Understanding orbitofrontal contributions to theory-of-mind reasoning: Implications for autism

Brain and Cognition 55 (2004) 209–219

www.elsevier.com/locate/b&c

Understanding orbitofrontal contributionsto theory-of-mind reasoning: Implications for autism

Mark A. Sabbagh

Department of Psychology, Queen�s University, Kingston, Canada K7L 3N6

Accepted 17 April 2003

Available online 21 February 2004

Abstract

Autism is a lifelong developmental disorder that is associated with severe difficulties with ‘‘theory-of-mind’’—the understanding

that others� behaviors are motivated by internal mental states. Here, we raise the possibility that research examining the neural bases

of theory-of-mind reasoning has the potential to inform researchers about the elusive functional neural impairments associated with

autism. Evidence from our lab and others� suggests that theory-of-mind reasoning may be fractionated into at least two functionally

and anatomically distinct neural circuits. Specifically, the ability to decode others� mental states from observable cues (such as facial

expressions) may rely on contributions from the orbitofrontal/medial temporal circuit within the right hemisphere. In contrast, the

ability to reason about others� mental states may rely left medial frontal regions. We conclude by reviewing evidence suggesting that

the developmental roots of autism might lie in abnormal functioning of the orbitofrontal/medial temporal circuit which may, in

turn, underlie the abnormal development of social-cognitive skills among individuals with autism.

� 2004 Elsevier Inc. All rights reserved.

1. Introduction

Researchers generally agree that human social inter-

action gains much of its richness and complexity becausewe possess a ‘‘theory-of-mind’’—an understanding of

how other�s behaviors are motivated by their internal

mental states, such as beliefs, desires, intentions, and

emotions (Wellman, 1990). The conceptual framework

underlying research on theory of mind has its roots in

developmental psychology. At present, issues sur-

rounding aspects of children�s development of a theory-

of-mind have come to guide research on children�ssocial-cognitive development (Taylor, 1996). Through

this work, researchers have established links between

theory-of-mind and executive functions (Carlson &

Moses, 2001; Frye, Zelazo, & Burack, 1998; Perner &

Lang, 1999), language development (Baldwin & Toma-

sello, 1998; Bloom, 2000; Sabbagh & Baldwin, 2001),

prosocial behavior, and emotional functioning (Dunn,

1999; Happ�e & Frith, 1996).

E-mail address: [email protected].

0278-2626/$ - see front matter � 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.bandc.2003.04.002

Perhaps because of its wide ranging applications,

theory-of-mind research has extended well beyond the

domain of developmental psychology. Indeed, the topic

has become an interdisciplinary hub for clinical, social,cognitive, and comparative psychologists and philoso-

phers interested in understanding the foundations of

everyday social cognition (Malle, Moses, & Baldwin,

2001). Still more recently, cognitive neurologists and

neuroscientists have begun to explore the neural bases of

theory-of-mind skills (see Siegal & Varley, 2002, for a

recent review). This latter branch of research is contrib-

uting to our developing understanding of how the cog-nitive skills that enable high-level social understanding

are organized in the human brain (Cacioppo et al., 2002).

Perhaps most importantly, this research has opened new

windows for understanding the neuropathological bases

of clinical disorders in which social-cognitive and theory-

of-mind skills may be specifically impaired (e.g., Doody,

Goetz, Johnstone, Frith, & Cunningham-Owens, 1998).

One disorder in which a theory-of-mind approach hasbeen especially fruitful is autism (Baron-Cohen, 1995).

Autism is a lifelong and debilitating neuro-cognitive

developmental disorder that affects between 1/250

mail to: [email protected]

210 M.A. Sabbagh / Brain and Cognition 55 (2004) 209–219

(Gillberg & Wing, 1999) and 1/500 (Fombonne, 1999)individuals. Autism is characterized by a triad of fea-

tures, including impaired social development, delayed

and deviant language, and an insistence on sameness

(American Psychiatric Association, 1994; Rutter, 1978).

Baron-Cohen (Baron-Cohen, 1995; Baron-Cohen, Les-

lie, & Frith, 1985) was one of the first to suggest that this

apparently disparate triad of symptoms may stem from

a fundamental deficit in theory-of-mind reasoning.Through his pioneering and continuing studies, it is now

well-established that many individuals with autism, in-

cluding high-functioning autism and Asperger syn-

drome, experience difficulties engaging theory-of-mind

reasoning (see Baron-Cohen, 2001, for a review).

