Accepted Manuscript What brain imaging did (not) tell us about the Inferior Frontal Gyrus in Theory of Mind – A commentary on Samson et al., (2015) Matthias Schurz, Matthias G. Tholen PII:

S0010-9452(15)00305-6

DOI:

10.1016/j.cortex.2015.08.011

Reference:

CORTEX 1573

To appear in:

Cortex

Received Date: 30 March 2015 Revised Date:

6 July 2015

Accepted Date: 8 August 2015

Please cite this article as: Schurz M, Tholen MG, What brain imaging did (not) tell us about the Inferior Frontal Gyrus in Theory of Mind – A commentary on Samson et al., (2015), CORTEX (2015), doi: 10.1016/j.cortex.2015.08.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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What brain imaging did (not) tell us about the Inferior Frontal Gyrus in Theory of Mind – A commentary on Samson et al., (2015)

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Centre for Cognitive Neuroscience, University of Salzburg, Austria

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Correspondence to:

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Matthias Schurz1 & Matthias G. Tholen1

Matthias Schurz.

Postal Address: Centre for Cognitive Neuroscience, University of Salzburg, Hellbrunnerstr.34, 5020 Salzburg, Austria.

Phone: (+43)/662/8044-5142; Fax:(+43)/662/8044-5126. E-mail: [email protected]

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1. Neuropsychological evidence on the IFG Studies on brain-damaged patients frequently report a co-occurrence of executive function and mentalizing deficits. Of particular interest, Samson and colleagues show a series of patient studies that link right lateral frontal cortex to a process with specific relevance for theory of mind (ToM): The ability

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to inhibit one’s own perspective (Samson, Apperly, & Humphreys, 2007; Samson, Apperly, Kathirgamanathan, & Humphreys, 2005; Samson, Houthuys, & Humphreys, 2015). In their most recent study, in this journal, Samson et al. (2015) show that self-perspective inhibition deficits cannot be simply equated to general executive control deficits. Samson et al. present a functional double-dissociation in a group of patients, which shows that patients impaired at inhibiting self-perspective do not have problems

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at inhibiting interference from another salient but irrelevant information when mentalizing. On the other hand, patients with severe executive function deficits do not show impairments in inhibiting self-

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perspective. The sites of brain damage found in the two patient groups point towards an important role of the right Inferior Frontal Gyrus (IFG) for self-perspective inhibition in ToM tasks.

2. What does functional brain imaging say about the IFG?

Brain imaging studies report diverse findings on the IFG in ToM, which we will review and try to reconcile with neuropsychological theories. In Table 1, we summarize functions of the IFG according to the 10 most cited review-papers on the neuroscience of ToM. (Arguably, other criteria could be used for

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selecting articles, like for example the most recent or most relevant to the current topic. However, we decided for number of citations, as it best reflects the dissemination of a theoretical view). To identify these papers, we performed a literature search with the key-words “theory of mind / mentalizing / mindreading” in all Web of Science databases. Further we limited our results to journals from the research

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areas “neuroscience / neurology” and document types “review”. Some of the reviews of the resulting list took into account both functional imaging and neuropsychological research (e.g. Adolphs, 2009; Lieberman, 2007) while others only focused on the former. Reviews relying on psychological disorders

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(Brune, 2005; Williams, Whiten, Suddendorf, & Perrett, 2001), cognitive development (Tomasello, Carpenter, Call, Behne, & Moll, 2005; Tomasello, Kruger, & Ratner, 1993), processing of eye gaze (Emery, 2000), or exclusively focusing on other brain areas (Decety & Lamm, 2007; Olson, Ploaker, & Ezzyat, 2007) were excluded.

Five out of the ten reviews ascribed the IFG a functional role in ToM (we also accepted if reviews used the term ventro-lateral prefrontal cortex (vlPFC) instead of IFG). We have summarized these accounts in Table 1. A remarkable variety of functions was suggested: attentional reorienting (Corbetta, Patel, & Shulman, 2008), mirroring (Frith & Frith, 1999), working memory (Spreng, Mar, & Kim, 2009) and inhibition / cognitive control (Lieberman, 2007). These different functions were in parts also linked to different sub-areas of the IFG. Theories about mirror functions (Frith & Frith, 1999; van Overwalle, 2009)

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referred to human homologue of area F5 - possible located around BA 44 in IFG and BA 6 in ventral premotor cortex (Morin & Grezes, 2008; Rizzolatti & Craighero, 2004). Theories about more executive functions such as working memory (Spreng et al., 2009) or self-perspective inhibition (Lieberman, 2007; Samson et al., 2015) referred to more ventral parts of the IFG, including vlPFC and BA 47. For

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comparison, Figure 1A shows the location of IFG, vlPFC and the neural locus for self-perspective inhibition as suggested by Samson et al. (2015). Finally, the ventral attention system discussed by

Corbetta et al. (2008) is assumed to span a range of lateral frontal areas, including large parts of the IFG.

