Catherine Sebastian | Royal Holloway, University of London (original) (raw)

Papers by Catherine Sebastian

Summary Recent brain imaging studies have demonstrated that the human brain continues to develop ... more Summary Recent brain imaging studies have demonstrated that the human brain continues to develop throughout the adolescent years. Although there are differences between male and female teenagers in terms of the time course of neural development, similar brain areas undergo significant restructuring in both sexes. Brain regions in which development is particularly protracted include the prefrontal cortex and the temporal-parietal cortex.

Adopting a temporally distant perspective on stressors reduces distress in adults. Here we invest... more Adopting a temporally distant perspective on stressors reduces distress in adults. Here we investigate whether the extent to which individuals project themselves into the future influences distancing efficacy. We also examined modulating effects of age across adolescence and reactive aggression: factors associated with reduced futurethinking and poor emotion regulation. Participants (N = 83, aged 12-22) read scenarios and rated negative affect when adopting a distant-future perspective, near-future perspective, or when reacting naturally. Self-report data revealed significant downregulation of negative affect during the distant-future condition, with a similar though non-significant skin conductance pattern. Importantly, participants who projected further ahead showed the greatest distress reductions. While temporal distancing efficacy did not vary with age, participants reporting greater reactive aggression showed reduced distancing efficacy, and projected themselves less far into the future. Findings demonstrate the importance of temporal extent in effective temporal distancing; shedding light on a potential mechanism for poor emotional control associated with reactive aggression.

Background: Children exposed to maltreatment show neural sensitivity to facial cues signalling th... more Background: Children exposed to maltreatment show neural sensitivity to facial cues signalling threat. However, little is known about how maltreatment influences the processing of social threat cues more broadly, and whether atypical processing of social threat cues relates to psychiatric risk. Methods: Forty-one 10-to 14-year-old children underwent a social rejection-themed emotional Stroop task during functional magnetic resonance imaging: 21 children with a documented history of maltreatment (11 F) and 19 comparison children with no maltreatment history (11 F). Groups were matched on age, pubertal status, gender, IQ, socioeconomic status, ethnicity and reading ability. Classic colour Stroop stimuli were also administered in the same paradigm to investigate potential differences in general cognitive control. Results: Compared with their peers, children who had experienced maltreatment showed reduced activation in the Rejection versus Neutral condition, across circuitry previously implicated in abuse-related posttraumatic stress disorder (PTSD), including the left anterior insula, extending into left ventrolateral prefrontal cortex/orbitofrontal cortex; left amygdala; left inferior parietal cortex (STS); and bilateral visual association cortex, encompassing the cuneus and lingual gyrus. No group differences in neural or behavioural responses were found for the classic colour Stroop conditions. Significant negative associations between activity in bilateral cuneus and STS during the rejection-themed Stroop and higher self-reported PTSD symptomatology, including dissociation, were observed in children exposed to maltreatment. Conclusion: Our findings indicate a pattern of altered neural response to social rejection cues in maltreated children. Compared to their peers, these children displayed relative hypoactivation to rejection cues in regions previously associated with PTSD, potentially reflecting an avoidant coping response. It is suggested that such atypical processing of social threat may index latent vulnerability to future psychopathology in general and PTSD in particular.

Psychopathy is a personality disorder characterised by atypical moral behaviour likely rooted in ... more Psychopathy is a personality disorder characterised by atypical moral behaviour likely rooted in atypical affective/motivational processing, as opposed to an inability to judge the wrongness of an action. Guilt is a moral emotion believed to play a crucial role in adherence to moral and social norms, but the mechanisms by which guilt (or lack thereof) may influence behaviour in individuals with high levels of psychopathic traits are unclear. We measured neural responses during the anticipation of guilt about committing potential everyday moral transgressions, and tested the extent to which these varied with psychopathic traits. We found a significant interaction between the degree to which anticipated guilt was modulated in the anterior insula and interpersonal psychopathic traits: anterior insula modulation of anticipated guilt was weaker in individuals with higher levels of these traits. Data from a second sample confirmed that this pattern of findings was specific to the modulation of anticipated guilt and not related to the perceived wrongness of the transgression. These results suggest a central role for the anterior insula in coding the anticipation of guilt regarding potential moral transgressions and advance our understanding of the neurocognitive mechanisms that may underlie propensity to antisocial behaviour. In the past decade there has been increasing interest in the neurocognitive processes that underlie moral cogni-tion 1. However, we still do not fully understand how these processes may contribute to both atypical and typical morality. Why, for example, do some of individuals routinely engage in irresponsible and immoral behaviour? And, more importantly, why do these individuals engage in this kind of behaviour in spite of apparently being capable of appropriate moral reasoning? Individuals with high levels of psychopathic traits, which include blunted affect and a lack of empathy and guilt, have an increased risk of engaging in irresponsible and antisocial behaviours 2. Yet, they do not appear to differ from individuals with low levels of these traits in relation to their moral judgment ability, i.e. the ability to judge whether an action is immoral or not 3–9 (though see refs 10, 11 for exceptions). However, they do report less difficulty in making decisions when faced with moral dilemmas 6,7,9 and present diminished neural responses in the amygdala and other regions typically associated with affective processing when they perform moral judgment tasks 4,5,8,12,13. Atypical moral behaviour in these individuals seems to stem not from an inability to compute moral judgments, but rather from a disruption of the affective and motivational components of moral processing that may be important for adjusting one's behaviour so as not to harm others 3,14,15. In other words, individuals with high levels of psychopathic traits seem to know what is wrong, but do not feel it to be wrong; and therefore fail to inhibit actions that may harm others. Previous neuroimaging studies on moral processing in psychopathy have relied on paradigms that involved judging actions from a third person perspective 5,13 and judging highly hypothetical and often extreme moral dilemmas (e.g. killing one person to save the lives of many) 4,8. It is still unclear whether individual differences in psychopathic traits are associated with atypical neural processing of first-person scenarios for more normative

