Objective Disruption of executive function is present in many neuropsychiatric disorders. However, determining the specificity of executive dysfunction within these disorders is challenging given high comorbidity of conditions. Here we investigated executive system deficits in association with dimensions of psychiatric symptoms in youth using a working memory paradigm, hypothesizing that common and dissociable patterns of dysfunction would be present. Methods We studied 1,129 youths who completed a fractal n-back task during fMRI at 3T as part of the Philadelphia Neurodevelopmental Cohort. Factor scores of clinical psychopathology were calculated using an itemwise confirmatory bifactor model, describing overall psychopathology as well as four orthogonal dimensions of symptoms including anxious-misery (mood / anxiety), behavioral disturbance (ADHD / conduct), psychosis-spectrum symptoms, and fear (phobias). The impact of psychopathology dimensions on behavioral performance and executive system recruitment (2-back > 0-back) were examined using both multivariate (matrix regression) and mass-univariate (linear regression) analyses. Results Overall psychopathology was associated with both abnormal multivariate patterns of activation and a failure to activate executive regions within the cingulo-opercular control network including the frontal pole, cingulate cortex, and anterior insula. Additionally, psychosis-spectrum symptoms were associated with hypo-activation of left dorsolateral prefrontal cortex, whereas behavioral symptoms were associated with hypo-activation of fronto-parietal cortex and cerebellum. In contrast, anxious-misery symptoms were associated with widespread hyper-activation of the executive network. Conclusions These findings provide novel evidence that common and dissociable deficits within the brain’s executive system are present in association with dimensions of psychopathology in youth.

Midlife decline in cognition, specifically in areas of executive functioning, is a frequent concern for which menopausal women seek clinical intervention. The dependence of executive processes on prefrontal cortex function suggests estrogen effects on this brain region may be key in identifying the sources of this decline. Recent evidence from rodent, nonhuman primate, and human subject studies indicates the importance of considering interactions of estrogen with neurotransmitter systems, stress, genotype, and individual life events when determining the cognitive effects of menopause and estrogen therapy.

The brain is organized into networks at multiple resolutions, or scales, yet studies of functional network development typically focus on a single scale. Here, we derive personalized functional networks across 29 scales in a large sample of youths (n = 693, ages 8–23 years) to identify multi-scale patterns of network re-organization related to neurocognitive development. We found that developmental shifts in inter-network coupling reflect and strengthen a functional hierarchy of cortical organization. Furthermore, we observed that scale-dependent effects were present in lower-order, unimodal networks, but not higher-order, transmodal networks. Finally, we found that network maturation had clear behavioral relevance: the development of coupling in unimodal and transmodal networks are dissociably related to the emergence of executive function. These results suggest that the development of functional brain networks align with and refine a hierarchy linked to cognition.

Executive functions are involved in the development of academic skills and are critical for functioning in school settings. The relevance of executive functions to education begins early and continues throughout development, with clear impact on achievement. Diverse efforts increasingly suggest ways in which facilitating development of executive function may be used to improve academic performance. Such interventions seek to alter the trajectory of executive development, which exhibits a protracted course of maturation that stretches into young adulthood. As such, it may be useful to understand how the executive system develops normally and abnormally in order to tailor interventions within educational settings. Here we review recent work investigating the neural basis for executive development during childhood and adolescence.