Elsevier

NeuroImage

Volume 56, Issue 3, 1 June 2011, Pages 1832-1838
NeuroImage

Specialization of right temporo-parietal junction for mentalizing and its relation to social impairments in autism

https://doi.org/10.1016/j.neuroimage.2011.02.067Get rights and content

Abstract

Over the last 25 years, “mindblindness” (deficits in representing mental states) has been one of the primary explanations behind the hallmark social-communication difficulties in autism spectrum conditions (ASC). However, highlighting neural systems responsible for mindblindness and their relation to variation in social impairments has remained elusive. In this study we show that one of the neural systems responsible for mindblindness in ASC and its relation to social impairments is the right temporo-parietal junction (RTPJ). Twenty-nine adult males with ASC and 33 age and IQ-matched Controls were scanned with fMRI while making reflective mentalizing or physical judgments about themselves or another person. Regions of interest within mentalizing circuitry were examined for between-group differences in activation during mentalizing about self and other and correlations with social symptom severity. RTPJ was the only mentalizing region that responded atypically in ASC. In Controls, RTPJ was selectively more responsive to mentalizing than physical judgments. This selectivity for mentalizing was not apparent in ASC and generalized across both self and other. Selectivity of RTPJ for mentalizing was also associated with the degree of reciprocal social impairment in ASC. These results lend support to the idea that RTPJ is one important neural system behind mindblindness in ASC. Understanding the contribution of RTPJ in conjunction with other neural systems responsible for other component processes involved in social cognition will be illuminating in fully explaining the hallmark social-communication difficulties of autism.

Research Highlights

► RTPJ is not selectively responsive to mental state information in autism. ► Lack of RTPJ mentalizing selectivity in autism generalizes across self and other. ► RTPJ mentalizing selectivity is related to variation in social impairment in autism.

Introduction

A hallmark of autism spectrum conditions (ASC) are marked impairments in reciprocal social interaction. At the cognitive level, one theory that can help explain such difficulties is the “mindblindness” theory of autism (Baron-Cohen, 1995, Frith, 2001). Mindblindness makes three predictions about the mechanisms involved in social-communication difficulties in ASC. First, there are underlying impairments in domain-specific mechanisms for representing mental state information. Second, deficits in these mechanisms generalize across the case of whether the target of the mental state is self or other. Third, impairment in domain-specific mechanisms for representing mental state information should be related to variation in reciprocal social impairment.

While behavioral studies have documented mentalizing impairments in autism, it has been difficult to take such information and tie it directly to the specific underlying neural systems involved in representing mental states. However, functional neuroimaging provides an opportunity to gain insight into the underlying neural systems involved in mindblindness. While there have been several neuroimaging studies on mentalizing in autism, they vary on many levels. This variation makes it difficult to tie directly back to the main predictions of the mindblindness theory (i.e. a deficit in domain-specific mechanisms for representing mental state information, applied to both self and other, and that such deficits relate back to variation in social impairment). For example, the types of tasks used to elicit mental state representation, vary greatly from study to study; from reading prosodic and nonverbal cues (Tesink et al., 2009, Wang et al., 2006, Wang et al., 2007), reading information from the eyes (Baron-Cohen et al., 1999), automatically attributing mental states to moving geometric shapes (Castelli et al., 2002, Kana et al., 2009), stories eliciting belief representation (Happé et al., 1996), narratives with demands for representing intentions (Mason et al., 2008), making judgments about “psychological traits” (Kennedy and Courchesne, 2008), judging whether the experimenter was being helpful or unhelpful (Gilbert et al., 2009), judging trustworthiness from faces (Pinkham et al., 2008), and making introspective emotion judgments versus judging the color of pictures (Silani et al., 2008). This wide variability may account for some of the lack of consistency across studies. The most replicable result appears to be hypoactivation of the dorsomedial prefrontal cortex (dMPFC) (Castelli et al., 2002, Happé et al., 1996, Kana et al., 2009, Kennedy and Courchesne, 2008, Silani et al., 2008, Wang et al., 2007). However, because of the marked variability amongst tasks it is hard to explain why other studies did not observe the same effect (Baron-Cohen et al., 1999, Gilbert et al., 2009, Mason et al., 2008, Pinkham et al., 2008, Tesink et al., 2009, Wang et al., 2006). Finally, with respect to tasks, it is not always apparent that the task used in any individual study can elicit engagement of all regions within the standard mentalizing circuit; that is, medial prefrontal cortex (MPFC), posterior cingulate cortex/precuneus (PCC), and bilateral temporo-parietal junction (RTPJ, LTPJ) (e.g., (Amodio and Frith, 2006, Frith and Frith, 2003, Jenkins and Mitchell, 2010, Saxe and Powell, 2006, Saxe et al., 2009)). This point is particularly important, because without a task that can elicit engagement of various regions within the mentalizing circuit in the comparison group, it is hard to tell whether these areas would have been sensitive to any real impairments if given a sensitive enough task. It is also particularly noteworthy that sample sizes of existing studies tend to be relatively low (range = 5–24; mean Control n = 14.72; mean ASC n = 14.63) and that not all studies directly investigate whether atypical neural systems involved in mentalizing relate to variation on clinical measures of social impairment.

