close

Вход

Забыли?

вход по аккаунту

?

Brain size and the human cranial base A prenatal perspective.

код для вставкиСкачать
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 between 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 orientated 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 results from a phylogenetic increase in the size of the brain
and its subcomponents (infra- and supratentorial volumes) 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 prenatal ontogenetic context. We measured the degree of
basicranial flexion, petrous reorientation, base lengths,
and endocranial volumes from high-resolution magnetic
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 increases of relative endocranial sizes across the sample,
and the hypotheses therefore predict correlated variations
of cranial base flexion and petrous orientation in accordance 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.
The cranial base of modern humans differs markedly 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 basioccipital has a more vertically inclined orientation
relative to the anterior cranial base (e.g., Keith,
1910; Duckworth, 1915; Zuckerman, 1955; Cameron, 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 factors 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 structural demands that appear to follow from these relations a multitude of hypotheses have been proposed, which phylogenetically link the modern
human morphology with, among others, brain expansion (i.e., phylogenetic encephalisation), obligatory bipedalism, and facial orthognathism (e.g.,
Biegert, 1963; Du Brul, 1977; Dean, 1988; Ross and
Ravosa, 1993). Most recently, some of these hypothetical associations have been assessed by analyzing interspecific trends among extant and fossil primates (e.g., Ross and Ravosa, 1993; Ross and
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 studies advanced possible ontogenetic mechanisms underlying the phylogenetic origin of the modern human 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-
©
2002 WILEY-LISS, INC.
Grant sponsor: Medical Research Council; Grant sponsor: Wellcome
Trust; Grant sponsor: University of London Intercollegiate NMR Research Service Scheme, Queen Mary and Westfied College.
*Correspondence to: Nathan Jeffery, Evolutionary Anatomy Unit,
Department of Anatomy and Developmental Biology, University College 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 interpretation is that the ontogenetic basis for phylogenetic 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 numerous 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, focusing on those aspects that uniquely characterize modern humans. Secondly, using this information it
tests phylogenetic hypotheses describing the interaction between the brain and cranial base, in a first
systematic attempt to evaluate possible ontogenetic
mechanisms that may contribute to the derived cranial morphology of modern humans.
PHYLOGENETIC PERSPECTIVE
Now often referred to as spatial-packing hypotheses, 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 anteroinferiorly, the anterior cranial base was deflected 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 established 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 encephalization (e.g., maintaining airway patency). Spoor
(1997) also found an interspecific association between cranial base flexion and relative brain size,
but in contrast to Ross and Henneberg (1995),
showed that modern humans do not deviate significantly from the primate trend. This discrepancy between the studies of Spoor (1997) and Ross and
Ravosa (1993) and Ross and Henneberg (1995) probably reflects differences in the landmarks used to
measure cranial base angle and length (see McCarthy, 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, modern humans follow the primate trend for the orientation of the foramen magnum, but their petrous
pyramids are less coronally orientated than predicted. As with base flexion, this could imply that
petrous reorientation is in some way constrained. A
recent study by Lieberman et al. (2000) adds considerable 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 posterior 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 problem which followed from disproportionate enlargement 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 sample 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 propose such a hypothesis. He suggested that differential enlargement of the cerebrum not only maximizes 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 necessitates a flexion between the cerebrum and brain-stem
that is matched by flexion of the midline basicranium. 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 different parts of the brain exhibit distinct scaling trajectories across extant primate species, and he hypothesized 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 interspecific evaluation of the influence of differential
encephalization revealed a significant correlation
between increases of cerebral volume over brainstem volume and cranial base flexion across extant
primates (Lieberman et al., 2000).
ONTOGENETIC PERSPECTIVE
The developmental literature contains several hypotheses, 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), formulated 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 basicranium. This is consistent with human fetal studies
showing that growth along the cranial base is significantly 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 together, 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 angulation (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 visualization these studies used. For example, Erdoglija
(1989) and Dimitriadis et al. (1995) employed x-raybased imaging techniques, i.e., plain film radiography and computed tomography, to visualize the fetal
cranial base. These modalities rely on the radiodensity of tissues to highlight morphologies. While
these techniques are suitable for imaging radiodense 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 technique 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 ontogenetic 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 compensatory mechanism for slower growth of the posterior
cranial base compared with that of the anterior cranial 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 sizable 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 enlargement within the confines of the posterior cranial fossa.