What is perhaps most compelling about many of

these cases is that, especially among high-functioning

individuals with autism, theory-of-mind deficits stand incontrast to surprising strengths in other areas of cogni-

tive functioning. For instance, individuals with autism

have difficulty recognizing emotional mental states in

pictures of eyes, but no trouble discerning other un-

derlying traits (such as gender or age) (Baron-Cohen,

Wheelwright, & Joliffe, 1999). Also, individuals with

autism have difficulty reasoning about others� false be-

liefs (i.e., beliefs that do not match the true state of theworld), but are adept at reasoning about non-mental

representations that also can be false such as photo-

graphs (Leslie & Thaiss, 1992). This pattern of findings

has been taken by some to suggest that individuals with

autism� theory-of-mind deficit represents a rather spe-

cific neuro-cognitive impairment (Baron-Cohen, 1994).

While there is general agreement now that social-

cognition is particularly impaired in autism, there isconsiderable debate regarding the best way to charac-

terize the neuro-cognitive nature of this impairment (see

commentary on Baron-Cohen, 1994). In our lab, we

have been attempting to gain insight into this question

by characterizing the neural correlates of theory-of-

mind reasoning in normally developing adults using the

same tasks that have been used to index a theory of

mind impairment in autism. This work has two mainresearch aims. First, by gaining an appreciation of the

functional cortical regions that are important for theo-

ry-of-mind reasoning, we can begin to develop hypoth-

eses regarding the neuro-cognitive processes that

distinguish theory-of-mind reasoning from reasoning in

other domains. Second, insights from this approach can,

in turn, provide a way of understanding how known

neuro-cognitive characteristics associated with autismmay map onto the primary social-cognitive deficits that

characterize this developmental disorder.

1.1. Separating component processes in theory-of-mind

Before discussing our work, it is important to func-

tionally define what is meant by Theory-of-Mind in a

way that makes it amenable to cognitive neuroscienceinvestigations. Researchers typically functionally define

theory-of-mind as a unitary skill that is engaged anytime

one needs to represent the mental states of others.

Sometimes, the skill is referred to by the term mind

reading (Whiten, 1991). Nonetheless, it is important to

note that theory-of-mind reasoning can be separated

into at least two component processes (see also Tager-

Flusberg, 2001): (1) detecting or decoding others� mentalstates based on immediately available observable infor-

mation and (2) reasoning about those mental states in

the service of explaining or predicting others� actions.Examples of detecting or decoding mental states might

include some of the relatively rudimentary skills, such as

identifying others� focus of attention based on eye gaze.

In contrast, examples of reasoning about mental states

within the context of explaining or predicting actionmay include some more complex aspects of theory of

mind reasoning, such as distinguishing jokes from lies,

or predicting story characters� behavior on the basis of

false beliefs.

Ordinarily, these two aspects of theory-of-mind work

in concert to produce reliable judgments about others�mental states. However, the distinction between these

two processes is important because they each rely pri-marily on different kinds of social-information process-

ing skills. Mental state decoding relies principally on

social information that is gleaned in the immediate and

observable environment (e.g., the person�s actions, toneof voice, facial expression, etc.). By contrast, reasoning

about others� mental states to explain or predict action

requires one to access knowledge and facts about either

the person in question, or their contextual circum-stances. For example, in order to correctly infer that

someone is sad because she got a poor mark on an exam

one needs to detect sadness from the observable infor-

mation, know that she received a poor mark, and per-

haps know that she had wanted to do well.

As was noted above, there is some evidence to suggest

that high-functioning individuals with autism have dif-

ficulties with both mental state decoding (e.g., poor atdecoding mental states relative to gender) and mental

state reasoning (e.g., poor at reasoning about beliefs

relative to photographs). The fact that the two compo-

nent processes involved in theory-of-mind reasoning

may be affected in autism has interesting implications

for understanding the neuro-cognitive bases of theory-

of-mind reasoning. One possibility is that detecting and

reasoning about mental states are subserved by partiallyoverlapping neural circuitry. The overlapping regions

may represent a circumscribed sub-circuit that is spe-

cialized for representing information relevant to ‘‘theo-

ry-of-mind’’ no matter what the specific task (see Frith

& Frith, 1999). If this were the case, this ‘‘theory-of-

mind’’ site may be a key to understanding the neuro-

pathology of autism. An alternative possibility is that, as

Fig. 1. Approximate topographic layout of the 128-channel Geodesic

Sensor Net used in our electrophysiological studies. All recordings

were digitized at 500Hz (bandpass filter: 0.1–200Hz) and referenced to

vertex. Scalp impedances were kept below 50kX throughout the entire

recording session. After recording, data were submitted to algorithmic

artifact rejection routines that identified and excluded trials that were

contaminated with artifact (e.g., eye blink, eye movement). Data from

artifact free trials were averaged to create the ERP, re-referenced using

the average reference derivation, corrected to 100-ms baseline, and

then filtered (low-pass: 15Hz) for analysis.

