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PII: S0149-7634(19)30077-6
DOI: https://doi.org/10.1016/j.neubiorev.2019.10.022
Reference: NBR 3587
Please cite this article as: Zahn R, de Oliveira-Souza R, Moll J, Moral Motivation and the
Basal Forebrain, Neuroscience and Biobehavioral Reviews (2019),
doi: https://doi.org/10.1016/j.neubiorev.2019.10.022
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pertain.
a
Cognitive and Behavioral Neuroscience Unit, D’Or Institute for Research
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Neuroscience, King’s College London, United Kingdom.
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c
The Federal University of the State of Rio de Janeiro, Rio de Janeiro,
Brazil.
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* Corresponding author
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e-mail: jorge.moll@idor.org.
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Highlights
Moral motivations drive humans to serve the needs of others and
society.
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bonding.
Abstract
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Moral motivations drive humans to sacrifice selfish needs to serve the needs
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of others and internalized sociocultural norms. Over the past two decades,
several brain regions have been associated with different aspects of moral
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cognition and behaviour. Only more recently, however, investigations have
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highlighted the importance of the basal forebrain for moral motivation. This
across mammal species, and the closely connected subgenual frontal cortex.
Keywords:
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cortex
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1. Introduction
urgent need to understand the roots of the sheer altruism of voluntary acts,
Significant advances have been made in identifying the key neural systems
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our review over a decade ago(Moll et al., 2005). Despite the rapidly
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expanding field of moral cognitive neuroscience(Fumagalli and Priori,
2012), only recently new research has started to unveil the brain systems
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underpinning moral motivations (being motivated to e.g. “help an orphan
child”), that are important for driving moral behaviour (e.g. “donating to a
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charity that benefits orphan children”, Box 1). In keeping with our view of
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require both cognitive components which specify the goal of one’s action
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motivation that postulate closely connected, but distinct roles of (1) goal
al., 2008; Nowak and Sigmund, 2005). Impaired moral motivations are
play the moral rules when self-interest is at stake but fail to do so otherwise
Over the last decade, novel evidence on the neural basis of moral
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motivations has emerged, and as we will show in this review, has
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septo-hypothalamic and subgenual frontal areas. These structures are closely
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connected anatomically (Box 2). In this review, we will integrate this recent
evidence for the first time to elucidate the role of these regions in moral
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motivation, for which we only had scarce evidence in our review over a
et al., 2012; Preston, 2013; Stack et al., 2002) and the role of the subgenual
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and the value of social outcomes (Moll et al., 2008; Moll et al., 2006).
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with those responsible for general reinforcement and social cognition (Moll
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lesion studies are able to identify brain regions that are necessary for a
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psychological wellbeing research.
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2. What are moral motivations?
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Morality can be operationally defined as the sets of customs and values
sharply defined as being driven by the needs of other people, including kin,
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cannot be determined.
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them as feelings. We may also use the term emotions synonymously with
feelings or sentiments.
