Neural substrates of child irritability in typically developing and psychiatric populations

Abstract

Irritability is an aspect of the negative affectivity domain of temperament, but in severe and dysregulated forms is a symptom of a range of psychopathologies. Better understanding of the neural underpinnings of irritability, outside the context of specific disorders, can help to understand normative variation but also characterize its clinical salience in psychopathology diagnosis. This study assessed brain activation during reward and frustration, domains of behavioral deficits in childhood irritability. Children (age 6–9) presenting in mental health clinics for extreme and impairing irritability (n=26) were compared to healthy children (n=28). Using developmentally-sensitive methods, neural activation was measured via a negative mood induction paradigm during fMRI scanning. The clinical group displayed more activation of the anterior cingulate and middle frontal gyrus during reward, but less activation during frustration, than healthy comparison children. The opposite pattern was found in the posterior cingulate. Further, in clinical subjects, parent report of irritability was dimensionally related to decreased activation of the anterior cingulate and striatum during frustration. The results of this study indicate neural dysfunction within brain regions related to reward processing, error monitoring, and emotion regulation underlying clinically impairing irritability. Results are discussed in the context of a growing field of neuroimaging research investigating irritable children.

Neurodevelopmental maturation as a function of irritable temperament

“…Although previous investigations into the neural underpinnings of temperament, both in the anxious [Fox et al, ; Guyer et al, ; Perez‐Edgar et al, ; Perlman and Pelphrey, ; Schwartz et al, ] and irritable [Deveney et al, ; Grabell et al, ; Perlman et al, , ] domains demonstrate distinct patterns of activation during negative emotion, our study only found this effect when examining the irritable domain. We propose two possible reasons for this unique finding.…”

Pediatric Irritability: A Systems Neuroscience Approach

“…For example, in a study using functional near infrared spectroscopy imaging in a sample of preschool children, decreased lateral PFC activity was associated with increased frustration tolerance [76]. In older youth, studies of frustration during fMRI or magnetoencephalography show associations between irritability and ACC, striatal, medial PFC, parietal and amygdala activity [73–75, 77] (Figure 3). Somewhat unexpectedly, in two fMRI studies irritability is associated with decreased amygdala activation during frustration [74,75].…”

Disruptive Mood Dysregulation Disorder (DMDD): An RDoC perspective

“…For example, compared to healthy controls, young children (ages 6- 9) with clinically significant symptoms of irritability exhibit decreased activation of the ACC in response to frustration (Perlman et al, 2015). This contrasts an earlier magnetoencephalography (MEG) study with a similar, yet older sample of children (ages 8- 17) with SMD, who showed greater activation of ACC, along with higher ratings of agitation and sadness, in response to negative feedback, as compared to healthy controls (Rich et al, 2011).…”