It has been shown that as cognitive demands of a non-emotional task increase, amygdala response t... more It has been shown that as cognitive demands of a non-emotional task increase, amygdala response to task-irrelevant emotional stimuli is reduced. However, it remains unclear whether effects are due to altered task demands, or altered perceptual input associated with task demands. Here, we present fMRI data from 20 adult males during a novel cognitive conflict task in which the requirement to scan emotional information was necessary for task performance and held constant across levels of cognitive conflict. Response to fearful facial expressions was attenuated under high (vs low) conflict conditions, as indexed by both slower reaction times and reduced right amygdala response. Psychophysiological interaction analysis showed that increased amygdala response to fear in the low conflict condition was accompanied by increased functional coupling with middle frontal gyrus, a prefrontal region previously associated with emotion regulation during cognitive task performance. These data suggest that amygdala response to emotion is modulated as a function of task demands, even when perceptual inputs are closely matched across load conditions. PPI data also show that, in particular emotional contexts , increased functional coupling of amygdala with prefrontal cortex can paradoxically occur when executive demands are lower.

Task-irrelevant emotional expressions are known to capture attention, with the extent of "emotion... more Task-irrelevant emotional expressions are known to capture attention, with the extent of "emotional capture" varying with psychopathic traits in antisocial samples. We investigated whether this variation extends throughout the continuum of psychopathic traits (and co-occurring trait anxiety) in a community sample. Participants (N = 85) searched for a target face among facial distractors. As predicted, angry and fearful faces interfered with search, indicated by slower reaction times relative to neutral faces. When fear appeared as either target or distractor, diminished emotional capture was seen with increasing affectiveinterpersonal psychopathic traits. However, moderation analyses revealed that this was only when lifestyle-antisocial psychopathic traits were low, consistent with evidence suggesting that these two facets of psychopathic traits display opposing relationships with emotional reactivity. Anxiety did not show the predicted relationships with emotional capture effects. Findings show that normative variation in high-level individual differences in psychopathic traits influence automatic bias to emotional stimuli.

Neuroimaging studies have shown continued structural and functional development in neural circuit... more Neuroimaging studies have shown continued structural and functional development in neural circuitry underlying social and emotional behaviour during adolescence. This article explores adolescent neurocognitive development in two domains: sensitivity to social rejection and Theory of Mind (ToM). Adolescents often report hypersensitivity to social rejection. The studies presented here suggest that this is accompanied by reduced responses in brain regions involved in emotion regulation. Studies on social rejection in adolescents with autism spectrum conditions will also be discussed. ToM is another social cognitive domain which undergoes neurocognitive development between adolescence and adult-hood. ToM refers to the ability to understand others' thoughts and intentions. Neuroimaging data suggest that the ability to integrate emotional information into ToM decisions continues to develop between adolescence and adulthood. In sum, these studies demonstrate ongoing development of social and emotional cognition during adolescence at both behavioural and neural levels, providing a neurocognitive framework for understanding adolescent behaviour.

Genetic, behavioural and functional neuroimaging studies have revealed that different vulnerabili... more Genetic, behavioural and functional neuroimaging studies have revealed that different vulnerabilities characterise children with conduct problems and high levels of callous-unemotional traits (CP/HCU) compared with children with conduct problems and low callous-unemotional traits (CP/ LCU). We used voxel-based morphometry to study grey matter volume (GMV) in 89 male participants (aged 10–16), 60 of whom exhibited CP. The CP group was subdivided into CP/ HCU (n = 29) and CP/LCU (n = 31). Whole-brain and regional GMV were compared across groups (CP vs. typically developing (TD) controls (n = 29); and CP/HCU vs. CP/LCU vs. TD). Whole-brain analyses showed reduced GMV in left middle frontal gyrus in the CP/HCU group compared with TD controls. Region-of-interest analyses showed reduced volume in bilateral orbitofrontal cortex (OFC) in the CP group as a whole compared with TD controls. Reduced volume in left OFC was found to be driven by the CP/HCU group only, with significant reductions relative to both TD controls and the CP/ LCU group, and no difference between these latter two groups. Within the CP group left OFC volume was significantly predicted by CU traits, but not conduct disorder symptoms. Reduced right anterior cingulate cortex volume was also found in CP/HCU compared with TD controls. Our results support previous findings indicating that GMV differences in brain regions central to decision-making and empathy are implicated in CP. However, they extend these data to suggest that some of these differences might specifically characterise the subgroup with CP/HCU, with GMV reduction in left OFC differentiating children with CP/HCU from those with CP/LCU.

