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Evidence of Non-Linear Associations between Frustration-Related Prefrontal Cortex Activation and the Normal:Abnormal Spectrum of Irritability in Young Children

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Abstract

Burgeoning interest in early childhood irritability has recently turned toward neuroimaging techniques to better understand normal versus abnormal irritability using dimensional methods. Current accounts largely assume a linear relationship between poor frustration management, an expression of irritability, and its underlying neural circuitry. However, the relationship between these constructs may not be linear (i.e., operate differently at varying points across the irritability spectrum), with implications for how early atypical irritability is identified and treated. Our goal was to examine how the association between frustration-related lateral prefrontal cortex (LPFC) activation and irritability differs across the dimensional spectrum of irritability by testing for non-linear associations. Children (N = 92; ages 3–7) ranging from virtually no irritability to the upper end of the clinical range completed a frustration induction task while we recorded LPFC hemoglobin levels using fNIRS. Children self-rated their emotions during the task and parents rated their child’s level of irritability. Whereas a linear model showed no relationship between frustration-related LPFC activation and irritability, a quadratic model revealed frustration-related LPFC activation increased as parent-reported irritability scores increased within the normative range of irritability but decreased with increasing irritability in the severe range, with an apex at the 91st percentile. Complementarily, we found children’s self-ratings of emotion during frustration related to concurrent LPFC activation as an inverted U function, such that children who reported mild distress had greater activation than peers reporting no or high distress. Results suggest children with relatively higher irritability who are unimpaired may possess well-developed LPFC support, a mechanism that drops out in the severe end of the irritability dimension. Findings suggest novel avenues for understanding the heterogeneity of early irritability and its clinical sequelae.

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Acknowledgements

Supported by NIMH grants K01 MH094467 PI: Susan Perlman, R21 MH100189 PI: Susan Perlman, and R01 MH107540: PI Susan Perlman.

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Authors and Affiliations

  1. Department of Psychiatry, Laboratory for Child Brain Development, University of Pittsburgh School of Medicine, Loeffler Building, 121 Meyran Avenue, Pittsburgh, PA, 15213, USA

    Adam S. Grabell, Yanwei Li & Susan B. Perlman

  2. Research Center for Learning Science, Key Laboratory of Child Development and Learning Science of Ministry of Education, Southeast University, Nanjing, Jiangsu, China

    Yanwei Li

  3. Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Jeff W. Barker & Theodore J. Huppert

  4. Department of Medical Social Sciences, Feinberg School of Medicine, and the Institute for Policy Research, Northwestern University, Chicago, IL, USA

    Lauren S. Wakschlag

Authors
  1. Adam S. Grabell
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  2. Yanwei Li
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  4. Lauren S. Wakschlag
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  5. Theodore J. Huppert
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  6. Susan B. Perlman
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Correspondence to Adam S. Grabell.

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Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

Conflict of Interests

Drs. Grabell, Barker, Wakschlag, Huppert and Perlman, and Ms. Li, report no competing interests.

Additional information

Portions of the findings included in this manuscript were presented as a poster at the Congress on Pediatric Irritability and Dysregulation, University of Vermont, Burlington, VT (October 21–22, 2015).

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Grabell, A.S., Li, Y., Barker, J.W. et al. Evidence of Non-Linear Associations between Frustration-Related Prefrontal Cortex Activation and the Normal:Abnormal Spectrum of Irritability in Young Children. J Abnorm Child Psychol 46, 137–147 (2018). https://doi.org/10.1007/s10802-017-0286-5

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