Brain Imaging and Behavior (2009) 3:5163

DOI 10.1007/s11682-008-9048-x

Age-Related Changes in the Anatomy of Language Regions

in Autism Spectrum Disorder
Tracey A. Knaus & Andrew M. Silver &
Kelli C. Dominick & Melanee D. Schuring &
Nancy Shaffer & Kristen A. Lindgren &
Robert M. Joseph & Helen Tager-Flusberg

Received: 15 December 2007 / Accepted: 17 September 2008 / Published online: 4 October 2008
# Springer Science + Business Media, LLC 2008

Abstract Impairments in language and communication

are core features of autism spectrum disorder (ASD). The
anatomy of critical language areas has been studied in
ASD with inconsistent findings. We used MRI to
measure gray matter volume and asymmetry of Heschls
gyrus, planum temporale, pars triangularis, and pars
opercularis in 40 children and adolescents with ASD
and 40 typically developing individuals, each divided into
younger (711 years) and older (1219 years) cohorts. The
older group had larger left planum temporale volume and
stronger leftward asymmetry than the younger group,
regardless of diagnosis. The pars triangularis and opercularis
together were larger in ASD than controls. Correlations
between frontal language areas with language and symptom
severity scores were significant in younger ASD children.
Results suggest similar developmental changes in planum
temporale anatomy in both groups, but group differences in
pars triangularis and opercularis that may be related to
language abilities and autism symptom severity.
Keywords Autism . Language . MRI . Asymmetry .
Development

T. A. Knaus (*) : A. M. Silver : K. C. Dominick :

M. D. Schuring : N. Shaffer : K. A. Lindgren : R. M. Joseph :
H. Tager-Flusberg
Department of Anatomy and Neurobiology,
School of Medicine, Boston University,
715 Albany Street L-814,
Boston, MA 02118, USA
e-mail: tknaus@bu.edu

Introduction
Cortical language regions
Perisylvian regions critical for language functions include
posterior regions, which consist of Heschls gyrus and the
posterior superior temporal gyrus, including the planum
temporale, and frontal areas, which are comprised of the
pars triangularis and pars opercularis. The anatomy of these
regions has been the focus of many studies in normal
healthy adults. Consistent asymmetry patterns of Heschls
gyrus, however, have not been established in normal
subjects. Leftward planum temporale asymmetry has been
found repeatedly and is one of the most consistent
asymmetries found in the human cortex (for review,
Shapleske et al. 1999). Less consistent asymmetry has been
found for the pars triangularis and pars opercularis, with
leftward asymmetry of these areas being found in some
studies (Foundas et al. 1995, 1996, 1998, 2001; Gauger et al.
1997), but not in others (Knaus et al. 2006, 2007; Tomaiuolo
et al. 1999). The pars triangularis and pars opercularis
together make up Brocas area and when measured together,
again some studies have demonstrated leftward asymmetry
(Albanese et al. 1989; Falzi et al. 1982), while others have
not (Robichon et al. 2000; Wada et al. 1975).
Although anatomical asymmetries of some of these
language areas have been found in infant and fetal brains
(Chi et al. 1977; Wada et al. 1975; Witelson and Pallie
1973), studies have indicated that the anatomy and
asymmetry of these critical language regions continue to
develop throughout childhood. Wada et al. (1975) found
greater degree of planum temporale asymmetry in adult
compared to infant brains and suggested that left planum
size increases with age. Cross-sectional and longitudinal
studies have indicated increases in gray matter density of

52

left perisylvian regions in children and adolescents up to

age 30 years (Sowell et al. 2001, 2003, 2004). Blanton et al.
(2001) demonstrated increases with age in complexity of
the inferior frontal region, length of the left inferior frontal
sulcus, and asymmetry of inferior frontal and temporal
regions in children. Similarly, Sowell et al. (2002) found
increased asymmetry of the Sylvian fissure in adolescents
and adults relative to children. Another study showed that
the temporal lobe was the last to mature, with the posterior
superior temporal gyrus maturing last within the temporal
lobe (Gogtay et al. 2004). There is some evidence that
these structural asymmetries may be related to language
functions (Foundas et al. 1994, 1996; Tzourio et al. 1998),
providing support for a close relationship between brain
and behavioral changes related to language development.
Cortical language regions in ASD
Pervasive developmental disorders are characterized by
severe and pervasive impairments in reciprocal social
interaction, communication and the presences of stereotyped behavior, interests and activities (American Psychiatric Association 1994). Nowadays, the term autism
spectrum disorder (ASD) is used as an umbrella term to
cover three of these disorders, which appear to share a
common etiology and developmental profile: autism,
pervasive developmental disorder-not otherwise specified
(PDD-NOS), and Asperger syndrome (Volkmar and Lord
2007). We use the term ASD throughout the paper to
acknowledge the range of participants used in prior studies
as well as in our sample. Individuals with ASD demonstrate
a wide range of language abilities, with some individuals
never developing functional language and others having
vocabulary, articulation, and grammar skills in the normal
range or above (Kjelgaard and Tager-Flusberg 2001). By
definition, Asperger syndrome is characterized by normal
range language skills, however both autism and PDD-NOS
include individuals with normal, impaired, or absent
language. Across the spectrum, children and adults with
ASD have deficits in pragmatic and discourse aspects of
language (for review, Tager-Flusberg et al. 2005).
Several studies have investigated the neurobiological
substrates of language in ASD. Posterior language regions
have been studied in ASD, but results have been inconsistent. Rojas et al. (2002) used manual tracings to measure
gray matter volume and asymmetry. They found no differences in Heschls gyrus and decreased left planum
temporale volume in adults with ASD compared to normal
controls, resulting in stronger leftward planum asymmetry
in controls. They later replicated this finding in a sample of
children (Rojas et al. 2005). McAlonan et al. (2005), using
voxel-based morphometry, had similar results, with decreased gray matter volume of left superior temporal gyrus

Brain Imaging and Behavior (2009) 3:5163

in children with ASD compared to normal controls.