Emotion regulation is the ability to recruit processes to influence emotion generation. In recent... more Emotion regulation is the ability to recruit processes to influence emotion generation. In recent years there has been mounting interest in how emotions are regulated at behavioural and neural levels, as well as in the relevance of emotional dysregulation to psychopathology. During adolescence, brain regions involved in affect generation and regulation, including the limbic system and prefrontal cortex, undergo protracted structural and functional development. Adolescence is also a time of increasing vulnerability to internalising and externalising psychopathologies associated with poor emotion regulation, including depression, anxiety and antisocial behaviour. It is therefore of particular interest to understand how emotion regulation develops over this time, and how this relates to ongoing brain development. How-ever, to date relatively little research has addressed these questions directly. This review will discuss existing research in these areas in both typical adolescence and in adolescent psychopathology, and will highlight opportunities for future research. In particular, it is important to consider the social context in which adolescent emotion regulation develops. It is possible that while adolescence may be a time of vulnerability to emotional dysregulation, scaffolding the development of emotion regulation during this time may be a fruitful preventative target for psychopathology.

Despite extensive research on the neural basis of empathic responses for pain and disgust, there ... more Despite extensive research on the neural basis of empathic responses for pain and disgust, there is limited data about the brain regions that underpin affective response to other people’s emotional facial expressions. Here, we addressed this question using event-related functional magnetic resonance imaging to assess neural responses to emotional faces, combined with online ratings of subjective state. When instructed to rate their own affective response to others’ faces, participants recruited anterior insula, dorsal anterior cingulate, inferior frontal gyrus, and amygdala, regions consistently implicated in studies investigating empathy for disgust and pain, as well as emotional saliency. Importantly, responses in anterior insula and amygdala were modulated by trial-by-trial variations in subjective affective responses to the emotional facial stimuli. Furthermore, overall task-elicited activations in these regions were negatively associated with psychopathic personality traits, which are characterized by low affective empathy. Our findings suggest that anterior insula and amygdala play important roles in the generation of affective internal states in response to others’ emotional cues and that attenuated function in these regions may underlie reduced empathy in individuals with high levels of psychopathic traits.

Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data have suggested ... more Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data have suggested that individuals with high levels of psychopathic traits show atypical responses to others' pain in a network of brain regions typically recruited during empathic processing (anterior insula, inferior frontal gyrus, and mid-and anterior cingulate cortex). Here, we investigated whether neural responses to others' pain vary with psychopathic traits within the general population in a similar manner to that found in individuals at the extreme end of the continuum. As predicted, variation in psychopathic traits was associated with variation in neural responses to others' pain in the network of brain regions typically engaged during empathic processing. Consistent with previous research, our findings indicated the presence of suppressor effects in the association of levels of the affective-interpersonal and lifestyle-antisocial dimensions of psychopathy with neural responses to others' pain. That is, after controlling for the influence of the other dimension, higher affectiveinterpersonal psychopathic traits were associated with reduced neural responses to others' pain, whilst higher lifestyle-antisocial psychopathic traits were associated with increased neural responses to others' pain. Our findings provide further evidence that atypical function in this network might represent neural markers of disrupted emotional and empathic processing; that the two dimensions of psychopathy might tap into distinct underlying vulnerabilities; and, most importantly, that the relationships observed at the extreme end of the psychopathy spectrum apply to the nonclinical distribution of these traits, providing further evidence for continuities in the mechanisms underlying psychopathic traits across the general population.

Developmental science, 2014

Individuals with autism spectrum disorders (ASD) have difficulty understanding other minds (Theor... more Individuals with autism spectrum disorders (ASD) have difficulty understanding other minds (Theory of Mind; ToM), with atypical processing evident at both behavioural and neural levels. Individuals with conduct problems and high levels of callous-unemotional (CU) traits (CP/HCU) exhibit reduced responsiveness to others' emotions and difficulties interacting with others, but nonetheless perform normally in experimental tests of ToM. The present study aimed to examine the neural underpinnings of ToM in children (aged 10–16) with ASD (N = 16), CP/HCU (N = 16) and typically developing (TD) controls (N = 16) using a non-verbal cartoon vignette task. Whilst individuals with ASD were predicted to show reduced fMRI responses across regions involved in ToM processing, CP/HCU individuals were predicted to show no differences compared with TD controls. The analyses indicated that neural responses did not differ between TD and CP/HCU groups during ToM. TD and CP/HCU children exhibited significantly greater medial prefrontal cortex responses during ToM than did the ASD group. Within the ASD group, responses in medial prefrontal cortex and right temporoparietal junction (TPJ) correlated with symptom severity as measured by the Autism Diagnostic Observation Schedule (ADOS). Findings suggest that although both ASD and CP/HCU are characterized by social difficulties, only children with ASD display atypical neural processing associated with ToM.

Psychological medicine, 2013

2014). Neural responses to fearful eyes in children with conduct problems and varying levels of c... more 2014). Neural responses to fearful eyes in children with conduct problems and varying levels of callous-unemotional traits.

