Mapping Morphological Similarity Network and Neurotransmitter Abnormalities in Cocaine Use Disorder: A Multimodal Neuroimaging Study
Dafa Shi, Shuohua Wu, Caiyu Zhuang, Guangsong Wang, Rui Wang, Yumeng Mao, Hongying Huang, Zhongruowen Ren, Mingyuan Dai, Gen Yan, Renhua WuObjective:
Cocaine Use Disorder (CUD) poses a major public health challenge, with no Food and Drug Administration-approved pharmacotherapies currently available. A deeper understanding of Morphometric Similarity Network (MSN) alterations and their associations with neurotransmitter systems in CUD may facilitate the development of targeted therapeutic strategies. We aimed to investigate the aberrant MSN patterns and their relationships with neurotransmitter distributions in CUD.
Methods:
This case-control study enrolled 70 patients with CUD and 57 age- and sex-matched healthy controls (HCs). Individual-level MSNs were constructed for each participant, and regional morphometric similarity (MS) strength was computed. Group differences in MSN connectivity and regional MS strength were compared between the CUD and HC groups. The JuSpace toolbox was employed to assess spatial correlations between regional MS alterations and specific neurotransmitter maps.
results:
Network-based statistic analysis revealed disrupted MSN connectivity in patients with CUD, primarily involving the prefrontal cortex, striatum, thalamus, frontoparietal control network, and insula. Regional MS strength abnormalities demonstrated significant spatial correlations with the neurotransmitter density distributions of the serotonergic, dopaminergic, glutamatergic, GABAergic, and cholinergic systems. These spatial correlations were further associated with CUD severity and weekly cocaine dose.
Results:
Network-based statistic analysis revealed disrupted MSN connectivity in patients with CUD, primarily involving the prefrontal cortex, striatum, thalamus, frontoparietal control network, and insula. Regional MS strength abnormalities demonstrated significant spatial correlations with the neurotransmitter density distributions of the serotonergic, dopaminergic, glutamatergic, GA-BAergic, and cholinergic systems. These spatial correlations were further associated with CUD severity and weekly cocaine dose.
Discussion:
These findings provide novel insights into the neuropathological mechanisms of CUD from the perspectives of gray matter morphometric covariance patterns and neurotransmitter systems. The consistency with existing findings further supports the clinical translational value of the neurotransmitter targets we have identified.
Conclusion:
Our findings revealed co-altered patterns of gray matter morphometric covariance and neurotransmitter interactions in CUD, providing novel insights into the neuropathological mechanisms of CUD and identifying potential therapeutic targets.