Imaging decision about whether to benefit self by harming others: Adolescents with conduct and substance problems, with or without callous-unemotionality, or developing typically

https://doi.org/10.1016/j.pscychresns.2017.03.004Get rights and content

Highlights

  • Conduct problem(CP) patients with/without limited prosocial emotions(LPE), controls.

  • Imaged playing a novel game requiring decisions about self-benefit and other-harm.

  • Network engaged: medial frontal, accumbens, bilateral insula, among other areas.

  • CP with LPE had less activation in right anterior insula during decision making.

Abstract

We sought to identify brain activation differences in conduct-problem youth with limited prosocial emotions (LPE) compared to conduct-problem youth without LPE and community adolescents, and to test associations between brain activation and severity of callous-unemotional traits. We utilized a novel task, which asks subjects to repeatedly decide whether to accept offers where they will benefit but a beneficent other will be harmed. Behavior on this task has been previously associated with levels of prosocial emotions and severity of callous-unemotional traits, and is related to empathic concern. During fMRI acquisition, 66 male adolescents (21 conduct-problem patients with LPE, 21 without, and 24 typically-developing controls) played this novel game. Within typically-developing controls, we identified a network engaged during decision involving bilateral insula, and inferior parietal and medial frontal cortices, among other regions. Group comparisons using non-parametric (distribution-free) permutation tests demonstrated LPE patients had lower activation estimates than typically-developing adolescents in right anterior insula. Additional significant group differences emerged with our a priori parametric cluster-wise inference threshold. These results suggest measurable functional brain activation differences in conduct-problem adolescents with LPE compared to typically-developing adolescents. Such differences may underscore differential treatment needs for conduct-problem males with and without LPE.

Introduction

Conduct disorder affects approximately 5% of U.S. adolescents and is associated with a number of negative outcomes (Coker et al., 2014). But conduct disorder is a heterogeneous phenotype. About 40% of conduct-disordered youth continue to exhibit clinically-meaningful levels of antisocial behavior into adulthood, while others apparently remit from high levels of antisocial behavior problems, having an adolescence-limited phenotype (Moffitt, 1993, Steiner and Dunne, 1997). Those with chronic antisocial trajectories account for a disproportionately large amount (about 50%) of all violent behaviors (Dodge and Pettit, 2003). In DSM-5, youths with conduct disorder may be categorized based on the presence or absence of “limited prosocial emotions” (LPE), which is characterized by high levels of callous-unemotional traits and is defined by four criteria: lack of remorse or guilt, callous lack of empathy, unconcerned about performance, and shallow or deficient affect. However, the LPE specifier is a relatively new construct and therefore most published work to date has used a related but distinct phenotype, high levels of callous-unemotional traits (i.e. a dimensional severity score (e.g., (Sebastian et al., 2012))) or a median split to categorize individuals with high and low levels of callous-unemotional traits (e.g., (Hwang et al., 2016)). High levels of callous-unemotional traits are stable through adolescence, predict persistent antisocial behavior problems, are associated with greater violence and aggression, and predict poorer outcomes to standard treatment (Frick et al., 2014). Conduct-disordered youth with and without high levels of callous-unemotional traits may have different biological mechanisms that underlie their problem behaviors (Blair et al., 2014) and more research is needed to identify those biological differences. In addition, more research is needed comparing results from these related but distinct phenotypes: LPE and high levels of callous-unemotional traits.