Findings from fetal studies are also consistent
with processes of ontogenetic differential encephalization. Marked increases in the supratentorial
portion of the brain occur in relation to the infratentorial portion during fetal development (GuihardCosta and Larroche, 1990, 1992). More importantly,
Moss et al. (1956) linked fetal differential encephalisation with changes of posterior fossa morphology. 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 cranial 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 fetal brain volume relative to cranial base length create 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 isometrically with brain volume, i.e., relative brain size remains unchanged and the hypothesis is not applicable; 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 infratentorial volume measured against the length of the
posterior cranial base create a “spatial-packing”
problem within the posterior cranial fossa that results in cranial base flexion and coronal petrous
reorientation. The three possible outcomes are essentially the same as those described for the general
spatial-packing hypothesis.
Differential encephalization
The third hypothesis predicts that prenatal increases of supratentorial volume relative to infratentorial 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 differential encephalization, and consequently the hypothesis is not testable; and 3) differential encephalization but no correlation with either base flexion
or coronal petrous reorientation, and hence the hypothesis 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 Developmental 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 reference 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 biparietal diameter while presenting the data in a
more readily interpreted format, i.e., that of gestational time. Other, perhaps more suitable age proxies (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 distribution 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 diameter) saddle coil; and a 6.2-cm birdcage coil, according to the size of the specimen; matrix size,
256 ⫻ 256; number of averages (NEX), 24 with typical scanning times of 18 –22 hr; and a T2-weighted
spin-echo multislice sequence (TR and TE were approximately 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 weighting 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 specimen. 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 landmark 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
Code
BPD (mm)
EGA
(weeks)
FOV
(mm)
Slice thickness
(mm)
UMSCL-163
UMSCL-39
QMWF49
UMSCL-61
QMWF7
UMSCL-2992
QMWF34
UMSCL-164
UMSCL-962
011A2
UMSCL-165
UMSCL-94
Z101
UMSCL-63
UMSCL-92
UMSCL-216
QMW35
QMW28
UMSCL-223
UMSCL-86
UMSCL-91
UMSCL-287
Z102
UMSCL-220
UMSCL-2222
UMSCL-221
UMSCL-210
ZN1
UMSCL-166
UMSCL-215
UMSCL-212
UMSCL-207
UMSCL-218
UMSCL-214
UMSCL-211
UMSCL-297
UMSCL-209
UMSCL-292
UMSCL-286
UMSCL-281
UMSCL-301
UMSCL-284
UMSCL-242
UMSCL-248
UMSCL-232
UMSCL-229
UMSCL-238
UMSCL-275
UMSCL-240
UMSCL-303
15.0
15.0
19.0
21.0
24.0
24.0
25.5
27.0
29.0
32.0
32.0
33.0
35.0
37.0
37.0
38.5
40.0
40.0
40.0
42.0
42.0
42.0
43.0
43.0
44.0
44.0
45.0
45.0
46.0
46.0
47.0
48.0
49.0
49.0
49.0
50.0
52.0
52.0
54.0
57.0
57.5
60.5
62.0
64.0
64.0
66.0
67.0
69.5
70.0
77.0
10.1
10.1
11.5
12.1
13.1
13.2
13.5
14.0
14.1
15.4
15.4
15.7
16.3
16.8
16.8
17.2
17.6
17.6
17.6
18.2
18.2
18.2
18.4
18.4
18.7
18.7
19.0
19.0
19.2
19.2
19.5
19.8
20.1
20.1
20.1
20.3
20.9
20.9
21.5
22.3
22.5
23.4
23.8
24.5
24.5
25.1
25.5
26.3
26.5
29.2
40
30
40
40
40
40
40
50
50
50
64
50
64
64
64
64
64
80
64
64
64
80
64
80
64
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
102.4
85
89.6
102.4
102.4
102.4
102.4
115.2
0.31
0.23
0.31
0.31
0.31
0.31
0.31
0.39
0.39
0.39
0.50
0.39
0.50
0.50
0.50
0.50
0.50
0.63
0.50
0.50
0.50
0.63
0.50
0.63
0.50
0.64
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.63
0.80
0.66
0.70
0.80
0.80
0.80
0.80
0.90
1
BPD, biparietal diameter; EGA, estimated gestation age; FOV,
imaging field of view. Specimens with codes commencing with
UMSCL are from University College London; codes starting with
Z, QMW, or 01 refer to those specimens from Queen Mary and
Westfield College, London.
