Substance Abuse in Emerging Adults: The Role of Neuromelanin and Ventral Striatal Response to Social and Monetary Rewards

Abstract

Perturbations in dopamine system function may increase risk of substance use disorder (SUD). We recently demonstrated that neuromelanin (NM) MRI signal in the substantia nigra, a non-invasive index of dopamine system function, is elevated in long term cocaine users (Cassidy et al., 2020). However, it is unclear whether elevated NM-MRI signal is linked to risk of SUD, or is a byproduct of long-term drug use. Our prior work failed to show relations between NM-MRI signal and functional engagement of ventral striatum during a monetary reward task. However, social experiences are commonly linked to drug use and relapse. Given that, NM-MRI signal may be more closely linked to ventral striatal engagement during social, rather than monetary reward processing. Emerging adults (n = 33, 21.88 ± 4.35 years) with varying levels of substance abuse, but without SUD, underwent NM-MRI and fMRI during social and monetary reward processing tasks. Voxelwise analysis within the substantia nigra (SN) demonstrated lower NM-MRI signal was associated with more severe substance abuse. Lower right ventral striatal engagement to social reward was also associated with more severe substance abuse. This relation was moderated by SN NM-MRI signal such that diminished striatal response to reward was associated with greater substance abuse among those with low NM-MRI signal, but lower substance abuse among those with high NM-MRI signal. Unexpectedly, higher right ventral striatal engagement during monetary reward was associated with more severe substance abuse. This relation was moderated by SN NM-MRI signal such that greater striatal response to reward was associated with greater substance abuse among those with low NM-MRI signal. Taken together, we provide preliminary evidence that, in emerging adults, low rather than high dopamine system function may increase risk of substance abuse, and strengthen the association between substance use and the brain's sensitivity to social and monetary outcomes in different ways.

Keywords: NM-MRI; adolescent SUD; fMRI; midbrain; peer feedback; risk factors.

Figure 1

fMRI-based monetary and social reward tasks.

Figure 2

Template NM-MRI images were created by averaging the spatially normalized NM-MRI images from all participants. Overlays reflect (A) anatomical substantia nigra (green) and crus cerebri (blue) masks; (B) results from voxelwise analysis showing a significant negative relation between substance abuse and NM-MRI signal in substantia nigra (red). (C) Scatter plot depicting this negative relation.

Figure 3

Depiction of moderating effect of NM-MRI signal on the relation between right ventral striatal response to social reward (vs. non-reward) and substance abuse. SD = standard deviation.

Figure 4

Depiction of moderating effect of NM-MRI signal on the relation between right ventral striatal response to monetary reward (vs. non-reward) and substance abuse. SD = standard deviation.