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Τρίτη 21 Αυγούστου 2018

Age-Related Trajectories of Functional Coupling between the VTA and Nucleus Accumbens Depend on Motivational State

Over-engagement of the mesolimbic dopamine system is thought to enhance motivation in adolescents. Whereas human neuroimaging has characterized event-evoked responses of the mesolimbic system in adolescents, research has yet to characterize state-dependent engagement (i.e., seconds to minutes) of this system in goal-relevant contexts. In the current longitudinal study, we characterized age-related changes in state-dependent coupling in male and female human participants ranging in age from adolescence to adulthood. Analyses focused on two key regions of the mesolimbic dopamine system, the ventral tegmental area (VTA) and nucleus accumbens (NAcc). Although there were no differences in VTA–NAcc functional coupling in a resting-state context, VTA–NAcc functional coupling was enhanced in preadolescence/early adolescence and decreased into adulthood in a motivational context, in which individuals had to translate goal-relevant cues into instrumental actions. Furthermore, we found that task-related activation in orbitofrontal cortex, middle temporal gyrus, and visual association cortex partially mediated age-related changes in state-dependent VTA–NAcc functional coupling. These results extend prior models of neurodevelopment by showing a relationship between cortical event-evoked activation and state-dependent increases in subcortical engagement of mesolimbic systems.

SIGNIFICANCE STATEMENT Adolescence is characterized by increased motivated behavior, which is thought to result from an over-engagement of mesolimbic dopamine systems. Rodent models show increases in state-dependent engagement of mesolimbic systems in adolescence. However, human neuroimaging research has mainly focused on event-evoked responses (i.e., reward cues). We show that in motivational contexts, there is increased state-dependent coupling across mesolimbic systems in preadolescence/early adolescence that decreases into adulthood and is further predicted by event-evoked cortical responses. Critically, these developmental trajectories were specific to motivationally relevant contexts and were not apparent during resting state. These findings extend emerging models of human development and suggest that state-dependent increases in dopamine signaling may underlie heightened motivation.



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