Neural Underpinnings of Irritability: fNIRS Evidence of Impaired Executive Function in Preschool Children

• In Event: 1-205 - Advances in Neurobiological Conceptualizations of Pediatric Irritability

Integrative Statement

Preschool age irritability is a normative feature of temperament but at the extreme, is a risk factor for social conflict, school problems, and psychopathology across the lifespan. However, the challenge of differentiating clinically salient irritability from developmentally-normative temperamental variation has impeded ability to pinpoint which irritable children are at the onset of a chronic psychopathology trajectory. Little is known about the neural mechanisms which underlie irritability and predict its associated clinical outcomes. Preschool is also a period of accelerated growth in executive function, raising the possibility that normative executive function might separate those irritable children who will go on to develop psychiatric disorders from those will maintain irritable temperament, but continue to mature normally. We present a model in which children who demonstrate decreased neural activation during executive function across preschool, along with high levels of irritability, will be those at the highest risk. We will discuss support for this model in the context of an ongoing longitudinal study.
One of the challenges of operationalizing a neurodevelopmental framework for psychopathologic processes is that different methodologies are needed at varying developmental periods. The acquisition of neural data is difficult in preschool children who are prone to movement and discomfort in unfamiliar environments. Thus, we used functional near infrared spectroscopy (fNIRS) to examine inhibitory control in the prefrontal cortex of 118 typically-developing preschoolers (age 4-5). FNIRS is a safe, non-invasive optical imaging technique, which is relatively movement insensitive and allows for social interaction.
We employed a novel inhibitory control task in which subjects were told the story of a group of children playing outside when it starts to rain. They were asked to press a button every time they saw a sun, in order to make the sun come back, but to inhibit their response when they saw a raincloud. We took a comprehensive approach to understanding the relationship between PFC activation and early childhood temperament during inhibitory control. All 15 temperament domains defined by the Children's Behavior Questionnaire (CBQ) were assessed using automatic feature selection via LASSO regression. Results indicate widespread inhibitory control effect within the PFC (Figure 1). LASSO results indicated that only the Anger/Frustration dimension was predictive of activation during the task, confirmed by follow-up robust regression analysis (Figure 2).
These findings support previous work showing relationships between irritability and prefrontal activation during executive function and extend those findings by demonstrating the specificity of the activation-irritability relationship among temperament dimensions. We expect that future work will note impaired lateral PFC functioning such that clinically irritable children demonstrate decreased lateral PFC activation during inhibitory control, indicative of an underdeveloped system for self-regulation. Developmentally sensitive neuroimaging techniques, combined with innovative and child-friendly behavioral data collection, has the potential to identify patterns of disruption in neural processes underlying executive function in highly irritable children so that targeted therapeutic interventions can be developed to reestablish a normative developmental trajectory.

Authors

• Susan Perlman, University of Pittsburgh
  Presenting Author

• Christina Hlutkowsky, University of Pittsburgh
  Non-Presenting Author

• Frank A Fishburn, University of Pittsburgh
  Non-Presenting Author