M.A. Sabbagh / Brain and Cognition 55 (2004) 209–219 211

is the case with language (Neville, Mills, & Lawson,1992; Pulvermueller, 2000), the different components of

theory-of-mind reasoning may be subserved by distinct

and non-overlapping circuitry. Individuals with autism

may be impaired on both components of theory of mind

for one of two reasons: (1) a fundamental deficit in both

systems or (2) a core deficit in one component—such as,

mental state detection—that affects appropriate devel-

opment of the other.Below, we will review evidence from our laboratory in

support of the hypothesis that different components of

theory-of-mind reasoning are associated with distinct,

non-overlapping neural systems. In particular, we will

review evidence suggesting that decoding others� mental

states is associated with anterior frontal systems, most

likely related to orbitofrontal/medial temporal circuit.

Moreover, these systems may be lateralized to the righthemisphere. In contrast, we will review evidence sug-

gesting that reasoning about mental states is related to a

relatively circumscribed area of medial prefrontal cor-

tex, that may be lateralized to the left hemisphere. After

reviewing this evidence, we will discuss the extent to

which our findings regarding the neural circuitry of

theory-of-mind relates to current hypotheses regarding

the developmental neuropsychological underpinnings ofautism (Dawson et al., 2002).

1.2. Neural correlates of decoding mental states

To date, very few studies have been designed specif-

ically with the goal of investigating the neural bases of

simply decoding mental states (see Haxby, Hoffman, &

Gobbini, 2002, for a recent review). However, someevidence bearing on this issue might come from studies

investigating the neural bases of facial emotion recog-

nition. Emotion is a mental state, and judgments about

others emotions can be made solely on the basis of im-

mediately available information. Neuropsychological

evidence suggests that bilateral amygdala damage im-

pairs recognition of emotional states, especially fear

(e.g., Adolphs, Tranel, Damasio, & Damasio, 1994;Calder et al., 1996). A role for medial temporal struc-

tures such as the amygdala in emotion identification has

also found some support in a small-scale MEG study

(Streit et al., 1999). In addition to the amygdala, there is

some evidence that individuals with ventral-medial

prefrontal lesions (including orbitofrontal cortex) are

impaired in their abilities to decode emotions from facial

expressions (Hornak, Rolls, & Wade, 1996).These studies have led to the intriguing hypothesis

that a circuit including the orbitofrontal cortex and

medial temporal regions (including the amygdala) may

be crucial for decoding others� emotional mental states

(Baron-Cohen, 1995; Rolls, 1996). However, interpre-

tation of these studies is limited somewhat by their small

scale, and by the fact that the stimuli used for emotional

judgments were different from ones used for controljudgments (e.g., gender, identity). A notable exception

comes from Baron-Cohen et al. (1999), who attempted

an fMRI investigation of emotional mental state de-

coding in which gender judgments of the same stimuli

were used as a control condition. Unfortunately, these

authors noted that there were a number of difficulties

with the precise design of their study that limited in-

terpretations of their results.

1.2.1. ERP study: Decoding mental states

We recently completed a study aimed at delineating

the spatial and temporal aspects of the neural systems

that are important for decoding others� emotional

mental states (Sabbagh, Moulson, & Harkness, in

press). To do this, we adapted the ‘‘Reading the Mind in

the Eyes’’ task (Baron-Cohen, Wheelwright, Hill, Raste,& Plumb, 2001) for use in a dense-array ERP paradigm

(see Fig. 1). In this modified version, 18 normal partic-

ipants first saw a word labeling either a mental/emo-

tional state (e.g., embarrassed) or a gender (e.g., female).

The word was then replaced with a fixation point, and

then a picture of eyes. Participants� task was to judge

(yes/no) whether the eyes depicted the emotion or gen-

der labeled by the preceding word. Event-related po-tentials were recorded time-locked to the onset of the


picture of the eyes, as participants made their decisions(see Fig. 2). Because emotional mental state and gender

judgments were made with respect to the same photo-

graphs, differences in ERP activity could not be attrib-

uted to general differences between stimuli.

