa MJ. 2000. The primate cranial
base: ontogeny, function, and integration. Am J Phys Anthropol
Yrbk 43:117–169.
Lieberman DE, McCarthy RC, Hiiemae KM, Palmer JB. 2001.
Ontogeny of postnatal hyoid and larynx descent in humans.
Arch Oral Biol 46:117–128.
Mandarim-de-Lacerda CA, Alves MU. 1992. Growth of the cranial
bones in human fetuses (2nd and 3rd trimesters). Surg Radiol
Anat 14:125–129.
Manson JD. 1968. A comparative study of the postnatal growth of
the mandible. London: Henry Kempton.
McCarthy RC. 2001. Anthropoid cranial base architecture and
scaling relationships. J Hum Evol 40:41– 66.
Melsen B. 1969. Time of closure of the spheno-occipital synchon-
drosis determined on dry skulls. A radiographic craniometric
study. Acta Odontol Scand 27:73–90.
Melsen B. 1971. The postnatal growth of the cranial base in
Macaca rhesus analyzed by the implant method. Tandlaege-
bladet 75:1320 –1329.
Mestre JC. 1959. A cephalometric appraisal of cranial and facial
relationships at various stages of human fetal development.
Am J Orthod 45:473.
Michejda M. 1971. Ontogenetic changes of the cranial base in
Macaca mulatta. Proceedings of the Third International Con-
ference on Primatology, Zurich, 1970. Volume 1. p 215–225.
Michejda M. 1972. The role of the basicranial synchondroses in
flexure processes and ontogenetic development of the skull
base. Am J Phys Anthropol 37:143–150.
Michejda M, Lamey D. 1971. Flexion and metric age changes of
the cranial base in the Macaca mulatta. I. Infants and juve-
niles. Folia Primatol (Basel) 14:84 –94.
Moss ML. 1958. The pathogenesis of artificial cranial deforma-
tion. Am J Phys Anthropol 16:269 –285.
Moss ML, Noback CR, Robertson GG. 1956. Growth of certain
human fetal cranial bones. Am J Anat 98:191–204.
Müller F, O’Rahilly R. 1980. The human chondrocranium at the
end of the embryonic period, proper, with particular reference
to the nervous system. Am J Anat 159:33–58.
Noback CR, Moss ML. 1956. Differential growth of the human
brain. J Comp Neurol 105:539 –555.
Plavcan JM, German RZ. 1995. Quantitative evaluation of cranio-
facial growth in the third trimester human. Cleft Palate
Craniofac J 32:394 – 404.
Putz VR. 1974. Skull configuration and pyramids. On the position
of pyramids within the cranial base. Anat Anz 135:252–266.
Rakic P, Sidman RL. 1970. Histogenesis of cortical layers in
human cerebellum, particularly the lamina dissecans. J Comp
Neurol 139:473–500.
Ross CF, Henneberg M. 1995. Basicranial flexion, relative brain
size, and facial kyphosis in Homo sapiens and some fossil homi-
nids. Am J Phys Anthropol 98:575–593.
Ross CF, Ravosa MJ. 1993. Basicranial flexion, relative brain
size, and facial kyphosis in nonhuman primates. Am J Phys
Anthropol 91:305–324.
Scheuerle AE. 1995. Recent advances in craniofacial genetics. J
Craniofac Surg 6:440 – 442.
Schultz AH. 1955. The position of the occipital condyles and of the
face relative to the skull base in primates. Am J Phys Anthropol
13:97–120.
Scott JH. 1954. The growth of the human face. Proc R Soc Med
47:9147–9158.
Scott JH. 1958. The cranial base. Am J Phys Anthropol 16:319 –
348.
Shapiro R, Robinson F. 1980. The embryogenesis of the human
skull. London: Harvard University Press.
Sherwood RJ, Meindl RS, Robinson HB, May RL. 2000. Fetal age:
methods of estimation and effects of pathology. Am J Phys
Anthropol 113:305–315.