Acknowledging these difficulties is an important first step if we are to attempt to gain a clearer understanding of which neural systems are specifically implicated in “mindblindness” in ASC. It is important that we do this because there are likely to be many component processes affecting the phenotypic variability in autistic social impairment (e.g., mindblindness, self-referential processes, face-processing, emotion, etc.) (Lombardo and Baron-Cohen, 2011, Lombardo and Baron-Cohen, 2010, Lombardo et al., 2011). By identifying specific neural systems that can account for these component processes (mindblindness being one of these component processes) we are in a better position to shed insight into the mechanisms that lead to autism (Happé et al., 2006, Lombardo et al., 2011).

In this study we directly address the main three predictions of mindblindness in ASC; that is, which neural systems are responsible for the domain-specific impairments in representing mental state information, whether deficits are observed across both self and other, and how (if at all) does the atypical functioning of these neural systems relate to variation on clinical measures of social impairment? We employ a mentalizing task known to elicit robust activation of the mentalizing circuit across both self and other in the general population (Lombardo et al., 2010b) and which is constrained to being selective to the demands of representing mental state information while holding constant semantic and social judgment demands and controlling for the target for which the judgment is about (self or other). Furthermore, our sample size is double that of the average sample size observed in existing studies, thus increasing statistical power to detect more subtle effects. Finally, we directly investigate whether any atypical neural systems involved in mentalizing are related variation on clinical measures of social impairment.

We predict that areas known to be involved in mentalizing, such as bilateral TPJ, PCC, and MPFC (Mitchell et al., 2005, Saxe and Kanwisher, 2003, Saxe and Powell, 2006, Saxe et al., 2009), would be less selective for representing mental state information in ASC. Furthermore, this decreased specialization for mentalizing should be a main effect of mentalizing and generalize across self and other, rather than being target-specific. Finally, decreased specialization for mentalizing should be associated with variation on clinical measures of reciprocal social impairment.

Section snippets

Participants

Thirty-three typical adult males (mean age 27.97 years ± 6.10 SD, range 18–42) and 33 male adults with ASC (mean age 26.59 years ± 7.04 SD, range 18–41) participated in this study. Both groups were matched on age and all subscales of the Wechsler Abbreviated Scales of Intelligence (Weschler, 1999) (see Table 1). ASC participants were all clinically diagnosed by ICD-10 criteria as Asperger syndrome (ICD-10, 1994). The Toronto Alexithymia Scale (Bagby et al., 1994), Autism Spectrum Quotient (AQ) (

Behavioral data

Behavioral data for task performance on the fMRI paradigm has been reported elsewhere (Lombardo et al., 2010a). Briefly reiterating these results for the specific comparisons of interest in this study (mentalizing vs. physical judgments), there was no significant interaction effect of Group × Judgment type (relevance rating, p > 0.40; reaction-time, p > 0.95), thus demonstrating that groups responded similarly while making mentalizing and physical judgments.

fMRI data

Our primary analysis was a

Discussion

This study assessed three fundamentally important questions relevant to the mindblindness theory of autism. First, we wanted to know which neural systems are responsible for the domain-specific difficulties in representing mental state information in autism. Second, we assessed whether such atypical neural systems for mentalizing are atypical both when the target of mentalizing is self or other. Third, we investigated how (if at all) such atypical neural mentalizing systems relate to variation

Financial disclosure

ETB is employed half time by the University of Cambridge and half time by GlaxoSmithKline plc. None of the other authors have any other biomedical financial interests or potential conflicts of interest.

Acknowledgments

We thank Jason Mitchell and Adrianna Jenkins for generously letting us use their stimuli, and Uta Frith, Andy Calder, Kevin Pelphrey, and two anonymous reviewers for their valuable discussion and comments. We also acknowledge financial support from the Medical Research Council (MRC) Autism Imaging Multi-Centre Study (AIMS) Consortium, a doctoral studentship to MVL by the Shirley Foundation and the Cambridge Overseas Trust, and from an MRC program grant to SBC. This work was conducted in

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