2
Excluded from study.
rather than a basicranial landmark, and its use is
inappropriate because it introduces variation from
facial growth (Enlow and Moyers, 1971). Ideally,
measures of CBA would attempt to approximate the
primary points of flexion, i.e., the spheno-ethmoidal,
midsphenoidal, and spheno-occipital synchondroses
(see Lieberman and McCarthy, 1999). However, not
all of the synchondroses were sufficiently resolved
with hrMRI throughout the period investigated. The
landmarks used were defined as follows (Fig. 2a,b;
Table 2): Fc, the center of the endocranial opening of
Fig. 2. High-resolution magnetic resonance images (hrMRI)
of fetal head, and schematic representations of measures taken
thereon. a: Midline hrMR image of fetal head. b: Sketch showing
measure of cranial base angle computed from coordinates for
foramen caecum (Fc), sella (S), and basion (Ba). c: Transverse
hrMR image at level of anterior semicircular canals and presphenoid. d: Sketch showing measure of interpetrosal angle computed
from coordinates for medialmost (Md) and lateralmost (Lt) attachments of tentorium cerebelli to petrous ridges. Scale bars, 10
mm.
the foramen caecum, seen as a pit on the cribriform
plate between the fetal crista galli and the endocranial wall of the frontal bone; S, the centerpoint of the
sella turcica; and Ba, the tip or point of greatest
curvature of the basioccipital on the anterior margin
of the foramen magnum.
A number of studies measured petrous orientation
using exocranial landmarks (e.g., Dean and Wood,
1981, 1984) and landmarks on the endocranial
petrosal surface (Putz, 1974; Spoor, 1997; Spoor and
Zonneveld, 1995, 1998), but these cannot be replicated in the developing fetus. Here, petrous orientation was approximated with a measure of interpetrosal angle (IPA). This was defined as the angle
between line segments fitted through the lateralmost to the medialmost attachments of the tentorium cerebelli to the petrous ridges (Fig. 2c,d; Table
2). In practice, landmarks were taken from coronal
images anterior to the cochleae and just anterior to
the sigmoid sulci.
Total, anterior, and posterior cranial base lengths
were measured as the distances between Fc, S, and
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
Landmarks
Basion
Foramen caecum
Ba
Fc
Sella
Medial petrous
S
Md
Lateral petrous
Lt
Linear measures
Total cranial base length
Anterior cranial base length
Posterior cranial base length
Angles
Cranial base angle
Interpetrosal angle
Volumes and areas
Endocranial volume
Supratentorial volume
Infratentorial volume
Midline area
Derived measures
Relative endocranial size
TBL
ABL
PBL
CBA
IPA
Definition
Midline point on anterior margin of foramen magnum
Midline point marking pit between fetal crista galli and endocranial wall of
frontal bone
Center of sella turcica in midline
Points marking medialmost tentorial attachments to left and right petrous
ridges
Points marking lateralmost tentorial attachments to left and right petrous
ridges
Total linear distance from basion (Ba) to sella (S), and sella to foramen caecum
(Fc)
Linear distance from sella (S) to foramen caecum (Fc)
Linear distance from basion (Ba) to sella (S)
Ventral angle between midline anterior cranial base (Fc-S) and posterior
cranial base (S-Ba)
Posterior angle between left and right line segments fitted through medialmost
(Md) and lateralmost (Mt) tentorial attachments to petrous ridges
EV
SV
IV
MA
Sum
Sum
Sum
Sum
IRE 1
Cube root of endocranial volume divided by total cranial base length (EV0.33/
TBL)
Cube root of infratentorial volume divided by posterior cranial base length
(IV0.33/PBL)
Sum of endocranial voxels below tentorium cerebelli, divided by sum of voxels
above tentorium (IV/SV)
Relative infratentorial size
RIE
Index of differential encephalisation
IDE
of
of
of
of
voxels within endocranial cavity
voxels within endocranial cavity above tentorium cerebelli
voxels within endocranial cavity below tentorium cerebelli
pixels representing midline plane of endocranial cavity
Ross and Ravosa (1993), the anterior cranial base
length Fc–S includes the cribriform plate. This is
because the ethmoid region is ontogenetically recognized 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 surface 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, infratentorial, and supratentorial volumes were measured 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 interest 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 volumes were calculated by subtracting infratentorial
volume from endocranial volume. All measurements
were taken by the same rater (N.J.) and are available upon request.