Sirianni JE. 1985. Nonhuman primates as models for human
craniofacial growth. In: Alan R, editor. Nonhuman primate
models for human growth and development. New York: Liss,
Inc. p 95–124.
Sirianni JE, Newell-Morris L. 1980. Craniofacial growth of fetal
Macaca nemestrina: a cephalometric roentgenographic study.
Am J Phys Anthropol 53:407– 421.
Sirianni JE, Swindler DR. 1979. A review of postnatal craniofa-
cial growth in old world monkeys and apes. Am J Phys An-
thropol Yrbk 22:80 –104.
Sirianni JE, Van Ness AL. 1978. Postnatal growth of the cranial
base in Macaca nemestrina. Am J Phys Anthropol 49:329 –340.
Sokal RR, Rohlf FJ. 1995. Biometry. New York: W.H. Freeman
and Co. p 593– 609.
Sperber GH. 1992. Current concepts in embryonic craniofacial
development. Crit Rev Oral Biol Med 4:67–72.
Sperber GH. 2001. Craniofacial development. London: B.C.
Decker, Inc. p 96 –97.
Spoor F. 1997. Basicranial architecture and relative brain size of
Sts 5. Australopithecus africanus and other Plio-Pleistocene
hominids. S Afr J Sci 93:182–187.
Spoor F, Zonneveld FW. 1995. Morphometry of the primate bony
labyrinth: a new method based on high-resolution computed
tomography. J Anat 186:271–286.
Spoor F, Zonneveld FW. 1998. Comparative review of the human
bony labyrinth. Am J Phys Anthropol 27:211–251.
Spoor F, Jeffery N, Zonneveld FW. 2000a. Imaging skeletal
growth and evolution. In: O’Higgins P, Cohen M, editors. De-
velopment, growth and evolution: implications for the study of
hominid skeletal evolution. London: Academic Press. p 123–
161.
Spoor F, Jeffery N, Zonneveld FW. 2000b. Using diagnostic radi-
ology in human evolutionary studies. J Anat 197:61–76.
Stephan H, Frahm H, Baron G. 1981. New and revised data on
volumes of brain structures in insectivores and primates. Folia
Primatol (Basel) 35:1–29.
Strait DS. 1999. The scaling of basicranial flexion and length. J
Hum Evol 37:701–719.
Strait DS, Ross CF. 1999. Kinematic data on primate head and
neck posture: implications for the evolution of basicranial flex-
ion and an evaluation of registration planes used in paleoan-
thropology. Am J Phys Anthropol 108:205–222.
Thesleff I. 1998. The genetic basis of normal and abnormal
craniofacial development. Acta Odontol Scand 56:321–325.
Thorogood P. 1987. Mechanisms of morphogenetic specification
skull development. In: Wolff JR, Sievers J, Berry M, editors.
Mesenchymal-epithelial interactions in neural development.
Berlin: Spinger-Verlag. p 141–152.
Thorogood P. 1988. The developmental specification of the verte-
brate skull. Development 103:141–153.
Thorogood P. 1993. Differentiation and morphogenesis of cranial
skeletal tissues. In: Hanken J, Hall BK, editors. The skull:
development. Chicago: Chicago University Press. p 112–153.
Tuckett F, Morriss-Kay GM. 1985. The ontogenesis of cranial
neuromeres in the rat embryo. II. A transmission electron
microscope study. J Embryol Exp Morphol 88:231–247.
van den Eynde B, Kjaer I, Solow B, Graem N, Kjaer TW,
Mathiesen M. 1992. Cranial base angulation and prognathism
related to cranial and general skeletal maturation in human
fetuses. J Craniofac Genet Dev Biol 12:22–32.
Virchow R. 1857. Untersuchungen über die Entwicklung des
Schädelgrundes im gesunden und frankhaften Zustande. Ber-
lin: Gesichissiblung und Gehirnbru.
Zuckerman S. 1955. Age changes in the basicranial axis of the
human skull. Am J Phys Anthropol 13:521–539.