Soonjo Hwang

Reward: Empirical Contribution: Temporal Discounting and Conduct Disorder in Adolescents

The current study examined temporal discounting (the decrease in subjective reward value as a function of increasing delay) in youths with conduct disorder (CD) and the extent to which this was modulated by level of psychopathic traits. In the temporal discounting task, participants were asked to choose between immediate rewards of varying values and a larger reward, held at a constant value (

Dual neurocircuitry dysfunctions in disruptive behavior disorders: Emotional responding and response inhibition

10), whose receipt was delayed by different time intervals across trials (e.g., 7 days, 360 days). The level of immediate reward necessary for selection over the larger, delayed reward is the measure of temporal discounting. Forty-six youths (21 with CD and 25 healthy youths) participated in this study. Compared with healthy youths, youths with CD chose significantly smaller amounts of immediate reward rather than the larger future rewards. This was the case even in youths with CD without comorbid attention-deficit/hyperactivity disorder. However, level of psychopathic traits did not modulate temporal discounting in this sample. These results are discussed in terms of neurobiological models of CD and psychopathic traits.

Neurodevelopmental changes in the responsiveness of systems involved in top down attention and emotional responding.

BACKGROUND To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10-18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits. METHOD Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (group×emotion by task) was conducted on the BOLD response data. RESULTS Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD. CONCLUSIONS These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patients specific pathophysiology.

Segregating attention from response control when performing a motor inhibition task. Segregating attention from response control

In this study, we aimed to investigate age related changes in systems implicated in top down attention and the implications of this for amygdala responses to emotional distracters. Fifty-one healthy subjects including 18 children (aged 10-14), 15 adolescents (aged 14-18), and 18 young adults (aged 18-25) completed the affective Stroop paradigm while undergoing functional MRI. While achieving comparable behavioral performance, children, relative to adolescents and adults, showed increased activation in areas including anterior cingulate gyrus and precentral gyrus in task relative to view trials. In addition, children showed increased activation within the amygdala and fusiform gyrus in response to emotional stimuli. Notably, the group difference within the amygdala was particularly pronounced during task trials. Also children showed increased connectivity between amygdala and superior frontal gyrus and bilateral postcentral gyrii in response to negative task trials. These data are consistent with previous work indicating less consolidated functional integrity in regions implicated in top down attention in children relative to older participants and extend this work by indicating that this less consolidated functional integrity leads to reduced automatic emotion regulation as a function of top down attention. Given that reduced automatic emotion regulation as a function of top down attention is considered a risk factor for the development of anxiety disorders, these data may contribute to an understanding of the increased risk for the development of these disorders at this age.

Disruptive Behavior Disorders: Taking an RDoC(ish) Approach

Considerable work has demonstrated that inferior frontal gyrus (IFG), anterior insula cortex (AIC) and the supplementary motor area (SMA) are responsive during inhibitory control tasks. However, there is disagreement as to whether this relates to response selection/ inhibition or attentional processing. The current study investigates this by using a Go/No-go task with a factorial design. We observed that both left IFG and dorsal pre-SMA were responsive to no-go cues irrespective of cue frequency. This suggests a role for both in the inhibition of motor responses. Generalized psychophysiological interaction (gPPI) analyses suggest that inferior frontal gyrus may implement this function through interaction with basal ganglia and by suppressing the visual representation of cues associated with no-go responses. Anterior insula cortex and a more ventral portion of pre-SMA showed greater responsiveness to low frequency relative to higher frequency stimuli, irrespective of response type. This may reflect the hypothesized role of anterior insula cortex in marking low frequency items for additional processing (cf. Menon and Uddin, 2010). Consistent with this, the gPPI analysis revealed significantly greater anterior insula cortex connectivity with visual cortex in response to low relative to high frequency cues.

Executive attention control and emotional responding in attention-deficit/hyperactivity disorder — A functional MRI study

The disruptive behavior disorders include Conduct Disorder (CD), Oppositional Defiant Disorder (ODD), and Attention Deficit Hyperactivity Disorder (ADHD). These disorders are highly comorbid with each other as well as with mood and anxiety disorders and personality disorders (particularly borderline personality disorder). The goal of this chapter is to consider these disorders from an RDoC(ish) approach. In other words, we will outline four functional processes and the behavioral implications of dysfunction within these processes. Moreover, we will briefly consider how dysfunction in one might increase the risk for the development of rather different behavioral problems that have been previously associated with rather different disorders. Our goal is to identify neurocognitive-based functional targets for treatment.

Emotional learning and the development of differential moralities: Implications from research on psychopathy