Statistical analyses
Measurements for each individual were computed
to the nearest pixel size rounded to tenths of a millimeter. For example, measures for individuals imaged 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 measurements were taken to the nearest degree, area measurements were taken to the nearest square millimeter, 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 endocranial volume over cranial base length. Relative infratentorial 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 repetitions 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 measurements 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
MS between fetuses
F
P2
Anterior cranial base length
Posterior cranial base length
Total cranial base length
Cranial base angle
Interpetrosal angle
Endocranial volume (⫻10⫺3)
Supratentorial volume (⫻10⫺3)
Infratentorial volume (⫻10⫺3)
Midline area (⫻10⫺2)
0.125
0.022
0.105
1.851
24.174
0.608
0.479
0.057
4.061
52.167
20.574
160.467
49.198
150.300
3,265.894
2,669.377
30.148
14,458.750
417.333
924.674
1,531.908
26.579
6.217
5,367.342
5,571.894
524.501
35.606
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.01
⬍0.001
⬍0.001
⬍0.001
⬍0.001
1
2
MS, mean square.
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 repeated measures from one individual fetus are the
same was accepted (P ⬍ 0.01).
The relationships between variables were evaluated by nonparametric methods and without logarithmic transformations. Spearman rank correlation coefficients (rrank) and model II reduced majoraxis (RMA) regression equations were employed to
investigate bivariate trends between variables
(Sokal and Rohlf, 1995). Complex trends were described with second-order polynomial regressions
and, in one case, a two-step RMA. Partial productmoment correlations were used to evaluate the effects of colinearities with age, nee biparietal diameter, 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 volumetric 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 represented by the sample.
Angular measures. Figure 3a plots CBA and IPA
against EGA. This reveals a significant positive correlation 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 petrous 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 notable increases (Fig. 3b). The slope of anterior base
length against EGA was almost twice that of the
posterior base (Table 5). This demonstrates that increases 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 ⫺
14,686x ⫹ 84,264 (R2 ⫽ 0.966). The enlargement
was markedly rapid, and described a 136-times increase 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 supratentorial 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 represent 48- and 158-fold increases of their initial
mean values at 10.1 weeks EGA, respectively. In
order to clarify these trends, volumes were linearized using cube roots, i.e., volume1/3 and plotted
against EGA (Fig. 3c). The slope of cube root supratentorial volume against EGA is over twice that of
cube root infratentorial volume against EGA (Table
5). These plots show that increases of overall endocranial volume are mostly due to increases of supratentorial volume as opposed to infratentorial volume. 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 comparisons 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 differential enlargement in which supratentorial volume 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.
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;
IV, infratentorial volume; SV, supratentorial volume; MA, midline endocranial area; s.d., one standard deviation; wks, weeks.
