Abstract
A key challenge for cognitive neuroscience is the development and validation of tasks that capture real-world cognitive phenomena and render them suitable for investigation within an MRI environment. Cognitive flexibility is necessary for a range of adaptive behaviors and is associated with optimal life outcomes, but as a psychological construct it has been difficult to operationalize and validate. Crucially, psychometrically validated tasks must be developed prior to their application to clinical populations to investigate the neural substrates of cognitive inflexibility. Here, we address these limitations by adapting a well-validated laboratory measure of cognitive flexibility to the scanner environment (Study I) and applied the neuroimaging results to characterize directed functional connectome profiles supportive of cognitive flexibility in children (Study II). First, the neural substrates of cognitive flexibility in a sample of 32 neurotypical adults (19-46 years) were characterized using task-based functional magnetic resonance imaging (fMRI). Results demonstrated that the fMRI-adapted task is reliable and showed convergent validity with the laboratory-based version of the task, which has previously been shown to measure cognitive flexibility. In line with our hypotheses, we observed activation in prefrontal, posterior parietal, insular, basal ganglia and thalamic regions in response to engaging cognitive flexibility, over and above low-level visual and motor processes. In Study II, heterogeneity in cognitive flexibility in children with a range of abilities (children with autism spectrum disorder [ASD], attention deficit/hyperactivity disorder [ADHD], and typically developing [TD] children) was parsed using directed functional connectivity profiles derived from resting-state fMRI data. Brain regions identified in Study I were used to guide region-of-interest (ROI) selection to estimate individual connectivity profiles in Study II. We expected to find at least three subgroups of children who differed in their network connectivity metrics and symptom measures. Unexpectedly, we did not find a stable or valid subgrouping solution, which suggests that categorical models of the neural substrates of cognitive flexibility in children may be invalid. Together, the results highlight the neurotypical correlates of cognitive flexibility in both children and adults within the frontoparietal and salience networks, and shed light on the validity of conceptualizing the neural substrates of cognitive flexibility categorically in children. Ultimately, this work may provide a foundation for the development of a revised nosology focused on neurobiological substrates of mental illness as an alternative to traditional symptom-based classification systems.