However, other studies using semi-automated methods
and focusing on asymmetry, have found the opposite, with
stronger leftward planum temporale asymmetry in boys
with ASD than in typically developing boys (de Foss et al.
2004; Herbert et al., 2002, 2005). de Foss et al. (2004)
compared ASD children with and without language
impairment to non-ASD children with and without language impairment. They found leftward planum asymmetry
in both language impaired groups, but not in the language
normal groups. Still other results have been reported;
Boddaert et al. (2004) found decreased gray matter
bilaterally in the ASD group compared to controls in the
superior temporal gyrus, with voxel-based morphometry
methods, while Bigler et al. (2003) utilizing semi-automated
volume measurements found no group differences in
superior temporal gyrus volume or asymmetry.
Anterior language areas have also been measured in
individuals with ASD, again with inconsistent findings
across studies. One voxel-based morphometry study found
decreased left gray matter volume of the pars triangularis in
adults with ASD compared to normal controls (Abell et al.
1999). Utilizing semi-automated measurements, Herbert et
al. (2005), reported similar results, with decreased leftward
pars triangularis asymmetry and increased rightward pars
opercularis asymmetry in boys with ASD compared to
typically developing boys. Other studies examining asymmetry, however, have found rightward asymmetry of the
pars triangularis in boys on the autism spectrum and
leftward pars triangularis asymmetry in controls (de Foss
et al. 2004; Herbert et al. 2002). de Foss et al. (2004)
found that boys with specific language impairment and
boys with ASD with language impairment had rightward
pars triangularis and opercularis asymmetry, while typically
developing boys and boys with ASD without language
impairment had leftward pars triangularis and opercularis
asymmetry. In contrast, McAlonan et al. (2005) found
smaller right volume of the pars triangularis in ASD
children compared to normal controls, using voxel-based
morphometry. For review of these studies, see Table 1.
Brain development in ASD
Developmental changes in cortical language areas in ASD
have not been extensively studied, but several studies
examining total brain size or lobar size have demonstrated a
different developmental trajectory of brain growth in ASD
relative to typically developing individuals (for reviews see,
Courchesne 2004; Courchesne and Pierce 2005; McCaffery
and Deutsh 2005; Redcay and Courchesne 2005). Some
cross-sectional studies have found larger brain size in
young children with ASD (24 year olds) relative to
typically developing children, with no differences in older

Manual

Voxel-based morphometry

Semi-automated

Semi-automated

Voxel-based morphometry

Semi-automated

Manual

Semi-automated

HG and PT volume and asymmetry

Volume

Asymmetry

Volume and asymmetry

Volume

Volume and asymmetry

HG and PT volume and asymmetry

Asymmetry

Volume

Measurement

Increased L>R PT in ASD

R>L PTR in ASD, L>R in TD
No differences in HG
Decreased L PT & decreased L>R PT in ASD
No differences in STG

Increased L>R PT in ASD

Decreased L>R PTR in ASD
Increased R>L POP in ASD
Decreased L STG in ASD
Decreased R PTR in ASD
No differences in HG
Decreased L PT & decreased L>R PT in ASD

R>L PTR & POP in LI groups, L>R in LN groups

L>R PT in LI groups, not in LN groups

Decreased bilateral STG in ASD

Decreased L PTR in ASD

Findings

TD = typically developing, LI = language impaired, LN = language normal, SLI = specific language impaired, DLD = developmental language delayed, RH = right-handed, L = left,
R = right, PTR = pars triangularis, HG = Heschls gyrus, PT = planum temporale, POP = pars opercularis

Rojas et al. 2005

McAlonan et al. 2005

Herbert et al. 2005

de Foss et al. 2004

Boddaert et al. 2004

Bigler et al. 2003

Rojas et al. 2002

Herbert et al. 2002

Voxel-based morphometry

Abell et al. 1999

15 ASD adults, 22-35 years

15 TD adults, 22-28 years
16 ASD boys, 7-11 years
15 TD boys, 7-11 years
15 adults with ASD, 19-47 years
15 TD, 17-47 years
38 ASD boys, 7-19 years
27 TD boys, 7-22
17 boys with reading disorder, 7-18 years
21 ASD children, 7-15 years
12 TD children, 7-15 years
16 ASD, LI boys, 6-13 years
6 ASD, LN boys, 6-13 years
9 SLI boys, 6-13 years
11 TD boys, 6-13 years
16 ASD children, 5-13 years
15 DLD children, 5-13 years
15 TD children, 5-13 years
17 RH, ASD children, 8-14 years
17 RH, TD children, 8-14 years
12 ASD boys, 5-16 years
12 TD boys, 5-16 years