Using this procedure, we found two aspects of the

ERP that distinguished mental state decoding from

gender decoding. The first component to show the

condition effect was the N270-400 that was present overfrontal and anterior temporal areas. We found that at

right hemisphere sites, the N270-400 component elicited

in the mental state decoding condition was more nega-

tive than in the gender decoding condition (see Fig. 3).

The N270-400 difference was not detected at left hemi-

sphere sites. The second ERP component to show a

condition effect was the P300. Specifically, the P300

elicited in the mental/emotional state condition wasmore positive than in the gender condition. The frontal

N270-400 differences and the P300 differences were the

only ones to meet significance criteria.

We conducted a source estimation analysis using the

low-resolution electromagnetic tomography (LORETA)

technique to identify candidate neural generators con-

tributing to the differences in scalp potentials at 320ms

post-stimulus.While this technique is limited by relatively

Fig. 2. Schematic of the structure of a single tria

Fig. 3. Three-dimensional spherical spline scalp interpolation of the voltage

stimulus with representative waveforms from regions that showed differences i

time period of N270-400 where condition differences were significant.

low spatial resolution, previous research has demon-strated that it can be effective in providing highly accurate

description of the cortical regions responsible for a given

effect (Pascual-Marqui, 1999). This analysis identified two

cortical regions that made strong contributions to the

scalp electrical differences: orbitofrontal cortex and me-

dial temporal cortex. While each of these areas showed

some bilateral activation within each region, higher levels

of activation were found in the right hemisphere.Of course, there are a number of problems with

source localization using ERP, and as such, these anal-

yses must be considered cautiously. It is noteworthy,

however, that these ERP findings dovetail nicely with

the neuropsychological data suggesting that orbito-

frontal and medial temporal lesions disrupt emotional

recognition. Thus, these findings do provide initial evi-

dence that the neural circuitry underlying one aspect oftheory-of-mind reasoning—decoding others� mental

states—may rely on neural circuits within orbitofrontal

and medial temporal regions.

1.3. Neural correlates of reasoning about mental states

Although the study described above represents one of

the first attempts to understand the neural correlates of

l in the mental state decoding ERP study.

of the difference wave (mental state—gender) sampled at 300ms post-

n the N270-400 component. Shaded regions of the waveforms represent

Table 1

Example of story from mental state reasoning task

Belief Photo

Fred put a flower and a bottle

of wine on the table

Fred put a flower and a bottle

of wine on the table

Fred showed them to his

friend Marianne

Fred showed them to his

friend Marianne

Marianne thought they

looked pretty

Marianne took a picture of

them with her camera

Then, Marianne fell asleep in

her room

Then, Marianne put her cam-

era away

While Marianne was asleep,

Fred moved the flower

Later on that day, Fred

moved the flower

Fred put the flower on the

piano

Fred put the flower on the

piano

He left the bottle of wine on

the table

He left the bottle of wine on

the table


decoding others� mental states, there is a fairly largebody of neuroimaging studies aimed at delineating the

neural correlates of reasoning about others� mental

states (see Frith & Frith, 2001, for a review). Typically,

these studies have relied on tasks in which the partici-

pants� neural activation is assessed as they perform tasks

that require reasoning about mental states as compared

with tasks that are closely matched, but do not require

reasoning about mental states. For instance, Fletcherand colleagues (Fletcher et al., 1995) developed a PET

paradigm in which participants were asked to predict or

explain behavior on the basis of either physical causality

or story characters� mental states. Similarly, Goel and

colleagues (Goel, Grafman, Sadato, & Hallett, 1995)

asked participants to make judgments about whether

objects would be considered familiar to either oneself or

an historical figure (e.g., Christopher Columbus). Eachof these studies, and a number of others that came later

(see Siegal & Varley, 2002), have converged on the result

that medial frontal areas, particularly in the left hemi-

sphere, make critical contributions to reasoning about

others� mental states.

When taken together with our findings on the neural

systems important for decoding others� mental states,

these findings seem to provide some evidence in supportof our hypothesis that decoding and reasoning about

mental states are subserved by non-overlapping neural

systems. Specifically, orbitofrontal and medial temporal

areas may be important for decoding mental states,

while medial frontal areas are important for reasoning

about mental states. Before drawing this conclusion,

however, it is important to consider some other inter-

pretations of the mental state reasoning studies. In eachof these studies, brain activation was demonstrated as

blood flow changes induced as participants reasoned

about mental state representations (like beliefs or per-

son-specific knowledge) relative to a control condition in

which participants reasoned about physical causation or

a real-world state of affairs. Arguably, then, the ‘‘mental

state’’ condition places more emphasis on the ability to

reason about abstract representations (e.g., beliefs) rel-ative to the other conditions. Thus, it remained possible

that left medial frontal cortex may be particularly im-

portant for making judgments about abstract represen-

tations, relevant to theory-of-mind or otherwise.