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As mentioned above, we conceive of moral motivation as consisting of
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both the motivational force and the associated goal. This definition
In this section, we will first review studies of patients with brain lesions
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beyond the scope of this review to systematically report all the brain regions
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Among others, two isocortical brain regions that have been implicated in
superior anterior temporal cortex (ATL) and the medial frontopolar cortex,
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3.1. Brain lesions and impaired moral behaviour
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prosocial behaviour, lesion studies provide important insights, even if they
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relate to less confined anatomical territories such as the ventral frontal areas
which contain but are not limited to the subgenual region. The 19 th century
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physician Leonore Welt provided the first review of patients who exhibited
1888),(Zahn et al., 2011a). In her article, she presented the case of a furrier
predominant damage to the right frontal lobe. Based on the location of the
injury found at autopsy in her case as well as in 12 others that she collected
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from the literature with similar changes in moral character, Welt concluded
that damage to the right medial orbital region was the common
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2000), which was independently associated with atrophy of right ATL and
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warmth(Sollberger et al., 2009). More recent studies have provided evidence
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associated with posterior medial orbitofrontal atrophy (Baez et al., 2016)
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close to the subgenual cortex. Loss of guilt was also reported by caregivers
Converging evidence from fMRI and patients with FTD linked the
versa(Zahn et al., 2009b),(Moll et al., 2011). These studies indicate that loss
dissociable (Box 3). Septal damage in FTD was associated with diminished
addition to guilt and pity(Moll et al., 2011). This showed that septal damage
empathic concern for other people, whilst frontopolar cortical damage was
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which is primarily related to upholding one’s social reputation rather than
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other negative emotions such as anger and disgust, whose impairment was
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associated with amygdala and dorsomedial FC damage(Moll et al., 2011),
the right superior ATL(Zahn et al., 2007) and different moral feelings in
2004). These results are further consistent with the hypothesis that frontal
and subcortical basal forebrain regions are necessary for core aspects of
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Taken together, lesions in the hypothalamus, the septal region and
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subgenual cortex (BA25) and the more anterior subgenual cingulate and
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subgenual orbitofrontal areas, led to changes in moral behaviour which
would be compatible with their proposed critical role for moral motivation.
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Lesions to other cortical brain regions which were shown to represent goals
cortex, (Wood and Grafman, 2003; Zahn et al., 2017)) and conceptual
quality of social behaviour (right superior ATL, (Zahn et al., 2009b)) led to
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changes in moral behaviour as well (Zahn et al., 2017) in keeping with the
notion that motivations rely both on the motivational force as well as the
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dorsomedial frontal and dorsal anterior cingulate cortices are usually not
2005). This does not preclude an important role of these regions in socio-
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review. For example, the dorsal anterior cingulate region is activated for
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evidence of selective social impairments. It is also important to note that
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such as strategic cooperation, more generally (Melloni et al., 2016) rather
frontopolar and angular gyrus atrophy and envy in moral situations was more
associations.
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(Eslinger and Damasio, 1985). This indicates the existence of at least partly
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discussed so far, however, have not made this direct comparison, which is
for investigating the neural basis of complex altruistic behaviour (Figure 2).
with decisions associated with pure monetary gain for oneself(Moll et al.,
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2006). The septal and subgenual cortex and the anterior medial
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the latter area being more active during costly choices. Moreover, septal
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activations were also detected when pairs of participants relied on
the septal area in donation behaviour has also been confirmed in more
activity was observed when healthy subjects observed sad faces when taking
2014).
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shock(FeldmanHall et al., 2012) (FeldmanHall et al., 2015). Moreover,
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charitable donation task(Hare et al., 2010) and correlated with individual
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differences in aversion to third-party harm(Wiech et al., 2013). A meta-
both found consistently in selfish and vicarious reward studies vs. low level
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for vicarious rewards as one might have expected on the basis of our review
the cited studies and this will bias the results against basal forebrain areas
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improve the otherwise high rate of signal dropout due to the vicinity of the
activations in small brain regions. This could explain why a more recent
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activations in the subgenual cortex (BA25) for altruistic vs. selfish decisions
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specifically encoded within the posterior subgenual cortex and adjacent
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2016). In contrast, non-overlapping responses in the ventral striatum
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tracked both selfish and prosocial reward prediction errors(Lockwood et al.,
recent study failed to show selective brain activations for altruistic choices
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altruistic choices; the cluster spread into the subgenual frontal area. This
however, had limited value in assessing these regions, because the number
of veterans with such lesions was very low. Further limitations of this study
were that MRI scans could not be carried out due to metal injuries, and so
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reliance on CT scans limited the precision of lesion mapping. In addition,
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that compensation as well as ageing-related and neurodegenerative changes
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were likely to have added variability to CT-detectable lesion-function
associations.