Method

Participants

Study

Table 1 Review of previous studies of anatomical language regions in ASD

Brain Imaging and Behavior (2009) 3:5163

53

54

children (Carper et al. 2002; Courchesne et al. 2001). This

has led to the hypothesis that in ASD, rapid brain growth
occurs during the first 12 years of life, which is then
followed by slow or discontinued growth. Providing further
support for this idea are studies examining brain volume in
toddlers, which have demonstrated larger volume in ASD
compared to typically developing toddlers (Hazlett et al.
2005; Sparks et al. 2002) and studies of adolescents and
adults which have not found differences in brain size
(Herbert et al. 2003; Rojas et al. 2002). Aylward et al.
(2002), however, found enlarged brain size in ASD children
relative to typically developing children, 812 years old,
with no differences in individuals over 12 years old. In
addition, some studies of adolescents and adults have
shown larger brain volume in ASD compared to normal
controls (Hardan et al. 2001; Piven et al. 1995, 1996).
These studies have demonstrated different developmental
trajectories in brain growth in individuals with ASD,
however the exact developmental trajectory in ASD
remains unresolved. One cross-sectional study has investigated developmental patterns in superior temporal gyrus,
however they did not find any differences between ASD
and controls, regardless of age (Bigler et al. 2003).
Current study
The purpose of this study was to examine age-related
changes in gray matter volume and asymmetry of critical
language areas, including Heschls gyrus, the planum
temporale, the pars triangularis, and the pars opercularis,
in a large sample of children and adolescents with ASD and
typically developing children and adolescents. In typically
developing individuals, studies have demonstrated developmental changes in gray matter and asymmetry of some of
these language regions and studies of ASD have indicated
differences in the developmental trajectory of brain growth.
No previous studies, however, have examined developmental changes in the anatomy of these language areas in
individuals with ASD. Manual measurements were used
because of their increased sensitivity to subtle group
differences. There is great individual variability in the
cortical anatomy of language regions and manual measurements are better able to take into account these individual
differences, by maintaining scans in native space, instead of
warping them into a standard space, as is usually necessary
for automated or semi-automated methods. Based on
previous studies of developmental changes in normal
controls (Blanton et al. 2001; Sowell et al. 2001, 2002,
2004), we predicted that in the typically developing group,
older children would have larger gray matter volume of left
perisylvian language regions and increased leftward asymmetry relative to younger children. Anatomical differences
of cortical language areas in individuals with ASD

Brain Imaging and Behavior (2009) 3:5163

compared to normal controls have been demonstrated, but

there are not prior studies that have examined age-related
changes in volume or asymmetry of these regions in ASD.
However, since ASD is a developmental disorder with
studies of brain growth indicating a different developmental
pattern, we expected that the ASD group would not show
the same differences in volume and asymmetry between
older and younger children as the typically developing
individuals.

Materials and methods

Participants
Participants were 40 children and adolescents with ASD
(autism or PDD-NOS), ages 719 years (mean = 12.22, SD =
3.30) and 40 typically developing children and adolescents,
ages 719 years (mean = 12.24, SD = 3.25). Participants in
each group were divided into a younger group (n = 20),
ages 711 years and an older group (n=20), ages 1219 years.
12 years was used as the division between the older and
younger groups as this roughly corresponds to the
division between pre-puberty and puberty and is similar
to cutoffs to classify children and adolescents used in
previous studies (Blanton et al. 2001; Sowell et al. 2002;
Aylward et al. 2002). All participants spoke English as their
first language. There were four females in the ASD group
(one younger and three older) and 4 in the control group
(two younger and two older). Based on writing hand, there
were eight left-handers with ASD (four younger and four
older) and three left-handed controls (two younger and one
older). A modified version of the Dean handedness
inventory (Piro 1998) was also administered to all but four
participants. The modified Dean handedness consists of 12
unimanual tasks and scores range from 24, indicating
complete left-handedness, to +24, indicating complete
right-handedness. Table 2 presents the descriptive statistics
for all participants. An analysis of variance (ANOVA) with
the factors diagnosis (ASD, typically developing) and age
(young, old) revealed no main or interaction effects on
handedness. However, since there are some indications that
language laterality may be different in left- and righthanders, with structural studies of these language regions
indicating differences between handedness groups (Foundas
et al. 1995; Habib 1989; Jncke et al. 1994; Steinmetz et al.
1991), we also ran all of our analyses with the left-handers
removed.
The Kaufman Brief Intelligence Test (KBIT-II; Kaufman
and Kaufman 2004) was administered to assess IQ, except
for two participants (one older ASD, one older control) who
were administered the Differential Ability Scales (DAS;
Elliot 1990) and the Wechsler Abbreviated Scale of

Brain Imaging and Behavior (2009) 3:5163

55

Table 2 Means and standard deviations of demographic information for each group
ASD

Age
Handedness
K-BIT VIQ
K-BIT NVIQ
K-BIT FSIQ
CELF receptive
CELF expressive
CELF total
ADOS Communication
ADOS social
ADOS total

Controls

Younger

Older

9.50
10.58
100.45
109.25
105.85
100.16
97.42
98.79
3.55
9.80
13.35

14.95
11.22
102.74
105.05
104.79
96.80
90.35
92.95
3.10
8.65
11.75

(1.32)
(15.08)
(20.35)
(13.88)
(17.18)
(16.55)
(16.19)
(16.69)
(1.79)
(2.33)
(3.92)

