Exploring real-time functional magnetic resonance imaging neurofeedback in adolescents with disruptive behavior disorder and callous unemotional traits

Introduction: Adolescents with increased callous unemotional traits (CU traits) in the context of disruptive behavior disorder (DBD) show a persistent pattern of antisocial behavior with shallow affect and a lack of empathy or remorse. The amygdala and insula as regions commonly associated with emotion processing, empathy and arousal are implicated in DBD with high CU traits. While behavioral therapies for DBD provide significant but small effects, individualized treatments targeting the implicated brain regions are missing. Methods: In this explorative randomized controlled trial we randomly assigned twenty-seven adolescents with DBD to individualized real-time functional magnetic resonance neurofeedback (rtfMRI-NF) or behavioral treatment as usual (TAU). Visual feedback of either amygdala or insula activity was provided during rtfMRI-NF by gauges and included a simple and concurrent video run plus a transfer run. A linear mixed model (LMM) was applied to determine improvement of self-regulation. Specificity was assessed by correlating individual self-regulation improvement with clinical outcomes. Results: The rtfMRI-NF (n = 11) and TAU (n = 10) completers showed comparable and significant clinical improvement indicating neither superiority nor inferiority of rtfMRI-NF. The exploratory LMM revealed successful learning of self-regulation along the course of training for participants who received feedback from the amygdala. A significant exploratory correlation between individual target region activity in the simple run and clinical improvement was found for one dimension of DBD. Conclusions: This exploratory study demonstrated feasibility and suggests clinical efficacy of individualized rtfMRI-NF comparable to active TAU for adolescents with DBD and increased CU traits. Further studies are needed to confirm efficacy, specificity and to clarify underlying learning mechanisms

Orbitofrontal control of conduct problems? Evidence from healthy adolescents processing negative facial affect

International audienceConduct problems (CP) in patients with disruptive behavior disorders have been linked to impaired prefrontal processing of negative facial affect compared to controls. However, it is unknown whether associations with prefrontal activity during affective face processing hold along the CP dimension in a healthy population sample, and how subcortical processing is affected. We measured functional brain responses during negative affective face processing in 1444 healthy adolescents [ M = 14.39 years (SD = 0.40), 51.5% female] from the European IMAGEN multicenter study. To determine the effects of CP, we applied a two-step approach: (a) testing matched subgroups of low versus high CP, extending into the clinical range [ N = 182 per group, M = 14.44 years, (SD = 0.41), 47.3% female] using analysis of variance, and (b) considering (non)linear effects along the CP dimension in the full sample and in the high CP group using multiple regression. We observed no significant cortical or subcortical effect of CP group on brain responses to negative facial affect. In the full sample, regression analyses revealed a significant linear increase of left orbitofrontal cortex (OFC) activity with increasing CP up to the clinical range. In the high CP group, a significant inverted u-shaped effect indicated that left OFC responses decreased again in individuals with high CP. Left OFC activity during negative affective processing which is increasing with CP and decreasing in the highest CP range may reflect on the importance of frontal control mechanisms that counteract the consequences of severe CP by facilitating higher social engagement and better evaluation of social content in adolescents

The effects of callous-unemotional traits and aggression subtypes on amygdala activity in response to negative faces

BACKGROUND Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing. METHODS We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8-18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task. RESULTS Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression. CONCLUSIONS Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment

The effects of callous-unemotional traits and aggression subtypes on amygdala activity in response to negative faces

BACKGROUND Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing. METHODS We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8-18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task. RESULTS Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression. CONCLUSIONS Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment