ABSTRACT
Cocaine use disorder (CUD) is a prevalent substance abuse disorder, and repetitive transcranial magnetic stimulation (rTMS) has shown potential in reducing cocaine cravings. However, a robust and replicable biomarker for CUD phenotyping is lacking, and the association between CUD brain phenotypes and treatment response remains unclear. Our study successfully established a cross-validated functional connectivity signature for accurate CUD phenotyping, using resting-state functional magnetic resonance imaging from a discovery cohort, and demonstrated its generalizability in an independent replication cohort. We identified phenotyping FCs involving increased connectivity between the visual network and dorsal attention network, and between the frontoparietal control network and ventral attention network, as well as decreased connectivity between the default mode network and limbic network in CUD patients compared to healthy controls. These abnormal connections correlated significantly with other drug use history and cognitive dysfunctions, e.g., non-planning impulsivity. We further confirmed the prognostic potential of the identified discriminative FCs for rTMS treatment response in CUD patients and found that the treatment-predictive FCs mainly involved the frontoparietal control and default mode networks. Our findings provide new insights into the neurobiological mechanisms of CUD and the association between CUD phenotypes and rTMS treatment response, offering promising targets for future therapeutic development.
Competing Interest Statement
The authors have declared no competing interest.
Clinical Trial
NCT02986438
Funding Statement
This work was supported in part by NIH grant nos. R01MH129694 and R21MH130956, and Lehigh University FIG (FIGAWD35), CORE, and Accelerator grants. Portions of this research were conducted on Lehigh University Research Computing infrastructure partially supported by NSF Award 2019035. AE was supported by NIH grant nos. DP1MH116506 and R44MH123373. GAF was supported by NIH grant nos. K23MH114023 and R01MH125886 and grants from the Brain and Behavior Research Foundation and One Mind Baszucki Brain Research Fund.
Author Declarations
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SUDMEX_CONN dataset: https://openneuro.org/datasets/ds003346/versions/1.1.2 SUDMEX_TMS dataset:https://openneuro.org/datasets/ds003037/versions/1.0.1 UCLA-CNP dataset: https://openneuro.org/datasets/ds000030/versions/00016 NYU dataset: http://fcon_1000.projects.nitrc.org/indi/retro/nyuCocaine.html
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Data Availability
All data produced are available online at http://fcon_1000.projects.nitrc.org/indi/retro/nyuCocaine.html https://openneuro.org/datasets/ds000030/versions/00016 https://openneuro.org/datasets/ds003037/versions/1.0.1 https://openneuro.org/datasets/ds003346/versions/1.1.2