1
141
134
19
52
129
117
190
227
212
277
520
886
1,121
1,678
1,998
2,456
3,110
4,328
1,663
1,931
1,381
2,637
3,815
2,979
4,055
6,008
5,597
2,733
9,333
18,468
29,071
47,431
66,843
92,440
126,523
192,960
273
382
221
266
272
435
581
433
416
558
1,348
2,580
2,898
4,459
5,913
8,050
10,453
15,050
1,933
2,306
1,558
2,860
4,069
3,303
4,555
6,297
5,748
3,290
10,680
21,048
31,969
56,548
72,757
100,490
136,975
208,010
74.3
77.0
76.0
75.8
79.3
87.7
83.3
81.8
91.5
6.4
9.3
11.2
12.3
14.1
15.5
16.4
18.1
18.7
10–13
13–15
15–17
17–19
19–21
21–23
23–25
25–27
27–29
wks
wks
wks
wks
wks
wks
wks
wks
wks
4
4
4
9
12
3
4
4
2
15–21
24–32
33–37
38.5–44
43–52
52–57
57.5–64
64–70
69.5–77
8.2
12.5
16.4
18.2
21.7
24.1
24.9
26.1
31.0
1.5
1.8
0.8
1.3
2.1
1.8
1.9
1.5
1.4
1.2
1.2
0.7
1.0
1.0
1.0
0.4
0.6
0.8
14.6
21.8
27.5
30.5
35.8
39.6
41.3
44.2
49.6
2.7
3.0
1.5
2.3
3.1
2.8
2.3
2.0
1.9
132.0
133.3
136.5
138.0
134.2
134.0
140.3
139.8
141.5
4.1
3.7
2.2
3.1
2.4
3.0
1.9
1.7
2.1
3.2
5.8
5.9
9.2
8.8
7.1
6.6
3.4
3.7
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
—
N
Age
EV (mm3)
IPA (°)
CBA (°)
TBL (mm)
PBL (mm)
ABL (mm)
BPD (mm)
TABLE 4. Descriptive statistics for fetal measurements at 2-week intervals1
IV (mm3)
SV (mm3)
MA (mm2)
FETAL ENCEPHALIZATION AND BASE ARCHITECTURE
331
General spatial-packing
In order to test the general model of spatial-packing (cube root volume/base length), a comparison of
square root midline endocranial area against cube
root of endocranial volume was made. This demonstrates that increases of the midline area are larger
than the overall increase in brain volume, and that
lateral brain expansion is not predominant (Table 5;
slope ⬎1 at P ⬍ 0.001).
Increases of relative endocranial size across the
sample were examined with a comparison of cube
root endocranial volume against total base length
(Table 5). The slope is significantly greater than 1
(P ⬍ 0.001). This shows that relative endocranial
size increases significantly across the sample. The
general spatial-packing hypothesis predicts that
this increase of relative endocranial size will correspond with a decrease of CBA and an increase of
IPA. However, the opposite relationship was found
for CBA, which shows a small, statistically significant correlation with relative endocranial size that
is positive rather than negative (Fig. 4a, Table 5). As
predicted, increases of interpetrosal angle are positively correlated to increases of relative endocranial
size, though only weakly (Fig. 4b, Table 5). Partial
correlation coefficients for CBA and IPA against relative endocranial size are insignificant, while holding biparietal diameter constant (r ⫽ ⫺0.017, ns; r ⫽
⫺0.064, ns).
Infratentorial spatial-packing
To evaluate variations of relative infratentorial
size across the sample, the cube root of infratentorial volume was compared against posterior base
length. This produces a slope that is significantly
greater than 1 (Table 5) and shows that relative
infratentorial size increased across the sample. The
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,
respectively). Thus, increases of infratentorial volume relative to posterior base length are not accommodated in the posterior cranial fossa by base flexion or coronal reorientation of the petrous bone.
Differential encephalization
Comparisons of supratentorial and infratentorial
volume against EGA, as well as IDE against EGA,
reveal differential enlargement in which the supratentorial volume increases disproportionately (Fig.
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 negative correlations (rrank ⫽ ⫺0.297, P ⬍ 0.05, and
⫺0.481, P ⬍ 0.001, respectively). However, as Figure 5 demonstrates, these trends are clearly biphasic, not linear. In the first phase, there is little variation of the index of differential encephalization
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 encephalization 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 explore these phases pragmatically, these data were
subdivided for each ordinate variable according to
mean abscissa value (Fig. 5). Each of the four subsets, two for both IPA and CBA, reflected their respective phases well and were analyzed separately.