Intelligence (WASI; Wechsler 1999), respectively. The

Clinical Evaluation of Language Fundamentals (CELF,
3rd ed; Semel et al. 1995) was administered to all but two
participants (one younger ASD, one younger control) to
assess language abilities. When left-handers were removed
there was only one younger control who did not have a
CELF. Four subtests were administered, which varied based
on the age of the subject. For participants 78 years old,
Concepts and Directions, Sentence Structure (receptive
language), Recalling Sentences, and Word Structure
(expressive language) subtests were given. For participants 9 years and older, Concepts and Directions, Word
Classes (receptive language), Formulated Sentences, and
Recalling Sentences (expressive language) subtests were
administered. Together, the receptive and expressive
subtest scores yielded a total language score.
For ASD participants, diagnoses were based on DSM-IV
criteria (American Psychiatric Association 1994) using the
Autism Diagnostic Interview-Revised (ADI-R; Rutter et al.
2003) and the Autism Diagnostic Observation Schedule,
Module 3 or 4 (ADOS; Lord et al. 1999). In addition, an
expert clinician (RMJ) confirmed that all individuals met
criteria for ASD. Based on ADI-R scores, the majority of
participants met criteria for a diagnosis of autism. Among
the younger group, 18 met criteria for autism and 2 for
PDD-NOS (one child missed by one point on the
communication algorithm score and one missed by one
point on the repetitive behavior algorithm score). Among
the older group 17 met criteria for autism and 3 for PDDNOS (each missed by one point on the repetitive behavior
algorithm score). Individuals with frank neurological
damage, with a known genetic disorder, who were born
prematurely (less than 35 weeks), or who had had
seizures within the last 3 years were excluded from the
study. Typically developing individuals also had no
history or current diagnosis of developmental, learning,
psychiatric, or neurologic disorders.

(2.23)
(13.75)
(21.83)
(13.33)
(17.27)
(21.12)
(19.35)
(21.17)
(1.68)
(3.08)
(4.39)

Younger

Older

9.54 (1.38)
15.15 (9.01)
117.50 (13.03)
113.90 (8.81)
118.40 (9.93)
118.11 (13.83)
115.16 (12.65)
118.37 (11.42)
-

14.93 (2.13)
17.42 (9.08)
119.53 (14.53)
109.95 (11.06)
117.21 (12.12)
113.15 (10.66)
107.60 (11.21)
111.45 (10.05)
-

Participants 18 years and older were informed of the

procedures and gave written consent prior to participation
in the study. For participants under 18 years old, parents
and participants were informed of the procedures and
parents gave written consent prior to the childs participation in the study. Children 12 years and older also
provided written assent prior to participation. All data in
this manuscript were collected in compliance with the
Boston University School of Medicine Institutional Review Board.
MRI acquisition
All participants were trained in a mock scanner prior to the
actual MR scanning. Volumetric MR images were acquired
on a Philips 3 T Intera scanner. T1-weighted images were
obtained as a series of 160, 1 mm gapless sagittal images.
TFE was used, with technical factors of: TR = 9.9 s, TE =
4.6, 256256 pixel matrix, 24 cm field of view, and eight
degree flip angle. Data sets were rotated into alignment
in the sagittal, axial, and coronal planes in order to
eliminate any head rotation and MRI scans were
maintained in real space. Each MRI scan series was
assigned a blind number to assure subject confidentiality
and to ensure that all volume measurements were
performed blind to group and subject.
MRI measurements
Total hemisphere volume Total hemisphere volume was
measured with the MEASURE program (Barta et al. 1997).
The BET tool in FSL (Smith 2002) was first used to
remove as much skull as possible, without removing any
brain. The contrast was then set and the MEASURE
program automatically outlined the brain. The midline slice
was identified and all outlining on this image was removed.
This slice was not included in the measure of left or right

56

hemisphere volume. The outlining was then manually

edited in each slice to remove any remaining non-brain
regions from the outline. This measurement included gray
and white matter and the thalamus, but excluded the
cerebellum and brainstem. For inter-rater reliability, a
subset of five brains (ten hemispheres) was measured by
four investigators. An intra-class correlation (ICC) was
calculated between the investigators volume measurements
across both hemispheres of the five brains. The ICC for
total brain volume was .97.
Regional volumes For each region of interest, the MEASURE program (Barta et al. 1997) was used to trace the
gray matter, using a mouse-driven cursor, while viewing
sagittal, coronal, and axial planes simultaneously. Boundaries were marked and saved in all three planes, ensuring
the accurate identification of the boundaries of each region,
and enabling the investigator to measure the full gray
matter volume using a three-dimensional approach. A
region was highlighted first in one of the three planes and
then viewed and corrected in the other planes. The
MEASURE program calculated the volume of each region
in cm 3, based on the slice thickness and the area
highlighted on each image.
Inter-rater reliability has previously been established for
this methodology for measuring each of these regions. For
this, ICCs were calculated between the first authors, who
completed all the measurements for this study, and a second
raters measurements of each region, across both hemispheres of five brains (Knaus et al. 2006). Intra-rater
reliability was re-established. For this, a subset of five
brains (ten hemispheres) was re-measured and ICCs were
calculated between the first measurements and the second
measurements of each region, across both hemispheres of
the five brains. ICC data are provided for each region in the
following sections.
Heschls gyrus Heschls is located within the Sylvian fossa,
just anterior to the planum temporale, and has a characteristic configuration in the sagittal plane, which appears most
commonly as a mushroom shape with variation including
a heart-shape or a double gyrus. The sagittal and coronal
planes were primarily used for measuring this region. The
coronal plane was used to define the anterior and posterior
boundaries. The anterior boundary was defined as the most
anterior image in which Heschls gyrus was clearly visible,
with a small amount of white matter lateral to the gyrus. In
the coronal slice immediately anterior to this image, the
ledge of white matter lateral to Heschls was not present
because Heschls gyrus had merged with it. The posterior
boundary was defined by Heschls sulcus, as the most
posterior coronal slice, which had a protrusion of gray
matter, at the junction of Heschls gyrus with the insula.

