From Irritability to Impairment: How Neurodevelopment of Executive Function and Parent-Child Neural Synchrony Influence the Transition from Normal to Abnormal

The overarching goal of this project is to launch a state-of-the-art program of research designed to investigate the neurodevelopment of irritability in early childhood from a novel, neurocognitive, and social interactional perspective. We will test the innovative hypothesis that developmental changes in executive function will moderate pathways to psychopathology using longitudinal, multimodal neuroimaging. Preschool age irritability is a normative feature of temperament but at the extreme, is a risk factor for 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. Methodological constraints include the lack of knowledge of the neurodevelopment of irritability, the absence of direct links between these neurodevelopmental markers and ecologically-valid, observable, social interactional behaviors, and reliance on a disorder-based approach, which lacks the specificity and developmental-sensitivity that dimensional perspectives provide. In order to decrease the lifespan mental health burden of preschool irritability, it is critical that we 1)identify specific biomarkers underlying early vulnerability for psychopathology 2)examine how the parenting environment moderates this vulnerability, and 3)target these deviant pathways with brain-based behavioral intervention. The goal of this project is to initiate a cutting-edge, neurodevelopmental investigation aimed at identifying aberrant from normative irritable trajectories as the foundation for future brain-based behavioral intervention. The intense developmental acceleration of executive function during the preschool period has been repeatedly linked to increasing use of the lateral prefrontal cortex (LPFC) and its efficient connectivity to parietal and subcortical regions. We propose a novel application of the neurodevelopment of executive function as a moderator of an emergent psychopathology trajectory. Specifically, we hypothesize that those irritable children who fail to develop executive function, and underlying LPFC function, along a normative trajectory will report increased symptoms of psychopathology at school-age. 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 quite difficult in preschool children who are prone to movement and discomfort in unfamiliar environments. We will, thus, employ Functional Near-Infrared Spectroscopy (fNIRS), a safe, non-invasive optical imaging technique, to examine the LPFC correlates of executive function in a community sample (n=150) enriched for high irritability at age 4 and followed up at age 5. At the transition to school-age (age 6), where a 50% rate of psychopathological symptoms have been reported in irritable children, a third fNIRS assessment will occur along with simultaneous functional magnetic resonance imaging (fMRI) to probe the connectivity of the LPFC to parietal and subcortical regions. We will also introduce a neuroimaging component to a standardized developmentally-based laboratory interaction task in order to investigate parent-child neural synchrony, a measure of the correlation between signals of brain activity of interacting individuals, as a moderator of clinical outcome. An ambitious program of longitudinal, multi-modal ne