These analyses revealed that CBA is not significantly 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 petrous bones is associated with disproportionate supratentorial 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
IPA ⫻ EGA
TBL ⫻ EGA
ABL ⫻ EGA
PBL ⫻ EGA
EV1/3 ⫻ EGA
SV1/3 ⫻ EGA
IV1/3 ⫻ EGA
IRE ⫻ EGA
MA1/2 ⫻ EV1/3
EV1/3 ⫻ TBL
CBA ⫻ IRE
IPA ⫻ IRE
IV1/3 ⫻ PBL
IPA ⫻ IDE, first phase
0.431
0.504
0.976
0.975
0.960
0.982
0.983
0.965
0.813
0.987
0.987
0.425
0.356
0.952
⫺0.349
**
***
***
***
***
***
***
***
***
***
***
**
*
***
*
0.98
1.60
2.10
1.33
0.78
2.65
2.62
0.98
0.02
1.10
1.26
60.79
99.43
1.25
⫺557.51
0.72 ⬎ 1.24
1.18 ⬎ 2.02
1.96 ⬎ 2.37
1.23 ⬎ 1.43
0.72 ⬎ 0.84
2.53 ⬎ 2.78
2.50 ⬎ 2.75
0.91 ⬎ 1.04
0.01 ⬎ 0.02
1.06 ⬎ 1.14
1.20 ⬎ 1.33
43.80 ⬎ 77.78
71.57 ⬎ 127.28
1.16 ⬎ 1.34
⫺749.64 ⬎ 365.39
117.49
48.75
⫺7.03
⫺5.61
⫺1.72
⫺15.15
⫺15.69
⫺2.73
0.75
⫺0.99
⫺6.23
71.63
⫺26.26
⫺0.60
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
Insight into the way morphological differences between closely related species emerge during ontogenetic 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 Ravosa, 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 interaction 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 basicranial 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
of soft tissues as well as cartilage and bone. The
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 adulthood (see Zuckerman, 1955; Schultz, 1955). The aggregate of findings suggests that cranial base angulation 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., Kvinnsland, 1971; Dimitriadis et al., 1995), and postnatal
flexion (e.g., Lieberman and McCarthy, 1999). Interestingly, 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 retention of the fetal condition. This suggests that temporally 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 nemestrina remains essentially unchanged during most of
the fetal period (Sirianni and Newell-Morris, 1980)
334
N. JEFFERY AND F. SPOOR
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 relation 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 regression line fitting is given (diagonal line).
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 human 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 primates.
A possible explanation for such precocity may be
found in comparisons between the order in which
the basicranial synchondroses fuse in modern humans and macaques. The synchondroses are major
centers for growth of the midline primate basicranium 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,
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 reorient coronally by some 15° over the period investigated. 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 between 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 plateau, 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 reorientation 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 authors assumed that its position remains stable relative 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 intercept, 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 semicircular canal, increases by some 30°, or 15° relative
to the midline, from 10 weeks until birth. This demonstrates coronal as opposed to sagittal reorientation 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 Newell-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 anteroposterior extension, the fronto-ethmoidal suture, sphenoethmoidal synchondrosis, and midsphenoidal synchondrosis. 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 posterior 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 encephalization. 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 comparisons of absolute volumes are of little value (see Jeffery, 1999). Notwithstanding this, the findings of
Jenkins (1921) and Koop et al. (1986) also demonstrate that the rate of supratentorial expansion
exceeds that of the infratentorial brain. This is commensurate with the process of differential encephalization 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 particular, 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 encephalization noted in the present study. GuihardCosta 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 reported in this study for late fetal life. This confirms
the suggestion that differential infratentorial, as opposed to supratentorial, enlargement occurs at some
point during the intervening period of the late third
fetal trimester to adulthood, since infratentorial volume must increase relative to supratentorial volume
for there to be an increase of IDE (infra/supra volume). 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 endocranial 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 during 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 endocranial 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 processes afford this likeness, as appears the case with
regard to cranial base angle.