This is a particularly important concern because, as

discussed above, individuals with autism have special

difficulties in reasoning about mental representations

(e.g., beliefs) while they are unimpaired in their ability tomake judgments about non-mental representations (e.g.,

photographs).

1.3.1. Reasoning about mental states: ERP study

With this in mind, we undertook a study that was

designed to investigate whether left prefrontal regions

make a greater contribution to reasoning about mental

representations relative to non-mental representations(see Sabbagh & Taylor, 2000, for fuller description of

this work). Our study took as its starting place the false

belief/false photograph dissociation apparent in autism.

In our study, 23 typically developing adults had to

reason about outdated (or false) beliefs and photo-

graphs. These beliefs and photographs were outdated in

the sense that the scene changed subsequent to the cre-

ation of the representation, and as such, the represen-tation no longer matched the scene. Participants read a

belief and a photo version of 40 stories for a total of 80

stories (see Table 1 for an example). Following each

story, participants were asked a series of control ques-

tions to ensure that they understood the story, and a test

question asking them to judge the contents of the rep-

resentation. The test question was constructed such that

participants could not answer until the final word ap-peared. ERPs were recorded to the onset of the final

word in the question. The events associated with the test

question and recording of ERPs are illustrated in Fig. 4.

The key results of this study are illustrated in Fig. 5.

Even in this tightly controlled comparison, reasoning

about mental states was uniquely associated with left

frontal activity beginning 300ms following the onset of

the stimulus. Specifically, the ERP was characterized bya slow-wave effect, which was more positive in the belief

condition relative to the photograph condition. This

slow-wave condition effect was remarkably focal—it was

present only on a cluster of four sites over lateral frontal

areas. This effect was mirrored at left parietal sites where

a slow-wave effect also existed, but in the opposite di-

rection: the ERP elicited in the belief condition was

more negative relative to the photograph condition. Thispattern of differences was maintained throughout the

recording epoch, and was most distinct at around

820ms.

Unfortunately, we were unable to conduct source

localization analyses on these data, because precise

electrode locations were not measured. Nonetheless, the

Fig. 4. Schematic of the structure of a single trial in the mental state reasoning ERP study. (A) Question presented, word-by-word, 200ms. ISI. (B)

ERP epoch events timeline (all stimuli on screen for 250ms).

Fig. 5. Three-dimensional spherical spline scalp interpolation of the voltage of the difference wave (mental state—gender) sampled at 820ms post-

stimulus with representative waveforms from regions that showed differences in the time period between 300 and 850ms post-stimulus. Shaded

regions of the waveforms represent time periods within which condition differences were significant.


pattern of differences is consistent with a left anterior

medial frontal generator that is suggested by the fMRIand PET studies reviewed briefly above. These findings

find converging evidence for the importance of medial

prefrontal regions of the left hemisphere in reasoning

about others� mental states.

2. Summary and discussion of ERP findings

One of the most striking aspects of our ERP studies is

that, when viewed together, there was essentially no

reliable overlap between the neural systems that were

associated with decoding versus reasoning about mental

states. In particular, the ERP differences that indexed

mental state decoding were localized to inferior frontaland anterior temporal regions of the right hemisphere.

Source localization analyses estimated that these ERP

differences may have been generated within orbitofron-

tal prefrontal and medial temporal regions of the right

hemisphere. In contrast, reasoning about others� mental

states was associated with ERP activity that was focal

over prefrontal areas of the left hemisphere. Although

we did not conduct source localization analyses on thesedata, the pattern of activity was consistent with a medial

frontal generator within the left hemisphere that has

been described in fMRI and PET studies of mental state

reasoning (see Frith & Frith, 2001).


These findings support the notion that no single brainarea is active when humans engage theory-of-mind rel-

evant informational content. Instead, the neural systems

that support successful theory-of-mind judgments are

distributed across different cortical regions. These find-

ings raise important questions regarding how to char-

acterize the contributions of these different neural

circuits. One possibility is that instead of there being one

specialized circuit for reasoning about mental states,there may be several—each one dedicated to carrying out

a specific step in the process of making appropriate

theory-of-mind judgments. For instance, there may be a

specialized pathway within the orbitofrontal/medial

temporal circuit that is specifically dedicated to decod-

ing mental states. It seems possible that one aspect of

this specialization may be its laterality. There are a

number of findings now that suggest that decodingothers� mental states from observable information may

be a skill that is lateralized to the right hemisphere

(Sabbagh, 1999; Sabbagh et al., in press). Comple-

menting this right lateralized orbitofrontal/medial tem-

poral circuit, there may be a specialized region of medial

frontal regions of the left hemisphere may be especially

important for reasoning about mental states. This hy-

pothesis gains support from the fair amount of consis-tency across studies that have used tasks that require

theory-of-mind reasoning and revealed activation of left

medial frontal areas (Frith & Frith, 1999; Siegal &

Varley, 2002).