Brain Imaging and Behavior (2009) 3:5163

Heschls is often bifurcated, at least partially, by an

intermediate sulcus. If Heschls fully split into two separate
gyri in the sagittal plane, only the most anterior gyrus (first
Heschls gyrus) was included in the measurement. When
Heschls completely split in the coronal plane, only the
most medial gyrus, which corresponds to the most anterior
(first) Heschls gyrus, was included in the measure.
However, when Heschls was only partially bifurcated, in
the sagittal or coronal plane, creating a heart-shaped gyrus,
the entire gyrus was included in the Heschls gyrus
measurement. The gray matter of Heschls gyrus was
measured in the coronal plane and then checked and
corrected in the sagittal plane. For inter-rater reliability,
the ICC was .84 and for intra-rater, the ICC was .97.
Planum temporale The planum temporale is located within
the Sylvian fossa, posterior to Heschls gyrus and lies on
the superior surface of the posterior superior temporal
gyrus. The anterior boundary was defined as Heschls
sulcus, and when present the second Heschls gyrus was
included in the planum measure. In the coronal plane, this
image was the same one used to define the anterior
boundary for Heschls gyrus, where Heschls was fully
visible and there was a small amount of white matter lateral
to it. If Heschls was completely bifurcated by an
intermediate sulcus, the posterior portion of the gyrus was
included in the planum measure. The posterior boundary
was defined in the sagittal plane, as the point where the
horizontal ramus of the Sylvian fissure turns upward into
the posterior ascending ramus, so neither the posterior
ascending ramus nor posterior descending ramus was
included in the planum temporale measurement. In cases
where the Sylvian fissure gently sloped upward, the knifecut method (Witelson and Kigar 1992) was utilized. The
horizontal ramus of the Sylvian fissure was followed to the
point where it intersected the vertical wall. When this point
changed from medial to lateral, more lateral images were
used for determining this boundary. If there was no
posterior ascending ramus, however, the end of the Sylvian
fissure was used as the posterior boundary. This boundary
was defined in the coronal plane as the most posterior slice
where the Sylvian fissure was clearly visible, before it
became intermixed with white matter. However, if the
Sylvian fissure extended into parietal regions, the posterior
boundary was defined as the image just anterior to the one
where the intraparietal sulcus appeared to encircle the
Sylvian fissure. This boundary appeared as small amounts
of gray matter visible through the white matter around
the Sylvian fissure. The planum temporale was measured
in the coronal plane, with Heschls sulcus, when present,
as the medial boundary. Laterally, the boundary for the
planum was the edge of the Sylvian fissure, not
including the lateral wall of the posterior superior

Brain Imaging and Behavior (2009) 3:5163

temporal gyrus. The planum temporale measurement was

then checked for accuracy in the sagittal plane. For interrater reliability, the ICC for this structure was .91 and for
intra-rater reliability, it was .95.
Pars triangularis The pars triangularis is located in the
anterior inferior frontal gyrus and is a triangular shaped
region, which extends from the Sylvian fissure. The sagittal
plane was predominantly used to measure this region
because it provides the clearest view of the pars triangularis. Defined in the sagittal plane, the anterior boundary
was the anterior horizontal ramus and the posterior
boundary was the anterior ascending ramus. Thus, the
posterior/superior bank of the anterior horizontal ramus and
the anterior/superior bank of the anterior ascending ramus
were included in the pars triangularis measurement. When
extra sulci, internal notches, occurred between these two
rami, the banks of these sulci were included in the
measurement. The lateral boundary was defined as the
most lateral sagittal image, prior to the rami being cut off,
so that surface gray matter was not included. At times, only
one of the sulci, either the anterior horizontal ramus or the
anterior ascending ramus, was cut off, while the full extent
of the other sulcus remained, in which case the bank of the
remaining sulcus was still measured on images as far lateral
as possible, until the sulcus was cut off. The medial
boundary was defined as the most medial sagittal image
in which the insula was clearly defined, prior to the white
matter intruding. At this boundary, the insula appeared with
clearly defined strips of white matter. The superior
boundary was the inferior frontal sulcus. The inter-rater
reliability ICC for this structure was .83. For intra-rater
reliability, the ICC was .99.
Pars opercularis The pars opercularis is also located in the
inferior frontal gyrus, posterior to the pars triangularis. It is
generally a U-shaped area, which extends from the Sylvian
fissure. The sagittal plane provides the best view of the pars
opercularis, so this plane of section was primarily used to
measure this region. In the sagittal plane, the anterior
boundary of the pars opercularis was defined as the anterior
ascending ramus and the posterior boundary was defined as
the precentral sulcus. Thus, the posterior/inferior bank of
the anterior ascending ramus and the anterior bank of the
precentral sulcus, up to the inferior frontal sulcus, were
included in the measurement. The inferior frontal sulcus,
also defined in the sagittal plane, was used as the superior
boundary. While on some images the precentral sulcus
connects with the Sylvian fissure, it was not continuous
with the Sylvian fissure throughout the full extent of the
pars opercularis. In addition, in some brains, the precentral
sulcus never fully connected with the Sylvian fissure. When
the precentral sulcus did not connect with the Sylvian

57

fissure, the pars opercularis was measured to the point

where the Sylvian fissure would have connected with the
precentral sulcus and the anterior bank of the precentral
sulcus was measured from the inferior frontal sulcus, down
until it disappeared. The lateral boundary was defined on
sagittal images as the most lateral image prior to the rami
being cut off, so that surface gray matter was not included.
At times, only one of the sulci, the anterior ascending
ramus or the precentral sulcus was cut off, while the other
one remained, in which case the bank of the remaining
sulcus was still measured on images as far lateral as
possible, until the sulcus was cut off. The medial boundary
was defined as one sagittal image lateral to the medial
boundary of the pars triangularis. The diagonal sulcus was
not included in the pars opercularis measurement, however,
other extra sulci that appeared between the anterior
ascending ramus and the precentral sulcus, were included.
The ICC for inter-rater reliability for this structure was .89
and for intra-rater reliability was .97.

