Elsevier

NeuroImage

Volume 52, Issue 4, 1 October 2010, Pages 1720-1726
NeuroImage

Selective functional integration between anterior temporal and distinct fronto-mesolimbic regions during guilt and indignation

https://doi.org/10.1016/j.neuroimage.2010.05.038Get rights and content

Abstract

It has been hypothesized that the experience of different moral sentiments such as guilt and indignation is underpinned by activation in temporal and fronto-mesolimbic regions and that functional integration between these regions is necessary for the differentiated experience of these moral sentiments. A recent fMRI study revealed that the right superior anterior temporal lobe (ATL) was activated irrespective of the context of moral feelings (guilt or indignation). This region has been associated with context-independent conceptual social knowledge which allows us to make fine-grained differentiations between qualities of social behaviours (e.g. “critical” and “faultfinding”). This knowledge is required to make emotional evaluations of social behaviour. In contrast to the context-independent activation of the ATL, there were context-dependent activations within different fronto-mesolimbic regions for guilt and indignation. However, it is unknown whether functional integration occurs between these regions and whether regional patterns of integration are distinctive for the experience of different moral sentiments. Here, we used fMRI and psychophysiological interaction analysis, an established measure of functional integration to investigate this issue. We found selective functional integration between the right superior ATL and a subgenual cingulate region during the experience of guilt and between the right superior ATL and the lateral orbitofrontal cortex for indignation. Our data provide the first evidence for functional integration of conceptual social knowledge representations in the right superior ATL with representations of different feeling contexts in fronto-mesolimbic regions. We speculate that this functional architecture allows for the conceptually differentiated experience of moral sentiments in healthy individuals.

Introduction

The ability to be motivated by moral values is uniquely human (Fehr and Fischbacher, 2003). The 18th century British philosophers, Adam Smith and David Hume suggested that our behaviour is guided by intuitive “moral sentiments” which express our moral approval or disapproval (Lamb, 1974). Here, we focus on moral sentiments related to violation of values that are of particular relevance for the understanding of common psychiatric disorders such as major depression (Berrios et al., 1992, O'Connor et al., 2002). We may experience different types of moral sentiments depending on who is the agent of a moral violation. Self-blaming sentiments, such as guilt are associated with self-agency, whereas other-blaming sentiments such as indignation are associated with another person being the social agent (Zahn et al., 2009a).

Previous fMRI studies have revealed activation of the anterior temporal lobe (ATL) and fronto-mesolimbic regions in response to morally relevant stimuli that often evoke the experience of moral sentiments (Heekeren et al., 2005, Moll et al., 2002, Moll et al., 2001, Shin et al., 2000, Takahashi et al., 2004). It has been hypothesized that the experience of such moral sentiments (e.g. guilt and indignation) is underpinned by integration between ATL and fronto-mesolimbic regions (Moll et al., 2005, Zahn et al., 2009a). In a previous study using fMRI, we found activation of the right superior anterior temporal lobe (ATL) that was present irrespective of the type of the moral sentiment experienced (i.e. context-independent). This stable ATL activation was accompanied by context-dependent activations within the subgenual cingulate cortex (extending into the septal area) selective for guilt and within the lateral orbitofrontal cortex (OFC) for indignation.

The context-independent activation of the right superior ATL during the experience of both guilt and indignation is consistent with a model which considers the ATL as a hub that represents abstract and concrete conceptual knowledge that is context-independent and necessary for differentiation and generalization of meaning (Lambon Ralph and Patterson, 2008, Lambon Ralph et al., 2009, Lambon Ralph et al., 2010, Patterson et al., 2007, Rogers et al., 2006, Rogers et al., 2004). According to this model, the ATL allows for the generation of “coherent concepts” across different domains and modalities (Lambon Ralph et al., 2010) such that objects and actions can be identified, understood and generalized across different contexts. ATL activation during fMRI has also been found when probing person-related information (Simmons et al., 2009, Tsukiura et al., 2008, Campanella and Belin, 2007). Further, the inferior anterior temporal region has been demonstrated to allow identification of faces (Kriegeskorte et al., 2007). Although, Simmons et al. (2009) were able to detect ATL activations for person-related information, they did not find activations for non-social inanimate objects as would have been predicted by a domain-general account of ATL function. This may be explained by the use of tasks that probe newly learned associations between object names (e.g. “The Newport building”) and functional features (“is used for voter registration”) that are not part of the generalizable definition of the coherent concept.

Recent evidence implicates the superior aspect of the right ATL in the representation of context-independent conceptual social knowledge which allows us to differentiate between different social behaviours (e.g. ‘stingy,’ ‘generous,’ ‘honest’ or ‘brave’) (Zahn et al., 2009b, Zahn et al., 2007, Zahn et al., 2009a), and is necessary to understand and emotionally evaluate the behaviours of ourselves and others. We hypothesized that these context-independent, conceptual representations of social behaviour can be flexibly embedded within different feeling contexts (Moll et al., 2005, Zahn et al., 2009a). This conceptual social knowledge was hypothesized to be an integral part of the experience of moral sentiments, acting to enrich feelings with differentiated meaning (Moll et al., 2005).

