Functional Connectivity of Substantia Nigra and Ventral Tegmental Area: Maturation During Adolescence and Effects of ADHD

Dopaminergic (DArgic) pathways play crucial roles in brain function and their disruption is implicated in various neuropsychiatric diseases. Here, we demonstrate in 402 healthy children/adolescents (12 ± 3 years) and 704 healthy young adults (23 ± 5 years) that the functional connectivity of DA pathways matures significantly from childhood to adulthood and is different for healthy children and children with attention-deficit/hyperactivity disorder (ADHD; N = 203; 12 ± 3 years). This transition is characterized by age-related increases in the functional connectivity of the ventral tegmental area (VTA) with limbic regions and with the default mode network and by decreases in the connectivity of the substantia nigra (SN) with motor and medial temporal cortices. The changes from a predominant influence of SN in childhood/adolescence to a combined influence of SN and VTA in young adulthood might explain the increased vulnerability to psychiatric disorders, such as ADHD, early in life. We also show that VTA and SN connectivity networks were highly reproducible, which highlights their potential value as biomarkers for evaluating DArgic dysfunction in neuropsychiatric disorders.