Analyses
Behavioral measures A multivariate analysis of variance
(MANOVA) was used to examine differences in IQ
between the ASD and control groups and between the
younger and older groups. Diagnosis and age group were
the independent variables and K-BIT verbal and nonverbal standard scores were the dependent variables.
Similarly, differences in language scores were examined
via MANOVA, with diagnosis and age group as
independent variables and CELF receptive and expressive
standard scores as dependent variables.
Volume To control for differences in total brain size, each
region was calculated as a proportion of total hemisphere
volume for all analyses. To examine differences in volume
between the ASD and control groups and between the
younger and older groups, MANOVA was used with
hemisphere as the within-subject independent variable,
diagnosis and age group as the between-subjects independent variables, and Heschls gyrus, planum temporale, pars
triangularis, and pars opercularis gray matter volumes as the
dependent variables. Since the pars triangularis and pars
opercularis together comprise Brocas area and some studies
have examined these regions together, the pars triangularis
and pars opercularis measures were also combined, creating
a total frontal language region. To examine differences in this
total frontal area, an ANOVA was performed with hemisphere as the within-subject independent variable, diagnosis
and age group as the between-subjects independent variables, and pars triangularis + pars opercularis gray matter
volume as the dependent variable.

58

Differences in Heschls gyrus configurations were also

examined. Chi-squares were performed for left and right
Heschls to examine the frequency of a partial split, full
split, or no split in each group. ANOVAs were also
performed to see if there were differences in size related
to the different configurations. Left or right Heschls gyrus
volume was the dependent variable and left or right
Heschls gyrus configuration (partial, full, or no split) was
the independent variable.
Asymmetry quotients For each region, asymmetry quotients
were calculated as (L-R)/[(L+R)/2], so that a positive
asymmetry quotient indicated leftward asymmetry and a
negative quotient indicated rightward asymmetry. To
examine group and age group differences in asymmetry,
MANOVA was utilized, with diagnosis and age group as
the independent variables and asymmetry quotients of
Heschls, planum, pars triangularis and pars opercularis as
the dependent variables. An ANOVA was also performed,
with diagnosis and age group as the independent variables
and pars triangularis + pars opercularis asymmetry quotient
as the dependent variable.
Correlations Pearson correlations were computed to examine the relationship between behavioral and anatomical
measures. For all correlations, regions proportional to
total hemisphere volume were used. Correlations between
left and right volume of each region with age were
calculated for the ASD and control groups. Correlations
were also computed for each group, between left and right
volumes of each region with CELF total standard score
and with autism symptom severity in the ASD groups.
Symptom severity was measured using the communication and social algorithm scores from the ADOS Module
3 or 4. Higher ADOS scores reflect increased symptom
severity.

Results
Behavioral measures The group data on IQ and language
scores are presented in Table 2. For IQ, at the multivariate
level, there was a significant main effect of diagnosis (F2,73 =
8.66, p<.001). The univariate level indicated significantly
higher verbal IQ (F1,74 =17.56, p<.001) scores in controls
than in the ASD group, but no significant group differences
in non-verbal IQ scores. There was no significant difference
between age groups or interaction between diagnosis
and age group. For the CELF, there was a significant
main effect of diagnosis (F2,73 =14.76, p<.001), with no
significant differences between age groups or interaction
between diagnosis and age group. For receptive (F1,74 =

Brain Imaging and Behavior (2009) 3:5163

22.31, p<.001) and expressive CELF (F1,74 =25.79, p<.001)

the control group had significantly higher scores than the
ASD group. Results were the same when left-handers were
removed.
Brain volume The means and standard deviations of the
volumes for total and regional brain volumes are presented
in Table 3. At the multivariate level, there was a significant
hemisphere effect (F4,73 =14.84, p<.001, partial 2 =.449).
This was significant for Heschls gyrus (F 1,76 = 31.71,
p <.001, partial 2 =.294) and planum temporale (F1,76 =
27.74, p<.001, partial 2 =.267), indicating significantly
larger volume in the left hemisphere than in the right.
There was also a significant hemisphere by age group
interaction (F4,73 =2.51, p=.049, partial 2 =.121). However, this was significant only for the planum temporale
(F1,76 =4.66, p=.034, partial 2 =.058) and indicated that
leftward asymmetry of the planum temporale was greater
in the older group than in the younger group, across both
diagnostic groups. At the multivariate level, there was no
significant effect of diagnosis. When left-handers were
removed the hemisphere effect was also significant for the
pars opercularis, indicating significantly larger right
volume than left. All other results were the same with
left-handers removed.
For the ANOVA examining total frontal language
volume, there was a significant main effect of diagnosis
(F1,76 =4.51, p=.037, partial 2 =.056), indicating that the
ASD group had larger pars triangularis + pars opercularis
volume than the control group (Fig. 1). There were no
significant hemisphere or age effects or interactions.
This result was the same without left-handers in the
sample.
The chi-squares examining differences in frequencies of
Heschls gyrus configurations were not significant. In all
four groups, for both right and left Heschls, most
individuals had no split. The next most common configuration in all groups in both hemispheres was a fully split
Heschls, with very few individuals having a partially split
gyrus. The ANOVAs examining configuration differences
in size were also not significant for either the left or the
right Heschls gyrus. Results were the same when lefthanders were removed.
Asymmetry quotients Table 4 presents the data on asymmetry quotients for each group. At the multivariate level,
there was a significant main effect of age group (F4,73 =
2.88, p=.029, partial 2 =.136). At the univariate level,
this was significant for the planum temporale (F1,76 =5.13,
p=.026, partial 2 =.063), indicating that the older group
had significantly larger planum asymmetry quotient (more
leftward) than the younger group (Fig. 2). There was no
significant effect of diagnosis.

