Investigating Structural and Functional Pathology in Cocaine use Disorder

Abstract

Cocaine use disorder (CUD) is a compulsive urge to seek and consume cocaine despite the inimical consequences. MRI studies from different modalities have shown that CUD patients exhibit structural and/or functional connectivity pathology among several brain regions. Nevertheless, both connectivities are commonly studied and analyzed separately, which may potentially obscure its relationship between them, and with the clinical pathology. Here, we compare and contrast structural and functional brain networks in CUD patients and healthy controls (HC). The existing body of research has predominantly concentrated on studying substance abuse within the Caucasian population. Gaining a comprehensive understanding of the distinctive challenges and cultural environments in which substance abuse disorders emerge among various populations is essential. For this study, we recruited 105 individuals of Mexican descent and carefully examined the T1-weighted, diffusion weighted imaging, resting-state fc-fMRI sequences and clinical metrics of these participants. Based on the previous work [53], we identified regions of interest (ROIs) that are known to have altered structural connectivity in CUD patients and examined their pairwise functional connectivity. The results demonstrated that CUD exhibited stronger connection between the right Posterior Cingulate and right Postcentral than HC which could suggest an increase in interoception potentially associated with compulsion behavior. We computed a battery of graph-based measures from multi-shell diffusion-weighted imaging (tc-dMRI) and resting state fc-fMRI to quantify local and global connectivity. We investigated the differences in functional and structural modalities between the two groups independently. Unimodal analysis showed an increase in the participation coefficient in Striatum among CUD compared to HC in the fc-fMRI modality which has been previously linked to the compulsive drug-seeking behavior observed in CUD. Multimodal fusion is a data driven approach that involves fusion of different brain modalities to gain a more comprehensive understanding of the brain’s structure and function. Multimodal fusion has played an important role in investigating joint functional and structural changes in neurological disorders like Alzheimer’s disease, schizophrenia, and epilepsy. This is the first study that uses multimodal fusion of graph theoretical measures to investigate topological alterations in CUD patients. We specifically used multimodal canonical component analysis plus joint independent component analysis (mCCA+jICA) to evaluate group differences and their association with clinical scores. When performing multimodal fusion analysis, we observed a higher betweenness centrality and lower participation coefficient in CUD patients indicating reorganization of functional networks. In addition to altered straiatal connectivity revealed by the unimodal approach, multimodal fusion revealed latent information about brain regions involved in impairment due to cocaine abuse. Overall, results revealed by our study not only concord with previous research in the field but also uncovered findings which could help in understanding the pathology of CUD and develop better pre-treatment/post-treatment intervention design.