A second possibility is that instead of being special-

ized, each of these circuits performs a domain-general

computation that is required when engaging different

theory-of-mind related processes, but not specific to thissocial-cognitive domain. For instance, orbitofrontal ar-

eas may be important not only for decoding mental

states but also for decoding the meaning of stimuli in

other non-social domains. Similarly, the left medial

frontal contributions could reflect a domain-general

cognitive contribution that happens to be heavily taxed

when participants are engaged in theory-of-mind rea-

soning.Our studies do not provide us with the opportunity to

determine whether we have indexed domain-specific or

domain-general neural systems. However, some insight

on this issue may be taken from examining the tasks that

we used—and that have been used with individuals with

autism—to reveal electrophysiological dissociations as-

sociated with theory-of-mind. In both the case of mental

state decoding and mental state reasoning, the taskswere chosen because the mental state and non-mental

state conditions are, at least on their surfaces, very well

matched in terms of peripheral domain-general cogni-

tive demands. For example, the cognitive demands in

the false belief task seem very similar to those required

in the false photograph task (e.g., working memory,

logical reasoning, etc.). Similarly, there is no a priori

reason to suspect that the information-processing de-mands associated with decoding mental states from

pictures of eyes would be quantitatively and qualita-

tively different from those required to decode gender.

From this basis, then, it seems reasonable to suggest that

our electrophysiological differences reveal the operation

of neural circuits functionally dedicated to decoding and

reasoning about mental states (e.g., Frith & Frith, 2001).

It is important to note, however, that the assumptionsregarding how well these experimental tasks are mat-

ched have not been assessed directly. Thus, it remains

possible that the neural systems we suggest are crucial

for decoding and reasoning about mental states may be

related to domain-general cognitive skills that are more

heavily tapped in course of these processes. Although no

research has investigated this possibility directly, it is

possible that the findings from our ERP studies mayprovide some hypotheses about candidate cognitive

skills that may be especially important for theory-of-

mind reasoning. For instance, reasoning about mental

states may be rely on contributions from left prefrontal

areas because this skill may be related to executive

functioning and ‘‘inhibitory control.’’ A number of re-

searchers have argued that prefrontal regions are asso-

ciated with executive functions including workingmemory (Smith & Jonides, 1998), error monitoring

(Gehring & Knight, 2000), and inhibitory control (Di-

amond, 1998). Moreover, recent research strongly sug-

gests that these executive skills are crucial for reasoning

about others� mental states (Carlson & Moses, 2001;

Russell, 1996). Together, these findings strengthen the

possibility that left frontal contributions to theory-of-

mind may be related to executive functions in children.One caveat is that the bulk of research from both animal

and human work suggests that the aspects of executive

function that are typically related to theory-of-mind

performance in children are located with in dorsal–lat-

eral prefrontal cortex as opposed to medial frontal

cortex. Clearly, more research is needed to better un-

derstand this discrepancy.

In a similar vein, decoding mental states may recruitneural circuitry within orbitofrontal contributions be-

cause these areas seem to play a special role in decoding

the content of emotionally reinforcing stimuli generally

(Rolls, 1996, this issue). A considerable amount of re-

search now suggests that the orbitofrontal cortex plays a

crucial role in decoding the content of gustatory and

olfactory stimuli (see Rolls, 1996, for a review). Simi-

larly, Bechara and colleagues have demonstrated thatindividuals with damage to orbitofrontal cortex have

difficulty with so-called gambling tasks—card games in

which they are required to distinguish ‘‘rewarding’’

decks from ‘‘punishing’’ decks (e.g., Bechara, Tranel, &

Damasio, 2000). Arguably, the emotional value of social

interaction crucially relies upon the ability to decode

others� mental states. Thus, when mental states are


decoded, they may be represented primarily as socialemotional reinforcers. It may be, then, that orbitofron-

tal contributions to mental state decoding may be re-

lated to the emotionally reinforcing character of mental

states themselves.

