The Development of Affective and Cognitive Striatal Neurobiology and Connectivity During Adolescence

CNBC Dissertation Defense
Center for the Neural Basis of Cognition (CNBC)

The Development of Affective and Cognitive Striatal Neurobiology and Connectivity During Adolescence

Bart Larsen
Graduate Student Researcher
University of Pittsburgh
November 30, 2017 - 9:00am
Martin Colloquium Center (4127 Sennott Square)

Abstract:

Adolescence is characterized by heightened reward-drive and sensation seeking behavior. Current neurodevelopmental theories hypothesize that this behavior is driven by the development of the brain’s dopaminergic reward system and a developmental imbalance in the influence of the reward system on behavior relative to in cognitive control systems. The striatum is an ideal target for investigating these hypotheses because it is a central hub of the dopaminergic reward system, receives inputs affective and cognitive control systems, and functions to influence action selection. Current evidence for the development of striatal dopaminergic neurobiology during adolescence has been limited to animal models of adolescence due to limitations on the available techniques to assess striatal dopaminergic neurobiology in vivo in the human adolescent. Studies 1 and 2 of this dissertation assess this limitation by assessing a novel tissue property that has been linked multiple aspects of striatal dopamine neurobiology: tissue iron. We first use two MRI metrics sensitive to tissue iron concentration to investigate age-related differences in striatal tissue iron in a developmental sample spanning from adolescence to adulthood (ages 12 – 30) and then conduct a combined PET/MRI experiment in an adult sample (ages 18 - 30) to evaluate the relationship between striatal tissue iron concentration and indices of dopamine neurobiology. We find age-related increases in striatal tissue iron throughout adolescence and a positive association between an MR metric of tissue iron concentration and a PET metric of dopamine concentration in the aspect of the striatum most strongly associated with reward processing, the ventral striatum. Finally, study 3 assesses the hypothesis that there is a developmental imbalance between the influence of affective reward systems and cognitive control systems of behavior during adolescence by investigating corticostriatal connectivity. Specifically, we identify areas of the striatum that integrate corticostriatal projections for brain areas involved affect and cognitive control and investigate age-related differences in the balance of these inputs. We find that the relative integrity of affective projections, in relation to projections from cognitive control systems, decreases with age and is positively associated with an index of reward-driven behavior.