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long as appropriate control conditions are used, they usually fail to reveal
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avoidance or on the positive feelings derived from such action (e.g. “warm
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In this section, we review research on moral feelings with a focus on
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guilt and pity/compassion, given their consistent associations with altruistic
often suffer from not being able to directly show which of the activated
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brain regions are related to motivating moral behaviour and which regions
sections.
al., 2011; Kedia et al., 2008; Morey et al., 2012; Seara-Cardoso et al., 2016;
et al., 2007),(Fehse et al., 2015; Kedia et al., 2008) compared against equally
cingulate cortex (extending posteriorly to the adjacent septal area and the
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more anterior pregenual cingulate area in several studies) when compared
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2012; Zahn et al., 2009c),(Basile et al., 2011; Morey et al., 2012). Septal
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and/or subgenual cingulate activations for guilt were found in several
guilt(Gifuni et al., 2016) (Bastin et al., 2016) have failed to detect these
regions. Because these reviews did not base their conclusions on studies
stimuli, and on those studies using optimised fMRI sequences for ventral
18
activations were not given prominence and this will be important in future
systematic reviews.
feelings such as compassion and guilt (Moll and Schulkin, 2009; Moll et al.,
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implicated in social attachment mechanisms in non-human animals,
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and Young, 2001; Stack et al., 2002; Swain et al., 2012). These brain
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structures include the preoptic-anterior hypothalamic area, septal nuclei and
associated basal forebrain regions (Stack et al., 2002). These areas host
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abundant receptors for neuropeptides (oxytocin, vasopressin), monoamines
Bartels and Zeki, 2004; Swain et al., 2007), and oxytocin receptor
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for positive or negative emotional valence and for the context of agency.
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scenarios(Rusch et al., 2014). A recent study confirmed the role of
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showing that the subgenual cortex was selectively activated for efforts
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benefitting anonymous fellow fans of one’s soccer club compared with
2009)). In this study, watching another player, that one could identify with,
for moral motivations and associated feelings, which drive altruistic choices
indicates that the septo-hypothalamic and subgenual frontal areas may play
20
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perceived group belongingness (see also Figure 1).
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4. Moral motivation in psychiatry: emerging applications
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The application of insights on the neural architecture of moral
disturbances.
and pity, with a spared ability to understand and manipulate others for
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keeping with a purported role of the septal nuclei for moral behaviour.
activation (Harenski and Hamann, 2006; Kiehl et al., 2004) and structure of
the right ATL(Gregory S and et al., 2012; Muller et al., 2008) and
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fasciculus(Craig et al., 2009) connecting anterior temporal and subgenual
areas. This suggests, that psychopathy is not only associated with basal
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forebrain dysfunction, but also with isocortical representations of more
al., 2013). This indicates that self-blaming emotional biases are a trait
been well established(Price and Drevets, 2010; Ressler and Mayberg, 2007).
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changes between a subgenual cingulate region and the right superior ATL
these findings.
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motivation and its neural underpinnings using psychological and
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using mindfulness meditation demonstrated that activity in the septal area
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was selectively associated with increased cooperation in the Ultimatum
and for translating them into novel treatments(Kim and Birbaumer, 2014;
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information about their current brain activity that is usually outside of their
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human capacities has become a hot topic of debate within the scientific,
decades(Hyman, 2011).
23
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involvement in moral vs. selfish motivations. Future studies are needed to
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within the septal and subgenual frontal continuum analogous to a similar
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proposal for hedonic reward value representations in the medial
causal social agency due to their closer connection with pregenual anterior
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Acknowledgements
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RZ was partly funded by the UK MRC (G09023042) and US Brain & Behavior
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Research Foundation (24715). ROS and JM were funded by IDOR. The authors
are thankful for discussions with Ivanei Bramati, Fernanda Tovar-Moll, Leonardo
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Fontenelle, Yotam Heineberg and João Ascenso.
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na
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Jo
25
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Boxes
Following the Aristotelian tradition, the perspective of virtue ethics highlighted the
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importance of attaining virtues by training oneself to act according to their
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Enlightenment – Francis Hutcheson, his successor Adam Smith, and David
others”, was considered the primary moral sentiment by Adam Smith(Lamb, 1974).