As was noted above, we cannot marshal strong evi-

dence in favor of either a domain-specific or domain-

general interpretation of our results regarding the neural

bases of decoding or reasoning about mental states. Onething that is clear, however, is that neural systems as-

sociated with either component of theory-of-mind are

distinguishable from those that are associated with

similar judgments in other domains.

3. Neurobiology of autism: Is there a core deficit?

From the outset, a primary motivation for conduct-

ing our studies was to better understand the neuro-

pathological factors that contribute to autism. This is an

important aim because although it is generally recog-

nized that the cognitive and social deficits seen in autism

have their roots in neurodevelopmental abnormalities,

researchers have had considerable difficulty in accu-

rately characterizing specific sites of pathology (Min-shew & Goldstein, 1998; Piven & O�Leary, 1997). More

specifically, neuroimaging studies have failed to con-

verge on a single focal defect that characterizes the au-

tistic brain (see Rumsey & Ernst, 2000, for a recent

review). There are likely a number of reasons for this

lack of convergence. For one, autism is a heterogeneous

disorder with respect to presentation characteristics.

Affected individuals can range from having profound IQdeficits to relatively normal intelligence. Or, affected

individuals may present either with or without epilepti-

form symptoms. These relatively large variations may

obscure more subtle common neural characteristics

among individuals.

A second, and perhaps more important, reason for

the lack of convergence is that autism is a developmental

disorder. Building on recent work in the domain of de-velopmental cognitive neuroscience, Karmiloff-Smith

(1997) argues that development itself plays an important

role in shaping the functional organization of neural

systems. As such, it does not necessarily follow that

individuals affected by a given developmental disorder

would have a characteristic brain lesion. Instead, the

whole pattern of functional brain organization must be

considered in light of abnormal initial states (e.g., Deb &Thompson, 1998; Elman et al., 1996). This shift in per-

spective militates for understanding the neuro-cognitive

bases of autism from a fundamentally developmental

perspective.

The theory-of-mind framework may provide an ex-

cellent route to adopting just this perspective. Delin-

eating the developmental trajectory of theory-of-mind

skills from infancy through the preschool period hasbeen a central concern for many researchers in the area

of cognitive development. Although even a partial re-

view of this literature is beyond the scope of this paper,

one consistent finding is that children are able to detect

or decode others� mental states before they are able to

reason about those mental states in a sophisticated

manner. One example of this progression is the case of

eye-gaze monitoring. Infants as young as 6-month-oldshow evidence of attending to others� direction of eye-

gaze (Hood, Willen, & Driver, 1998), although it is not

until the age of 18-months (Baldwin, 1991) or later (Lee,

Eskritt, Symons, & Muir, 1998) that they are able to

reliably use this information to reason about others�intentions in a sophisticated manner. Research suggests

that this progression may also hold for later developing

aspects of theory-of-mind reasoning, such as under-standing of knowledge—even young children seem to be

able to reliably indicate whether someone is knowl-

edgeable (Bartsch & Wellman, 1994; Pratt & Bryant,

1990), but they have difficulty reasoning on the basis of

that information (Wimmer, Hogrefe, & Perner, 1988).

That decoding emerges prior to reasoning in the

theory-of-mind domain has important implications for

autism. Specifically, given that autism is a develop-mental disorder, it may be the case that at the core of

this disorder is the ability to engage the right orbito-

frontal/medial temporal circuit that we hypothesize

makes an important contribution to mental state de-

coding. This core deficit may, in turn, lead to additional

abnormalities in functional brain organization, and

theory of mind reasoning. A key piece of evidence in

evaluating this question comes from determining whe-ther young children with autism are specifically impaired

on tasks designed to tap orbitofrontal/medial temporal

functioning relative to other anterior systems.

Unfortunately, the evidence in this regard is sparse.

Dawson and colleagues (Dawson et al., 2002) recently

reported that autistic and non-autistic children who are

matched for mental age do not differ from one another

on tasks that are typically thought to tap dorsolateralversus orbitofrontal functioning (Dawson et al., 2002).

