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

Ka Shu Lee, Cheyanne Hagan, Mina Hughes, Grace Cotter, Eva McAdam Freud, Katharina Kircanski, Ellen Leibenluft, Melissa Brotman, Wan-Ling Tseng
doi: https://doi.org/10.1101/2022.01.14.475556
Ka Shu Lee
1Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom
2Yale Child Study Center, Yale School of Medicine, New Haven, CT, United States
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  • For correspondence: kashu.lee@psy.ox.ac.uk
Cheyanne Hagan
2Yale Child Study Center, Yale School of Medicine, New Haven, CT, United States
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Mina Hughes
2Yale Child Study Center, Yale School of Medicine, New Haven, CT, United States
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Grace Cotter
2Yale Child Study Center, Yale School of Medicine, New Haven, CT, United States
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Eva McAdam Freud
2Yale Child Study Center, Yale School of Medicine, New Haven, CT, United States
3Division of Psychology and Language Sciences, University College London, London, United Kingdom
4Anna Freud National Centre for Children and Families, London, United Kingdom
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Katharina Kircanski
5Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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Ellen Leibenluft
5Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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Melissa Brotman
5Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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Wan-Ling Tseng
2Yale Child Study Center, Yale School of Medicine, New Haven, CT, United States
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Abstract

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 irritability measures and fMRI task domains.

Results Systematic review revealed small sample sizes (median = 58, mean age range = 8–16 years) with heterogeneous sample characteristics, irritability measures, tasks, and analytical procedures. Meta-analyses found no evidence for neural activation convergence of irritability across neurocognitive functions related to emotional reactivity, cognitive control, and reward processing, nor within each domain. Sensitivity analyses partialing out variances driven by heterogeneous tasks, irritability measures, stimulus types, and developmental ages all yielded null findings.

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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 17, 2022.
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Systematic Review and Meta-Analysis: Task-based fMRI Studies in Youths with Irritability
Ka Shu Lee, Cheyanne Hagan, Mina Hughes, Grace Cotter, Eva McAdam Freud, Katharina Kircanski, Ellen Leibenluft, Melissa Brotman, Wan-Ling Tseng
bioRxiv 2022.01.14.475556; doi: https://doi.org/10.1101/2022.01.14.475556
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Systematic Review and Meta-Analysis: Task-based fMRI Studies in Youths with Irritability
Ka Shu Lee, Cheyanne Hagan, Mina Hughes, Grace Cotter, Eva McAdam Freud, Katharina Kircanski, Ellen Leibenluft, Melissa Brotman, Wan-Ling Tseng
bioRxiv 2022.01.14.475556; doi: https://doi.org/10.1101/2022.01.14.475556

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