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Hutcheson postulated that “benevolence” motivates virtuous actions and thereby
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“moral emotions” rather than “moral sentiments” with some variation as to which
emotions are considered moral(Eisenberg, 2000; Tangney et al., 2007). The German
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ability to judge what is morally right and wrong (“principium diiudicationis”) from
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opposed the view that moral actions could be defined by the experienced moral
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sentiments, which were thought to originate from the external senses. He claimed
instead that true moral actions are motivated directly by respect (“Achtung”) for
the moral law, which is self-generated and an act of free will(Kant, 1786). Kant
further pointed out that respect for the moral law is the impression of a moral
value that opposes our selfishness. Moral actions are those guided by a principle
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that the individual wants to become a general law. Thus, moral motivations as
defined by the opposing schools of moral philosophy are either the respect for
schools in that those motivations that enable us to overcome self-interest are key to
evidence and theories about the structure and dynamics of subjective experiences
principles” or “feelings of guilt”, and their neural underpinnings. Beyond the realm
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of pure empirical science, however, lies the contemporary philosophical debate
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virtue theory and their implications for free will, moral realism and moral
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philosophy in general (Casebeer, 2003),(Harris, 2011; Kahane, 2012; Walter, 2001).
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briefly review and summarise the complex anatomy of this region. The medial BF
comprises the more anteriorly located subgenual cingulate cortex (subgenual parts
of areas 24, 32 and, 33), the posterior subgenual cortex (area 25), Broca’s
oxytocin and vasopressin in the human brain(Loup et al., 1991) and comprise a core
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node of the human “default mode” network(Bado et al., 2014). Laterally, the BF
encompasses the nucleus accumbens and ventral pallidum, the amygdala and the
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basal nucleus of Meynert(Nauta and Domesick, 1981/1993). The medial and lateral
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BF structures are heavily interconnected by the medial forebrain bundle, Broca’s
The orbitofrontal, subgenual, and paraolfactory areas, anterior insula and temporal
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pole (TP) are given anatomic unity by the uncinate fascicle, representing endpoints
states. (A) Subgenual: structures underneath the genu (“knee”) of the corpus
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callosum at this level are represented by the posterior subgenual cortex (area 25),
subgenual cingulate cortex (subgenual parts of areas 24, 32, and 33). The subgenual
cortex ( [OFC], area 11) including the subgenual sector of the paracingulate cortex
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which some atlases consider to be part of area 32 (B) Precommissural: the medial
septal nuclei, which make up the surface of the ventromedial wall of the cerebral
hemisphere at this level, are represented by the paraterminal and paraolfactory gyri
(Broca’s paraolfactory area). Note that area 25 has also been described as extending
more posteriorly(Price and Drevets, 2010) into the region here identified as
paraolfactory area. (C) Commissural: the anterior commissure [AC] pierces the basal
pallidum [VP]), which is laterally coextensive with the basal nucleus of Meynert and
the ansa peduncularis [AP]; the AP connects the amygdala [Amyg] with the
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ventromedial hypothalamus (not shown).