Brain Imaging and Behavior (2009) 3:5163

59

Table 3 Means and standard deviations of total hemisphere volume and gray matter volume of each region, proportional to total hemisphere
volume for each group
ROI

Hemi

Total
HG
PT
PTR
POP
PTR+POP

ASD

Left
Right
Left
Right
Left
Right
Left
Right
Left
Right
Left
Right

Controls

Younger (n=20)

Older (n=20)

Younger (n=20)

Older (n=20)

670.94
669.13
.0025
.0019
.0036
.0030
.0017
.0016
.0028
.0029
.0045
.0045

682.93
677.41
.0024
.0021
.0034
.0024
.0015
.0015
.0027
.0028
.0042
.0043

670.70
663.48
.0025
.0021
.0033
.0030
.0013
.0013
.0024
.0027
.0037
.0040

691.87
689.76
.0024
.0021
.0038
.0027
.0013
.0014
.0026
.0026
.0040
.0041

(72.10)
(65.61)
(.00056)
(.00053)
(.00130)
(.00084)
(.00068)
(.00066)
(.00068)
(.00087)
(.00124)
(.00127)

(79.66)
(75.26)
(.00072)
(.00049)
(.00091)
(.00096)
(.00056)
(.00073)
(.00079)
(.00081)
(.00108)
(.00129)

(43.96)
(45.68)
(.00053)
(.00065)
(.00091)
(.00103)
(.00054)
(.00062)
(.00073)
(.00075)
(.00113)
(.00115)

(54.91)
(60.97)
(.00059)
(.00048)
(.00112)
(.00089)
(.00068)
(.00063)
(.00060)
(.00063)
(.00117)
(.00097)

HG = Heschls gyrus, PT = planum temporale, PTR = pars triangularis, POP = pars opercularis

For the total frontal language region, there were no

significant age differences for pars triangularis + pars
opercularis asymmetry quotient and no differences in
asymmetry quotients were found comparing ASD and
controls. All asymmetry quotient results were the same
when left-handers were removed.
Correlations There was a significant positive correlation
between age and left planum temporale size in the control
group (r=.364, p=.021). Other significant brain-behavior
correlations were found only in the younger ASD group.
The right pars triangularis volume was negatively correlated with the CELF total language score (r=.516, p=.024),
and left pars triangularis volume was positively correlated
with ADOS communication scores (r=.595, p=.006) and
ADOS social scores (r=.552, p=.012). The left pars
Frontal Language Region Group Differences

Frontal Language Volume

0.005
0.0045

triangularis + pars opercularis volume was also correlated

with ADOS communication (r=.497, p=.026) and ADOS
social (r=.467, p=.038) scores. When left-handers were
removed from the sample, there were a few additional
correlations. In the ASD group, age was negatively
correlated with the right planum temporale volume (r=
-.369. p=.038). In addition, in the younger ASD group, the
right pars triangularis was correlated with ADOS communication (r=.526, p=.036) and social (r=.497, p=.050) scores.
There was no significant correlation between left pars
triangularis + pars opercularis and ADOS social scores.

Discussion
There were several interesting findings in this study. In
controls, there was significantly stronger leftward planum
temporale asymmetry in the older group than the younger
group. This was also found in the ASD group. There was

0.004

Table 4 Means and standard deviations of asymmetry quotients for

each region for each group

0.0035
0.003

ROI AQ

0.0025
0.002
0.0015
0.001
0.0005
0
Left

Right
Hemisphere
Controls

HG
PT
PTR
POP
PTR+POP

ASD

Controls

Younger
(n=20)

Older
(n=20)

Younger
(n=20)

Older
(n=20)

.267
.151
.088
.011
.016

.156
.368
.023
.016
.006

.231
.119
.050
.120
.068

.116
.342
.064
.009
.036

(.25)
(.42)
(.36)
(.40)
(.35)

(.24)
(.51)
(.51)
(.33)
(.33)

(.35)
(.43)
(.64)
(.29)
(.35)

(.28)
(.36)
(.59)
(.26)
(.29)

ASD

Fig. 1 Differences between ASD and controls in pars triangularis+pars

opercularis volume

A positive asymmetry quotient indicates leftward asymmetry and a

negative asymmetry quotient indicates rightward asymmetry. AQ =
asymmetry quotient