Current biology : CB, 2013

Children with conduct problems (CP) persistently violate others&a... more Children with conduct problems (CP) persistently violate others' rights and represent a considerable societal cost. These children also display atypical empathic responses to others' distress, which may partly account for their violent and antisocial behavior. Callous traits index lack of empathy in these children and confer risk for adult psychopathy. Investigating neural responses to others' pain is an ecologically valid method to probe empathic processing, but studies in children with CP have been inconclusive. Using functional magnetic resonance imaging (fMRI), we measured neural responses to pictures of others in pain (versus no pain) in a large sample of children with CP and matched controls. Relative to controls, children with CP showed reduced blood oxygen level-dependent responses to others' pain in bilateral anterior insula (AI), anterior cingulate cortex (ACC), and inferior frontal gyrus, regions associated with empathy for pain in previous studies. In the CP group, callous traits were negatively associated with responses to others' pain in AI and ACC. We conclude that children with CP have atypical neural responses to others' pain. The negative association between callous traits and AI/ACC response could reflect an early neurobiological marker indexing risk for empathic deficits seen in adult psychopathy.

Background: Childhood maltreatment is strongly associated with increased risk of psychiatric diso... more Background: Childhood maltreatment is strongly associated with increased risk of psychiatric disorder. Previous neuroimaging studies have reported atypical neural structure in the orbitofrontal cortex, temporal lobe, amygdala, hippocampus and cerebellum in maltreated samples. It has been hypothesised that these structural differences may relate to increased psychiatric vulnerability. However, previous studies have typically recruited clinical samples with concurrent psychiatric disorders, or have poorly characterised the range of maltreatment experiences and levels of concurrent anxiety or depression, limiting the interpretation of the observed structural differences.

Methods: We used voxel-based morphometry to compare grey matter volume in a group of 18 children (mean age 12.01 years, SD = 1.4), referred to community social services, with documented and well-characterised experiences of maltreatment at home and a group of 20 nonmaltreated children (mean age 12.6 years, SD = 1.3). Both groups were comparable on age, gender, cognitive ability, ethnicity and levels of anxiety, depression and posttraumatic stress symptoms. We examined five a priori regions of interest: the prefrontal cortex, temporal lobes, amygdala, hippocampus and cerebellum.

Results: Maltreated children, compared to nonmaltreated peers, presented with reduced grey matter in the medial orbitofrontal cortex and the left middle temporal gyrus.

Conclusions: The medial orbitofrontal cortex and the middle temporal gyrus have been implicated in reinforcement-based decision-making, emotion
regulation and autobiographical memory, processes that are impaired in a number of psychiatric disorders associated with maltreatment. We speculate that grey matter disturbance in these regions in a community sample of maltreated children may represent a latent neurobiological risk factor for later
psychopathology and heightened risk taking.

Keywords: maltreatment, child abuse, orbitofrontal cortex, middle temporal gyrus, voxel-based morphometry.

The British journal of psychiatry : the journal of mental science, 2013

Childhood adversity is associated with significantly increased risk of psychiatric disorder. To d... more Childhood adversity is associated with significantly increased risk of psychiatric disorder. To date, functional magnetic resonance imaging (fMRI) studies of children have mainly focused on institutionalisation and investigated conscious processing of affect. To investigate neural response to pre-attentively presented affect cues in a community sample of children with documented experiences of maltreatment in the home. A masked dot-probe paradigm involving pre-attentive presentation of angry, happy and neutral facial expressions was employed. Eighteen maltreated children were compared with 23 carefully matched non-maltreated peers. Increased neural response was observed in the right amygdala for pre-attentively presented angry and happy faces in maltreated v. non-maltreated children. Level of amygdala activation was negatively associated with age at onset for several abuse subtypes. Maltreatment is associated with heightened neural response to positive and negative facial affect, even to stimuli outside awareness. This may represent a latent neural risk factor for future psychiatric disorder.

"Objective: In children with conduct problems, high levels of callous-unemotional traits are asso... more "Objective: In children with conduct problems, high levels of callous-unemotional traits are associated with amygdala hypoactivity to consciously perceived fear, while low levels of callous-unemotional traits may be associated with amygdala hyperactivity. Behavioral data suggest that fear processing deficits in children with high callous-unemotional traits may extend to stimuli presented below conscious awareness (preattentively). The authors investigated the neural basis of this effect. Amygdala involvement was predicted on the basis of its role in preattentive affective processing in healthy adults and its dysfunction in previous studies of conduct problems.

Method: Functional MRI was used to measure neural responses to fearful and calm faces presented preattentively (for 17 ms followed by backward masking) in boys with conduct problems and high callousunemotional traits (N=15), conduct problems and low callous-unemotional traits (N=15), and typically developing comparison boys (N=16). Amygdala response to fearful and calm faces was predicted to differentiate groups, with the greatest response in boys with conduct problems and low callous-unemotional traits and the lowest in boys with conduct problems
and high callous-unemotional traits.

Results: In the right amygdala, a greater amygdala response was seen in boys with conduct problems and low callous-unemotional
traits than in those with high callous-unemotional traits. The findings were not explained by symptom levels of conduct disorder, attention-deficit hyperactivity disorder, anxiety, or depression.

Conclusions: These data demonstrate differential amygdala activity to preattentively presented fear in children with conduct problems grouped by callous-unemotional traits, with high levels associated with lower amygdala reactivity. The study’s findings complement increasing evidence suggesting that callous-unemotional traits are an important specifier in the classification of children with conduct problems."

Archives of general psychiatry, 2012

Context: Reduced neural responses to others' distress is hypothesized to play a critical role in ... more Context: Reduced neural responses to others' distress is hypothesized to play a critical role in conduct problems coupled with callous-unemotional traits, whereas increased neural responses to affective stimuli may accompany conduct problems without callousunemotional traits. Heterogeneity of affective profiles in conduct problems may account for inconsistent neuroimaging findings in this population.

