Systematic Review and Meta-analysis: Task-based fMRI Studies in Youths With Irritability

Objective: Childhood irritability, operationalized as disproportionate and frequent temper tantrums and low frustration tolerance relative to peers, is a transdiagnostic symptom across many pediatric disorders. Studies using task-dependent functional magnetic resonance imaging (fMRI) to probe neural dysfunction in irritability have increased. However, an integrated review summarizing the published methods and synthesized fMRI results remains lacking.Method: We conducted a systematic search using irritability terms and task functional neuroimaging in key databases in March 2021, and identified 30 studies for our systematic review. Sample characteristics and fMRI methods were summarized. A subset of 28 studies met the criteria for extracting coordinate-based data for quantitative meta-analysis. Ten activation-likelihood estimations were performed to examine neural convergence across ir-ritability measures and fMRI task domains.Results: Systematic review revealed small sample sizes (median = 58, mean age range = 8-16 years) with heterogeneous sample characteristics, ir-ritability measures, tasks, and analytical procedures. Meta-analyses found no evidence for neural activation convergence of irritability across neuro-cognitive functions related to emotional reactivity, cognitive control, and reward processing, or within each domain. Sensitivity analyses partialing out variances driven by heterogeneous tasks, irritability measures, stimulus types, and developmental ages all yielded null findings. Results were compared with a review on irritability-related structural anomalies from 11 studies.Conclusion: The lack of neural convergence suggests a need for common, standardized irritability assessments and more homogeneous fMRI tasks. Thoughtfully designed fMRI studies probing commonly defined neurocognitive functions may be more fruitful to elucidate the neural mechanisms of irritability. Open science practices, data mining in large neuroscience databases, and standardized analytical methods promote meaningful collaboration in irritability research.