Hypotheses
General spatial-packing. This hypothesis suggests that increases of brain size (volume) relative to
length of the midline cranial base create a spatialpacking problem that drives cranial base flexion and
coronal reorientation of the petrous bones. The findings 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 predicted outcome. The fetal cranial base retroflexed
rather than flexed in relation to increases of relative
brain size. This raised the suspicion that the individual trends of these variables with age, nee head
size, were superimposed in the computation of the
simple rank correlation, which showed an association between relative encephalization and retroflexion. 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 appear to corroborate the idea that spatial packing is
the driving force behind petrous reorientation. However, 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 pertinent to question the robusticity of the rank correlation here. This misgiving is justified. The partial
correlation shows that interpetrosal angle is not
associated with relative endocranial size while controlling for biparietal diameter. Thus, the partial
correlation coefficients indicate that cranial base angulation 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 hypothesis 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 infratentorial 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 infratentorial spatial-packing hypothesis is not corroborated 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 undergoes a relative increase in rate of enlargement during a later period of development than that investigated here. This latent and more pronounced
cerebellar expansion may create a spatial-packing
problem that affects a change of basicranial morphology, as per the hypothesis. More work is needed
in this area to evaluate the temporal scope of mechanisms 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 decreases 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 corroborate the hypothesis. However, the hypothesis was
seemingly corroborated by the small correlation observed 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 compounded in the analysis. This was confirmed by the
partial correlations while holding for biparietal diameter. 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 independent of increases of absolute and relative endocranial 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 observed 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 remain 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 human fetal material from the same period. Any extrapolation 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 undertaken. In addition, the aims of the present study
were strictly focused on the effects of brain enlargement, in its various forms. Other potential mechanistic 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 explanations for changes of the human fetal cranial
base, and their permutations, are exhausted.
The fetal basicranium appears to remain unperturbed by considerable changes in both brain size
and shape, suggesting that the pattern of variation
taken by the fetal cranial base is partially a consequence of variables other than structural demands.
Notwithstanding those mechanisms not yet tested,
the demonstration of independence implies that fetal 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 activity, and tissue morphogenesis, to architectural variations). 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 enlargement 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, similar genotypes are gradually overlaid with the structural demands of growth during ontogeny to produce
different phenotypes.
Some insight can be gained by exploring the disparity between results from the interspecific studies
cited and the ontogenetic findings reported here. In
nearly every case, the findings of this study contradict 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 correlation between differential encephalization (telencephalon/brain-stem) and cranial base angle is
insignificant. The authors indicated that the unadjusted 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 adjustment. 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 Ravosa (1993), it is still robust enough to support the
spatial-packing hypothesis. Such seemingly irreconcilable differences point to a more fundamental incongruity, whereby ontogenetic and interspecific
studies produce results pertaining to different
processes (e.g., Zuckerman, 1955; Sirianni and
Swindler, 1979).
Ontogeny and phylogeny are clearly interconnected, but to what extent and is this link constant?
Clearly, the interchange occurs at the adult intraspecific 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, ontogeny is the stochastic accumulation of somatic variations against the backdrop of decreasing inherited
control of morphology. The core of this idea is wellestablished 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 postnatal basicranium. Thus, the period of ontogeny examined 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 proposed that inconsistency results from generally
tighter regulation of primate fetal development compared with the adult primate form. In other words,
the adult interspecific studies, by comparison, highlight biomechanistic-driven changes across taxa,
while the results presented here indicate that intrinsic controls are not yet sufficiently relaxed in the
early fetus to allow for such marked relationships.
This predicts that intraspecific studies of fetal development 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 patterns in the relaxation of control exist between species, thereby contributing to interspecific differences
later in life, and that modern humans exhibit a
comparatively extended period of tighter morphological control. This predicts that developmental studies across primate taxa will demonstrate that certain species group trends are consistent with adult
interspecific trends owing to the comparatively earlier relaxation of control, perhaps even at the fetal
stage of life.
Despite such insights, a number of questions remain unanswered. In particular, the essential problem remains of distinguishing adaptations incorporated 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 sufficient phenotype, and from morphologies produced
by the mechanistic knock-on effects of adaptive
change. Only by combining ontogenetic and interspecific 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 condition of the modern human skull.