Summary Recent brain imaging studies have demonstrated that the human brain continues to develop ... more Summary Recent brain imaging studies have demonstrated that the human brain continues to develop throughout the adolescent years. Although there are differences between male and female teenagers in terms of the time course of neural development, similar brain areas undergo significant restructuring in both sexes. Brain regions in which development is particularly protracted include the prefrontal cortex and the temporal-parietal cortex.

Adopting a temporally distant perspective on stressors reduces distress in adults. Here we invest... more Adopting a temporally distant perspective on stressors reduces distress in adults. Here we investigate whether the extent to which individuals project themselves into the future influences distancing efficacy. We also examined modulating effects of age across adolescence and reactive aggression: factors associated with reduced futurethinking and poor emotion regulation. Participants (N = 83, aged 12-22) read scenarios and rated negative affect when adopting a distant-future perspective, near-future perspective, or when reacting naturally. Self-report data revealed significant downregulation of negative affect during the distant-future condition, with a similar though non-significant skin conductance pattern. Importantly, participants who projected further ahead showed the greatest distress reductions. While temporal distancing efficacy did not vary with age, participants reporting greater reactive aggression showed reduced distancing efficacy, and projected themselves less far into the future. Findings demonstrate the importance of temporal extent in effective temporal distancing; shedding light on a potential mechanism for poor emotional control associated with reactive aggression.

Background: Children exposed to maltreatment show neural sensitivity to facial cues signalling th... more Background: Children exposed to maltreatment show neural sensitivity to facial cues signalling threat. However, little is known about how maltreatment influences the processing of social threat cues more broadly, and whether atypical processing of social threat cues relates to psychiatric risk. Methods: Forty-one 10-to 14-year-old children underwent a social rejection-themed emotional Stroop task during functional magnetic resonance imaging: 21 children with a documented history of maltreatment (11 F) and 19 comparison children with no maltreatment history (11 F). Groups were matched on age, pubertal status, gender, IQ, socioeconomic status, ethnicity and reading ability. Classic colour Stroop stimuli were also administered in the same paradigm to investigate potential differences in general cognitive control. Results: Compared with their peers, children who had experienced maltreatment showed reduced activation in the Rejection versus Neutral condition, across circuitry previously implicated in abuse-related posttraumatic stress disorder (PTSD), including the left anterior insula, extending into left ventrolateral prefrontal cortex/orbitofrontal cortex; left amygdala; left inferior parietal cortex (STS); and bilateral visual association cortex, encompassing the cuneus and lingual gyrus. No group differences in neural or behavioural responses were found for the classic colour Stroop conditions. Significant negative associations between activity in bilateral cuneus and STS during the rejection-themed Stroop and higher self-reported PTSD symptomatology, including dissociation, were observed in children exposed to maltreatment. Conclusion: Our findings indicate a pattern of altered neural response to social rejection cues in maltreated children. Compared to their peers, these children displayed relative hypoactivation to rejection cues in regions previously associated with PTSD, potentially reflecting an avoidant coping response. It is suggested that such atypical processing of social threat may index latent vulnerability to future psychopathology in general and PTSD in particular.

Psychopathy is a personality disorder characterised by atypical moral behaviour likely rooted in ... more Psychopathy is a personality disorder characterised by atypical moral behaviour likely rooted in atypical affective/motivational processing, as opposed to an inability to judge the wrongness of an action. Guilt is a moral emotion believed to play a crucial role in adherence to moral and social norms, but the mechanisms by which guilt (or lack thereof) may influence behaviour in individuals with high levels of psychopathic traits are unclear. We measured neural responses during the anticipation of guilt about committing potential everyday moral transgressions, and tested the extent to which these varied with psychopathic traits. We found a significant interaction between the degree to which anticipated guilt was modulated in the anterior insula and interpersonal psychopathic traits: anterior insula modulation of anticipated guilt was weaker in individuals with higher levels of these traits. Data from a second sample confirmed that this pattern of findings was specific to the modulation of anticipated guilt and not related to the perceived wrongness of the transgression. These results suggest a central role for the anterior insula in coding the anticipation of guilt regarding potential moral transgressions and advance our understanding of the neurocognitive mechanisms that may underlie propensity to antisocial behaviour. In the past decade there has been increasing interest in the neurocognitive processes that underlie moral cogni-tion 1. However, we still do not fully understand how these processes may contribute to both atypical and typical morality. Why, for example, do some of individuals routinely engage in irresponsible and immoral behaviour? And, more importantly, why do these individuals engage in this kind of behaviour in spite of apparently being capable of appropriate moral reasoning? Individuals with high levels of psychopathic traits, which include blunted affect and a lack of empathy and guilt, have an increased risk of engaging in irresponsible and antisocial behaviours 2. Yet, they do not appear to differ from individuals with low levels of these traits in relation to their moral judgment ability, i.e. the ability to judge whether an action is immoral or not 3–9 (though see refs 10, 11 for exceptions). However, they do report less difficulty in making decisions when faced with moral dilemmas 6,7,9 and present diminished neural responses in the amygdala and other regions typically associated with affective processing when they perform moral judgment tasks 4,5,8,12,13. Atypical moral behaviour in these individuals seems to stem not from an inability to compute moral judgments, but rather from a disruption of the affective and motivational components of moral processing that may be important for adjusting one's behaviour so as not to harm others 3,14,15. In other words, individuals with high levels of psychopathic traits seem to know what is wrong, but do not feel it to be wrong; and therefore fail to inhibit actions that may harm others. Previous neuroimaging studies on moral processing in psychopathy have relied on paradigms that involved judging actions from a third person perspective 5,13 and judging highly hypothetical and often extreme moral dilemmas (e.g. killing one person to save the lives of many) 4,8. It is still unclear whether individual differences in psychopathic traits are associated with atypical neural processing of first-person scenarios for more normative