Background There are suggestions that patients with attention-deficit/hyperactivity disorder (ADHD) show impairment in executive attention control and emotion regulation. This study investigated emotion regulation as a function of the recruitment of executive attention in patients with ADHD. Methods Thirty-five healthy children/adolescents (mean age = 13.91) and twenty-six children/adolescents with ADHD (mean age = 14.53) participated in this fMRI study. They completed the affective Stroop paradigm viewing positive, neutral and negative images under varying cognitive loads. A 3-way ANOVA (diagnosis-by-condition-by-emotion) was conducted on the BOLD response data. Following this, 2 3-way ANOVAs (diagnosis-by-condition-by-emotion) were applied to context-dependent psychophysiological interaction (gPPI) analyses generated from a dorsomedial frontal cortex and an amygdala seed (identified from the BOLD response ANOVA main effects of condition and emotion respectively). Results A diagnosis-by-condition interaction within dorsomedial frontal cortex revealed reduced recruitment of dorsomedial frontal cortex as a function of increased task demands in the children/adolescents with ADHD relative to healthy children/adolescents. The level of reduction in recruitment of dorsomedial frontal cortex was significantly correlated with symptom severity (total and hyperactivity) measured by Conners Parent Report Scale in the children/adolescents with ADHD. In addition, analysis of gPPI data from a dorsomedial frontal cortex seed revealed significant diagnosis-by-condition interactions within lateral frontal cortex; connectivity between dorsomedial frontal cortex and lateral frontal cortex was reduced in the patients with ADHD relative to comparison youth during congruent and incongruent task trials relative to view trials. There were no interactions of group, or main effect of group, within the amygdala in the BOLD response ANOVA (though children/adolescents with ADHD showed increased responses to positive images within temporal cortical regions during task trials; identified by the diagnosis-by-condition-by-emotion interaction). However, analysis of gPPI data from an amygdala seed revealed decreased connectivity between amygdala and lentiform nucleus in the presence of emotional stimuli in children/adolescents with ADHD (diagnosis-by-emotion interaction). Conclusion The current study demonstrated disrupted recruitment of regions implicated in executive function and impaired connectivity within those regions in children/adolescents with ADHD. There were also indications of heightened representation of emotional stimuli in patients with ADHD. However, as the findings were specific for positive stimuli, the suggestion of a general failure in emotion regulation in ADHD was not supported.

Melanoma Cell Lines Contain a Proteasome‐Sensitive, Nuclear Cytoskeleton‐Associated Pool of β‐Catenin

In this paper, we will argue that (1) four classes of norm can be distinguished from a neuro‐cognitive perspective; (2) learning the prohibitive power of these norms relies on relatively independent emotional systems; (3) individuals with psychopathy show selective impairment for one of these emotional learning systems and two classes of norm: care based and justice based; and (4) while emotional learning systems are necessary for appropriate moral development/reasoning, they are not sufficient for moral development/reasoning.

Discrepancy in perception of bullying experiences and later internalizing and externalizing behavior: A prospective study

Recent studies have shown that colon carcinoma and melanoma cells that contain either deletions of APC or activating mutations in β-catenin contain elevated levels of both cytoplasmic and nuclear β-catenin.1–4 Similar results were reported following proteasome inhibition of cells containing wild-type β-catenin. Furthermore, in cells containing mutated β-catenin or wild-type β-catenin but no APC, the β-catenin protein has an exceptionally long half-life. These findings led to the hypothesis that lack of APC function or β-catenin mutation result in elevated levels of nuclear βcatenin secondary to elevation of a soluble, proteasome-resistant cytosolic pool of the protein. However, β-catenin exists in several subcellular locations, and little is known of the effect of β-catenin mutations/APC deletions on the response of these pools to proteasome inhibition. To further examine this question, we studied three previously described melanoma cell lines,3 1241, which expresses APC but carries a Ser37Æ Phe37 (S37F) β-catenin mutation in the GSK3ß phosphorylation site; 928, which expresses wild-type β-catenin but no detectable APC; and 1011, which contains both wild-type β-catenin and APC. In this study, the three melanoma cell lines were treated with the proteasome inhibitor ALLnL (100 μM)5,6 for 6 hours, and the β-catenin steady-state level in several subcellular fractions was compared with that of untreated cells. As predicted from previous studies, soluble β-catenin in 1011 cells was sensitive to proteasome inhibition, but the soluble β-catenin fraction of both 928 and 1241 cells was resistant to proteasome-mediated degradation. A novel finding of this study is that the detergent-insoluble β-catenin fraction from all three cell lines retained proteasome sensitivity. To clarify the nature of this detergent-insoluble fraction, we lysed cells in detergent-free buffer and prepared soluble, microsomal, and pellet fractions, which were analyzed for β-catenin content. As expected, the β-catenin steady-state level in 1011 cells was increased primarily in the soluble fraction after proteasome inhibition. In contrast, in 928 and 1241 cells, β-catenin protein markedly accumulated only

Looming Threats and Animacy: Reduced Responsiveness in Youth with Disrupted Behavior Disorders

Discrepancy in perception of bullying experiences may lead to later internalizing or externalizing behavior in adolescents. A 1,663 South Korean 7th and 8th graders (mean age: 13.1 and 14.1 years old), were seen for a follow-up study to examine the relationships between the discrepancy in perception of their bullying experiences (defined as discrepancy between self- and peer-reports of bullying experiences) and internalizing or externalizing behavior at follow-up. Bullying was assessed by self- and peer-report. The discrepancy in perception of bullying experiences was defined by the concordance or discordance between self- and peer-reports. Internalizing and externalizing behavior was evaluated using the Youth Self Report and Child Behavior Checklist, at baseline and follow-up. Two by two ANCOVA was performed with a factorial design, categorizing discrepancy in perception of bullying experiences based on the agreement between self-report and peer-report. Internalizing/externalizing behavior-at-follow-up was used as an outcome, adjusting for other known risk factors for internalizing/externalizing behavior, including baseline internalizing/externalizing behavior, and bullying experiences. Adolescents with perceptions of bullying experiences discrepant from peer-reports showed increased internalizing/externalizing behavior at follow-up. Bullying also stands out as an independent risk factor for the development of future externalizing behavior even among adolescents with accurate perceptions of bullying experiences. These specific groups of youth warrant more focused assessment and intervention.