The growing research literature on the neuroscience of callous-unemotional traits and antisocial behavior problems in adolescence has implicated multiple areas of impairment including poor emotional empathy, exaggerated threat responsivity, impaired reinforcement-based decision making and punishment processing, and impaired response inhibition (Blair et al., 2016, Byrd et al., 2014). But problems of empathizing may be particularly relevant to callous-unemotional traits (e.g., see Fig. 1 in (Blair et al., 2016)) and such deficits in emotional empathy may impact the development of conditioned associations between one's harmful behaviors and others’ negative reactions to those behaviors (Blair et al., 2014). Empathy, broadly defined, may be studied in various ways in the MRI environment. To date this adolescent literature has tested brain activation while: viewing pictures of painful injuries and asking subjects to imagine the injury is occurring to “Yourself” vs. “Someone Else” (Marsh et al., 2013); viewing fearful or other emotional facial expressions (Viding et al., 2012); and choosing endings to cartoon scenarios where the cartoons require understanding the internal states and perspectives of the characters to choose correct endings and test cognitive and emotional theory of mind (Sebastian et al., 2012). Some work has also shown that the emotional deficits seen in youth with psychopathic traits while viewing fearful facial expressions are not secondary to group differences in top-down attentional control (White et al., 2012). The developmental consequences of such deficits in emotional empathy can be in turn studied through examining care-based moral development (Blair et al., 2016) and moral determinations (Harenski et al., 2014). Together these studies provide very important advances in our understanding of callous-unemotional traits and demonstrate that differences in activation, especially of the amygdala (Marsh et al., 2008, Sebastian et al., 2012) and anterior insula (Blair et al., 2016), may be particularly important to those differences in emotional empathy seen among youth with high levels of callous unemotional traits.

Conduct-disordered individuals often engage in behaviors that violate the rights of others or social norms, and in turn, such behaviors often cause substantive familial disruption (Dodge and Pettit, 2003); thus many of the problems caused by these youth result from decision making in a self-versus-others (Self:Other) context. In this study, we aimed not at passive viewing of images or scenarios in the Magnetic Resonance Imaging (MRI) environment, but toward studying active decision-making about actual behaviors. Some studies have utilized advanced modeling in reinforcement learning paradigm (White et al., 2014b) and passive avoidance tasks (White et al., 2016a) to better understand decision making in this population. Here we aim to build on this growing literature by studying decision making, but within a Self:Other context. Prior work has utilized versions of the Ultimatum Game to study decisions to punish the unfair behavior of others (e.g., (White et al., 2014a)). Van den Bos and colleagues (van den Bos et al., 2014) compared antisocial youth and controls while playing the Ultimatum Game and demonstrated differences in activation of the right inferior frontal gyrus and right temporal parietal junction, though these findings were not significantly associated with levels of callousness within delinquent youth. White and colleagues (White et al., 2016b) extended this work by examining the tendency to retaliate in response to perceived unfairness of others. The study benefitted from utilizing samples of antisocial youth with and without high levels of callous-unemotional traits but the findings regarding retaliatory behavior were specific to conduct disorder with low levels of callous-unemotional traits. With the Ultimatum Game, we can examine how much people are willing to give up to punish a bad actor (i.e., costly punishment). In the game utilized in this study, the Altruism-Antisocial (AlAn's) game, we examine a related but distinctly different construct: how much are people willing to refrain from taking for themselves in order to help a good actor (i.e., what we have previously called costly helping; Sakai et al., 2016a). Our prior publications examining this game out of the MRI environment support that individuals with high levels of callousness tend to both take more for themselves and leave less for the beneficent other, compared to comparison participants (Sakai et al., 2012, Sakai et al., 2016a). Thus, while results examining costly punishment to date appear to be more specific to conduct disorder and may evoke systems more related to acute threat response (Blair et al., 2016), this early work with the AlAn's game raises the possibility that differences in costly helping are more strongly related to levels of callousness and in turn, may be related more to paradigms relevant to care-based moral decision making and emotional empathy. The AlAn's game was designed to examine decision-making with MRI.

One challenge in studying youth with conduct problems and LPE is the very common co-morbidity in this population. For example, more than half of conduct-disordered adolescents may have a co-occurring substance use disorder (Coker et al., 2014). Co-morbid ADHD and depression are also common (Sakai et al., 2016b). One approach is to study subjects without co-morbid disorders, selecting those youths with only conduct disorder and LPE. However, among conduct-disordered youths, greater co-morbidity predicts persistent antisocial behavior problems (Moffitt et al., 2001, Myers et al., 1998). Thus, excluding co-morbidity would bias results towards atypical, less severely affected samples (Krueger, 1999). An alternate strategy is to utilize other conduct-problem youths (i.e., with serious antisocial behavior problems but scoring at about average levels for callous-unemotional traits) as a control (Hwang et al., 2016). We have previously demonstrated that patients with conduct disorder with and without LPE have similar patterns of co-morbidity in terms of prevalence of depression, ADHD, and specific substance use disorders when recruited in the same manner as done in this study (Sakai et al., 2016b). A small set of work in detained adolescents has shown similar results (Colins and Vermeiren, 2013, Van Damme et al., 2016). Therefore, including both typically-developing adolescents and youth with serious conduct problems without high levels of callous-unemotional traits as comparison groups, as in prior important work (Viding et al., 2012, White et al., 2016b, Hwang et al., 2016), may provide a useful strategy to reduce confounds driven by some co-morbid disorders. But such an approach will not control for all confounds. For example, adolescent patients may differ in conduct disorder severity (e.g., symptom count; (Sakai et al., 2016b)). Thus controlling for such differences in analyses may still be required.

