A generalizable functional connectivity signature characterizes brain dysfunction and links to rTMS treatment response in cocaine use disorder

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 establish a corss-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, like non-planning impulsivity. We used the CUD-discriminative FCs to predict rTMS treatment response in CUD patients receiving either active (N = 25) or sham rTMS (N = 20) separately, finding that the most predictive FCs for active treatment responses were involving the frontoparietal control and default mode networks. Our findings provide insights into the neurobiological mechanisms of CUD and the association between CUD phenotypes and rTMS treatment response, offering promising targets for future therapeutic development.

Brain Connectomics Markers for Response Prediction to Transcranial Magnetic Stimulation in Cocaine Use Disorder

“…We used ACC seed-based connectivity for VAS prediction. Multiple studies have consistently reported the structural and functional changes in this region in CUD 45,46 and also its relationship with VAS 47 . Results showed that the connectivity of ACC with precentral gyrus, occipital cortex, and pre/post-central gyrus predicted greater reduction in VAS for 2w, 3m, and 6m after rTMS application, respectively.…”

The Mexican dataset of a repetitive transcranial magnetic stimulation clinical trial on cocaine use disorder patients: SUDMEX TMS

“…A participants checklist with the specific MRI sequences acquired can be found in supplementary material. To date, the present dataset has been used to examine the short and long-term clinical benefits of rTMS and their impact on functional connectivity 10 , to identify cognitive deficits of CUD participants by machine learning algorithms 11 , to improve diffusion MRI segmentation methods using deep learning 12 , to predict clinical outcomes using microstructural changes 13 , and to identify a generalizable functional connectivity signature characterizes brain dysfunction in cocaine use disorder 14 . Altogether, this dataset could serve for the study of the longitudinal impact of rTMS as a promising add-on treatment for CUD, as well as to test new neuroimaging algorithms and analysis techniques.…”

“…Its content focuses on the behavior of depression, with vegetative, cognitive, and anxiety symptoms having the greatest weight in the total calculation of the scale. The cutoff points to define severity are no depression (0-7); mild depression (8)(9)(10)(11)(12)(13)(14)(15)(16); moderate depression (17)(18)(19)(20)(21)(22)(23); and severe depression (≥24) 40 .…”