However, this same group of researchers has also re-

ported two very intriguing findings that indirectly link

variability in orbitofrontal functioning to both autism

and to theory-of-mind. First, Dawson and colleagues

(Dawson, Meltzoff, Osterling, & Rinaldi, 1998; Dawson,

Osterling, Rinaldi, Carver, & McPartland, 2001) have

shown that individuals with autism are relatively moreimpaired than mental age matched controls on the de-

layed non-matching to sample task, which taps the

ability to form rules regarding the links between stimuli

and rewards. This is important because research has

shown that this skill is mediated through ventromedial

prefrontal cortex, including orbitofrontal cortex (Meu-

nier, Bachevalier, & Mishkin, 1997). Second, across all


participants, tasks associated with orbitofrontal func-tioning was more likely to be impaired in the ability to

establish ‘‘joint attention,’’ which requires the ability to

detect others� attentional and intentional states based on

the direction of their eye gaze. Developmentally, chil-

dren�s abilities to establish joint attention is widely re-

garded as one of the first milestones on the road to

acquiring a theory-of-mind (Moore, 1999). Moreover, it

is gaining validity as one of the earliest warning signs ofautism (Baird et al., 2000). These findings linking joint

attention abilities with ventral-medial prefrontal func-

tion provide converging evidence for both (1) the fun-

damental role of ventral-medial regions in decoding

mental states (including joint attention), and (2) the

possibility that aspects of orbitofrontal dysfunction may

play a crucial role in understanding the developmental

neuropsychological factors that lead to the social deficitsevidenced by individuals with autism.

Finally, it should be noted that this hypothesis re-

garding the central importance of the orbitofrontal/

medial temporal circuit for both social cognition and

autism extends a long standing hypothesis regarding the

pathological role of the hippocampus and amygdala in

autism. Bachevalier (1994) and others have argued from

the basis of neuropsychological, animal lesion, andneuroimaging studies that the medial temporal lobe is an

important source of dysfunction in autism (see also

Howard et al., 2000). By including a role for orbito-

frontal regions, we may gain important insight into the

neuro-cognitive bases of the theory-of-mind deficits as-

sociated with autism.

4. Conclusions and potential clinical implications

In summary, our findings suggest first that there is no

one highly circumscribed neural circuit that is active any

time one engages in theory-of-mind relevant reasoning.

Instead, the neural circuitry that underlies the ability to

decode mental states from facial displays differs from

that underlying the ability to reason about mental states.Specifically, orbitofrontal cortex may be especially im-

portant for decoding mental states, while left medial

frontal regions may be important for reasoning about

mental states. It is presently unclear as to whether a

domain-specific or domain-general interpretation of

these neuro-cognitive contributions is most warranted.

Nonetheless, these findings may provide a springboard

for exploring some hypotheses about the neuropatho-logical bases of autism. Specifically, it seems possible

that autism may be characterized by a core deficit in the

functioning of the orbitofrontal/medial temporal circuit

that may underlie their difficulties in decoding mental

states. Given that decoding mental states is widely

considered to be the earliest emerging building block of

theory-of-mind development, it could be that a funda-

mental abnormality in mental state decoding is the basisof social cognitive deficits in autism.

We would like to conclude with a speculation about

the possible clinical implications of our findings. A

principal aim of therapists working with individuals

with autism is to improve their social functioning skills.

We, along with others, have hypothesized that the ‘‘core

deficits’’ associated with autism lie in the orbitofrontal/

medial temporal circuit that is important for decodingmental states. In contrast, the left prefrontal regions that

are important for reasoning about mental states may be

relatively less affected. If this were the case, it is possible

that individuals with autism may reveal strengths in

their ability to reason about mental states if the links

between mental states and their observable correlates

(e.g., facial expression) were made more transparent.

Put in another way, perhaps an effective therapeuticstrategy would be to help individuals with autism to

recognize mental states by presenting their contents

more transparently. For instance, individuals with au-

tism might have difficulty recognizing that someone is

sad, but if told explicitly, may be able to make appro-

priate judgments regarding that person�s attendant

mental states.

There is some evidence to suggest that this might bethe case. For instance, Wellman et al. (2002) have shown

that when others� mental states are made explicit

through the use of cartoon-like ‘‘thought bubbles’’ in-

dividuals with autism can solve basic theory-of-mind

tasks, including false belief. Similarly, Tager-Flusberg

(2001) reviews evidence suggesting that individuals with

autism can use language-based strategies to ‘‘hammer

out’’ solutions to problems that require reasoning aboutothers� mental states. More research is required to de-

termine whether these strategies lead to lasting im-

provements in social cognitive skills in individuals with

autism. Nonetheless, this approach may ultimately be an

effective way of capitalizing on the neuro-cognitive

strengths of individuals with autism to better their ev-

eryday social cognitive skills.

Acknowledgments

This article was prepared with support of an NSERC

Discovery Grant. The author thanks Sid Segalowitz and

PhilZelazo for very helpful comments on aprevious draft.

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Understanding orbitofrontal contributions to theory-of-mind reasoning: Implications for autism