Neural mechanisms of reward processing in adolescent irritability

Abstract

Irritability is impairing and prevalent across pediatric psychiatric disorders and typical development, yet its neural mechanisms are largely unknown. This study evaluated the relation between adolescent irritability and reward‐related brain function as a candidate neural mechanism. Adolescents from intervention‐seeking families in the community (N = 52; mean age = 13.80, SD = 1.94) completed a monetary incentive delay task to assess reward anticipation and feedback (reward receipt and omission) during fMRI acquisition. Whole‐brain analyses, controlling for age, examined brain activation and striatal and amygdala connectivity in relation to irritability. Irritability was measured using the parent‐ and youth‐reported Affective Reactivity Index. Irritability was associated with altered reward processing‐related activation and connectivity in multiple networks during reward anticipation and feedback, including increased striatal activation and altered ventral striatum connectivity with prefrontal areas. Our findings suggest that irritability is associated with altered neural patterns during reward processing and that aberrant prefrontal cortex‐mediated top‐down control may be related to irritability. These findings inform our understanding of the etiology of youth irritability and the development of mechanism‐based interventions.

Irritability‐related neural responses to frustrative nonreward in adolescents with trauma histories: A preliminary investigation

“…In addition, across task conditions, youths with greater irritability exhibited hypoactivation and amygdala hypoconnectivity. Overall, our results (both the regions identified as well as the pattern of opposite responses in youths with higher versus lower levels of irritability) are in line with prior work (Deveney et al, 2013;Dougherty et al, 2018;Kryza-Lacombe et al, 2021;Scheinost et al, 2021;Stoddard et al, 2017;Tseng et al, 2019Tseng et al, , 2020Wiggins et al, 2016). As an interesting side note, right and left amygdala networks both evidenced significant associations with irritability, but not in the same regions/task conditions; although our results do not clearly support a particular lateralized view of amygdala function, these asymmetric patterns suggest differing emotional functions for left and right amygdala networks.…”

“…(both the regions identified as well as the pattern of opposite responses in youths with higher versus lower levels of irritability) are in line with prior work (Deveney et al, 2013;Dougherty et al, 2018;Kryza-Lacombe et al, 2021;Scheinost et al, 2021;Stoddard et al, 2017;Tseng et al, 2019Tseng et al, , 2020Wiggins et al, 2016). As an interesting side note, right and left amygdala networks both evidenced significant associations with irritability, but not in the same regions/task conditions;…”

“…for multiple reasons: first, because the adolescence period represents a crucial shift in reward processing neural circuitry (Galván, 2014); second, because frustrative nonreward is a subset of reward processing; third, to extend and build on our prior work which identified irritability-related alterations using a monetary incentive delay task (Dougherty et al, 2018;Kryza-Lacombe et al, 2021); and last, to provide the basis for a developmentally appropriate task that can be used even with young children, given the child-friendly nature of this task.…”

Systematic Review and Meta-Analysis: Task-based fMRI Studies in Youths with Irritability

“…Four studies sampled treatment-seeking and at-risk youths in the local community. 11, 37, 45 Two studies assessed irritability symptoms more broadly in healthy community samples. 20, 26 Three studies constituted part of a large-scale research project (EU-Aggressotype and EU-MATRICS project 38 ; Bipolar offspring study 43 ; IMAGEN 19 ).…”

“…Since including all available contrasts from the identified studies would introduce within-group effects from those that reported alternative analyses of similar contrasts, which could impact the Modeled Activation (MA) values in the software algorithm, 31, 35 we carefully selected the more interpretable and relevant contrast(s) with respect to the study’s key research interest (e.g., angry vs. neutral faces for facial emotion processing studies; 36 reward vs. nonreward conditions during reward anticipation, and performance feedback conditions wherever possible for reward processing studies). 37 For studies that reported more than one relevant contrast with the same control condition (e.g., negative faces vs. shapes and positive faces vs. shapes 38 ), the respective coordinates were pooled as one experiment as recommended. 31, 32, 35 Given that more studies reported significant task-related neural responses when analyzing parent-reported (k=4) than child-reported (k=1) irritability symptoms alone, we prioritized contrasts based on parent report to reduce informant-related variances across individual studies.…”