Ghazi Nayereh, Garza-Villarreal Eduardo A, Soltanian-Zadeh Hamid
School of Electrical and Computer Engineering, University of Tehran, Tehran, Iran.
Institute of Neurobiology, National Autonomous University of Mexico (UNAM) Campus Juriquilla, Queretaro, Mexico.
Sci Rep. 2025 May 2;15(1):15336. doi: 10.1038/s41598-025-99113-6.
Cocaine use disorder (CUD) is a worldwide health problem with limited effective treatment options. The therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) is gaining more attention following evidence of its role on craving reduction in CUD. However, the heterogeneity of results underscores a pressing need for biomarkers of treatment outcome. We asked whether brain connectomics together with clinical assessments can predict response to add-on rTMS therapy for CUD better than solely conventional clinical assessments. Forty-four randomly assigned CUD patients underwent the 2-week double-blind acute phase [Sham (n = 20, 2f./18m.) and Active (n = 24, 4f./20m.)], in which they received 2 daily sessions of rTMS on the left dorsolateral prefrontal cortex. Subsequently, 19 and 14 patients continued to an open-label maintenance phase of two weekly rTMS sessions for 3 and 6 months, respectively. Pre and post treatment resting-state brain functional connectivity as well as two clinical scores of craving were measured to predict the subsequent response to rTMS therapy. Two conventional clinical scores, namely Cocaine Craving Questionnaires (CCQ) and Visual Analogue Scale (VAS) were used as craving level assessments. We used a priori seed-driven connectivity of Left Dorsolateral Prefrontal Cortex (LDLPFC) and Anterior Cingulate Cortex (ACC) together with the connectivity from a whole-brain multi-voxel pattern analysis at each time point to predict the reduction in craving after rTMS. The combination of connectivity changes and baseline craving severity improved the prediction of individual craving compared to the prediction with only the initial craving severity. The predictive model from the combination of neuromarkers could explain 45 to 97 percent of variance in craving changes assessed by two different clinical scores. We used leave-one-subject-out cross-validation to support the generalizability of our findings. Our results indicate that employing neuromarkers from resting-state functional connectivity of pre and post condition of CUD patients receiving add-on rTMS therapy increases the power of predicting craving changes and support the idea that neuromarkers may offer improvements in precision medicine approaches.
可卡因使用障碍（CUD）是一个全球性的健康问题，有效的治疗方案有限。重复经颅磁刺激（rTMS）的治疗潜力在有证据表明其在减少CUD渴望方面发挥作用后，正受到越来越多的关注。然而，结果的异质性凸显了对治疗结果生物标志物的迫切需求。我们询问，与单纯的传统临床评估相比，脑连接组学结合临床评估是否能更好地预测CUD患者对附加rTMS治疗的反应。44名随机分配的CUD患者接受了为期2周的双盲急性期治疗[假刺激组（n = 20，2名女性/18名男性）和真刺激组（n = 24，4名女性/20名男性）]，在此期间，他们每天接受2次对左侧背外侧前额叶皮质的rTMS治疗。随后，19名和14名患者分别继续进入为期3个月和6个月的开放标签维持期，每周进行2次rTMS治疗。测量治疗前后静息态脑功能连接以及两个渴望临床评分，以预测随后对rTMS治疗的反应。使用两个传统临床评分，即可卡因渴望问卷（CCQ）和视觉模拟量表（VAS）作为渴望水平评估。我们使用先验种子驱动的左侧背外侧前额叶皮质（LDLPFC）和前扣带回皮质（ACC）连接，以及每个时间点全脑多体素模式分析的连接，来预测rTMS后渴望的降低。与仅用初始渴望严重程度进行预测相比，连接性变化和基线渴望严重程度的组合改善了对个体渴望的预测。神经标志物组合的预测模型可以解释两种不同临床评分评估的渴望变化中45%至97%的方差。我们使用留一法交叉验证来支持我们研究结果的普遍性。我们的结果表明，采用接受附加rTMS治疗的CUD患者治疗前后静息态功能连接的神经标志物，可提高预测渴望变化的能力，并支持神经标志物可能改善精准医学方法的观点。
