Structural connectivity of neural reward networks in youth at risk for substance use disorders

Abstract

Background: Having a positive family history of alcohol use disorders (FHP), as well as aberrant reward circuitry, has been implicated in the initiation of substance use during adolescence. This study explored the relationship between FHP status and reward circuitry in substance naïve youth to better understand future risky behaviors.

Methods: Participants were 49 FHP and 45 demographically matched family history negative (FHN) substance-naïve 12-14 year-olds (54 % female). Subjects underwent structural magnetic resonance imaging, including diffusion tensor imaging. Nucleus accumbens and orbitofrontal cortex volumes were derived using FreeSurfer, and FSL probabilistic tractography probed structural connectivity and differences in white matter diffusivity estimates (e.g. fractional anisotropy, and mean, radial, and axial diffusivity) between fiber tracts connecting these regions.

Result: FHP and FHN youth did not differ on nucleus accumbens or orbitofrontal cortex volumes, white matter tract volumes, or percentages of streamlines (a proxy for fiber tract count) connecting these regions. However, within white matter tracts connecting the nucleus accumbens to the orbitofrontal cortex, FHP youth had significantly lower mean and radial diffusivity (ps < 0.03) than FHN youth.

Discussion: While white matter macrostructure between salience and reward regions did not differ between FHP and FHN youth, FHP youth showed greater white matter coherence within these tracts than FHN youth. Aberrant connectivity between reward regions in FHP youth could be linked to an increased risk for substance use initiation.

Keywords: Adolescence; Cognitive control; Diffusion tensor imaging (DTI); Family history of alcohol use disorders; Nucleus accumbens; Orbitofrontal cortex; Probabilistic tractography; Reward circuitry; Structural connectivity; Substance use disorders; White matter integrity.

Fig. 1

Example from one participant showing the FreeSurfer derived parcellations for the nucleus accumbens (blue) and orbitofrontal cortex (green). Each participant’s nucleus accumbens and orbitofrontal cortex was derived individually. ProbtrackX used the nucleus accumbens as the seed region and the orbitofrontal cortex as the target region to determine the percentage of streamlines that connected the two regions

Fig. 2

Example of one participant’s ProbtrackX results. Areas in yellow-red indicate the streamlines extending from the nucleus accumbens (blue) to the orbitofrontal cortex (green). These results were derived individually for each participant