60

Brain Imaging and Behavior (2009) 3:5163

Planum Temporale Age Differences

Planum Temporale AQ

0.6
0.5
0.4
0.3
0.2
0.1
0
Controls

ASD
Group
Younger

Older

Fig. 2 Age differences in planum temporale asymmetry quotients for

both the control and ASD groups. AQ = asymmetry quotient

also a significant correlation between age and left planum

temporale size, found only in controls. We also found larger
frontal language region volume in the ASD group compared to controls and this was found across the age groups.
There were significant correlations in the younger ASD
group between frontal language regions and measures of
language and autism severity.
The finding of increased leftward asymmetry of the
planum temporale in controls partly supported our hypothesis of increased left volume and leftward asymmetry of
language areas in older compared to younger individuals.
This finding is consistent with previous studies of typically
developing individuals, demonstrating increased asymmetry of temporal language regions in adolescents compared
to adults (Sowell et al. 2001) and differences in asymmetry
of the Sylvian fissure in adolescents and adults compared to
children (Sowell et al. 2002). These developmental changes
in anatomy may also be related to age-related changes in
language functions. It was surprising that we did not find a
significant interaction between diagnosis and age group,
rather increases in leftward asymmetry with age were
equivalent between the typically developing and ASD
groups. This did not support our hypothesis, but is
consistent with one previous study that found no developmental differences in the superior temporal gyrus between
ASD and controls. One interesting difference, however, was
in the correlations with age. In the control group, the left
planar volume increased with age. In ASD, we did not find
this correlation and when left-handers were removed, the
right planum temporale decreased with age in this group.
So, although both groups had increased leftward asymmetry, these correlations suggest that there may be different
mechanisms. More studies, however, need to examine
developmental changes in these critical language areas.

An unexpected finding in our study was increased

frontal language region volume in the ASD group compared to controls. Brocas area has been shown to be
involved in the organization of articulatory sequences and
inner speech (Stuss and Benson 1986, cited in Dmonet et
al. 1992), in subvocal rehearsal (Paulesu et al. 1993), and in
the initiation of speech (Alexander et al. 1990). The pars
triangularis and pars opercularis are also involved in
semantic encoding and retrieval and in on-line manipulation
of semantic representations (Blumenfeld et al. 2006).
Functional neuroimaging studies have demonstrated that
this region may also be important for phonological
(Dmonet et al. 1992; Zatorre et al. 1996) and syntactic
processing (Dapretto and Bookheimer 1999; Embick et al.
2000). Both anatomical (Abell et al. 1999; de Foss et al.
2004; Herbert et al. 2002, 2005; McAlonan et al. 2005) and
functional studies utilizing language tasks (Gaffrey et al.
2007; Harris et al. 2006; Just et al. 2004; Kana et al. 2006)
have indicated differences in these frontal areas in
individuals on the autism spectrum, which may be
related to differences in language development. Findings,
however, of anatomical studies have been inconsistent
and increased pars triangularis and opercularis volume in
ASD has not previously been reported. This, however, is
the only study that has performed manual measurements
of these critical frontal language regions in ASD, which
may better take into account differences in individual
anatomy than more automated methods. The sample size
was also larger than many previous anatomical studies of
ASD. More studies need to be conducted that focus on
both anatomical and functional differences of these
frontal areas.
Differences in pars triangularis and pars opercularis
volume could be due to differences in language abilities
between the groups, as controls had significantly higher
CELF scores than the ASD group, however, significant
correlations of these regions with behavioral measures were
only found in the younger ASD group. Correlations in the
control groups were probably not found due to the smaller
range of CELF scores found in those groups. In the younger
ASD group, larger right pars triangularis volume was
associated with lower language scores on the CELF. This
finding may be related to suggestions that a lack of pruning
of tissue, especially in the right hemisphere, in individuals
with neurodevelopmental language disorders may contribute to problems with language (Beaton 1997; Morgan and
Hynd 1998). It is unclear, however, why this correlation
would not be found in the older group of ASD
individuals. In the younger group, larger left pars
triangularis and left frontal language volumes were
associated with more severe communication and social
autism symptoms, indicating that these regions may be
involved in language and social functions.

Brain Imaging and Behavior (2009) 3:5163

In summary, there were age-related changes in the

planum temporale in both typically developing individuals
and individuals on the autism spectrum, with both groups
having increased leftward asymmetry in older than younger
individuals. Group differences were found in frontal
language regions, with the ASD group having larger
volume than controls, with no age effects. There are several
limitations to this study. One limitation is that this was a
cross-sectional study, rather than a longitudinal study,
which would be able to directly assess developmental
changes in behavior and brain anatomy. Another limitation
is that the ASD individuals in this study had a wide range
of functioning levels and language abilities. Larger sample
sizes would be necessary, so that these groups could be
further broken down based on functioning level or language
abilities so that variability related to these could be
examined within the group. Another limitation is that
because the study involved manual tracings, only specific
regions, with well-defined anatomical boundaries were
examined and other potentially important language regions
were not examined in this study. Future studies should use
longitudinal designs to further explore the developmental
trajectory of cortical language regions in ASD.
Acknowledgments This study was supported by a program project
grant from the National Institute on Deafness and Other Communication Disorders (U19 DC 03610), which is part of the NICHD/
NIDCD funded Collaborative Programs on Excellence in Autism, as
well as funding for the GCRC at Boston University School of
Medicine (M01-RR0533). This study was also supported by NINDS
F30 NS055511. We thank Lin Themelis for help with screening and
scheduling participants and Danielle Delosh for help with measurements of total hemisphere volume. We also extend our sincere
gratitude to the children and families who participated in this study.

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