Autism, Asperger syndrome and brain mechanisms
for the attribution of mental states to animated
shapes
Fulvia Castelli,
1
Chris Frith,
2
Francesca HappeÂ
3
and Uta Frith
1
1
Institute of Cognitive Neuroscience,
2
Wellcome
Department of Cognitive Neurology, Institute of Neurology,
University College London and
3
Institute of Psychiatry,
Kings College London, London, UK
Correspondence to: Uta Frith, Institute of Cognitive
Neuroscience, University College London,
17 Queen Square, London WC1N 3AR, UK
E-mail: u.frith@ucl.ac.uk
Summary
Ten able adults with autism or Asperger syndrome and
10 normal volunteers were PET scanned while watching
animated sequences. The animations depicted two tri-
angles moving about on a screen in three different con-
ditions: moving randomly, moving in a goal-directed
fashion (chasing, ®ghting), and moving interactively
with implied intentions (coaxing, tricking). The last con-
dition frequently elicited descriptions in terms of mental
states that viewers attributed to the triangles (mentaliz-
ing). The autism group gave fewer and less accurate
descriptions of these latter animations, but equally
accurate descriptions of the other animations compared
with controls. While viewing animations that elicited
mentalizing, in contrast to randomly moving shapes, the
normal group showed increased activation in a pre-
viously identi®ed mentalizing network (medial prefron-
tal cortex, superior temporal sulcus at the temporo-
parietal junction and temporal poles). The autism
group showed less activation than the normal group in
all these regions. However, one additional region, extra-
striate cortex, which was highly active when watching
animations that elicited mentalizing, showed the same
amount of increased activation in both groups. In the
autism group this extrastriate region showed reduced
functional connectivity with the superior temporal sul-
cus at the temporo-parietal junction, an area associated
with the processing of biological motion as well as with
mentalizing. This ®nding suggests a physiological cause
for the mentalizing dysfunction in autism: a bottleneck
in the interaction between higher order and lower
order perceptual processes.
Keywords: anterior cingulate; autism; extrastriate cortex; superior temporal sulcus; temporal poles; Theory of Mind
Abbreviations: BA = Brodmann area; FFA = fusiform face area; FuG = fusiform gyrus; GD animations = animations
eliciting descriptions of goal directed behaviour; IOcG = inferior occipital gyrus; Rd animations = animations of randomly
moving shapes, eliciting simple behavioural descriptions; SPM = statistical parametric mapping; SFG = superior frontal
gyrus; STS = superior temporal sulcus; TG = temporal gyrus; TmP/Am = temporal pole adjacent to amygdala; ToM =
Theory of Mind; ToM animations = animations eliciting mental state attributions
Introduction
The pervasive tendency to explain one's own and others'
actions in terms of beliefs, desires and goals has been termed
`Theory of Mind' (ToM) or `mentalizing'. According to one
in¯uential theory, autism is the result of impaired mentaliz-
ing, as manifest in a lack of social insight and impaired
communication. This theory was ®rst tested by Baron-Cohen
et al. (1985). Reviews of recent experimental studies indicate
that the original ®ndings have been replicated, and that this
area of research has become a very active branch of cognitive
neuroscience (Baron-Cohen et al., 2000). By comparing tasks
that differ only in the mentalizing component, experiments
have ruled out that mentalizing dif®culty is due to greater task
complexity or lower general ability (e.g. Perner et al., 1989;
Leslie and Thaiss, 1992; Sodian and Frith, 1992). Evidence
suggests that even able individuals with high-functioning
autism read minds differently. Although their performance on
standard laboratory tests of false belief attribution can be
perfect, they experience long developmental delays when
ãGuarantors of Brain 2002
Brain (2002), 125, 1839±1849

acquiring the skill and are prone to errors on more advanced
tests of ToM (HappeÂ, 1994; Klin, 2000; Baron-Cohen et al.,
2001; Roeyers et al., 2001).
There is overwhelming evidence that symptoms of autism
result from abnormal brain development, probably as the
result of genetic factors (for reviews see Bailey et al., 1996;
Happe and Frith, 1996). However, information on structural
brain abnormalities in autism to date has been sparse as well
as inconsistent. This is probably due to a number of factors,
including the dif®culty of carrying out post-mortem studies,
the technical challenges presented by the need to quantify
structural images, and the extreme heterogeneity of the
autism spectrum. In the ®rst histopathological studies,
Bauman and Kemper (1994) described cellular abnormalities,
in particular reduced neuronal cell size and increased cell
packing density in the hippocampal complex, subiculum,
entorhinal cortex, amygdala, mamillary body, medial septal
nucleus and anterior cingulate gyrus. Outside the limbic
system, reduced numbers of Purkinje cells were found in the
posterior and inferior regions of the cerebellum. In a more
recent neuropathological study, abnormalities in the limbic
system were not investigated, but pathology was found in
various cortical regions including the cerebellum and the
brain stem (Bailey et al., 1998). This study also documented
enlarged brain size in autism.
