Executive functioning moderates neural mechanisms of irritability during reward processing in youth.

Pediatric irritability is the most robust indicator of transdiagnostic psychopathology risk. It is associated with altered neural reward processing, including neural networks related to cognitive control, and better cognitive control has been hypothesized to mitigate irritability. We evaluated the relationship of executive functioning (EF) with irritability-related neural correlates of reward processing in youths with varying levels of irritability. Participants (N = 51, mean age=13.80 years, SD=1.94) completed a monetary incentive delay task during multiband fMRI acquisition. Irritability and EF were measured via the Affective Reactivity Index and the NIH Toolbox cognition battery, respectively. Whole-brain analyses, controlling for age, examined the moderating role of EF on irritability-related brain activation and connectivity (seeds: striatum, amygdala) during reward anticipation and performance feedback. Irritability-related neural patterns during reward processing depended on EF, in occipital areas during reward anticipation and limbic, frontal, and temporal networks during performance feedback. Higher irritability combined with higher EF was associated with neural patterns opposite to those observed for higher irritability with lower co-occurring EF. Although preliminary, findings suggest that EF may buffer irritability-related reward processing deficits. Additionally, individual differences in EF and their relation to irritability may be related to varied etiologic mechanisms of irritability with important implications for personalized prevention and intervention.

Reward-related neural correlates in adolescents with excess body weight.

The functional and connectivity reward processing in adults with excessive body weight is well documented, though is relatively less researched during adolescence. Given that reward and inhibition may be highly malleable during adolescence, it is unknown how impulsive behaviors, potentially stemming from impaired inhibitory control and heightened sensitivity to rewarding cues, relate to increases in body weight in adolescents. Adolescents (N = 76; mean age = 14.10 years, SD = 1.92) with varied body mass index (BMI) performed a child-friendly monetary incentive delay task during functional magnetic resonance imaging, to study reward processing during the anticipation of rewards (cue) and reactions to feedback about rewards (feedback). Our results show that adolescents with greater BMI z-score show neural activation and ventral striatum connectivity alterations in networks implicated in reward, salience detection, and inhibitory control. These bottom-up reward and top-down inhibitory control networks, as well as interactions between these networks were prevalent during the anticipation period (when the cue is presented) as well as when receiving feedback about whether one has received a reward. Specifically, our results were mainly driven by failure to receive a reward in the feedback period, and the anticipation of a potential reward in the anticipation period. Overall, we provide evidence for heightened reward salience as well as inhibitory control deficits that, in combination, may contribute to the impulsive behaviors that lead to higher BMI in adolescents.

Neural and behavioral correlates of inhibitory control in youths with varying levels of irritability.

BACKGROUND: Irritability, a relatively lowered threshold for anger, is prevalent in typically and atypically developing youths. Inhibitory control, the ability to suppress behaviors counter to goals, is essential for regulating emotions, including anger. Understanding how irritability relates to behavioral and neural markers of inhibitory control may inform interventions. METHODS: Youths (N=52; mean age=13.78) completed a Flanker task on an iPad to measure behavioral correlates of inhibitory control; a subsample (n=19; mean age=13.21) additionally completed a similar task while undergoing fMRI acquisition to evaluate inhibitory control on a neural level. Irritability was measured using the Affective Reactivity Index. Associations between irritability and inhibitory control were evaluated behaviorally (via Pearson correlations), and neurally (via ANCOVAs with whole-brain activation and amygdala connectivity). RESULTS: fMRI results indicated that higher levels of irritability were associated with aberrant activation (in middle frontal gyrus, amygdala/parahippocampal gyrus, anterior cingulate, lentiform nucleus/striatum) and left amygdala connectivity (with middle temporal gyrus, parahippocampal gyrus, posterior cingulate, fusiform gyrus, and thalamus). Behavioral results were mixed. LIMITATIONS: Longitudinal studies are needed to characterize changes in neural circuitry and delineate whether the brain profiles precede or are a consequence of symptoms. Larger samples powered to examine multiple irritability-related symptom dimensions will be necessary to elucidate shared vs. disorder-specific irritability mechanisms. CONCLUSIONS: Findings suggest that pediatric irritability may be related to neural processes involving inhibitory control. Further, findings underscore the importance of neuroimaging in investigating symptom dimensions such as irritability, as neuroimaging may be more sensitive in detecting underlying abnormalities compared to behavioral data alone.