CONCLUSIONS
Data were collected from a sample of human fetuses ranging from 10 –29 weeks of gestation in order 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 coronally 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 components superoanterior to the tentorium cerebelli
increase at rates exceeding those of inferoposterior components.
4) Lastly and most importantly, the findings of this
study show that cranial base angulation and petrous reorientation are associated with increases
of vault size, which represent age, rather than
increases of relative brain sizes. Given the notable increases of relative sizes observed, this suggests that fetal basicranial morphology is regulated more intrinsically than proposed by the
hypotheses tested, though many other mechanistic 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 anonymous referees for their comments and suggestions.
LITERATURE CITED
Anagnostopoulou S, Karamaliki DD, Spyropoulos MN. 1988. Observations 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. Gegenbauers 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. Embryological considerations. Trans R Soc Can 18:115–123.
Cameron J. 1930. The human and comparative anatomy of Cameron’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. dissertation, University of Paris.
Dabelow A. 1931. Über Korrelationenin der phylogenetischen
Entwicklung der Schädelform II. Die Beziehungen zwischen
Gehirn und Schädelbasisform bei den Mammalien. Gegenbauers Morphol Jahrb 67:84 –133.
Dean MC. 1988. Growth processes in the cranial base of hominoids 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 Anthropol 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 palatal development in human embryos and fetuses. Am J Anat
167:495–522.
Diewert VM. 1985. Development of human craniofacial morphology during the late embryonic and early fetal periods. Am J
Orthod 88:64 –76.
Dimitriadis AS, Haritanti-Kouridou A, Antoniadis K, Ekononmou 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. Cambridge: Cambridge University Press.
Enlow DH. 1976. The prenatal and postnatal growth of the human basicranium. In: Bosma JF, editor. Symposium on development 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 trimester 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, Spraggins TA, Starewicz PM. 1989. Magnetic resonance imaging
based brain morphometry: development and application to normal 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 restatement of the biogenetic law. Zool J Linn 35:81–101.
Giles WB, Philips CL, Joondeph DR. 1981. Growth in the basicranial synchondroses of the adolescent Macaca mulatta. Anat
Rec 199:259 –266.
Gould SJ. 1977. Ontogeny and phylogeny. London: Harvard University Press.
Gould SJ, Lewontin RC. 1979. The spandrels of San Marco and
the Panglossian paradigm: a critque of the adaptationist programme. Proc R Soc Lond [Biol] 205:581–598.
Guihard-Costa AM, Larroche JC. 1990. Differential growth between 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 evolutionary biology. Oxford: Oxford University Press.
Herring SW. 1993. Epigenetic and functional influences on skull
growth. In: Hanken J, Hall BK, editors. The skull: development. Chicago: Chicago University Press. p 153–207.
Hofer HO. 1969. On the evolution of the craniocerebral topography 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: methods 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. Volumetric 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 development of cranial base in normal Korean fetuses. Anat Rec
246:524 –534.
Leutenegger W. 1987. Neonatal brain size and neurocranial dimensions in Pliocene hominids: implications for obstetrics. J
Hum Evol 16:291–296.
Levihn WC. 1967. A cephalometric roentgenographic cross-sectional 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 synchondrosis 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. Tandlaegebladet 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 Conference 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 juveniles. Folia Primatol (Basel) 14:84 –94.
Moss ML. 1958. The pathogenesis of artificial cranial deformation. 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 craniofacial 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 hominids. 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 craniofacial growth in old world monkeys and apes. Am J Phys Anthropol 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. Development, 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 radiology 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 flexion and an evaluation of registration planes used in paleoanthropology. 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 vertebrate 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. Berlin: Gesichissiblung und Gehirnbru.
Zuckerman S. 1955. Age changes in the basicranial axis of the
human skull. Am J Phys Anthropol 13:521–539.
Документ
Категория
Без категории
Просмотров
0
Размер файла
296 Кб
Теги
base, cranial, prenatal, size, brain, perspectives, human
1/--страниц
Пожаловаться на содержимое документа