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Abstract social concepts such as “honour” and “honesty” are used to describe
social and moral values which operate at a higher level of abstraction than simple
and guide our behaviour(Schwartz and Bilsky, 1987). FMRI studies have shown that
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the ATLs, especially within their right superior sectors(Skipper et al., 2011),(Zahn
et al., 2007), are selectively more activated when considering social concepts than
they are for non-social concepts(Ross and Olson, 2010; Zahn et al., 2015; Zahn et
ATL activation increased with the richness of detail with which social concepts
describe social behaviour(Zahn et al., 2007) in keeping with the role of the ATLs in
2008),(Patterson et al., 2007). Activation in the right superior ATL was reproduced
when making emotional rather than semantic judgments about social values(Zahn et
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al., 2009c). Interestingly, activation in this region was independent of the emotional
(valence: positive vs. negative(Zahn et al., 2007),(Zahn et al., 2011a; Zahn et al.,
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2009c), moral sentiment: guilt vs. pride vs. gratitude vs. indignation(Zahn et al.,
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2009c)) and agency (self vs. other) context, supporting the hypothesis that the ATL
studies using non-invasive “virtual lesion” methods that employ brain stimulation
stimulation (TMS)) and lesion mapping have provided important hints on the brain
regions that are necessary for moral behaviours and choices(Tassy et al., 2012). TMS
or tDCS studies using two-person economic games show that the right dorsolateral
prefrontal cortex (DLPFC) is necessary for making choices that maximise one’s
reputation(Knoch et al., 2009) and for social norm compliance under punishment
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threats(Ruff et al., 2013), findings that are consistent with the suggested role of this
region in reducing subjective values associated with the pursuit of immediate self-
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interest(Hare et al., 2009). Decisions to uphold social norms in these experiments
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do not necessarily rely on moral motivation, because these decisions could also be
tDCS reduced guilt and increased deceitful behaviour, facilitating lying in mock
that damage to the (mostly left) DLPFC, but not to the orbitofrontal cortex,
impaired honesty concerns. The economic decision task enabled teasing apart
honesty concerns from altruistic preferences per se. Whereas all groups were equally
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DLPFC lesion patients were less concerned about honesty and thus indulged more
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in sending “false messages”. These results highlight the roles of the DLPFC and
al., 2009; Hayashi et al., 2013) and value computations(Prevost et al., 2010). In
patients with FTD, reduced resting glucose metabolism in the septal region and
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behaviours, and indicate that the DLPFC and lateral orbitofrontal cortices are key
for responses that enforce honesty, self-reputation concerns, self-control and third-
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contribution to moral motivation is most likely related to its representation of long-
term consequences of social behaviour (Wood and Grafman, 2003; Zahn et al.,
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2017) and thus its importance for representing goals of moral motivations.
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Figure legends
Figure 1
frontopolar and anterior superior temporal cortices enable more complex moral
goals. These are closely integrated with reward and behavioural reinforcement
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systems, including the ventral tegmental area (VTA), ventral striatum (VStr), medial
forebrain bundle (MFB), raphe nuclei and the amygdalae (Amyg). These regions are
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further integrated with the anterior and posterior medial (ant and post mOFC) and
lateral (lat OFC) sectors of the orbitofrontal and dorsolateral (DLPFC) prefrontal
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cortices, pregenual anterior cingulate cortex (ACC), superior anterior temporal
cortex (Sup ATL) and posterior superior temporal sulcus (pSTS) and temporo-
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parietal junction (TPJ).
that moral cognition, emotion and motivation emerge from network integration via
temporal binding. Neural components having core roles for moral motivation: (1)
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et al., 2008),(Rusch et al., 2014); (2) anterior prefrontal / frontopolar cortex [FPC],
which stores event and action sequences(Krueger et al., 2007b; Shima et al., 2007;
Wood and Grafman, 2003; Zahn et al., 2017) enabling long-term goal
representations; (3) anterior temporal cortex (especially the right Sup ATL),
pSTS/TPJ, encoding perceptual social features such as emotional face and body
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Figure 2
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Functional imaging the basal forebrain in moral motivation
Recent fMRI studies have implicated basal forebrain regions in social decision-
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MRI responses of the subgenual cingulate cortex / septal area during charitable
activation selective for prosocial vs. selfish prediction errors which was higher in
trust game. Activity in subgenual cortex (not shown) and in septal area / nucleus
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al., 2011).
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Panel a|, adapted from (Moll et al., 2014), panel b| adapted from (Krueger et al.,
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2007a), panel c| adapted from (Morelli et al., 2014), panel d| adapted from (Rusch
et al., 2014), panel e| adapted from (Zahn et al., 2009a), panel (f) adapted from
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(Moll et al., 2006) , all with permission. Panel g| reproduced from (Smith et al.,
2010), with permission. Panels (h) and (i) adapted from (Chang et al., 2011), with
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permission.
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