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We argue that the variety of functions ascribed to the IFG probably reflects that researchers had different types of ToM (measured by different tasks) in mind when discussing the area. In a recent metaanalysis (Schurz, Radua, Aichhorn, Richlan, & Perner, 2014), we looked at task-related brain activity in ToM. The results are shown in Figure 1B, with the outlines of the IFG highlighted for guidance. Our meta-analysis found activation in IFG only for social animations and mind in the eyes tasks. We give examples for these tasks in Table 2. On the right side, we found activation in dorsal parts of the IFG pars

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triangularis for both task groups, and in more ventral parts of right pars triangularis for mind in the eyes. On the left side, we found much broader activation. For social animations, activation spanned middle frontal gyrus, large parts of IFG pars triangularis, and anterior insula. For mind in the eyes, left frontal activation was even more extended, spanning large parts of IFG and precentral gyrus and parts of middle

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frontal gyrus as well as insula. Typically, these two tasks are assumed to be involved in mirroring processes, and not linked to self-perspective inhibition. In line with that, we concluded in our metaanalysis (Schurz et al., 2014) that the common element of the mind in the eyes and the social animations

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tasks is engagement of mirror neurons due to identification of actions implied by movements in animations and identification of emotions shown in eyes (in concert with the limbic system). No other functions were designated to the IFG at that point.

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However, we now take a second look at our meta-analysis results: Given the other functions the IFG is supposed to play in mentalizing, it is surprising that it did not activate for other tasks in the meta-

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analysis. In particular, we will consider the case of self-perspective inhibition. We argue that two tasks are expected to rely particularly strong on this function. First, false belief tasks require participants inhibiting their knowledge about the true state of affairs in order to understand the other’s false belief, as already discussed by Samson et al. (2015). A second task that may engage self-perspective inhibition is a strategic

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game, in particular in a competitive setting. Playing a competitive strategic game requires the separation between self and other, or in other words, keeping apart the (potentially conflicting) goals of oneself and the opponent (Decety, Jackson, Sommerville, Chaminade, and Meltzoff, 2004). Similar demands are posed by the card game used in the experiments by Samson et al. (2015). In some trials, perspectives of players were in conflict, e.g. Player A desired the next card to be red, but Player B desired it to be blue.

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Right IFG patients were particularly prone to imputing their own desire to the other player here. Thus, there is a parallel between the card game used in Samson et al. (2015) and strategic games in our imaging

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meta-analysis, which leads us to speculate that both contain self-perspective inhibition. Taken together, we see a link to self-perspective inhibition for false belief and strategic games, but not for other tasks featured in the meta-analysis. As shown in Figure 1, neither false belief nor strategic games activate the IFG in the meta-analysis, which does not seem to support findings from neuropsychological research. However, the apparently negative findings can be explained by the control conditions used.

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3. The effect of control condition

We expected IFG activation for false-belief and strategic games in the meta-analysis. False belief tasks in the meta-analysis used a photo task as control. Here, participants were asked about the outdated

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content shown on a picture (e.g. “A photo shows the apple hanging on a tree …”), while things in reality have changed (e.g. “… while the photo was developed, a strong wind blew the apple from the tree”). As discussed by Saxe (2010), the photo control task has similar executive demands as the false belief task. We speculate that this could also apply to self-perspective inhibition: Participants need to inhibit their knowledge about the true state of affairs (e.g. the apple is on the ground) in order to respond according to what is shown on the photo (e.g. the apple is hanging on the tree). Interestingly, an fMRI study by Saxe, Schulz, and Jiang (2006) found equally high levels of activation for false belief and photo task in the dorso-lateral prefrontal cortex (middle frontal gyrus). The authors did not, however, look at the patterns in the IFG. We speculate that the photo control task could also activate the IFG to some extent, explaining why no activation shows up in the contrast false belief > photo. An argument can also be made for

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strategic games. Here the studies in the meta-analysis asked for playing against a computer algorithm in the control task. Similar as for playing against a human, to understand the strategy or principles behind the computer algorithm, participants need to keep separated their own goals from the computer’s plans. In this respect, it is fair to say that also for some other and very prominent components of the ToM

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network, imaging studies found equal activation levels for well-matched control conditions. For example, Saxe and Powell (2006) showed that the ventro-medial prefrontal cortex is equally active for reading stories about other’s bodily sensations (e.g. “Sheila skipped breakfast … By the time she got off the train, she was starving.”) and other’s thoughts (e.g. “Nicky knew that his sister’s flight from San Francisco was delayed ten hours…”). Perner, Aichhorn, Kronbichler, Staffen, and Ladurner (2006) found that the left

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temporo-parietal junction, the precuneus, and the dorso-medial prefrontal cortex (z=36) are equally

activated by stories about false belief and by stories about false signs (e.g. “The sign to the monastery

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points to the path through the woods. While playing the children make the sign point to the golf course. According to the sign the monastery is now in the direction of the . . . golf course/woods?”). These findings make clear that the IFG deserves similar theoretical interest as other areas of the ToM network. The recent findings by Samson et al. (2015) draw particular attention on the area, as they are showing that self-perspective inhibition is a special process not simply attributable to general executive functions. To gain a full understanding of the IFG’s role in ToM, we encourage future imaging

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studies to use a wider range of control conditions.