It has been shown that as cognitive demands of a non-emotional task increase, amygdala response t... more It has been shown that as cognitive demands of a non-emotional task increase, amygdala response to task-irrelevant emotional stimuli is reduced. However, it remains unclear whether effects are due to altered task demands, or altered perceptual input associated with task demands. Here, we present fMRI data from 20 adult males during a novel cognitive conflict task in which the requirement to scan emotional information was necessary for task performance and held constant across levels of cognitive conflict. Response to fearful facial expressions was attenuated under high (vs low) conflict conditions, as indexed by both slower reaction times and reduced right amygdala response. Psychophysiological interaction analysis showed that increased amygdala response to fear in the low conflict condition was accompanied by increased functional coupling with middle frontal gyrus, a prefrontal region previously associated with emotion regulation during cognitive task performance. These data suggest that amygdala response to emotion is modulated as a function of task demands, even when perceptual inputs are closely matched across load conditions. PPI data also show that, in particular emotional contexts , increased functional coupling of amygdala with prefrontal cortex can paradoxically occur when executive demands are lower.

Task-irrelevant emotional expressions are known to capture attention, with the extent of "emotion... more Task-irrelevant emotional expressions are known to capture attention, with the extent of "emotional capture" varying with psychopathic traits in antisocial samples. We investigated whether this variation extends throughout the continuum of psychopathic traits (and co-occurring trait anxiety) in a community sample. Participants (N = 85) searched for a target face among facial distractors. As predicted, angry and fearful faces interfered with search, indicated by slower reaction times relative to neutral faces. When fear appeared as either target or distractor, diminished emotional capture was seen with increasing affectiveinterpersonal psychopathic traits. However, moderation analyses revealed that this was only when lifestyle-antisocial psychopathic traits were low, consistent with evidence suggesting that these two facets of psychopathic traits display opposing relationships with emotional reactivity. Anxiety did not show the predicted relationships with emotional capture effects. Findings show that normative variation in high-level individual differences in psychopathic traits influence automatic bias to emotional stimuli.

Neuroimaging studies have shown continued structural and functional development in neural circuit... more Neuroimaging studies have shown continued structural and functional development in neural circuitry underlying social and emotional behaviour during adolescence. This article explores adolescent neurocognitive development in two domains: sensitivity to social rejection and Theory of Mind (ToM). Adolescents often report hypersensitivity to social rejection. The studies presented here suggest that this is accompanied by reduced responses in brain regions involved in emotion regulation. Studies on social rejection in adolescents with autism spectrum conditions will also be discussed. ToM is another social cognitive domain which undergoes neurocognitive development between adolescence and adult-hood. ToM refers to the ability to understand others' thoughts and intentions. Neuroimaging data suggest that the ability to integrate emotional information into ToM decisions continues to develop between adolescence and adulthood. In sum, these studies demonstrate ongoing development of social and emotional cognition during adolescence at both behavioural and neural levels, providing a neurocognitive framework for understanding adolescent behaviour.

Genetic, behavioural and functional neuroimaging studies have revealed that different vulnerabili... more Genetic, behavioural and functional neuroimaging studies have revealed that different vulnerabilities characterise children with conduct problems and high levels of callous-unemotional traits (CP/HCU) compared with children with conduct problems and low callous-unemotional traits (CP/ LCU). We used voxel-based morphometry to study grey matter volume (GMV) in 89 male participants (aged 10–16), 60 of whom exhibited CP. The CP group was subdivided into CP/ HCU (n = 29) and CP/LCU (n = 31). Whole-brain and regional GMV were compared across groups (CP vs. typically developing (TD) controls (n = 29); and CP/HCU vs. CP/LCU vs. TD). Whole-brain analyses showed reduced GMV in left middle frontal gyrus in the CP/HCU group compared with TD controls. Region-of-interest analyses showed reduced volume in bilateral orbitofrontal cortex (OFC) in the CP group as a whole compared with TD controls. Reduced volume in left OFC was found to be driven by the CP/HCU group only, with significant reductions relative to both TD controls and the CP/ LCU group, and no difference between these latter two groups. Within the CP group left OFC volume was significantly predicted by CU traits, but not conduct disorder symptoms. Reduced right anterior cingulate cortex volume was also found in CP/HCU compared with TD controls. Our results support previous findings indicating that GMV differences in brain regions central to decision-making and empathy are implicated in CP. However, they extend these data to suggest that some of these differences might specifically characterise the subgroup with CP/HCU, with GMV reduction in left OFC differentiating children with CP/HCU from those with CP/LCU.