In addition to this context-independent ATL activation there was context-dependent activation of the subgenual cingulate cortex extending into the septal area during the experience of guilt (Zahn et al., 2009a). The septal region comprises the ventral part of the human septum (i.e. “septum verum”) and can be distinguished from the septum pellucidum (Andy and Stephan, 1968). The septum verum contains a group of basal forebrain nuclei that have greatly increased in size with phylogeny from lower animals to humans (Andy and Stephan, 1968). Previous fMRI studies have found activations in various parts of the septal region and the adjacent subgenual cingulate cortex (further referred to as septal region/subgenual cingulate cortex (SSC)) for tasks that are associated with affiliative feelings such as altruistic (Moll et al., 2006), and trust-based decisions (Krueger et al., 2007), as well as for both passive viewing (Zahn et al., 2009c) and emotional judgements of guilt-evoking stimuli (Zahn et al., 2009a). These studies did not specifically dissociate the emotional and cognitive aspects of affiliative feelings as they are highly interdependent (Moll et al., 2005). Guilt is ultimately pro-social in nature (Moll et al., 2008) since it is derived from our concern for the wellbeing of other individuals (Weiss et al., 1995) and enhances relationships by promoting maintenance of attachment to loved ones (Baumeister et al., 1994). Thus, the activation of the SSC during the experience of guilt is in line with evidence suggesting that this region is involved in affiliative feeling contexts. We speculate that parts of the SSC region may represent affiliative values of social behaviours which are important for evaluating, planning and choosing between different social actions.

Interestingly, abnormalities in the subgenual cingulate cortex have been found consistently in patients with major depression (Drevets and Savitz, 2008, Ebert and Ebmeier, 1996, Ressler and Mayberg, 2007). These patients often experience guilt in an “inappropriate” manner (DSM-IV, American Psychiatric Association, 2000); that is, the experience of guilt becomes overgeneralized to inappropriate contexts. Patients may also feel something which they clearly label as guilt, but are unable to tie to a specific transgression or misdeed (Berrios et al., 1992). It has been hypothesized that in order to experience guilt in a differentiated fashion, conceptual social knowledge in the ATL must be integrated with affiliative feeling contexts represented in the SSC (Moll et al., 2008, Zahn et al., 2009c). If such conceptual knowledge is not well integrated, then guilt may be experienced inappropriately as it is in major depression (Berrios et al., 1992, O'Connor et al., 2002).

In contrast to the guilt-selective activation of the SSC, the experience of indignation was associated with activation of the lateral OFC (Zahn et al., 2009a), one of a number of regions including the insula and dorsomedial prefrontal cortex (PFC) that have been implicated in the experience of negative emotions such as anger, disgust and contempt (Blair et al., 1999, Calder et al., 2000, Fitzgerald et al., 2004, Seymour et al., 2007). That this region is activated during the experience of negative moral sentiments is in accordance with its role in the representation of non-affiliative punishment/reward values and outcomes of both sensory, (Rolls, 2004, Small et al., 2001) and abstract reinforcers such as money (O'Doherty et al., 2001).

Although the above results suggest that the SSC, lateral OFC and ATL play an important role in the experience of guilt and indignation, it is unknown whether functional integration occurs between these regions and whether there are distinct patterns of integration for different moral sentiments. It is well established that cognitive functions depend on functional integration across anatomically distributed networks (Friston, 2010), yet conventional fMRI analyses are not suited to investigate which regions within a given network interact to support a given cognitive function. Standard analyses of Blood-Oxygenation-Level-Dependent (BOLD) effects revealing two brain regions responding to a psychological stimulus do not indicate that there are psychologically and physiologically relevant interactions occurring between these areas. Psychophysiological interaction (PPI) analyses, however, can elucidate whether functional integration occurs between regions and whether this integration changes during different psychological contexts (Friston et al., 1997). PPI analysis is based on a regression model which includes the interaction term of the psychological variable convolved with an estimate of the neural activity in a seed region, as a predictor variable. As such, this analysis probes the association between two brain regions during a given psychological condition. Thus, a change in the association between the two brain regions due to a change in the psychological context would be reflected in the change of the regression slope. If this change is significant, a significant PPI effect is said to occur (Friston et al., 1997). Thus, PPI analyses reveal fundamentally different information to standard BOLD effect analyses that do not explore interactions or coupling of activation between regions.

Here, we used PPI analysis with a right superior ATL seed region to test two hypotheses: 1) There is selective integration between the right superior ATL and SSC during the experience of guilt compared with indignation, and 2) There is selective integration between the right superior ATL and lateral OFC for indignation compared with guilt.

Section snippets

Materials and methods

Here, we briefly summarize the fMRI methods we used in this paper. Standard BOLD effect results, imaging and behavioural data acquisition methods have previously been reported (Zahn et al., 2009a).

Imaging results

There were no significant PPI effects for comparisons of guilt vs. indignation and indignation vs. guilt when individual frequencies of guilt and indignation were used as covariates of no interest. All results reported below are from analyses including individual frequencies of guilt and indignation as covariates of interest. There were no significant effects in any of our Tier 1 a priori ROIs (posterior superior temporal sulcus/temporo-parietal junction, anterior temporal lobes, ventromedial

Discussion

A previous study has demonstrated that the right superior ATL is activated irrespective of the type of moral sentiment experienced, together with sentiment-selective activations in different fronto-mesolimbic regions (Zahn et al., 2009a). However, it was unknown whether there is functional integration between these regions. Using a PPI analysis, we were able to confirm our hypotheses that there is selective functional integration between the right superior ATL and the SSC for guilt and between

Acknowledgments

This study was supported by NINDS (USA) intramural funding to J.G. and a German National Academy of Sciences Leopoldina Fellowship funded by the Federal Ministry of Education and Research (BMBF-LPD 9901/8-122) to R.Z. S.G. was funded by an MRC PhD studentship. R.Z. was supported by a Stepping Stones Fellowship from the Faculty of Medical and Human Sciences, The University of Manchester, UK. J.M. was supported by the LABS-D'Or Hospital Network, Rio de Janeiro, Brazil. E.A.S. was funded by a

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