Figure 1. (A) The IFG shown on a macroanatomic map (left panel), the vlPFC shown on a Brodmann

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map (middle panel), and fMRI findings linked to self-perspective inhibition (right panel) as reviewed by Samson et al. (2015). (B) Results from meta-analyses on different ToM tasks, reviewed in Schurz et al. (2014). Maps were thresholded at voxel-wise threshold of p < .005 uncorrected and a cluster extent

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threshold 10 voxels.

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ACCEPTED MANUSCRIPT Table 1. The IFG’s function in most influential reviews on theory of mind. Reviews

IFG /

Specification

Hemi.

Function

Parts of MFG, IFG,

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Attentional reorienting

F5

n.a.

Mirroring actions

vlPFC

n.a.

Self-perspective inhibition

Spreng et al., 2009

vlPFC, BA 47

n.a.

Van Overwalle, 2009

F5

L, R

Adolphs, 2009

-

Buckner & Caroll, 2007

-

Corbetta et al., 2008

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vlPFC

Frith & Frith, 1999 Frith & Frith, 2006

-

Gallagher & Frith, 2003

-

Lieberman, 2007 -

Working memory

Mirroring actions

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Singer, 2006

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AI, FO

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Abbreviations: MFG... Middle frontal gyrus, IFG... Inferior frontal gyrus, AI... Anterior Insula, FO... Frontal Operculum, F5... human homologue to monkey F5 (roughly BA 44/6), vlPFC... ventro-lateral Prefrontal Cortex.

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Img.

Experimental task

Control Task

False belief vs. photo

fMRI

Read a short vignette involving a person holding a false

Read a false-photograph vignette. Answer a question concerning

2003

n=21

belief. Answer a question about her belief. e.g. 'John

the outdated content in the photo. e.g. ‘A photograph was taken of

told Emily that he had a Porsche. Actually, his car is a

an apple hanging on a tree branch. The film took half an hour to

Ford. Emily doesn't know anything about cars so she

develop. In the meantime, a strong wind blew the apple to the

believed John. When Emily sees John's car, she thinks it

ground. The developed photograph shows the apple on the …?

is a …?’ (Porsche or Ford).

(tree or ground).’

Trait Judgments

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Saxe

fMRI

Read an adjective. Indicate whether it can be true for a

Read an adjective. Indicate whether it can be true for an object. e.g.

2002

n=34

hypothetical person. e.g. '”nervous” … can it be true

'”sundried” … can it be true for “grape”?’

for “David?”?’

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Strategic Games

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Mitchell

Kircher

fMRI

Play the prisoner’s dilemma game (iterated version).

Play the prisoner’s dilemma game (iterated version). You play with

2009

n=14

You play with a human player for game points. Both

a computer.

players choose a cooperative or defective strategy on each trial. If both players choose defective, they gain almost no game points at all. If both choose

cooperative, both gain some game points. If players choose differently, the defective player gains more

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points.

Social Animations

Castelli

PET

Watch a video animation of two interacting triangles

Watch video animation of two randomly moving triangles.

2000

N=6

(e.g. mother and child are playing). Explain verbally

Explain verbally what was happening (after fMRI).

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what was happening (after fMRI).

Mind in the Eyes

fMRI

View photographs of eyes. Indicate which of two words

Cohen

n=12

(e.g., concerned versus unconcerned) describes the

1999

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Baron-

View photographs of eyes. Indicate if the person is male or female.

mental state of that person.

Rational Actions

Brunet 2000

fMRI

View a cartoon story and predict what will happen

View a cartoon story and predict what will happen based on

n=8

based on intentions of a character (no false belief).

physical causality. Choose a logical story ending from several

Choose a logical story ending from several options

options shown in pictures. e.g. A person is standing in front of a

shown in pictures. e.g. A prisoner is in his cell. First, he

slide. A large ball is coming down this slide, heading towards the

breaks the bars of his prison window. Then he walks to

person standing there. Participants must indicate what will happen

his bed. Participants must indicate what will happen

next … the ball is knocking over the person / the ball is resting on

next … the prisoner ties a rope from the sheets on his

the ground and the person is standing next to it.

bed /the prisoner shouts out loud.

1

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A. The Inferior Frontal Gyrus Self-perspective inhibition

vlPFC

IFG Pars… opercularis triangularis orbitalis

BA 44 BA 45

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BA 47

B. Activation in Theory of Mind Social Animations (n=14)

Trait Judgments (n=15)

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False Belief vs. photo (n=15)

Strategic Games (n=9)

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Mind in the Eyes (n=10)

Rational Actions (n=10)