Emotion regulation is the ability to recruit processes to influence emotion generation. In recent... more Emotion regulation is the ability to recruit processes to influence emotion generation. In recent years there has been mounting interest in how emotions are regulated at behavioural and neural levels, as well as in the relevance of emotional dysregulation to psychopathology. During adolescence, brain regions involved in affect generation and regulation, including the limbic system and prefrontal cortex, undergo protracted structural and functional development. Adolescence is also a time of increasing vulnerability to internalising and externalising psychopathologies associated with poor emotion regulation, including depression, anxiety and antisocial behaviour. It is therefore of particular interest to understand how emotion regulation develops over this time, and how this relates to ongoing brain development. How-ever, to date relatively little research has addressed these questions directly. This review will discuss existing research in these areas in both typical adolescence and in adolescent psychopathology, and will highlight opportunities for future research. In particular, it is important to consider the social context in which adolescent emotion regulation develops. It is possible that while adolescence may be a time of vulnerability to emotional dysregulation, scaffolding the development of emotion regulation during this time may be a fruitful preventative target for psychopathology.

Despite extensive research on the neural basis of empathic responses for pain and disgust, there ... more Despite extensive research on the neural basis of empathic responses for pain and disgust, there is limited data about the brain regions that underpin affective response to other people’s emotional facial expressions. Here, we addressed this question using event-related functional magnetic resonance imaging to assess neural responses to emotional faces, combined with online ratings of subjective state. When instructed to rate their own affective response to others’ faces, participants recruited anterior insula, dorsal anterior cingulate, inferior frontal gyrus, and amygdala, regions consistently implicated in studies investigating empathy for disgust and pain, as well as emotional saliency. Importantly, responses in anterior insula and amygdala were modulated by trial-by-trial variations in subjective affective responses to the emotional facial stimuli. Furthermore, overall task-elicited activations in these regions were negatively associated with psychopathic personality traits, which are characterized by low affective empathy. Our findings suggest that anterior insula and amygdala play important roles in the generation of affective internal states in response to others’ emotional cues and that attenuated function in these regions may underlie reduced empathy in individuals with high levels of psychopathic traits.

Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data have suggested ... more Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data have suggested that individuals with high levels of psychopathic traits show atypical responses to others' pain in a network of brain regions typically recruited during empathic processing (anterior insula, inferior frontal gyrus, and mid-and anterior cingulate cortex). Here, we investigated whether neural responses to others' pain vary with psychopathic traits within the general population in a similar manner to that found in individuals at the extreme end of the continuum. As predicted, variation in psychopathic traits was associated with variation in neural responses to others' pain in the network of brain regions typically engaged during empathic processing. Consistent with previous research, our findings indicated the presence of suppressor effects in the association of levels of the affective-interpersonal and lifestyle-antisocial dimensions of psychopathy with neural responses to others' pain. That is, after controlling for the influence of the other dimension, higher affectiveinterpersonal psychopathic traits were associated with reduced neural responses to others' pain, whilst higher lifestyle-antisocial psychopathic traits were associated with increased neural responses to others' pain. Our findings provide further evidence that atypical function in this network might represent neural markers of disrupted emotional and empathic processing; that the two dimensions of psychopathy might tap into distinct underlying vulnerabilities; and, most importantly, that the relationships observed at the extreme end of the psychopathy spectrum apply to the nonclinical distribution of these traits, providing further evidence for continuities in the mechanisms underlying psychopathic traits across the general population.

Developmental science, 2014

Individuals with autism spectrum disorders (ASD) have difficulty understanding other minds (Theor... more Individuals with autism spectrum disorders (ASD) have difficulty understanding other minds (Theory of Mind; ToM), with atypical processing evident at both behavioural and neural levels. Individuals with conduct problems and high levels of callous-unemotional (CU) traits (CP/HCU) exhibit reduced responsiveness to others' emotions and difficulties interacting with others, but nonetheless perform normally in experimental tests of ToM. The present study aimed to examine the neural underpinnings of ToM in children (aged 10–16) with ASD (N = 16), CP/HCU (N = 16) and typically developing (TD) controls (N = 16) using a non-verbal cartoon vignette task. Whilst individuals with ASD were predicted to show reduced fMRI responses across regions involved in ToM processing, CP/HCU individuals were predicted to show no differences compared with TD controls. The analyses indicated that neural responses did not differ between TD and CP/HCU groups during ToM. TD and CP/HCU children exhibited significantly greater medial prefrontal cortex responses during ToM than did the ASD group. Within the ASD group, responses in medial prefrontal cortex and right temporoparietal junction (TPJ) correlated with symptom severity as measured by the Autism Diagnostic Observation Schedule (ADOS). Findings suggest that although both ASD and CP/HCU are characterized by social difficulties, only children with ASD display atypical neural processing associated with ToM.

Psychological medicine, 2013

2014). Neural responses to fearful eyes in children with conduct problems and varying levels of c... more 2014). Neural responses to fearful eyes in children with conduct problems and varying levels of callous-unemotional traits.

Current biology : CB, 2013

Children with conduct problems (CP) persistently violate others&a... more Children with conduct problems (CP) persistently violate others' rights and represent a considerable societal cost. These children also display atypical empathic responses to others' distress, which may partly account for their violent and antisocial behavior. Callous traits index lack of empathy in these children and confer risk for adult psychopathy. Investigating neural responses to others' pain is an ecologically valid method to probe empathic processing, but studies in children with CP have been inconclusive. Using functional magnetic resonance imaging (fMRI), we measured neural responses to pictures of others in pain (versus no pain) in a large sample of children with CP and matched controls. Relative to controls, children with CP showed reduced blood oxygen level-dependent responses to others' pain in bilateral anterior insula (AI), anterior cingulate cortex (ACC), and inferior frontal gyrus, regions associated with empathy for pain in previous studies. In the CP group, callous traits were negatively associated with responses to others' pain in AI and ACC. We conclude that children with CP have atypical neural responses to others' pain. The negative association between callous traits and AI/ACC response could reflect an early neurobiological marker indexing risk for empathic deficits seen in adult psychopathy.