Most of the cases studied to date had not only autism, but
also mental retardation and epilepsy so that the speci®city of
the ®ndings remains uncertain. Preliminary neuroanatomic
data are available from one case of Asperger syndrome. Small
neuronal cell size and increased cell packing density were
found throughout the amygdala and the entorhinal cortex,
while other parts of the limbic system appeared to be normal
(Bauman, 1996). Structural imaging studies with high-
functioning individuals with autism are now also beginning
to contribute to the gradually emerging picture of the extent
and type of neuroanatomic abnormalities. Again, inconsist-
encies make it dif®cult to draw ®rm conclusions.
Abnormalities in a volumetric study suggest that frontal
lobe cortex volume is increased in a subset of children with
autism and that this increase correlates with the degree of
cerebellar abnormality (Carper and Courchesne, 2000). Abell
et al. (1999), using voxel-based morphometry, found relative
decreases of grey matter in paracingulate sulcus and inferior
frontal gyrus, and increases in periamygdaloid regions and
middle temporal and inferior temporal gyrus. Howard et al.
(2000), using a different type of analysis, also showed
increases in periamygdaloid regions, while Aylward et al.
(1999) found reduced volumes of amygdala and hippocam-
pus. These latter structural studies are complemented by
®ndings from a case with congenital left amygdala abnor-
mality and Asperger syndrome. This individual, although of
normal intelligence, showed profound failure on mentalizing
tasks (Fine et al., 2001).
Given the scarcity and the inconsistencies of the available
anatomical data on the brain in autism, and given that a core
symptom of autism is impaired social cognition, interest has
turned to investigating brain activity associated with social
cognition in general and with mentalizing in particular. To
date, six functional imaging studies of normal volunteers,
using PET or fMRI, have been reported that were explicitly
concerned with mentalizing. In these studies, mental states
had to be attributed on the basis of historical knowledge (Goel
et al., 1995), stories (Fletcher et al., 1995; Gallagher et al.,
2000; Vogeley et al., 2001), cartoons (Gallagher et al., 2000),
cartoon strips (Brunet et al., 2000) and animated geometric
shapes (Castelli et al., 2000). In all these studies activity
associated with mentalizing was seen in three brain regions:
an anterior region of medial prefrontal cortex/anterior
cingulate cortex, an area in anterior temporal lobes close to
the amygdala, and the superior temporal sulcus at the
temporo-parietal junction. These consistent ®ndings suggest
that the rudiments of a mentalizing network in the brain are
being identi®ed.
Is this network dysfunctional in the case of autism, as the
behavioural results suggest, and what might cause the
dysfunction? So far, two functional neuroimaging studies of
individuals with high-functioning autism (including Asperger
syndrome, the subgroup without language or cognitive delay)
have explicitly addressed mentalizing, while others have
studied the perception of faces without an explicit require-
ment for mentalizing. Since faces are an important cue for the
attribution of mental states, commonalities between these two
types of studies in autism might emerge. In a PET study,
Happe et al. (1996) compared brain activation in ®ve
individuals with autistic disorder with six controls while
reading stories with a baseline of unconnected sentences. For
stories that required mentalizing, the autistic group activated
the same network of regions as the controls, but showed
signi®cantly less activity in medial prefrontal cortex. In an
fMRI study, Baron-Cohen et al. (1999) compared six adults
with autism with 12 controls. Subjects were asked to judge
inner states from photographs of faces in which only the eyes
could be seen, and to decide which of two simultaneously
presented words best described the mental/emotional state.
The baseline condition involved judging gender from the
eyes. During performance of the mentalizing task, activity
was seen in many brain areas including the three listed above.
People with autism showed signi®cantly less activity in the
amygdala.
In one study of face perception, Critchley et al. (2000)
scanned nine people with autistic disorder and nine controls
while they observed faces that had neutral expressions or had
expressions of happiness or anger. Subjects judged either the
expression or the gender of the faces. In another study,
Schultz et al. (2000) scanned 14 participants with autism
spectrum disorder and 28 controls while discriminating
between pairs of non-expressive faces, pairs of familiar
objects or pairs of patterns. In both studies activity was seen
in a region of fusiform gyrus widely accepted to be
specialized for the perception of faces (Kanwisher et al.,
1997), and this activity was signi®cantly lower in both
autistic groups. The autistic groups showed greater activation
1840 F. Castelli et al.