Trajectories of Response Inhibition Development in Adolescence

Abstract

Adolescence is a pivotal developmental period during which cognitive control and the ability to suppress maladaptive impulses undergo profound refinement. Despite extensive behavioral and imaging studies in humans, the neural circuit mechanisms that drive the maturation of inhibitory control remain poorly understood. To address this gap, we performed a longitudinal multimodal study in macaque monkeys spanning the transition from puberty to adulthood, combining behavioral measurements, prefrontal neurophysiology, and structural neuroimaging within the same individuals. Behavioral performance in multiple variants of the antisaccade task improved dramatically across adolescence. In parallel, prefrontal cortical neurons exhibited robust developmental increases in task-related firing, particularly around the generation of goal-directed saccades, indicating maturation of neural representations supporting inhibitory control. Strikingly, trajectories of behavioral improvement and neural activity maturation were tightly predicted by the development of long-range white matter pathways linking frontal cortex with distributed brain networks. These findings identify white matter development as a key systems-level mechanism underlying the emergence of mature inhibitory control and prefrontal neural dynamics and establish a primate framework for understanding developmental vulnerabilities associated with neuropsychiatric disorders that emerge in adolescence and early adulthood.