Brain multimodal co-alterations related to delay discounting: a multimodal MRI fusion analysis in persons with and without cocaine use disorder

Abstract

Background: Delay discounting has been proposed as a behavioral marker of substance use disorders. Innovative analytic approaches that integrate information from multiple neuroimaging modalities can provide new insights into the complex effects of drug use on the brain. This study implemented a supervised multimodal fusion approach to reveal neural networks associated with delay discounting that distinguish persons with and without cocaine use disorder (CUD).

Methods: Adults with (n = 35) and without (n = 37) CUD completed a magnetic resonance imaging (MRI) scan to acquire high-resolution anatomical, resting-state functional, and diffusion-weighted images. Pre-computed features from each data modality included whole-brain voxel-wise maps for gray matter volume, fractional anisotropy, and regional homogeneity, respectively. With delay discounting as the reference, multimodal canonical component analysis plus joint independent component analysis was used to identify co-alterations in brain structure and function.

Results: The sample was 58% male and 78% African-American. As expected, participants with CUD had higher delay discounting compared to those without CUD. One joint component was identified that correlated with delay discounting across all modalities, involving regions in the thalamus, dorsal striatum, frontopolar cortex, occipital lobe, and corpus callosum. The components were negatively correlated with delay discounting, such that weaker loadings were associated with higher discounting. The component loadings were lower in persons with CUD, meaning the component was expressed less strongly.

Conclusions: Our findings reveal structural and functional co-alterations linked to delay discounting, particularly in brain regions involved in reward salience, executive control, and visual attention and connecting white matter tracts. Importantly, these multimodal networks were weaker in persons with CUD, indicating less cognitive control that may contribute to impulsive behaviors.

Keywords: Cocaine; Delay discounting; Drug addiction; Impulsivity; Magnetic resonance imaging; Multimodal fusion.

Fig. 1

Multimodal group-discriminating IC₆. For each modality, spatial maps are shown at a threshold of $\left|Z\right|$ ≥ 2.5. For gray matter volume (GMV) and fractional anisotropy (FA), the component loadings are positive. Positive Z-values (red regions) means that COC− have higher GMV and FA compared to COC+. For regional homogeneity (ReHo), the components loadings are negative. Positive Z-values (red regions) means that COC− have lower connectivity compared to COC+, while negative Z-values (blue regions) means that COC− have higher values compared to COC+. The scatter plots on the right show the relationship of the component loadings to delay discounting