Background: Childhood maltreatment is strongly associated with increased risk of psychiatric diso... more Background: Childhood maltreatment is strongly associated with increased risk of psychiatric disorder. Previous neuroimaging studies have reported atypical neural structure in the orbitofrontal cortex, temporal lobe, amygdala, hippocampus and cerebellum in maltreated samples. It has been hypothesised that these structural differences may relate to increased psychiatric vulnerability. However, previous studies have typically recruited clinical samples with concurrent psychiatric disorders, or have poorly characterised the range of maltreatment experiences and levels of concurrent anxiety or depression, limiting the interpretation of the observed structural differences.

Methods: We used voxel-based morphometry to compare grey matter volume in a group of 18 children (mean age 12.01 years, SD = 1.4), referred to community social services, with documented and well-characterised experiences of maltreatment at home and a group of 20 nonmaltreated children (mean age 12.6 years, SD = 1.3). Both groups were comparable on age, gender, cognitive ability, ethnicity and levels of anxiety, depression and posttraumatic stress symptoms. We examined five a priori regions of interest: the prefrontal cortex, temporal lobes, amygdala, hippocampus and cerebellum.

Results: Maltreated children, compared to nonmaltreated peers, presented with reduced grey matter in the medial orbitofrontal cortex and the left middle temporal gyrus.

Conclusions: The medial orbitofrontal cortex and the middle temporal gyrus have been implicated in reinforcement-based decision-making, emotion
regulation and autobiographical memory, processes that are impaired in a number of psychiatric disorders associated with maltreatment. We speculate that grey matter disturbance in these regions in a community sample of maltreated children may represent a latent neurobiological risk factor for later
psychopathology and heightened risk taking.

Keywords: maltreatment, child abuse, orbitofrontal cortex, middle temporal gyrus, voxel-based morphometry.

The British journal of psychiatry : the journal of mental science, 2013

Childhood adversity is associated with significantly increased risk of psychiatric disorder. To d... more Childhood adversity is associated with significantly increased risk of psychiatric disorder. To date, functional magnetic resonance imaging (fMRI) studies of children have mainly focused on institutionalisation and investigated conscious processing of affect. To investigate neural response to pre-attentively presented affect cues in a community sample of children with documented experiences of maltreatment in the home. A masked dot-probe paradigm involving pre-attentive presentation of angry, happy and neutral facial expressions was employed. Eighteen maltreated children were compared with 23 carefully matched non-maltreated peers. Increased neural response was observed in the right amygdala for pre-attentively presented angry and happy faces in maltreated v. non-maltreated children. Level of amygdala activation was negatively associated with age at onset for several abuse subtypes. Maltreatment is associated with heightened neural response to positive and negative facial affect, even to stimuli outside awareness. This may represent a latent neural risk factor for future psychiatric disorder.

"Objective: In children with conduct problems, high levels of callous-unemotional traits are asso... more "Objective: In children with conduct problems, high levels of callous-unemotional traits are associated with amygdala hypoactivity to consciously perceived fear, while low levels of callous-unemotional traits may be associated with amygdala hyperactivity. Behavioral data suggest that fear processing deficits in children with high callous-unemotional traits may extend to stimuli presented below conscious awareness (preattentively). The authors investigated the neural basis of this effect. Amygdala involvement was predicted on the basis of its role in preattentive affective processing in healthy adults and its dysfunction in previous studies of conduct problems.

Method: Functional MRI was used to measure neural responses to fearful and calm faces presented preattentively (for 17 ms followed by backward masking) in boys with conduct problems and high callousunemotional traits (N=15), conduct problems and low callous-unemotional traits (N=15), and typically developing comparison boys (N=16). Amygdala response to fearful and calm faces was predicted to differentiate groups, with the greatest response in boys with conduct problems and low callous-unemotional traits and the lowest in boys with conduct problems
and high callous-unemotional traits.

Results: In the right amygdala, a greater amygdala response was seen in boys with conduct problems and low callous-unemotional
traits than in those with high callous-unemotional traits. The findings were not explained by symptom levels of conduct disorder, attention-deficit hyperactivity disorder, anxiety, or depression.

Conclusions: These data demonstrate differential amygdala activity to preattentively presented fear in children with conduct problems grouped by callous-unemotional traits, with high levels associated with lower amygdala reactivity. The study’s findings complement increasing evidence suggesting that callous-unemotional traits are an important specifier in the classification of children with conduct problems."

Archives of general psychiatry, 2012

Context: Reduced neural responses to others' distress is hypothesized to play a critical role in ... more Context: Reduced neural responses to others' distress is hypothesized to play a critical role in conduct problems coupled with callous-unemotional traits, whereas increased neural responses to affective stimuli may accompany conduct problems without callousunemotional traits. Heterogeneity of affective profiles in conduct problems may account for inconsistent neuroimaging findings in this population.