Sex differences present a second complication in studying youth with conduct disorder and high levels of callous-unemotional traits. Conduct disorder is more common in males than females but when considering persistent antisocial behavior problems, these sex differences become quite pronounced (Eme, 2007). Similarly, males on average have higher levels of callous-unemotional traits than females (Essau et al., 2006). Therefore, this study describes a male-only sample to eliminate potential confounds of sex.

We present here for the first time results from a novel decision-making task, the AlAn's game, in the MRI environment with three groups of male adolescents: typically-developing youths, patients with conduct problems without LPE, and patients with conduct problems with LPE. Participants underwent fMRI neuroimaging as they repeatedly decided whether or not to take actions that benefitted themselves but harmed a beneficent other. In the application for the NIH grant funding this work, we hypothesized that adolescents with serious conduct problems and LPE would differ from the two other groups in activity of the “paralimbic system,” including orbitofrontal, anterior cingulate, insula, amygdala, and superior temporal/angular gyrus. In addition, our approach allows examining the relationship between severity of callous-unemotional traits (dimensional measure) and brain activation, and secondarily also allows examining how results change when dividing patients into high and low callous-unemotional traits by median split, in comparison to our pre-hoc approach (i.e. dividing groups based on the LPE specifier).

Section snippets

Methods

The study protocol and consents were approved by the Colorado Multiple Institutional Review Board. All adolescents under age 18 provided written assent and their parent's written consent. Youth who were 18 years of age provided written consent to study participation.

Network engaged by decision

Within typically-developing adolescents the contrast ΔBOLD(Active Trial – Calculation) demonstrated prominent activation in medial frontal regions, bilateral inferior frontal gyrus and insula, thalamus, midbrain, caudate, precuneus and right inferior parietal regions (see Supplementary material Fig. 3, Table 1A).

Group comparisons

Three-group whole-brain comparisons in ΔBOLD(Active Trial – Calculation) demonstrated a significant activation difference between groups during decision in the right insula, inferior

Discussion

Within typically-developing adolescents, we identify a network engaged during decision. The network is remarkably similar to prior studies of alternative approaches to presenting Self:Other consideration in normative populations (Hein et al., 2016, Sommer et al., 2014). However, our main aim was to identify regions in this network associated with high levels of callous-unemotional traits. Our three-group analyses demonstrate activation differences in the right anterior insula. Those with LPE

Conclusions and future directions

We demonstrate three brain regions where activation during Self:Other decisions is related to callousness among conduct-problem youths. Our game offers a unique opportunity to explore how brain regions may be related to actual behaviors, perhaps bringing us one step closer to understanding not only how youth with LPE differ in brain activity, but how those differences in brain activity may lead to maladaptive behaviors. Inferior parietal lobule is easily accessible to brain stimulation

Disclosures

Dr. Crowley served on the National Advisory Council of the National Institute on Drug Abuse, and on a Task Force of the American Psychiatric Association for drafting the Diagnostic and Statistical Manual of Mental Disorders, Edition 5, receiving travel reimbursement from those organizations. Dr. Sakai received reimbursement in 2012 for completing a policy review for the WellPoint Office of Medical Policy & Technology Assessment (OMPTA), WellPoint, Inc., Thousand Oaks, CA. He also served as a

Funding

Research support from National Institute on Drug Abuse (NIDA) grant DA031761, the Kane Family Foundation and the Hewit Family Foundation. Dr. Mikulich-Gilbertson's effort is also supported by National Institute on Drug Abuse grant DA034604. The funders had no role in: the study design; the collection, analyses or interpretation of the data; the writing of the report; or in the decision to submit this manuscript for publication.

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